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Cardiovascular

Manual
for the Advanced
Practice Provider

Mastering the Basics

Richard Musialowski
Krista Allshouse
Editors

123
Cardiovascular Manual for the Advanced
Practice Provider
Richard Musialowski • Krista Allshouse
Editors

Cardiovascular Manual
for the Advanced
Practice Provider
Mastering the Basics
Editors
Richard Musialowski Krista Allshouse
Sanger Heart and Vascular Institute Atrium Health
Atrium Health Levine Childrens’ Congenital Heart
Charlotte, NC, USA Center
Charlotte, NC, USA

ISBN 978-3-031-35818-0 ISBN 978-3-031-35819-7 (eBook)

https://doi.org/10.1007/978-3-031-35819-7

© The Editor(s) (if applicable) and The Author(s), under exclusive license to Springer Nature
Switzerland AG 2023
This work is subject to copyright. All rights are solely and exclusively licensed by the Publisher,
whether the whole or part of the material is concerned, specifically the rights of translation,
reprinting, reuse of illustrations, recitation, broadcasting, reproduction on microfilms or in any
other physical way, and transmission or information storage and retrieval, electronic adaptation,
computer software, or by similar or dissimilar methodology now known or hereafter developed.
The use of general descriptive names, registered names, trademarks, service marks, etc. in this
publication does not imply, even in the absence of a specific statement, that such names are
exempt from the relevant protective laws and regulations and therefore free for general use.
The publisher, the authors, and the editors are safe to assume that the advice and information in
this book are believed to be true and accurate at the date of publication. Neither the publisher nor
the authors or the editors give a warranty, expressed or implied, with respect to the material
contained herein or for any errors or omissions that may have been made. The publisher remains
neutral with regard to jurisdictional claims in published maps and institutional affiliations.

This Springer imprint is published by the registered company Springer Nature Switzerland AG
The registered company address is: Gewerbestrasse 11, 6330 Cham, Switzerland
Foreword

It is with honor that I write this foreword to the first Cardiovascular Manual
for the Advanced Practice Provider. In my over thirty-year cardiovascular
career, I have witnessed the inception, acceptance, growth, indispensability,
and leadership of advanced practice providers (APPs) to the cardiovascular
care (CV) team. This is corroborated now by nearly 7000 CV team members
in the American College of Cardiology (ACC) worldwide. Recent innovative
new pathways to both associate (AACC) and fellow (FACC) status ensure this
continued growth and leadership. These designations are awarded each year at
ACC’s annual scientific sessions convocation and emphasize the importance
of APPs to the College’s mission to “transform cardiovascular care and
improve heart health for all.” Furthermore, the APP numbers continuing global
growth will promote the College’s vision of “a world where science, knowl-
edge, and innovation optimize cardiovascular care.” In short, APPs are now
essential to the CV team, and this manual will aid in the best care of complex
cardiovascular patients as well as filling a previously unmet clinical need.
Much appreciation goes to Richard Musialowski, MD, FACC, Director of
CV Education at Sanger Heart and Vascular Institute/Atrium Health, and
Krista Allshouse, PA-C, who conceived and kick-started this manual. Much
credit goes to Amy Winiger, DNP, FACC, who has shown the far-reaching
possibilities that APPs can achieve in cardiology today, as well as Kathy
Venable, PA-C, who trailblazed and has led our own APP program at Sanger
Heart and Vascular Institute/Atrium Health for over 30 years. This program
now employs over 120 APPs. Nationally, George Rodgers, MD, MACC,
Eileen Handberg, Ph.D., FACC, and Janet Wyman, DNP, FACC, have led the
ACC CV Team section to become one of the strongest forces for advocacy
and advancement of the ACC in the past decade.
I close with admiration and awe for all those who have contributed not
only to the writing of this manual but to the acceleration of APP leadership
within the CV team. This manual will become an invaluable resource in the
optimal care of all our cardiovascular patients.

Sanger Heart & Vascular Institute/Atrium Health B. Hadley Wilson

Charlotte, NC, USA
Clinical Professor of Medicine, Wake Forest University-Atrium Health,
Charlotte, NC, USA
President, American College of Cardiology, Washington, DC, USA
May 1, 2022

v
Letter from Editor

Dear Readers,

Why was this manual created? It was the brainchild of the editors after many
long discussions about how advanced practice providers (APPs) are currently
used in the healthcare setting, the future of our work, and APP education.
How can we best prepare a new graduate from PA/NP school, a resident, or
an APP changing specialties to practice in cardiology? In today’s environ-
ment of ultra-specialized APPs, how can we best give them a broad knowl-
edge base in cardiology? Then it hit us! Write a Cardiovascular Manual BY
APPs working in cardiology FOR these new APPs. What would these sea-
soned providers want their new colleagues to know in each of their areas of
expertise? And the book was born: Cardiovascular Manual for the Advanced
Practice Provider.
There were many discussions regarding other learning, outside of books.
It is critical for new providers to learn from the entire healthcare team. Each
aspect of patient care is important and a provider can learn from each of these
specialties, especially nursing. Nurses provide patient care for hours on end,
whether that is an 8, 10, or 12 h shift and gain an exorbitant amount of infor-
mation about the patient during this time. Listen to them! They will always
know the patient better than you. Respect everyone in the care team; they all
have different jobs to do, but are equally important. The more you talk to and
ask questions to the care team, the more likely they will come to you with
concerns or questions, which will improve patient care and communication.
You do not want to be unapproachable.
You also should become a leader in your field and to the entire care team.
Everyone is busy but as a provider, you should be the guide for care and take
responsibility of the patient. Lead by doing. Be a leader in the way you direct
care, create a team-based care team, and educate. Accept education gladly
from other care providers. It is all a learning experience. Don’t be afraid to be
vulnerable and admit you don’t know something. It is the only way to learn.
Put the effort in to educate yourself outside of the job—go to conferences,
read and LISTEN!
We hope this publication serves you well in your journey to becoming a
well-rounded and spectacular Cardiovascular APP!
Thank you to Dr. Ronald Sing for jump starting our idea by allowing us to
help with his book Interventional Critical Care. We appreciate the opportu-
nity to be involved.

vii
viii Letter from Editor

We also want to thank the following people for their help obtaining images
for this work:

Tom Johnson, M.D. F.A.C.C., F.A.S.E.

Markus Scherer, M.D. F.A.C.C., F.A.S.E.
Kristi Johnson, RDCS, F.A.S.E.
Cody Frye, RDCS, F.A.S.E.
Amar Parikh, M.D.
Joshua Lisenby
Shannon Culver
Nainesh Patel, M.D., F.A.C.C., F.S.C.A.I.

Sincerely,
Richard Musialowski and Krista Allshouse
Contents

Part I Introduction

1
Cardiac Anatomy, Physiology, and Exam�� 3
Richard Musialowski and Krista Allshouse
2 Basic Hemodynamics �� 13
Courtney Bennett and Amanda Solberg

Part II Coronary Artery Disease

3
Acute Coronary Syndrome (ACS) ST Segment Elevation
Myocardial Infarction�� 21
Amy Winiger and George P. Rodgers
4
ACS Non-ST Elevation Myocardial Infarction (NSTEMI)�� 31
Michelle Ross and John Cedarholm
5
Outpatient Management of Coronary Artery Disease�� 43
Michelle Ross and John Cedarholm
6
Surgical Management of Coronary Artery Disease�� 53
Elisabeth A. Powell and Larry Watts

Part III Cardiac Electrophysiology

7 Antiarrhythmic and Anticoagulant Agents �� 63

Craig J. Beavers
8 Bradycardia�� 81
Hannah Kibler and Sharon Vannoy
9 Atrial Arrhythmias�� 91
Lora Raines
10 Ventricular Tachycardia�� 113
Robert Hipp
11 Cardiac Channelopathies�� 121
Krista Allshouse

ix
x Contents

12 Introduction to Cardiac Ablation �� 127

Krista Allshouse
13 Introduction
to Electrophysiology Devices�� 131
Jamie A. Dietrich
14 Cardioversion �� 139
Lora Raines
15 Cardiac Syncope�� 141
Krista Allshouse and Richard Musialowski

Part IV Structural/Valvular Heart Disease

16 Aortic Valve Disease�� 149

Anne Booke, Michael Rinaldi, Elisabeth A. Powell, Larry
Watts, and Richard Musialowski
17 Mitral Valve Disease�� 165
Anne Booke, Michael Rinaldi, Elisabeth A. Powell, Larry
Watts, and Richard Musialowski
18 Tricuspid Valve Disease �� 177
Anne Booke, Michael Rinaldi, Elisabeth A. Powell, Larry
Watts, and Richard Musialowski
19 Infective Endocarditis�� 183
Allen Stephens, Todd McVeigh, Cary Ward, Elisabeth A.
Powell, and Larry Watts

Part V Cardiomyopathies/Congestive Heart Failure

20 Heart
Failure with Reduced Ejection Fraction (HFrEF)�� 197
Lauren Eyadiel and Bridget Rasmussen
21 Heart
Failure with Preserved Ejection Fraction (HFpEF)�� 221
Carolina D. Tennyson
22 Pulmonary Vascular Disease �� 225
Lyn Shelton and Joe Mishkin
23 Pericardial Disease�� 245
Ashley McDaniel and Richard Musialowski

Part VI Shock

24 Cardiogenic Shock �� 257

Courtney Bennett and Amanda Solberg
25 Introduction
to Mechanical Support�� 265
Courtney Bennett and Amanda Solberg
Contents xi

Part VII Peripheral Vascular Disease

26 Carotid Artery Stenosis (CAS)�� 271

Trent Gabriel and Frank R. Arko III
27 Peripheral Arterial Disease (PAD)�� 279
Trent Gabriel, Amber Amick, and Frank R. Arko III
28 Diseases of the Aorta�� 291
Tracy Totten and Frank R. Arko III

Part VIII Adult Congenital Heart Disease (ACHD)

29 ACHD�� 307
Amanda Green and Jorge Alegria

Part IX Ambulatory/Preventative Cardiology

30
Prevention of Cardiometabolic Disease �� 331
Allison W. Dimsdale and Christopher Kelly

Part X Emergency Department Evaluation of Chest Pain

31
Acute Evaluation of Chest Pain�� 347
Devin Stives and Richard Musialowski

Part XI Cardiovascular Disease in Pregnancy

32
Cardiovascular Disease in Pregnancy�� 359
Cindy Sing and Malissa J. Wood
Index 373
Part I
Introduction
Cardiac Anatomy, Physiology,
and Exam
1
Richard Musialowski and Krista Allshouse

Embryologic Development The great vessels (aorta and pulmonary

artery) arise from the aortic arch. Through septa-
The fetal heart begins as a simple tube in the third tion, the pulmonary artery and aorta divide into
week of gestation and develops to a four cham- two separate vessels. These tubes are in continu-
bered beating structure by approximately week 7 ation with the developing and rotating ventricles.
to 8 [1]. Valves develop according to their loca- These vessels create the semilunar valves seen in
tion in the embryonic tube and differentiate from the aortic and pulmonic positions. The coronary
the ventricle they arise within. The right ventricle arteries arise above the semilunar valves in the
(RV) will always produce a three to four leaflet developing aorta. A connection persists between
tricuspid valve (TV). The left ventricle (LV) will the aorta and pulmonary artery during fetal
always produce a two-leaflet mitral valve (MV). development, called the ductus arteriosus. This
Septation occurs dividing both the atria and ven- structure empties blood from the uninflated fetal
tricles into two separate and genetically different lungs and pulmonary artery into the aorta in
pairs. utero. The spontaneous breathing of the infant
Septation of the embryonic atria creates two after birth causes a subsequent fall in the pulmo-
independent chambers with a small residual com- nary vascular resistance (PVR) and the removal
munication called the foramen ovale. Placental of the placenta causes an increase in systemic
blood (oxygenated) is preferentially shunted vascular resistance (SVR), resulting in abrupt
across this structure into the left atrium, LV, and closure of the ductus, creating two separate cir-
into the fetal aorta. At delivery, the LA pressure cuits: pulmonary (unoxygenated) and systemic
exceeds the RA pressure and closes this connec- (oxygenated).
tion. Fifteen percent of the population will have a Abnormalities during development can occur
persistent patent foramen ovale (PFO) into at any point, resulting in a variety of congenital
adulthood. cardiac defects. The advancement of surgical
techniques and medical therapies have improved
the survival of patients with congenital heart dis-
R. Musialowski
Sanger Heart and Vascular Institute, Atrium Health, ease, and many are now living well into adult-
Charlotte, NC, USA hood (see Chap. 29).
e-mail: [email protected]
K. Allshouse (*)
Atrium Health, Levine Childrens’ Congenital Heart
Center, Charlotte, NC, USA
e-mail: [email protected]

© The Author(s), under exclusive license to Springer Nature Switzerland AG 2023 3

R. Musialowski, K. Allshouse (eds.), Cardiovascular Manual for the Advanced Practice Provider,
https://doi.org/10.1007/978-3-031-35819-7_1
4 R. Musialowski and K. Allshouse

xcitation Contraction Coupling

E membrane proteins called voltage-gated chan-
(ECC) nels. These channels are ion-specific and allow
additional sodium and calcium ions into the cell,
Each cardiac cycle is a rapid process of electrical depo- specifically at the T-tubule. The impulse then
larization and muscle contraction with active electrical spreads to surrounding cells via gap junctions,
repolarization and muscle relaxation. The timing is microtubule structures that allow sodium and cal-
well organized, and deviations of this process may cium ions to rapidly flow to the next cell. This ion
result in distinct cardiac dysfunction (Diagram 1). flow spreads rapidly throughout the whole heart
ECC begins with the spontaneous phase 4 so that when one cell is depolarized, all cells
depolarization of pacemaker cells due to the become depolarized at a speed of 0.5 m/s!
influx of sodium and calcium ions, i.e. the funny At this point, the electrical excitation is com-
current [2]. This is known as automaticity and pleted, and repolarization begins with shifts of
cells with this characteristic are present within other ions (mainly potassium) out of the cell.
the sinoatrial node (SAN), atrial tissue, atrioven- This reset of the transmembrane potential or
tricular (AV) node, and ventricular myocytes. refractory period is essential for the next impulse
The speed of spontaneous depolarization deter- to occur. This is seen as phase 3 on the action
mines the heart rate, and thus the P-to-P interval. potential and is associated with the QT interval
Once the depolarization meets a threshold, phase on EKG. Energy expenditure in the form of ATP
0 of the action potential begins (Fig. 1.1). within the membrane exchange pumps is essen-
Propagation of the electrical impulse on the cell tial in this process. When the calcium enters the
membrane alters the chemical structure of trans- cell in phase 2 of the action potential, it binds to

Diagram 1
1 Cardiac Anatomy, Physiology, and Exam 5

A I. Troponin I can restrict the actin and myosin

Action Potential interaction while in the resting state. Troponin C
2 binds the excitation released calcium ions caus-
ing a loosening of the troponin I/actin complex
0 Force revealing the myosin-binding sites.
In the resting state, the myosin heads have
Cai 2+
ADP and inorganic phosphate bound to them. The
0.1 s
3 calcium-troponin directed transformation of
tropomyosin causes the presentation of the actin
4 binding sites. Interaction of the actin and myosin
heads releases the bound ADP and inorganic
phosphate creating cytosolic ATP. This release
causes a conformational change in the myosin
Ca influx Ca extrusion head resulting in the sliding of the actin and myo-
2+
Ca 3Na
+ sin by each other called the “power stroke” and
contraction results. Contraction is coordinated in
every cell at the same time! The reformed cyto-
1Ca2+
ADP solic ATP now binds to the contracted myosin
Ca release
heads and the molecule is split back to ADP and
3Na
+ SR
phosphate. This energy expenditure results in
2K+ Ca uptake
myosin conformation changes and the fibrils slide
ATP H+ back, thus establishing the resting state. Calcium
is pumped back into the SR against a gradient by
+ sarcoplasmic reticulum calcium ATPase
Na
+ Na
(SERCA2A), occurring during phase 3 and repo-
larization of the action potential (Diagram 1).
Fig. 1.1 Phase 4 depolarization is spontaneous due to the
This whole process from the initiation within
funny current that determines the heart rate [2]. Phase 0
depolarization is due to rapid sodium influx that occurs the sinus node to propagation to the AV node
after opening of voltage-gated channels due to the funny takes less than 180 ms, or the PR interval. This
current depolarization. During phase 2, calcium ions is the moment the atria contract. This same
influx as well. These calcium ions are essential to cause
impulse proceeds into the ventricle in the same
the muscle contraction necessary for cardiac function.
The force line is the representation of muscle contraction. ECC process with resultant QRS of 80 ms and
Electrical repolarization (phase 3) is occurring during ventricular contraction. The repolarization of
mechanical contraction. Calcium homeostasis is regulated the ventricle (refractory period) takes about
by the sarcoplasmic reticulum that releases and resets the
300 ms and corresponds to the QT interval.
gradients for the next contraction [3]. Adapted from
Figure 1Cell calcium 2020 Jan; 85:102129 Phase 4 of the action potential is reached and
the cycle begins again.
Alterations in the SERCA2 calcium homeosta-
the ryanodine receptors on sarcoplasmic reticu- sis are pathologic in HfrEF and the diastolic dys-
lum which releases a flood of calcium throughout function of HFpEF [4]. Since diastole requires
the muscle cells (Diagram 1). molecular energy, disease states that reduce cellu-
Cardiac muscle fibrils are made up of thick lar energy (i.e., ischemia) alter calcium homeosta-
myosin and thin actin filaments. Intertwined sis and impair diastolic function (see Sect. 5).
between these two structures is a protein com- Sympathetic nervous system innervation alters cal-
plex called tropomyosin. This structure is com- cium flows thus increasing heart rate and contrac-
posed of multiple proteins with specific tility. Antiarrhythmic medications alter the action
responsibilities. Troponin T is bound to the potential resulting in changes in conduction, repo-
tropomyosin, troponin C, and troponin larization, and ekg morphology (see Chap. 7).
6 R. Musialowski and K. Allshouse

Conduction System diac cycle. The P wave originates in the SA

node and is the first waveform of the cardiac
The specialized cells of the sinoatrial node (SAN) cycle. It is associated with atrial contraction.
are located in the upper portion of the right atrium The beginning of the P wave to the deflection
near the entrance to the superior vena cava. The of the QRS is called the P-R interval. This is
impulse arises due to automaticity of these cells the time the impulse starts in the sinus node,
and propagates through the atria. In the crux or propagates across the atria, and is slowed down
center of the heart, there is fibrous tissue surround- in the AV node. This interval approximates AV
ing the atrioventricular node (AVN). This fibrous node function. Normal is less than 200 ms.
tissue acts as a brake to slow down and organize (Longer than this time suggests AV node
the impulse. The organized impulse proceeds dysfunction.)
through the bundle of His and continues down the The QRS is the impulse proceeding through to
right and left bundles. The left bundle then splits the right and left bundles to depolarize the ven-
into the left anterior fascicle which is a relatively tricles, normally taking 80–100 ms. Pathology of
organized structure and a diffuse left posterior fas- the conduction system and ventricles causes this
cicle. These bundles are cardiac cells that have dif- interval to widen. Medication and abnormal met-
ferentiated for electrical conduction [5]. Blood abolic states also affect the QRS duration.
supply is important to the function of this system The QT segment corresponds to phase 3 of the
and coronary ischemia can cause electrical abnor- action potential and is associated with repolariza-
malities resulting in both tachycardia and brady- tion of the ventricle. Atrial repolarization is hid-
cardia. Metabolic abnormalities can also alter den in the QRS complex. This interval is heart
function of this system (see the EP Section). rate dependent. It is also influenced by many
medications, pathology, and autonomic influ-
ences. This interval is important in the assess-
Electrocardiogram (EKG or ECG) ment and management of ventricular
arrhythmias.
The normal QRS complex on an EKG is seen The P to P and R to R intervals are used to
in Fig. 1.2. This is a graphic representation of discuss rhythm interpretation. These intervals
the electrical impulse and conduction of a car- link different cardiac cycles together.

Fig. 1.2 Normal EKG with intervals

1 Cardiac Anatomy, Physiology, and Exam 7

Cardiac Anatomy MV are further described by their individual

cusps (Fig. 1.3). Abnormalities in any part of this
As stated in the embryology section, two separate apparatus will result in pathology of the valve
circuits are created during development. The right opening and closure. This is discussed in detail in
atrium (RA) and ventricle (RV) are separated by a the Sect. 4 on structural heart disease.
three to four leaflet structure called the tricuspid The tricuspid valve is similar with papillary
valve (TV). The RV is continuous with the pulmo- muscles, chordae tendineae, and leaflets. There is
nary artery and its pulmonary valve. Deoxygenated a septal, anterior, and posterior leaflet.
blood enters the RA and is pumped to the lungs The center or crux of the heart is an important
for oxygenation. After pulmonary capillary oxy- crossroad of electrical and mechanical cardiac
genation, the blood collects into the left atrium function (Fig. 1.4). The AVN is located within the
(LA) from the pulmonary veins. The left ventricle membranous septum. It is located near the septal
(LV) receives the oxygen- rich blood after it leaflet of the TV and below the right and non-
crosses a two leaflet valve called the mitral valve coronary cusps of the AV annulus. Also, the sep-
(MV). Ventricular systole moves blood through tal attachments of the MV anchor here as well. In
the left ventricular out flow tract (LVOT) into the Fig. 1.3, the approximation of the atrioventricular
aorta opening the aortic valve. Tissue perfusion and semilunar valves is seen. These valves are all
throughout the body occurs and the deoxygenated anchored in the fibrous crux.
blood returns to the RA through the superior This anatomy is important when infection
(SVC) or inferior vena cava (IVC) (Fig. 1.4). A occurs as multiple valves may be involved,
detailed discussion of the important hemody- increasing mortality. Also, aortic valve endocar-
namic features is contained in Chap. 2. ditis is associated with acute conduction interrup-
The atrioventricular valves (AV) and its appa- tion (see Chap. 19). Intervention of the aortic
ratus have specific functions necessary to gener- valve annulus can be complicated by disruption
ate stroke volume and thus cardiac output. of the AVN and bundle branches (see Sect. IV).
Papillary muscles are structures that are part of
the myocardial wall whose role is to contract dur-
ing ventricular systole and pull the valve leaflets Coronary Arteries
close to avoid regurgitation of blood backward
into the atria. The mitral valve has two muscles, Normal coronary artery anatomy is seen in
one medially and one laterally. The anterior and Fig. 1.5 with three epicardial arteries. The left
posterior leaflets are attached to the papillary main artery gives rise to the left anterior
muscles by chordae tendineae. The leaflets of the descending (LAD) and left circumflex (LCX).

Anterior semilunar cusp of pulmonary valve

AC
RC Right semilunar cusp of pulmonary valve
Left semilunar cusp of pulmonary valve LC

RCC Right semilunar cusp of aortic valve

Left semilunar cusp of aortic valve LCC
NCC Posterior semilunar cusp of aortic valve
A1
Anterior cusp of mitral valve
P1 A Anterior cusp of tricuspid valve
A2
A3
P2
Posterior cusp of mitral valve S Posterior cusp of tricuspid valve
P3 P

Septal cusp of tricuspid valve

Fig. 1.3 Nomenclature of the cardiac valves

8 R. Musialowski and K. Allshouse

DIASTOLE SYSTOLE

Pulmonary valve
Bicuspid (Mitral)
Pulmonary valve valve
Bicuspid (Mitral) valve

Aortic valve
Aortic valve
Tricuspid valve Tricuspid valve

Pulmonary valve
Pulmonary valve
(closed)
(open)
Aortic valve Aortic valve
(closed) (open)

Right
Left ventricle
ventricle Right
ventricle
Left
ventricle

Bicuspid (Mitral) valve Tricuspid valve Bicuspid (Mitral) valve Tricuspid valve
(open) (open) (closed) (closed)

Fig. 1.4 Work of the heart valves

The LAD branches into diagonal vessels. This

vascular distribution is the most important as it
Left Circumflex supplies the ventricular septum, which is very
Right Left Anterior Descending important during ventricular systole to generate
stroke volume and cardiac output. The LCX
branches into marginal vessels. This distribution
is important in blood supply to the posterior
medial papillary muscle supporting the mitral
valve. Ischemia of the RCA and LCX is associ-
ated with ischemic mitral regurgitation due to a
single blood supply from the PDA to this mus-
cle. The right coronary artery (RCA) supplies
the SA node. The posterior descending artery
(PDA) arises from the right coronary 80% of the
Fig. 1.5 Normal coronary anatomy time and supplies the AV node. Ischemia in the
RCA often results in bradycardia due to isch-
emia in these nodes.
1 Cardiac Anatomy, Physiology, and Exam 9

Physical Examination holosystolic as they begin immediately after S1.

of the Cardiovascular System: The quality is flat since the pressure generated in
Pearls and Techniques the ventricles is constant. Mitral valve regurgita-
tion traditionally radiates toward the axilla from
The stethoscope has two options to listen to the the apex. Tricuspid regurgitation often does not
patient. The flat surface is called the diaphragm. radiate but increases in intensity with inspiration.
It is best utilized for higher pitched sounds, Antegrade systolic flow across a stenotic aortic
including lung and bowel sounds. The other side, and pulmonic valve creates a murmur that
the bell, does not have a diaphragm over the con- increases in intensity as flow across the valve
tact area and is open to air. This is best utilized increases (crescendo). As the ventricle completes
for lower pitched sounds including S3 and bruits. its contraction, the pressure decreases and the
It is good practice to listen over an area of interest intensity of the murmur decreases (decrescendo).
with both the bell and the diaphragm to assess for Radiation of the systolic murmur is essential to
all frequency of sounds [7]. There are specific determine if the pathology is atrioventricular or
locations on the chest wall to best hear specific semilunar valve.
valves. Figures 1.6 and 1.7 demonstrate the best
anatomic location and correlation with specific
valves. Every heart sound has different character-
istics that need to be assessed during auscultation
(Tables 1.1 and 1.2).
The first heart sound (S1) is at the beginning
of ventricular systole. The movement of blood
within the heart results in a closure of the mitral
and tricuspid valves. If these atrioventricular
valves are incompetent, blood flows back into the
atria and a murmur will result. The specific
pathology causing the incompetence will decide
the characteristics of the murmur. Mitral and tri-
cuspid regurgitation are traditionally described as

Fig. 1.7 Heart location within thorax

Table 1.1 Murmur descriptions

Location Area Best Heard (see Fig. 1.6)
Timing Systole or diastole: use radial pulse to assist
Pitch High or low
Radiation Where is it directed: neck, back, axilla,
anterior, posterior
Duration Early diastole
Holosystolic
Mid or late systolic
Intensity 1–4 for diastolic (1–3 most common)
1–6 for systolic (2–3/6 most common)
Quality Harsh, soft, blowing, crescendo,
decrescendo
Fig. 1.6 Areas of auscultation
10 R. Musialowski and K. Allshouse

Table 1.2 Heart Sounds, Respiration, and the Cardiac increases the intensity of all right-sided murmurs.
Cycle
Increased venous return prolongs the right ven-
Systolic Murmur AS, PS, MR, TR tricular ejection time, prolonging pulmonic valve
Diastolic AI, PI closure (P2) and thus normally splits the second
murmur
Both systolic AS/AI, PS/PI, patent ductus
heart sound. During exhalation, the RV flow
and diastolic arteriosus (PDA) “machine like” decreases and P2 can disappear with only A2
Diastolic sound Softer S3 after S2, louder S4 before heard. A LBBB causes the RV to contract and
S1 closes the PV first. At expiration, the sounds will
Second heart Normal splits with inspiration due to be split. With inspiration, the P2 is delayed and
sound and temporary delay P2 closure
respiration Paradoxical splits in expiration due merges with the A2 component and thus no lon-
A2-P2 to LBBB and delayed A2 closure ger split with inspiration. This is paradoxical
interaction Fixed split and independent of splitting. If the pulmonary blood flow or pressure
respiration due to fixed delay of P2 is chronically elevated, the P2 component is per-
closure from pulmonary
hypertension manently delayed, or fixed, in the cardiac cycle.
Pericardial Rarely heard and commonly has a This is a common finding in ASD or pulmonary
friction rub systolic component sounding like hypertension.
velcro™ Since the QRS on the EKG is ventricular sys-
Right-sided All increase in intensity with
tole, the first heart sound occurs shortly after the
murmurs PS, PI, inspiration
TR QRS, while the diastolic second sound occurs
during ventricular repolarization and after the T
wave (see Fig. 1.8).
After the ventricle begins to relax, it causes A fourth heart sound (S4) is usually located
negative pressure, opening the AV valves, closing near the heart’s apex over the mitral area. S4 is
the pulmonic and aortic (semilunar) valves, and relatively short in duration and may occur only
making the second heart sound (S2). This relax- intermittently. It commonly sounds like a split S1
ation is ventricular diastole and all sounds after but is located at the apex, away from the atrioven-
S2 are diastolic. Incompetence of the semilunar tricular valves. It has a lower pitch than S1 and is
valves will cause flow backward into the ventri- best appreciated with the bell. S4 associated with
cles immediately following S2 causing a short left atrial systole and is caused by blood entering
diastolic murmur. Diastolic atrioventricular mur- a left ventricle already having elevated end dia-
murs are rare and out of the scope of this stolic and volume. Therefore, it is appreciated
discussion. prior to S1 and within the PR interval. It is associ-
Murmurs should be described by the terms ated with hypertensive cardiac disease and may
included in Table 1.1 and should be recorded in be intermittent depending on the afterload state
the medical record as such. These include timing, of the patient.
pitch, radiation, location, duration, quality, and A sequence of S1, S2, S3 is referred to as a ven-
intensity. Diastolic murmurs are graded on a tricular gallop. The S3 is heard shortly after S2 and
scale of 1–4 and systolic murmurs on a scale 1–6. before the P wave which is during the rapid and
Grade 1 is barely audible, grade 2 is louder, grade passive filling phase of the ventricles. It is softer
3 is loud but no thrill is present. Grade 4 is loud in intensity and can be intermittently present and
with an associated thrill and grade 5 has a thrill best heard with the bell. This is associated with
and can be heard with the stethoscope partially ventricular volume and pressure overload. A
off the chest. Grade 6 is the loudest, with a thrill right-sided S3 appears and varies with inspiration
and heard with the stethoscope completely off the due to isolated RV overload as seen in pulmonary
chest. HTN and pulmonary embolus (PE). This is best
Remember, normal inspiration causes an herd in the epigastric region (see Chap. 22). Left-
increase in the venous return to the right side of sided S3 does not vary with respiration and is
the heart. This increase in volume and flow associated with HFrEF (see Chap. 20).
1 Cardiac Anatomy, Physiology, and Exam 11

Fig. 1.8 Heart sounds in relation to EKG. Adapted from: 10: 1–4511–8999-0, ISBN-13: 978–1–4511-8999-5.
Jessica Shank Coviello DNP, APRN, ANP-BC, ed. 2014. STAT!Ref Online Electronic Medical Library. https://
Auscultation Skills: Breath & Heart Sounds - 5th Ed. online.statref.com/document/-GdzwbJZ8Qx3IotUtwjgnD
Philadelphia, PA. Lippincott Williams & Wilkins. ISBN-

Bruit: chronic arterial insufficiency and specific arterial

Blood flow within a vessel that is obstructed examination are discussed in Chap. 27. The
creates a sound due to the higher velocity and tur- pulses can be described as bounding in hyperdy-
bulence created by the obstruction. It is like namic states or in clinical presentation with pro-
obstructing the flow at the end of a garden hose. longed runoff due to low afterload (see Chap.
The sound is higher pitched and radiated toward 16).
the direction of flow. It is not a murmur since this Peripheral Edema:
examination is occurring in the neck, legs, or This is displacement of serous fluids outside
abdominal location. It is systolic in nature. the vascular space into the interstitial tissues. It is
Rarely, diastolic or continuous sounds can be characterized based on the severity when
heard. When listening to the neck vessels, the depressed on a scale from 1 to 4. Commonly seen
bruit must be distinguished from aortic stenosis in the legs but can progress in some disease states
(AS) since this murmur will often radiate to the like Cor pulmonale (see Chap. 22). If it is present
carotid arteries (see Chaps. 16 and 26). diffusely throughout the body of the patient, it is
called anasarca.

Pulse Assessment
References
A scale from 0 to 4 is utilized. No palpable pulse
is 0/4 with normal being 4/4. Commonly, the 1. Sadler TW. Langman’s medical embryology. 14th ed.
Philadelphia: Wolters Kluwer; 2019.
extremities are evaluated in assessment for 2. DiFrancesco D. The role of the funny current in pace-
peripheral arterial disease (PAD). Signs of maker activity. Circ Res. 2010;106:434–46.
12 R. Musialowski and K. Allshouse

3. Hilgemann DW. Control of cardiac contraction by 6. Zipes DP, Libby P, Bonow RO, Mann DL, Tomaselli
sodium: Promises, reckonings, and new beginnings. GF, Braunwald E, editors. Braunwald’s heart disease:
Cell Calcium. 2020;85:102129. a textbook of cardiovascular medicine, Single Volume.
4. Chien KR, Ross J Jr, Hoshijima M. Calcium and hert 11th ed. Philadelphia, PA: Elsevier; 2019.
failure: the cycle game. Nat Med. 2003;9:508–9. 7. Coviello JS, editor. Auscultation skills: breath & heart
5. Josephson’s Clinical Cardiac Electrophysiology: sounds. 5th ed. Philadelphia, PA: Lippincott Williams
Techniques and Interpretations 6th Edition by Dr. & Wilkins; 2014.
David Callans. Publisher, LWW.
Basic Hemodynamics
2
Courtney Bennett and Amanda Solberg

Cardiac Cycle the cardiac output divided by body surface area

(L/min/M sq). This is a standardization tool used
The cardiac cycle is divided into two phases: sys- especially in the management of cardiogenic
tole and diastole (Fig. 2.1). The Wiggers diagram shock and transplantation.
demonstrates the pressure and volume changes The ejection fraction (EF) is the proportion of
throughout the cardiac cycle and how these end-diastolic volume that is ejected during each
changes correlate with the ECG and cardiac aus- systolic contraction and is commonly used as a
cultation (S1-S4). noninvasive assessment of stroke volume.
Systole occurs when the AV valves close (S1) Afterload, or the pressure the ventricle pumps
and the ventricles begin to contract (see Chap. 1). against, can affect stroke volume. Systemic vas-
During systole, ventricular pressure increases cular resistance (SVR) impacts the left ventricle
through isovolumetric contraction and rapid ejec- while pulmonary vascular resistance (PVR)
tion, and then begins to fall during isovolumetric impacts the right. These pressures are calculated
relaxation. The onset of systole correlates with using the mean arterial pressure minus the CVP
the R-wave on the ECG. Blood volume is ejected or mean pulmonary artery pressure minus the
through the pulmonic and aortic valves (some- PCWP divided by the CO. These measurements
times referred to as semilunar valves) into the and calculations are obtained from a right heart
systemic and pulmonary vasculature. Stroke vol- catheterization or pulmonary artery catheter
ume (SV) is the amount of blood pumped out of (Swan-Ganz) catheter placement. Normal hemo-
the ventricle during each systolic contraction. A dynamic values are listed in Table 2.1.
normal stroke volume is 70–80 mL. The volume CO ( L / min ) = SV × HR
of blood remaining in the ventricular chamber
after ejection is called the end systolic volume. MAP − CVP
SVR ( Wood U ) =
The cardiac output (CO) is the SV times the CO
heart rate (HR). CO is the volume of blood
mPAP − PCWP
pumped by both ventricles per unit of time. In a PVR ( Wood U ) =
normal resting heart, this would be approxi- CO
mately 5–6 L per minute. Cardiac index (CI) is SV
EF ( % ) = ×100
EDV
C. Bennett · A. Solberg (*)
Mayo Clinic, Rochester, MN, USA Diastole occurs when the ventricles relax and
e-mail: [email protected]; pressure within the ventricles decreases. The ini-
[email protected]

© The Author(s), under exclusive license to Springer Nature Switzerland AG 2023 13

Fig. 2.1 Wiggers

diagram showing a
visual representation of
the cardiac cycle
showing heart sounds,
pressure, left ventricular
(LV) volume, and ECG
comparison during.
Permission from http://
creativecommons.org/
licenses/by/4.0/

Table 2.1 Normal hemodynamic values diastolic volume is the amount of blood the ven-
RA pressure 0–8 mmHg tricles can hold at the end of diastole as the AV
PA diastolic 15–30 mmHg valves close (S2). The end diastolic volume of an
PA systolic 4–12 mmHg average adult heart is approximately 130 mL of
PA mean 10–20 mmHg
blood.
PCWP 6–15 mmHg
CO 4–7 L/min
This end-diastolic volume is also known as
CI 2.5–3.6 L/min/m2 preload and is defined as the degree of stretching
SVR 800–1200 dynes/cm5 that occurs in the ventricles at the end of diastole.
SVRI 1970–2390 dynes/cm2/m5 A pulmonary capillary wedge pressure (PCWP)
PVR 0.5–2 Woods units (W.U.) obtained from a pulmonary artery catheter is
SvO2 65–75% used to measure left ventricular end-diastolic
pressure as a marker of left ventricular preload.
End-diastolic volume can also be measured by
tial phase of diastole is passive filling of the ven- 2-D echocardiogram and Doppler echocardiogra-
tricles from the atria after opening of the phy can be used to estimate left ventricular filling
atrioventricular (AV) valves due to ventricular pressures. Central venous pressure (CVP) from a
relaxation. In a normal heart, most ventricular central venous catheter or right atrial pressure
filling occurs during this passive phase of dias- (RAP) from a pulmonary artery catheter are used
tole. Atrial contraction occurs following passive to estimate right ventricular preload in the
ventricular filling and correlates with the P-wave absence of significant tricuspid valve pathology.
on the ECG. This contributes up to 20–30% of Both PCWP and RAP pressure tracings consist
the end diastolic volume of the ventricles. End of positive and negative deflections (Fig. 2.2).
2 Basic Hemodynamics 15

Fig. 2.2 Atrial pressure a v

tracing; a-, c-, and c
v-waves and x- and
y-descent
x y

Fig. 2.3 RA tracing (light blue) and PA tracing (yellow) compared to the ECG and radial arterial tracing (red)

The a-wave follows the P-wave on the ECG and Using these measurements to evaluate patients
correlates with atrial contraction. At the bedside, in real-time can be valuable in the management
the a-wave of the PCWP tracing is slightly of advanced heart failure and cardiogenic shock
delayed when compared to the a-wave seen on as an adjunct to standard care. Figure 2.3 shows
the RA tracing. This is due to the longer fluid the pulmonary artery pressure (PAP) and RAP
filled tubing used while obtaining the PCWP with ECG and arterial line data.
tracing. Pressure falls within the atria as they The Frank-Starling Law represents the rela-
empty into the ventricles and correlates with the tionship between stroke volume and ventricular
x-descent. A c-wave or “bump” can sometimes end-diastolic volume. As the volume of the blood
be appreciated in the right atrium as the tricuspid in the ventricles increases, stroke volume
valve begins to close. This finding is not seen on increases until the volume or myocardial stretch
a PCWP tracing because the signal is diminished exceeds the ability to contract effectively. When
as the pressure is transmitted a further distance cardiac dysfunction occurs, ventricular end-
within the pulmonary artery catheter. The v-wave diastolic volume increases, and stroke volume
correlates with atrial filling during ventricular decreases due to decreased contractility.
systole. The y-descent occurs during early ven- Figure 2.4 shows graphically representation of
tricular diastole after the AV valves open and the relationship of pressure and volume during
atrial pressure begins to decrease. the cardiac cycle.
16 C. Bennett and A. Solberg

Fig. 2.4 Pressure- 140

volume loop of the
cardiac cycle
120

Left Ventricular Pressure (mmHg)

100 Aortic valve closes

80
Aortic valve opens

Stroke Volume
60

20
Mitral valve opens
Mitral valve closes
0
40 50 60 70 80 90 100 110 120 130 140
Left Ventricular Volume (mL)
Part II
Coronary Artery Disease

Amy Winiger George P. Rodgers

Introduction

Atherosclerosis is the development of plaques made up of fatty and pro-

inflammatory material in and on the walls of arteries. This may affect any
arterial bed, but it is especially problematic when it affects the coronary arter-
ies. Coronary atherosclerosis is the number one cause of death in the
USA. There are several risk factors for coronary atherosclerosis. The non-
modifiable risk factors are age, male gender, and family history of premature
coronary artery disease. Premature onset is defined as the onset in a first-
degree relative male before the age of 55, or first-degree relative female
before the age of 65.
There are, however, several modifiable risk factors, which include hyper-
lipidemia, hypertension, diabetes mellitus, metabolic syndrome, cigarette
smoking, obesity, a sedentary lifestyle, and heavy alcohol intake. There are
many laboratory and imaging markers of coronary atherosclerosis, and these
include elevated lipoprotein (a), hyper-homocystinuria, elevated high-
sensitive C-reactive protein, and coronary artery calcification seen on multi-
detector CT.
The current paradigm of atherosclerosis is an injury/inflammation para-
digm. First consider the structure of the artery. The intima (tunica intima) is
one layer of endothelium over the media (tunica media). The media layer
consists of smooth muscle cells. Finally, the adventitia (tunica externa) is the
outermost layer separated from the medial layer by fibrous elastic lamina
(Fig. 1).

A. Winiger
Atrium Health/Sanger Heart and Vascular Institute, Charlotte, NC, USA
e-mail: [email protected]
G. P. Rodgers
Ascension Texas Cardiovascular, Austin, TX, USA
e-mail: [email protected]
18

Fig. 1 Development of atherosclerotic plaque

Coronary Artery Disease
Coronary Artery Disease 19

The development of coronary atherosclerosis begins early in life. Fatty

streaks, which are mainly intracellular lipid accumulation, are the first patho-
logic evidence of atherosclerosis. These occur within the intimal lining of the
aorta and are sometimes evident within the first decade of life. By the third
decade of life, these intracellular lipid accumulations have developed into
small extracellular pools of lipids that are the first evidence of atheromas.
In the fourth decade of life, these emerging atheromas may become hard-
ened and sclerotic with fibrosis, thus referred to as fibroatheroma. These
lesions further transform through increased smooth muscle and collagen
deposition and develop into mature atherosclerotic plaque (Fig. 1). Thus far,
the development of coronary atherosclerosis has been silent; the individual
has no symptoms. However, if the mature plaque becomes very large, it may
obstruct the coronary artery to a degree (>70%) so that flow to the myocar-
dium is reduced during exercise. This would produce myocardial ischemia
and the individual may experience symptoms referred to as stable exertional
angina (Fig. 2).
If an atherosclerotic plaque becomes significantly inflamed, it may exhibit
a thinning of the fibrous cap that covers the extracellular pool of lipids. This
is referred to as a “vulnerable plaque” because if the thinned fibrous cap
becomes unroofed or ruptures, it will expose the lipid pool to the circulating
blood elements. This results in immediate thrombus formation. Thrombus
begets more thrombus such that the lumen of the coronary artery at this site
may become seriously obstructed. This is the underlying pathophysiology of
acute coronary syndrome (Type I MI).
20

ATHEROSCLEROSIS

1. 2. 3. 4. 5.
NORMAL ARTERY ENDOTHELIAL FATTY STREAK STABLE (FIBROUS) UNSTABLE
DISFUNCTION FORMATION PLAQUE FORMATION PLAQUE FORMATION

Fig. 2 Progression of atherosclerosis over time

Coronary Artery Disease
Acute Coronary Syndrome (ACS)
ST Segment Elevation Myocardial
3
Infarction

Amy Winiger and George P. Rodgers

Anatomy and Physiology the faster the heart rate, the higher the oxygen
demand. In addition, an increase in left ventricu-
Coronary arteries supply oxygenated blood to the lar contractility and left ventricular wall stress
myocardium of the heart. They are located on the caused by an elevation in blood pressure increases
outer surface of the heart (epicardial), originating the myocardial demand for more oxygen. This
from the aorta (see Chap. 1). The left main (LM) balance between the oxygen demand of the myo-
coronary artery originates at the left coronary cardium and the ability to supply the oxygen,
cusp and bifurcates into the left anterior descend- through coronary blood flow, will determine
ing, or LAD, and the left circumflex artery whether the downstream myocardium becomes
(LCX). The LAD supplies the left ventricle ante- under-perfused, or ischemic. Different clinical
rior wall, anterior portion of the intraventricular coronary syndromes can be described based on
septum and a portion of the right ventricular wall. the condition of the coronary arteries and hemo-
The diagonal branches arise from the left anterior dynamic requirements.
descending. The circumflex artery supplies the
lateral and posterior regions of the left ventricle
(LV). The obtuse marginal (OM) branches arise Definition of STEMI
from the circumflex artery. The right coronary
artery supplies the right ventricle and the poste- “in the absence of left ventricular (LV) hypertro-
phy or left bundle branch block (LBBB) is defined
rior lateral branch. The right coronary artery
by the European Society of Cardiology/ACC/
(RCA) also supplies the sinoatrial node (SA AHA/World Heart Federation Task Force for the
node) and the atrial ventricular node (AV node) universal definition of Myocardial Infarction as
(see Fig. 3.1). new ST elevation of the J point in at least 2 con-
tiguous leads of >(0.2 mV in men or >1.5 mm
Coronary blood flow occurs during ventricular
(0.15) mV in women in leads V2–V3, and/or of
diastole. The myocardial oxygen requirement is >1 mm (0.1 mV) in other contiguous chest leads,
influenced by the oxygen demand of the tissues: or limb leads” [8, p. e83].

A. Winiger (*) The definition of acute coronary syndrome (ACS)

Atrium Health/Sanger Heart and Vascular Institute, is suspicion or confirmation of acute myocardial
Charlotte, NC, USA ischemia or infarction [1]. There are three types
e-mail: [email protected] of ACS: ST elevation MI (STEMI), non-ST ele-
G. P. Rodgers vation MI (NSTEMI), and unstable angina pecto-
Ascension Texas Cardiovascular, Austin, TX, USA ris (UAP) [1]. The definition of a STEMI is
e-mail: [email protected]

© The Author(s), under exclusive license to Springer Nature Switzerland AG 2023 21

Image by Matthew Allshouse

EKG Location Coronary Distribution

Anterior-V1-4 LAD

Septal-V1-V2 Prox. LAD

Lateral-I, aVL, V5-V6 LCx

Inferior-II, III, aVF RCA (85%) or LCx (15%)

Posteriolateral-V7, V8, V9 RCA or LCx

Right Ventricle-V1, V4R RCA

adapted from Localization of the occluded vessel in acute myocardial infarction.

R. Samir, K. Amr. Published 18 February 2020. Medicine.

Fig. 3.1 EKG localization and related coronary distribution. (Image by Matthew Allshouse)

symptoms of myocardial ischemia with an EKG rapid, focused history should be obtained using
revealing ST elevation with the release of bio- the OLD CARTS format [3]. Ask about the
markers, the result of myocardial injury. patient’s symptoms. These include pain Onset,
As discussed in the introduction, a STEMI Location, Duration (does it wax and wane?),
describes the rupture of the atherosclerotic plaque Character (description of what they feel, “ele-
in a coronary artery due to disruption of the phant on their chest?”, sharp, dull, heavy),
fibrous cap and the lipid core becoming exposed Aggravating/Alleviating Factors (activity, posi-
to the blood stream [2]. This instantly incites tion, medication), Radiation, Timing (when did it
thrombosis, which may completely occlude the start and what were you doing? How long did it
lumen of the artery and stop the blood flow and last?) and Severity (1–10 with 10 being worst
oxygen delivery downstream. This cessation of pain ever felt). OPQRST is an alternative way to
distal blood flow causes muscle cell death, perform rapid questioning regarding symptoms
referred to as myocardial infarction. This is a which includes: Onset, Provoking, Quality,
medical emergency. “Time is muscle” because Radiation, Severity, Timing of the pain (see
with every minute that passes, there is more Chap. 31).
necrosis and progressive permanent injury to the Also, the patient’s chart should be reviewed,
heart muscle. paying special attention to prior coronary artery
bypass surgery or percutaneous revasculariza-
tion (PCI). The provider should attempt to
Evaluation obtain past procedure notes to determine grafts
and/or stenting previously performed. It is
Any encounter with a patient begins with a his- important to note if the patient was fully revas-
tory and physical exam. The initial bedside evalu- cularized. Prior testing should be reviewed
ation should occur very quickly in a patient with including echocardiograms, stress tests, MRI/
suspected ACS. The goal should be to complete CTs, etc. Old EKGs and medications should be
the interview and evaluation within 5 min. A reviewed.
3 Acute Coronary Syndrome (ACS) ST Segment Elevation Myocardial Infarction 23

Symptoms Diagnostics

The patient presenting with STEMI will often A STAT EKG, and labs, including high sensitiv-
display classic signs and symptoms including ity troponin, electrolytes, kidney and liver func-
extreme pressure-like chest discomfort that is tion, CBC, and INR should be performed.
substernal, associated shortness of breath, dia- Troponin elevation is very specific for cardiac
phoresis, and potential nausea/vomiting on pre- cellular death. The levels vary based on which
sentation to the emergency department. type of troponin your facility uses. Any eleva-
Differential diagnosis of severe anterior chest tion above normal is due to cell death. The more
pain may include pericarditis, aortic dissection, elevated, the more muscle necrosed. The tropo-
costochondritis, gastroesophageal reflux, peptic nin levels may not be elevated initially but will
ulcer disease, esophageal spasm, pulmonary elevate over hours to days, and thus should be
embolism, biliary colic, pneumonia, or coronary trended.
vasospasm (Chap. 31). A skillset that is critical to any cardiovascular
practitioner is interpretation of acute coronary
syndrome locations on the electrocardiogram.
Physical Exam Figure 3.1 will assist you with remembering what
each lead of the 12-lead EKG represents. A
Prior to entering the patient’s room, assess: how STEMI is characterized by one or more millime-
does the patient look? Does the patient appear to ters of ST elevation in two or more contiguous
be in pain (clutching his/her chest with Levine’s leads [6]. Contiguous refers to leads that are
sign) [3]? Is the patient diaphoretic, anxious, or assessing a certain territory of the heart. Typically,
nauseous/vomiting [4]? Rapid physical exam the contiguous leads are fed by a single coronary
should be performed including special focus on artery.
heart sounds (are there extra heart sounds indicat- The EKG correlates with the coronary anat-
ing valve dysfunction or heart failure), jugular omy. The anterior precordial leads V2-V4 corre-
venous distention, or rales [5]. While completing spond to the anteroseptal walls of the heart
the rapid physical exam, specific questions supplied by the LAD (Fig. 3.1). In this example,
should tailored to the catheterization lab. These EKG (Fig. 3.2), urgent cardiac catheterization
may include whether the patient is followed by a confirmed type I MI in the LAD distribution
physician for any chronic medical problems such (Fig. 3.3) and primary stenting was completed
as undergoing treatment for cancer. Do they have (Fig. 3.4).
any upcoming surgeries which may influence Limb leads 1 and aVL view the lateral aspect
anticoagulation and antiplatelet decisions? The of the heart. This distribution is often perfused
patient should be asked if they have had any his- by the LCX. The distal anterior precordial leads
tory of bleeding including stroke or GI bleeding, V5 and V6 correspond with the apex and can be
and if so, was this due to dual antiplatelet therapy supplied by the LAD, LCX, or PDA. Notice the
(DAPT)? If there is any question of whether the ST depression of V1-V2 in Fig. 3.5. If these
patient should be taken to the catheterization lab, depressions are seen with STEMI in the inferior
communicate with the interventional cardiolo- leads, this is a posterior extension of the STEMI
gist. It is always better to over communicate and not reciprocal changes. This is large and
rather than under communicate. It may also be high-risk MI and is at risk for decompensation to
necessary to take the lead in the ED to coordinate cardiogenic shock. Figures 3.6 and 3.7 show the
and get the patient to the catheterization lab in an cardiac catheterization films of the left circum-
urgent manner. Do not be afraid to direct the flex occlusion and percutaneous coronary inter-
healthcare team! vention (PCI).
24 A. Winiger and G. P. Rodgers

Fig. 3.2 STEMI in anterior leads V1-V5 with reciprocal changes

Fig. 3.3 Type I MI in LAD Fig. 3.4 LAD after PCI

Limb leads II, III, and aVF are evaluating this vessel arises from the RCA (right domi-
the inferior portion of the heart corresponding nant) with 20% arising from the LCX (left
to the posterior descending artery (PDA). dominant). Type I STEMI of the RCA causes
Vessel dominance is described as the vessel ST segment elevation of these inferior leads
that gives rise to the PDA. In 80% of patients, (Fig. 3.8).
3 Acute Coronary Syndrome (ACS) ST Segment Elevation Myocardial Infarction 25

Fig. 3.5 Inferior and posterolateral STEMI

Fig. 3.6 Left circumflex occlusion

Fig. 3.7 Primary PCI of left circumflex
26 A. Winiger and G. P. Rodgers

Fig. 3.8 STEMI inferior leads

Fig. 3.9 RCA occlusion

Fig. 3.10 RCA post intervention

3 Acute Coronary Syndrome (ACS) ST Segment Elevation Myocardial Infarction 27

Figures 3.9 and 3.10 show the catheterization ies (angiogram). In a STEMI, the angiogram will
films of inferior STEMI. show an abrupt cut-off of the coronary artery or
complete occlusion. The occlusion can be crossed
with a coronary wire and using this wire as a
Imaging/Management monorail, a balloon is placed at the site of the
occlusion and is inflated to open the artery. Next,
Once the diagnosis of STEMI has been con- another balloon with a stent crimped on it is
firmed, the interventional cardiologist should be brought into the coronary artery over the coro-
alerted, and the catheterization laboratory noti- nary wire and expanded into the walls of the
fied. The lab and physician are sometimes acti- artery, stenting open the artery. Unfractionated
vated prior to the patient’s arrival in the ED by heparin is given during the procedure. This is
EMS if symptoms and EKG are consistent with a called primary angioplasty and has been shown
STEMI. It has been found that it is critical to to reduce mortality in STEMI (see images of
open the affected artery and restore blood flow as PCI). PCI requires a skilled interventional cardi-
quickly as possible. Percutaneous coronary inter- ologist and team of catheterization lab staff to
vention (PCI) or coronary balloon angioplasty perform the procedure safely. This is usually per-
and stenting is the most effective way to open an formed at tertiary hospitals.
occluded artery. Timeliness is critically impor- In some settings, PCI is not available, and
tant with “door to balloon time” used as the met- thrombolytic therapy must be used to medically
ric throughout the world. This is the time from open the coronary artery. The choice between
when the patient arrives at the hospital (door PCI or thrombolytic therapy using tissue plas-
time) to when the first inflation of the angioplasty minogen activator (TPA), or TNK, has been
balloon occurs (balloon time). The goal of the carefully studied. In several head-to-head trials,
“door to balloon time” is to open the artery within PCI was shown to be superior to thrombolytics.
90 min. This is derived from an important obser- However, thrombolysis may be more practical in
vational study showing that the best results with rural settings where PCI is not universally avail-
the lowest mortality rates for STEMIs occur in able (greater than 2 h away for primary PCI).
patients with a door to balloon time of less than After PCI, medical therapy is essential. Dual
90 min [7]. Nationally, this is the target for any anti-platelet therapy is essential for reducing
STEMI. After 12 h of total occlusion time of a thrombosis within the stented artery. Typically,
coronary artery, the myocardial infarction is the patient is loaded with antiplatelet medication,
complete and there is little tissue left to salvage, which includes a P2Y12 inhibitor (clopidogrel,
and late revascularization may be dangerous prasugrel, or ticagrelor) as well as low dose aspi-
leading to complications of the STEMI rin. This dual antiplatelet therapy (DAPT) will be
(Table 3.2). continued for 12 months. High-potency statins
A cardiac catheterization involves bringing (Atorvastatin 40–80 mg daily or Rosuvastatin
the patient to the catheterization laboratory. 20–40 mg daily) and beta blockers are prescribed
Conscious sedation may be administered as per in the post STEMI setting according to the guide-
physician preference. Arterial access sites are lines. If a patient has a reduced ejection fraction
prepped (radial vs. femoral artery). The interven- (EF), LVEF less than 50 percent, typically an
tional cardiologist accesses the artery with a nee- angiotensin converting enzyme inhibitor (ACE
dle, and a sheath is placed in the artery. Since the inhibitor) or angiotensin receptor blocker (ARB)
complication rate of femoral access is higher, is added to the regimen. If the LVEF is less than
radial artery access is preferred. A catheter over a 40 percent, Entresto (angiotensin receptor
guidewire is advanced to where the coronary blocker and neprilysin inhibitor (ARNI), ACE
arteries originate off the aorta. Contrast dye is inhibitor or an ARB is used. In addition,
injected into the coronary arteries while fluoros- Spironolactone, a mineral corticoid receptor
copy (x-ray) is used to take pictures of the arter- antagonist (MRA) might be added to the regi-
28 A. Winiger and G. P. Rodgers

Table 3.1 Complication of cardiac catheterization and Table 3.2 Complications of STEMI
PCI
Cardiogenic Shock Arrhythmia (VT, Torsade’s)
Hematoma at arteriotomy Bleeding: GI bleeding, Ventricular septal Papillary muscle rupture and
site intracranial hemorrhage defect acute mitral regurgitation
Pseudoaneurysm CVA/TIA Ventricular free wall Apical ventricular thrombus
Retroperitoneal hematoma Local nerve injury at rupture and embolization
arteriotomy site Ischemic Ventricular aneurysm
Vascular compromise distal Embolization cardiomyopathy
to arteriotomy atheromatous material Pericarditis (Dressler’s AV node injury and heart
Complications of closure syndrome) block
device-infection

men. All have been shown to reduce mortality deployment of a vascular access occlusion
and reduce hospital readmissions in STEMI device at the end of the PCI. Urgent Vascular
patients with severe depression of LV systolic Surgery consultation is needed. Finally, nerve
function (LVEF <40%) [8]. injury may occur following PCI. Less common
It is essential that the patient is closely moni- complications may include GI bleeding evi-
tored for potential complications post PCI. denced by a drop in Hgb with hematemesis or
Complications of cardiac catheterization can melena, or intracranial hemorrhage diagnosed
include peri-procedural bleeding which is the with head CT after change in neurologic status
most frequent complication of PCI and associ- is observed due to anticoagulation therapy dur-
ated with poor clinical outcomes (Table 3.1) [9]. ing the PCI. The APP should evaluate for hema-
Age, kidney function, and cardiogenic shock toma or pain at the access site, decreased distal
increase risk for bleeding complications [10, pulses to the access site, abdominal or back
11]. Use of multiple antithrombotic and antico- pain, if femoral access is used [16]. Vitals must
agulants increase the incidence of periproce- be monitored looking for tachypnea, tachycar-
dural bleeding. Women have an increased risk dia which results from increased oxygen demand
of bleeding complications due to the smaller in the setting of acute blood loss. The patient
size of the femoral artery [12, 13, 14]. Obesity is may also appear pale, cold, and clammy if they
also a higher risk due to decreased ability to rec- are losing blood and hemorrhagic shock is
ognize bleeding. Hematomas at the arteriotomy developing. Rapid and direct communication
site may form. The patient may develop a pseu- with the interventionalist and vascular surgeon
doaneurysm if the site heals inappropriately. is essential if bleeding is suspected.
The pseudoaneurysm is diagnosed with ultra- STEMI complications may be significant
sound (US) and may require thrombin injection (Table 3.2). The first is impairment of LV func-
to manage this complication. Retroperitoneal tion which may be transient or permanent. This
hematoma is a potentially life-threatening com- occurs due to ischemia or infarction of the mus-
plication where bleeding occurs in the retroperi- cle tissue of the ventricle. Transmural tissue
toneal space. Acute lower abdominal pain after necrosis complications may present 3–5 days
femoral access requires consideration for retro- after the myocardial infarction, especially in situ-
peritoneal bleeding, and this is diagnosed with ations where the patient did not have the benefit
CT scan of the abdomen [15]. Vascular compro- of early PCI or thrombotic therapy. This necrosis
mise distal to the arterial access may occur, can result in papillary muscle infarction, result-
especially in patients who already have a large ing in severe mitral regurgitation due to a flail
amount of peripheral vascular disease. This mitral valve leaflet. This event may lead to flash
complication would be seen as loss of distal pulmonary edema due to acute severe mitral
pulses, pain, and pallor and may occur after regurgitation. If the necrosis occurs within the
3 Acute Coronary Syndrome (ACS) ST Segment Elevation Myocardial Infarction 29

LV septum, there can be ventricular septal wall Clinical Pearls

rupture resulting in a VSD and heart failure • Family history of premature CAD is male <55
symptoms with a new loud murmur. Ischemic or first-degree relative women female <65.
VSD is a surgical emergency. A free wall rupture • Time is muscle: the longer an area is ischemic,
may result which is usually fatal. Occasionally, the more muscle dies.
blood will fill the pericardium resulting in tam- • It is critical to know if an AMI patient had
ponade without death and is a surgical emer- prior CABG or stents and the location of
gency. A rupture may cause a pseudoaneurysm, these.
and the patient is fortunate to have survived. • Goal door to balloon time is <90 min!!
Severe damage to the heart muscle may result in • Review any old EKGs if possible. Pay particu-
a permanent reduction in LV function, called lar attention to previous LVH with strain, left
ischemic cardiomyopathy. If the infarct is local- bundle branch blocks, or Q-waves.
ized to the apex, the patient may develop an LV • Quickly assess patients’ history of bleeding
aneurysm which may cause ventricular arrhyth- (GIB or head bleed) and history of prior TIA
mias. Many of these complications require surgi- or CVA to guide management with
cal intervention. antiplatelets.
Another significant complication from acute • Remember to consider alternative causes for
MI is tachyarrhythmia and bradyarrhythmia. See ST elevations, particularly if the clinic picture
Part III for arrhythmia details. Ventricular tachy- is not consistent with ST-elevation MI, and if
cardia, and ventricular fibrillation may result indicated rule out dissection or obtain head
from acute ischemia and may cause sudden car- CT prior to cath lab (aortic dissection, cocaine
diac death (SCD) early in STEMI. induced vasospasm, pulmonary embolism,
subarachnoid hemorrhage, etc.).
• Patients treated with 324 mg aspirin, 80 mg
Follow-Up atorvastatin, 4000 U IV heparin prior to trans-
fer to PCI facility. Loading with Plavix per
Post MI, the patient is often admitted to the car- PCI center protocol. Caution with nitroglyc-
diac ICU for monitoring to include the above erin in RCA infarct.
stated complications. An echocardiogram will • When discussing patient’s pertinent medical
likely be completed to evaluate the heart function history with referring provider, inquire
and valves. The patient will be on continuous about any significant comorbidities that
telemetry monitoring for arrhythmias. patient is currently being treated for. If the
Assessment for post procedural complications is patient is being treated for cancer, review
very important in the first 24 h after STEMI their notes for treatment plan and prognosis.
presentation. If possible, talk to the provider directly.
All patients that have suffered acute coronary Overall prognosis can help guide clinical
syndrome, and especially STEMI have a class 1 decision making.
indication for cardiac rehab. This is a supervised • Obtain patient’s EMR and date of birth. If
program that is three 1-hour sessions per week time allows, review previous medical records,
for 12 weeks. The intradisciplinary healthcare including if patient has previous cardiac his-
team of RNs, exercise physiologists, and dieti- tory, and any previous cardiac imaging.
cians educate the patient on their medications, Review of patient’s labs—particularly creati-
exercise regimen, and Mediterranean diet. The nine prior to taking to cath lab.
patients also meet others who have coronary • Standard guideline directed medical therapy
artery disease; they form a support system for post intervention includes DAPT (unless
each other. patient on systemic OAC), high dose statin
30 A. Winiger and G. P. Rodgers

therapy, beta-blocker, and when indicated ACE/ tion myocardial infarction. J Am Coll Cardiol.
2006;47(6):2180–6.
ARB/ARNI when LVEF <40% or anterior MI. 8. O’Gara PT, et al. 2013 AACF/AHA guideline for the
• If patient is on novel oral anticoagulation management of ST-elevation myocardial infarction. J
(NOAC), ask rationale for treatment plan. If Am Coll Cardiol. 2013;61(4):e78–e140.
patient is on NOAC, provide detailed docu- 9. Ferrante et al. (2016). Radial versus femoral access for
coronary interventions across the entire spectrum of
mentation and plan of care for anticoagulation patients with coronary artery disease: a meta-analysis
going forward. For example, DAPT therapy of randomized trials. JACC Cardiovasc Interv, 9(14),
for 1 month, in addition to NOAC, then dis- 1419–1434.
continue aspirin. 10. Chhatriwalla AK, et al. Association between bleed-
ing events and in-hospital mortality after percu-
• Arrange follow-up appointments prior to dis- taneous coronary intervention. J Am Med Assoc.
charge. Include patient in discussion, they are 2013;3903(10):1022–9.
more likely to follow up if office is closer to 11. Kubler P, et al. In patients undergoing percutaneous
their home. Prescribe enough refills for anti- coronary intervention with rotational atherectomy
radial access is safer and as efficient as femoral
platelet medication for 1 year. access. J Interv Cardiol. 2018;31:471–7.
12. Daughtery SL, et al. Patterns of use and comparative
effectiveness of bleeding avoidance strategies in men
and women following percutaneous coronary inter-
ventions. J Am Coll Cardiol. 2013;61(20):2070–8.
References 13. Kwok CS, et al. Effect of access site, gender, and
indication on clinical outcomes after percutane-
1. Kumar V, et al. Robbins and Cotran pathologic basis ous coronary intervention: insights from the British
of disease. 9th ed. Philadelphia, PA: Elsevier. Cardiovascular Intervention Society. Am Heart J.
2. DeLemos J, Omland T. Chronic coronary artery dis- 2015;170(1):164–172.e5.
ease. A companion to Braunwald’s heart disease. 14. Ndrepepa G, et al. Bleeding after percutaneous inter-
Philadelphia, PA: Elsevier; 2018. vention in women and men matched for age, body
3. Lilly LS. Pathophysiology of heart disease. 5th ed. mass index, and type of antithrombic therapy. Am
Wolters Kluwer; 2021. Heart J. 2013;166(3):534–40.
4. Benjamin IJ, et al. Andreoli and Carpenter’s Cecil 15. Sorajja P, Holmes DR. 2021. Periprocedural bleeding
essentials of medicine. 9th ed. Philadelphia, PA: in patients undergoing percutaneous coronary inter-
Elsevier. vention. Up to Date.
5. Schiffman FJ, Wing EJ. Cecil essentials of medicine. 16. Rodgers GP, et al. 2020 ACC clinical competencies
10th ed. Elsevier; 2022. for nurse practitioners and physician assistants in
6. Bielinsky J. 2022. Contiguous leads and the EKG. adult cardiovascular medicine: a report of the ACC
https://cme4life.com/acute-c are-c me/contiguous- Competency Management Committee. J Am Coll
leads-ekg/. Cardiol. 2020;2020(75):2483–517.
7. McNamara RL, et al. Effect of door-to-balloon time
on mortality in patients with ST segment eleva-
ACS Non-ST Elevation Myocardial
Infarction (NSTEMI)
4
Michelle Ross and John Cedarholm

Introduction vated troponin occurring secondary to plaque rup-

ture or erosion is considered a Type I MI (this
The term acute coronary syndrome (ACS) refers includes STEMI and NSTEMI). Myocardial injury
to ST elevation MI (STEMI), NSTEMI, and occurring due to acute oxygen supply and demand
unstable angina (UA.) STEMI and NSTEMI are mismatch, without plaque rupture, is defined as a
caused by acute disruption of a coronary plaque Type II MI. In this case, myocardial cell death
resulting in partial or complete obstruction of occurs because of the inability to meet the oxygen
flow through a coronary artery by a superimposed demand of the tissue or in the presence of profound
thrombus. The diminished blood flow and reduc- metabolic derangement. The patient may have chest
tion in oxygen supply results in ischemia and pain, ECG changes with or without the presence of
ultimate infarct of myocardium. This usually CAD. Examples can be seen in patients presenting
causes symptoms of angina at rest (unstable with a COPD exacerbation, rapid atrial fibrillation,
angina), may cause ECG changes, and results in severe anemia, along with many other presentations
elevated troponins. Unstable angina without (see Table 4.1). It is very important to make this dis-
infarction may have a similar presentation to tinction as the mortality rate of type II MI is higher
NSTEMI, but without a troponin release. than type I and type II may not require invasive
evaluation [1] Treatment of the underlying cause of
the Type II MI is the best treatment option, not an
ype I and Type II Myocardial
T invasive evaluation or anticoagulation.
Infarction
Table 4.1 Etiologies of myocardial cell death in Type II
MI
As stated in the Chap. 3, Myocardial infarction can
CKD/ESRD
be classified as type I and type II. This is important
Heart failure (acute and/or chronic)
distinction for patient care and prognosis. An ele- Sepsis/critical illness
Pulmonary embolism
M. Ross (*) Myocarditis
Atrium Health/Sanger Heart & Vascular Institute, Stress cardiomyopathy (Takotsubo)
Charlotte, NC, USA Cardiotoxic drugs
e-mail: [email protected] CPR/defibrillator shocks
Chest trauma (cardiac contusion)
J. Cedarholm
Stroke
Lake Norman Regional Medical Center,
Mooresville, NC, USA Anemia
e-mail: [email protected]

© The Author(s), under exclusive license to Springer Nature Switzerland AG 2023 31

Assessment and Diagnosis Table 4.2 Key historical questions summarized

1. Symptoms
History (a) What made you decide to come to be evaluated
today? What changed?
(b) What were you doing when these symptoms
A good history and physical exam will often help started?
to expedite therapy and avoid unnecessary test- (c) Is it the first time you have had them? Have they
ing. Below are the standard questions rapid changed?
assessment questions (see Chaps. 3 and 31). (d) What makes them better or worse? Deep
inspiration, being recumbent, getting anxious/
upset, stretching, or palpation?
• Duration—Onset of symptoms. (e) Are there associated symptoms? Nausea,
• Location—radiation. vomiting, dizziness, palpitations, dyspnea?
• Have these symptoms occurred before? 2. Do you have any history of CAD, MI, previous
• Have the symptoms changed in frequency, stent, or CABG?
duration, associated symptoms, or ease of (a) If so, when was this? Obtain reports of
catheterization and/or specifics of how many
onset? bypass grafts are present and where they are
• Aggravating or alleviating factors. located
• Recent changes in medications. 3. Does this feel like what you experienced prior to
any previous coronary event?
4. Have you had to adjust your daily activities to
Patients that present with possible ACS should
accommodate your symptoms?
all undergo rapid assessment (as mentioned in the 5. Any recent medication changes? (Did an
STEMI chapter) to determine hemodynamic sta- antianginal therapy get stopped? Did the patient
bility, evaluate for shock, critical arrhythmia, or stop any medications on their own?)
other etiology that would require emergent stabi- 6. HTN, dyslipidemia, diabetes, tobacco abuse (when
and how long), family history of early onset CAD?
lization or additional emergent treatment.
(a) Often patients will say they have no medical
Patients can have a myriad of symptoms which issues. Remember that this may simply be
may or may not include actual chest pain. Many because they haven’t seen a physician in years
patients struggle to describe their symptoms (see 7. Any recent illnesses?
Table 4.2). In many cases, the patient has been 8. Hx of CVA, GIB, contraindications for DAPT/
heparin?
having episodes of angina or an anginal equiva-
9. Recent changes in daily activities (eating out,
lent for days or even weeks. It is important to ask exercise, travel, illness, missing medications)
the patient about a broad range of symptoms that
typically present with activity and resolve upon
rest. It is common for a patient to say that they Patients who have a history of coronary dis-
have no “pain.” Asking the patient if they have ease or myocardial infarction may have a clear
chest pain, pressure, fullness, or tightness will description of their prior symptoms. Always ask
often help the patient describe their angina. if their current discomfort is like what they expe-
Offering different locations such as the chest, rienced with their previous coronary event or
either shoulder, under shoulder blades, upper intervention. Patients presenting with UA or
back, neck, or jaw is also important to elucidate NSTEMI may have had atypical anginal symp-
how they feel their pain. Patients often think that toms, such as believing they were having reflux.
if they do not have an elephant sitting on their left A timeline of change in symptoms is important.
chest, a cardiac etiology is unlikely. Additionally, Is the discomfort different from a month ago? Is
increased dyspnea with exertion and/or easy fati- it happening more frequently over the last few
gability may be present. In some patients, such as days or weeks? Has it started occurring at rest or
women or those who have diabetes, dyspnea may woken the patient from sleep? Did it begin com-
be the only presenting symptom. ing and going over the last couple days?
4 ACS Non-ST Elevation Myocardial Infarction (NSTEMI) 33

Physical Exam (Fig. 4.2). These changes are present within

adjacent leads and correspond to a coronary
The physical exam on a patient with an NSTEMI artery vascular distribution. Arrhythmias includ-
may be normal if they have already received ther- ing Torsades may suggest ischemia, especially if
apy for their anginal symptoms. Often, the patient there are other ischemic changes noted (Fig. 4.2).
has received aspirin and nitroglycerin in tablet or Arrhythmias and ischemic ST and T-wave
paste form. Findings may be much more subtle changes demonstrate a high-risk EKG, and
than in patients presenting with a urgent management is indicated. The EKG
STEMI. However, in the patient stating that they changes may change when anginal symptoms
no longer have chest pain or dyspnea, physical are treated or resolve. The ST and T waves may
exam is still important for your differential not completely normalize but have persistent
diagnosis. Physical exam findings may be corre- abnormalities. Wellen’s sign or syndrome is
lated with the elevated troponin, adding to likeli- biphasic T wave segments that persist after the
hood of the diagnosis. This includes findings resolution of anginal symptoms (see Fig. 4.3). It
such as significant tachycardia, new arrythmia, is suggestive that the artery was occluded with
significant elevation above their baseline blood spontaneous resolution within the past 24 h. This
pressure or significant anemia. is a high-risk EKG finding and suggestive of
unstable plaque and repeat occlusion is proba-
ble. It is important to compare the current EKG
Diagnostics with any prior ECGs available to assess for an
acute change. Patients may have very abnormal
EKG—An EKG should be obtained for patients EKG findings; however, they may be unchanged
with angina or possible anginal equivalent. ACS/ from historical EKGs. If the EKG is normal,
NSTEMI may present with new T wave inver- serial EKGs should be obtained to evaluate for
sion (Fig. 4.1), ST-segment depression >1 mm developing ischemic changes [1]. Occasionally,
which may be horizontal or down sloping an EKG that is abnormal at baseline may appear

Fig. 4.1 Isolated T wave inversion in a vascular distribution

34 M. Ross and J. Cedarholm

Fig. 4.2 High risk ischemic EKG with Torsades and ST depression

Fig. 4.3 Wellens Sign with biphasic T wave seen in leads V2-V5

“more normal” with an ACS. This is called elevate troponin levels. These arrhythmias with
pseudo normalization. A normal ECG does NOT RVR may also cause a type II MI in a patient with
rule out an ACS/NSTEMI. CAD due to supply-demand mismatch. Both
NSTEMI patients may also be found to have arrythmias and critical laboratory results should
arrythmias. Atrial fibrillation or flutter with rapid be addressed (severe anemia) before directing the
ventricular response (RVR) can result from patient for further cardiac testing or invasive
NSTEMI and cause further chest discomfort and management.
4 ACS Non-ST Elevation Myocardial Infarction (NSTEMI) 35

Troponin Trending ering but has a pleiotropic effect of decreasing

the inflammatory response within the endothe-
The trending of troponin value is a key part of the lium. This also aids in protecting the cardiac
initial assessment. Early detection of an elevated endothelium during coronary intervention. Statin
level allows for a rapid diagnosis of a possible is given regardless of the patient being on daily
ACS. Troponin should be measured on presenta- statin therapy. Patients who have not tolerated
tion and again between 3–6 h later. If using a high statin therapy in the past (not a true allergy) can
sensitivity troponin, visible upward trends may generally tolerate the one-time dose of pre-
be seen in as early as 2 h. It is not uncommon for procedural statin. This should be evaluated on a
the initial troponin in the ACS patient to be nega- case-by-case basis. If the patient has a true allergy
tive, so trending troponin is important for deter- to aspirin, the case should be discussed with your
mining NSTEMI (Type I MI). attending physician prior to administration
The timing of symptom onset and the initial (Table 4.3) [2].
troponin result can be helpful with your differen- Once a Type I MI NSTEMI is diagnosed, a
tial. If the patient is unable to say what time the heparin bolus should be administered and ACS-
symptoms began, the time of ER presentation dose heparin drip initiated, unless there is a con-
should be used. High sensitivity troponin (hsT) traindication. There is no indication for
elevation is not diagnostic for an ACS. High sen- anticoagulation for a type II MI. It is reasonable
sitivity troponins may stay relatively low and to initiate full anticoagulation on presentation if
may remain level over multiple samples which the type of MI is unclear. Once type I has been
can be indicative of a diagnosis other than excluded, early discontinuance is recommended
NSTEMI, like type II MI. However, a troponin to avoid bleeding complications. A risk assess-
level trending upward or significantly elevated on ment must be completed before administering
presentation is suspicious of a NSTEMI. The heparin. Has the patient had any recent surgery,
clinical presentation is very important to guide head injury, CVA, or another comorbidity that
decision making. It is essential to determine if the may increase the risk of bleeding? Is the patient
presentation is type I or type II MI since the man- on an anticoagulant, if so, what for, when was the
agement and prognosis are very different. last dose? Chronic anticoagulation will likely not
contraindicate the use of heparin in the setting of
ACS but may affect the timing of cardiac cathe-
Management terization and short-term anticoagulation
therapy.
Initial Medical Therapy Enoxaparin verses unfractionated heparin:
and Stabilization Though full dose subcutaneous enoxaparin at
1 mg/kg bid has been shown to improve out-
STEMI and the need for immediate primary PCI comes in ACS, IV unfractionated heparin is the
must be excluded first (see Chap. 3). Once preferred anticoagulant during acute presenta-
STEMI is excluded, stabilization of the patient tion. In the catheterization laboratory, activated
and reduction of ongoing ischemia is essential.
If ACS (type I MI) is suspected, four 81 mg
Table 4.3 ACS/NSTEMI initial treatment guidelines
aspirin should be chewed upon arrival, provided
there are no strong contraindications. These are Four 81 mg Aspirin—chewed
Heparin bolus
generally given by medics or the ER prior to car-
Initiation of ACS dose heparin drip
diology evaluation. Aspirin decreases platelet Atorvastatin 80 mg PO
activation. The 4 × 81 mg aspirin should be given Documenting all the above, including what was given
even if the patient takes 81 mg aspirin daily. The by medic or ER
patient should also receive Atorvastatin 80 mg. If any of the initial treatments cannot be administered,
Statin therapy is not only beneficial for lipid low- you must document why you could not give them [1]
36 M. Ross and J. Cedarholm

clotting times (ACTs) are used to measure the diagnoses, so that they can participate in their
appropriate dose of IV heparin to prevent coro- care is critical.
nary and stent thrombosis during the procedure
and to guide sheath removal. There is no reliable
method to determine the dose of supplemental Invasive Verses Noninvasive
enoxaparin needed in the catheterization lab. Evaluation
Converting from weight-based enoxaparin to IV
heparin in the catheterization laboratory has been If after a history, examination, ECG and Troponin
shown to significantly increase bleeding risks evaluation, there is a strong suspicion for
associated with the procedure and should be NSTEMI or UA, then an invasive workup (car-
avoided. diac catheterization) should be pursued urgently
Glycoprotein 2B3A Inhibitors (eptifibatide or rather than a noninvasive workup. If the patient is
tirofiban): Historically, these agents were used stabilized without ongoing chest pain or ECG
prior to intervention to stabilize patients with changes, this can often wait up to 24 h.
ACS. However, due to increased bleeding risks, Noninvasive testing when ACS/NSTEMI has
these agents are usually reserved for severe clearly been diagnosed may be contraindicated.
refractory ischemia prior to catheterization or for Timing of invasive strategy becomes a factor
patients who cannot undergo an emergent proce- for those patients who present with significant
dure due to logistics. 2B3AIs are occasionally comorbidities. Patients with heart failure exacer-
started in the catheterization laboratory due to bation, abnormal renal studies, abnormal CBC
significant thrombus burden and may be contin- findings, or chronic anticoagulation are some co-
ued post-catheterization for up to 12 h. morbidities that may delay invasive testing. In
Antiplatelet agent prior to catheterization certain cases, the catheterization lab may not be
(clopidogrel or ticagrelor): This is an area of readily available, due to location or timing of pre-
controversy. ACC guidelines have encouraged sentation. Patients may present with ACS/
preprocedural loading with either ticagrelor or NSTEMI in the middle of the night, over a week-
clopidogrel in patients with clear-cut ACS/ end or to a hospital that has no catheterization
NSTEMI. However, if a patient requires CABG, lab, etc. A thoughtful approach looks at the entire
this process may result in very high bleeding case on order to determine what plan of care is
rates at CABG or a delay in surgery for up to the safest and most appropriate. Criteria for early
5 days due to a required drug to wash out period. invasive strategy are demonstrated in Table 4.4.
Ticagrelor has been shown to have early mor- Delayed invasive strategy, defined as >24 but
tality benefit and is clearly the preferred agent <72 h is recommended for patients with diabetes
over clopidogrel. There are no FDA indications mellitus, renal insufficiency, LVEF <40% or con-
for preprocedural loading of prasugrel in ACS as gestive heart failure, recent PCI, prior CABG,
it has not been evaluated in this setting. Prasugrel post-infarction angina, or GRACE risk score of
should be loaded in the catheterization laboratory >109 and <140 [1].
once PCI is planned. [3]
Once the history, physical exam, and initial
testing are completed, the results should be dis-
Table 4.4 Early invasive strategy <24 h from
cussed with the patient. Treatment options based presentation
on evidence-based guidelines should be dis-
Rise in troponin consistent with type I MI
cussed in shared decision making with the patient Dynamic ST segment and T wave changes
and family or healthcare POA as appropriate. Hemodynamic instability-shock
Keep in mind that while providers may make Electrical instability
these diagnoses and decisions daily, often our Persistent unstable symptoms on optimal medical
patients have never been in this situation. therapy
Educating the patient in the setting of new or old GRACE score > 140
4 ACS Non-ST Elevation Myocardial Infarction (NSTEMI) 37

Cardiac Catheterization (Fig. 4.4) Table 4.5 Risks of cardiac catheterization

• Allergy to contrast
Conscious sedation may be administered as per – Premedication with 40 mg of prednisone the
evening prior and the morning of the procedure,
physician preference in the catheterization labo-
diphenhydramine 50 mg PO or IV 1 h prior to
ratory. Arterial access sites are prepped (radial or procedure
femoral artery). The interventional cardiologist – Emergent management is administration of
accesses the artery with a needle, and a sheath is methylprednisolone 40 mg or hydrocortisone
placed in the artery. Since the complication rate sodium succinate 200 mg IV Q4 hours prior to
procedure and diphenhydramine 50 mg PO or IV
of femoral access is higher, radial artery access is 1 h prior to procedure. (ref)
preferred. Radial artery access has been shown to • Contrast-induced nephropathy
decrease mortality by reducing the risk of bleed- – Risk is 2.5% with Cr < 2 mg/dL, but rises to
ing and vascular complications. A catheter over a 30.6% with Cr > 3.0 mg/dL
guidewire is advanced to where the coronary – Minimizing contrast given and volume expansion
with pre-procedure NS helps to mitigate this risk
arteries originate off the aorta. Contrast dye is
• Vascular complication
injected into the coronary arteries while fluoros- – Pseudoaneurysm
copy (x-ray) is used to take pictures of the arter- – Detected as a pulsatile mass with bruit
ies (angiogram). The individual cardiac arteries – Best diagnosed by arterial US
are injected with contrast dye and visualized by • Bleeding
the interventional cardiologist in real time. Once – Localized large hematoma
the coronary anatomy has been visualized, revas- – Retroperitoneal hemorrhage
• Thromboembolism
cularization may be considered. Commonly, per-
– Distal to access site is cool to the touch, pale in
cutaneous coronary revascularization is color, pulses absent, changes in sensation
performed in the same setting as diagnostic cath- – Emergent vascular surgery consultation
eterization. However, depending on anatomy, • Periprocedural myocardial infarction
medical therapy or CABG may be recommended. – Incidence is greatly influenced by comorbidities
and extent of coronary disease
There are risks to this invasive procedure. Severe
• CVA
risks include death, stroke of type I MI (Table 4.5). – <1% risk
– Secondary to micro embolism post PCI
• Coronary artery perforation
– <1% risk
– A large proportion of these require a surgical
intervention
• Death
– <1% risk in elective PCI [4]

ercutaneous Coronary Intervention

P
(PCI) Figs. 4.5 and 4.6

There are multiple forms of percutaneous cor-

onary intervention (PCI): placement of coronary
stents (bare metal stent—BMS or drug eluting
stent—DES), plain old balloon angioplasty
(POBA), and atherectomy by laser or rotational
device. Not all areas of stenosis are treated by
PCI. The primary goal of the procedure is to treat
the lesion that is causing the ischemia and associ-
Fig. 4.4 Interventional cardiologist performing a cardiac ated symptoms. If coronary intervention is pur-
catheterization in the lab sued in the setting of ACS, complete
38 M. Ross and J. Cedarholm

bleeding complication. Suture-based devices

such as Perclose® may be used to approximate
edges of the arteriotomy. There are metallic clips
such as StarClose® which are also a method to
physically approximate the edges of the arteriot-
omy. Dissolving collagen plugs can be used, such
as Angioseal®. Collagen plugs can often be felt
by the patient and may be a source of concern;
however, the ability to palpate the collagen device
is normal and not an indication for alarm. It will
dissolve over time. The method of closure is
determined in the lab and not usually a primary
Fig. 4.5 Right coronary artery with proximal region of
focus for the advanced care practitioner, how-
stenosis ever, the method of closure used can aid in the
determination of future access if the patient
requires a repeat catheterization.
Post-catheterization procedure protocols are
based on the site accessed, the procedure com-
pleted, and the physician preference. Primarily
this involves rest, stabilization of the access site
with compression. Radial access sites use a band
that goes around the wrist and is inflated with air,
to hold pressure. Increments of air are released
from the band at specified intervals to avoid
bleeding until it can be totally removed. One of
the most immediate and potentially life-
threatening complications is bleeding. The
patient may begin developing a swollen area
Fig. 4.6 Right coronary artery post percutaneous coro- under the access site. This may be very firm to the
nary intervention and stent placement touch and expands suddenly or there may be
bleeding from the site. The most important action
revascularizing of other significant lesions will at this point is to put heavy pressure on the cath-
be considered, either in the same procedure or in eterization incision site manually until an alterna-
a later “staged” setting. PCI for ACS has been tive option is available. Additionally, examination
shown to improve mortality in addition to to assess the limb distal to the arteriotomy is criti-
improving symptoms. cal. Should a distal extremity become pale and
Surgical revascularization or Coronary Artery pulseless, the circulation has been compromised
Bypass Grafting (CABG) will be considered if and limb ischemia occurs. This requires emer-
patient has complex coronary blockages such as gent evaluation by Vascular Surgery to re-
3 vessel CAD in a diabetic, left main disease, or establish circulation. [4–7] Pseudoaneurysms can
complex and diffuse lesions not easily amenable also form and may be found prior to discharge or
to PCI (see Chap. 6). Sometimes lesions are not at follow-up. A pseudoaneurysm is formed when
amenable to either PCI or CABG. Maximal med- blood leaks out into the surrounding tissue of the
ical therapy may be required with the administra- arteriotomy after closure. These can be felt as a
tion of two anti-anginal therapies (see Chap. 5). swollen and often pulsatile enlarged area around
At the end of the PCI, femoral arteriotomy the catheterization access site (radial or femoral
closure may be achieved by various strategies. artery). This requires urgent ultrasound of the
The method of closure does not decrease the risk- area to assess if there is a pseudoaneurysm pres-
4 ACS Non-ST Elevation Myocardial Infarction (NSTEMI) 39

ent. If present and depending on size, some may High dose/high potency statin—atorvastatin
resolve on their own. Others require injection of 40 or 80 mg, rosuvastatin 20 or 40 mg are the rec-
thrombin under ultrasound guidance by interven- ommended statins post ACS. Please see previous
tional radiology. Some may require consultation discussion in this chapter.
from the vascular surgery team. Antiplatelet agents: All patients should be on
DAPT for 1 year post ACS whether they received a
PCI, CABG, or will be treated medically. These
edical Therapy at Discharge
M agents reduce the risk of thrombotic events in coro-
of Patients with ACS nary arteries in Type I MI, with and without a stent
placement. This includes aspirin and one other
Betablockers—should be used in all patients with agent listed below. Ticagrelor or prasugrel are the
ACS at discharge depending on HR and BP. Most preferred agents in patients with ACS. Notably
commonly, this will be metoprolol tartrate 12.5– clopidogrel is the least expensive agent but is also
50 mg bid. Alternatively, metoprolol succinate not as effective in ACS patients. Prasugrel is
can be used once per day at 25–100 mg. Beta generic and generally less expensive but has mul-
blocker should be continued for at least 1 year. tiple contraindications as noted below. Ticagrelor is
During a myocardial infarction, the sympathetic indicated but a high percentage of patients com-
nervous system is stimulated, increasing the plain a sense of breathlessness due its chemical
workload on the heart. This can lead to expansion similarity to adenosine (see Table 4.6). [3]
of the infarcted area and increase risks for arryth-
mias. Betablockers serve to decrease the effect of
Table 4.6 Commonly used antiplatelet agents
the sympathetic nervous systems response to the
infarct. They continue to do this while the heart is P2Y12 receptor inhibitors
Clopidogrel • 300 mg or 600 mg loading dose
healing, post infarct. If a patient has a reduced EF (Plavix) • 75 mg daily
of less than 40%, metoprolol succinate or • 5 days wash out period before a
carvedilol are the preferred betablockers to be surgical procedure
used at discharge, to help prevent ventricular • Rash is likely presentation if patient
has an allergy
remodeling and improve mortality (see Chap. 20).
Prasugrel • 60 mg loading dose
ACEI/ARBs/ARNI—all patients with EF ≤40% (Effient) • 10 mg daily
should also be placed on one of these agents at dis- • 7 days wash out before surgical
charge and titrated up to maximal dose as an outpa- procedure
• Contraindicated in patient with CVA
tient (see Chap. 20). These drugs help improve
or TIA history
cardiac remodeling and decrease afterload. • Contraindicated if weight less than
Aldosterone Antagonists—should be consid- 60 kg or age over 75 years
ered in all patients with EF of ≤40% but can be • NOT indicated for patients being
treated medically for ACS
considered also at first post hospital follow-up
Ticagrelor • 180 mg loading dose
(see Chap. 20). (Brilinta) • 90 mg BID
Aspirin (non-coated) 81 mg per day. 325 mg • 5 days wash out period before
only increases bleeding risk, so 81 mg is the pre- surgical procedure
ferred dose. This is also important for patients on • Dyspneic sensation in some people
deter its use
ticagrelor as high dose aspirin can decrease • Aspirin dose must be only 81 mg
ticagrelor’s efficacy. If the patient has a true aspi- QD if also on Ticagrelor (aspirin
rin allergy, there are aspirin desensitization pro- doses above 100 mg decrease
tocols that can be completed. This may require efficacy of Ticagrelor)
• Some patients, generally older, have
ICU monitoring. This protocol may be completed additional GI upset or generalized
prior to intervention or after but should be evalu- sensations of feeling unwell
ated on a case-by-case basis with your attending • May cause bradyarrhythmia or
physician. [5, 8, 9] pauses in some patients
40 M. Ross and J. Cedarholm

Cardiac Rehabilitation contiguous leads can be indicative of ischemia.

Deep T waves (or biphasic) in V1 and V2 can
These programs are strongly encouraged in all indicate proximal LAD disease.
patients who have been diagnosed with • ASA 324 mg chewed, atorvastatin 80 mg,
ACS. Patients receive initial education while heparin bolus are the initial medications on
inpatient. This is followed by an organized presentation.
exercise program that lasts approximately • Post-catheterization: bleeding at catheteriza-
12 weeks. Patients are monitored with teleme- tion site.
try and vital signs as they resume physical –– hold pressure constant → obtain assistance
activity in cardiac rehab. It also includes educa- from catheterization lab and nursing,
tion consisting of dietary management, stress –– distal pulses, pallor, numbness → emergent
management, and assistance with overall risk vascular surgery eval,
factor modification. Those that participate have –– pulsatile, enlarged catheterization site →
been shown to have reductions in mortality and US for pseudoaneurysm,
reinfarction. –– increased pain on right flank or lower back
after femoral access may indicate possible
retroperitoneal bleed,
Patient Education Prior to Discharge • Antiplatelet dosing:
–– Clopidogrel 75 mg Daily.
For many patients, ACS/CAD is a new diagnosis –– Prasugrel 10 mg daily—NOT for previous
and can be very traumatic, especially to younger CVA patient, <60 kg, or medical manage-
patients. It is important to clarify test results and ment without PCI.
answer any questions. Anxiety and depression –– Ticagrelor 90 mg BID—patients may have
are often present at discharge. Affirmation of feelings of dyspnea or overall general
their fears and reassurance of improvement with weakness (more in elderly).
cardiac rehab is important. Having the patient • High dose statin—Atorvastatin 40 mg–80 mg,
write down questions to bring to their first outpa- Rosuvastatin 20 mg–40 mg.
tient appointment can be very helpful. Discussing • GDMT for Ejection fraction 40% or less in
tobacco cessation plans with patients who smoke addition to ACS management.
should happen prior to discharge as well. The • DAPT × 1 year with statin and ASA therapies
patient is a captive audience and has likely not lifelong.
smoked in about 48 h since admission. Use this • If on anticoagulation for other comorbidity,
opportunity to guide them to cessation. Ideally recommendations to stop aspirin and only use
these patients are discharged with follow-up clopidogrel with the full anticoagulation
within 7–10 days. Early follow-up helps to agent. After 1 year discontinue clopidogrel
address fears, questions, and new concerns. It and initiate aspirin 81 mg in its place.
allows early titration of goal directed medical
therapy or changes in medical therapy due to
intolerance. This helps avoid medical non-
compliance and return ED visits. [4] References

Clinical Pearls 1. Amsterdam E, Wenger N, Brindis R, et al. 2014 AHA/

ACC guideline for the management of patients with
• EKG with new T wave inversion, ST segment non–ST-elevation acute coronary syndromes: a report
horizontal or down sloping depression in two of the American College Of Cardiology/American
4 ACS Non-ST Elevation Myocardial Infarction (NSTEMI) 41

Heart Association task force on practice guide- www.ncbi.nlm.nih.gov/pubmed/22980117. https://

lines. Circulation. 2014;130(25):e344–426. http:// doi.org/10.5539/gjhs.v4n1p65.
ovidsp.ovid.com/ovidweb.cgi?T=JS&NEWS=n&C 6. Chiarito M, Cao D, Nicolas J, et al. Radial versus
SC=Y&PAGE=fulltext&D=ovft&AN=00003017- femoral access for coronary interventions: an updated
201412230-00017. https://doi.org/10.1161/ systematic review and meta-analysis of randomized
CIR.0000000000000134. trials. Catheter Cardiovasc Interv. 2021;97(7):1387–
2. Patti G, Pasceri V, Colonna G, et al. Atorvastatin 96. https://onlinelibrary.wiley.com/doi/abs/10.1002/
pretreatment improves outcomes in patients with ccd.29486. https://doi.org/10.1002/ccd.29486.
acute coronary syndromes undergoing early percu- 7. Levine GN, Bates ER, Blankenship JC, et al.
taneous coronary intervention. J Am Coll Cardiol. 2011 ACCF/AHA/SCAI guideline for percuta-
2007;49(12):1272–8. https://www.clinicalkey.es/ neous coronary intervention. J Am Coll Cardiol.
playcontent/1-s2.0-S0735109707006614. https://doi. 2011;58(24):e44–e122. https://www.clinicalkey.es/
org/10.1016/j.jacc.2007.02.025. playcontent/1-s2.0-S0735109711028762. https://doi.
3. Schüpke S, Neumann F, Menichelli M, et al. org/10.1016/j.jacc.2011.08.007.
Ticagrelor or prasugrel in patients with acute coronary 8. Schwartz GG, Olsson AG, et al. Effects of atorvastatin
syndromes. N Engl J Med. 2019;381(16):1524–34. on early recurrent ischemic events in acute coronary
https://doi.org/10.1056/NEJMoa1908973. syndromes the MIRACL study: a randomized con-
4. Mancini GBJ, Hartigan PM, Shaw LJ, et al. Predicting trolled trial. JAMA. 2001;285(13):1711–8. https://doi.
outcome in the COURAGE trial (clinical outcomes org/10.1001/jama.285.13.1711.
utilizing revascularization and aggressive drug evalu- 9. Pasceri V, Patti G, Nusca A, et al. Randomized
ation): coronary anatomy versus ischemia. JACC trial of atorvastatin for reduction of myocar-
Cardiovasc Interv. 2014;7(2):195–201. https://www. dial damage during coronary intervention: results
ncbi.nlm.nih.gov/pubmed/24440015. https://doi. from the ARMYDA (atorvastatin for reduction of
org/10.1016/j.jcin.2013.10.017. MYocardial damage during angioplasty) study.
5. Tavakol M, Ashraf S, Brener SJ. Risks and compli- Circulation. 2004;110(6):674–8. http://circ.ahajour-
cations of coronary angiography: a comprehensive nals.org/cgi/content/abstract/110/6/674. https://doi.
review. Global. J Health Sci. 2012;4(1):65–93. https:// org/10.1161/01.CIR.0000137828.06205.87.
Outpatient Management
of Coronary Artery Disease
5
Michelle Ross and John Cedarholm

Introduction Assessment and Diagnosis

Patients who have been diagnosed with coronary History obtained for the visit should include ask-
disease and ischemic symptoms will follow-up ing about any recent hospitalizations and a review
with a cardiologist. It is important to know the of the inpatient chart. Medications should be
following to guide further management: (a) Has reviewed carefully. They are often changed at
the patient ever had a coronary intervention or discharge from the hospital and patients are often
surgery? (b) When and what interventions were unclear of the doses. Always encourage a review
done? (c) What are the indications of the cardiac of the medication bottles specifically. Specific
medications? It is important to keep in mind that attention should be paid to antiplatelet therapies,
medications can serve multiple purposes, such as anticoagulants, and lipid medications. Is the
an antihypertensive medication also serving as an patient on guideline-directed therapies? Should
antianginal agent. Medication therapies should they be on dual antiplatelet therapy? Any of their
be used as appropriate to manage angina, heart other cardiac medications changed?
rates, and hypertension. Patients may present for an evaluation of new
The patient’s baseline level of functioning symptoms because a medication was altered by
helps us understand the level of stress they put on another provider. For example, a medication
the heart. Are they always sedentary? Were they being stopped due to hypotension, resulting in a
active and walking miles daily, but now walking change in anti-anginal coverage. Are they using
minimally only a few days a week? The patient SL NTG? How often? More than usual? Asking
needs to be seen as a full picture, not only diag- if the patient has had chest pain, pressure, full-
nostic images, and comorbidities. ness, or any symptoms like their anginal equiva-
lent is important. Inquire about their activities
and any changes in their activity tolerance. Are
their symptoms consistent with what they experi-
enced prior to a previous coronary event/inter-
M. Ross (*)
Atrium Health/Sanger Heart & Vascular Institute, vention? Keep in mind that some patients have
Charlotte, NC, USA only fatigue or dyspnea as a symptom. Table 5.1
e-mail: [email protected] explains the classification of angina. This stan-
J. Cedarholm dardization is important for long-term surveil-
Lake Norman Regional Medical Center, lance to determine a change in characteristic of
Mooresville, NC, USA symptoms.
e-mail: [email protected]

© The Author(s), under exclusive license to Springer Nature Switzerland AG 2023 43

Table 5.1 Classes of angina area of ischemia or stenosis, even if there is no

CLASS 1—angina only present with prolonged or very indication for invasive evaluation. They often
strenuous activity describe feeling as if they are “just waiting to have
CLASS 2—angina only with moderate activity, slightly
a heart attack.” This can cause anxiety levels that
limiting daily activities
CLASS 3—angina with minimal activity, activities of interfere with daily functioning, so discussion of
daily living, moderately limiting why you are doing a test and what you may find
CLASS 4—angina with any activity or at rest, severely should be had before testing. This allows the
limiting [1] patient to be part of shared decision making.

Regular visits should include a full physical Stress Testing in Intermediate-Risk

examination, including weight and height (BMI), Chest Pain
blood pressure, heart rate, and oxygen saturation.
Patients should be encouraged to monitor their Bayes rule postulates that the posttest probability
blood pressure at home, as it may be falsely ele- of CAD is a function of the pretest probability of
vated at a medical office. Frequency of measure- disease. If there is a low probability of CAD, then
ment can be recommended based on the anything abnormal could be a false positive and
individual patient. If medications are being testing is not recommended. Conversely, if there
titrated to a maximum tolerated dose, such as a is a high likelihood of CAD, a negative test would
beta blocker after a myocardial infarction, more not rule out disease [1]. Testing done with inter-
frequent measurements can be obtained. Patients mediate pretest probability has the greatest ben-
benefit from directions on obtaining appropriate efit. Pretest probability can be estimated based on
blood pressure measurement (see Chap. 30). age of the patient, gender, and type of chest pain.
Patients should have both feet on the floor, arm The discussion below is the assessment of inter-
resting in an elevated position, such as on a table. mediate-risk patients in which a true positive or
The cuff should not be placed over clothing and true negative will alter patient care.
the patient should be encouraged to rest for a few As stated earlier in this section, coronary
minutes prior to measuring and to remain still artery narrowing of >70% is the degree of nar-
and silent while it is being measured. rowing that causes symptoms. The assessment
tools discussed here are designed to assess for
lesions of 70% or greater. These assessment tools
Diagnostics will guide further workup and management.
There are many tools to assess for symptom-
Cardiovascular testing may need to be consid- atic CAD. The first decision that needs to be
ered. If the patient is having symptoms of con- made is whether structural or physiologic testing
cern, an ECG should be obtained to evaluate for is needed. Physiologic testing will show ischemic
signs of ischemia, arrythmia, or new infarct. significance, but not severity. Sometimes, both
Evaluate for new t-wave inversion, new q-waves, modalities are needed in clinical decision mak-
ST-segment depression, heart block, or arrhyth- ing. Examples of structural and physiologic test-
mia. If a patient was recently discharged from the ing are given in Table 5.2.
hospital after a coronary event, an ECG should be
obtained. After a myocardial infarction, the ECG
Table 5.2 Noninvasive mechanism to evaluate for symp-
can change considerably from the hospital dis-
tomatic CAD
charge to the follow-up visit.
Structural Physiologic
If further testing is being considered, consider Cardiac CT cMRI
what you will do with the results, knowing that Nuclear
the patient must live with those results. A person Echocardiography
may develop significant anxiety if they have an Stress EKG
5 Outpatient Management of Coronary Artery Disease 45

Structural Imaging Table 5.4 Options to assess for symptomatic CAD

Stress modality Imaging
The test of choice in this category is coronary Treadmill EKG tracing
Nuclear
artery CT imaging. Cardiac CT will determine if Echocardiography
there is a structural lesion of 70% or greater but Vasodilator cMRI
the physiology of true ischemia is not easily Adenosine/regadenoson Nuclear
obtained from the images. The resolution of this Chronotropic enhancement Echo
modality has markedly improved for the assess- Dobutamine
ment of CAD. The images appear similar to those
obtained from invasive evaluation in the cardiac cardial oxygen consumption. The modalities
catheterization laboratory. The true benefit of this differ in the assessment of the ischemia, and the
test is the negative predictive value. A normal interpretation of abnormalities is test specific.
scan without CAD rules out ischemia as the cause Additional imaging is required to assess the
of chest pain. There is predictive value as well. severity of ischemia. Sometimes, more than one
The cardiovascular event rate is low over the next modality may be used in evaluation of the same
10 years in patients with negative scans. The lim- patient. The different ischemia-inducing modali-
itations of this modality are listed in Table 5.3. ties are listed in Table 5.4.
The most important limitation is previous stent- Treadmill stress testing is the hallmark of
ing or significant coronary calcifications, which physiologic testing. Exercise is preferred if pos-
would cause this test to be read as non-diagnos- sible as this provides prognostic information
tic. In this situation, a physiologic imaging along with ischemia evaluation. Using this
modality should be considered. The coronary CT modality, myocardial oxygen consumption is
scan protocol may require beta blocker therapy to increased by increasing both heart rate and blood
slow the heart rate into the 50-bpm range to opti- pressure.
mize image quality. This test should be used with
caution in patients with newly diagnosed cardio- Rate pressure product ( RPP )
myopathies as the administered beta blocker may = Peak heart rate ´ Peak systolic blood pressure
cause cardiovascular collapse and cardiogenic
shock in decompensated patients. Cardiac cathe- A value of >20,000 is suggestive of adequate
terization is often the best and safer test for isch- myocardial stress and is used to assure the pre-
emic evaluation in these patients. dictive value of the test. A second proxy of ade-
quate myocardial stress is the target heart rate. A
heart rate of 85% maximal predicted heart rate
Physiologic Testing (MPHR) is the standard. As a reminder, the for-
mula is:
The cornerstone of physiologic testing is evaluat- MPHR = 220 - age
ing for myocardial ischemia by increasing myo-
Treadmill stress testing can be used alone to
Table 5.3 Limitations to coronary CT interpretation assess for ischemia, but the sensitivity and spec-
Previous stenting Blooming artifact limits ificity are low. Often, additional imaging is
accuracy of stenosis severity needed to improve the positive and negative pre-
Coronary artery Blooming artifact dictive values. The most predictive result from
calcification
the treadmill is duration of exercise as it is an
Renal failure Dye-induced nephropathy
Morbid obesity Impaired image resolution
assessment of functional capacity. The standard
Patient compliance Impaired image resolution exercise protocol is called the Bruce Protocol
Severe decompensated Beta blocker administration with each stage being 3 min at an increasing
HFrEF may cause cardiovascular treadmill speed and incline. Completion of a
collapse stage determines the degree of oxygen con-
46 M. Ross and J. Cedarholm

sumption, measured in metabolic equivalents or adenosine and, less commonly, dobutamine.

METS. This value is important for standardiza- Dobutamine is a positive ionotropic and chrono-
tion of activities and utilized for many clinical tropic agent. This combination increases myocar-
decisions like preoperative cardiac risk assess- dial oxygen demand but has significant side
ment and candidacy for cardiac transplantation. effects and an increased risk of inducing
The longer exercise time and higher METS tachyarrhythmias.
achieved on the treadmill confer improved car- Adenosine and its analogues do not increase
diovascular mortality risk, even if CAD is pres- myocardial oxygen demand but alters oxygen
ent. This is the main reason anyone who can delivery. Adenosine is a coronary artery vasodila-
navigate the treadmill should be stressed in this tor. Atherosclerotic disease prevents the dilation
fashion. Some studies suggest that even in of the diseased segment. The vasodilator will cre-
patients with an abnormal stress test, if 10 ate a drop in pressure across the stenosis by dilat-
METS is achieved, medical management has the ing the normal arterial segments. Flow across a
same outcome as revascularization and medical coronary artery lesion is also reduced. These
therapy should be considered. vasodilators must be used with imaging modali-
If the baseline EKG is acceptable, the EKG ties to assess the reduction in flow and determine
tracing can be interpreted for ischemia. Resting ischemia. The images that are obtained will sug-
LBBB, ST segment depression, or paced rhythm gest ischemia in different ways.
precludes EKG interpretation, and additional Single Photon Emission Computed
imaging should be added to the treadmill evalua- Tomography (SPECT) has been the main imaging
tion. Table 5.5 lists the criteria to determine a modality for many years. A radioisotope of the
positive treadmill stress test. element technetium is attached to a red blood cell
ST segment elevation is a strongly positive with an agent called sestamibi. The red blood cell
finding, and the test should be terminated imme- is tagged and can be evaluated to assess blood
diately to avoid risk of death. The location of the flow. Images are obtained at rest and after rein-
elevation correlates with the location of the isch- jected stress images. Comparing the images will
emic distribution. In Fig. 5.1, the elevation is in determine if there is limited uptake at rest which
the LAD distribution. ST segment depression is suggestive of scar. Reduction of radioactive
does not correlate with the location of CAD but is counts after stress suggests ischemia. Examples
a marker of ischemia. In Fig. 5.2, the ST segment of these findings are seen in Fig. 5.3.
depression is across multiple vascular distribu- The gamma rays emitted from the technetium
tions and nonspecific. The multifocal VT seen on are captured by a gamma camera and computer-
the exercise tracing is also high risk for sudden ized. This program will assess the counts within
death. 1:10,000 stress patients have cardiac arrest specific coronary artery vascular distributions.
during treadmill stress testing. Severe aortic ste- By convention, the distribution with the highest
nosis is a contraindication to treadmill testing counts is deemed “normal” by the program. The
due to the risk of sudden death. other vascular distributions are then compared to
Pharmacologic stress testing is used when the “normal” distribution. The flaw of this pro-
treadmill utilization is not an option. Table 5.6 cess is when all arteries are equally diseased, and
includes the main indications for pharmacologic the scan can be falsely normal when multivessel
testing. The pharmacologic agents utilized are disease is present. This can occur in up to 15% of
all scans. Patient selection will reduce the risk of
Table 5.5 Criteria for positive EKG stress test these false-negative results. This is one of the
Flat or down sloping ST segments lasting into recovery main reasons to assure the appropriate selection
ST segment elevation in a vascular distribution of patients based on pretest probability and assure
Reproduction of exertional angina true positive and negative results.
Exercise-induced hypotension Attenuation artifact is due to the physics of
Exercise-induced Torsades/VT gamma rays. Soft tissue will prevent counts in a
5 Outpatient Management of Coronary Artery Disease 47

Fig. 5.1 EKG showing ST segment elevation in early treadmill stress testing

Fig. 5.2 EKG showing salvos of torsades during treadmill stress testing

Table 5.6 Pharmacologic stress Indications Contraindications

testing Left bundle branch block (LBBB) Bronchospasm
Ventricular pacemaker Bradycardia/heart block
Inability to navigate treadmill Tachyarrhythmias—AFIB with
RVR, VT
Chronotropic incompetence
48 M. Ross and J. Cedarholm

Fig. 5.3 Abnormal SPECT nuclear images. Green arrow shows normal LAD distribution perfusion at rest. Red arrow
shows a reduction of counts in the apical segment at rest suggestive of remote infarction. White arrows show a LAD
distribution of counts after exercise suggestive of ischemia. The white arrow on the left shows complete reversibility
when compared to the green arrow and suggests CAD >70%. The right arrow appears worse when compared to the red
arrow suggesting ischemia superimposed on previous infarct

vascular distribution from reaching the gamma in an MRI scan. Specific coronary artery lesions
camera. These areas can be misinterpreted as are not seen with MRI. This stress modality is a
ischemia or infarction. Commonly, the reader physiologic test with respect to the coronary
will be able to determine if these areas are, in arteries. The MRI does give structural informa-
fact, artifact or a true defect. This attenuation arti- tion about the rest of the heart. Due to the require-
fact contributes to the false-positive tests associ- ments of an MRI scanner, availability is often
ated with this modality. Anterior attenuation limited.
artifact is more common in women due to breast In a patient with an ischemic defect, the size
tissue interference. Inferior artifact is more com- of the imaging defect can be prognostic. However,
mon in males due to a thicker diaphragm adjacent unless the defect involves a significant section of
to the inferior walls of the myocardium. myocardium, the risk of invasive coronary inter-
Stress MRI is emerging as an excellent alter- vention may outweigh the benefit. This group can
native to SPECT testing. Adenosine is still used include patients being evaluated prior to a non-
to vasodilate, but MRI imaging and parameters cardiac surgery, elderly patients who are at higher
can assess tissue flow with gadolinium adminis- risk for cardiac catheterization, and persistent
tration. In addition to stress data, a large amount anginal symptoms with known areas of unrevas-
of structural data can be seen with high resolution cularized disease including chronic total occlu-
5 Outpatient Management of Coronary Artery Disease 49

sion (CTO). Stress testing is generally not done Cholesterol Lowering Agents
for asymptomatic surveillance. However, if HMGCoA reductase inhibitors are commonly
patient had an absence of symptoms with a previ- referred to as Statins (see Table 5.1). Statins bind
ous MI or significant coronary lesion and is to receptors on a reductase enzyme, inhibiting the
>2 years since invasive evaluation, testing should production of LDL by the liver. This production
be considered. In patients with history of surgical occurs primarily overnight, and therefore statins
bypass, the test free period is approximately are most effective if administered in the evening.
5 years, but should be evaluated on a case-by- All coronary patients should remain on statin
case basis [2]. therapy life-long to aid in lowering lipid levels.
One other form of stress testing should be Additionally, statins have a pleiotropic benefit of
mentioned. Stress echoes can be done for very decreasing the inflammatory response within
specific reasons such as evaluation of hypertro- endothelium and stabilizing plaque that has
phic cardiomyopathy gradients across the LVOT already been formed. Side effects of statins
obstruction. Stress echo is not used commonly include muscle pain, usually in the proximal
due to its limitations and feasibility. It is com- large muscle groups, bilaterally. The symptoms
pleted by doing a baseline echo, having the generally resolve once the statin has been
patient exercise, and then laying them down for stopped. A lower dose or a weaker statin can be
another echo while HR is still elevated. There is tried and may not have the same side effects. If
difficulty with obtaining images while the heart the patient develops significant muscle pain, they
is still “stressed,” and a correct interpretation is should discontinue the statin and have laboratory
dependent on appropriate image acquisition. evaluation for rhabdomyolysis. This is a rare side
Echocardiogram—Ischemic symptoms can be effect.
nonspecific and mimic valvular or CHF symp- Immediately after a coronary event or inter-
toms. Complaints may include increased fatigue, vention, high dose statin therapy consisting of
lack of endurance, or dizziness. An echocardio- atorvastatin 40–80 or rosuvastatin 20–40 mg
gram can evaluate for a change in wall motion should be initiated (Table 5.7). For patients who
abnormalities, ejection fraction, and valvular have had multiple cardiac events or one major
dysfunction to further guide therapy. event and multiple comorbidities, a goal LDL of
Cardiac catheterization may be considered in <70 mg/dL is recommended. If the patient is also
patients having anginal symptoms despite medi- a diabetic, an LDL goal of <50 mg/dL should be
cal therapy. The initial plan involves titration and considered. Ezetimibe 10 mg can be added if
addition of anti-anginal therapies. If the patient is LDL goal is not achieved on the highest tolerated
on two antianginal therapies that have been appro- statin dose. Ezetimibe inhibits cholesterol absorp-
priately up titrated and are still experiencing angi- tion in the small intestine, lowering available
nal symptoms or their previously stable symptoms
have increased in severity, frequency, or duration,
then catheterization is appropriate [2]. Table 5.7 Statin intensity and dosing
% of 30–49%
LDL ≥50% - high moderate <30% low
lowering intensity intensity intensity
Management
Statin Atorvastatin Atorvastatin Simvastatin
40–80 mg 10–20 mg 10 mg
Antiplatelet Therapy Rosuvastatin Rosuvastatin Pravastatin
Lifelong aspirin 81 mg daily is recommended. 20–40 mg 5–10 mg 10–20 mg
Aspirin at 325 mg does not additionally reduce Simvastatin Lovastatin
20–40 mg 20 mg
mortality but increases bleeding risk. Aspirin is Pravastatin
an irreversible antiplatelet agent, helping prevent 40–80 mg
thrombosis within arteries [3]. See Chap. 4 for Lovastatin
full discussion on antiplatelet agents. 40–80 mg
50 M. Ross and J. Cedarholm

cholesterol for the liver. This agent has minimal Beta-blockers—decrease heart rate and lower
side effects and is very well tolerated. There is no blood pressure, thereby reducing cardiac oxygen
mortality benefit of this agent alone without the demand. Optimally, metoprolol or carvedilol is
high dose/high potency stain therapy. used as a first-line antianginal therapy. These
Should the goal LDL not been met with should be titrated to maximal tolerated levels.
these two therapies, then a PCSK-9 inhibitor They are often limited by bradycardia or patient
should be considered. PCSK-9 inhibitors block developing a side effect, such as fatigue and erec-
the molecule that helps break down LDL recep- tile dysfunction (ED).
tors. This agent results in more LDL receptors Calcium channel blockers—control the influx
being available to clear LDL from the blood- of calcium into smooth muscle cells of the vascu-
stream. The medication comes prepared in sin- lar system, limiting contraction, and promoting
gle use injections that are self-administered vasodilation. These agents improve oxygen
every 2 weeks. The cost of these medications delivery and reduce oxygen consumption by low-
must be considered before prescribing as the ering blood pressure (afterload). Amlodipine is
cost can be prohibitory. In patients with coro- often initiated as a second-line agent. This
nary artery disease who are unable to tolerate improved BP control but does not affect heart
high dose statin therapy, moderate dose therapy rate. The primary side effect reported is lower
can be initiated. The goal LDL reduction is extremity edema. It is generally most pronounced
30–49%. If a PCSK-9 inhibitor is used, the at higher doses and does resolve upon cessation
patient should stay on the highest tolerated dose of the medication.
of statin and ezetimibe. It is used as an adjunct Nitrates—Nitroglycerine (NTG) relaxes
therapy, not a replacement [4]. smooth muscle cells resulting in vasodilation.
Nitrates work in the venous system reducing ven-
Antianginal Therapy tricular preload and by decreasing afterload in
Antianginal therapies are important for the man- the arteriole system. This leads to decreased
agement of ongoing coronary symptoms. Patients workload on the heart and increased blood flow
with CAD not amenable to revascularization and/ to coronary arteries. This group of medications is
or microvascular dysfunction (MVD) are the the class of choice for patients with MVD and
main indications for antianginal therapy. The dif- symptoms rapidly improve with these agents.
ferent classes of medications lower myocardial Isosorbide is a long-acting nitrate that will lower
oxygen consumption and improve oxygen deliv- blood pressure but will not affect heart rate; how-
ery to the working myocardium. The patients’ ever, often patients develop headaches. The head-
observations of their symptoms can help guide ache improves with continued administration and
the need for antianginal adjustment. Patients are should be discussed with the patient during the
encouraged to regularly engage in cardiac exer- initiation of the medication. Nitroglycerine prep-
cise. This activity helps patients to monitor their arations are also contraindicated in patients who
symptoms by assessing their overall functional take medications for erectile dysfunction as con-
status. If they are regularly exercising, they can comitant use can result in extreme refractory
watch for changes in their capacity. These symp- hypotension. Patients may still use sublingual
toms may include increased dyspnea, early (SL NTG) in addition to long-acting NTG if they
fatigue, dizziness or palpitations, discomfort in have discomfort that is consistent with exertional
their chest or upper back that may resolve with angina. They may use it prior to activity to pre-
rest. Patients can monitor their blood pressure vent angina. One tablet should be placed under
and heart rate at home looking for any changes the tongue every 5 min, for a maximum of three
that occur over time. Annual ischemic testing is doses, until the anginal symptoms have resolved.
no longer recommended. Patients should be edu- If symptoms do not resolve, then medical atten-
cated that exercise is their method of “stress test- tion may be required. The effects of SLNTG are
ing” themselves. short acting. Tablets should burn under the tongue
5 Outpatient Management of Coronary Artery Disease 51

and if not are likely expired. Often patients need • Pretest probability of each patient should be
reassurance as to when it is safe to administer assessed to order the correct test and minimize
NTG. It is beneficial to remind the patient that false-positive and false-negative results.
they will likely need to lay down due to blood • If you won’t believe the result, or it won’t
pressure drop. Also, nitroglycerine is not a tradi- change management, DON’T order the test!
tional pain medication and is not addictive. It • If symptoms are clearly cardiac or non-car-
may also resolve symptoms aside from cardiac diac, no testing is required because the test
discomfort such as gastrointestinal discomfort, may result in false-positive or negative results.
and the relief is not diagnostic for a cardiac etiol- • Always walk the patient on a treadmill, if pos-
ogy of symptoms. sible, to obtain functional capacity and prog-
Ranolazine—works primarily for smaller ves- nostic data.
sel disease. One benefit of this medication is that • The addition of imaging improves the positive
it does not decrease blood pressure or heart rate. predictive value of testing.
This makes it beneficial when trying to treat isch- • If there is known CAD or stented segments,
emic chest pain in patients limited by hemody- coronary CT is usually not the correct test for
namics. It also does not increase risk of arrythmia. chest pain evaluation.
Often patient’s will have an awareness that their • MVD may have the same exertional symp-
symptoms have improved or become less severe toms, abnormal stress testing, and response to
within a few days of starting the medication. The medical therapy without epicardial CAD.
administration of ranolazine is entirely for anti- • Lifelong antiplatelet and statin therapies are
anginal symptoms, so it is reasonable to discon- important GDMT for long-term management
tinue it, if there is no improvement. It is of CAD.
exceptionally well tolerated. It does prolong the
QT interval and is contraindicated in liver disease
[5].
References
Behavior Modification
Exercise and dietary recommendations can be 1. Gibbons RJ, Chatterjee K, Daley J, et al. ACC/AHA/
ACP-ASIM guidelines for the management of patients
made. Address modifiable risk factors (HTN, lip- with chronic stable angina: executive summary and
ids, DM, tobacco, obesity) at each visit, educat- recommendations: a report of the American college
ing the patient on the goals and what needs to be of cardiology/American heart association task force
done to maintain or achieve them. on practice guidelines (committee on management
of patients with chronic stable angina). Circulation.
1999;99(21):2829–48. http://circ.ahajournals.
Pearls org/cgi/content/extract/99/21/2829. https://doi.
• Complete versus incomplete revascularization org/10.1161/01.CIR.99.21.2829.
is important information to know in an outpa- 2. Conti CR. Grading chronic angina pectoris (myo-
cardial ischemia). Clin Cardiol. 2010;33(3):124–5.
tient with chest pain. https://onlinelibrary.wiley.com/doi/abs/10.1002/
• Medical management for stable chest pain clc.20766. https://doi.org/10.1002/clc.20766.
may reduce the need for invasive procedures. 3. Grundy SM, Stone NJ, Bailey AL, et al. 2018 AHA/
• Attention to hospitalization discharge medica- ACC/AACVPR/AAPA/ABC/ACPM/ADA/AGS/
APhA/ASPC/NLA/PCNA guideline on the manage-
tions is important to avoid complications in ment of blood cholesterol: executive summary: a report
the outpatient setting. of the American college of cardiology/American heart
• There are minimal indications for asymptom- association task force on clinical practice guidelines.
atic stress testing in patients with CAD and J Am Coll Cardiol. 2019;73(24):3168–209. https://
www.ncbi.nlm.nih.gov/pubmed/30423391. https://
should be avoided. doi.org/10.1016/j.jacc.2018.11.002.
52 M. Ross and J. Cedarholm

4. Gulati M, Levy PD, Mukherjee D, et al. 2021 AHA/ 5. Amsterdam E, Wenger N, Brindis R, et al. 2014 AHA/
ACC/ASE/CHEST/SAEM/SCCT/SCMR guideline ACC guideline for the management of patients with
for the evaluation and diagnosis of chest pain: exec- non–ST-elevation acute coronary syndromes: a report
utive summary: a report of the American college of of the American college of cardiology/American
cardiology/American heart association joint commit- heart association task force on practice guide-
tee on clinical practice guidelines. J Am Coll Cardiol. lines. Circulation. 2014;130(25):e344–426. http://
2021;78(22):2218–61. https://www.ncbi.nlm.nih. ovidsp.ovid.com/ovidweb.cgi?T=JS&NEWS=n&C
gov/pubmed/34756652. https://doi.org/10.1016/j. SC=Y&PAGE=fulltext&D=ovft&AN=00003017-
jacc.2021.07.052. 201412230-00017. https://doi.org/10.1161/
CIR.0000000000000134.
Surgical Management of Coronary
Artery Disease
6
Elisabeth A. Powell and Larry Watts

Coronary artery bypass grafting is a surgical pro-

cedure performed to reestablish blood flow to the
diseased coronary arteries. Atherosclerosis devel-
ops within the artery walls creating narrowing of
the artery. Blood flow and myocardial perfusion
are decreased distal to the areas of stenosis,
resulting in ischemia and potentially, myocardial
infarction. In coronary artery bypass grafting
(CABG), an artery or vein is used as a conduit to
deliver blood distal to the stenosis, bypassing the
disease (Fig. 6.1).
A multitude of factors are considered when
determining the best modality for coronary revas-
cularization. Numerous studies have compared
percutaneous coronary intervention (PCI) to cor-
onary artery bypass grafting (CABG) for revas-
cularization. These studies assessed risk to
benefit ratios, long term patency, and overall sur-
vival rates. Although PCI is an appropriate option
when stenting is feasible, CABG is the gold stan-
Fig. 6.1 CABG. (a) Ascending aorta (b) Bypass grafts
dard for revascularization in patients with left coming off aorta (c) Right atrium (d) Right ventricle
main disease, significant multivessel coronary
artery disease (CAD) with decreased LV func-
tion, or when stenting is unsuccessful.

E. A. Powell (*)
Banner University Medical Center, Tucson, AZ, USA
e-mail: [email protected]
L. Watts
Atrium Health/Sanger Heart and Vascular Institute,
Charlotte, NC, USA
e-mail: [email protected]

© The Author(s), under exclusive license to Springer Nature Switzerland AG 2023 53

Indications for CABG provides blood flow to a large portion of the left
ventricle extending all the way to the apex. The
In general, patients are considered for CABG if diagonal artery, in contrast, only supplies a small
they have one of the following: area of the anterior and lateral left ventricle. A
bypass placed to the proximal left anterior
• Left main disease >50%. descending artery (LAD) revascularizes a larger
• Diffuse 3 vessel CAD (disease >50% in the area of myocardium than bypassing a stenosis at
LAD, circumflex, and right territories). the distal end of a diagonal artery. Proximal or
• 2 vessel CAD with significant stenosis in the mid-vessel stenoses will yield more benefit from
proximal LAD (categorized as ≥70%) bypass than a distal stenosis given the territory
• Significant stenosis, but coronary is not ame- the vessel feeds beyond the blockage.
nable to PCI. Guidelines published by The American
• Patient is undergoing another cardiac opera- College of Cardiology (ACC) and American
tion and coronary artery disease is present. Heart Association (AHA) are available to assist
in medical decision making and are demonstrated
Consideration for surgical revascularization is in Fig. 6.2. These guidelines are based on a com-
multifactorial and a diseased artery’s eligibility prehensive literary review on studies, trials, and
for bypass depends on both the severity and loca- evidence-based medicine which evaluate both
tion of the stenosis. The severity of the stenosis in indications to improve symptoms and anatomic
the native vessel must be >50% to be eligible for indications to improve survival [1]. In patients
bypass, and >70% to be considered a significant with significant left main stenosis and complex
stenosis. Moderate to high grade stenosis ensures disease unable to be safely stented, studies have
blood will flow preferentially down the bypass shown that CABG is the gold standard for revas-
graft and into the coronary artery without com- cularization and portends an improved survival
peting with the natural flow from the proximal over PCI and medical therapy [1]. CABG has
native artery. also shown to be superior to PCI in multivessel
The location of the stenosis is also important. CAD with ischemic cardiomyopathy and EF
The area of myocardium that is supplied by the ≤50% [1]. If multivessel CAD is present with an
coronary artery is directly proportional to the EF ≥50%, surgical revascularization is still rea-
benefit gained from bypassing the artery. For sonable for improved survival, especially with
comparison, the left anterior descending artery the presence of Diabetes [1].
6 Surgical Management of Coronary Artery Disease 55

SIHD
Indications to Anatomic Recommended
improve indications
symptoms to improve survival
Reasonable
Refractory angina on
medical therapy?
May be reasonable

YES No

Revasularization
Left main disease?
(1)

YES No

Significant left main Multivessel CAD with

stenosis and high anatomy suitable for
anatomic complexity CAD? PCI or CABG?

YES No No YES

Suitable candidate for Ischemic cardiomyopathy

GDMT
CABG? EF ≤50%?

YES No
YES No
Suitable candidate for EF >50% and
Heart Team CABG? triple-vessel disease
CABG CABG PCI
discussion
(1) (1) (2a)
(1) YES No

GDMT with
or without
EF <35% EF <35%-50%
PCI

CABG Heart Team

CABG CABG PCI
(2a) discussion
(1) (2b) (2b)
(1)

GDMT with or
without PCI

Fig. 6.2 Revascularization in patients with Stable care of patients with stable CAD. It is not meant to encom-
Ischemic Heart Disease (SIHD) CABG indicates coro- pass every patient scenario or situation, and clinicians are
nary artery bypass graft; CAD, coronary artery disease; encouraged to us a Heart Team approach when care deci-
EF, ejection fraction; GDMT, guideline-directed medical sions are unclear and to see the accompanying supportive
therapy; PCI, percutaneous coronary intervention; and text for each recommendation. Additionally, in situations
SIHD, stable ischemic heart disease. This algorithm sum- that lack sufficient data to make formal recommendations
marizes the recommendations in this guideline for the for care. (Adapted from [1])

The current guidelines by the ACC and AHA balanced analysis towards high-risk patients with
recommend a multidisciplinary approach to sur- supportive decision making. This is beneficial if
gical decision making. The heart team consists of the decision between high-risk surgical revascu-
the cardiologist, interventionalist and cardiotho- larization versus PCI vs medical management is
racic surgeon. Prior to intervention, a discussion unclear [1].
with the entire team ensures a well-rounded and
56 E. A. Powell and L. Watts

Preoperative Assessment ing should be considered to investigate various

and Calculating Risk disease processes.
Determining surgical risk is vital in determin-
In addition to cardiac catheterization, preopera- ing if a patient is an appropriate candidate for
tive work up includes a comprehensive history cardiac surgery. The Society of Thoracic
and physical, laboratory tests, and various imag- Surgeons (STS) has developed a risk calculator
ing modalities. Every preoperative patient should which allows providers to determine the mortal-
begin with the same basic work up to assess base- ity risk along with various morbidities for certain
line function and any abnormalities. Refer to cardiac surgeries [2]. These surgeries include
Table 6.1. CABG, isolated aortic valve replacement (AVR),
A carotid artery duplex is recommended to isolated mitral valve repair (MVr), isolated mitral
assess for carotid stenosis in patients with neuro- valve replacement (MVR), CABG + AVR, CABG
logical symptoms or a history of a CVA to ensure +MVr, and CABG+MVR. This calculator pro-
appropriate blood flow during cardiopulmonary vides percentages of predicted risk in nine differ-
bypass (see Table 6.2). Pulmonary disease or sig- ent categories based on STS data and research
nificant smoking history should be assessed with [3]. Refer to Table 6.3.
an arterial blood gas (ABG) and pulmonary func- The risk calculator is available on the STS
tion tests in consideration of intubation. Prior to website: https://riskcalc.sts.org/stswebriskcalc/
undergoing cardiac surgery, a transthoracic echo- calculate
cardiogram should also be completed to assess This calculator is meant to aid in, not define,
heart and valve function. Consultation for surgi- decision making. This tool should be combined
cal clearance should be made to respective spe- with physical assessment, frailty testing, clinical
cialist groups for underlying comorbidities at risk judgment, and discussions with both members of
with surgery. Preoperative assessment is both the care team and patient to determine if patient
patient and surgeon specific and additional test- is an appropriate surgical candidate. The calcula-
tor is based on a database of greater than 30 years
of patient information. It is utilized to help pre-
Table 6.1 Baseline preoperative testing
dict risks of cardiac surgery. Common categories
Comprehensive metabolic panel
utilized are 30-day mortality, risk of prolonged
Complete blood count
ventilation, risk of requiring post operative dialy-
Prothrombin time (PT-INR)
Partial thromboplastin time (PTT) sis, stroke, among many other categories. A sur-
Hemoglobin A1C gical mortality risk of >8% is considered high.
Type and screen These high-risk patients often require Heart Team
Pregnancy test (if female, childbearing age) discussions to determine optimal medical care
MRSA nasal swab and delivery. This may include a hybrid of surgi-
Urinalysis-potential
cal revascularization and PCI.
Electrocardiography
Chest xray

Table 6.3 STS risk calculator categories

Table 6.2 Other potential preoperative testing Mortality
TSH Stroke
Platelet mapping Renal failure
Vein mapping Prolonged ventilation or reintubation (>24 h)
Pulmonary function testing Mediastinitis/deep sternal wound infection
Arterial blood gas Need for reoperation during hospital stay
Carotid duplex Major morbidity or mortality
Upper extremity arterial duplex Long length of stay (longer than 14 days)
Consults to medical specialists Short length of stay (shorter than 6 days)
6 Surgical Management of Coronary Artery Disease 57

Conduit Selection Table 6.4 Bypass conduit recommendations. Adapted

from [1]

The primary objective of coronary bypass is to Best practices for the use of bypass conduits in CABG
• Objectively assess palmar arch completeness and
revascularize the myocardium. This reduces
ulnar compensation before harvesting the radial
symptoms, increase survival rates, and decreased artery. Use the arm with the best ulnar
mortality. To obtain these goals, a vital part of the compensation for radial artery harvesting
planning process prior to surgery is conduit and • Use radial artery grafts to target vessels with
target vessel selection. The conduits used in subocclusive stenoses
• Avoid the use of the radial artery after transradial
CABG to provide blood supply to the coronary
catheterization
arteries are the internal mammary arteries, radial • Avoid the use of the radial artery in patients with
artery, greater and lesser saphenous vein, and less chronic kidney disease and a high likelihood of
commonly, the gastroepiploic artery. rapid progression to hemodialysis
Extensive literary reviews and meta-analysis • Use oral calcium channel blockers for the first
postoperative year after radial artery grafting
have demonstrated the superiority of arterial con-
• Avoid bilateral percutaneous or surgical radial
duits versus venous conduits in CABG. Arterial artery procedures in patients with coronary artery
conduits have demonstrated greater patency disease to preserve the artery for future use
rates, quality, and durability over time leading to • Harvest the internal mammary artery using the
greater survival rates and decreased morbidities. skeletonization technique to reduce the risk of
sternal wound complications
This increased patency is due to many physical • Use an endoscopic saphenous vein harvest
and biological factors. When compared to venous technique in patients at risk of wound complications
conduits, arterial conduits have similar functional • Use a no-touch saphenous vein harvest technique in
and structural properties to the coronary artery, patients at low risk of wound complications
the ability to sustain arterial pressure on a cellular • Use the skeletonized right gastroepiploic artery to
graft right coronary artery target vessels with
level, decreased rates of thrombosis, and signifi- subocclusive stenosis if the operator is experienced
cantly decreased evidence of atherosclerosis at with the use of the artery
the time of follow-up [4].
Although arterial conduits have shown
improved patency and durability, venous con- the gold standard for grafting of the left anterior
duits are still accepted and utilized in given cir- descending artery (LAD). The LIMA lies in
cumstances. Conduit selection for CABG is proximity to the LAD and is grafted onto the
multifactorial and depends on both clinical fac- LAD while remaining attached to the left subcla-
tors of the patient and anatomical characteristics vian artery (in situ). Given the importance of the
of the physical stenosis. Best practices for con- LAD and the superiority of the IMA, this graft
duit selection and surgical decision making are has shown to greatly increase survival, decrease
outlined in Table 6.4. mortality and morbidities, and increase graft
patency rates after CABG [5].
The Society of Thoracic Surgeons recom-
Internal Mammary Artery mends the use of bilateral IMAs for CABG if the
degree and location of the stenosis is agreeable
The internal mammary artery is the number one and there is no excessive risk of sternal complica-
most utilized conduit in cardiac surgery. This tions [5]. Sternal complications of infection, non-
artery has a low rate of atherosclerosis making it union, or poor healing with the harvest of bilateral
very durable with greater long-term patency rates IMAs are a potential risk given the decrease of
when compared to other conduits. The location arterial blood supply to the sternum after removal
of the mammary artery along the sternum pro- of the arteries. This risk is greatest in patients with
vides for easy accessibility and harvest is diabetes due to a higher risk for infection and
obtained without the need of an additional inci- slower wound healing. This risk can be reduced if
sion. The left internal mammary artery (LIMA) is the IMA is harvested skeletonized, leaving the
58 E. A. Powell and L. Watts

Fig. 6.4 Endoscopically harvested radial artery. Photo

Credit: Roy Keller, CSFA

Fig. 6.3 Skeletonized left internal mammary artery

in-situ preserved renal function [1]. If patients have
chronic renal failure or known need for hemodi-
alysis in the future, radial artery utilization is not
surrounding vasculature behind and intact on the recommended. A radial artery that has been har-
chest wall. Demonstration of a skeletonized IMA vest endoscopically is demonstrated in Fig. 6.4.
harvest is shown in Fig. 6.3. Counseling on smok- Before harvesting the radial artery, it is impor-
ing cessation to decrease vasoconstriction, strict tant to ensure the patient’s hand will continue to
glycemic control to reduce risk of infection, and have an arterial blood supply via the ulnar artery
consideration of enhanced sternal stabilization and an intact palmer arch. This can be assessed
with sternal closure all aid in sternal healing and physically by performing a modified Allen’s Test.
decrease risk of complications [5]. To complete this test, the patient elevates their
hand and clenches their fist while the provider
occludes both the ulnar and radial artery to exsan-
Radial Artery guinate the hand. While still occluding the arter-
ies, the patient opens their hand which should
The radial artery is the second preferred conduit appear blanched. The ulnar artery pressure is
over the IMAs in CABG for longevity and qual- then released while still compressing the radial
ity. Advancements in postoperative medical ther- artery. If the hand regains color, blood flow has
apy to prevent radial spasm with calcium channel re-entered the hand, demonstrating a patent ulnar
blockers and improvement in target selection artery and complete arch. This same test may be
have greatly improved patency rates of radial completed using a pulse oximeter or doppler.
conduits [5]. The selected target for the radial Completion of the palmer arch may be assessed
artery must be a coronary artery with significant more specifically with an arterial duplex study.
stenosis (>70% stenosis for left sided grafts,
>90% stenosis for right sided grafts) to prevent
radial spasm, competitive flow, and early graft Greater and Lesser Saphenous Vein
failure. With these improvements, recent studies
have demonstrated greater patency rates and sur- Guidelines from the ACC, AHA, and STS recom-
vival benefits for the radial artery when compared mend utilization of arterial conduits over venous,
to the saphenous vein conduit [1]. The radial yet the greater saphenous vein (GSV) remains the
artery is now recommended as conduit choice for second highest used conduit for CABG next to
the most important vessel requiring bypass, sec- the LIMA. This is due to its accessibility, length,
ond to the LAD [1]. It should be considered in versatility, and relative ease of use. Although the
patients <75 years old, women, and patients with long-term patency rate for saphenous vein grafts
6 Surgical Management of Coronary Artery Disease 59

Fig. 6.7 Endoscopically harvested greater saphenous

vein graft

The lesser saphenous vein is less frequently

used in CABG surgery. Its role and patency are
the same as the greater saphenous, however it is
smaller in diameter and its anatomical position in
Fig. 6.5 Greater saphenous vein during endoscopic
harvest the posterior lower leg make it difficult to har-
vest. The lesser saphenous vein terminates in the
popliteal vein so the length of the lesser saphe-
nous is also substantially shorter. It is most often
utilized in redo operations where the greater
saphenous has already been utilized, or if the
patient has had vein ablation or stripping of the
greater saphenous.

Gastroepiploic Artery

The gastroepiploic artery is the least utilized con-

duit in CABG. This is due to difficulty in expo-
sure and harvest, short conduit length, and
variation in size along the length of the artery [5].
This option is usually only considered when the
Fig. 6.6 Cauterization of branch during endoscopic vein other conduits have already been harvested in
harvest of the greater saphenous
prior operations or are inadequate. Like the radial
artery, the gastroepiploic artery is prone to spasm
is inferior to arterial conduits, it is still an and is only recommended to be used on coronary
accepted choice for non-LAD targets. arteries with a severe level of stenosis (>90%).
Improvements in harvest techniques and techno-
logical advances with endoscopic vein harvesting
have improved conduit quality, patency rates, and References
decreased wound complications. Demonstration
of greater saphenous vein harvest utilizing the 1. Lawton JS, Tamis-Holland JE, Bangalore S, Bates
ER, Beckie TM, Mischoff JM, et al. ACC/AHA/SCAI
endoscopic technique is shown in Figs. 6.5 and guideline for coronary artery revascularization, a report
6.6. The finished product is demonstrated in of the American College of Cardiology/American
Fig. 6.7. If the patient has known, or suspected, Heart Association Joint Committee on clinical practice
venous stasis or varicosities, vein mapping may guidelines. J Am Coll Cardiol. 2021;2022:79.
2. The Society of Thoracic Surgeons; 2022. https://www.
be beneficial to assess quality and size of the sts.org/resources/risk-calculator.
saphenous vein prior to harvest.
60 E. A. Powell and L. Watts

3. O’Brien SM, Feng L, He X, Xian Y, Jacobs JP, bypass grafting. JACC: basic to translational. Science.
Badhwar V, et al. The Socieity of Thoracic Surgeons 2021;6(4):388–96.
2018 adult cardiac surgery risk models: part 2 - 5. Aldea GS, Bakaeen FG, Pal J, Thourani VH, Firestone
statistical methods and results. Ann Thorac Surg. S, Mitchell JD, et al. The Society of Thoracic Surgeons
2018;105:1419–28. clinical practice guidelines on arterial conduits for
4. Gharibeh L, Ferrari G, Ouimet M, Grau JB. Conduits’ coronary artery bypass grafting. Ann Thorac Surg.
biology regulates the outcomes of coronary artery 2015;101(2):801–9.
Part III
Cardiac Electrophysiology

Satish Misra

The cardiac conduction system is a complex and highly regulated system

including both specialized impulse generation regions, specialized conduc-
tion fibers, and the intrinsic properties of myocytes that facilitate propagation
of electrical activity through the heart. The beat-to-beat properties of these
components are dynamic, affected by intrinsic cardiac factors, such as isch-
emia or pressure overload, as well as extrinsic factors, like circulating inflam-
matory cytokines and the autonomic nervous system. Acquired and inherited
disorders at each of these levels are associated with a wide range of pathology
that will be encountered in the general cardiology practice. In this section, we
will review these conditions as well as their management.
The cornerstone of management of arrhythmia disorders includes anti-
arrhythmic therapy, cardiovascular implantable electronic devices (CIEDs),
and catheter ablation. Management of relevant comorbid conditions is also
critical. For example, for patients with atrial fibrillation, effective manage-
ment of comorbidities such as diabetes mellitus and sleep apnea has been
associated with reduced arrhythmia burden as have behavioral modification
that leads to weight loss and increased aerobic exercise.
Anti-arrhythmic therapy will be reviewed in detail in this section. It is
important to recognize that medical therapy is suppressive while catheter
ablation, which will also be discussed, is potentially curative for many condi-
tions including SVT, PVCs, and atrial flutter. For others, such as atrial fibril-
lation and ventricular tachycardia, it can often be more effective for arrhythmia
suppression than medication therapy and help avoid associated toxicities,
particularly with Class III agents. Procedural complication rates are low and
with modern electro-anatomic mapping systems, can be completed without
radiation exposure.

S. Misra
Atrium Health/Sanger Heart and Vascular Institute, Charlotte, NC, USA
e-mail: [email protected]
62 Cardiac Electrophysiology

CIED therapy includes pacemakers and implantable cardioverter-

defibrillators (ICDs) which can be single chamber, dual chamber, or biven-
tricular. Pacemakers are used to manage the disorders of impulse generation
and propagation that lead to symptomatic bradyarrhythmias such as heart
block and sinus node dysfunction. In addition, biventricular systems, which
include pacing leads for both the right and left ventricle, can help correct the
abnormal mechanics associated with left bundle branch block which can con-
tribute to systolic dysfunction. Finally, ICDs can help prevent sudden death
associated with ventricular arrhythmias. Modern devices also include sophis-
ticated heart failure monitoring algorithms which incorporate a range of
physiologic data collected by these devices.
Electrophysiology as a field has seen rapid evolution over the past ten
years, a trend that is likely to continue. In the catheter ablation arena, new
modalities of ablation using different forms of energy to eliminate abnormal
tissue are emerging such as pulsed field ablation. In addition, increases in
computing power as well as advances in catheter/electrode design have
enabled very high-density mapping of the heart’s electrical activity, some-
times reaching thousands of measurements, and processing of that informa-
tion to reflect information about underlying abnormalities in real-time. Novel
CIEDs are also being developed including leadless pacing systems that can
be implanted in both the atria and ventricles. In addition, there is a rapid evo-
lution toward the use of conduction system pacing, whereby pacing leads are
implanted in deep septal positions to recruit the native conduction system,
thereby creating a more normal ventricular contraction with every heartbeat.
In this section, we will review the foundational knowledge that will help
enable you to provide effective care for patients with arrhythmia disorders
and collaborate with your electrophysiology colleagues to ensure the best
outcomes for your patients.
Antiarrhythmic and Anticoagulant
Agents
7
Craig J. Beavers

Anticoagulation Therapy the antiarrhythmic agents, it is important to select

the agent that optimizes efficacy and reduces risk
As outlined in the atrial fibrillation section (Chap. of bleeding. Decisions should be made based on
9), one of the core goals in management is to pre- patient factors including renal function, liver
vent or reduce the risk of stroke and systemic function, weight, age, ability to adhere to regi-
embolism. The preferred strategy to decrease risk men, cost, and other factors. In addition, the
is systemic anticoagulation. The Atrial patient should have education provided about
Arrhythmia chapter will provide the recommen- their anticoagulation at each encounter including
dations of when and to whom anticoagulation benefits and risks (Tables 7.1 and 7.2).
therapy should be prescribed. However, as with

C. J. Beavers (*)
University of Kentucky College of Pharmacy,
Lexington, KY, USA
e-mail: [email protected]

© The Author(s), under exclusive license to Springer Nature Switzerland AG 2023 63

Corresponding
Pharmacological Electrophysiological Major clinical likely therapeutic Example Pharmacokinetic Common dose(s) Cardiovascular Non-cardiovascular
targets effects applications mechanisms drug(s) parameters in adults adverse events events
Class 0: Hyperpolarization-activated cyclic nucleotide-gated (HCN) channel blockers
HCN channel Inhibition of Ir Potential new off Reduced in SAN Ivabradine Half-life: Oral: 5 mg twice Bradycardia, Phosphene
mediated reducing the label applications automaticity Distribution 2 h; daily; hypertension, (transient enhanced
pacemaker current sino-atrial node for effective ~6 h maintenance: atrial fibrillation brightness in limited
(Ir) block (SAN) phase 4 tachyarrhythmias Bioavailability: 7.5 mg twice area of visual field,
pacemaker (e.g. inappropriate ~40% daily halos, image
depolarization rate sinus tachycardia; Metabolism: decompositions,
(decreased not atrial Extensively colored bright
automaticity) fibrillation [AF]) intestinal and lights, or multiple
hepatic via images; occurs in
CYP3A4 first 2 months and
(CYP3A4 substrate) most cases resolve
Excretion: Feces with
and urine (~4% has discontinuation).
unchanged drug)
C. J. Beavers
Corresponding
Pharmacological Electrophysiological Major clinical likely therapeutic Example Pharmacokinetic Common dose(s) Cardiovascular Non-cardiovascular
targets effects applications mechanisms drug(s) parameters in adults adverse events events
7
Class Ia: Voltage-gated Na + channel blockers
Nav 1.5 open state, Reduction in peak INa, Supraventricular Reduction in Quinidine Half-life: 4–10 h QRS Thrombocytopenia,
intermediate action potential (AP) tachyarrhythmias, ectopic ventricular/ Bioavailability: prolongation cinchonism, pruritis,
dissociation generation, with particularly atrial automaticity; >80% with toxic rash
kinetics; often increased excitation recurrent AF; reduction in Metabolism: doses, torsades
concomitant K+ threshold ventricular accessory pathway Substrate: CYP2C9 de pointes (not
channel block tachycardia, conduction; (minor), CYP2E1 dose related)
ventricular increase in (minor), CYP3A4 Monitoring:
fibrillation refractory period, (major), ECG as needed,
(including short decrease reentrant P-glycoprotein at least every
QT syndrome tendency (Pgp; minor) 6 months
[SQTS] and Inhibits: CYP2D6
Brugada (strong) CYP3A4
syndrome) (weak), Pgp
Excretion: Urine
Disopyramide Half-life: 4–10 h Oral: 100– Heart failure Anticholinergic
Antiarrhythmic and Anticoagulant Agents

Bioavailability: 200 mg every 6 h exacerbations; (contraindicated in

>80% torsades de narrow-angle
Metabolism: pointes glaucoma); dry
Extensively Monitoring: mouth; urinary
intestinal and ECG as needed, retention;
hepatic via at least every constipation, blurry
CYP3A4 6 months vision
(CYP3A4 substrate)
Excretion: Urine
Procainamide Half-life: 3–4 h IV: 10–17 mg/kg Hypotension, Limited with
Bioavailability: Not (ideal body cardiac intravenous use
applicable given weight) at a rate arrhythmias,
intravenous of 20–50 mg/min heart failure
administration or 100 mg every exacerbation
Metabolism: 5 min; Monitoring:
Substrate: CYP2D6 maintenance Telemetry
(minor) infusion: 1–6 mg/
Excretion: Urine min
(continued)
65
Table 7.1 (continued)
66

Corresponding
Pharmacological Electrophysiological Major clinical likely therapeutic Example Pharmacokinetic Common dose(s) Cardiovascular Non-cardiovascular
targets effects applications mechanisms drug(s) parameters in adults adverse events events
Class Ib: Voltage-gated Na+ channel blockers
Nav 1.5 open state; Reduction in peak INa, Ventricular Reduction in Lidocaine Half-life: 120 min Intravenous (IV): Bradycardia, Dizziness,
rapid dissociation; AP generation with tachyarrhythmias ectopic ventricular Bioavailability: Not 1–1.5 mg/kg cardiac nervousness,
INa window current increased excitation (ventricular automaticity; applicable due bolus, repeat at arrhythmia unsteady gait,
threshold tachycardia, reduction in intravenous 0.5–0.75 mg/kg Monitoring: gastrointestinal
ventricular delayed administration every 5–10 min Telemetry distress, nausea,
fibrillation), afterdepolarization Metabolism: (up to 3 mg/kg); vomiting, tremor
particular after a (DAD) induced Substrate: CYP1A2 follow with
myocardial triggered activity; (major), CYP2A6 continuous
infarction reduced reentrant (minor), CYP2B6 infusion at
tendency by (minor); CYP2C9 1–4 mg/min)
converting (minor), CYP3A4
unidirectional (major)
block, particularly Excretion: Urine
in ischemic, Mexiletine Half-life: 9–15 h Oral: 150– Exacerbation of Dizziness,
partially Bioavailability: 200 mg every cardiac nervousness,
depolarized >80% 8–12 h; adjust arrhythmia unsteady gait,
myocardium Metabolism: dose as needed in Monitoring: gastrointestinal
Substrate: CYP1A2 50–100mg ECG as needed, distress, nausea,
(major), CYP2D6 increments no at least every vomiting, tremor
(major) more frequently 6 months
Inhibits: CYP1A2 than every
(moderate) 2–3 days up to
Excretion: Urine 300 mg every
8–12 h
C. J. Beavers
Corresponding
Pharmacological Electrophysiological Major clinical likely therapeutic Example Pharmacokinetic Common dose(s) Cardiovascular Non-cardiovascular
targets effects applications mechanisms drug(s) parameters in adults adverse events events
7
Class 1c: Voltage-gated Na+ channel blockers
Nav 1.5 inactivated Reduction in peak INa Supraventricular Reduction in Propafenone Half-life: 9–15 h Oral: Atrial flutter Metallic taste,
state; slow AP generation and tachyarrhythmias ectopic ventricular/ Bioavailability: Immediate with 1:1 dizziness
dissociation with increase (atrial tachycardia, atrial automaticity; >80% release: 150 mg conduction,
excitation threshold atrial flutter, atrial reduction in Metabolism: every 8 h with ventricular
fibrillation, and DAD-induced Substrate: CYP1A2 increase every tachycardia,
tachycardias triggered activity; (minor), CYP2D6 3–4 days up to may unmask
involving reduced reentrant (major), CYP3A4 300 mg every 8 h; Brugada-type
accessory tendency by (major) 450 mg once for ST elevation,
pathways); converting Inhibits: CYP1A2 pill in pocket contraindicated
ventricular unidirectional (weak), CYP2D6 dosing with coronary
tachyarrhythmias block to (weak); P-gp Extended release: disease
resistant to other bidirectional block; Excretion: Urine 225 mg every Monitoring:
treatment in the slowed conduction 12 h; dose may ECG as needed,
absence of and reduced of increase every at least every
structural heart excitability 5 days up to 6 months
Antiarrhythmic and Anticoagulant Agents

disease, premature particularly at 425 mg every

ventricular rapid heart rates 12 h
contraction, blocking reentrant Flecainide Half-life: 10–18 h Oral: 50–300 mg/ Atrial flutter Dizziness,
catecholaminergic pathways showing Bioavailability: day in divided with 1:1 headache, visual
polymorphic depressed >80% doses 8–12 h (can conduction, blurring
ventricular conduction Metabolism: go up to 400 mg ventricular
tachycardia Substrate CYP1A2 for ventricular tachycardia,
(minor) and arrhythmias may unmask
CYP2D6 (major) management) Brugada-type
Excretion: Urine ST elevation,
with some fecal contraindicated
with coronary
disease
Monitoring:
ECG as needed,
at least every
6 months
(continued)
67
Table 7.1 (continued)
68

Corresponding
Pharmacological Electrophysiological Major clinical likely therapeutic Example Pharmacokinetic Common dose(s) Cardiovascular Non-cardiovascular
targets effects applications mechanisms drug(s) parameters in adults adverse events events
Class 1d: Voltage-gated Na+ channel blockers
Nav 1.5 late current Reduction in late Na+ Ventricular Decrease AP Ranolazine Half-life: 7 h Oral: 500 to Bradycardia, Dizziness,
current (INa) affecting tachycardia, as a recovery time; Bioavailability: 1000 mg twice hypotension, headache,
AP recovery, potential new class reduction in early >76% daily, may prolonged QT constipation
refrac4toriness, of drugs for the afterdepolarization Metabolism: increase to Monitoring:
repolarization management of (EAD) induced Substrate: CYP2D6 1000 ng twice ECG as needed,
reserve, and QT tachyarrhythmias triggered activity (minor), CYP3A4 daily as needed at least every
interval (major), P-gp 6 months, renal
(minor) function
Inhibits: CYP2D6
(weak), CYP3A4
(weak), P-gp
Excretion: Urine
C. J. Beavers
Corresponding
Pharmacological Electrophysiological Major clinical likely therapeutic Example Pharmacokinetic Common dose(s) Cardiovascular Non-cardiovascular
targets effects applications mechanisms drug(s) parameters in adults adverse events events
7
Class II: Autonomic inhibitors and activators
Class IIa
Non-selective Inhibition of Sinus tachycardia Reduction in SAN Non-selective Refer to drug Refer to drug Bradycardia, Dizziness, fatigue
β- and selective adrenergically or other types of automaticity; β inhibitors: reference/package reference/package hypotension
β1-adrenergic induced Gs tachycardic, reduction in AVN Carvedilol, insert for each insert for each Monitoring:
receptor inhibitors protein-mediated including automaticity; propranolol, agent’s agent’s dosing Blood pressure
effects of increased supraventricular reduction in nadolol. pharmacokinetic information and heart rate
adenylyl kinase (atrial fibrillation, ectopic ventricular/ Selective information
activity and cyclic atrial flutter, atrial atrial automaticity; β1-adrenergic Note: atenolol is
AMP with effects of tachycardia), reduction in EAD-/ inhibitors: cleared renally and
including slowed arrhythmias; rate DAD-induced Atenolol, should be avoided
SAN pacemaker rate control of atrial triggered activity; bisoprolol, in patient with renal
fibrillation and reduced SAN betaxolol, disease
ventricular reentry; reduction esmolol,
tachyarrhythmias in AVN conduction metoprolol
(ventricular terminating reentry (tartrate and
Antiarrhythmic and Anticoagulant Agents

tachycardia, succinate)
premature
ventricular
contraction)
Note: Atenolol,
propranolol, and
nadolol used in
long QT syndrome;
nadolol used in
catecholaminergic
polymorphic
ventricular
tachycardia
(continued)
69
Table 7.1 (continued)
70

Corresponding
Pharmacological Electrophysiological Major clinical likely therapeutic Example Pharmacokinetic Common dose(s) Cardiovascular Non-cardiovascular
targets effects applications mechanisms drug(s) parameters in adults adverse events events
Class IIb
Non-selective Activation of Accelerating rates Increase escape Isoproterenol Half-life: 2.5–5 min Intravenous: Cardiac Flushing, dizziness,
β-adrenergic adrenergically of ventricular ventricular Bioavailability: Not 2–10 mcg/min IV; arrhythmias, headache,
receptor activators induced Gs-protein escape rhythm in automaticity; applicable due to titrate to patient hypertension hypokalemia
effects of increasing cases of complete suppression of intravenous response Monitoring:
adenylyl kinase atrioventricular Brady-cardia administration Heart rate,
activity and cAMP; block before dependent Metabolism: None blood pressure,
decrease in RR and definitive EAD-related Excretion: Urine potassium
PR intervals pacemaker triggered activity
implantation;
acquired,
often-drug related,
bradycardia-
dependent torsades
de pointes
Class IIc
Muscarinic M2 Inhibition of Mild or moderate Increase in SAN Atropine Half-life: 3–4 h Intravenous, Cardiac Hyperthermia,
receptor inhibitors supraventricular symptomatic sinus automaticity; Bioavailability: Not intramuscular: arrhythmias dizziness,
(SAN, atrial, AVN) bradycardia; increase in AVN applicable due to 0.5–1 mg every Monitoring: confusion,
muscarinic M2 supra-His, AVN, conduction intravenous 3–5 min; 1 mg Heart rate, electrolytes
cholinergic receptors; conduction block, administration preferred for blood pressure, abnormalities
decrease RR and PR elg. In vagal Metabolism: None severe electrolytes,
intervals syncope or acute Excretion: Urine bradyarrhythmia; mental status
inferior myocardial maximum total
infarction dose 3 mg
C. J. Beavers
Corresponding
Pharmacological Electrophysiological Major clinical likely therapeutic Example Pharmacokinetic Common dose(s) Cardiovascular Non-cardiovascular
targets effects applications mechanisms drug(s) parameters in adults adverse events events
7
Class IId
Muscarinic M2 Activation of Sinus tachycardia Reduction in SAN Digoxin Half-life: 38 h Oral: 0.125– Cardiac Digoxin toxicity
receptor activators supraventricular or supraventricular automaticity; Bioavailability: 0.25 mg daily arrhythmias (nausea, vomiting,
(SAN, atrial, AVN) tachyarrhythmias reduced SAN 70–85% Intravenous: Monitoring: visual disturbances
muscarinic M2 reentry; reduction (formulation 0.25–0.5 mg over Heart rate, [yellow, blurred
cholinergic receptors in AVN conduction dependent) several min, with blood pressure, vision, halos],
activates K channels, terminating reentry Metabolism: a repeat dose of electrolytes, lethargy,
hyperpolarizing the Substrate: CYP3A4 0.35 mg every 6 h digoxin level, arrhythmias, worse
SAN and shortening (minor), P-gp to a maximum serum creatinine with hypokalemia)
APDs in atrial and Excretion: Urine dose of 1.5 mg
AVN tissue over 24 h
Class IIe
Adenosine A1 Activation of Acute termination Reduction in SAN Adenosine Half-life: <10 s Intravenous: Cardiac Headache,
receptor activators adenosine A1 of AVN automaticity; Bioavailability: Not Initial 6 mg IV arrhythmia, dizziness, facial
receptors in tachycardia and reduction in AVN applicable push (rapid, with chest pressure flushing,
supraventricular cAMP mediated conduction, Metabolism: None 20 mL saline Monitoring: gastrointestinal
Antiarrhythmic and Anticoagulant Agents

tissue (SAN, atrial, triggered VTs; terminating flush); if not ECG, heart rate, distress, neck
AVN) activates G differentiation of reentry; reduction effective within blood pressure discomfort, dyspnea
protein-coupled sinus versus atrial in EAD-/DAD- 1–2 min, 12 mg
inward rectifying K+ tachycardia induced triggered maybe given; may
channels and IKAdo activity repeat 12 mg
current bolus if needed.
hyperpolarizing the Maximum single
SAN and shortening dose 12 mg. Note:
APDs in atrial and Initial dose
AVN tissue should be reduced
to 3 mg if patient
is currently
receiving
carbamazepine or
dipyridamole, has
a transplanted
heart or if
adenosine
administered via
central line
(continued)
71
Table 7.1 (continued)
72

Corresponding
Pharmacological Electrophysiological Major clinical likely therapeutic Example Pharmacokinetic Common dose(s) Cardiovascular Non-cardiovascular
targets effects applications mechanisms drug(s) parameters in adults adverse events events
Class III: K+ channel blockers and openers (note this table will focus on class IIIa; IIB or IIc not highlighted due to lack of currently approved agents at time of publication)
Class IIIa-voltage dependent K+ channel blockers
Nonselective K+ Block of multiple K+ Ventricular Increase in AP Amiodarone Half-life: Supraventricular Sinus Pulmonary (acute
channel blockers channel targets tachycardia in recovery time; 40–55 days arrhythmias bradycardia, hypersensitivity
resulting in prolonged patients without increase in Bioavailability: Intravenous: QTc pneumonitis,
atrial, Purkinje, and/ structural heart refractory period 35–65% 150 mg over prolongation, chronic interstitial
or ventricular disease or with with decrease Metabolism: 10 min, then cardiac infiltrates);
myocyte AP recovery, remote myocardial reentrant tendency; Substrate: CYP1A2 1 mg/min for 6 h, arrhythmias hepatitis; thyroid
increased ERP, and infarction note: Amiodarone (minor), CYP2C19 then 0,5 mg/min Monitoring: (hypothyroid or
reduced (amiodarone only) also slows sinus (minor), CYP2C8 for 18 h. Continue Blood pressure, hyperthyroid):
repolarization tachyarrhyhtmias node rate and (minor), CYP2D6 for a total load up heart rate, ECG, Photosensitivity;
reserve; prolonged with Wolff- atrioventricular (minor), CYP3A4 to 10 g; may history and blue-grey skin
QT intervals Parkinson white conduction (has (major), P-gp finish load with physical exam discoloration with
syndrome; atrial class II and IV (minor) oral dosing. every chronic high doses;
fibrillation with properties) Inhibitor: CYP2C9 Oral: 600– 3–6 months, nausea; ataxia;
atrioventricular (weak), CYP2D6 800 mg daily in pulmonary tremor; alopecia
conduction via (weak), CYP3A4 divided doses for function test,
accessory pathway (weak), P-gp a total of 10 g chest X-ray
(amiodarone only); Excretion: Feces load then every
ventricular maintenance of 3–6 months,
fibrillation and 200–400 mg once liver function
premature daily test baseline and
ventricular Ventricular semiannually;
contraction arrhythmias: electrolytes,
(amiodarone only); Intravenous: thyroid function
Tachyarrhyhtmias 150 mg over tests before
associated with 10 min, then treatment and
supraventricular 1 mg/min for 6 h, periodically
arrhythmias and then 0,5 mg/min thereafter
atrial fibrillation for 18 h. Continue (3–6 months);
for a total load up regular
to 10 g; may ophthalmic
finish load with exams
oral dosing.
Oral: 400 mg every
C. J. Beavers

8–12 h for 1–2

weeks, followed by
200–400 mg once
daily
Corresponding
Pharmacological Electrophysiological Major clinical likely therapeutic Example Pharmacokinetic Common dose(s) Cardiovascular Non-cardiovascular
targets effects applications mechanisms drug(s) parameters in adults adverse events events
7
Dronedarone Half-life: 13–19 h Oral: 400 mg Bradycardia, Anorexia, nausea,
Bioavailability: twice daily with new onset or hepatotoxicity,
Without food: 4%, meals worsening heart pulmonary toxicity
with high fat meal failure (death
15% increased in
Metabolism: patients with
Substrate: CYP3A4 symptomatic
(major) heart failure),
Inhibits: CYP2D6 prolonged QTc/
(weak), CYP3A4 torsades de
(moderate),P-gp pointes
Excretion: Feces Monitoring:
ECG (at least
every
3 months), heart
rate, blood
Antiarrhythmic and Anticoagulant Agents

pressure, signs/
symptoms of
heart failure,
signs of
pulmonary
toxicity, liver
enzymes
(continued)
73
74
Table 7.1 (continued)
Corresponding
Pharmacological Electrophysiological Major clinical likely therapeutic Example Pharmacokinetic Common dose(s) Cardiovascular Non-cardiovascular
targets effects applications mechanisms drug(s) parameters in adults adverse events events
Kv11.1 (HERG) Prolonged atrial, Ventricular Increase in AP Dofetilide Half-life: ~ 10 h Oral: Note CrCl Torsades de Headache,
channel-mediated Purkinje and tachycardia in recovery time; (extended with renal and QTc interval pointes dizziness, nausea
rapid K+ 1current ventricular myocyte patients without increase in impairment) must be Monitoring:
(IK) blockers AP recovery, increase structural heart refractory period Bioavailability: determined prior ECG
ERP, and reduced disease or with with decrease >90% to first dose. If monitoring,
repolarization remote myocardial reentrant tendency Metabolism: QTc > 440 ms baseline and
reserve; prolonged infarction (sotalol Substrate: CYP3A4 (>500 ms in regular serum
QT intervals only) (major) patients with creatine,
tachyarrhyhtmias Excretion: Renal ventricular electrolytes
with Wolff- conduction
Parkinson white abnormalities),
syndrome; atrial doffetilide is
fibrillation with contraindicated.
atrioventricular Adjust dose in
conduction via those with CrCL
accessory pathway <60 mL/min.
(sotalol only); Patient requires
ventricular hospitalization for
fibrillation and 3 days when
premature starting
ventricular Initial 500mcg
contraction (sotalol twice daily
only); (reduce dose
Tachyarrhyhtmias based on QTc and
associated with CrCl; refer to
supraventricular package insert)
arrhythmias1 and
atrial fibrillation
C. J. Beavers
Corresponding
Pharmacological Electrophysiological Major clinical likely therapeutic Example Pharmacokinetic Common dose(s) Cardiovascular Non-cardiovascular
targets effects applications mechanisms drug(s) parameters in adults adverse events events
7
Ibutilide Half-life: 2–12 h Intravenous: Torsades de Nausea
Bioavailability: Not <60 kg: 0.01 mg/ pointes
applicable kg over 10 min
Metabolism: None ≥60 kg: 1 mg
Excretion: Urine over 10 min
Sotalol Half-life: 12 h Note CrCl and Bradycadia, Brochospasm
Bioavailability: QTc interval must torsades de
Well absorbed; be determined pointes
decreased by ~20% prior to first dose. Monitoring:
by meals compared If CrCl ≤ 60 mL/ ECG
to fasting min, dose monitoring,
Metabolism: None adjustment baseline and
Excretion: Renal warranted. Please regular serum
see package creatine,
insert. electrolytes,
Oral: 80 mg twice heart rate
Antiarrhythmic and Anticoagulant Agents

daily
Intravenous:
75 mg infused
over 5 h twice
daily
(continued)
75
76
Table 7.1 (continued)
Corresponding
Pharmacological Electrophysiological Major clinical likely therapeutic Example Pharmacokinetic Common dose(s) Cardiovascular Non-cardiovascular
targets effects applications mechanisms drug(s) parameters in adults adverse events events
Class IV: Ca2+ (note this table will focus on class IVa; IVb, IVc,IVd, IVe not highlighted due to lack of currently approved agents at time of publication)
Class IVa: Surface membrane Ca2+ channel blockers
L-type Ca2+ current Block Ca2+ current Supraventricular Reduction in AVN Diltiazem Half-life: 3–9 h Oral: Bradycardia, Headache
blockers (ICa), resulting in arrhythmias and conduction, (depending on Immediate release: hypotension,
inhibition of SAN ventricular terminating immediate or 30 mg four times peripheral
pacing, inhibition of tachycardia reentry; reduction extended release) daily; increase as edema
AVN conduction, without structural in EAD-/ Bioavailability: needed to achieve Monitoring:
prolonged ERP, heart disease; rate DAD-induced ~40% rate control; usual Blood pressure,
increased AP control of atrial triggered activity Metabolism: doses 120– heart rate
recovery time fibrillation Substrate: CYP2C9 480 mg/day in 3–4
(minor), CYP2D6 doses
(minor), CYP3A4 Extended release:
(major), P-gp Initial 120 mg
(minor) once daily or in 2
Inhibits: CYP2D6 divided doses;
(weak), CYP3A4 increase as
(moderate) needed; usual
Excretion: Urine dose 120–
480 mg/day
Intravenous:
Bolus dose:
0.25 mg/kg (actual
body weight) over
2 min. If rate
control
insufficient after
15 min a repeat
bolus dose of
0.35 mg/kg can be
given
Continuous
infusion: Initial
5–10 mg/h;
infusion rate
maybe increased in
C. J. Beavers

5 mg/h increments
every 10–15 min
up to maximum of
15 mg/h
Corresponding
Pharmacological Electrophysiological Major clinical likely therapeutic Example Pharmacokinetic Common dose(s) Cardiovascular Non-cardiovascular
targets effects applications mechanisms drug(s) parameters in adults adverse events events
7
Verapamil Half-life: 2–12 h Oral: Bradycardia, Headache,
Bioavailability: Immediate hypotension, constipation
20–35% release: Initial peripheral
Metabolism: 40 mg three to edema
Substrate: CYP1A2 four times daily; Monitoring:
(minor), CYP2B6 increase as Blood pressure,
(minor), CYP2C9 needed to achieve heart rate
(minor), CYP3A4 rate control;
(major), P-gp maximum dose:
(minor) 480 mg/day in
Inhibitor: CYP1A2 3–4 doses
(weak), CYP3A4 Extended release:
(moderate), P-gp 120–180 mg once
Excretion: Urine daily; maximum
daily dose 480 mg
Intravenous:
Antiarrhythmic and Anticoagulant Agents

Bolus dose:
5–10 mg over
2 min if rate
control
insufficient after
15–30 min a
repeat bolus dose
of 0.35 mg/kg can
be given
Continuous
infusion: Initial
5 mg/h; infusion
rate maybe
increased in
5 mg/h
increments every
15–30 min up to
maximum of
20 mg/h
AP-action potential; APD-action potential duration; AVN-atrioventricular node; CrCL- creatinine clearance; DAD-delayed afterdepolarization; EAD- early afterdepolarization;
ERP- effective refractory period; P-gp-P-glycoprotein SAN- sino-atrial node
Adapted from the references [1–3]
77
Table 7.2 Oral anticoagulants used in stroke prevention for AF
78

Characteristic Warfarin Dabigatran Apixaban Edoxaban Rivaroxaban

Mechanism of Vitamin K antagonist Direct thrombin Factor Xa Factor Xa Factor Xa inhibition
action inhibitor inhibition inhibition
Standard dosing 5 mg daily (avoid loading doses), 150 mg twice 5 mg twice daily 60 mg daily 20 mg daily with evening meal
adjust to achieve INR 2–3 daily
Renal Consider starting doses of ≤2.5 mg 75 mg twice 2.5 mg twice daily 30 mg daily 15 mg daily (CrCl 15–50 mL/min)
impairment daily if: daily (CrCL If at least two of (CrCl
dosing • Age ≥65 15–30 mL/min) three criteria: 15–50 mL/min)
• Weight ≤70 kg • Age ≥80
Poor nutritional status • Weight
• Significant hepatic disease ≤60 kg
• Increase bleeding risk SCr ≥1.5 mg/dL
• Known warfarin sensitivity
• Decompensated HF
Hepatic Consider starting doses of ≤ 2.5 mg No adjustment Child-Pugh class Child-Pugh Child-Pugh class B:
impairment daily if: B: class B: Avoid Avoid or use with caution
dosing • Age ≥65 Avoid or use with or use with Child-Pugh class C:
• Weight ≤70 kg caution caution Avoid use
Poor nutritional status Child-Pugh class Child-Pugh
• Significant hepatic disease C: class C: Avoid
• Increase bleeding risk Avoid use use
• Known warfarin sensitivity
• Decompensated HF
Time to peak 5–7 days 1–3 h 1–2 h 1–2 h 2–4 h
Half-life (h) ~40 h 8–15 h 12 h 10–14 h 7–11 h
Excretion Hepatic, primarily through CYP2C9 80% renal 25% renal, 75% 50% renal; 66% renal (one-half as inactive form)
fecal also, bile, feces
Metabolized CYP2C9, CYP1A2, CYP3A4, P-gp P-gp and CYP3A4 P-gp P-gp and CYP3A4
CYP2C19
P-gp and/or Consider higher starting dose, monitor Avoid use Avoid use Avoid use Avoid use
strong CYP3A4 INR closely
inducers
P-gp inhibitors Not applicable If CrCl <50 mL/ Not applicable 30 mg daily Not applicable
min, avoid use or
reduce dose
C. J. Beavers
7
Dual P-gp and Consider lower starting dose, monitor Not applicable Avoid use Not applicable • Avoid use
strong CYP INR closely • No dose • No dose change needed with concomitant
inhibitors change needed clarithromycin
with
concomitant
clarithromycin
Dual P-gp and Monitor INR closely Not applicable Use with caution Not applicable If CrCl <80 mL/min, avoid use unless benefit justifies
moderate potential risk
CYP3A4
inhibitors
Reversal strategy Vitamin K, prothrombin complex Idarucizumab Andexanet alfa Andexanet alfa Andexanet alfa and prothrombin complex concentrate
concentrate, or fresh frozen plasma and prothrombin and
complex prothrombin
concentrate complex
concentrate
Antiarrhythmic and Anticoagulant Agents

Package inserts from https://www.nlm.nih.gov

79
80 C. J. Beavers

References 2. Zimetbuam P. Antiarrhyhtmic drug therapy for atrial

fibrillation. Circulation. 2012;125:381–9.
3. Package inserts from https://www.nlm.nih.gov.
1. Lei M, Lin W, Terrar D, Huang CL. Modernized clas-
sification of cardiac antiarrhythmic drugs. Circulation.
2018;138:1879–96.
Bradycardia
8
Hannah Kibler and Sharon Vannoy

Sinus Node Dysfunction Sinus Bradycardia

Sinus node dysfunction (SND) is often used to In some individuals, including trained athletes, a
describe abnormalities of impulse conduction heart rate below 50 bpm is acceptable and a nor-
originating from the Sinoatrial (SA) node. mal variant. Bradycardias can be noted as a mani-
Degenerative changes in sinus node tissue occur festation of increased vagal tone, normal aging,
throughout the lifespan and can lead to altera- and are common in the elderly population as a
tions in the generation or conduction of impulses, result of disease progression such as in hypothy-
such as a prolonged pauses or sinus bradycardic roidism. Symptomatic bradycardia is due to
episodes. Sinus node dysfunction is most com- reduced cardiac output, which is a function of
mon in individuals over 70 years of age. Sick stroke volume and heart rate. The need for inter-
sinus syndrome (SSS) refers to the symptomatic vention is determined by the presence of
expression of sinus node dysfunction in patients symptoms.
resulting in fatigue, presyncope, syncope, dizzi-
ness, dyspnea, and other outward signs of cardiac
output. Sinus Pause
Tachycardia- bradycardia syndrome refers to a
condition, when an individual has a co-morbid A sinus pause, or sinus arrest, is the failure of the
conduction abnormality resulting in a rapid atrial sinus node to generate an atrial depolarization for
rate, such as atrial fibrillation, atrial flutter, or a period of time, generally defined as 3 seconds
other supraventricular tachycardia. Upon conver- or longer between atrial contractions. Pauses can
sion from the tachycardia, the sinus node fails to result from a block of the normal impulse from
efficiently create an impulse resulting in a pause the sinoatrial tissue or due to failure of the sinus
or bradycardia. Patients may or may not be symp- node to depolarize. Nocturnal pauses are com-
tomatic with the conversion pause or bradycardia monly related to obstructive sleep apnea, which
which results. should be considered in the differential for
assessment and in the treatment plan. Pauses are
also more common in patients with tachycardia-
H. Kibler · S. Vannoy (*) bradycardia syndrome occurring when the
Atrium Health Wake Forest Baptist, tachyarrhythmia terminates and the sinus node is
Winston-Salem, NC, USA in recovery. The presence of sinus pauses, in
e-mail: [email protected]; absence of symptoms, does not always warrant
[email protected]

© The Author(s), under exclusive license to Springer Nature Switzerland AG 2023 81

Table 8.1 Causes of bradycardia

Medications Tissue disorders Metabolic Miscellaneous
Antiarrhythmics Amyloidosis Hyper/hypokalemia Acute MI
Beta blockers Cardiomyopathies Hypocalcemia Autonomic dysfunction
Calcium Channel blockers Ischemic, non-ischemic, Hypothermia Cardiac surgery
(non-dihydropyridine) infiltrative Hypoxia CABG, TAVR, maze,
Digoxin Connective tissue disease Ion channel valve
Interferon RA, SLE, scleroderma dysfunction Replacement, ablation
Lithium Hemochromatosis Hypothyroidism
Methyldopa Sarcoidosis Infection
Opioids Degenerative fibrosis Lyme disease, typhoid
Risperidone fever
Psychotropic meds Dengue fever, malaria
Sympatholytics Guillain-Barre
Illicit drugs Obstructive sleep apnea
Toxins
Goldberger et al. [1], Kusumoto et al. [2], Semelka and Gera [3]

intervention and can be associated with various implantation can provide symptom relief through
physiologic and pathologic conditions as well as rate responsive pacing (see Chap. 13).
extrinsic factors including medications, electro-
lyte imbalance, increased vagal tone, and others
(see Table 8.1). Frequent sinus pauses lasting Atrioventricular Blocks
longer than 3 seconds and are symptomatic war-
rant consideration for pacing support. A disturbance of impulse conduction between
the atria and ventricles is known as atrioven-
tricular (AV) block or heart block. This can
Chronotropic Incompetence occur if there is delayed conduction, intermit-
tent loss of conduction, or complete loss of
Chronotropic incompetence is defined as the conduction from the atria to the ventricles. AV
inability of the heart rate to adjust appropriately block/heart block is categorized based on the
in concordance with increased physical activity severity of the impulse conduction distur-
or cardiovascular demand. Patients can present bance. The types of AV block will be addressed
with fatigue, lightheadedness, dyspnea on exer- separately below.
tion, or syncope associated with activity. Further
criteria for diagnosis of chronotropic incompe-
tence, which is well established, includes the fail- irst Degree AV Block (See Figs. 8.1
F
ure of the individual to reach 80% of their and 8.2)
maximum predicted heart rate at peak exercise.
This can be evaluated with exercise stress testing First-degree heart block is defined as prolonged
on a treadmill or bicycle. It is important to thor- conduction from the atria to the ventricles with a
oughly assess individuals in whom there is suspi- PR interval greater than 200 ms. This can be sec-
cion for chronotropic incompetence as the ondary to a conduction delay at the AV node and/
condition is also associated with increased risk of or the His-Purkinje system. The site of delay can
coronary artery disease and is seen in approxi- be difficult to differentiate, though one clue is
mately one-third of individuals with congestive response to exercise. Increased sympathetic tone
heart failure [4]. In these patients, pacemaker can increase conduction velocity in AV node
8 Bradycardia 83

Fig. 8.1 Sinus rhythm with first-degree AV block. PR interval ~ 250 ms

Fig. 8.2 Sinus rhythm with first-degree AV block. PR interval ~420 ms.

thereby shortening the PR interval if that is where gressive PR interval prolongation followed by a
the delay is occurring; absent PR shortening single non-conducted P wave.
would suggest a lower level of delay. Mobitz Type II appears on the ECG as a con-
stant PR interval with intact conduction followed
by a single non-conducted P wave.
econd-Degree AV Block (See
S Mobitz I and Mobitz II block refer to ECG
Figs. 8.3 and 8.4) patterns. Mobitz I block is more commonly at the
level of the AV node and more responsive to
Second-degree heart block is characterized by changes in autonomic tone, occurring for exam-
intermittent conduction from the atria to the ven- ple frequently with sleep in patients otherwise
tricles. There are two separate types: normal AV conduction. Mobitz II block, con-
Mobitz Type I is also referred to as versely, can be both in the AV node and His-
Wenckebach. This is noted on the ECG by pro- Purkinje system, the latter to be suspected when
84 H. Kibler and S. Vannoy

Fig. 8.3 Mobitz Type I (Wenckebach). PR interval gradually prolongs until a QRS is dropped and the next PR interval
is shorter than the one prior to the drop

Fig. 8.4 Mobitz Type II. PR interval of conducted beats is stable, every other beat is dropped and QRS is narrow indi-
cating block in the AV node

conduction disease (bundle branch or fascicular though this finding is reflective of more
block) is present. This form of AV block is less advanced disease.
responsive to changes in autonomic tone.

hird Degree/Complete Heart Block

T
dvanced/High-Grade AV Block
A (Fig. 8.6)
(Fig. 8.5)
Third-degree heart block is characterized by the
High-grade AV block, which is differentiated absence of conduction between the atria to the
from third-degree (complete) AV block, ventricles. This is also frequently described as a
denotes intermittent conduction from the atria complete dissociation between the atria and the
to the ventricles. When conducting from the ventricles. The ventricular rate is consequently
atria to the ventricles, the PR interval is con- driven by an escape rhythm. Portions of the con-
stant; however, there can be two or more conduction system have enhanced automaticity with
secutive non- conducted P waves (unlike impulse generation at rates that classically slow
second-degree heart block type II, where there as the site of escape moves lower in the conduc-
is only a single non-conducted P wave). The tion system. Escape rhythms from the AV node
mechanism of block is like Mobitz II AV block, below the level of block are often quite stable and
8 Bradycardia 85

Fig. 8.5 Advanced or high-grade heart block

Fig. 8.6 Third-degree/complete heart block with LBBB escape rhythm

marked by a QRS complex nearly identical to ically unstable heart rates, or presenting with
baseline. Escape rhythms from the lower conduc- syncope. Often, patients with complete heart
tion system or ventricle, or wide complex block have compensatory hypertension due to
escapes, are much less stable and high risk for increased SVR. Do not treat the hypertension.
hemodynamic instability. Placement of tempo- Vasodilating the patient may cause hemodynamic
rary pacemakers should be strongly considered in instability due to fixed cardiac output from the
patients with wide escape rhythms, hemodynam- bradycardia.
86 H. Kibler and S. Vannoy

Conduction System Abnormalities to a block in conduction within the right bundle,

the impulse reaches the RV through myocardial
Additional conduction abnormalities occur cell-to-cell conduction which is much slower.
within the bundle branch system. The normal Electrocardiographic signs of RBBB include an
QRS interval ranges from 0.06–0.10 seconds; initial small r wave in V1 and V2 (the right precor-
however, if a bundle branch block is present, the dial leads) and a small q wave in leads I, aVL, V5,
QRS duration is 0.12 seconds or longer. Despite and V6 as septal depolarization from the left bun-
the conduction delay associated with a bundle dle is unaffected. Often the rSR’ pattern that
branch block, many patients remain asymptom- results in V1 and V2 is coined “rabbit ears” given
atic. Changes in morphology related to bundle the appearance of the two points on the R waves.
branch blocks can be best identified in various Right bundle branch blocks are the most com-
leads on the 12-lead ECG. In addition to the mon conduction disorder of the ventricular con-
widened QRS interval, the QRS complex will duction system and can occur without any
have an abnormal shape. Furthermore, as depo- underlying cause or obvious pathology. Acutely,
larization is abnormal in a BBB, repolarization a RBBB can be seen in patients with ischemia or
is also abnormal which results in T-wave inver- anterior MI and in additional associated condi-
sion. Most commonly, this is noted in opposing tions such as heart failure, valvular heart disease,
deflection patterns of the QRS complex and and pulmonary embolism. Notably, the presence
T-waves of the same beat. of a RBBB in a patient without significant heart
disease does not increase risk of cardiovascular
(CV) death; thus, if the patient is otherwise
Right Bundle Branch Block (Fig. 8.7) asymptomatic, no treatment is indicated. In
patients with known CV disease, having a RBBB
The electrical impulse of a right bundle branch is an independent risk factor for all-cause mortal-
block (RBBB) is conducted through the intraven- ity. In the setting of acute MI or the post MI
tricular septum down the faster conducting left period, a RBBB is associated with increased risk
bundle branch to the left ventricle. However, due of mortality.

Fig. 8.7 Right bundle

branch block
morphology
(Cardiology, Chang [5]:
Springer)
8 Bradycardia 87

Left Bundle Branch Block (Fig. 8.8) heart block leading to implantation of a
pacemaker.
In a left bundle branch block (LBBB), electricity Due to the mechanism of the delayed conduc-
moves quickly down the right bundle branch to tion in a LBBB, the right ventricle receives the
depolarize the right ventricle. Next the impulse is electric impulse before the left ventricle. In time,
carried more slowly across the interventricular this can cause remodeling of the left ventricle due
septum and finally to the left ventricle, which is to alterations in left ventricular perfusion,
in opposition to normal depolarization. mechanics, and workload. In the setting of heart
Electrocardiographic characteristics of a LBBB failure, the presence of a LBBB is an independent
include a deep, wide QRS complex in lead V1 and predictor of mortality despite other risks associ-
a large R wave in lead V6, as well as a wide QRS ated with underlying disease, gender, or age. In
complex with a T-wave in the opposite direction comorbid heart failure with reduced ejection
from the primary QRS deflection [6]. Often a left fraction, <35%, a QRS interval greater than
axis deviation is also present. 150 ms, and Class II or greater symptoms of heart
Conditions associated with LBBB include failure, cardiac resynchronization therapy (CRT)
myocardial infarction (MI), hypertension, is reasonable and may be recommended.
severe aortic stenosis (AS), Lenégre disease (a
primary degenerative disease of the conduction
system), and various cardiomyopathies. Cardiac Left Anterior Fascicular Block (LAFB)
surgery and trans-catheter aortic valve replace-
ment as well as primary amyloidosis are all The left bundle branch further divides into the
associated with increased risk of conduction anterior and posterior fascicles. Conduction
disease. Left bundle branch blocks are more down the left bundle depolarizes the interventric-
common in the elderly and in those with heart ular septum and causes a septal Q-wave in leads
disease and should signal the need for further I, aVL, and V6. If the anterior fascicle is not con-
investigation as to causation such as echocar- ducting, the impulse proceeds from posterior to
diography or stress testing. Of note, if a LBBB anterior resulting in a profound Left axis. The Q
is found in the presence of acute MI, the patient wave is present in the lateral leads as stated
has much greater risk of developing complete above. A small R wave is present with a very

Fig. 8.8 Left bundle

branch block
morphology
(Cardiology, Chang [5]:
Springer)
88 H. Kibler and S. Vannoy

Fig. 8.9 First degree AV block with LAFB and RBBB

negative deflection in leads II and III as well. If ahelpful, initial test. Interpretation of the ECG
RBBB is present with a left axis, consider a rhythm with attention to interval lengths and
LAFB which is called bifascicular block. If first waveforms and can further direct diagnosis and
degree block is also seen, it is called trifascicularmanagement. Based on the patient’s history,
block and has a higher risk of symptomatic bra- symptoms, physical exam, and ECG findings,
dycardia (see Fig. 8.9). further evaluation with ambulatory cardiac mon-
itoring may be completed. Home monitoring
allows for a quantitative evaluation of arrhyth-
Evaluation and Management mia as well as correlates the patient’s symptoms
of Conduction Abnormalities with the timing and type of arrhythmia. The type
of monitoring is dependent upon the frequency
To evaluate causes of bradycardia, a thorough of symptoms. If the individual is experiencing
history and physical exam should be performed. daily symptoms, home monitoring through a
When taking the history, emphasis should be wearable device is reasonable, noting more
placed on evaluation of the timing and relation- accurate diagnosis with longer recordings of
ship of symptoms to activity, meals, stress, posi- 2–4 weeks as compared to a 24-to-48-hour mon-
tion changes, and other triggers. A list of current itoring window. For patients with less frequent
medications, both prescription and non-symptoms of arrhythmia, or if syncope is the
prescription, are also vital to evaluating causa- chief symptom, an implantable loop recording
tion. Furthermore, the family history and device should be considered. Furthermore, based
complete cardiac history should be investigated. on clinical history, if chronotropic incompetence
A comprehensive physical examination includ- is suspected, ambulatory heart monitoring and
ing carotid pulses and auscultation for bruits, exercise stress testing is appropriate. As previ-
peripheral pulses, heart sounds (to assess for ously discussed, patients who have nocturnal
structural/valvular disease), obtaining orthostatic sinus pauses should be evaluated for sleep apnea.
vitals, and assessing for signs of systemic illness Laboratory studies to identify causes of bra-
are of importance. dycardia are directed by findings noted within the
Following the history and physical exam, a history and physical. Given potential underlying
12-lead electrocardiogram (ECG) is the most etiologies of thyroid disease, metabolic syn-
8 Bradycardia 89

dromes, electrolyte imbalance, and infectious indicated. Temporary and permanent pacing will
processes, a metabolic panel including magne- be discussed in Chap. 13.
sium, a complete blood count, and thyroid func-
tion testing are reasonable to assess. Guidelines Pearls
also support that individual with conduction dis- • Symptoms are the defining factors determin-
ease be screened with Lyme titers, if they reside ing whether bradycardia needs treatment.
in endemic regions. For younger patients present- • Look for underlying causes of bradycardia
ing with advanced blocks, further investigation before recommending permanent pacing.
for connective tissue diseases such as sarcoidosis • Type 1 and Type II Mobitz I do not need
and amyloidosis is warranted. Lastly, in patients treatment.
with conduction disorders caused by genetic • March out the P waves and then the R waves
mutations including SCN5A sodium channel and to determine their relationship.
LMNA (Lamin A/C) mutations, it is recom- • Normal PR is <200 ms.
mended that their first-degree relatives likewise • Normal QRS 0.6–0.10.
undergo gene testing (Table 8.1).
For patients with incidentally diagnosed first-
degree AV block and second-degree type I AV
block, no immediate pacing intervention is References
required. Consideration of exercise stress testing,
particularly with second-degree type I AV block 1. Goldberger A, Goldberger Z, Shvilkin A. Sinus and
escape rhythms. In: Goldberger A, Goldberger Z,
is recommended to ensure adequate chronotropic Shvilkin A, editors. Goldberger’s clinical electrophys-
competence. A transthoracic echocardiogram is iology: a simplified approach. Philadelphia: Elsevier
recommended to evaluate for structural heart Inc; 2018. p. 122–9.
disease. If this is unrevealing for abnormality and 2. Kusumoto F, Schoenfeld M, Barrett C, Edjertons
J, Ellenbogen K, Gold M, et al. 2018 guideline on
the patient is asymptomatic, observation without the evaluation and Management of Patients with
further intervention can be considered. Bradycardia and Cardiac Conduction Delay: a report
Ambulatory monitoring (2–4 weeks) is appropri- of the American College of Cardiology/American
ate to ensure that there is no further underlying Heart Association task force on clinical practice
guidelines and the Heart Rhythm Society. Circulation.
AV nodal disease such as second-degree type II 2019;140(8):e382–482. https://doi.org/10.1161/
AV block or high-degree AV block. CIR.0000000000000628.
For patients with symptomatic second-degree 3. Semelka M, Gera J. Sick sinus syndrome: a review.
type II AV block, high-degree AV block or third- Am Fam Physician. 2013;87(10):691–6.
4. Camm A, Fei L. Chronotropic incompetence-part II:
degree AV block temporary pacing may need to clinical implications. Clin Cardiol. 1996;19:503–8.
be considered while further workup for reversible 5. Chang B. Cardiology. In: Lecker SC, editor. The ulti-
causes is performed. Furthermore, if no revers- mate medical school rotation guide. Cham: Springer;
ible cause is identified or if the patient will 2021. https://doi.org/10.1007/978-3-030-63560-2_16.
6. Geiter H. Understanding bundle branch blocks. Nurs
require AV nodal blocking agents for manage- Crit Care. 2010;5(6):5–8. https://doi.org/10.1097/01.
ment of comorbidities, then permanent pacing is CCN.0000389043.40866.b5.
Atrial Arrhythmias
9
Lora Raines

Introduction with different electrophysiologic properties

and are dependent on these pathways [1, 2].
According to the 2015 ACC/AHA/HRS Guidelines
for the Management of Adult Patients with SVT,
women have higher incidence of PSVT than men, Inappropriate Sinus Tachycardia
and persons over age 65 have >5 times the risk of
developing PSVT than younger persons [1]. Anatomy and Physiology
SVTs typically have a narrow QRS complex
on an ECG, but they may have a wide QRS com- The sinus node is the heart’s natural pacemaker.
plex if (1) there is a baseline bundle branch block It is located in the superior lateral portion of the
present, (2) there is aberrancy, or (3) a bypass right atrium near its junction with the superior
tract is present [1, 2]. SVTs typically occur due to vena cava. It consists of pacemaker cells that can
enhanced automaticity of certain cells with pace- generate electrical impulses. The blood supply
maker capabilities (automatic SVT) or the pres- for the sinus node typically originates from the
ence of a re-entry circuit that allows for rapid right coronary artery. The rate of electrical
impulse conduction (re-entrant SVT). There are impulses that originate from the sinus node can
also triggered mechanisms for SVT. vary, but normal sinus rhythm is typically 60–100
beats per minute. Sinus bradycardia is when the
• SVTs due to enhanced automaticity occur rate is less than 60 beats per minute. Sinus tachy-
because of abnormalities in impulse initiation cardia is when sinus rates are greater than 100
and typically exhibit spontaneous firing rates beats per minute. There is also sinus arrhythmia,
faster than the sinus node (though sinus tachy- in which the impulses are still originating from
cardia occurs due to enhanced automaticity of the sinus node, but the timing of the impulses is
the sinus node) [1, 2]. irregular. This is a normal in healthy, young indi-
• SVTs due to re-entry exhibit abnormal con- viduals and due to elevated vagal tone.
duction of an electrical impulse due to the When the sinus node fires, the electrical activ-
existence of two separate electrical pathways ity travels through the right and left atrium down
to the AV node. The initial indication of sinus
node activity on the ECG is the P wave, although
the P wave represents activation of the atria.
L. Raines (*) Because the sinus node is in the high right atrium,
Wellstar Health System, Marietta, GA, USA the right atrium depolarizes before the left atrium.
e-mail: [email protected]

© The Author(s), under exclusive license to Springer Nature Switzerland AG 2023 91

R. Musialowski, K. Allshouse (eds.), Cardiovascular Manual for the Advanced Practice Provider,
https://doi.org/10.1007/978-3-031-35819-7_9
92 L. Raines

Therefore, the first half of the P wave is due to will demonstrate sinus tachycardia while upright,
right atrial activation and the second half of the P and rates improve in the supine position.
wave is due to left atrial activation. On an ECG,
normal sinus rhythm is indicated by a sinus P
wave before every QRS with 1:1 conduction. A Physical Exam Correlations
sinus P wave should be upright in lead II and will
typically be upright in leads I, aVF, and V3-V6 On exam, the rhythm will be regular, but tachy-
[3]. Sinus rhythm will gradually increase and cardic. Correlation with clinical conditions will
decrease on ECG or telemetry in response to help determine if the sinus tachycardia is an
exercise or increased metabolic needs (i.e., appropriate response to a particular stimulus, or
fever). inappropriate and pathologic. Signs of potential
secondary causes should be considered during
the exam, such as hyperthyroidism, hyper-
Pathology/Description cortisol state (Cushing’s signs), heart failure,
shock, or infection.
As mentioned, sinus tachycardia refers to sinus
rhythm in which the rates are greater than 100
beats per minute. Impulse rates are governed by Diagnosis/Imaging
the sympathetic and parasympathetic divisions of
the autonomic nervous system. Increases in para- ECG findings associated with sinus tachycardia
sympathetic activity decrease impulse rates and have already been discussed and should be com-
increases in sympathetic activity increase impulse bined with the patient’s clinical condition to dis-
rates. Heart rates up to 200–220 beats per minute cern if the sinus tachycardia is appropriate or
can be observed with maximal sympathetic stim- inappropriate. Another helpful diagnostic tool is
ulation [3]. There are several factors that can continuous cardiac rhythm monitoring. In the
result in sinus tachycardia including physiologic, outpatient setting, cardiac rhythm monitors pro-
pharmacologic, or pathologic factors. Some of vide data over several days (24 h to 30 days) to
these may be normal and appropriate, while oth- help determine average heart rate, minimal and
ers are pathologic. Some factors that can cause maximal rates, and heart rate trends. In the inpa-
elevation in sinus rates include physical activity, tient setting, continuous telemetry is typically
emotional responses, hypovolemia/dehydration, used for the same purposes.
anemia, hypoxia, hypotension, obstructive or Though not discussed in detail in this section,
restrictive conditions (such as acute PE, pericar- a tilt table test (or simply having the patient stand
ditis, pericardial effusion, MI), heart failure, thy- in the office) can be used to diagnose postural
roid abnormalities, pain, fever, and treatment orthostatic tachycardia syndrome (POTS). An
with beta agonists [2, 3]. Sinus Tachycardia is increase in heart rate ≥ 30 bpm beyond baseline
considered appropriate if there is an attributable that is sustained within 10 min of being in an
underlying cause. upright position is diagnostic for POTS in an
Inappropriate sinus tachycardia occurs when adult patient. Blood pressure usually remains
the rhythm occurs without any known or discern- stable in the POTS patient.
able cause. Rates are typically inappropriately
elevated at rest as well. One of the main causes of
inappropriate sinus tachycardia is enhanced auto- Management
maticity of the pacemaker cells of the sinus node
[2]. A clinical condition akin to inappropriate If there is an underlying cause of the sinus tachy-
sinus tachycardia is postural orthostatic tachycar- cardia, rates will improve once the underlying
dia syndrome (POTS). In this condition, patients condition is treated or stimulus is withdrawn.
9 Atrial Arrhythmias 93

There is usually no need for pharmacologic ther- Pathology

apy in this setting.
For patients with inappropriate sinus tachy- Atrial tachycardias may be precipitated by other
cardia, prognosis is typically benign, and devel- medical conditions or occur independently.
opment of tachycardia induced cardiomyopathy Multifocal atrial tachycardia is commonly asso-
is rare [1]. For this reason, treatment may not be ciated with other comorbid conditions. The most
necessary and is typically aimed at reducing any common associated condition is underlying pul-
associated symptoms. According to the guide- monary disease, but other associated conditions
lines, pharmacologic treatment may include include pulmonary hypertension, coronary dis-
ivabradine, which can reduce sinus node rates ease, and valvular disease [1, 2].
(Class IIa), as well as beta blockers and non-
dihydropyridine calcium channel blockers (dilti-
azem, verapamil), assuming there are no Imaging
contraindications (Class IIb) [1]. Some patients
may benefit from a combination of ivabradine Typical ECG findings in focal atrial tachycardia
and beta blockers (Class IIb) [1]. include a narrow complex tachycardia (unless
Sinus node ablation is not typically performed baseline BBB present) with atrial rates between
for inappropriate sinus tachycardia because risks 100–250 bpm, ventricular rates >100 bpm, and P
can significantly outweigh benefits and include waves with a single morphology [1–3]. The P
the potential for development of symptomatic waves of a focal atrial tachycardia are different
bradycardia requiring pacemaker placement, than sinus P waves, and characteristics of the P
phrenic nerve injury, and SVC syndrome due to wave morphology can help an experienced pro-
narrowing of the SVC and RA junction [1]. vider narrow down the location of the focal AT
(superior vs inferior, left atrium vs right atrium).
However, the exact location of a focal AT is gen-
Atrial Tachycardia erally determined by mapping during an EP study
[1]. In Fig. 9.1, the P wave axis is similar to the
Anatomy/Physiology sinus node, and the focus is located in the
RA. The prolonged PR interval and P wave loca-
Atrial tachycardia is an example of an SVT that tion within the previous T wave suggests an ecto-
originates somewhere in the atria other than in pic atrial rhythm since the PR interval often
the sinus node, and usually occurs due to shortens in sinus tachycardia. The AV node will
enhanced automaticity of the cells in that region determine the ventricular rate of atrial tachycar-
(though there are some ATs that may occur due to dia. If there is abnormal conduction through the
an intra-atrial micro-reentrant mechanism or trig- node, intermittent block will occur (Fig. 9.2).
gered activity) [1, 2]. Figure 9.3 shows an example of sinus rhythm
Atrial tachycardias may be focal (arising from with a sudden onset of an atrial tachycardia. The
a single focus) or multifocal (arising from multi- axis of the P wave suddenly changes, and this
ple foci). Common sites of origination include morphology is sustained in the arrhythmia. The
the annulus of the mitral or tricuspid valve, the rhythm is not initiated by a PAC but begins with
right or left atrial free wall, the left atrial append- increased automaticity at a focus different from
age, pulmonary veins, superior and inferior vena the sinus node.
cava, coronary sinus, coronary cusps, and crista Typical ECG findings for multifocal atrial
terminalis [1]. Focal AT occurs more frequently tachycardia (MAT) include P waves with at least
in the right atrium than the left atrium [1]. Atrial three different morphologies with atrial rates
tachycardias are typically paroxysmal with >100 bpm [1, 3] (Fig. 9.4) Because there are at
abrupt onset and offset, though they can be inces- least three different foci in different locations,
sant in some patients. there will be variability in the PR interval and R-R
94 L. Raines

Fig. 9.1 EKG of atrial tachycardia

Fig. 9.2 Atrial tachycardia with variable conduction-flat baseline visible and P waves clearly visible

Fig. 9.3 Strip of atrial

tach. The first beat being
sinus, then change in P
wave morphology
during the tachycardia
9 Atrial Arrhythmias 95

Fig. 9.4 EKG of multifocal atrial tachycardia (MAT). Note the 3+ morphologies of the P wave

interval, which can sometimes lead to an errone- • Adenosine can be helpful to restore sinus
ous diagnosis of atrial fibrillation. However, rhythm or diagnose the mechanism of the
unlike atrial fibrillation, an isoelectric line should tachycardia (Class IIa).
be clearly visible between P waves [1, 3]. –– Automatic focal AT: may see transient
suppression.
–– Triggered focal AT: adenosine can
Management effectively terminate.
–– Re-entrant focal AT: adenosine will likely
As previously mentioned, atrial tachycardias may not be effective.
be precipitated by other medical conditions or • IV amiodarone may be reasonable to restore
occur independently. For some, treatment of an sinus rhythm or slow ventricular rate in hemo-
underlying condition or mechanism may result in dynamically stable patients.
termination of the arrhythmia. Otherwise, • IV Ibutilide may be reasonable to restore
treatment for focal atrial tachycardia involves
sinus rhythm in hemodynamically stable
pharmacologic therapy or ablation. patients.

Focal Atrial Tachycardia Ongoing management [1]

• Catheter ablation as alternative to pharmaco-
Acute Management [1] logic therapy (Class I).
• IV beta blockers or non-dihydropyridine cal- –– Success rates usually >90–95% with com-
cium channel blockers (diltiazem/verapamil) plication rate <1–2%.
in hemodynamically stable patients (Class I). • Oral beta blockers or non-dihydropyridine
• Synchronized cardioversion in hemodynami- calcium channel blockers if no other contrain-
cally unstable patients (Class I). dication exists (Class IIa).
96 L. Raines

• Flecainide or propafenone in patients without typically triggered when a premature beat enters
structural heart disease or ischemic heart dis- one of these pathways when that pathway is
ease (Class IIa) in combination with beta recovered and not in the refractory phase, but
blocker, verapamil, or diltiazem. while the other pathway is still in the refractory
• Oral sotalol or amiodarone may be reason- phase, further details of which are reviewed
able, but due to risk of proarrhythmia, need to below.
balance risk and benefits (Class IIb). Clues that may help an experienced provider
determine if an SVT is AVNRT, either typical or
Multifocal Atrial Tachycardia atypical, include: (1) characteristics of the start
First-line treatment is typically aimed at manag- and end of the arrhythmia, (2) identifiable trig-
ing the underlying associated condition if one is gers, (3) R-P interval length/relation of the P
identified. However, if further treatment is wave to the QRS.
needed, management typically includes attempts
at slowing AV node conduction. Antiarrhythmic
medications are not generally helpful [1]. Pathology/Description

Acute Management [1] There are two types of AVNRT—typical and

• IV metoprolol or verapamil (Class IIa). atypical. The EKG during both forms of AVNRT
–– If no other contraindication to its use exists, will appear minimally different. The difference
verapamil is likely preferred over beta can only be confirmed during an invasive EP
blocker therapy since beta blockers can study.
worsen underlying pulmonary disease,
especially those with bronchospasm as the Typical AVNRT
etiology of the rhythm. Typical AVNRT is usually triggered by a prema-
ture atrial complex (PAC), which is blocked at
Ongoing Management [1] the refractory fast pathway and travels down the
• Oral verapamil or diltiazem is reasonable for fully recovered slow pathway to the ventricle
patients with recurrent, symptomatic MAT (anterograde conduction) [2, 3]. Once the impulse
(Class IIa). reaches the end of the slow pathway, it exits and
• Metoprolol is reasonable, but typically travels down the His bundle to activate the ven-
avoided in patients with pulmonary disease tricles, while simultaneously traveling back up
(Class IIa). the fast pathway to the atria (retrograde conduc-
tion) [2, 3]. The atria are then reactivated, and the
electrical impulse then re-enters the slow path-
V Node Reentry Tachycardia
A way and travels the same circuit repeatedly
(AVNRT) resulting in a re-entrant tachycardia [2, 3]. Typical
AVNRT is also called “slow-fast” AVNRT for
Anatomy and Physiology this reason. Atrial and ventricular activation is
nearly simultaneous [2, 3].
AV Node Reentry Tachycardia (AVNRT) is the
most common type of SVT, and the anatomic Atypical AVNRT
substrate is a re-entry circuit consisting of fast In atypical AVNRT, anterograde conduction
and slow pathways (dual pathways) within or occurs via the fast pathway, and retrograde con-
around the AV node [1, 2]. The slow pathway has duction occurs via the slow pathway, again result-
a shorter refractory period, while the fast path- ing in a re-entrant tachycardia [2, 3]. This is also
way has a longer refractory period. AVNRT is called “fast-slow” AVNRT.
9 Atrial Arrhythmias 97

Physical Exam Correlations near the end of the QRS complex (Fig. 9.5) [3].
Since the P wave is located closer to the prior
AVNRT is typically well tolerated in patients QRS complex than the subsequent QRS com-
with structurally normal hearts. Symptoms may plex, typical AVNRT may be called a “short RP
include palpitations, shortness of breath, feelings tachycardia.” These retrograde P waves will be
of anxiety, lightheadedness, and possibly chest inverted in the inferior leads because of the retro-
pain. Syncope can occur if rates are fast enough. grade activation of the atria [2, 3].
If the SVT occurs in patients with coronary dis-
ease, cardiomyopathy, or valvular stenosis, they Atypical AVNRT
may develop hypotension, ischemia, heart fail- The ECG will usually show a narrow complex
ure, or syncope. Prognosis in the absence of heart tachycardia with regular R-R intervals and a ret-
disease is usually quite good [1]. rograde P wave in front of the next QRS [3].
Because of the location of the P wave, the RP
interval is longer than the PR interval and may be
Imaging termed as “long RP tachycardia” [1, 2].

ECGs and continuous cardiac rhythm monitoring

are performed to help confirm the presence of an Management
SVT suspected to be AVNRT. Ventricular rates
are typically 180–200 bpm but may have a wider cute Management [1]
A
range. Both Holter monitors and continuous • Vagal maneuvers should be first-line treat-
telemetry monitors are helpful for diagnosis. ment/intervention (Class I). Examples:
–– Valsalva.
Typical AVNRT –– Carotid sinus massage after absence of
ECGs will show a narrow complex tachycardia bruit is confirmed.
with regular R-R intervals, and because of the –– Ice-cold wet towel to face.
nearly simultaneous atrial and ventricular activa- • If vagal maneuvers are not effective, adenos-
tion, P waves may be buried in the QRS and not ine is the first-line drug choice (Class I).
visible on the ECG. However, if activation of the –– Considered both therapeutic and diagnos-
atria and ventricles are not exactly in synch, a ret- tic. Adenosine will be successful in con-
rograde P wave may be observed on the ECG verting AVNRT in ~95% of patients and

Fig. 9.5 EKG of typical AVNRT. Red arrows points to retrograde P wave immediately after QRS suggestive of AVNRT
98 L. Raines

may more clearly reveal atrial activity in –– Radiofrequency or cryoablation may be

arrhythmias such as atrial tachycardia or utilized—acute success rates are equiva-
atrial flutter. lent, however, with cryoablation, there is
–– The initial dose is 6 mg given rapidly. If the lower chance of AV block but higher rate of
first dose of adenosine does not convert the recurrence observed long term.
patient to sinus rhythm, up to two more • Oral beta blockers are recommended in those
doses of adenosine can be given at 12 mg who are not candidates for or prefer not to
each. undergo ablation (Class I).
• Synchronized cardioversion in hemodynami- • Flecainide or propafenone—reasonable for
cally unstable patients if vagal maneuvers or patients who do not have structural or isch-
adenosine do not convert the tachycardia or emic heart disease in those who are contrain-
aren’t feasible (Class I). dicated or prefer not to undergo, catheter
• Synchronized cardioversion (Class I) in hemo- ablation and in whom rate control medications
dynamically stable patients when pharmaco- (BBs/CCBs) are ineffective or contraindicated
logic therapy isn’t successful or is (Class IIa).
contraindicated (i.e., Bronchospasm). • If minimally symptomatic, no pharmacologic
• IV beta blockers or IV non-dihydropyridine therapy or ablation is reasonable (Class IIa).
calcium channel blockers are reasonable if no • Oral sotalol or dofetilide may be reasonable in
other contraindications exist in hemodynami- patients who are not candidates for, or prefer
cally stable patients without pre-excitation not to undergo, ablation (Class IIb).
(Class IIa). –– These medications can be used in patients
• Oral beta blockers, diltiazem, or verapamil with structural heart disease or coronary
may be reasonable in hemodynamically stable artery disease, but initiation is done in the
patients assuming no other contraindications inpatient setting with continuous telemetry
to their use (Class IIb). monitoring and serial ECGs due to poten-
• IV amiodarone can be considered in hemody- tial for QT prolongation and torsades de
namically stable patients if other therapies are pointes. Typically, these agents are reserved
contraindicated or ineffective (Class IIb). for patients who are not responsive to or
are not candidates for treatments already
ngoing Management [1]
O outlined.
If episodes are short, infrequent, and well toler- • Pill-in-the-pocket (self-administered) acute
ated, or if the patient can terminate episodes eas- doses of as needed oral beta blockers or cal-
ily with vagal maneuvers, no prophylactic cium channel blockers may be reasonable if
treatment may be needed. Some patients may AVNRT is infrequent and well-tolerated
respond well to as needed, “pill in the pocket” (Class IIB).
short acting beta blockers or calcium channel
blockers. Another option is daily, longer acting
beta blocker or calcium channel blocker therapy. AV Re-entry Tachycardia (AVRT)

• Oral verapamil or diltiazem for patients who Anatomy and Physiology

are not candidates for, or do not wish to
undergo, catheter ablation if no other contra- AV Reentry tachycardia (AVRT) is the second
indication exists (Class I). most common type of SVT. The anatomic sub-
• Catheter ablation (Chap. 12) of the slow path- strate for this type of SVT is a reentry circuit
way (slow pathway modification) is first-line involving the AV node and a bypass tract, which
treatment (Class I). directly connects the atrium and the ventricle [1].
–– Success rates typically >95%. Because of the direct connection between the
–– Risk of AV block is <1%. atrium and ventricle, the normal conduction
9 Atrial Arrhythmias 99

through the AV node and His-Purkinje system • Antidromic AVRT—the impulse travels from
can be bypassed. These bypass tracts are also the atrium to the ventricles in the anterograde
referred to as accessory pathways and can be direction through the bypass tract and returns to
manifest or concealed. They can conduct antero- the atrium via the AV node in the retrograde
grade (A-V conduction), retrograde (V-A con- direct [1, 2]. Antidromic AVRT exhibits a wider
duction), or both. [1, 2] complex QRS because the ventricles are acti-
Pathways are manifest if they conduct in the vated outside of the normal conduction system
anterograde direction and demonstrate pre- through the bypass tract [3]. (In rare instances,
excitation with a short PR interval and a delta an antidromic AVRT may consist of two bypass
wave on the ECG [1–3]. Pre-excitation occurs tracts instead of a bypass tract and the AV node.
when a specific area of ventricular myocardium
is excited early due to the accessory pathway and In AVRT, the AV node is typically the slower
starts to conduct prior to the impulse traveling pathway and the bypass tract is typically the faster
down the His-Purkinje system to cause depolar- pathway, though this is not always the case [2].
ization of the myocardium. This causes the PR The reentry circuit in AVRT is known as a macro-
interval to appear shorter as the ventricle starts reentry tachycardia because it involves a larger
contracting shortly after the P wave. The “delta” amount of cardiac tissue than that of AVNRT [2,
wave is the combination of the normal conduc- 3]. Because of the size of the circuit, the atria and
tion down the AV node and early excitation of an ventricles are not activated in synchrony, so P
area of myocardium caused by conduction down waves are typically seen on the ECG and not bur-
the accessory pathway. Manifest pathways can ied within the QRS if the QRS is narrow. As with
conduct in both the anterograde and retrograde AVNRT, there are typical and atypical forms of
direction but may only conduct in the antero- AVRT and P waves can occur after (typical) or
grade direction. Experienced providers may be before (atypical) the QRS [2]. It may not be pos-
able to localize the bypass tract based on certain sible to distinguish AVNRT and AVRT from the
ECG characteristics. ECG alone, however, there may be higher suspi-
Pathways are concealed if they only conduct cion for one or the other based on length of the RP
retrograde and do not demonstrate pre-excitation interval (typically >80 ms in AVRT due to the
on the ECG [1, 2]. larger tissue mass and time needed to traverse the
re-entry circuit), and proximity of the retrograde P
wave to the QRS for the same reason [2]. In
Pathology/Description AVNRT, the P wave is generally closer or con-
nected to the QRS complex, but in AVRT, the P
When a bypass tract is present, an impulse can wave is likely separated from the QRS complex.
travel from the atrium to the ventricle via the AV
node or via the bypass tract.
anagement of Orthodromic AVRT
M
• Orthodromic AVRT—the impulse travels (Narrow Complex AVRT)
from the atrium to the ventricles in the antero-
grade direction through the AV node and Management of narrow complex AVRT is similar
returns to the atrium via the bypass tract in the to the management of AVNRT described earlier,
retrograde direction [1, 2]. Orthodromic because the AVRT circuit is dependent on the AV
AVRT exhibits a narrow complex QRS node for conduction of the tachyarrhythmia.
because the ventricles are activated through Thus, anything that interferes with conduction
the AV node, which is the normal activation through the AV node can also inhibit an AVRT
pathway [3]. arrhythmia.
100 L. Raines

cute management [1]

A ischemic heart disease who have AVRT and/or
• Vagal maneuvers (Class I). pre-excited AF and are not candidates for, or
• Adenosine (Class I) can convert orthodromic prefer not to undergo, catheter ablation (Class
AVRT in 90–95% of patients. IIa).
• Synchronized cardioversion in hemodynami- –– These agents slow or block conduction
cally unstable patients if vagal maneuvers and over the accessory pathway.
adenosine ineffective or not feasible (Class I). • Oral dofetilide or sotalol may be reasonable in
• Synchronized cardioversion in hemodynami- patients with AVRT and/or pre-excited AF
cally stable patients when pharmacologic who are not candidates for, or prefer not to
therapy is ineffective or not feasible (Class I). undergo, catheter ablation (Class IIa).
• Synchronized cardioversion in hemodynami- –– Can be used in patients with structural or
cally unstable patients with pre-excited atrial ischemic heart disease but need to consider
fibrillation (AF) (Class I). risk of QT prolongation/torsades/medica-
• Ibutilide or IV procainamide in patients with tion interactions, and other possible
pre-excited AF who are hemodynamically contraindications.
stable (Class I). • Oral amiodarone may be considered with
–– Both medications can decrease ventricular AVRT and/or pre-excited AF patients who are
rate by slowing conduction over the acces- not candidates for, or prefer not to undergo,
sory pathway and may possibly terminate catheter ablation in whom BB/CCB/fle-
AF. cainide/propafenone are ineffective or contra-
• IV diltiazem, verapamil, or beta blockers can indicated (Class IIb).
be effective for orthodromic AVRT who do not –– Need to consider possible toxicities associ-
have pre-excitation on resting ECG during ated with long-term amiodarone use.
sinus rhythm (Class IIa). • Oral BB/CCB may be reasonable for patients
• IV BB/CCB can be considered in patients with orthodromic AVRT and pre-excitation on
with orthodromic AVRT who have pre- resting ECG who are not candidates for, or
excitation on resting ECG and have not prefer not to undergo, catheter ablation (class
responded to other therapies (Class IIb), how- IIb), however, these patients may develop AF
ever, these therapies have a risk of enhancing during an episode of AVRT and be at increased
conduction over the accessory pathway if the risk of rapid conduction over the accessory
AVRT converts to AF and the ability of pathway, so need to exercise caution with
promptly perform electrical cardioversion these agents.
must be available should this occur. • Oral digoxin may be reasonable in ortho-
• IV digoxin, IV amiodarone, IV and oral BB/ dromic AVRT without pre-excitation if not a
CCB are potentially harmful in patients with candidate for, or prefer not to undergo, cathe-
pre-excited AF (Class III) because these medi- ter ablation (Class IIb).
cations can enhance conduction over the • Oral digoxin potential harmful in patients
accessory pathway, increase ventricular rate, with AVRT or AF and pre-excitation on rest-
and increase risk of ventricular arrhythmias. ing ECG (Class III) because digoxin shortens
the refractory period of the accessory
ngoing Management [1]
O pathway.
• Catheter ablation of accessory pathway (class
I) in patients who have had AF and/or AVRT.
–– 93–95% success rate Wolff-Parkinson-White
• Oral BB/CCB in patients without pre-
excitation on resting ECG (Class I). WPW Pattern Vs WPW Syndrome
• Oral flecainide or propafenone is reasonable The distinguishing factor here is the presence or
in patients without structural heart disease or absence of arrhythmia. Patients with WPW pat-
9 Atrial Arrhythmias 101

tern have pre-excitation that is manifest on the slurring of the initial portion of the QRS com-
ECG in the absence of symptomatic arrhythmia. plex, known as a delta wave [1]. The delta wave
Patients with WPW syndrome have pre-excitation may be more or less prominent depending on a
that is manifest on the ECG associated with couple of factors: (1) the proximity of the bypass
symptomatic arrhythmias. tract to the sinus node and (2) how much of the
As previously outlined, impulse conduction myocardium is activated via the bypass tract [1,
through the AV node is delayed, but this same 2] (see Fig. 9.6a, b ).
delay does not occur in the bypass tract. One of the primary concerns with WPW is the
Therefore, the impulse travels faster down the risk of sudden cardiac death. This is because of
bypass tract, resulting in premature activation of the absence of the delay in impulse conduction
the ventricles [1, 2]. Because of the earlier ven- down the accessory pathway. This is of particular
tricular activation, the characteristic ECG find- concern, for example, if a patient with WPW also
ings of WPW include a short PR interval and a develops atrial fibrillation. With atrial fibrillation,

Fig. 9.6 (a) EKG of WPW. A delta wave is visible at the beginning of the QRS complex. (b) Another EKG of WPW
102 L. Raines

the atrial rate can range from 300–600 beats per the slowing properties and governance that the
minute. In patients without an accessory path- AV node has [2] (see Fig. 9.7). In some patients,
way, the AV node acts as a gatekeeper between atrial fibrillation could degenerate to ventricu-
the atria and the ventricles, and, though it may lar fibrillation. For this reason, AV nodal agents
allow for some degree of rapid conduction to the should also be avoided [1, 2]. Another reason
ventricle, it will not allow all the atrial impulses adenosine and AV nodal agents may not be pre-
to conduct through. Thus, the ventricular rate will ferred is that the circuit may include two
generally only be allowed to increase to a rate bypass tracts instead of the AV node and a
around 200 bpm or so (though this upper rate can bypass tract. If the AV node is not involved,
vary) when the AV node/His-Purkinje system is then agents directed at slowing AV node con-
utilized. Accessory pathways do not have the duction will not be effective. First-line agents
same gatekeeping properties of the AV node. for the acute management of wide complex
Therefore, the hundreds of impulses generated AVRT include the antiarrhythmics procain-
from atrial fibrillation conducting ungoverned amide and ibutilide [2]. These antiarrhythmics
down an accessory pathway can lead to ventricu- are effective at blocking bypass tracts and are
lar fibrillation. not negatively inotropic. Amiodarone can also
be considered [2]. In unstable patients with
rapid ventricular rates, DC cardioversion is
Imaging recommended.
Management of Asymptomatic Patients with
Management of wide complex AVRT can be a Asymptomatic Pre-excitation [1]:
bit more challenging than management of nar-
row complex AVRT. For starters, it may be dif- • In asymptomatic patients with pre-excitation,
ficult to differentiate wide complex AVRT from the findings of abrupt loss of conduction over
ventricular tachycardia. This type of AVRT a manifest pathway during exercise testing in
may also respond to vagal maneuvers if the AV sinus rhythm or intermittent loss of pre-
node is involved in the circuit. However, ade- excitation during ECG or ambulatory moni-
nosine is likely not the first-line agent for wide toring are useful to identify patients at low risk
complex AVRT [1, 2]. Adenosine can trigger of rapid conduction over the pathway (Class
atrial fibrillation in some patients, which could I).
result in a potentially lethal outcome if the very • EP study is reasonable in asymptomatic
rapid atrial impulses are then forced down the patients with pre-excitation to risk stratify for
bypass tract (fast pathway), which doesn’t have arrhythmic events (Class IIa).

Fig. 9.7 Pre-excited atrial fibrillation

9 Atrial Arrhythmias 103

• Catheter ablation of an accessory pathway is direction the impulse travels is opposite—that is,
reasonable in asymptomatic patients with pre- the impulse travels down the septum and back up
excitation in an EP study that identifies a high the lateral free wall of the right atrium in a clock-
risk of arrhythmic events, including rapidly wise direction [1]. Part of this circuit involves an
conduction pre-excited AF (Class IIa). area in the right atrium between the ostium of the
• Catheter ablation of the accessory pathway is tricuspid valve and the inferior vena cava, known
reasonable in asymptomatic patients if the as the cavotricuspid isthmus (CTI) [1, 2].
presence of pre-excitation precludes specific Therefore, typical and reverse typical atrial flut-
employment (such as with pilots) (Class IIA). ters are also known as CTI-dependent atrial
• Observation, without further evaluation or flutters.
treatment, is reasonable in asymptomatic Atrial flutters can also occur in the left atrium
patients with pre-excitation (Class IIa). near the pulmonary veins or around scar or surgi-
cal lesions. Other circuits include paths around
Management of Symptomatic Patients with the mitral annulus and re-entry involving the LA
Manifest Accessory Pathways [1]: roof. This type of flutter is termed atypical flutter
(or non-isthmus dependent) and circuits are cat-
• In symptomatic patients with pre-excitation, egorized as either macro-re-entrant or micro-re-
the findings of abrupt loss of conduction over entrant [1, 2] (Fig. 9.8).
the pathway during exercise testing in sinus Patients with atrial flutter are at increased risk
rhythm or intermittent loss of pre-excitation of having concomitant atrial fibrillation or of
during ECG or ambulatory monitoring are developing atrial fibrillation in the future.
useful for identifying patients at low risk of According to the 2015 AHA/ACC/HRS SVT
developing rapid conduction over the pathway guidelines, 22–50% of patients developed AF
(Class I). after CTI ablation after mean follow-up of
• An EP study is useful in symptomatic patients 14–30 months and risk factors for developing AF
with pre-excitation to risk stratify for life- included LV dysfunction, presence of structural
threatening arrhythmic events (Class I). or ischemic heart disease, inducible AF, and
increased left atrial size [1].
Patients with atrial flutter are at the same risk
Atrial Flutter of thromboembolism as patients with atrial fibril-
lation, and recommendations for anticoagulation
Anatomy and Physiology are the same for atrial flutter as for atrial fibrilla-
tion [1].
Atrial flutter is a type of macro-re-entrant SVT,
and the re-entry circuit occurs within the right
atrium. The atrial rate is usually about 250–350 Imaging
beats per minute, and the classic ECG pattern of
atrial flutter is the characteristic regular “saw- ECG
tooth” appearance of the flutter waves [3]. The • The classic ECG pattern of atrial flutter is the
circuit can be counterclockwise or clockwise [1, characteristic regular “sawtooth” appearance
2]. of the atrial flutter waves; the atrial rate is typ-
Typical atrial flutter, or counter-clockwise ically 250–350 bpm and the ventricular rate
atrial flutter, is the most common type of atrial can be variable [3]. QRS will usually be nar-
flutter. In typical atrial flutter, an impulse travels row unless there is a pre-existing bundle
down the lateral free wall of the right atrium and branch block or aberrancy.
back up the septum in a counter-clockwise direc- • Typical atrial flutter: flutter waves are usually
tion [1]. In reverse typical flutter, or clockwise inverted in leads II, III, and AVF and upright
flutter, the re-entry circuit is the same, but the in V1 [2, 3] (Fig. 9.9).
104 L. Raines

Fig. 9.8 EKG of atypical atrial flutter. The flutter waves are less sawtooth in appearance, narrow, and organized as seen
in lead V1

Fig. 9.9 EKG of typical atrial flutter. Note the negative flutter waves in the inferior leads

• Reverse typical flutter: flutter waves are usu- • Atrial rate: the atrial rate with atrial flutter is
ally upright in leads II, III, and AVF and typically 250–350 bpm. Atrial rate with
inverted in V1 [2, 3]. atrial tachycardia is typically 150–250 bpm
[2, 3].
For some, differentiating atrial flutter and • P wave morphology: in atrial flutter the P
atrial tachycardia can be difficult. Some helpful wave is usually inverted in leads II, III,
tips for ECG differentiation include the AVF. Atrial tachycardia usually shows upright
following: P wave in lead II, III, AVF [2, 3].
9 Atrial Arrhythmias 105

Management of coronary artery disease, renal function, and

presence of ECG abnormalities such as IVCD/
Acute management of atrial flutter is typically bundle branch block, QRS duration, QT dura-
focused on patient stability, anticoagulation for tion [2, 4]. In patients with a pacemaker or
stroke prevention, rate control, and conversion to defibrillator with the presence of an atrial pac-
sinus rhythm. Atrial flutter can be more difficult ing wire, rapid atrial pacing is useful for acute
to rate control than atrial fibrillation. conversion of atrial flutter (Class I)—this is
known as pace termination and recommenda-
Acute Management tions for anticoagulation are the same as that
• In unstable patients in whom atrial flutter is for pharmacologic and electrical cardiover-
poorly tolerated, direct current cardioversion sion [1].
is a Class I recommendation [1].
• If a patient is stable and not in decompensated
heart failure or hypotensive, rate control with Anticoagulation
AV nodal agents, such as the nondihydropyri-
dine calcium channel blockers or beta block- Anticoagulation should be considered in all
ers, can be attempted and have a class I patients, especially if the onset of arrhythmia
recommendation [1]. duration is greater than 48 hours or unknown.
• IV amiodarone can be useful for rate control The CHA2DS2VASc score is used to calculate
in the absence of pre-excitation in patients stroke risk and components include CHF/LV dys-
with flutter and CHF when BB are contraindi- function, hypertension, age, diabetes, prior
cated or ineffective (Class IIa) [1]. stroke/TIA, presence of vascular disease, and
–– Amiodarone has less negative inotropic gender. In the acute setting, if not contraindi-
effect than BB/CCB and may produce less cated, IV heparin can be utilized with subsequent
hypotension [1]. transition to a direct oral anticoagulant (apixa-
–– Though unlikely to convert a patient to ban, rivaroxaban, or dabigatran) or warfarin
sinus rhythm, the potential to do so exists, (once INR therapeutic). Anticoagulation should
so potential risks and benefits should be be continued uninterrupted for at least 1 month
considered for patients with flutter ≥48 h post cardioversion, but possibly longer depend-
duration who are not adequately anticoagu- ing on the CHA2DS2VASC score [1, 5].
lated [1].
• In stable patients, conversion to sinus rhythm Ongoing Management
can be achieved electrically with direct cur- Long-term treatment for right-sided (typical and
rent cardioversion, or pharmacologically, with reverse typical) atrial flutter includes consider-
an antiarrhythmic drug. Prior to proceeding ation of EP study and flutter ablation (Class I rec-
with cardioversion (either electric or pharma- ommendation) [1]. Because the re-entry circuit
cologic), if arrhythmia onset is >48 h or involves the cavotricuspid isthmus, that area is
unknown, the presence of a left atrial append- usually the target site for ablation. Ablation has a
age thrombus will need to be ruled out, either very high success rate for treatment and elimina-
by TEE or CT [1]. The most common antiar- tion of right-sided atrial flutter and should be
rhythmic agents (Chap. 7) used for converting considered for most patients who are otherwise
a patient to sinus rhythm include procain- not contraindicated for ablation. Patients will
amide (1A antiarrhythmic), flecainide or need to be able to tolerate anticoagulation for up
propafenone (1C antiarrhythmics), and amio- to 1 month prior to ablation and 4–6 weeks post
darone or Ibutilide (Class III antiarrhythmics). flutter ablation [1, 5].
Factors to consider when choosing an agent For patients who are hemodynamically stable,
for pharmacologic cardioversion include the but otherwise contraindicated or do not wish to
presence of structural heart disease, presence undergo catheter ablation, beta blockers/calcium
106 L. Raines

channel blockers are useful with Class I recom- conditions, such as hypertension and diabetes [2,
mendation [1]. 5]. Atrial fibrillation is a progressive condition in
As previously mentioned, patients with atrial which episodes generally increase in frequency
flutter are at increased risk of developing or hav- and duration over time and may become persis-
ing concomitant atrial fibrillation. Up to 80% or tent if left untreated. Similar to atrial flutter, atrial
more of patients who undergo typical flutter abla- fibrillation is associated with increased risk of
tion will develop AF within 5 years [1]. For this stroke and CHF.
reason, even if atrial flutter is treated with abla-
tion, ongoing surveillance for development of
atrial fibrillation should be considered, as well as Anatomy and Physiology
addressing risk factors. One method for ongoing
monitoring includes placement of an ambulatory Atrial fibrillation is a supraventricular arrhythmia
monitor to look for atrial fibrillation. Other meth- that is characterized by uncoordinated atrial
ods emerging include wearables or patient- activity, with atrial rates >350 bpm [2, 4, 5]. As a
centered monitoring devices including watches result, there is a decrease in the atrial mechanical
with ECG capabilities (e.g., Apple Watch®) and function with an associated irregular ventricular
the FDA-approved KardiaMobile® EKG response. The uncoordinated atrial activity results
monitor. in the loss of effective atrial contraction, also
known as “atrial kick”, and can decrease ventric-
ular filling and cardiac output [4, 5]. The mecha-
Atrial Fibrillation nisms that underlie AF are likely multifactorial
and involve multiple independent reentrant wave-
Atrial fibrillation is a relatively common arrhyth- lets that exist within the atria, and are primarily
mia and prevalence increases with age (Table 9.1). initiated by focal triggers that originate at or near
Symptoms associated with atrial fibrillation have the pulmonary veins in the left atrium [2, 4, 5].
a wide distribution and range from completely Structural and electrophysiologic abnormalities
asymptomatic to severe. It is typically associated can alter the properties of atrial tissue and allow
with underlying structural heart disease (CAD, for abnormal impulse initiation or conduction.
CHF, valvular heart disease) and other chronic Some precipitants include alcohol, drugs, caf-
feine, exercise, stress/emotion, sleep apnea, obe-
Table 9.1 Definitions of atrial fibrillation
sity, and hyperthyroidism [4, 5].
• Paroxysmal AF—self-terminating or intermittent;
resolves spontaneously or within 7 days of onset [5]
• Persistent AF—rhythm is sustained greater than Physical Exam Correlation
7 days. Fails to self-terminate but can be terminated
with pharmacologic or electric cardioversion [5] Symptoms can be variable and range from no
• Long-standing persistent AF—continuous AF of symptoms to fatigue, shortness of breath, palpita-
greater than 12 months duration [5]
• Permanent AF—this term is used when the decision tions/cardiac awareness, weakness, dizziness,
has been made to stop attempts at restoring sinus lightheadedness, hypotension, heart failure, and
rhythm [5] even syncope. Some patients who are initially
• Nonvalvular AF—AF that occurs in the absence of asymptomatic may develop heart failure symp-
moderate to severe mitral stenosis or a mechanical
toms if tachycardia-induced cardiomyopathy
heart valve [6]
• Valvular AF—generally refers to AF that occurs in occurs. Some patients present with TIA or stroke
the setting of moderate to severe mitral stenosis or in symptoms. If associated with valvular heart dis-
the presence of an artificial (mechanical) heart valve ease, a murmur may be present on exam. Pulse
[6] rate will be irregularly irregular.
9 Atrial Arrhythmias 107

Imaging • Cardiac CT:

–– A structural cardiac CT can also evaluate
• ECG/telemetry monitoring: the LAA for thrombus reliably.
–– Characteristic ECG findings include irreg- • Ischemic evaluation in those without previ-
ular R-R intervals, absence of discrete P ously diagnosed CAD is helpful in guiding
waves, and irregular atrial activity (which pharmacotherapy since some antiarrhythmics
may be fine or coarse) [2, 5] (see Fig. 9.10). are contraindicated in patients with underly-
–– There are several types of wearable devices ing CAD. Options for ischemic evaluation
available as well, that have ECG recording include stress testing, CT of the coronaries,
capabilities. One such device is the Apple cardiac MRI with stress, or cardiac catheter-
Watch™. Another device is the Kardia- ization. Decision on which type of test is pur-
Mobile® device (or AliveCor® monitor). sued is typically guided by associated
• Transthoracic echocardiogram: symptoms, history, and if any possible contra-
–– All patients with AF should have an echo- indication to a particular test exists (ex. renal
cardiogram performed. This is helpful in dysfunction for CT/catheterization, etc.).
determining LVEF, evaluation of the LA • Thyroid testing to evaluate for clinical or sub-
and RA sizes, and determine if there is any clinical hyperthyroidism.
concomitant valve disease.
• Transesophageal echocardiogram:
–– A transesophageal echo is more sensitive Management
for evaluating possible left atrial append-
age (LAA) thrombus and should be per- • Rate control (Chap. 7).
formed in patients being considered for –– Beta blockers.
either pharmacologic or electric cardiover- Metoprolol.
sion if duration of AF is > 48 h or unknown Atenolol.
[5] (see Fig. 9.11). Carvedilol.

Fig. 9.10 EKG of atrial fibrillation with irregular R-R rhythms other than AF: NSR with PAC’s, wandering atrial
intervals. No discernible P waves or PR interval confirms pacemaker, MAT are often misdiagnosed as AF
the diagnosis of AF. Irregular R to R intervals can be
108 L. Raines

method is irreversible and results in pace-

maker dependency, so is usually reserved
as a last option [5, 6].
• Rhythm control.
• There are multiple considerations when choos-
ing an appropriate antiarrhythmic agent,
including presence/absence of CAD, left ven-
tricular function, LV wall thickness, renal
function, liver function, ECG characteristics
such as QT interval, presence of IVCD/BBB,
AV block, and other medications that can be
relative or absolute contraindications if used
alongside a particular antiarrhythmic [5, 6].
Drug selection is mainly guided by safety,
rather than efficacy [5]. Risks of initiating an
antiarrhythmic should be considered, includ-
ing that of proarrhythmia. Antiarrhythmic
drugs can prolong the QT interval and risk
causing torsades de pointes [4–6]. We want to
avoid precipitating ventricular arrhythmias in
an attempt to suppress atrial arrhythmias.
• Antiarrhythmic drugs for the treatment of
atrial fibrillation (Chap. 7):
–– Class IA [5, 6].
Disopyramide.
Fig. 9.11 Image of clot seen in left atrial appendage
• Negative inotrope.
• May be desirable in patients with
Esmolol. hypertrophic cardiomyopathy asso-
Propranolol. ciated with dynamic LVOT obstruc-
–– Calcium tion. Otherwise avoided in structural
channel blockers—nondihydropyridine. heart disease.
• Diltiazem. • Strong anticholinergic side effects.
• Verapamil. –– Class IC—these agents are for use in
–– Digoxin. patients without CAD/CHF/structural heart
–– Amiodarone can be used for rate control in disease [5, 6].
certain situations. Flecainide.
–– A heart rate control strategy (resting HR • Can be initiated as an outpatient.
<80 bpm) is reasonable for symptomatic • Monitor QRS duration: do not want
patients. – ACC/AHA/HRS and AFFIRM duration to exceed > 15% baseline.
[5, 6]. Propafenone.
–– A lenient rate control strategy (resting HR –– Class III.
<110 bpm) may be reasonable if a patient is Amiodarone [2, 4–6].
asymptomatic and LV function preserved. – • Can be initiated inpatient or
ACC/AHA/HRS and AFFIRM [5, 6]. outpatient.
–– Permanent pacemaker implant followed by • Has a large volume of distribution
AV nodal ablation can be one method for and long half-life, so typically loaded
rate control if the arrhythmia is refractory at higher doses with subsequent
to pharmacologic therapy. However, this taper over several weeks.
9 Atrial Arrhythmias 109

• P robably the most effective antiar- from the left atrial myocardial cells that
rhythmic for maintenance of sinus extend into the pulmonary veins. Because
rhythm for patients with AF. of this, atrial fibrillation ablation involves
• Can be used in patients with or with- pulmonary vein isolation as the primary
out CHF or structural heart disease. target for ablation. However, triggers can
• Potential toxicities include liver, thy- also arise from the posterior wall of the
roid, lung, eye, skin among others left atrium, ligament of Marshall, SVC/
and need surveillance with LFTs/ IVC, coronary sinus, and LA appendage,
TFTs every 6 months and yearly so these areas can also be ablated.
PFTs/CXR and eye exams. Though somewhat newer over the past
Dofetilide (Tikosyn®) [5, 7]. few years, hybrid atrial fibrillation abla-
• Must be initiated in the inpatient set- tion is becoming more common. This
ting with continuous telemetry and type of ablation involves both electro-
serial ECG monitoring. Want QT pro- physiology and cardiac surgery, and
longation no more than 15% baseline. patients undergo both catheter-based
• Concern for QT prolongation and endocardial ablation, as well as surgical
torsades. epicardial ablation.
• MULTIPLE drug interactions and Catheter ablation has been shown to be
contraindications. an effective treatment for patients who
• Dose adjusted based on QT interval, previously failed antiarrhythmic medi-
renal function. Contraindicated if cations, however recent studies have
baseline QT > 440 sec. shown ablation to be an appropriate first
Dronedarone [5]. line treatment without first needing to
• A structural analogue of amioda- trial and/or fail antiarrhythmic therapy.
rone, but without the iodine compo- Therefore, early referral to electrophysi-
nent of amiodarone. Lower ology should be considered, especially
incidence of adverse events com- in younger patients.
pared to amiodarone, but also not as • Anticoagulation.
effective. • Anticoagulation should be considered in all
• For use in patients who do not have patients, especially if the onset of arrhythmia
CHF. duration is greater than 48 h or unknown [5].
• Monitor LFTs. The CHA2DS2VASc score is used to calcu-
• Used less frequently due to late stroke risk and components include: CHF/
contraindications. LV dysfunction, hypertension, age, diabetes,
Sotalol [5]. prior stroke/TIA, presence of vascular disease,
• Renally cleared, so caution/contrain- and gender [6]. According to the most recent
dication in patients with CKD. ACC/AHA/HRS guidelines (2019), for
• Typically initiated inpatient, but patients with a CHA2DS2VASc score of 2 or
some experts may consider outpa- greater in men, and 3 or greater in women,
tient initiation in certain patients oral anticoagulants are recommended [6].
with close surveillance. –– IV heparin.
Can worsen CHF. In the acute setting, if not contraindicated,
Options for rhythm control other than antiar- IV heparin can be utilized with subse-
rhythmic therapy include: quent transition to a direct oral anticoagu-
–– Cardioversion. lant (apixaban, rivaroxaban, or dabigatran)
–– Atrial fibrillation ablation [2, 4–6]. or warfarin (once INR therapeutic).
AF is often triggered by ectopic focal –– Apixaban (Eliquis®) [5, 6].
discharges, which most commonly arise Direct Factor Xa Inhibitor.
110 L. Raines

Dose based on weight (60 kg), serum Notable points regarding the newer direct oral anticoagu-
lants (DOACs). More information can be found by refer-
creatinine (1.5 mg/dL), and age encing the trials noted above, as well as specific drug
(80 years). packaging inserts
Doses: 5 mg BID; otherwise, 2.5 mg Fewer drug interactions than warfarin
BID if meets 2 of the above criteria. More rapid onset/offset
Able to be used in patients with ESRD Less risk of intracranial bleeding when compared with
on dialysis. warfarin
Notable trial: ARISTOTLE. Bridging with heparin should be individualized and
may not be needed
–– Rivaroxaban (Xarelto®) [5, 6].
DOACs are not to be utilized in patients with valvular
Direct Factor Xa Inhibitor. AF or mechanical valve prosthesis.
Dose based on renal function due to pre- Twice daily dosing (apixaban, dabigatran) vs daily
dominant renal clearance. dosing (rivaroxaban, edoxaban)
Administered once daily with the eve- Rivaroxaban should be taken with food
Consideration and dose adjustment in patients with
ning meal to ensure adequate
CKD and ESRD
absorption.
Doses: 20 mg daily; 15 mg daily for cre-
atinine clearance 30–49 mL/min. tion. For patients with AF and without a
Notable trial: ROCKET AF. mechanical heart valve, decisions on
–– Dabigatran (Pradaxa) [5, 6]. bridging should balance risk of stroke
Direct thrombin inhibitor. and risk of bleeding, as well as the dura-
Renally cleared, dose based on renal tion of time off anticoagulation.
function. Reversal agent: vitamin K.
Doses: 150 mg BID; 75 mg BID for cre-
atinine clearance 15–30 mL/min. eft Atrial Appendage Occlusion
L
Notable trial: RE-LY. For patients with contraindication to long-term
–– Edoxaban [6]. anticoagulation, exclusion of the left atrial
Doses: 60 mg daily for creatinine clear- appendage via a percutaneous strategy can be
ance 50–95 mL/min; 30 mg daily for considered [5, 6]. One such device for left
creatinine clearance 15–50 mL/min. atrial appendage occlusion is the Watchman®
Direct Factor Xa inhibitor. device. Another device is the Amplatzer
Notable trial: ENGAGE-AF. Amulet®. These devices are typically placed in
–– Warfarin [5, 6]. the cardiac catheterization lab or EP lab via a
A vitamin K antagonist with multiple femoral catheter approach. Patients will require
action sites along the coagulation short-term anticoagulation after device place-
cascade. ment but will not require long-term
Requires regular PT/INR monitoring anticoagulation.
with goal 2–3 for AF in the absence of a
mechanical heart valve. Cryptogenic Stroke
Warfarin is the recommended oral anti- If a person has a stroke with unknown cause or
coagulant for those with mechanical etiology, and if external ambulatory monitoring
heart valves and target INR is based on is unrevealing, placement of an implantable loop
the type and location of the prosthetic recorder is reasonable to identify silent atrial
valve. (Supported by results from the fibrillation.
RE-ALIGN trial).
Bridging is required for patients with Clinical Pearls
AF and a mechanical heart valve if the • DOACs have quicker onset, fewer drug inter-
procedure requires warfarin interrup- actions and lower bleeding risk than Warfarin.
9 Atrial Arrhythmias 111

• Warfarin is the drug of choice for valvular 2015 ACC/AHA/HRS guideline for the Management
of Adult Patients with supraventricular tachycardia. J
atrial fibrillation. Am Coll Cardiol. 2016;67(13):e27–e115.
• First-line treatment of SVT is always depen- 2. Baltazar RF. Basic and bedside electrocardiography.
dent on patient stability. Philadelphia: Wolters Kluwer; 2009.
• Short RP tachycardias: typical AVNRT, ortho- 3. Wagner GS. Marriott’s practical electrocardiogra-
phy. 10th ed. Philadelphia: Lippincott, Williams &
dromic AVRT, junctional tachycardia. Wilkins; 2001.
• Long RP tachycardias: atypical AVNRT, atrial 4. Mann DL, Zipes DP, Libby P, Bonow RO, Braunwald
tachycardia, sinus tachycardia. E, editors. Braunwald’s heart disease. A textbook of
• Avoid AV nodal blocking agents with WPW cardiovascular medicine, vol. 1. 10th ed. Philadelphia,
PA: Elsevier; 2015.
(or pre-excited atrial fibrillation). 5. January CT, Wann LS, Alpert JS, Calkins H,
• Typical flutter is counterclockwise, around the Cigarroa JE, Cleveland JC Jr, Conti JB, Ellinor PT,
CTI, with negative appearance of the flutter Ezekowitz MD, Field ME, Murray KT, Sacco RL,
wave. Stevenson WG, Tchou PJ, Tracy CM, Yancy CW,
American College of Cardiology/American Heart
• The earlier, the better for atrial fibrillation Association Task Force on Practice Guidelines. 2014
ablation. AHA/ACC/HRS guideline for the management of
patients with atrial fibrillation. J Am Coll Cardiol.
2014;64(21):e1–76.
6. January CT, Wann LS, Calkins H, Chen LY, Cigarroa
JE, Cleveland JC Jr, Ellinor PT, Ezekowitz MD, Field
References ME, Furie KL, Heidenreich PA, Murray KT, Shea JB,
Tracy CM, Yancy CW. 2019 AHA/ACC/HRS focused
1. Page RL, Joglar JA, Caldwell MA, Calkins H, Conti update of the 2014 AHA/ACC/HRS guideline for the
JB, Deal BJ, Estes NAM 3rd, Field ME, Goldberger management of patients with atrial fibrillation. J Am
ZD, Hammill SC, Indik JH, Lindsay BD, Olshansky Coll Cardiol. 2019;74(1):104–32.
B, Russo AM, Shen WK, Tracy CM, Al-Khatib SM. 7. Tikosyn treatment guidelines.
Ventricular Tachycardia
10
Robert Hipp

Introduction acutely in the presence of ischemia. Arrhythmias

secondary to acute ischemia are often faster and
Ventricular tachycardia (VT) is wide complex more irregular than ones caused by chronic scar
tachyarrhythmia with a QRS duration greater or structural heart disease.
than 120 ms and a heart rate greater than 100 bpm
[1]. It is defined as 3 or more premature ventricu-
lar contractions with a heart rate greater than Pathophysiology
120% of the underlying rate. It can be nonsus-
tained (greater than 3 beats) or sustained (greater The mechanism for initiation of VT is either
than 30 seconds or with hemodynamic compro- abnormal automaticity, triggered activity, or re-
mise). In acute presentations, any wide-complex entry. In the case of re-entry, there must be an
tachycardia should be treated as VT until proven early stimulus such as a PVC as well as a sub-
otherwise. strate to sustain the arrythmia. Re-entry is the
VT can be described based on QRS morphol- most common mechanism of ventricular arrhyth-
ogy to include monomorphic, polymorphic, and mias and often occurs in the presence of struc-
ventricular fibrillation. Monomorphic VT has a tural heart disease [3]. Triggered and automatic
consistent QRS morphology from beat to beat ventricular arrythmias are less common and are
[2]. Polymorphic VT has a consistent deviation in caused by changes to the cardiac action potential
QRS morphology between beats [2]. Ventricular resulting in abnormal impulse formation [1].
fibrillation (VF) is a disorganized tachyarrhyth-
mia with no clear QRS complexes and leads to
sudden hemodynamic compromise given failure Re-entry
of relevant cardiac contraction.
In some cases, VT is caused by the presence of Ventricular Tachycardia is most caused by a re-
chronic ventricular scar which leads to abnormal entrant circuit in the ventricle due to a direct
impulse formation and propagation. These pre- insult (such as an MI) leading to remodeling (scar
sentations often have regular R-R intervals and formation) [3]. Re-entrant circuits often cause
monomorphic morphology. VT can also occur monomorphic VT with regular R-R intervals.
Scar-related re-entry is commonly seen in
R. Hipp (*) patients with heart disease from infarction and
Cardiac Electrophysiology, Hospital of the University fibrosis, but can also occur with other types of
of Pennsylvania, Philadelphia, PA, USA cardiomyopathies. Other causative conditions
e-mail: [email protected]

© The Author(s), under exclusive license to Springer Nature Switzerland AG 2023 113
R. Musialowski, K. Allshouse (eds.), Cardiovascular Manual for the Advanced Practice Provider,
https://doi.org/10.1007/978-3-031-35819-7_10
114 R. Hipp

include cardiac sarcoidosis, arrhythmogenic right QT prolongation occurs with lengthening of

ventricular cardiomyopathy (ARVC), surgical the action potential duration (phase 3) and allows
correction of congenital heart disease, and myo- for PVC to fall on the T wave, initiating polymor-
carditis [2]. phic VT. Hypokalemia and a prolonged QT inter-
Re-entry circuits form in the area or zone val (either genetic Long QT syndrome or taking
between myocardial scar and healthy tissue. QT offending medications) can increase the pos-
Circuits can be subendocardial, epicardial, or sibility of this arrhythmia [1]. Ion channel dys-
extend through the entire thickness of the myo- function (inherited or otherwise) may also
cardium [3]. These regions blending live myo- lengthen repolarization leading to the develop-
cytes with fibrotic areas allow for abnormal ment of early after depolarizations (EADs) and
impulse propagation and areas of slow conduc- triggered extrasystoles [3].
tion. When an appropriately timed premature Catecholaminergic polymorphic ventricular
ventricular beat occurs, re-entry is triggered. A tachycardia (CPVT) is a VT occurring with
single large scar can have several VT circuits increased catecholamine release (such as with
(with different QRS morphologies) arising from exertion) or during a severe emotional distur-
it using different exit sites. bance. This occurs in the setting of a structurally
normal heart without the fibrotic changes associ-
ated with reentry [3]. Bidirectional VT is a hall-
Automaticity mark of CPVT but may also be seen with digoxin
toxicity.
Abnormal automaticity leading to ventricular
arrhythmia is caused by changes in phase 4 of the
cardiac action potential where the myocardial Symptoms
cells are spontaneously depolarizing at a consid-
erably faster rate than normal [4]. Abnormal Most patients are highly symptomatic when
automaticity is associated with acute, reversible experiencing ventricular tachycardias. Common
conditions such as electrolyte abnormalities, symptoms include dizziness, lightheadedness,
hypoxemia, and acute MI [3]. Some VT may not palpitations, or shortness of breath. In some
be associated with underlying heart disease and cases, particularly in the setting of fast VTs, the
has characteristic locations and EKG appearance patient can become hemodynamically unstable
(i.e., RVOT-VT). and develop syncope or have a cardiac arrest.
Rarely, patients may have minimal symptoms
besides a generalized feeling of fatigue, espe-
Triggered Activity cially if the VT has a slow rate.

Electrolyte imbalance, sympathomimetic drugs,

catecholaminergic polymorphic ventricular Physical Exam
tachycardia (CPVT), pause dependence, and QT
offending medications are also causes of VT The patient in VT will have a tachycardic rate
independent of scar or fibrotic changes [3]. Low with potential jugular venous pulsation “cannon
potassium, magnesium, and calcium levels are all A waves” due to A-V dissociation. These waves
known to change action potentials, while con- are caused by atrial contraction against a closed
genital or medication acquired QT prolongation tricuspid valve during the ventricular arrhythmia.
impacts repolarization allowing for the develop- Blood pressure may be low, and patients may be
ment of VT, or more commonly torsade de tachypneic. There may also be signs of compro-
pointes. mised cardiac output including poor peripheral
10 Ventricular Tachycardia 115

perfusion, mental status changes, signs of heart firming SVT. Always compare EKG in VT to
failure. EKG in sinus!

EKG features favoring VT

wide QRS (>140 ms)
Diagnostics AV dissociation
fusion beats
Making a diagnosis of VT is based on several capture beats
ECG findings including heart rate greater than extreme axis deviation
100 bpm, QRS duration greater than 120 ms, and chest lead concordance
a grossly regular R to R interval although there R-S > 100 ms
may be subtle variation from beat to beat during
initiation (Fig. 10.1) [1, 3]. Confirmation of a ventricular tachycardia
AV dissociation (Fig. 10.2) is seen with the diagnosis can be definitively ascertained through
arrows illustrating P waves superimposed within electrophysiologic testing. In the electrophysiol-
the ventricular complexes. There is concordance ogy lab, catheters are positioned in the right ven-
through the precordial leads (Figs. 10.1 and tricle via the femoral or jugular vein. Programmed
10.3), and r-S > 100 ms in any single precordial electrical stimulation (PES) is delivered via these
lead [5]. Figure 10.4 is also consistent with a catheters to simulate various sequences of PVCs
diagnosis of VT. These findings are critical in the with the intention of inducing the clinical arrhyth-
differentiation of VT from supraventricular mia. In patients with an internal cardioverter defi-
tachycardia (SVT), however, if there is any brillator (ICD), PES can be performed
uncertainty, always assume it is VT until proven noninvasively via the device. Whether performed
otherwise. Figure 10.5 reveals a regular, wide invasively or noninvasively, an external defibril-
complex tachycardia (WCT), but upon review the lator should be nearby and prepared to defibril-
r-S ratio is <80 ms, thus ruling out VT and con- late the patient should they become

Fig. 10.1 Wide complex tachycardia converting to sinus rhythm with different QRS morphology suggestive of VT
116 R. Hipp

Fig. 10.2 Wide complex tachycardia with arrows demonstrating P waves and atrioventricular (AV) disassociation

Fig. 10.3 Burst of wide complex tachycardia which is monomorphic and concordant suggestive of VT

hemodynamically unstable following induction personal history of syncope, as well as family

of VT or VF. history, specifically exploring premature deaths
Once the patient is stable, identification of a in immediate relatives, is critical. The ECG in
cause should be pursued. Subsequent treatment sinus rhythm will be the first diagnostic test to
can then be tailored to the patient-specific disease potentially shed light on the etiology of the VT.
process. A complete history, closely assessing for Cardiac ischemia or scar, hypertrophic cardiomy-
10 Ventricular Tachycardia 117

Fig. 10.4 A r-s interval of >100 ms suggestive of VT

Fig. 10.5 A wide complex tachycardia (WCT) and a QRS interval <100 ms is suggestive of SVT. Also, compare to
EKG in sinus rhythm below-the complexes are similar
118 R. Hipp

opathy, ARVC, Brugada, and Long QT are just (AAD) therapy is reasonable using a medication
some of the diseases that may be apparent with such as amiodarone. This is a class III antiar-
this simple tool. rhythmic and works by blocking the potassium
A full ischemic evaluation is critical given the channels. Intravenous lidocaine can also be used
prominence of coronary disease as a cause of for arrhythmia suppression (Chap. 7). Should
ventricular arrhythmias. This includes either that fail and the patient becomes unstable, IV
stress testing with imaging and/or cardiac cathe- sedation and synchronized direct current cardio-
terization and possible revascularization [6]. version is needed. If the VT degrades into VF, the
Echocardiography should be done to further patient should have immediate unsynchronized
quantify the LVEF, as well assess for structural defibrillation.
abnormalities that would lead to a clear etiology Polymorphic VT is likely to be brief and spon-
of VT/VF. Advanced imaging with cardiac MRI taneously stop, at which point immediate atten-
using gadolinium-based contrast agents can help tion to the QT duration in sinus rhythm is
identify areas of delayed enhancement, repre- required. If the QT duration is normal (less than
senting myocardial scar and fibrosis. 440 ms in men and less than 460 ms in women)
A signal averaged ECG reviews hundreds of during sinus rhythm, the patient should be treated
QRS complexes from surface tracings and can like monomorphic VT as previously mentioned.
identify late potentials following the QRS com- However, if, during sinus rhythm, they have a
plex that may not be identified on a traditional prolonged QT interval they should be treated
ECG. These late potentials can represent slow with magnesium to suppress or reduce the ampli-
conduction secondary to fibrotic changes of a tude of EADs and isoproterenol to increase the
re-entry circuit [1]. heart rate. Of note, a QTc greater than 500 ms in
Finally, genetic testing should be arranged if both men and women is associated with malig-
there is no identifiable cause of the arrhythmia, to nant arrhythmias, specifically torsade de pointes.
further confirm the diagnosis or for planning for Patients should be quickly assessed for elec-
cascade family testing [2]. trolyte disturbances and treatment should be
started to stabilize the ion channels. The possibil-
ity of acute myocardial ischemia should be
Acute Management assessed. If this is thought to be the cause of the
arrhythmia, the patient will require cardiac cath-
Upon presentation, all wide complex tachycar- eterization and prompt revascularization [1].
dias should be treated as ventricular tachycardia Again, it is paramount to always rule on the
until proven otherwise [1]. The acute treatment of side of any WCT being VT over SVT. Intravenous
VT/VF revolves around the hemodynamics of the adenosine can be given to the hemodynamically
patient. Any patient that is in monomorphic VT stable patient in a WCT to potentially confirm
with hemodynamic collapse requires synchro- SVT diagnosis.
nized direct current cardioversion to restore sinus
mechanism. Synchronization is a setting on the
defibrillation device that tracks the QRS to avoid Long-Term Treatment
decompensation to VF by a shock on the T wave
(R on T). If they are in sustained polymorphic VT Chronic treatment, baring side effects or contra-
or VF, they will need immediate defibrillation indications, will more than likely include beta
due to either rapidly changing, or unstable QRS blockade and possible antiarrhythmic therapy for
complexes. ongoing malignant arrhythmia suppression [3].
If a patient presents in stable monomorphic Beta blockade has been proven to increase sur-
VT with adequate organ perfusion, an attempt at vival, but the combination of beta blockade and
restoring sinus rhythm with antiarrhythmic drug amiodarone leads to improved outcomes and less
10 Ventricular Tachycardia 119

VT recurrence. The use of antiarrhythmic ther- • VT is common with underlying structural or

apy does not increase survival but controls cardiovascular heart disease.
arrhythmias and improves symptoms [3]. For an • VT may be due to re-entry, triggered, or auto-
episode of VT lasting greater than 30 s and not in matic substrates.
the setting of a reversible cause such as acute • Acute treatment is maintaining hemodynamic
myocardial infarction including cardiac arrest or stability and restoration of sinus rhythm.
VT in the setting of low EF, placement of a sec- • Chronic treatment may include antiarrhyth-
ondary prevention implantable cardiac defibrilla- mics, ablation, or ICD placement.
tor is necessary [7]. Furthermore, catheter
ablation of VT can be considered if medications
are ineffective or not tolerated for monomorphic
VT [6]. Areas of live cells within the scar or areas References
of slow conduction may be targeted. Most origi-
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self-assessment. 1st ed. Wiley-Blackwell; 2006.
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polymorphic VT, the PVC focus can be targeted. dia. [Updated 2021 Aug 11]. In: StatPearls [Internet].
Treasure Island, FL: StatPearls Publishing; 2022.
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3. Fogoros R. Electrophysiologic testing. 5th ed. Wiley-
Conclusion Blackwell; 2012.
4. Antzelevitch C, Burashnikov A. Overview of
Ventricular tachycardia is a potentially life- basic mechanisms of cardiac arrhythmia. Card
threatening arrhythmia that affects hundreds of Electrophysiol Clin. 2011;3(1):23–45. https://doi.
org/10.1016/j.ccep.2010.10.012.
thousands of Americans every year with varying 5. Brugada P, Brugada J, Monts L, Smeets J, Andries E. A
presentation and etiology. Acute treatment is cen- new approach to the differential diagnosis of a regular
tered around maintaining hemodynamic stability tachycardia with a wide QRS complex. Circulation.
and restoring normal sinus rhythm. The patient 1991;83(5):1649–59. https://doi.org/10.1161/01.
cir.83.5.1649.
should then undergo a thorough workup to deter- 6. Cronin EM, Bogun FM, Maury P, Peichl P, Chen
mine the underlying cause which will inform the M, Namboodiri N, Aguinaga L, Leite LR, Al-Khatib
long-term treatment plan. This plan can include SM, Anter E, Berruezo A, Callans DJ, Chung MK,
any combination of chronic antiarrhythmic ther- Cuculich P, D’Avila A, Deal BJ, Della Bella P,
Deneke T, Dickfeld TM, et al. 2019 HRS/EHRA/
apy, implantable cardioverter defibrillator, and APHRS/LAHRS expert consensus statement on cath-
ablation. eter ablation of ventricular arrhythmias. Europace.
2019;21(8):1143–4. https://doi.org/10.1093/europace/
Pearls euz132.
7. 2017 AHA/ACC/HRS ventricular arrhythmia and
• Wide complex tachycardia should be treated prevention of sudden cardiac death guidelines.
as VT until proven otherwise. Circulation. 2018;138(13):e210–71.
• Can try adenosine if patient stable to help in
diagnosis of VT vs. SVT.
Cardiac Channelopathies
11
Krista Allshouse

Introduction channelopathy suspected. Genetic testing is not

only important to obtain a specific diagnosis with
Primary inherited arrhythmia syndromes or high clinical suspicion, but to risk stratify, guide
“channelopathies” are a set of disorders in which therapy, and provide screening for relatives.
one or more of the cardiac ion channels functions Recently, it has been more common to use multi-
abnormally. Mutations in genes encoding critical gene or whole exome sequencing using a blood
ion channels, most commonly sodium, calcium, or buccal swab. These tests have high sensitivity,
and potassium channels, are the cause of the car- can identify multiple gene mutations simultane-
diac pathology. This has various implications on ously, and can identify “modifier” genes which
cardiac conduction including resultant Long or affect expression or intensity of expression in the
Short QT Syndrome, Brugada Syndrome, and patient. Interpretation is complicated and testing
Catecholaminergic Polymorphic Ventricular should only be completed by providers versed in
Tachycardia (CPVT), all of which are considered counseling on the implications of the results.
channelopathies. There are often “variants of unknown signifi-
Channelopathies may be identified after an cance” identified. These are genetic variants but
individual cardiac arrest, family history of sud- the specific location on the gene is not specifi-
den cardiac death (SCD), or clinical suspicion cally associated with a disease.
based on evaluation after a syncopal event.
Patients with channelopathies generally have
structurally normal hearts. The more recent wide- Long QT Syndrome
spread use of genetic testing has allowed provid-
ers to better identify patients at risk and initiate The first identified and most common channelop-
treatment. This may, in turn, lower the overall athy is the Long QT Syndrome (LQTS). This syn-
risk to the patient and immediate family drome occurs when the QT interval on the EKG is
members. prolonged due to either a congenital mutation or
The Guidelines for Sudden Cardiac Death and acquired due to medications, electrolyte abnor-
Arrhythmia Evaluation recommend genetic test- malities, metabolic disorders, ischemia, or intra-
ing as a part of diagnosis, depending on specific cranial pathology. The most common
QT-prolonging medications are listed on the
K. Allshouse (*) Crediblemeds.org website. Important offending
Atrium Health, Levine Childrens’ Congenital Heart medications to know would be specific antiemet-
Center, Charlotte, NC, USA ics, PPIs, SSRIs, antipsychotics, and some antibi-
e-mail: [email protected]

© The Author(s), under exclusive license to Springer Nature Switzerland AG 2023 121
R. Musialowski, K. Allshouse (eds.), Cardiovascular Manual for the Advanced Practice Provider,
https://doi.org/10.1007/978-3-031-35819-7_11
122 K. Allshouse

otics/antifungals. Many frequently used where QT was measured. In atrial fibrillation,

medications including Zofran, Benadryl, Pepcid, the average of 5 consecutive QT intervals should
Protonix, Celexa, Paxil, Imodium, Zithromax, be measured and then averaged, due to the poten-
and antiarrhythmics are on the list. The most com- tial irregularity of the R-R interval (Figs. 11.1
monly associated electrolyte abnormalities asso- and 11.2).
ciated with QT prolongation are hypokalemia, When the QT prolongs, it predisposes the
hypomagnesemia, and hypocalcemia. patient to R-on-T phenomenon which is where a
The QT interval is the total electrical sum of PVC occurs during a vulnerable period of repo-
ventricular depolarization and repolarization. It larization of the ventricule (during the T wave).
is measured from the beginning of the QRS com- This triggers polymorphic ventricular tachycar-
plex to the end of the T wave on a 12-lead dia, or Torsades de Pointes (TdP). Torsades can
EKG. A normal QT interval is <440 ms in a male be preceded by a long-short R-R interval or bra-
or <460 ms in a female. It should shorten with dycardia causing “pause-dependent” ventricular
higher heart rates and lengthen with slower heart tachycardia (VT).
rates. The corrected QT interval (QTc) is calcu- The prevalence of the genetic type of LQTS
lated by measuring the intervals on EKG and occurs in about 1/2000 individuals. The risk of
using a formula to correct for the heart rate. death in untreated LQTS is 21% in the year after
There are various correction formulas that can be a first syncopal event but decreases to ~1% over
used including Bazett, Framingham, Hodges, 15 years if treated [7]. SCD can be the initial pre-
and Fredericia to adjust for heart rate. The Bazett sentation of this syndrome. Arrhythmias are more
(most common) formula for the corrected QT common in younger patients and can occur
(QTc) interval is QT/ √ R-R (see below) and around menses or childbirth.
should be directly measured rather than relying The congenital form of LQTS can be caused
on the computer read, which is often inaccurate. by multiple gene mutations with 13 types now
The QT interval should be measured in leads V5 identified. Approximately 15–20% of patients
or II. The limb lead with the sharpest end of the with a prolonged QT are gene positive and less
T wave can also be used. The R-R interval should than 5–10% are de novo mutations. The most
be measured immediately preceding the beat common types are Long QT I, II, and III. Romano-

Fig. 11.1 Measure QT and previous R-R. Then calculate QTc with formula: measured QT/√R-R
11 Cardiac Channelopathies 123

Fig. 11.2 Long QT interval on EKG

Ward syndrome is the autosomal-dominant form gangliectomy (sympathetic denervation) is also

and Jervell-Lange Nielson syndrome is autoso- an option for non-responders to therapy or if
mal recessive and associated with congenital therapy cannot be tolerated. This procedure is
deafness. LQTS1 is associated with a gene muta- accomplished with a video-assisted thoraco-
tion in KCNQ1 and described as an event occur- scopic technique (VATS procedure) where the
ring during exertion, especially during swimming. left stellate ganglion and a few left thoracic
LQTSII has a gene mutation in KCNH2 and is ganglion are removed, blocking sympathetic
classically associated with ventricular arrhythmia signals to the heart.
triggered by a startle or by emotional stress.
LQTS3 is a defect in SCN5A and is associated
classically with ventricular arrhythmia and car- Short QT Syndrome
diac arrest during sleep.
Treatment of all types of Long QT Syndrome This condition is due to an accelerated repolar-
includes a reduction in adrenergic tone and pre- ization phase of cardiac conduction. Short QT is
vention of ventricular arrhythmias. Beta block- defined as a QTc ≤340 ms or ≤360 ms with a
ers are indicated in all diagnosed patients, with pathogenic gene mutation or family history.
nadolol being the preferred agent and proprano- Associated genes are inherited in an autosomal-
lol as the second-line agent due to therapeutic dominant fashion in KCNH2, KCNQ1, and
characteristics including being non-cardiose- KCNJ2. EKG may also show peaked T waves.
lective. Beta blockers are most effective in This is an uncommon disorder but is associated
patients with LQTS1 as it blocks the epineph- with 40% of patients having a cardiac arrest by
rine released during exertion. Mexiletine, fle- age 40. Other arrhythmias are common, espe-
cainide, or ranolazine may also be added for cially atrial fibrillation, and diagnosis may be
LQTS3 patients. Implantable cardioverter defi- elicited by a stress test or electrophysiology
brillators (ICDs) are recommended in patients study. No risk factors for SCD have been identi-
with resuscitated SCD, syncope, ventricular fied other than syncope. Treatment consists of
arrhythmia, or other high-risk features such as ICD implantation, hydroquinidine, or other anti-
significantly prolonged QT or significant fam- arrhythmics depending on specific gene mutation
ily history. Left cervicothoracic stellectomy/ (Fig. 11.3).
124 K. Allshouse

Fig. 11.3 Short QT interval on EKG

Fig. 11.4 Brugada pattern with PVC falling on a T wave, initiating polymorphic VT

Brugada Syndrome

Brugada syndrome (BrS) is a disorder character-

ized by right precordial ST elevation on EKG
with or without right bundle branch block, pre-
disposing to SCD. SCD risk is due to polymor-
phic VT degenerating to ventricular fibrillation
(VF) (see Fig. 11.4). It usually presents in males
in the 3rd or 4th decade of life as syncope or
SCD. The prevalence is about 1/5–10,000, more
commonly in Southeast Asia (where it is known
as the Widow Ghost who comes in the night to
carry off the souls of their young males).
Diagnosis can be made based on symptoms and
emergence of Type I pattern in leads V1 or V2
(Fig. 11.5). The sensitivity may be increased with
these leads moved to the second intercostal space.
The pattern may emerge during fever or with pro-
vocative testing. There are three patterns associ-
Fig. 11.5 Type I Brugada pattern Type 1
ated with Brugada syndrome, Type I, II, and
11 Cardiac Channelopathies 125

III. Diagnosis can only be made in the setting of causes syncope, cardiac arrest, or SCD with a
Type I pattern but Type II and III may manifest structurally normal heart. Exertion or emotional
Type I pattern in the setting of fevers or provoca- stress precedes the event and baseline EKG is
tive testing. Type I pattern is associated with normal or shows resting bradycardia. Patient
increased risk of SCA (see below). may have Premature Ventricular Contractions
The most common gene mutation is in SCN5A (PVCs), bidirectional VT (Fig. 11.6), or TdP
with genetics being positive in only about 25% of during exercise test (Fig. 11.7). This condition
patients. Brugada syndrome is inherited in an can coexist with LQTS, BrS, or hypertrophic
autosomal-dominant fashion. Management con- cardiomyopathy. Mean age of symptom onset is
sists of avoiding certain drugs (BrugadaDrugs. 8 years old but the potential for a first syncopal
org) and aggressively treating fever. ICDs are event may not occur until adulthood. The more
reserved for high-risk patients (syncope or SCD). common gene defect is an autosomal-dominant
While often used, beta blockers are of more lim- mutation in RYR2 but less commonly CPVT
ited efficacy in patients with Brugada syndrome. may be due to a recessive mutation in CASQ2.
Quinidine has been shown to be effective in pre- Genetics are positive in 65% of CPVT patients
vention of recurrent ventricular arrhythmias in and 30% of patients have SCD as their first pre-
patients with this syndrome. More recently, cath- sentation. Treatment consists of a beta blocker.
eter ablation has shown favorable outcomes as Flecainide has also shown to be effective in
well, targeting abnormal tissue on the epicardial patients with symptoms despite beta blocker
RVOT surface that has been implicated as the ini- therapy. ICD implantation is indicated in
tiating substrate for ventricular arrhythmia in patients with recurrent ventricular arrhythmia
these patients. (VA) despite beta blocker therapy although they
must be used with caution as ICDs shocks can
increase adrenergic tone which can further pro-
CPVT mote VA in these patients. Specific risks versus
benefits must be weighed due to possible VT
Catecholaminergic Polymorphic Ventricular storm with ICD shocks. Left cardiac sympa-
Tachycardia (CPVT) is a condition of adrenergi- thetic denervation is also a potential added
cally mediated ventricular arrhythmia that therapy.

Fig. 11.6 Bidirectional VT in a patient with CPVT

126 K. Allshouse

Fig. 11.7 Rhythm on a stress test of a patient with CPVT

in infants, children and adolescents. Philadelphia:

Pearls Wolters Kluwer; 2022. p. 534–50.
• QTc = QT/√R-R. 2. Wilde AAM, Ackerman MJ. Beta blockers in the treat-
• LQTS1 = KCNQ1 gene mutation, events with ment of congenital LQT syndrome: is one beta-blocker
superior to another. JACC. 2014;64(13):1359–61.
exertion. 3. Ackerman MJ. Genetic purgatory and the cardiac
• LQTS2 = KCNH2 gene mutation, events with channelopathies: exposing the variants of uncer-
startle. tain/unknown significance issue. Heart Rhythm.
• LQTS3 = SCN5A gene mutation, events with 2015;12(11):2325–31.
4. Ackerman MJ, et al. HRS/EHRA expert consen-
sleep. sus statement on the state of genetic testing for the
• Beta blockers for all Long QT-Nadolol or channelopathies and cardiomyopathies. Europace.
Propranolol are best. 2011;13(8):1077–109.
• Brugada-Type 1 pattern in V1, V2-3rd or 4th 5. HRS/EHRA/APHRS expect consensus statement on
the diagnosis and management of patient with inher-
decade of life, more in males. ited primary arrhythmia syndromes. 2013.
• CPVT-VT with adrenaline-RYR2 or CASQ2. 6. Cho Y. Left cardiac sympathetic denervation: an
important treatment option for patients with hereditary
ventricular arrhythmias. J Arrhythm. 2016;32(5):340–
3. Published online 2015 Oct. 29. https://doi.
org/10.1016/j.joa.2015.08.002.
Further Reading 7. Schwartz PJ, Crotti L, Insolia R. Long-QT syn-
drome: from genetics to management. Circ Arrhythm
1. Moss AJ, Adams FH. Cardiac channelopathies, Electrophysiol. 2012;5(4):868–77. https://doi.
syncope and SCD (Chapter 20). In: Heart disease org/10.1161/CIRCEP.111.962019.
Introduction to Cardiac Ablation
12
Krista Allshouse

An electrophysiology study (EPS) is a cardiac based on catheter position to define impulse

procedure performed in a specialized lab by a propagation in the heart.
cardiac electrophysiologist to diagnose and treat Baseline recordings of the intracardiac electri-
arrhythmias. Prior to the procedure, patients are cal signals are taken in sinus rhythm (Fig. 12.1).
sedated using conscious sedation or general anes- Normal cardiac conduction properties are mea-
thesia, access sites are sterilely prepped, and sured such as the conduction through the AV
catheters are placed via the left and right femoral node and His bundle. Diagnostic pacing maneu-
veins (and potentially other veins such as the vers are then carried out to test the conduction
internal jugular vein) into specific areas of the system and induce arrhythmias. These can iden-
heart. These may include the high right atrium, tify the presence of conduction pathways that
HIS bundle area, coronary sinus, right ventricle, may mediate arrhythmias, such as a slow path-
and may also be placed into the left heart via a way within the AV node or an accessory atrioven-
puncture of the atrial septum for left-sided tricular pathway in WPW. Sympathomimetic
arrhythmias (transseptal puncture) (Fig. 12.2). drugs such as isoproterenol or dobutamine can
An arterial line may also be placed for blood also be used to support blood pressure and help
pressure monitoring. Systemic heparin is used for with arrhythmia induction. Additionally, map-
anticoagulation during the procedure while cath- ping catheters can be used to measure the electri-
eters are in the body. Fluoroscopy is sometimes cal potentials of specific areas of myocardium to
used for catheter placement as well. These cath- identify signals or scar tissue which may form an
eters are attached to the recording systems for arrhythmic substrate. This mapping can be done
signal analyzation (Fig. 12.1). Most procedures endocardially in the right heart, via trans-atrial
are also performed with electroanatomic map- septal puncture or retrograde aortic access in the
ping systems which use a combination of mag- left heart, and epicardially via subxiphoid access.
netic sensors and impedance measurements A hybrid procedure involving all the mapping
within intracardiac catheters. External references options may be needed as well. These may help
to triangulate catheter position within the heart define the mechanism of arrhythmia and guide
are used to generate three-dimensional cardiac treatment.
models. Electrical measurements are tracked Once a specific arrhythmia is found, ablation
may be undertaken with radiofrequency (heat
K. Allshouse (*) energy) or cryoablation (freezing energy). The
Atrium Health, Levine Childrens’ Congenital Heart choice of modality used depends on the specific
Center, Charlotte, NC, USA arrhythmia and where the ablation site is anatom-
e-mail: [email protected]

© The Author(s), under exclusive license to Springer Nature Switzerland AG 2023 127
R. Musialowski, K. Allshouse (eds.), Cardiovascular Manual for the Advanced Practice Provider,
https://doi.org/10.1007/978-3-031-35819-7_12
128 K. Allshouse

Fig. 12.1 EP recording system screen with surface EKG leads on top (white), coronary sinus catheter recordings in
green, HIS bundle recording in yellow, and right ventricle recordings in red

Post-procedurally, catheters are removed, and

hemostasis is obtained using a variety of methods
including manual compression, temporary skin
sutures, and closure devices. A period of bedrest
is generally required. Depending on the proce-
dure type and duration, the patient may be dis-
charged the same day or the following morning.
Immediately post-procedure, the patient will be
closely monitored including evaluation of periph-
eral pulses in the legs, access site assessments,
vital signs, and neurologic evaluations to make
sure there are no complications. Post procedure
labs may be ordered per physician protocol and
patient should be monitored on telemetry and
have a post procedure EKG completed.
The risks of these procedures may include
groin bleeding/hematoma formation, pseudoaneu-
rysm, retroperitoneal bleeding, stroke, cardiac per-
foration, arrhythmia requiring cardioversion, or
death. Specific types of ablation procedures may
Fig. 12.2 Fluoroscopy image of catheter placement in also carry unique risks. For example, atrial fibrilla-
the heart: high right atrium (HRA), coronary sinus (CS),
His bundle (His), and right ventricle (RV) [1]
tion ablation is associated, rarely, with atrio-
esophageal fistula (AE) in which esophageal
injury during ablation leads to an esophageal-left
ically located. Post-ablation testing is then com- atrial fistula. Generally presenting 2–4 weeks post-
pleted to make sure the conduction system ablation, aorto-enteric fistulas are life-threatening
remains unaffected, rule out additional arrhyth- and prompt recognition increases survival Right
mias, and to make sure the ablated arrhythmia is phrenic nerve injury is possible with atrial fibrilla-
terminated. tion ablation as well as right atrial ablation in spe-
12 Introduction to Cardiac Ablation 129

cific areas. Epicardial ablation can be associated Further Reading

with abdominal organ injury due to subxiphoid
access. Ablation of AV nodal re-entrant tachycar- Dick M. Clinical cardiac electrophysiology in the young.
2nd ed. New York: Springer; 2015.
dia and WPW can be associated with heart block Fogoros RN, Mandrola JM. Fogoros’ electrophysiologic
requiring permanent pacemaker. testing. 6th ed. Wiley; 2018.
Steinberg JS, Mittal S. Electrophysiology, the basics. A
companion guide for the cardiology fellow during the
EP rotation. Philadelphia, PA: Lippincott, Williams,
References and WIlkins; 2010.

1. Wenzl FA, Manninger M, Wunsch S, et al. Post-cardiac

injury syndrome triggered by radiofrequency ablation
for AVNRT. BMC Cardiovasc Disord. 2021;21:611.
https://doi.org/10.1186/s12872-021-02436-1.
Introduction to Electrophysiology
Devices
13
Jamie A. Dietrich

Basics of Pacemakers left ventricular function and clinical heart failure.

In fact, RV apical pacing produces a LBBB on
The components of a permanent pacemaker are EKG. This is especially important since patients
the pulse generator on the chest and the leads. with left bundle branch block and QRS duration
The leads are insulated wires that deliver electri- of >150 ms with HFrEF have indication for
cal impulses from the generator to the myocar- CRT. Leads can also be placed on the epicardium
dium and can sense cardiac depolarization. The surgically if pacing is indicated and there is dif-
leads are most commonly transvenous, which ficulty anatomically accessing the appropriate
means they go through the vein to the cardiac cardiac chambers.
chambers. Leads are usually placed through the Leadless pacemakers are a newer type of
subclavian vein. Leads can be placed in the right pacemakers which are placed into the right ven-
atrium, right ventricle, or the epicardial surface tricle. These devices only provide single chamber
of the left ventricle via the coronary sinus. In the pacing support with some capability to track and
right ventricle, leads can be placed in the RV pace according to atrial activity. These are typi-
myocardium or targeted to the conduction sys- cally indicated in patients with permanent atrial
tem. In the latter setting, leads are positioned at fibrillation, tachycardia bradycardia syndrome
either the His bundle or deeply embedded in the with low pacing requirements or patients with
interventricular septum to engage the left bundle intermittent heart block with limited life expec-
with a goal of engaging the conduction system to tancy. These devices can also be considered in
generate more physiologic pacing. When there is patients who have higher than normal infectious
a right and left ventricular lead in place, the risks or recurrent device infections [1]. Clinical
device is referred to as a biventricular or cardiac trials are now ongoing with dual chamber lead-
resynchronization therapy (CRT) device. A less pacing systems Fig. 13.1.
CRT-P is a biventricular pacemaker, and a CRT-D Sensing is the term used to describe the detec-
is a biventricular pacemaker with defibrillator. tion of electrical activity in a particular cardiac
When patients frequently pace in the right ven- chamber. The leads detect the depolarization of
tricle, it can result in loss synchrony between the the local myocardium where they are implanted
left and right ventricles and result in worsening and transmit this data to the pulse generator. The
magnitude of the signal is measured in millivolts
J. A. Dietrich (*) (mV). Sensitivity is a device setting defining the
Atrium Health Wake Forest Baptist, threshold, in mV, at which the device will recog-
Winston-Salem, NC, USA nize that depolarization of the cardiac chamber in
e-mail: [email protected]

© The Author(s), under exclusive license to Springer Nature Switzerland AG 2023 131
R. Musialowski, K. Allshouse (eds.), Cardiovascular Manual for the Advanced Practice Provider,
https://doi.org/10.1007/978-3-031-35819-7_13
132 J. A. Dietrich

which the lead is positioned has occurred. For leads to under pacing; undersensing leads to
example, suppose for a lead in the right atrium overpacing [2].
that during atrial depolarization, a signal measur- The pacing threshold is the minimum amount
ing 2 mV is measured. If the sensitivity of the of energy, measured in voltage delivered over
device is 1 mV, the device will recognize that the time, needed to depolarize enough local myocar-
atrium has depolarized; if set to 3 mV, it will not. dium to drive full depolarization of the cardiac
If the pacemaker senses the atrial or ventricu- chamber. The parameters above are determined
lar depolarization it was looking for, then it will at the time of pacemaker implant and are moni-
not pace (inhibit). If it does not sense the atrial or tored over time [2]. They can sometimes vary in
ventricular depolarization it was looking for, then the setting of certain medications or marked met-
it will pace the heart. A common analogy used to abolic derangements [2].
describe the sensitivity settings is that of a fence. The current is defined as the electricity flow,
If a tall fence or higher sensitivity setting is in which can be in either direction from the heart to
place, the pacemaker cannot see a lot of electrical the pacemaker or from the pacemaker to the
activity over the fence, so it is less sensitive. If a heart. Impedance is anything that opposes the
short fence or low sensitivity setting is in place, normal flow of current. Ohm’s law is defined as
the pacemaker can see electrical impulses over voltage (V) = current (I) × resistance (R)
the fence, so it is more sensitive. Oversensing Resistance is another term for impedance. This is
a measurement by the device to track the func-
tionality. If there are abnormalities in the imped-
ance, it usually indicates a problem with the leads
(either lead fracture or insulation break).
The pacemaker code consists of four letters
which conveys the mode in which the pacemaker
is operating. The letters describe in order the
chamber paced, chamber sensed, function, or
pacing response to a sensed beat and rate respon-
siveness. This code is used when describing sin-
gle and dual chamber pacemakers (see
Table 13.1).
For example, the most common type of pace-
maker setting is DDDR. This means that the
pacemaker can pace in both the right atrium and
right ventricle, sense the intrinsic electrical activ-
ity in both chambers, track the atrial activity with
inhibition of ventricular pacing, and pacing that
is rate adaptive. VVI is another common setting
that might be seen with patients in permanent
Fig. 13.1 Leadless pacemaker is seen within the heart. atrial fibrillation who need pacing support. This
No evidence of pacemaker pulse generator or traditional means that the pacemaker will pace in the right
leads are seen on the CXR ventricle, sense in the right ventricle, and then
not deliver a stimulus if intrinsic beat is sensed in
Table 13.1 Pacemaker code [3]
Chamber paced Chamber sensed Function Rate responsive
O = none O = none O = none O = none
A = atrium A = atrium I = inhibition R = rate adaptive
V = ventricle V = ventricle T = tracking
D = dual D = dual D = dual
13 Introduction to Electrophysiology Devices 133

the ventricle. If the patient will remain in atrial porary or permanent pacemaker can be placed.
fibrillation, there is no need to provide pacing It can be uncomfortable for the patient, and
support to the atrium. The mode depends on the sedation is typically required. It also can be lim-
indication for which the pacemaker is placed. In ited by high capture thresholds since the pace-
a patient with sinus node dysfunction who has a maker is external. Once the pacing pads have
problem with conduction in the right atrium, it been applied to the patient, the heart rate should
would be reasonable to program AAI or AAIR be set at 60–80 bpm. Energy output in a tempo-
but it is more common in the United States to rary pacemaker is measured in current (mA)
place a dual chamber device and program rather than voltage. Typically, output should be
DDD. In a patient with problems through the AV programmed at 10 mA and then turned up until
node, the mode is typically DDD or DDDR. Rate capture is achieved, which is usually
responsiveness means that the pacemaker can 50–100 mA. Capture is always verified by
increase the heart rate during exertion to meet the assessing the pulse of the patient, not only look-
metabolic demands of the body. Pacemakers typ- ing at the monitors.
ically have an accelerometer in the generator Transvenous pacing is using a temporary
which can sense movement and respond with pacemaker wire placed through either the inter-
increase in heart rate. Application of a magnet to nal jugular or femoral vein and then into the right
a pacemaker results in asynchronous pacing ventricle to provide pacing support. This can be a
modes, AOO, VOO, or DOO meaning the device floating temporary pacing wire, sometimes with a
does not sense intrinsic impulses [3]. balloon at the tip for stability, or an active fixation
Another important function of dual chamber lead with a helix that can be used to fixate the
pacemakers is the ability for mode switching. lead into the myocardium. The patient is also
Tracking is a normal pacemaker behavior where bedbound in this case with limited mobility.
the device senses activity in one chamber (atrium) Complications such as infection or lead migra-
and then delivers a stimulus in another chamber tion (perforation) arise more frequently if these
(ventricle). The reason for mode switching is that are left in place for longer than 48 h.
one would not want to pace the ventricle at the
atrial rate during atrial fibrillation or flutter,
which could be as high as 300 bpm [3]. This Indications for Pacemakers
means that if the atrial rate is high as occurs in
atrial fibrillation or atrial flutter, the pacemaker Current class I recommendations for pacemakers
will automatically switch to a mode where it does include:
not track.
1. Symptomatic sinus node dysfunction that
leads to symptomatic bradycardia. This is the
Temporary Pacemakers most common indication for pacemaker
placement. This indication also includes
There are several types of temporary pacemakers patient with tachycardia-bradycardia syn-
including transcutaneous pacing and temporary drome and chronotropic incompetence.
transvenous pacemakers. 2. Second-degree Mobitz type II atrioventricular
Transcutaneous pacing is using external pac- (AV) block with symptoms, with wide QRS
ing pads as well as an external cardiac monitor/ escape or with block during exercise without
defibrillator to pace the patient. The indication ischemia present.
for transcutaneous pacing is in patients with 3. Complete heart block/advanced second-
second- or third-degree heart block with hemo- degree HB with symptoms, pauses >3 s,
dynamic compromise refractory to medical escape <40 bpm, wide escape, ablation of AV
therapy such as atropine or dopamine until the node, AF with brady and pauses >5 s while
bradyarrhythmia resolves or a transvenous tem- awake.
134 J. A. Dietrich

4. Fascicular block with intermittent CHB with for the events should appear on the following
symptoms or second degree with or without pages.
symptoms. 4. Lead impedance: An abrupt or greater than
30% change in lead impedance can signal a
It is important to remember that the above are lead fracture or insulation break.
indications for permanent pacemakers regardless 5. Atrial arrhythmia burden or mode switches:
of symptoms and not attributable to reversible or Some devices will report AT/AF burden in
physiologic causes. If patients develop symptom- terms of percentage. You can also get infor-
atic AV block because of GDMT for which there mation about how many episodes of mode
is not alternative treatment, permanent pacing is switching occurred. This can give you impor-
also recommended [4]. tant diagnostic information about atrial fibril-
Another important patient population to keep lation burden.
in mind are those patients with neuromuscular 6. Pacing percentages: If a patient is pacing
diseases associated with conduction disorders. more than 40% in the right ventricle (LBBB),
These include myotonic dystrophy or Kearns- this could lead to a pacemaker-induced car-
Sayre syndrome. These patients may develop diomyopathy due to loss of synchrony
second- or third-degree AV block. In the pres- between the ventricles. An echocardiogram
ence of these blocks or if the His bundle to ven- would be the next step to assess, especially if
tricular myocardium time is greater than 70 ms the patient is symptomatic or the pacing per-
(noted on intracardiac electrograms during EP centages have increased from prior device
study), then permanent pacemaker is indicated reports. In patients with LVEF <50% and high
with defibrillator capability if needed and mean- burden of ventricular pacing, upgrade to
ingful survival of greater than 1 year is expected biventricular pacing (CRT-P) can be
[4]. considered.

Interpreting Device Interrogations Implantable Cardioverter

Defibrillators (ICDs)
There are several important data points to review
with each device interrogation. The device Basic Principles of Defibrillators
reports will have varying formats depending on
the manufacturer, but most of the important An ICD can both pace and defibrillate the heart.
information will be on the first page of the report. The pacemaker functions apply to the ICD as
Six key things to note are: well. In addition, the ICD technology can recog-
nize lethal arrhythmias such as ventricular tachy-
1. Battery life (estimated in years): If a device cardia (VT) and ventricular fibrillation (VF). The
has reached elective replacement interval or device can either pace the patient out of the
ERI, it is approaching time for a generator rhythm (for ventricular tachycardia) or deliver
change. Typically, the devices have 3 months synchronized or unsynchronized shocks. This
from the date of ERI to safely replace the bat- pacing is called antitachycardia pacing or ATP.
tery without compromising the device The ICD uses the heart rate to decide if a
function. rhythm should be treated. The settings are called
2. Settings: The pacemaker code will be put on “zones.” Different zones can be used for VT and
this, and it is important to know if it is DDDR, VF. Commonly, patients who are on an antiar-
VVIR, etc. rhythmic such as amiodarone can have a slower
3. Events: If any high atrial rates, ventricular VT, so it can be necessary to make the zone lower
rates or mode switches have occurred, these in order to sense the VT and treat it appropriately
will be contained in this summary. The EGMs [5]. Modern ICDs also have algorithms to try to
13 Introduction to Electrophysiology Devices 135

recognize SVT and avoid shock delivery. These

algorithms are based on the morphology of the
signal detected in reference to regular rhythm,
relationship of atrial and ventricular activity, and
characteristics at onset of the rapid rhythm.
It is important to remember that an ICD can
provide therapy inappropriately for a tachycar-
dia. This can occur when a patient has atrial
fibrillation with rapid ventricular response among
other SVTs. Reviewing a device interrogation
and EGMs for a patient with a shock is important
to ensure that the shock was appropriate [5].
Institutions have various shock protocols if a
patient receives an ICD shock. If a patient
receives one shock, it is important to review
device interrogation as well as to ask about symp-
toms that could have precipitated the shock Fig. 13.2 Dual chamber ICD with a lead in the RV and
including ischemia or worsening heart failure. one in the RA
Typically, the patient does not need to come to
clinic or the emergency room for this. If multiple
shocks are delivered in a short period of time, the
patient should go to the closest emergency room.
VT storm is defined as three or more ICD shocks
in a 24 h period and is a medical emergency [5].

Temporary Defibrillators

There are temporary defibrillators called wear-

able cardioverter defibrillator (WCD). WCD is a
class IIb recommendation after acute myocardial
infarction in patients with an LVEF of less than
or equal to 35%. It may be used if a patient has an
infection necessitating removal of a device as a Fig. 13.3 Biventricular ICD with a wire in the RV, RA,
stop gap measure until a new device can be placed and a LV lead at the 5 o’clock position
[5].
sinus. Subcutaneous ICDs are devices that are
implanted in the upper left abdominal area and
Permanent Defibrillators have no part of the device in the vasculature [5].
Subcutaneous ICDs are devices that are implanted
ICDs can be single chamber with one lead in the in the left axillary region with a lead that courses
right ventricle, dual chamber with one lead in the from there to the parasternal region (Fig. 13.4).
right atrium and one in the right ventricle (see These devices are fully extravascular and offer
Fig. 13.2) or biventricular (Fig. 13.3). A CRT-D the advantage of reduced infection risk, avoiding
is an ICD with one lead in the right ventricle and vascular compromise and comfort in some
one lead in the left ventricle via the coronary patients. It is not capable of pacing.
136 J. A. Dietrich

4. For secondary prevention in patients with

nonischemic cardiomyopathy if they have had
sudden cardiac arrest or sustained VT [5].

Patients with hypertrophic cardiomyopathy

have increased risk of sudden death. There are
numerous risk factors, risk modifiers, as well as
high risk substrates. Risk stratification should be
performed every 1–3 years in these patients to
determine the need for an ICD [5]. Indications
for subcutaneous defibrillators are typically
patients without any need for a pacemaker func-
tion or in patients with high infectious risk or
recurrent device infections. Many young patients
Fig. 13.4 Sub-cutaneous ICD generator in place on left
with hypertrophic cardiomyopathy receive sub-
lateral chest with lead running along the sternum tunneled
under the skin cutaneous defibrillators if indicated as the
patients are younger and likely to live longer than
a transvenous system would last [6]. Other indi-
Indications for Defibrillators cations for subcutaneous defibrillators include
having cardiac anatomy that is difficult to access
Primary prevention ICD means that the patient or in patients with active lifestyles.
has not had sustained VT or cardiac arrest.
Secondary prevention means that the patient has
had sustained VT or cardiac arrest. Sustained VT Interpreting Device Interrogations
is defined as at least 30 s of VT [5].
Class I indications for ICDs include: The same principles as with pacemaker interro-
gations apply here. The important differences
1. For primary prevention in patients with isch- include any tachycardia events, ICD therapies
emic heart disease who are greater than which include antitachycardia pacing (ATP) or
40 days from MI and/or more than 90 days shocks. The EGMs on the device interrogation
from revascularization despite maximally tol- are important to review as well to get a sense if
erated GMDT with an EF ≤ 35% with at least the shock was appropriate or not.
class II NYHA symptoms or with an
EF ≤ 30% with NYHA class I symptoms.
Patients need to have a life expectancy of Common Problems
greater than 1 year. and Troubleshooting Pacemakers
2. For secondary prevention in patients with and ICDs
ischemic heart disease regardless of LVEF or
have syncope thought to be cardiac in etiol- Cardiac device manufacturers provide a great
ogy with LVEF less or equal to 35%. Patients deal of support for devices. It is important to
need to have life expectancy of greater than remember that a call can be placed to the cardiac
1 year. device company for an interrogation or trouble-
3. For primary prevention in patients with non- shooting. Often, the representatives can assist in
ischemic cardiomyopathy with HF NYHA programming changes. Most device clinics also
class II-III symptoms and LVEF less than or employ cardiac device technicians to check and
equal to 35% despite maximally tolerated monitor devices in the clinic. These individuals
GDMT. Patients need to have life expectancy can be invaluable in terms of knowledge and
of greater than 1 year. troubleshooting devices.
13 Introduction to Electrophysiology Devices 137

One of the most common problems with a Then you can turn the milliamps on the device
permanent pacemaker or ICD is either a lead console slowly to see if this changes. Consider
fracture or a break in the insulation of the wire. ordering a chest x-ray at this point to check lead
The lead impedance (measured in ohms) will position. Acute causes of failure to capture
provide information on the integrity of a lead. include lead dislodgement or malposition, which
An abrupt or greater than 30% change in the lead can be more common with temporary pacemak-
impedance is concerning. If a lead itself frac- ers or in the immediate post-operative period
tures, the impedance or resistance will go up. If after implantation of a permanent device.
the insulation is broken, the impedance or resis- Premature battery depletion is another cause of
tance will go down. This also can result in pre- loss of capture. Depending on the indication for
mature battery depletion and oversensing. If a the device, the patient may need to be admitted
lead problem is suspected based on the device for expedited generator change. Other causes
interrogation, the next step is to obtain a chest include battery at end of life of device, lead frac-
x-ray, both anterior posterior and lateral [4]. If ture, insulation breach, fibrosis where the lead is
there is an abrupt rise or fall in the impedance on implanted, as well as metabolic derangements
the RV lead in patient with history of complete [7].
heart block or who is dependent on their device, Undersensing means there is a failure to sense
the patient may need to be hospitalized to man- the intrinsic activity. Pacing spikes will be seen
age this issue. Lead fractures can also manifest where they should not be present on telemetry or
themselves as loss of capture, oversensing, and an EKG. Commonly, pacemaker spikes may be
undersensing. seen within intrinsic QRS complexes. To correct
Loss of capture means that a pacemaker spike this, the fence or sensitivity needs to be lowered
can be seen on the monitor, but no depolarization so that the device appropriately senses chamber
of the heart occurs (Fig. 13.5). If you are evaluat- depolarization. The lead may need to be replaced
ing a patient with a temporary transvenous pace- if programming changes do not correct the
maker, the first step is to check all the connections. problem.

Fig. 13.5 Loss of capture in a dual chamber pacemaker secondary to end of life. There are no QRS waveforms seen
after any pacemaker spikes
138 J. A. Dietrich

Oversensing means there is inappropriate • RV apical pacing appears as LBBB on EKG,

detection of a signal that is not intrinsic activity. while biventricular pacing may have a more
There is a lack of pacing activity when there RBBB morphology.
should be spikes on telemetry or EKG. To correct • Magnet over a pacemaker asynchronously
this, the fence needs to be raised so that back- paces at a preprogrammed rate.
ground noise is not detected by the device as • Magnet over an ICD suspends any arrhythmia
chamber depolarization. In emergency settings, therapies but does not affect the pacing
the device sensitivity can be set to least sensitive function.
(highest mV level) or asynchronous, where pac- • Oversensing = underpacing; undersensing =
ing occurs at a fixed rate and sensing is disabled overpacing.
by utilizing the magnet. The lead may need to be
replaced if programming changings do not cor-
rect the problem.
One of the other issues encountered on a References
device interrogation maybe called lead noise.
This essentially means there is an issue interfer- 1. Weachter R. Leadless cardiac pacemaker therapy.
An overview for the hospitalist. Am J Hosp Med.
ing with the device’s ability to sense the intrinsic 2018;2(3):2018.016. https://doi.org/10.24150/
activity. This can be due to lead fracture or insu- ajhm/2018.016.
lation breach, oversensing, interactions between 2. Kenny T. The nuts and bolts of cardiac pacing. Wiley-
leads, or electromagnetic interference from exter- Blackwell; 2005.
3. Wang P. Pacemakers. 2022. American College of
nal source. If the noise is on a RV lead in an ICD, Cardiology Self-Assessment Program. www.acc.org.
there would be concern that the device could pro- 4. Kusumoto F, Schoenfeld M, Barrett C, Edgerton J,
vide inappropriate shocks to the patient as it Ellenbogen K, Gold M, Goldschlager N, Hamilton R,
thinks the noise is VF. There are some algorithms Joglar J, Kim R, Lee R, Marine J, McLeod C, Oken
K, Patton K, Pellegrini C, Selzman K, Thompson
on ICDs which can differentiate lead noise from A, Varosy P. 2018 ACC/AHA/HRS guideline on the
VT/VF and withhold detection if there is lead evaluation and management of patients with bradycar-
noise noted on the RV lead. dia and cardiac conduction delay. J Am Coll Cardiol.
There may be times when the defibrillator 2019;74(7):e51–e156. https://doi.org/10.1016/j.
jacc.2018.10.044.
function of an ICD should be turned off urgently 5. Chen J. Implantable cardioverter-defibrillator. 2022.
or a programmer is not available. This could American College of Cardiology Self-Assessment
occur if a patient is having recurrent inappropri- Program. www.acc.org.
ate shocks or if a patient is at end of life. Placing 6. Al-Khatib S, Stevenson W, Ackerman M, Bryant W,
Callans D, Curtis A, Deal B, Dickfield T, Field M,
a magnet overtop of the ICD will suspend any Fonarow G, Gillis A, Granger C, Hammill S, Hlatky
arrhythmia therapies but will not interfere with M, Joglar J, Kay G, Matlock D, Myerburg R, Page
the pacing programing of a defibrillator if it is R. 2017 AHA/ACC/HRS guideline for management
needed [5]. of patient with ventricular arrhythmias and the pre-
vention of sudden cardiac death. J Am Coll Cardiol.
2018;72(14):e91–e220. https://doi.org/10.1016/j.
Clinical Pearls jacc.2017.10.054.
• CRT has leads in right and left ventricle to 7. Sabbagh E, Abdelfattah T, Karim M, Farah A, Grubb
resynchronize the “squeeze”. B, Karim S. Causes of failure to capture in pacemak-
ers and implantable cardioverter-defibrillators. J Innov
• CRT should have a high percentage of biven- Card Rhythm Manag. 2020;11(2):4013–7.
tricular pacing to get maximal benefit.
Cardioversion
14
Lora Raines

Cardioversion refers to the restoration of sinus some cases, a CT scan may be performed to rule
rhythm, either by electrical cardioversion out LAA thrombus.
(DCCV) or pharmacologic cardioversion. Direct
current cardioversion is performed by delivering
an electrical shock that is synchronized with the Pharmacologic Cardioversion
QRS to avoid inducing ventricular fibrillation.
Pharmacologic cardioversion is performed by Certain antiarrhythmics may be used to try to
administering an antiarrhythmic agent for the convert a patient to sinus rhythm. Some of the
purpose of restoring sinus rhythm. Patients most common drugs used are high dose flecainide
should be adequately anticoagulated prior to pro- or propafenone and ibutilide [1, 2]. Pharmacologic
ceeding with either electric or pharmacologic cardioversion should be performed in the hospital
cardioversion and should continue oral anticoag- during continuous telemetry monitoring [1].
ulation (OAC) for at least 4 weeks post cardiover- For patients receiving Ibutilide, the major risk
sion [1]. is QT prolongation and development of polymor-
phic VT. ECG monitoring should be continuous
and should be continued for ≥4 hours after
Electrical Cardioversion administration [2].
An oral dose of flecainide or propafenone can
For patients undergoing electrical cardioversion, be used to try to restore sinus rhythm. Because
electrodes are placed in an anteroposterior loca- conversion to sinus rhythm may be associated
tion. The patient is then sedated, and once they with bradycardia due to sinus node or AV node
are no longer conscious, a synchronized electri- dysfunction, the initial conversion trial should be
cal shock is delivered in an attempt to restore nor- performed in a monitored setting with continuous
mal sinus rhythm. The primary risk associated ECG/telemetry [1, 2].
with a cardioversion is stroke. Depending on
whether or not a patient has been adequately anti-
coagulated, a TEE may be performed just prior to Recommendation for Prevention
the cardioversion to rule out a LAA thrombus. In of Thromboembolism [3]

• For patients with AF or Aflutter of 48 hours

L. Raines (*) duration or longer (or if duration unknown),
Wellstar Health System, Marietta, GA, USA anticoagulation with warfarin (INR 2–3), a
e-mail: [email protected]

© The Author(s), under exclusive license to Springer Nature Switzerland AG 2023 139
R. Musialowski, K. Allshouse (eds.), Cardiovascular Manual for the Advanced Practice Provider,
https://doi.org/10.1007/978-3-031-35819-7_14
140 L. Raines

factor Xa inhibitor, or a direct thrombin inhib- anticoagulation therapy may be considered

itor is recommended for at least 3 weeks before DCCV, without need for post-
before and at least 4 weeks after cardiover- cardioversion anticoagulation.
sion, regardless of CHA2DS2VASc score or
method (electrical or pharmacologic) (Class
I). Clinical Pearls
• For patients with AF or Aflutter of more than • Patients can be converted with electricity or
48 hours duration (or unknown duration) that medications.
requires immediate cardioversion due to • If a patient is in an atrial arrhythmia > 48
hemodynamic instability, anticoagulation hours, they should have an atrial thrombus
should be started as soon as possible and con- ruled out prior to elective cardioversion of any
tinued for at least 4 weeks after DCCV unless kind.
contraindicated (Class I). • Any patient post cardioversion should be anti-
• After DCCV for AF of any duration, decision coagulated for at least 4 weeks after
on long-term OAC should be based on risk of conversion.
both thromboembolism and bleeding (Class • CHA2DS2VASc score is used to evaluate
I). patient’s stroke risk.
• If AF/Aflutter duration less than 48 hours with
CHA2DS2VASc ≥ 2 in men and ≥ 3 in women,
administration of heparin, factor Xa inhibitor,
or direct thrombin inhibitor is reasonable as
References
soon as possible before cardioversion, fol-
lowed by long-term therapy (Class IIa). 1. January CT, Wann LS, Alpert JS, Calkins H, Cigarroa
• For patients with AF/AFL duration 48 hours JE, Cleveland JC Jr, Conti JB, Ellinor PT, Ezekowitz
or longer (or unknown) who have not been MD, Field ME, Murray KT, Sacco RL, Stevenson
WG, Tchou PJ, Tracy CM, Yancy CW, American
anticoagulated for the preceding 3 weeks, it is
College of Cardiology/American Heart Association
reasonable to perform a TEE before cardio- Task Force on Practice Guidelines. 2014 AHA/ACC/
version and proceed with cardioversion if no HRS guideline for the management of patients with
LA/LAA thrombus is identified, provided that atrial fibrillation. J Am Coll Cardiol. 2014;64(21):e1.
2. Baltazar RF. Basic and bedside electrocardiography.
anticoagulation is started before the TEE and
Philadelphia: Wolters Kluwer; 2009.
maintained for at least 4 weeks after cardio- 3. January CT, Wann LS, Calkins H, Chen LY, Cigarroa
version (Class IIa). JE, Cleveland JC Jr, Ellinor PT, Ezekowitz MD, Field
• In patients with AF/AFL of less than 48 hours ME, Furie KL, Heidenreich PA, Murray KT, Shea JB,
Tracy CM, Yancy CW. 2019 AHA/ACC/HRS focused
duration with CHA2DS2VASc = 0 in men and
update of the 2014 AHA/ACC/HRS guideline for the
1 in women, initiation of IV heparin, factor Xa management of patients with atrial fibrillation. J Am
inhibitor, or direct thrombin inhibitor vs no Coll Cardiol. 2019;74(1):104–32.
Cardiac Syncope
15
Krista Allshouse and Richard Musialowski

Table 15.1 Cardiac causes of syncope

Introduction and Pathophysiology
Electrical Structural
VT/Torsades HCM
Cardiovascular syncope is described as a sudden VF AS
loss of consciousness with loss of postural tone. Bradycardia: SSS-sinus arrest, MS
This clinical presentation may be caused by conversion pause, marked sinus brady Atrial
Heart block myxoma
tachycardia, bradycardia, and hypotension.
Tachycardia: SVT, WPW with atrial fib Tamponade
Syncopal events are common, occurring 3% in Inherited channelopathy-LQTS, Pulmonary
men and 3.5% in women over a lifetime accord- Brugada, CPVT HTN
ing to the Cleveland Clinic [1]. These events PE
become more common as individuals age. There Adapted from chart Recognizing Life-Threatening Causes
are many causes, some of which are more con- of Syncope. Cardiology Clinics. Vol. 31, Issue 1, P51–66.
Feb. 1, 2013
cerning. Cardiac syncope is the most concerning
etiology as it carries a 1-year mortality rate of
20–40%. The high risk of patient mortality occurs Symptoms
within 1–6 months after an event especially in
patients with structural heart disease. Thorough Cardiac syncope often occurs suddenly, without
evaluation for the underlying cause of a syncopal preceding symptoms. It is often associated with
event is essential for risk stratification and prog- true loss of consciousness, and the patient often
nosis. Cardiac etiologies may be divided into incurs traumatic injury from the loss of postural
electrical and obstructive. Electrical causes tone. Some patients may experience chest pain,
include bradycardic or tachycardic arrhythmias. shortness of breath, palpitations, or dizziness
Obstructive causes include HCM, valvular dis- before a syncopal episode. Syncope often has
ease, tamponade, and pulmonary embolus (PE) prodromal symptoms including sweating, nau-
(see Table 15.1). sea, or near loss of consciousness. Symptoms
prior to the event are important to ascertain, as
cardioinhibitory syncope allows the patient to sit
K. Allshouse (*)
Atrium Health, Levine Childrens’ Congenital Heart or lay down before they lose consciousness (see
Center, Charlotte, NC, USA cardioinhibitory below). The presence of these
e-mail: [email protected] prodromal symptoms often suggests an etiology
R. Musialowski other than high risk cardiac syncope.
Sanger Heart and Vascular Institute, Atrium Health, Most acute syncope evaluations are completed
Charlotte, NC, USA on an inpatient basis if the patient has underlying
e-mail: [email protected]

© The Author(s), under exclusive license to Springer Nature Switzerland AG 2023 141
R. Musialowski, K. Allshouse (eds.), Cardiovascular Manual for the Advanced Practice Provider,
https://doi.org/10.1007/978-3-031-35819-7_15
142 K. Allshouse and R. Musialowski

cardiac disease or if the event appears to be high dysfunction or hypertrophic cardiomyopathy

risk (i.e., resulting in injury). The etiology of (HCM). Vital signs including BP and HR may
more than half of syncopal events may be dis- show abnormalities, including orthostatic
cerned from the history alone. Detailed history- changes. Abnormal extra heart sounds (S3, S4) or
taking is critical to guide additional testing. It is displaced impulses may be noted.
imperative to be aware of “red flags” indicating
more concerning symptoms including syncope
related to exercise (either during or after), syn- Diagnostics
cope without preceding symptoms or with resul-
tant significant injury. Traumatic facial injuries EKG is the first test that should be performed
are highly suggestive of cardiac syncope. Seizure- with syncope. This may show evidence of isch-
like activity and loss of bowl or bladder control emia, abnormalities in conduction, including
are also concerning but less common with car- signs of block, arrhythmia, or QT interval
diac syncope. These symptoms more commonly prolongation.
lead to a diagnosis of seizure disorder. Seizures Transthoracic echocardiography should be
may occur in severe syncope of any etiology due completed to assess for structural disease if any
to hypoperfusion of the brain. abnormalities are found on physical exam.
It is critical to obtain a specific, detailed his- Echocardiography can assess for valvular abnor-
tory regarding the syncopal episode. The events malities, HCM, abnormal coronary origins in
preceding the syncopal event should be discussed. young adults, and evaluate for decreased LV
This includes symptoms, relation to activity, how function. Risk of death with low EF and syncope
the patient looked to others, any resultant injury, is high (see Ventricular Tachycardia, VT). If the
and how quickly the patient recovered. The etiology of syncope appears to be non-cardiac by
patient’s last conscious recollection before the history, echocardiography is not required.
event and the first memory afterward is very Other tests may be done based upon the find-
important to determining the diagnosis. Ask about ings of the initial workup. If no structural disease
any similar symptoms in the past. is found, a patient can have ambulatory monitor-
The patient’s medical history should be ing such as event or looping monitors.
reviewed including medical problems, daily Subcutaneous loop recorders may be implanted
medications, over the counter meds/supplements, for suspicious or recurrent events.
and any new medications recently started. Syncope can occur in a patient with a previ-
Exercise habits and tolerance should be ascer- ously implanted pacemaker. Interrogation of the
tained. Social history is important regarding device is important to determine the potential
smoking, vaping, or use of illicit or synthetic cause including device malfunction and exact
drugs. Family history should be obtained includ- rhythm during the syncopal event. Think of an
ing any history of sudden cardiac death (SCD) implanted pacemaker as a continuous monitor of
before age 50, unexplained motor vehicle acci- the cardiac rhythm. Representatives of the device
dents, SIDS deaths or drownings, ICDs/PPMs, manufacturers are always available for
and seizure disorders. assistance.
Stress testing may be done to rule out exercise-
induced arrhythmias and ischemia if the event
Physical Exam occurred with activity. If underlying coronary
artery disease or congestive heart failure is sus-
A full cardiovascular exam is warranted to evalu- pected, a cardiac catheterization may be war-
ate potential causes of syncope. Patients with a ranted. An electrophysiology study may be
cardiac etiology of syncope may have structural needed to test the patient’s conduction system
findings such as a systolic murmur of valvular and evaluate for ventricular arrhythmias.
15 Cardiac Syncope 143

Management POTS, is a subset of this condition where the

heart rate increases 30 beats per minute within 10
If patient has structural disease, management minutes of upright posture during a TILT table
will be guided by specific disease type. Referral test without the blood pressure drop of ortho-
to a cardiac specialist should be considered. A static hypotension. TILT table testing has limited
patient with significant HCM and syncope will utility and should be considered only if the his-
likely need medical treatment and potential tory of POTS is unclear.
ICD. Syncope with a reduced EF and structural Management of this constellation of symp-
heart disease must be treated as potential VT and toms consists of intense oral hydration, salt sup-
EP evaluation and ICD should be considered. If plementation, lower extremity exercises (the
a valvular or coronary anomaly is found, surgery Dallas protocol), and compression sleeves for the
may be the treatment recommendation. If the calves. Some patient symptoms improve with
patient has ischemia on EKG or stress testing, medications such as fludrocortisone, a mineralo-
cardiac catheterization may be needed for evalu- corticoid or midodrine, a vasoconstrictor (alpha
ation and ultimate treatment. Symptomatic bra- adrenergic agonist). Some patients may also have
dycardia is a common cause of sudden, improvement with taking selective serotonin
unprovoked syncope. If the EKG shows conduc- reuptake inhibitors, regulating their menstrual
tion abnormalities, pacemaker implantation may cycle (OCPs), and other therapies. Many centers
be needed (see bradycardia). If the EKG shows now have multidisciplinary Dysautonomia
QT segment abnormalities suggestive of a chan- Clinics for difficult cases. Difficult to manage
nelopathy, further testing may be needed (see patients may have concomitant collagen vascular
Chap. 11). There are other unusual etiologies disease or significant spinal injury.
that may require specialized management includ- Patients with high risk and unexplained syn-
ing pulmonary hypertension, cardiac tampon- copal events may not be allowed to drive for
ade, and PE. 6 months (state dependent) following the event
Another common type of syncope is neurocar- unless underlying cause is corrected.
diogenic. This is an umbrella term describing
various types of syncope including reflex syn- Clinical Pearls
cope, vasodepressor syncope, postural syncope,
and autonomic dysfunction. This may be • Facial or other severe trauma after syncope is
described as the “common faint” and occurs in a suggestive of a cardiac cause.
patient with a normal heart. Prodromal symp- • Syncope with structural heart disease or car-
toms occur more slowly with preceding symp- diomyopathy is high risk and ventricular
toms of lightheadedness, blurry/blackened tachycardia must be considered.
vision, muffled hearing, sweating, and nausea. • Prodromal symptoms often suggest a non-
Patients tend to be pale, bradycardic, and sweaty cardiac cause of syncope.
immediately prior to and after an episode. • The clinical history is important to determine
Recovery of mentation is usually quick when the etiology of syncope.
supine. The mechanism is not well understood
but is thought to involve dysfunction of the auto-
nomic nervous system, orthostatic intolerance,
and intravascular volume depletion. Further Reading
Patients may complain of dizziness while
upright, tingling of the ears, nose, fingers, nau- 1. Dick M. Clinical cardiac electrophysiology in the
young. 2nd ed. New York: Springer; 2006/2015.
sea, headaches, fatigue, atypical sharp stabbing 2. Eagle KA, Balinga RR. Practical cardiology.
chest pain, and palpitations. It can be worse in the Evaluation and treatment of common cardiovascular
heat, during menses or with febrile illness. disorders. Philadelphia, PA: Lippincott, Williams and
Postural Orthostatic Tachycardia Syndrome, Wilkins; 2013.
Part IV
Structural/Valvular Heart Disease

Anne Booke Michael Rinaldi

Elisabeth A. Powell Larry Watts
Rick Musialowski

Introduction

The heart valves have very important and specific functions which will be
further discussed in this chapter. These valves are instrumental in creating
cardiac output as described in Chap. 2. The bedside description of the cardiac
cycle is defined by the opening and closing of the valves during ventricular
systole and diastole. The heart sounds (S1 and S2) heard during physical
examination are the closure of the atrioventricular and semilunar valves,
respectively. This synchronized series of valve open and closure allows
proper movement of blood oxygenating the tissues with each cardiac
contraction.
Pathologic changes of the valves result in very specific disease states with
corresponding physical examination findings. These pathologies may be
described as stenotic or regurgitant. As the leaflets degenerate due to age and
other etiologies, the structure of the leaflets and/or supportive apparatus will
change. Depending on the valve and underlying etiology of the changes, the
leaflets will develop reduced mobility (stenosis) and restrict the forward
movement of blood. The leaflets may become incompetent and allow blood
to reverse course back to the cardiac chamber just exited (regurgitant). Often,
there is a combination of both pathologies.

A. Booke · M. Rinaldi
Interventional and Structural Heart Cardiology, Atrium Health/Sanger Heart and
Vascular Institute, Charlotte, NC, USA
e-mail: [email protected]
L. Watts · R. Musialowski
Atrium Health/Sanger Heart and Vascular Institute, Charlotte, NC, USA
e-mail: [email protected]; [email protected];
[email protected]
E. A. Powell
Banner University Medical Center, Tucson, AZ, USA
e-mail: [email protected]
146 Structural/Valvular Heart Disease

These different disease states cause a diverse spectrum of symptoms and

physical findings. Stenotic pathology of the aortic and pulmonic valves
produces a crescendo/decrescendo murmur due to rapidly changing pressure
and volume of blood flow during ventricular systole. This murmur will radi-
ate according to the path of blood flow after passing over the stenotic valve
leaflets. Incompetence of mitral and tricuspid valves results in a holosystolic
blowing murmur as blood flows back into the atria at a fixed pressure and
volume. Radiation of these murmurs also follows the direction of the turbu-
lent blood flow. These systolic murmurs are noted between S1 and S2.
Incompetence of the aortic and pulmonic valves produces diastolic murmurs
as the high pressure of the great vessels pushes blood back in the ventricles
during ventricular diastole. These sounds occur after the second heart sound
(S2) and are decrescendo in nature due to a runoff of great vessel pressure.
Diastolic sounds of the mitral and tricuspid valves are rare and difficult to
auscultate.
The management of valve disease is dependent on the valve and specific
pathology. This chapter will review the cardiac valves with relevant examples
of regurgitant and stenotic physiology. This is a rapidly advancing field with
changes in management of valvular heart disease ever evolving. Surgical
intervention with replacement and repair has an important role. Catheter
based interventions are rapidly developing with less associated morbidity and
mortality. Collaborative patient management using structural heart teams,
advanced cardiovascular imaging, and therapeutic discussions are critical for
best practice management.

General Information About Valve Disease

In evaluating patients with known or suspected valvular disease, transthoracic

echocardiography (TTE) is the primary test for assessment of the valve anat-
omy, etiology, concurrent valve disease, ventricular function, and associated
abnormalities such as aortic dilatation. For stenotic valves, key measurements
include the maximum velocity, mean gradient, and valve area. For regurgitant
valves, key measurements include the regurgitant orifice area, regurgitant
volume, and regurgitant fraction as determined by Doppler readings.
Assessment of pulmonary systolic pressures along with RV size and function
is also important. When indicated, additional testing is obtained, including
but not limited to chest X-ray, stress testing, transesophageal echocardiogra-
phy TEE, CT heart, cardiac MRI, and cardiac catheterization for measure-
ment of hemodynamics.
The American College of Cardiology (ACC) and American Heart
Association (AHA) Indications for surveillance echocardiogram vary depend-
ing on stage of valvular disease and patient symptomatology. At a minimum,
patients should be seen for yearly examination. Additionally, patients should
report changes in their symptoms and a physical exam should be performed
at each visit with echo performed if there are changes in exam. The purpose
of follow-up is to prevent consequences of valvular heart disease, including
alterations of ventricular function and pulmonary circulation, and to deter-
mine when referral is indicated for consideration of intervention (Fig. 1).
Structural/Valvular Heart Disease

Stage Aortic Stenosis Aortic Regurgitation Mitral Stenosis Mitral Regurgitation

Progressive Every 3-5 y Every 3-5 y Every 3-5 y Every 1-2 y

(Stage B) (mild severity; Vmax 2.0-2.9 m/s) (mild severity) (MV area >1.5 cm2) (moderate severity)

Every 1-2 y Every 1-2 y Every 3-5 y

(moderate severity; Vmax 3.0-3.9 m/s) (moderate severity) (mild severity)

Severe asymptomatic Every 6-12 mo Every 6-12 mo Every 1-2 y Every 6-12 mo
(Stage C1) (Vmax >4 m/s) Dilating LV: more frequently (MV area 1.0-1.5 cm2) Dilating LV: more frequently

Every year
(MV area <1.0 cm2)

Adapted from (6)

Fig. 1 Type of valve lesion. (Adapted from Otto CM, Nishimura RA, Bonow RO, Carabello BA, Erwin JP III, Gentile F. 2020 ACC/AHA Guideline for the management of
patients with valvular heart disease: a report of the American College of Cardiology/American Heart Association Joint Committee on clinical practice guidelines. J Am Coll
Cardiol. 2021;77(4):e25–e197)
147
Aortic Valve Disease
16
Anne Booke, Michael Rinaldi, Elisabeth A. Powell,
Larry Watts, and Richard Musialowski

Bicuspid Aortic Valve (BAV)

BAV is the most common congenital cardiac

anomaly (see Chap. 29), affecting 0.5–2.0% of
adults, with males more commonly than females
at about 3:1 predominance (Fig. 16.1) [1, 2]. The
pathology can occur as an incomplete separation
of the cusps during fetal development or when
only two leaflets develop as seen in Fig. 16.2.
Patients with BAV are at risk for developing iso-
lated AI, AS, a combination of AS and AI, along
with infective endocarditis. 20–40% of patients
with BAV develop an aortopathy involving the
aortic root, ascending aorta, or less frequently
aortic coarctation [1]. Aortopathy may also occur
independently of valvular disease and consists of
dilation of aortic sinuses, ascending aorta, or aor- Fig. 16.1 CT Image of normal aortic cusps and origin of
tic arch placing these patients at increased risk for coronary arteries. The circular structure at the white arrow
aortic dissection. The prevalence of BAV in first is the Left Main coronary artery arising above the left
degree relatives is 20–30% [1]. A specific genetic coronary cusp (LCC). The RCA origin arises above the
right cusp but is in a different plane and not seen in this
cause has not been identified and it is reasonable image
to screen first degree relatives with TTE to look

A. Booke (*) · M. Rinaldi · L. Watts for the presence of BAV or asymptomatic dilation
R. Musialowski of ascending aortic and aortic sinuses.
Sanger Heart and Vascular Institute, Atrium Health, TTE is indicated in patients with BAV to eval-
Charlotte, NC, USA
e-mail: [email protected]; uate valve morphology, severity of AS and AI,
[email protected]; the Sinuses of Valsalva, the sinotubular junction
[email protected]; (STJ), and the ascending aorta. When morphol-
[email protected] ogy cannot be fully assessed by TTE, Cardiac CT
E. A. Powell or CMR angiography is indicated for better
Banner University Medical Center, Tucson, AZ, USA assessment. Annual aortic imaging is recom-
e-mail: [email protected]

© The Author(s), under exclusive license to Springer Nature Switzerland AG 2023 149
R. Musialowski, K. Allshouse (eds.), Cardiovascular Manual for the Advanced Practice Provider,
https://doi.org/10.1007/978-3-031-35819-7_16
150 A. Booke et al.

(3) rheumatic heart disease affecting the aortic

valve [1, 2]. Mediastinal radiation has also been
associated with scarring, fibrosis, and calcifica-
tion of aortic leaflets [2].

• Degeneration occurs due to vascular atheroscle-

rosis, endothelial dysfunction, lipid accumula-
tion, inflammatory cell activation, and cytokine
release with eventual deposition of calcium
hydroxyapatite [3]. Patients typically develop
symptoms in the 6th- 8th decades of life.
• Patients with BAV typically have larger aortas
and are at increased risk for associated aor-
topathy and usually will develop symptoms
one decade before patients with tricuspid aor-
tic valve.
Fig. 16.2 Two closed aortic coronary cusps (right and • Rheumatic changes result in commissural
left) seen with regurgitation (blue jet) during diastole. fusion, sometimes resulting in a bicuspid-
EKG at the bottom of the image shows the blue circle appearing valve. Rheumatic heart disease is
before the QRS and confirms ventricular diastole and a
much less common in developed countries.
closed aortic valve. The closure is eccentric when com-
pared to a trileaflet valve Rheumatic AS is almost always associated
with involvement of the mitral valve (mitral
stenosis) and aortic insufficiency [1, 2].
mended in patients with BAV and significant aor- • Currently, there is no medical therapy that
tic dilation (>4.0 cm). remarkably slows or reverses the aging pro-
The timing and type of surgical intervention in cess of the aortic valve.
aortic valve replacement are dependent on anat-
omy, patient characteristics, and institutional As the aortic valve narrows, the left ventricle
expertise (see Fig. 6 from the 2020 AHA/ACC (LV) must overcome the impedance to blood
Valve Guidelines) [1]. (See further discussion in flow, resulting in increased LV systolic and dia-
surgical AS section). stolic pressures with concentric hypertrophy.
The timing and type of intervention for Over time this reduces ventricular compliance
patients with BAV with AS or AI are like those resulting in increasing LV end diastolic pressures
for trileaflet valves, although most interventions (LVEDP), or preload, and subsequent remodel-
commonly occur about a decade before those ing of the left atrium. Due to increasing afterload
patients with trileaflet valves. the LV contractile function declines over time.
The cardiac output along with the LV aortic pres-
sure gradient decline, and there is a rise in the
Aortic Stenosis (AS) mean left atrial pressure, pulmonary artery pres-
sures, and right ventricular pressures [2]. In
Etiology/Pathophysiology of Aortic advanced stages of AS, patients may develop
Stenosis severe pulmonary hypertension resulting in RV
dysfunction, secondary tricuspid regurgitation,
The three main causes of aortic stenosis are (1) and pulmonary venous hypertension [2].
degeneration of the trileaflet valve, (2) calcifica- Aortic stenosis is a progressive disease. The
tion of a congenital bicuspid aortic valve (BAV), average rate of progression per year in Moderate
16 Aortic Valve Disease 151

AS (peak aortic velocity 3–3.9 m/s on echocar- Symptoms

diography) is an increase in velocity of 0.3 m/s,
increase in mean pressure gradient by 7 mmHg, AS is an insidious disease with a long latency
and decrease in AVA by 0.1 cm [4]. Severe AS period with the most common reported symptom
(aortic velocity >/=4.0 m/s), rapidly progresses to being dyspnea or decreased exercise tolerance.
symptoms with an event-free survival rate of The classic triad of severe AS includes conges-
30–50% at 2 years [1]. See Table 16.1 for stages tive heart failure (CHF), syncope, and angina.
of progressive aortic valve disease. The progression of symptoms and severity of
Patients with severe AS may have concomi- aortic valve disease is associated with a high rate
tant degrees of MR that may improve with of death (~ 50% in the first 2 years after symp-
replacement of the aortic valve. In patients with toms appear) [1, 6].
concomitant rheumatic AS and MS, the decreased Dyspnea results from narrowing of the aortic
cardiac output induced by the MS lowers the valve orifice along with elevated pulmonary pres-
pressure gradient across the aortic valve, mask- sures due to elevated LV diastolic pressures
ing the severity of the AS [2]. (LVEDP) in the setting of impaired relaxation
Cardiac Amyloidosis is also frequently and reduced LV compliance [2].
associated with AS in elderly patients with a Angina occurs given the imbalance between
9–15% incidence [1]. As amyloid will persist oxygen supply and demand. Exertional syncope
post valve intervention, it is associated with occurs because the LV cannot increase stroke
poor long-term prognosis for the patient volume (SV), and thus cardiac output (CO) dur-
despite valvular intervention. When cardiac ing exercise given the narrowed aortic orifice in
amyloidosis is clinically suspected, amyloid combination with vasodilation of peripheral mus-
labs and CMR should be considered prior to cle beds with exercise (decreased systemic vas-
valvular intervention [1]. cular resistance, or SVR).

Table 16.1 Stages of aortic stenosis

Stage Definition Symptoms Valve anatomy Valve hemodynamics
A At risk of AS None BAV (or other congenital valve Aortic Vmax <2 m/s with
anomaly) normal leaflet motion
Aortic valve sclerosis
B Progressive AS None Mild to moderate leaflet Mild AS: Aortic Vmax
calcification/fibrosis of a bicuspid 2.0–2.9 m/s or mean ΔP
or trileaflet valve with some <20 mm Hg
reduction in systole motion
[or] Moderate AS: Aortic Vmax
3.0–3.9 m/s or mean ΔP
20–39 mm Hg
Rheumatic valve changes with
commissural fusion
C: Asymptomatic severe AS
C1 Asymptomatic None Severe leaflet calcification/fibrosis Aortic Vmax ≥ 4 m/s or mean
severe AS or congenital stenosis with severely ΔP ≥ 40 mm Hg
reduced leaflet opening
Exercise testing is AVA typically is ≤1.0 cm2 (or
reasonable to AVAi 0.6 cm2/m2) but not
confirm symptom required to define severe AS
status
Very severe AS is an aortic
Vmax ≥ 5 m/s or mean
ΔP ≥ 60 mm Hg
Adapted from [5]
152 A. Booke et al.

Patients may also exhibit symptoms of vol- afterload which may result in falsely low aortic
ume overload such as orthopnea, lower extremity valve gradients [1].
edema, or paroxysmal nocturnal dyspnea. Dobutamine Stress Echo (DSE). May be used
to evaluate the asymptomatic patient or those with
low flow, low gradient (LFLG) AS (see below).
Physical Exam/Cardiac Studies This is a class 2a indication in asymptomatic
patients to assess for angina, dizziness, or abnor-
The AS murmur is a mid to late peaking systolic mal BP response [1]. DSE increases the CO and
murmur, commonly low-pitched and rough, helps determine if the AVA is truly less than
heard at the second right intercostal space/the severe. If the gradients and AVA worsen in sever-
base of the heart. The AS murmur often radiates ity with the increased flow from dobutamine, the
to the carotid arteries and to the apex of the heart stenosis is severe. DSE should be avoided in
where it may be confused with the MR murmur, symptomatic patients given high risk of complica-
and this is known as the Gallavardin effect [2]. tions including syncope, VT/VF, and death.
The intensity of the murmur does not directly Asymptomatic patients with symptoms provoked
correlate with the severity of stenosis. The mur- by DSE should be considered symptomatic.
mur may even become softer with increasing CT imaging. CT is used to further evaluate the
severity. The absence of the second heart sound degree of aortic calcification, valve area, aortic
suggests critical stenosis. annulus, and concomitant cardiac disease. Aortic
ECG. There is no close correlation between valve calcification is a strong predictor of clinical
AS and ECG findings, although LVH is often outcomes and Agatston units are a measurement
present. of calcification. Per 2020 ACC/AHA guidelines,
Labs: There are no labs that correlate with the sex-specific Agatston unit thresholds for
AS, but an elevated serum BNP may be a severe AS are 1300 in women and 2000 in men
marker of subclinical HF and LV (Fig. 16.4) [1]. The ESC guidelines further break
decompensation. it down as men >3000 Agaston units and women
Echocardiogram. TTE assesses thickening >1600 have a high likelihood, men >2000 and
and calcification of aortic valve leaflets, along women >1200 are likely, and men <1600 and
with mean aortic gradient, calculated valve area, women <800 are unlikely [5].
LV/RV function, concomitant valve disease, Cardiac Catheterization. Cardiac catheteriza-
visualization of proximal aorta, and estimation of tion is used for further hemodynamic assessment
pulmonary pressures (Table 16.2 and Fig. 16.3). of the aortic valve. Those that are undergoing
The improvement in echocardiographic technol- evaluation for aortic valve intervention often
ogy and its ability to accurately define valve require cardiac catheterization to assess the
dynamics help determine the timing of interven- degree of coronary artery disease prior to treat-
tion. Patients with poorly controlled hyperten- ment of AS. With improvement in imaging tech-
sion (high SVR) should be optimized prior to nology, direct hemodynamic assessments with
undergoing echo to avoid flow effects of increased catheterization are less common.

Table 16.2 Echocardiographic parameters assessing Evaluation/Management

aortic stenosis severity
Normal Mild Moderate Severe As clinicians it is important to assess patient
Mean gradient ~5 ≤20 20–39 ≥40
(mmHg)
symptomatology. When reported symptoms
Calculated valve 2.5–4.5 >1.5 1.0–1.5 ≤1.0 worsen or murmur intensity on exam changes,
area (cm2) repeat TTE is indicated. TTE monitors the degree
Peak Vmax (m/s) 2.0– 3.0–3.0 ≥4.0 of severity and concomitant valve disease along
2.9 with ventricular remodeling. Routine surveil-
16 Aortic Valve Disease 153

Fig. 16.3 Doppler of severe Aortic Stenosis. Mean gradient 52 mmHg, Peak velocity max >4 cm/s and aortic valve
area (AVA) 0.62 cm2 suggestive of severe AS

Fig. 16.4 CT images of severe calcific aortic stenosis. Left image during ventricular diastole with closed trileaflet
valve. Right image shows reduced opening and a severely reduced area of <1 cm2

lance every 6–12 months is indicated in patients and hemodynamic states. Examples include but
with AS to time intervention on the valve. are not limited to anemia, GI bleed, surgery,
It is important to remember that degree and pregnancy, and acute illness.
severity of aortic stenosis by TTE and symptom- Low-flow-low-gradient (LFLG) AS is a diag-
atology may change in various clinical scenarios nostic and therapeutic challenge. This occurs in
154 A. Booke et al.

the setting of decreased systolic dysfunction or in Aldactone, beta-blockers, and biventricular pacing
the setting of significantly hypertrophied LV with as hemodynamics allow (see sect. 5). Clinicians
a small LV cavity despite a normal left ventricu- should avoid abruptly lowering blood pressure in
lar ejection fraction (LVEF) [2]. Patients with AS AS patients and use caution with the addition of
with low EF (<50%) may present with decreased betablockers in uncompensated patients [1].
aortic valve area, but low mean gradient or veloc- Caution with over-diuresis as the preload reduction
ity and may have low flow low gradient aortic will reduce stroke volume, especially if LV cavity
stenosis. Severe AS with LV systolic dysfunction is small [1]. Nitrates should also be used cautiously,
attributable to afterload mismatch must be distin- or avoided, in AS as they will cause vasodilatation
guished from primary myocardial dysfunction and decreased preload resulting in hypotension.
with only moderate AS.
Low flow is arbitrarily defined by a stroke vol-
ume index (SVi) ≤ 35 mL/m2 - a threshold that is Intervention
under current debate. The ESC defines four broad
categories of AS: Symptomatic AS has a dismal prognosis and early
intervention is recommended. Caveats to this are
1. High gradient AS (mean gradient ≥40 mmHg, those with severe comorbidities and unlikeliness
peak velocity ≥ 4.0 m/s, valve area ≤ 1 cm2). of improving quality of life, malignancy, or
Severe AS assumed irrespective of LV func- expected survival of <1 year. Once severe AS is
tion and flow conditions [7]. confirmed, or concern for severe AS is suspected,
2. Low-flow, low-gradient AS with reduced patients should be referred to a valve center for
LVEF (mean gradient <40 mmHg, valve evaluation for aortic valve replacement (AVR)
area ≤ 1 cm2, LVEF <50%, SVi ≤ 35 mL/m2). either surgically or by a transcatheter approach.
Low dose DSE is recommended to distinguish Eligibility for AVR depends on the presence of
between true severe and pseudo-severe aortic symptoms, the preservation of left ventricular
stenosis (increase in valve area to >1.0 cm2 ejection fraction (LVEF), and the degree of steno-
with increased flow) and identify patients sis. According to the 2020 ACC/AHA guidelines,
with no flow or contractile reserve [7]. recommendations for intervention are categorized
3. Low-flow, low-gradient AS with preserved into classes ranging from recommended to may/
LVEF (mean gradient <40 mmHg, valve might be reasonable. Recommendations are based
area ≤ 1 cm2, LVEF ≥50%, SVi ≤ 35 mL/m2). on surgical benefit to risk ratios [1]. The indica-
Typically encountered in hypertensive elderly tions for SAVR, as defined by the ACC/AHA
patients with small LV size and marked hyper- guidelines, are outlined in Table 16.3.
trophy. May also result from conditions asso- Without intervention, symptomatic AS has a
ciated with low stroke volume such as poor prognosis of 50% mortality within 2 years,
moderate/severe MR, severe TR, severe MS, reducing to less than 1 year with the development
large VSD, and severe RV dysfunction [7]. of symptomatic left heart failure [8]. Surgical
4. Normal-flow, low-gradient aortic stenosis with intervention is still recommended in asymptom-
preserved LVEF (mean gradient <40 mmHg, atic patients, but the prognosis is better with the
valve area ≤ 1 cm2, LVEF ≥50%, SVi >35 mL/ risk of sudden death less than 1% per year [8].
m2). These patients usually have only moder- Timing of intervention for asymptomatic patients
ate AS although in a symptomatic patient depends on physiological factors indicating heart
without other explanation for symptoms a low strain. Reduction of LVEF, elevated BNP >3x
index of suspicion should be maintained [7]. normal, and rapid progression of disease on TTE
are all indications.
Standard Guideline Directed Medical Therapy Current data is limited regarding progression
(GDMT) drug therapy for LV function should be of aortic dilation and risk of dissection after AVR
continued including diuretics, ACE-I/ARB/ARNI, in patients with a bicuspid aortic valve (BAV) [1].
16 Aortic Valve Disease 155

Table 16.3 Indications for surgical aortic valve replace- cal, and anatomic factors are considered for the
ment ( SAVR)
best therapeutic option (see below).
Class 1 (Recommended) As part of the decision between TAVR vs
Symptomatic Severe, high-grade AS (Vmax ≥ 4 m/s
SAVR, the multidisciplinary team will look at
AS or ΔP mean ≥ 40 mm Hg)
Severe Low-flow, Low-gradient AS
age (< 65 years), comorbidities, predicted life
with LVEF < 50% (Vmax < 4 m/s and expectancy, implantation risk, prosthesis durabil-
AVA ≤ 1.0 cm2 at rest and Vmax ≥ 4 ity, potential need for sequential procedures
m/s and AVA ≤ 1.0 cm2 at any flow (valve in valve vs redo operation) to determine
rate with dobutamine stress
echocardiogram
what is the best option for an AVR patient.
Severe low-gradient AS with LVEF > Lifetime management for valve disease is a criti-
50% and AS most common cause of cally important concept in younger patients
symptoms (AVA ≤ 0.6 cm2 and stroke undergoing AVR who will likely outlive the first
volume index < 35 mL/m2)
valve. TAVR valves appear harder to remove than
Asymptomatic Severe AS with LVEF < 50%
AS SAVR and may require full root replacement.
Severe AS when patient undergoing
another cardiac surgery (i.e. CABG)
Class 2a (Reasonable) Aortic Valve Pre-Intervention Testing
Asymptomatic Exercise treadmill test with ↓ BP or
AS exercise capacity
As discussed under surgical management for cor-
Vmax ≥ 5 m/s and low surgical risk
BNP > 3× normal and low surgical risk
onary artery disease (Chap. 6), surgical work-up
Rapid disease progression and low begins with establishing patient’s baseline condi-
surgical risk tion with a full history, physical, and diagnostic
Class 2b (may/might be reasonable) work up. Refer to Tables 6.1 and 6.2 in Chap. 6
Asymptomatic Severe AS with reduction of LVEF to for discussion on preoperative assessment.
AS <60% on 3 serial studies
Along with the standard preoperative testing,
Asymptomatic Moderate AS and patient undergoing
AS another cardiac surgery all patients undergoing cardiac surgery should
Adapted from [5]
have a cardiac catheterization to assess for coro-
nary artery disease. With the use of coronary CT,
certain patients may have coronary arteries
Current guidelines recommend aortic root and/or cleared by CT, thus avoiding cardiac catheteriza-
ascending aorta replacement at the time of SAVR tion. This is especially important in patients with
due to severe AS if the diameter is >4.5 cm [1]. AS since concurrent CAD is common [1]. If
Refer to section on BAV intervention and chapter obstructive coronary disease is present, CABG
on aortic aneurysms for further discussion and should be completed at the time of the SAVR or
guidelines. PCI should be considered prior to TAVR.
Evaluation for AVR includes assessment by a Cardiac CTA is essential to determine aortic
cardiac surgeon and interventional cardiologist valve anatomy, annular size and shape, extent and
and often includes advanced imagers, physician distribution of valve and vascular calcification,
assistants, nurse practitioners, and nurse naviga- risk of coronary ostial obstruction, aortic root
tors as part of the care team. The team will dimensions, optimal fluoroscopic projections for
evaluate the patient and review all clinical imag- valve deployment, and feasibility of vascular
ing to determine if the patient is best served by access for TAVR (femoral, subclavian, axillary,
surgical aortic valve replacement (SAVR) or carotid, transcaval, or transapical). While CTA
transcatheter aortic valve replacement (TAVR). may be able to ascertain patency of coronary
Risk assessment is a foundational element of pre- arteries, coronary angiography is generally rec-
procedural evaluation of patients with valvular ommended to establish severity of CAD.
heart disease (VHD). The Society of Thoracic While studies have shown that CABG at the
Surgeons (STS) score and other technical, clini- time of SAVR improves outcomes in patients with
156 A. Booke et al.

significant coronary obstruction, revasculariza- cal candidates over age 65. TAVR was first per-
tion prior to TAVR remains controversial and is formed in 2002 and has undergone several
the subject of an ongoing randomized trial. multicenter trials known as the Placement of
Generally, most operators will revascularize prox- Aortic Transcatheter Valves (PARTNER) Trials.
imal severe disease supplying significant myocar- Valve selection in TAVR is based on several
dial territory particularly if angina is a prominent measurements obtained from cardiac CT imag-
component of the patients’ symptoms. ing. Sizing of the valve is important to avoid aor-
When indicated, patients may also undergo tic rupture during valve deployment, valve
cardiac MRI, carotid ultrasound, pulmonary dislocation with embolization, or resultant peri-
function testing, and if they have other comor- valvular leak if the valve is undersized. Patient
bidities may be referred to other specialties or prosthetic mismatch (as determined by patient
undergo further testing prior to AVR. body surface area to valve size) is to be avoided
In patients undergoing valve surgery, it is because symptoms may not improve after the
imperative to take a dental health history and note valve intervention.
any prominent dental caries, abscesses, or poor TAVR is performed under mild sedative or
dental hygiene. If there are issues of concern, the general anesthesia (Fig. 16.5). Once sedated, vas-
patient should be evaluated and cleared by a den- cular arterial access is obtained, most commonly
tal professional preoperatively to decrease the femoral access but those with unfavorable femo-
risk of endocarditis after the placement of a pros- ral anatomy may require alternative access such
thetic valve. as subclavian, axillary, carotid, transcaval, or
Preoperative work up is both patient and sur- transapical. In the procedural lab, a clear view of
geon specific. Surgical and medical decision the aortic annulus is established on fluoroscopy,
making is multifactorial and should include a balloon aortic valvuloplasty is performed in select
multidisciplinary team. patients with aortic stenosis, and then the heart is
The STS risk calculator may be utilized to aid rapidly paced to produce ventricular standstill
in decision making and risk mitigation prior to while the bioprosthetic aortic valve is deployed.
SAVR. Further discussion on the STS risk calcu- Procedural risks include vascular complications,
lator can be reviewed in Chap. 6: Surgical man- electrical conduction disturbance, bleeding,
agement for coronary artery disease. For risk stroke, MI, renal dysfunction, and death.
categories covered with the STS calculator, refer
to Table 6.3 in that chapter. In general, the overall
operative mortality for an isolated SAVR in AVR Procedural Conduction
T
patients under 70 years old is considered low at Management
1–3%, with a slight rise to 4–8% in older popula-
tions [8]. Currently, the STS calculator does not All TAVR patients require rapid ventricular pac-
calculate the risk for aortic valve repair. ing during deployment in order to produce ven-
tricular standstill and accurate positioning of the
prosthesis. Patients at increased risk of requiring
Transcatheter Aortic Valve permanent pacemaker have preexisting LBBB,
Replacement (TAVR) RBBB, atrial fibrillation with innately slow ven-
tricular response, and those with short membra-
TAVR is a less invasive method for AVR than tra- nous septum lengths. This cohort of patients may
ditional surgery. It has been shown to improve receive a temporary pacing wire (often an active
survival, reduce HF hospitalization, reduce symp- fixation lead via the right internal jugular vein)
toms in nonsurgical candidates, and has been for at least 48 hours.
shown to be an alternative to surgery with lower For patients with new LBBB at discharge or
stroke, death, and major complications compared RBBB that was present pre-procedure that did
to surgery in both intermediate and low risk surgi- not progress to advanced heart block requiring
16 Aortic Valve Disease 157

Fig. 16.5 TAVR for

aortic stenosis

a b c

pacemaker implant during their hospital stay, a month, and 1 year following discharge with an
2-week monitor is typically placed at discharge ECG and TTE at 1 month and 1 year.
to monitor for progression of heart block. There are no guidelines for echocardiographic
follow up of TAVR patients, but many practices
advocate yearly TTE given the uncertainties
Post TAVR Valve Implant around durability and the higher rates of develop-
Management ment of hypo attenuated leaflet thickening
(HALT) and partial valve thrombosis (see bio-
Post procedure patients are placed on aspirin 81 mg prosthetic valve dysfunction section below).
indefinitely and Plavix 75 mg for 3 months; aspirin
monotherapy is used in patient with high bleeding
risk (HBR). Of note that regimen may change if urgical Management of Aortic
S
patients have an indication for systemic oral antico- Stenosis
agulation (OAC), recent coronary stenting with lon-
ger indication for dual antiplatelet therapy (DAPT), Aortic valve replacement (AVR) is the treatment
increased risk for bleeding, or other factors. of choice for AS and the most common reason for
If the patient has an indication for OAC, it is surgical intervention on the aortic valve [8].
recommended that OAC is continued for life with During surgical aortic valve replacement (SAVR),
optional addition of aspirin which can be with- the heart is placed on cardiopulmonary bypass,
held in patients with HBR. For patients undergo- the heart is arrested, and the patient’s native valve
ing surgical procedures requiring cessation of is removed. After debridement of any residual
antiplatelet and anticoagulation agents, it is safe calcification is complete, a prosthetic valve is
to briefly withhold all agents without the need for sewn in, ensuring not to block the left and right
bridging. Patients are typically seen at 1 week, 1 coronary ostium which sits right above the aortic
158 A. Booke et al.

valve. Replacement of the AV is recommended in ous complication to either the mother or the fetus
severe AS and considered reasonable in moderate during pregnancy in one-third of the women with
AS when patient is already undergoing cardiac mechanical valves [1].
surgery for another purpose, such as CABG. An implanted mechanical AV is demonstrated
in Fig. 16.6. Here the On-X™ valve, constructed
of pyrolytic carbon, is demonstrated. This patient
Valve Selection in SAVR will require lifelong anticoagulation with
Warfarin.
Given the stenotic and calcified nature of the If a patient does not want to take lifelong anti-
valve leaflets in aortic stenosis, repair of the leaf- coagulation, is not felt to be an appropriate candi-
lets is not justified. AVR with either a biopros- date for vitamin K antagonists (VKA), or is
thetic valve or mechanical valve is the standard elderly, then a bioprosthetic valve is an appropri-
of care. Refer to Fig. 11 in the 2020 AHA/ACC ate valve choice. These “tissue valves” are con-
Valve Guidelines for current prosthetic valve rec- structed from bovine or porcine conduit and have
ommendations [1]. decreased longevity and valve durability when
Valve selection is a serious, multi-faceted compared to the mechanical valve. Deterioration
decision made between surgeon and patient of the valve occurs sooner in younger vs older
which is continually evolving. Patient’s age, patients (> 65 years old). In general, the risk of
medical compliance, ability to tolerate lifelong valve deterioration requiring reoperation is 22%
anticoagulation, and patient’s individual desires in patients 50 years old, 30% in patients 40 years
must all be considered. The 2020 ACC/AHA old, and 50% in patients 20 years old [1].
Guidelines recommend mechanical valves in Although tissue valves do not require long-term
patients younger than 50 years old and biopros- anticoagulation, 3–6 months of VKA anticoagu-
thetic valves for patients greater than 65 years lation is reasonable if the patient is at low risk for
old. This requires consideration of the patient’s bleeding. This decreases stroke risk until the bio-
life expectancy and potential need for a reopera- prosthetic valve is endothelialized [1].
tion if the patient’s lifespan exceeds the longevity Replacement of a patient’s native aortic valve
of the selected valve. Mechanical valves are the with a bioprosthetic tissue valve is demonstrated
valve of choice in younger patients (<50 years in Fig. 16.7 and post-operative CT imaging is
old), as they are extremely durable and will not seen in Fig. 16.8.
degenerate over time. With mechanical valves,
strict life-long anticoagulation with warfarin is
required to prevent thrombus formation.
Thrombus on a mechanical valve may lead to
thromboembolic events such as stroke, or throm-
bose the physical valve leaflets, preventing leaf-
lets from opening or closing. When implanting a
mechanical valve, the patient must fully under-
stand the risks associated with chronic anticoagu-
lation and the implications of subtherapeutic
INRs or medical noncompliance. Another impor-
tant consideration in the placement of a mechani-
cal valve is the chance of pregnancy in young
women (Chap. 34). In the case of pregnancy,
there are multiple anticoagulation alternatives Fig. 16.6 Aortic valve replacement with a mechanical
valve. Viewed from the ascending aorta down into the left
during each trimester; however, no therapy is ventricle. (a) valve tester demonstrating functional open-
consistently safe for both mother and fetus. Given ing leaflets. (b) prosthetic valve leaflets. (c) Valve sewing
the anticoagulation requirement, there is a seri- ring
16 Aortic Valve Disease 159

Fig. 16.7 Aortic valve replacement with bioprosthetic Fig. 16.9 Bioprosthetic aortic valve with thrombus (HALT)
valve and restricted leaflet mobility on CT as shown by arrows

are outlined in Fig. 12 in the 2020 AHA/ACC Valve

Guidelines [1].

ortic Bioprosthetic or Mechanical

A
Valve Dysfunction

Bioprosthetic aortic valves may thrombose or

degenerate overtime. Thrombosis most com-
monly occurs in the first 3 months following
implantation but has also been described years
later [1]. While bioprosthetic valves are less
thrombogenic than mechanical valves, the diag-
Fig. 16.8 Normal appear bioprosthetic valve on cardiac
CT nosis of subclinical thrombosis has increased
with the use of CT imaging.
Bioprosthetic thrombosis appears more com-
With advancements in the durability of biopros- mon with transcatheter valves versus with surgi-
thetic valves and the introduction of the TAVR, cal valves and leaflet thrombosis should be
potentially negating the need for a re-sternotomy at suspected with increased transvalvular gradients
the time of valve replacement, bioprosthetic valves by TTE imaging. When transvalvular gradients
have been justified in a younger population. At the are increased, then cardiac CT should be
same time, advancements with the mechanical obtained to evaluate. Early hypoattenuated leaf-
valves are leading to lower anticoagulation recom- let thickening (HALT) occurs in at least 10% of
mendations, creating a safer and more tolerated TAVR patient and prognostic information is
valve. These advancements and the role of the uncertain [9]. While HALT is not associated
TAVR have created a gray area in the guidelines for with mortality or cerebrovascular events, it is
patients between the ages of 50 and 65 years old. associated with symptomatic valve deterioration
This is a situation where surgeon-patient discus- and patients are placed on systemic anticoagula-
sions, critical thinking, and judgment are crucial in tion [9] (Fig. 16.9).
medical decision making. Current guidelines for Bioprosthetic aortic stenosis can occur with
anticoagulation management for valve replacement both mechanical and bioprosthetic valves and
160 A. Booke et al.

may be due to thrombus formation leading to sternal border. The closure of the aortic valve
abnormal leaflet mobility, pannus ingrowth, or (A2) is usually absent.
structural valve deterioration due to degeneration
by leaflet thickening or calcification [1]. Patients I ntervention/Management of Acute AI
with symptomatic bioprosthetic stenosis should Medical therapy, including IV diuretics or
be referred to Valve Centers for consideration of vasodilators, can help reduce LV afterload to
valve replacement, either with redo surgery or allow for temporary stabilization, although
transcatheter valve in valve therapy. surgery should not be delayed, especially in
Bioprosthetic insufficiency may occur in the setting of hypotension, pulmonary edema, or
setting of leaflet tear or infective endocarditis end-organ hypoperfusion. In patients with
destroying the valve leaflet resulting in heart fail- hypertension, blood pressure can be controlled
ure and is an indication for patients to be referred with initiation of ACE/ARB or dihydropyri-
to a Valve Center for replacement. These are dine CCBs. Beta-blockers, while they can help
patients that should be rapidly referred for assess- in patients if indicated in acute aortic dissec-
ment. See Fig. 14 in the 2020 AHA/ACC Valve tion, should be avoided in acute AI as they will
guidelines for recommendations [1]. block compensatory tachycardia necessary for
cardiac output, resulting in hypotension and
shock. Intra-aortic balloon pumps are also
ortic Insufficiency (AI) or Aortic
A contraindicated.
Regurgitation (AR) Acute severe AI is a surgical emergency.
Surgical intervention of acute is dependent on the
Acute Aortic Insufficiency acuity of the deficiency and development of
symptoms. A sudden change in hemodynamics
Etiology requires urgent surgical intervention.
Acute AI most commonly occurs in the setting of
endocarditis, trauma, and/or aortic dissection. In
endocarditis, vegetation causes direct disruption Chronic Aortic Insufficiency
of the valve coaptation, or physical perforation of
the leaflets (see Chap. 19). In aortic dissection, Etiology
aortic valve insufficiency is secondary to the dila- Chronic AI may be caused by primary valve dis-
tion of the aortic root, stretching the valves so ease, primary root disease, or secondary causes.
they do not coapt, or dissection of the valve com- The most common cause for AI in high income
missure (see Chap. 28). countries is BAV and in low to middle income
Acute AI results in a sudden increase of vol- countries is rheumatic heart disease [1].
ume in the LV at the end of diastole (preload), due Membranous subaortic stenosis may lead to
to valve incompetence, leading to rapid hemody- thickening and scarring of aortic leaflets resulting
namic instability and flash pulmonary edema. in AI and in ~15% of patients with a VSD, there
is prolapse of the aortic cusp resulting in AI [2].
Physical Exam Marked aortic annular dilatation, retrograde
Acute AI may have no murmur due to rapid aortic dissection involving the annulus, or medi-
equalization of pressure. There will be a wide cal degeneration of the ascending aortic in condi-
pulse pressure and low diastolic pressure. When tions such as Marfan’s, idiopathic aortic dilation,
the murmur is better appreciated on the right ster- osteogenesis imperfecta, and severe chronic
nal border, concern should be raised for aortic hypertension may also result in AI. AI is less
dissection [3]. The murmur may be a high- commonly seen secondary to syphilis and anky-
pitched, blowing decrescendo diastolic murmur losing spondylitis. AI commonly occurs with
heard best at the third intercostal space of the left infective endocarditis.
16 Aortic Valve Disease 161

In patients with chronic AI, the LV stroke vol- linium enhancement having worse outcomes.
ume increases resulting in an increase in LVEDP TEE can further assess the aortic valve, cardiac
(preload). The LV hypertrophies and dilates catheterization with aortic angiography and CT
resulting in increased preload and afterload, and scan can further assess the aorta. Six months to
once LV adaptive measures fail, the LV function yearly echocardiographic surveillance is indi-
deteriorates [2]. In chronic AI, there is commonly cated to optimize timing surgical intervention
elevation in LA, PA wedge, PA, and RV pres- (Fig. 16.10).
sures. Patients with AI may experience myocar- In asymptomatic patients with chronic AI,
dial ischemia secondary to increased myocardial medical therapy should be initiated for hyperten-
oxygen requirements from LV dilation or sion, heart failure, or other comorbidities. In
hypertrophy. asymptomatic patients, treatment of systolic BP
Since the development of AI is slow, the left to <140 mmHg is recommended. Patients with
ventricle (LV) has time to compensate for the severe AI with or without LV dysfunction, who
gradual increase in preload. The LV diameter are prohibitive surgical risks, GDMT with ACE/
slowly dilates resulting in eccentric hypertrophy. ARB, sacubitril/valsartan, or dihydropyridine
As the LV compensates for the increased volume, CCBs is recommended [1].
the onset of symptoms and need for surgery are TAVR for AI is technically challenging given
delayed. Patients will complain of dyspnea first, dilation of aortic annulus or root and lack of aor-
with progression to orthopnea, PND, diaphoresis, tic valve calcification to act as scaffolding for the
angina, and lower extremity edema. aortic valve. The aortic bioprosthesis can migrate,
creating a significant paravalvular leak. In
Physical Exam patients who are surgical candidates, TAVR
An AI murmur is a high-pitched, blowing decre- should not be performed.
scendo diastolic murmur heard best at the third Surgical intervention for chronic AI is depen-
ICS of the LSB and the closure of the aortic valve dent on the presence of symptoms. If a patient’s
(A2) is usually absent. When the murmur is bet- severe AI becomes symptomatic, surgery is war-
ter appreciated on the right, sternal border con- ranted regardless of LV function [1]. If a patient
cern should be raised for aortic dissection [3]. with severe AI remains asymptomatic, the timing
Severe AI is associated with a wide pulse pres- of surgery becomes dependent on the presence of
sure and low diastolic pressure. decreased LV function. These parameters are a
left ventricular ejection fraction (LVEF) below
Evaluation/Management 55% or increase of left ventricular end-systolic
ECG. ECG may demonstrate LVH, lateral (I, dimension of >50 mm seen on cardiac imaging
aVL, V5, V6) ST-depressions of T-wave inver- [1]. If the patient requires another cardiac opera-
sions, left axis deviation, QRS widening. tion, such as a CABG, the aortic valve should be
Imaging Studies. TTE provides diagnostic repaired/replaced simultaneously if moderate or
information about the etiology and mechanism of severe AI is present at the time of the index oper-
AI and evaluates degree of LVEF and LV cham- ation [1]. (See Fig. 4 in the 2020 AHA/ACC
ber remodeling. TTE is useful in the evaluation of Valve Guidelines [1]).
a dilated aortic annulus and root, aortic dissec- AI is surgically corrected by performing an
tion, and primary leaflet morphology. aortic valve replacement (SAVR) or an aortic
When TTE measurements are discordant with valve repair (SAVr). A SAVR entails removing
clinical findings, Cardiac MRI (CMR) can be the patient’s aortic valve and replacing the entire
used. CMR accurately quantifies the regurgita- apparatus with either a bioprosthetic valve or a
tion severity and LV remodeling. In asymptom- mechanical valve. Aortic valve replacement
atic patients, CMR is predictive of those who remains the gold standard treatment of aortic
will require surgery and who will have incom- valve disease when the cause of AI stems pri-
plete reverse modeling, and those with late gado- marily from the valve leaflets. Insufficiency from
162 A. Booke et al.

Fig. 16.10 TTE Image of severe AI with ventricular dila- right panel shows a green arrow pointing at the regurgitant
tation. The left panel of Fig. 16.10 shows the mitral valve jet filling the LVOT, and this AI jet swirls into the LV
is open (red arrow) confirming ventricular diastole. The (black arrow) suggestive of severe and acute AI

a bicuspid valve, endocarditis, or annular dila-

tion warrants valve replacement. A valve repair
involves maintaining the native valve and repair-
ing the defect that is causing the valve to leak.
SAVr is gaining popularity with numerous
advances in techniques and reproducible results.
Aortic valve repair or “valve-sparing” operations
are becoming commonplace when the regurgita-
tion is secondary to coaptation from a dilated
aortic root or aortic aneurysm. In these scenar-
ios, the aortic leaflets otherwise appear func-
tional. This type of repair is demonstrated in Fig. 16.11 Aortic root replacement with a native valve-
Fig. 16.11. Here the patient’s aneurysmal root sparing repair due to aortic aneurysm and insufficiency.
was replaced with a tube graft and the native Photo Credit: Bob Hooker, MD
valve was resuspended within. This technique
re-establishes coaptation of the native leaflets may become a more prominent treatment for
with no residual aortic insufficiency. As under- aortic valve insufficiency.
standing of the mechanics and geometry of the Current data is limited regarding progression
aortic valve expand, surgical repair techniques of aortic dilation and risk of dissection after AVR
continue to improve. With time, the durability of in patients with a bicuspid aortic valve (BAV).
the AV repair may become more apparent and Current guidelines recommend aortic root and/or
16 Aortic Valve Disease 163

ascending aorta replacement at the time of SAVR References

due to severe AI if the diameter is >4.5 cm [1].
Refer to section on BAV intervention and chapter 1. Otto CM, Nishimura RA, Bonow RO, Carabello BA,
Erwin JP III, Gentile F. 2020 ACC/AHA guideline for
on aortic aneurysms for further discussion and the management of patients with valvular heart dis-
guidelines. ease: a report of the American College of Cardiology/
American Heart Association Joint Committee on
Preoperative Assessment clinical practice guidelines. J Am Coll Cardiol.
2021;77(4):e25–e197.
and Calculating Risk 2. Loscalzo J, Fauci A, et al. Harrison’s principles of
Preoperative assessment and risk stratification internal medicine. 21st. ed, Volume 1 and Volume 2.
are the same for aortic valve intervention New York: McGraw Hill; 2022.
regardless of etiology. Preoperative work-up 3. Lawton JS, Tamis-Holland JE, Bangalore S, Bates
ER, Beckie TM, Mischoff JM, et al. 2021 ACC/AHA/
includes a detailed history and physical exam SCAI guideline for coronary artery revasculariza-
including dental history, and also basic lab and tion, a report of the American College of Cardiology/
imaging modalities. Preoperative cardiac cath- American Heart Association Joint Committee on
eterization should be completed to assess for clinical practice guidelines. J Am Coll Cardiol. 2022,
79:e21–e129.
coronary artery disease. Refer to similar section 4. The Society of Thoracic Surgeons. 2022. https://www.
under Surgical Management of CAD Tables sts.org/resources/risk-calculator.
6.1, 6.2, and 6.3. Again, the overall operative 5. O'Brien SM, Feng L, He X, Xian Y, Jacobs JP,
mortality for an isolated AVR in patients under Badhwar V, et al. The Society of Thoracic Surgeons
2018 adult cardiac surgery risk models: part 2 - sta-
70 years old is considered low at 1–3% and tistical methods and results. Ann Thorac Surg. 2018,
increases to a risk of 4–8% in older populations 105:1419–28.
[8]. 6. Taramassa M, et al. Tricuspid regurgitation, predict-
ing the need for intervention, procedural success, and
recurrence of disease. JACC Cardiovasc Imaging.
Valve Selection 2019;12(4):605–21. https://doi.org/10.1016/j.
As with AS, if the aortic valve is unrepairable, jcmg.2018.11.034.
the next step is valve selection between a 7. Vahanian A, Beyersdorf F, Praz F, Milojevic M, Baldus
mechanical or a bioprosthetic valve. This deci- S, Bauersachs J, Capodanno D, Conradi L, De Bonis
M, De Paulis R, Delgado V, Freemantle N, Gilard M,
sion is multifactorial and is based on age, medi- Haugaa KH, Jeppsson A, Jüni P, Pierard L, Prendergast
cal compliance, risk of lifelong anticoagulation, BD, Sádaba JR, Tribouilloy C, Wojakowski W, ESC/
and the patient’s individual desires. Valve selec- EACTS Scientific Document Group, ESC National
tion is a serious, multi-faceted decision made Cardiac Societies. 2021 ESC/EACTS Guidelines for
the management of valvular heart disease: Developed
between surgeon and patient which is continu- by the Task Force for the management of valvular heart
ally evolving. Recent advancements in technol- disease of the European Society of Cardiology (ESC)
ogy for both types of valves have made them and the European Association for Cardio-Thoracic
more acceptable to outlying patients. Surgery (EACTS). Eur Heart J. 2022;43(7):561–632.
8. Chung J, Shum-Tim D. The current indications and
Bioprosthetic valves are becoming more dura- options for aortic valve surgery. J Surg. 2014;2(1).
ble while mechanical valves require lower levels 9. Hein M, Schoechlin S, Schulz U, Minners J, Breitbart
of anticoagulation. Refer to the section on AS P, Lehane C, Neumann F-J, Ruile P. Long-term follow-
for further discussion. up of hypoattenuated leaflet thickening after trans-
catheter aortic valve replacement. JACC Cardiovasc
Interv. 2022;15(11):1113–22.
Mitral Valve Disease
17
Anne Booke, Michael Rinaldi, Elisabeth A. Powell,
Larry Watts, and Richard Musialowski

Mitral Insufficiency/Mitral
Regurgitation (MR)

Acute Mitral Insufficiency

Acute MR is related to primary valve pathology

affecting the leaflets, chords, papillary muscle, or
mitral anulus. Infective endocarditis may cause
leaflet tears or chordal rupture. Myxomatous
mitral valves degenerate over time which may
result in spontaneous chordal rupture. Papillary
muscle rupture, most commonly the posterome-
dial papillary muscle, may occur as a complica-
tion of inferior STEMI resulting in acute
MR. Acute MR may also be seen in transient
ischemia and in patients with blunt chest wall
trauma. Acute MR results in acute volume over-
load resulting in pulmonary congestion and a low
forward cardiac output. Rapid diagnosis is essen-
tial as these patients are at elevated risk for hemo-
dynamic compromise (Figs. 17.1 and 17.2) [1].

A. Booke · M. Rinaldi · L. Watts · R. Musialowski

Sanger Heart and Vascular Institute, Atrium Health, Fig. 17.1 Long axis view on CT showing the cusps start-
Charlotte, NC, USA ing at lateral A1 under the left atrial appendage to medial
e-mail: [email protected]; A3
[email protected];
[email protected];
[email protected] Acute MR may not have a murmur but can
E. A. Powell (*) still be the etiology of cardiogenic shock. The
Banner University Medical Center, Tucson, AZ, USA MR jet on TTE may be unimpressive but in the
e-mail: [email protected]

© The Author(s), under exclusive license to Springer Nature Switzerland AG 2023 165
R. Musialowski, K. Allshouse (eds.), Cardiovascular Manual for the Advanced Practice Provider,
https://doi.org/10.1007/978-3-031-35819-7_17
166 A. Booke et al.

Chronic Mitral Insufficiency

Etiology and Pathophysiology

MR results from an abnormality or disease pro-
cess affecting one of the components of the mitral
valve apparatus. To assess and manage chronic
mitral insufficiency, it is important to distinguish
between primary (degenerative, disease of the
mitral valve apparatus) and secondary (func-
tional, disease of the ventricle or atria) MR
(Table 17.1). Primary MR is related to disease of
the mitral apparatus, one or more components of
the mitral valve (leaflets, chordae tendineae,
papillary muscles, annulus, adjacent myocar-

Fig. 17.2 Short axis view on CT showing the coaptation
dium) which causes valve incompetence with
of the anterior and posterior leaflets and cusps. The loca-
tion of pathology is communicated using this cusp resultant systolic regurgitation. Cord rupture with
nomenclature flail segment is a common cause of many etiolo-
gies (Fig. 17.3). Secondary MR occurs in a struc-
turally normal mitral valve, where disease or
setting of hemodynamic compromise with no enlargement of the atria or ventricles may cause
other cause for deterioration, TEE is especially annular enlargement, papillary muscle displace-
helpful for further evaluation. ment, leaflet tethering, or malcoaptation. MR in
Vasodilatory therapy, including nitroprusside the setting of hypertrophic cardiomyopathy
or nicardipine, may help improve hemodynamic occurs secondary to anterior papillary muscle
compensation, although use of medications may displacement and systolic anterior motion (SAM)
be limited in the setting of hypotension. An intra- of the anterior mitral valve leaflet into the LV out-
aortic balloon pump (IABP) can be used to help flow tract (see Chap. 20).
stabilize the patient by decreasing LV afterload, With MR, the LV emptying (afterload) is
increasing forward output, and decreasing the reduced and consequently the LV is decompressed
regurgitant volume. into the left atrium. As LV volume increases over-
Prompt recognition, management, and urgent time, the severity of the MR and the LV contractile
mitral valve repair is lifesaving in acute severe reserve diminishes, and increased LA volume with
primary MR. Multidisciplinary team-based dis-
cussions are essential in this high-risk group.
Urgent surgical intervention may be required. In Table 17.1 Classification of mitral regurgitation
patients with prohibitive surgical risk and favor- Primary: Leaflet Secondary: Myopathic
able anatomy, emergent transcatheter end-to-end Pathology Abnormality
repair (TEER) could be considered. Mitral valve prolapse Dilated cardiomyopathy
(MVP)
Rheumatic valve Papillary muscle ischemia
urgical Intervention for Acute MR
S disease
Urgent mitral valve intervention is warranted to Cleft mitral valve Regional wall motion
re-establish hemodynamics, reduce strain on the abnormality causing leaflet
heart, and alleviate symptoms. This could require tethering
Endocarditis with Mitral annular calcification
repair or replacement depending on the etiology leaflet destruction
of the acute decompensation. A team-based Radiation valvopathy Dilated atria causing atrial MR
approach is essential in this high-risk cohort of Connective tissue
patients. disorders
17 Mitral Valve Disease 167

Fig. 17.3 Flail P2 segment left arrow. The ruptured cord and leaflet tip is pointing back into atria which is the hallmark
of a flail leaflet. Severe 4 + primary MR on color doppler is shown by the arrow in the right panel

progressive LA enlargement is associated with

decreased cardiac output [1]. Chronic MR is often Symptoms
progressive as LA enlargement places increased Severe chronic MR can be asymptomatic for
tension on the posterior mitral leaflet, worsening extended periods of time but inevitably is associ-
the degree of MR, causing progressive dilation of ated with the development of exertional dyspnea,
the LA and LV [1]. This may lead to a perpetuating fatigue, and eventually clinical heart failure
cycle of worsening MR with increasing LV vol- including lower extremity edema, orthopnea, and
ume. The unloading of the LV with flow back into ascites. Patients in acute heart failure may pres-
the LA increases the LVEF thus a “normal” LVEF ent with acute pulmonary edema. Once the LA
in significant MR is ~70%. When the LVEF dilates enough, patients will develop atrial fibril-
declines toward 60% and the LVESD is <40 mm, lation as well.
LV dysfunction is present. With severe chronic
MR, patients begin to develop pulmonary hyper- hysical Exam/Cardiac Studies
P
tension and may develop secondary TR along with The traditional murmur of secondary MR is a
right heart failure. holosystolic blowing murmur originating at the
apex and directed toward the axilla. The primary
MR murmur is often harsher in quality and may
radiate anteriorly from apex to the lower left
168 A. Booke et al.

sternal border and is often confused with aortic Table 17.2 Carpentier classifications
stenosis. This MR murmur will not change with Type 1 (normal • The leaflets are normal but
respiration nor radiate to the carotids, confirm- leaflet motion) flattened with lack of central
coaptation resulting in a central
ing the diagnosis. jet
• Caused from annular dilation
from progressive atrial or
Imaging Modalities ventricular dilation (e.g., atrial
dilation secondary to chronic AF)
or leaflet perforation
KG
E • This is a less common form of
In patients with severe MR, the ECG may show secondary MR
evidence of atrial or ventricular enlargement. Type 2 • Primary leaflet pathology with
(increased prolapse or flail of one or both
Atrial fibrillation is a common finding as well.
leaflet motion) leaflets
• T he most common form of
Echocardiography primary MR
TTE is an excellent screening study for the detec- Type 3a • Restricted leaflets relatively
tion of mitral insufficiency. Its severity is graded (restricted immobile in both systole and
leaflet diastole
as 1+ (mild), 2+ (moderate), 3+ (moderately motion—systole • Seen in rheumatic disease
severe), and 4+ (severe) with 3–4+ considered of diastole) • In contrast to rheumatic mitral
clinically relevant and can be associated with stenosis, the leaflets are partially
symptoms. When patients develop change in fixed open
• Always some degree of mixed
symptomatology, repeat TTE is indicated. stenosis present
For patients with less than severe MR but exer- • This is a less common form of
tion symtoms, exercise treadmill echocardiography primary MR
can be helpful to demonstrate more severe MR Type 3b • Restricted leaflets during systole
(restricted only
with activity. This includes assessment to pulmo- leaflet • Related to chronic LV failure
nary artery pressures. Cardiopulmonary exercises motion— with wall motion abnormality of
testing (CPET) may also determine the hemody- systole) the inferoposterior wall and
namic significance of MR. associated tethering of the
posterior leaflet leading to a
TEE, given its high degree temporal resolu- posteriorly directed jet
tion, is primarily used to determine the mecha- • T he most common form of
nism of MR and is used to guide both surgical secondary MR
and transcatheter therapies (Fig. 17.3). While
TEE can be used to quantify the severity of MR,
TEE can underestimate the severity due to proce- valve repair [2]. The Carpentier classifications
dural sedation, which decreases SVR and after- are listed in Table 17.2. The Carpentier system-
load. Blood pressure challenge with pressors can atic approach to repair involves quadrangular
be used to better assess severity during TEE. leaflet resection of prolapse, placement of normal
Because TTE can have diagnostic limitations, chords to the prolapsing leaflet tissue if needed
the quantification of MR can be challenging. for support, and placement of a ring prosthesis to
Cardiac MRI can be used for quantification of remodel the annulus for stability and improved
MR severity and is the gold standard for severity coaptation of the leaflets [2]. Although tech-
assessment. niques and technology have evolved with time,
Imaging modalities are used to assess the these same concepts are utilized today.
pathology of MR to determine methodology for
repair or replacement. Alain Carpentier MD, the anagement of Primary MR
M
father of mitral valve repair, developed a com- Patients with primary MR should be treated with
plete classification system to describe the pathol- GDMT for hypertension, volume overload, and
ogies of MR and the associated approaches to LV dysfunction.
17 Mitral Valve Disease 169

Patients with severe primary MR should be ably if they have concomitant severe TR, severe
referred to a surgeon for evaluation. Refer to RV failure, pulmonary hypertension, and less
Fig. 8 from the guidelines [1]. For patients who severe MR in proportion to LV systolic dysfunc-
are poor surgical candidates with primary MR, tion. For example, patients with an EF 15–20%
transcatheter edge-to-edge repair (TEER) can be and 2–3+ MR are less likely to respond favorably
considered as an alternative. Clinical trials of to TEER and should be considered for advanced
surgery vs TEER have shown lower complica- heart failure therapies such as VAD or transplant
tions and quicker recovery with TEER but better if appropriate.
procedural success with surgery. Surgical repair Atrial functional MR (AF MR) is another cat-
is associated with a 95% ≤1+ residual regurgita- egory of secondary MR (Carpentier 1) where
tion, while TEER can be associated with an 80% LVEF may be preserved and annular dilation
≤1+ residual leak in contemporary studies. In from progressive LA enlargement can result in
patients with rheumatic mitral valve disease, lack of coaptation of the leaflets. Maintenance of
with thickened or calcified leaflets and subvalvu- SR appears to reduce progression of MR and
lar involvement surgical repair is less suitable should be achieved if possible. Diuretics and ade-
and TEER is likely not feasible. quate BP management may reduce MR severity.
For patients with persistent severe symptomatic
anagement Secondary MR
M MR, surgical mitral valve repair or replacement
When secondary MR exists with systolic LV dys- or TEER could be considered but is less well
function, the primary therapy is guideline studied (See Fig. 9 in 2020 AHA/ACC Valve
directed medical therapy for systolic heart failure Guidelines) [1].
including beta blockers, ACE-I/ARB/ ARNI,
mineralocorticoid receptor antagonists, SGLT-2 ranscatheter Edge-to-Edge Mitral
T
inhibitors, hydralazine nitrates, and diuretics Valve Repair (mTEER)
(Class 1). For patients with EF ≤35% and LBBB, TEER improves quality of life, hospitalization
CRT can also reduce MR severity (Class 1). In rate, and survival for patients with systolic heart
patients with obstructive CAD, revascularization failure despite maximally tolerated GDMT, as
can also improve LV function and reduce studied in the COAPT trial. During mTEER, a
MR. Patients with systolic CHF should have patient is placed under general anesthesia and
medications uptitrated at regular intervals with TEE guidance is used to guide the positioning of
contact every 1–2 weeks until maximum-toler- mitral clip and assess the reduction of MR. Right
ated dosing is achieved and once GDMT is maxi- femoral venous access is obtained and with trans-
mized TTE should be repeated to reassess MR septal puncture, the implanting physician gains
degree. An example of this would be secondary direct access to the mitral valve. The clip grasps
MR related to inferoposterior wall motion abnor- the diseased cusp of the anterior leaflet and
mality with chronic systolic CHF (Carpentier 3b) simultaneously grasps the posterior leaflet, caus-
which is a disease of the left ventricle. ing reduction in leaflet mobility and will result in
If persistent severe 3–4+ MR remains present, a degree of mitral stenosis. It is important for
and EF is between 25 and 50% with LVEDV physicians to monitor the degree of MS prior to
<7 cm, transcatheter edge-to-edge mitral valve release of the clip as if resultant MS is too high
repair (TEER) can be considered based on data the patient will not receive symptomatic relief.
from the COAPT trial (Class 2a). TEE is per- Utilization of the intraoperative TEE helps deter-
formed to assess anatomic feasibility. Surgical mine if additional clip placement is indicated and
repair or replacement can be considered in the degree of resultant MS with clip placement.
patients without suitable anatomy for TEER who Post-procedure providers may increase beta
are surgical candidates although the data for ben- blockade to slow heart rate and decrease any
efit is less robust (Class 2b). For both TEER and degree of MS. Figure 17.4 demonstrates what
surgical MVR, patients will respond less favor- mitral clip implantation looks post deployment.
170 A. Booke et al.

bility, lower rates of thromboembolism, resistance

to endocarditis, and does not require anticoagula-
tion therapy in most patients [2]. Techniques and
concepts regarding MV repair are continually
evolving and range from simple to comprehen-
sive. Simple repairs may only involve placement
of an annular ring to support the valve while
complicated repairs involve both the anterior and
posterior leaflet, as well as the chordae. The goal
of the repair is to re-establish the integrity of the
valve, improve coaptation of the leaflets, and
decrease annulus size if dilation exists.
Fig. 17.4 Red arrow is a deployed TEER clip to the In the operating room, MV repairs are imme-
A2P2 segments of the mitral valve for a flail segment with diately assessed by a certified advanced imaging
resultant two channels during ventricular diastole (green
physician via TEE. If the MV repair is inade-
arrows)
quate, immediate MV replacement should be
considered while still in the OR.
Antithrombotic therapy following TEER is Mitral valve replacement is warranted when
studied to be aspirin 81 mg indefinitely and the leaflets are not salvageable due to presence of
Plavix 75 mg for 2 months post procedure. In calcification, perforation, infection, or the pres-
patients with atrial fibrillation or other indica- ence of rheumatic disease. If repair is attempted
tions for systemic oral anticoagulation, the regi- in rheumatic disease, the risk of reoperation is
men is adjusted. 50–60% of patients within 20 years [1].

urgical Management of Mitral

S urgical Intervention for Chronic
S
Regurgitation Primary MR
The timing of surgical intervention for MR The timing of surgery depends on the severity of
depends on the acuity of the MR (acute vs the disease and LV function. Unlike surgical treat-
chronic) and the cause of the MR (primary vs ment of the aortic valve or mitral stenosis, the lack
secondary). Mortality rates for primary MR of symptoms should not delay the timing of inter-
decrease with early surgical intervention before vention for primary MR. In mitral valve prolapse
symptoms and LV systolic dysfunction (LVEF affecting only half of the posterior leaflet, mitral
≤60% or ESD ≥ 40 mm) occur [1]. Once a valve repair is the gold standard of care with out-
patient develops symptoms and LVEF ≤60, the comes superior to both biological and mechanical
prognosis is poor [1]. This was confirmed by a valve replacement [1]. Studies demonstrate that
recent data analysis completed by the STS dem- patients who undergo mitral valve repair for pri-
onstrating reduced survival associated with late mary MR have a life expectancy equal to that of
referral for surgical intervention [3]. Close moni- the general population after surgery, regardless of
toring of MR progression with imaging surveil- age [4]. When mitral valve repair is successful,
lance, despite presence of symptoms, is vital in operative mortality rate is <1%, with 95% free-
planning surgery before LV dysfunction deterio- dom from reoperation and 80% freedom from
rates [1]. recurrent moderate or severe MR at 15–20 years
In MR, surgical correction can be accom- postoperatively [1]. In accordance with the ACC/
plished by either mitral valve repair (MVr) or AHA guidelines, if severe primary MR is isolated
mitral valve replacement (MVR). Mitral valve to less than half of the posterior leaflet and only
repair is preferred over mitral valve replacement simple repair to the posterior leaflet is necessary,
and should be attempted if leaflets are salvage- MV replacement is considered harmful and
able. Valve repair is shown to have superior dura-
17 Mitral Valve Disease 171

should not be completed unless MV repair has Risk stratification for MV repair and MV
been attempted and failed [1]. replacement can be calculated on the STS web-
site. Refer to Chap. 6 for further discussion and
urgical Intervention for Chronic
S Table 6.3 for a list of categories assessed with the
Secondary MR risk calculator.
In chronic secondary MR, the role of surgical
intervention is controversial. MR is multifactorial urgical Approach and Valve Selection
S
and restoration of MV competence does not miti- As discussed above, MV repair is preferred to
gate the underlying cardiac pathology. Although it MV replacement in the setting of MR. Surgical
has not been shown to directly improve survival, approach begins with visual assessment of the
surgical intervention has been shown to improve mitral valve apparatus to determine if repair is
functional outcomes and reduce symptoms [5]. feasible. Figure 17.5 depicts visualization of the
According to the ACC/AHA guidelines, MV mitral valve via the left atrium during surgery.
surgery for chronic secondary MR is warranted: [1] This mitral valve has a flail posterior leaflet
resulting in severe MR.
• In the presence of severe symptoms when the
valve is not favorable to TEER.
• When patient is undergoing CABG with
severe MR and LV dysfunction secondary to
CAD.
• When severe MR is isolated from annular
dilation related to atrial fibrillation, MV sur-
gery with MAZE procedure may be
reasonable.

With surgical intervention of chronic second-

ary MR, MV replacement should be considered
in cases with ischemic or dilated cardiomyopa-
thy. The durability of a mitral repair depends on
the regression of the underlying dilation, and if
the dilation progresses postoperatively, the repair
Fig. 17.5 Mitral valve with flail posterior leaflet. (a)
will not be durable and survival is limited [1].
Anterior leaflet. (b) Posterior leaflet. (c) Chordae Tendinae

Preoperative Assessment
and Calculating Risk
As with other cardiac surgeries, a detailed history,
physical, and a myriad of diagnostic testing is com-
pleted to determine patient’s baseline status and
operative risk. A cardiac catheterization should be
completed to assess for any coronary artery disease
that may need to be addressed during the operation.
A thorough dental history should also be obtained
to rule out a disease process which may put patient
at increased risk for developing endocarditis post-
operatively. Refer to previous chapters regarding
preoperative assessment for further discussion and
Tables 6.1 and 6.2 in Chap. 6. Fig. 17.6 Insertion of valve sutures to implant an annulo-
plasty ring into mitral position for mitral repair
172 A. Booke et al.

competent valvular coaptation is demonstrated in

Fig. 17.8.
If the mitral valve is unable to be repaired and
replacement is necessary, the type of prosthesis
needs to be addressed. This discussion must be
completed with the patient preoperatively, even if
a MV repair is planned. Refer to the chapters on
valve selection under surgical management of
aortic valve disease for further discussion.

Mitral Stenosis

The etiology of mitral stenosis is most commonly

Fig. 17.7 Insertion of an annuloplasty ring for mitral rheumatic or degenerative (Table 17.3).
repair utilizing sutures from Fig. 17.6 Rheumatic fever is the leading cause of mitral
valve disease worldwide and rheumatic MS is
more common in women (80% case) compared
to men [1]. Clinical presentation can vary, and
patients may present earlier in life, even in their
teens. Patients presenting at a younger age, often
have commissural fusion but pliable, noncalci-
fied mitral valve leaflets [1]. Patients presenting
later in life more commonly have calcified
fibrotic mitral leaflets in addition to commissural
fusion and subvalvular involvement [1].
Degenerative mitral stenosis is seen in elderly
patients with significant mitral annular
calcification.
The normal mitral valve orifice is 4–6 cm2 and
when the mitral orifice is <2 cm2 the left atrial
Fig. 17.8 Mitral valve repair of Fig. 17.5 with triangular pressure rises to generate blood flow across the
resection of P2 and placement of ring
narrowed orifice into the LV. To compensate for
increased left atrial pressure, both pulmonary
With MV repairs, an annuloplasty ring is
always placed to support the annulus and provide
Table 17.3 Causes of mitral stenosis
structure, regardless of the type or complexity of
repair. Sutures are first placed along the annulus Rheumatic fever worldwide
Degenerative from age
(Fig. 17.6) and then the annuloplasty ring is para-
Congenital
chuted down into the correct position (Fig. 17.7). Chest radiation
Once the repair is complete, the valve is assessed Systemic lupus
intra-operatively for residual valvular leak prior Rheumatoid arthritis
to closure. Successful mitral valve repair with Carcinoid heart disease
17 Mitral Valve Disease 173

venous and arterial wedge pressures rise, which are exacerbated by physical exertion, tachycar-
contributes to exertional dyspnea. Untreated, dia, volume shifts, fever, severe anemia, preg-
longstanding MS causes passive backward trans- nancy, and thyrotoxicosis.
mission of the elevated left atrial pressure trig-
gering pulmonary arterial constriction, resulting hysical Exam/Cardiac Studies
P
in pulmonary changes and subsequent pulmonary The mitral stenosis murmur is best heard at the
hypertension, RV enlargement with tricuspid apex and described as an opening snap with a low
regurgitation, and right heart failure [1]. In pitched, rumbling, diastolic murmur. It is very
patients with severe MS, cardiac output is near difficult to appreciate.
normal at rest but fails to rise substantially with ECG. If there is left atrial enlargement, it may
exertion. be reflected by the p wave. In patients with pul-
Patients with mitral stenosis are at increased monary hypertensions, the ECG may show right
risk of developing atrial fibrillation and axis deviation and RV hypertrophy [6].
thrombi in the left atrium (valvular atrial Echocardiogram. TTE is used to evaluate
fibrillation). mitral leaflets along with extent of valvular calci-
fication into the mitral apparatus, the transvalvu-
Symptoms lar gradient, degree of chamber enlargement and
The most common presenting symptom is exer- function, concomitant tricuspid valve disease,
tional dyspnea or cough, followed by exercise and pulmonary pressures. TEE may be used to
intolerance. Patients may also present with symp- obtain superior images of the mitral valve for
toms of right heart failure. Symptoms from MS planning of intervention (see Fig. 17.9).

Fig. 17.9 Echo showing mitral stenosis. Heavily calci- panel suggestive of severe mitral stenosis. Note the tricus-
fied and reduced mobility of the mitral leaflets in the left pid valve is open confirming diastole
panel with restricted diastolic mitral flow in the right
174 A. Booke et al.

Table 17.4 Stages of mitral stenosis

Stage Definition Symptoms Valve Anatomy Valve Hemodynamics

A At risk of MS None Mild valve doming during diastole Normal transmitral flow velocity

Rheumatic valve changes with Increased transmitral flow velocities

commissural fusion and diastolic
B Progressive MS None doming of the mitral valve leaflets Mitral valve area >1.5 cm2
Planimetered mitral valve area
Diastolic pressure half-time <150 ms
>1.5 cm2
Rheumatic valve changes with Mitral valve area £1.5 cm2
commissural fusion and diastolic
C Asymptomatic severe MS None doming of the mitral valve leaflets Diastolic pressure half-time ³150 ms

Planimetered mitral valve area

£1.5 cm2
Decreased exercise Rheumatic valve changes with Mitral valve area £1.5 cm2
tolerance commissural fusion and diastolic
Symptomatic severe MS doming of the mitral valve leaflets Diastolic pressure half-time ³150 ms
D
Extertional dyspnea
Planimetered mitral valve area
£1.5 cm2

Adapted from (6)

Cardiac Catheterization. Left and right heart

catheterization is helpful for hemodynamic
assessment and to assess concomitant disease.
Staging of MS requires the combination of
patient symptomatology, valve anatomy and
hemodynamics, along with assessment of cardiac
consequences from MS, as seen in Table 17.4.

itral Stenosis Management

M
Patients with rheumatic mitral stenosis and valvu-
lar atrial fibrillation, prior embolic event, or LAA
thrombus should be initiated on warfarin (INR goal
2–3). There is no evidence to support DOACs in
atrial fibrillation secondary to MS. Control or low-
ering of heart rate with beta blockers or calcium
channel blockers are useful as it lengthens the dia-
Fig. 17.10 Yellow arrow shows a markedly enlarged left
stolic filling period, lowers the LA pressure, and atrial appendage (LAA) with the organized thrombus on
decreases symptoms. Cardioversion may be per- CT imaging. DOACs are contraindicated for treatment of
formed but does not durably restore sinus rhythm. thrombus associated with mitral stenosis
Amiodarone is most effective in maintaining sinus
rhythm post cardioversion [7]. Diuretics, digoxin, (PMBC) versus surgery. TEE will further evalu-
and ivabradine may also help improve symptoms. ate the mitral valve anatomy, presence of MR,
Patients with clinically significant rheumatic and left atrial appendage thrombus (Fig. 17.10).
MS (mitral valve area ≤ 1.5 cm2 and diastolic
mitral gradient ≥5–10 mmHg) should be fol- Degenerative, Nonrheumatic
lowed annually with TTE. TTE helps determine Calcific MS
the severity of stenosis and when severe MS is Calcific MS is the result of calcification of the mitral
present will help determine the suitability for annulus that extends into the leaflets bases resulting
Percutaneous Mitral Balloon Commissurotomy in narrowing of the annulus and progressive leaflet
17 Mitral Valve Disease 175

rigidity [1, 8]. There is usually no commissural toms out to 20 years [9]. In symptomatic patients
fusion and typically the leaflet tips are unaffected with severe rheumatic MS (valve area ≤ 1.5 cm2),
[1, 8]. Degenerative MS is usually observed in the < 2+ moderate MR, and absence of LA thrombus,
elderly population and progression of MS is vari- PMBC is recommended [9]. Contraindications to
able and may range from 1 to 9 mmHg annually PMBC are listed in Table 17.5.
(Fig. 17.9). The prognosis for patients with this type An anatomic mitral morphology score can be
of MS is extremely poor with a 50% mortality used to determine the suitability of PMBC and to
within 5 years [1]. These patients are typically at evaluate the appearance of the commissures and
high risk for any intervention given the extent of degree of calcification. Clinical factors such as age,
calcification, advanced age, and comorbidities. NHYA class, presence/absence of atrial fibrillation,
Medical management is the same as for rheu- and Wilkins score assist in predicting outcome.
matic MS. Degenerative MS is not amenable to The Wilkins score uses echocardiographic param-
PMBC and severe mitral annular calcification eters to grade rheumatic MS for possible PMBV
(MAC) limits surgical options given the difficulty using characteristics of (1) leaflet mobility, (2) leaflet
in attaching a prosthetic mitral valve and risk of thickening, (3) leaflet calcification, and (4) sub val-
narrowing the mitral orifice. MV repair is usually vular thickening. Each characteristic can have four
not feasible and MV replacement is the treatment points if the disease is more severe for a maximum
of choice. Due to the risk, current guidelines rec- of 16. A score of <8–9 are considered candidates for
ommend surgical intervention only once the MS PMBV depending on degree of mitral insufficiency
becomes severe, patient become extremely symp- and a score of >9–10, especially with moderate MR
tomatic, and medical therapy is no longer effec- should be considered for surgery.
tive [1]. The evaluation of transcatheter therapies Mitral valve repair or replacement are both
(TMVR) in the mitral position is ongoing. A mul- utilized in the surgical treatment of MS. The sur-
tidisciplinary team approach is essential in these gical approach to MS depends on the pathology
complex patients. of the disease, the involvement of the valve leaf-
lets, and the extent of calcification present. As
heumatic Mitral Stenosis Intervention
R stated above, PMBC is the first-line therapy for
The optimal treatment of patients with rheumatic Rheumatic MS unless contraindicated. According
MS is either percutaneously mitral balloon com- to the ACC/AHA, MV surgery for rheumatic MS
missurotomy (PMBC) or surgery (Fig. 7 in 2020 is warranted in the following patients [1]:
AHA/ACC Valve Guidelines [1]). PMBC is per-
formed by advancing balloon catheters across the • Severe MS (mitral valve area ≤ 1.8 cm2),
mitral valve and expanding them to split the • MS with severe limiting symptoms,
mitral commissures. Long-term follow-up dem- • Who are not a candidate for PMBC given
onstrated that at 10 years 70–80% of patients unfavorable valve morphology or presence of
with a good initial PMBC result were free of left atrial thrombus,
symptoms, and 30–40% remained free of symp- • Previous failure of PMBC, and
• Already undergoing cardiac surgery for
another reason.
Table 17.5 Contraindications for percutaneous mitral
balloon commissurotomy in rheumatic MS
Like PMBC, the preferred approach to surgical
• Mitral valve area > 1.5 cm2
management is mitral valve repair with commis-
• Left atrial thrombus
• More than mild MR
surotomy. During surgical commissurotomy, a
• Severe or bicommissural calcification sternotomy is completed, the heart is placed on car-
• Absence of commissural fusion diopulmonary bypass, and under direct visualiza-
• Concomitant CAD requiring surgery tion the fissure between the mitral leaflets is
• Severe concomitant aortic or tricuspid valve disease separated. This technique is not routinely per-
requiring surgery formed by surgeons in the United States and should
176 A. Booke et al.

only be completed at experienced centers [1]. If Guidelines [1]. Figure 17.11 demonstrates a
neither a PMBC repair nor open commissurotomy mitral valve replacement with a bioprosthetic
can be completed, then a mitral valve replacement valved conduit viewed from the left atrium. The
may be considered in rheumatic stenosis. mitral bioprosthetic conduits are manufactured as
As with other cardiac surgeries, a detailed his- a trileaflet valve for structural support.
tory, physical, and a myriad of diagnostic testing
are completed to determine patient’s baseline sta-
tus and operative risk. As with any valve surgery, References
a thorough dental history should be obtained to
rule out a disease process which may put patient 1. Otto CM, Nishimura RA, Bonow RO, Carabello BA,
Erwin JP III, Gentile F. 2020 ACC/AHA Guideline for
at risk for endocarditis postoperatively. Risk the management of patients with valvular heart dis-
stratification for MV repair and MV replacement ease: a report of the American College of Cardiology/
can be calculated on the STS website. Refer to American Heart Association Joint Committee on
Chap. 6, Table 6.3 for a list of categories assessed clinical practice guidelines. J Am Coll Cardiol.
2021;77(4):e25–e197.
with the risk calculator. 2. Fedak PWM, McCarthy PM, Bonow RO. Evolving
concepts and technologies in mitral valve repair.
Mitral Valve Selection Circulation. 2008;117(7):963–74.
Provider and patient must jointly decide between a 3. Gammie JS, Chikwe J, Badhwar V, Thibauld DP,
Vemulapalli S, Thourani VH. Isolated mitral valve
bioprosthetic and mechanical valve conduit in case surgery: The Society of Thoracic Surgeons adult
a valve replacement is warranted. This decision is cardiac surgery database analysis. Ann Thorac Surg.
multifactorial and is based on patient age, life 2018;106(3):716–27.
expectancy, medical compliance, and ability to tol- 4. Watts TMF, Brescia AA, Murray SL, Burn DA,
Wisniewski A, Romano MA, Bolling SF, Michigan
erate long-term systemic anticoagulation. Refer to Mitral Research Group (MMRG). Degenerative mitral
the section on valve selection under surgical man- valve repair restores life expectancy. Ann Thorac Surg.
agement of aortic stenosis for further discussion. 2020;109(3):494–801.
The ACC/AHA guidelines for mitral valve 5. Bonow RO, O’Gara PT, Adams DH, Badhwar V,
Bavaria JE, Elmariah S, et al. 2019 AATS/ACC/
replacement recommend mechanical valves in SCAI/STS expert consensus systems of care docu-
patients <65 years old and tissue valves in ment: operator and institutional recommendations and
patients ≥65 years old [1]. A mechanical valve in requirements for transcatheter mitral valve interven-
the mitral position for mitral stenosis has the tion. J Am Coll Cardiol. 2020;76(1):96–117.
6. Hein M, Schoechlin S, Schulz U, Minners J, Breitbart
highest long-term embolic risk and requires strict P, Lehane C, Neumann F-J, Ruile P. Long-term follow-
therapeutic INR levels postoperatively. Refer to up of hypoattenuated leaflet thickening after trans-
Figs. 11 and 12 for the 2020 AHA/ACC Valve catheter aortic valve replacement. JACC Cardiovasc
Interv. 2022;15(11):1113–22.
7. O'Brien SM, Feng L, He X, Xian Y, Jacobs JP, Badhwar
V, et al. The Society of Thoracic Surgeons 2018 adult
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S, Bauersachs J, Capodanno D, Conradi L, De Bonis
M, De Paulis R, Delgado V, Freemantle N, Gilard M,
Haugaa KH, Jeppsson A, Jüni P, Pierard L, Prendergast
BD, Sádaba JR, Tribouilloy C, Wojakowski W, ESC/
EACTS Scientific Document Group, ESC National
Cardiac Societies. 2021 ESC/EACTS Guidelines for
the management of valvular heart disease: developed
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9. The Society of Thoracic Surgeons. 2022. https://www.
Fig. 17.11 Mitral valve replacement with a bioprosthetic sts.org/resources/risk-calculator.
valve
Tricuspid Valve Disease
18
Anne Booke, Michael Rinaldi, Elisabeth A. Powell,
Larry Watts, and Richard Musialowski

Tricuspid Insufficiency/ remodeling to maintain cardiac output [2]. This

Regurgitation (TI/TR) cycle progresses until clinical signs of right heart
failure develop (see Chap. 22). Severe, refractory
Etiology TR is associated with hepatic and renal failure
due to venous hypertension.
TR is categorized as primary or secondary.
Secondary is more common, occurring in >90%
of patients with TR (Table 18.1). At least 70% of Symptoms
adults have some degree of TR [1]. Most primary
TR is related to implantable devices. Functional Symptoms of TR are due to two pathologic
TR is secondary to dilation of the RA/RV annu- mechanisms: pulmonary congestion and central
lus with leaflet tethering and is associated with venous congestion. Patients develop fatigue,
pulmonary hypertension, atrial fibrillation, car- exertional dyspnea, and also symptoms associ-
diomyopathy, and mitral disease. Functional TR ated with right heart failure including orthopnea,
is associated with pulmonary hypertension, RV abdominal bloating or right upper abdominal dis-
dilation, RV infarction, or cardiomyopathy. comfort, PND, and peripheral edema.
Importantly, TR is an independent predictor of Physical exam findings with TR include
mortality. systolic murmur that increases in intensity
In early TR, right atrial dilation occurs, result-
ing in annular dilatation. This process causes Table 18.1 Etiology of tricuspid regurgitation
reduction in leaflet coaptation and with progres- Secondary (normal
sion of TR, adaptive RV dilation occurs with RV Primary (abnormal leaflets) leaflets)
Rheumatic disease LV dysfunction
Congenital heart disease- RV infarction
A. Booke · M. Rinaldi · L. Watts · R. Musialowski Ebstein’s anomaly
Sanger Heart and Vascular Institute, Atrium Health, Myxomatous changes Pulmonary
Charlotte, NC, USA hypertension
e-mail: [email protected]; Carcinoid heart disease Infiltrative disease of
[email protected]; the RV
[email protected]; Iatrogenic - device entrapment, Atrial annular dilation
[email protected] biopsy injury
Radiation Left sided valve
E. A. Powell (*)
disease
Banner University Medical Center, Tucson, AZ, USA
e-mail: [email protected] Chronic RV pacing

© The Author(s), under exclusive license to Springer Nature Switzerland AG 2023 177
R. Musialowski, K. Allshouse (eds.), Cardiovascular Manual for the Advanced Practice Provider,
https://doi.org/10.1007/978-3-031-35819-7_18
178 A. Booke et al.

with inspiration, prominent JVD, peripheral Trace to mild degrees of TR are commonly
edema, hepatomegaly, ascites, and a third detected on TTE in patients with normal valves
heart sound that also increases with inspira- and are of no physiological consequence [3].
tion (RV S3).

Management
Evaluation
Medical therapy is limited and attention should
ECG. Usually non-diagnostic, although may see be focused on reversing any underlying causes of
signs of RA or RV enlargement, bizarre RBBB TR. Management of heart failure is the first
pattern, evidence of prior inferior MI, or atrial approach to management of TR, with the use of
fibrillation [3]. diuretics to treat volume overload and medical
Imaging. The etiology and severity of TR are therapy for patients who have pulmonary arterial
assessed by TTE (Fig. 18.1). When indicated, hypertension (PAH), particularly WHO type II
TEE, MRI, or CT scan may be used to provide (see Chap. 22). Patient with volume overload and
additional information about the tricuspid valve hepatic congestion are more responsive to torse-
and RV function. Particular attention should be mide over furosemide. Use of loop diuretics can
paid to TR grade/regurgitant jet, valve morphol- be limited as RV function worsens or in those
ogy (annular dimension, leaflet coaptation/tether- with low output syndrome. Patients with reduced
ing), enlargement of RA/RV/IVC to properly LVEF contributing to TR should be initiated on
stage TR, pulmonary systolic pressure, and GDMT to offload the LV. In patients with TR sec-
degree of hepatic vein reversal [4]. ondary to annular dilation from atrial fibrillation

Fig. 18.1 The left panel shows a closed tricuspid valve with defect and annular dilatation. The right panel shows a
green arrow indicating severe secondary tricuspid regurgitation
18 Tricuspid Valve Disease 179

it is beneficial to restore sinus rhythm. There are the primary cause for TR stems from left-sided
limited options for patients who have advanced heart disease, the number one indication for sur-
TR with end-stage heart failure and low cardiac gical intervention is the presence of severe TR at
output [3, 4]. the time of a left-sided valve operation [3]. When
Timing of intervention upon the tricuspid possible, a repair should be attempted prior to
valve is tricky as the disease can progress quickly, replacement. Repairs are preferred to replace-
is often associated with concomitant pulmonary ment in TR as they do not require long-term anti-
hypertension or permanent atrial fibrillation, and coagulation, have greater durability, and are
also a poor prognosis. resistant to endocarditis. Repair of the tricuspid
Surgical treatment is performed for select valve usually only requires an annuloplasty ring
patients with valvular disease. Surgical interven- or band to decrease annular dilation, create sup-
tion should be completed with the presence of port, and improve coaptation of the leaflets. A
moderate to severe TR at the time of a left-sided TVr with an annuloplasty ring is demonstrated in
valve operation. Once the left-sided valve lesion Fig. 18.2.
is corrected and there is reduction of the right Replacement of the tricuspid valve is reason-
ventricular afterload, TR may not improve. If the able when the valve is unrepairable or in select
TV is not intervened upon at the time of the left- secondary forms of TR. Valves should undergo
sided valve surgery, there is a 25% chance that replacement when the TR is a primary defect in
there is progression of the TR if certain risk fac- the valve leaflet such as with injury from device
tors are present [3]. These risk factors include leads, endocardial biopsy, trauma, or in infec-
dilated annulus >4.0 cm, history of right-sided tious endocarditis. TV replacement should also
HF, and atrial fibrillation [3]. If the TR is not cor- be completed if a TV repair has failed. A TVR
rected at the time of the initial operation, and with a bioprosthetic valve is demonstrated in
does not improve postoperatively, reoperation for Fig. 18.3 Guidelines for surgical intervention of
severe isolated TR is associated with a periopera- TR are outlined in Fig. 10 in the 2020 AHA/ACC
tive mortality of 10–25% [3]. Even in cases Valve Guidelines [3].
where only mild to moderate secondary TR Isolated TR intervention is rare and periopera-
exists, tricuspid valve (TV) intervention should tive mortality risk is considered high. Intervention
still be considered. is more dependent on the presence of right-sided
Transcatheter tricuspid valve interventions are heart failure, progressive RV dilation, and dys-
emerging as an alternative for highly symptom- function. According to the ACC/AHA guidelines,
atic patients who are felt to be too high risk for isolated TV surgery is considered reasonable in
conventional open-heart surgery and research is
ongoing in determining effectiveness. There are
currently no guidelines addressing transcatheter
tricuspid valve therapies. Novel transcatheter
therapies are evolving and include “leafletplasty”
with clip therapy, valve replacement, percutane-
ous repair, and annuloplasty.

urgical Management of Tricuspid

S
Regurgitation

Surgical treatment of moderate to severe TR can

be accomplished by either tricuspid valve repair Fig. 18.2 Tricuspid valve repair with placement of an
(TVr) or tricuspid valve replacement (TVR). As annuloplasty ring
180 A. Booke et al.

catheterization to assess for coronary artery dis-

ease. If cardiac disease is present, CABG should
be completed at the time of the valve surgery.
The STS does not include tricuspid valve
repair/replacement as part of their STS risk cal-
culator. However, patient statistics and outcomes
may be viewed in the database to aid in the sur-
geon’s justification for risk assessment. In the
cases involving tricuspid valve surgery, a pro-
vider must account for physical assessment,
frailty, clinical judgment, and multidisciplinary
Fig. 18.3 Tricuspid valve replacement with a biopros- team discussions to determine if patient is an
thetic valve appropriate surgical candidate.

patients with severe primary TR if symptomatic

or severe secondary TR which has responded Valve Selection
poorly to medical therapy [3]. Surgery is also
deemed reasonable in asymptomatic patients With tricuspid regurgitation, valve repair is the
with severe primary TR and progressive RV dila- preferred surgical approach. In tricuspid valve
tion or systolic dysfunction [3]. repair, an annuloplasty ring is placed to correct
The timing of surgical intervention is prefer- dilation, improve coaptation, and provide support
rable before the onset of significant RV dys- to the valvular apparatus. If repair is not feasible,
function or end-organ damage. Once these are tricuspid valve replacement is warranted. The
present, surgery has a significantly increased surgical decision-making regarding valve selec-
risk with mortality rates of 8–20% and the addition is complex, multifactorial, and based on
tional risk of RV failure [3]. In specific cases patient age, life expectancy, medical compliance,
where patients develop acute severe primary and ability to tolerate long-term anticoagulation.
TR, TV surgery should be considered urgent Refer to the section on valve selection under sur-
and completed prior to the onset of RV dysfunc- gical management of aortic insufficiency in
tion [3]. Acute TR may develop from injury to Chap. 16 for further discussion.
the valve apparatus, and survival is directly Currently, there is no superiority between bio-
related to RV function. prosthetic and mechanical valves in TV replace-
ment [5]. This may change as transcatheter TVR
modalities evolve and percutaneous valve-in-
Preoperative Assessment valve replacements gain popularity.
and Surgical Risk

Preoperative assessment for tricuspid valve sur- Tricuspid Stenosis

gery begins with a history, physical, and baseline
diagnostic testing. Dental evaluation is recom- Tricuspid stenosis is most frequently rheumatic in
mended preoperatively to decrease the risk of origin and often coexists with TR. Given that TS
endocarditis following the placement of a pros- is primarily rheumatic in origin, it is often associ-
thetic valve. Refer to previous chapters regarding ated with rheumatic MS. Rare causes of tricuspid
preoperative assessment for further discussion stenosis are congenital, carcinoid, drug induced,
and Chap. 6: Tables 6.1 and 6.2. endocarditis, and right atrial tumors. As diastolic
Along with the standard preoperative testing pressures rise, systemic venous congestion occurs,
and transesophageal echo (TEE), all patient’s resulting in right-sided heart failure. Cardiac out-
undergoing cardiac surgery should have a cardiac put falls and fails to rise with exertion.
18 Tricuspid Valve Disease 181

Symptoms Refer to the chapter on aortic stenosis for further

discussion on valve selection.
Patients will experience exertional dyspnea that During tricuspid valve surgery, there are mul-
is out of proportion to the hepatomegaly, ascites, tiple areas to be mindful of during suture place-
and edema they experience [6]. Severe TS is ment. The right coronary artery (RCA) lies in the
associated with hepatic congestion resulting in AV groove with close approximation to the pos-
cirrhosis, jaundice, malnutrition, anasarca, and terior leaflet of the tricuspid valve. Placement of
ascites. valve sutures may result in functional stenosis or
direct suturing of the coronary artery [5]. Care
should also be taken at the level of the AV node.
Evaluation The AV node lies along the anteroseptal commis-
sure at the base of the septal leaflet. Injuring the
Often the murmur of TS is missed given that usu- AV node during repair or replacement with valve
ally there is concomitant MS. If the provider can stitches may result in AV nodal blockade [5].
auscultate the TS murmur, one might hear an Indication and timing of surgical intervention
opening snap with a diastolic murmur along the for TS is dependent on severity of disease and
left lower sternal border that worsens with inspi- timing of concomitant left-sided valve interven-
ration [6]. tions. Isolated tricuspid valve disease is rare.
TTE will provide the most useful information, Rheumatic disease is the primary cause of TS and
although tricuspid stenosis is most often over- occurs concurrent with rheumatic mitral valve
looked. One should evaluate valve anatomy and disease. Once surgical intervention of the mitral
assess the subvalvular apparatus. Stenosis is sig- valve is undertaken, the tricuspid valve is simul-
nificant when the mean transvalvular gradient is taneously addressed. Both the ACC/AHA guide-
≥5 mmHg [2]. lines and the European Society of Cardiology
(ESC) recommend tricuspid valve surgery on (1)
patients with severe TS at the time of operation
Management/Intervention for left-sided valves and (2) on isolated TV with
symptomatic, severe TS [5].
Patients with TS also often have TR and exhibit Overall, tricuspid stenosis is rare in the given
marked systemic venous congestion. Diuretics population and is infrequently seen as an isolated
are the mainstay of management but have limited procedure in the operating room.
long-term efficacy [6]. Intervention is usually
performed concomitantly with left-sided valve
disease in symptomatic patients despite optimal References
medical therapy.
Percutaneous tricuspid balloon valvuloplasty 1. Zoghabi WA, et al. Recommendations for evaluation
of the severity of native valvular regurgitation with
frequently induces significant tricuspid insuffi- two-dimensional and Doppler echocardiography. J
ciency and long-term results are lacking [2]. Am Soc Echocardiogr. 2003;16(7):777–802.
2. Vahanian A, Beyersdorf F, Praz F, Milojevic M,
Baldus S, Bauersachs J, Capodanno D, Conradi L,
De Bonis M, De Paulis R, Delgado V, Freemantle N,
urgical Management of Tricuspid
S Gilard M, Haugaa KH, Jeppsson A, Jüni P, Pierard
Stenosis L, Prendergast BD, Sádaba JR, Tribouilloy C,
Wojakowski W, ESC/EACTS Scientific Document
Tricuspid valve replacement is the surgical treat- Group, ESC National Cardiac Societies. 2021 ESC/
EACTS Guidelines for the management of valvular
ment of choice for tricuspid stenosis (TS). Given heart disease: developed by the Task Force for the
the calcific nature of the leaflets in stenotic dis- management of valvular heart disease of the European
ease, the native leaflets are not amenable to repair. Society of Cardiology (ESC) and the European
182 A. Booke et al.

Association for Cardio-Thoracic Surgery (EACTS). recurrence of disease. JACC Cardiovasc Imaging.
Eur Heart J. 2022;43(7):561–632. 2019;12(4):605–21. https://doi.org/10.1016/j.
3. Otto CM, Nishimura RA, Bonow RO, Carabello BA, jcmg.2018.11.034.
Erwin JP III, Gentile F. 2020 ACC/AHA guideline for 5. Cevasco M, Shekar PS. Surgical management
the management of patients with valvular heart dis- of tricuspid stenosis. Ann Cardiothorac Surg.
ease: a report of the American College of Cardiology/ 2017;6(3):275–82.
American Heart Association Joint Committee on 6. Loscalzo J, Fauci A, et al. Harrison’s principles of
clinical practice guidelines. J Am Coll Cardiol. internal medicine. 21st. ed, Volume 1 and Volume 2.
2021;77(4):e25–e197. New York: McGraw Hill; 2022.
4. Taramassa M, et al. Tricuspid regurgitation, predict-
ing the need for intervention, procedural success, and
Infective Endocarditis
19
Allen Stephens, Todd McVeigh, Cary Ward,
Elisabeth A. Powell, and Larry Watts

Symptoms Table 19.1 Symptoms in infective endocarditis

Symptom Patients affected (%)
Symptoms of infective endocarditis are diverse Fever 80–95
and often nonspecific. The most common pre- Chills 40–70
senting symptoms are fever, chills, weakness, Weakness 40–50
and malaise. Patients may also present with dys- Malaise 20–40
pnea which can be indicative of a severe lesion Sweats 20–40
Anorexia 20–40
causing onset of heart failure. See Table 19.1 for
Headache 20–40
presenting symptoms [1]. Dyspnea 20–40
The diagnosis of IE based upon physical Cough 20–30
examination findings alone can be difficult and is Weight loss 20–30
often missed due to the variability of disease pre- Myalgia/arthralgia 10–30
sentation [2]. Patients can present with nonspe- Stroke 10–20
cific primary symptoms over a course of weeks to Confusion/delirium 10–20
Nausea/vomiting 10–20
months [3]. IE should be on the differential diag-
Edema 5–15
nosis in patients presenting with sepsis without
Chest pain 5–15
an obvious cause, as well as in patients who pres- Abdominal pain 5–15
ent with a fever of unknown origin and have IE Hemoptysis 5–10
Back pain 5–10
Adapted from Braunwald’s Heart Disease Textbook (10th
Edition) Page 1527
A. Stephens (*) · T. McVeigh · C. Ward
Duke University Health System, Durham, NC, USA
e-mail: [email protected];
[email protected]; [email protected] risk factors (see Table 19.3). Acute presentations
E. A. Powell of IE can progress rapidly, as patients can present
Banner University Medical Center, Tucson, AZ, USA with sudden onset of heart failure, stroke, sys-
e-mail: [email protected]
temic or pulmonary embolization, severe sepsis
L. Watts with fevers, rigors, or septic shock.
Atrium Health/Sanger Heart and Vascular Institute,
Charlotte, NC, USA
e-mail: [email protected]

© The Author(s), under exclusive license to Springer Nature Switzerland AG 2023 183
R. Musialowski, K. Allshouse (eds.), Cardiovascular Manual for the Advanced Practice Provider,
https://doi.org/10.1007/978-3-031-35819-7_19
184 A. Stephens et al.

Physical Exam

The most common physical examination findings

are shown in Table 19.2 with fever (present in
80–90% of patients) and a cardiac murmur (pres-
ent in 75–85% of patients) being the two most
prevalent. Although IE is commonly associated
with a heart murmur (typically due to valvular
regurgitation), new murmurs are present in less
than 50% of cases [4]. A worsening of a pre-
existing heart murmur accounts for the remainder
of murmurs found on physical exam in IE. A cen-
tral neurologic abnormality, such as focal deficits Fig. 19.1 Ischemic digit from emboli (red), Osler’s node
consistent with a cerebrovascular accident, can (black), and Janeway spots (yellow) in a patient with
MSSA endocarditis
be identified in 20–40% of IE patients [5]. An
abdominal exam can elicit nonspecific findings
of tenderness, which can be suggestive of splenic untreated IE. Approximately 75% of patients
embolization and infarction when in the left with IE are now diagnosed within 30 days of the
upper quadrant [1]. The spleen was found to be onset of infection, so these long-term findings are
the second-most common site of septic emboliza- less commonly seen [2].
tion after the brain in one study [1]. The diagnosis of IE cannot be excluded on
The classic diagnostic findings of Janeway history and physical exam findings alone. Given
lesions (painless hemorrhagic macules on the the variety of patient presentations and varying
soles and palms), Osler nodes (painful, erythem- physical exam findings, misdiagnosis and delays
atous nodular lesions on the pads of the fingers in diagnosis are common. These delays can post-
and toes), and Roth spots (retinal hemorrhages) pone definitive management and contribute to
are vascular and immunologic phenomena increased mortality due to progressive structural
(Fig. 19.1). Acute IE can often evolve too quickly heart damage that can eventually become irrepa-
for the development of these phenomena [6]. rable [2].
These classically described findings are more
characteristic of later stages of subacute,
Risk Factors

Table 19.2 Physical findings in infective endocarditis The incidence of IE is influenced by a variety of
Patients affected risk factors, both cardiac and non-cardiac
Physical Findings (%) (Table 19.3). In less developed countries, rheu-
Fever 80–90 matic degenerative heart disease remains the
Heart murmur 75–85 most common risk factor. In developed countries,
New murmur 10–50
the most common risk factors include intrinsic
Changing murmur 5–20
Central neurologic abnormality 20–40 cardiac factors (history of prior infective endo-
Splenomegaly 10–40 carditis, congenital heart disease), followed by
Petechiae/conjunctival 10–40 pre-existing valve disease, such as mitral or aor-
hemorrhage tic regurgitation, and the presence of implanted
Splinter hemorrhages 5–15 devices. Non-cardiac risk factors include IV drug
Janeway lesions 5–10
use, immunocompromising conditions, such as
Osler nodes 3–10
Retinal lesion or Roth spot 2–10
cancer or diabetes, and recent dental or surgical
procedures [7].
19 Infective Endocarditis 185

Table 19.3 Endocarditis risk factors Table 19.4 HACEK organisms

Age >60 years old Hemophilic parainfluenzae
IV drug use Aggregatibacter actinomycetemcomitans
History of prior endocarditis Cardiobacterium hominis
Poor dentition or recent dental procedure Eikenella corrodens
Presence of intracardiac device or prosthetic valve Kingella kingae
History of valvular heart disease (rheumatic disease,
congenital heart disease such as aortic stenosis or
bicuspid aortic valve) Table 19.4) are fastidious gram-negative bacilli
Indwelling intravenous catheter that are difficult to grow in culture and are less
Immunosuppression common causes of subacute IE. If these organ-
Hemodialysis patients
isms are considered, discussion with the ID spe-
cialist and microbiology laboratory is important
for appropriate testing to be performed. Fungi are
Pathology/Description extremely rare as cause of IE. Unfortunately,
some patients with endocarditis can have nega-
Infective endocarditis occurs when an underlying tive blood cultures, most commonly because of
valvular or nonvalvular structural abnormality recent antimicrobial exposure [1].
results in turbulent blood flow leading to endo-
thelial injury [1]. This injury results in an inflam-
matory response releasing cytokines and tissue Imaging
factors causing platelets and thrombin to adhere
to the sub endothelium. This ultimately forms a Echocardiography is a key modality in the diag-
microthrombotic lesion and bacteria in the blood nosis of endocarditis and is a major component of
stream then adhere to the microthrombus. This the Duke criteria (see below). Traditional trans-
colonization leads to additional bacterial replica- thoracic echocardiography (TTE) has a sensitiv-
tion and formation of an infective vegetation. ity for vegetation detection between 50–60%
These vegetations have high bacterial density and while transesophageal echocardiography (TEE)
are poorly infiltrated by neutrophils, allowing has a sensitivity close to 90%. Both modalities
them to easily grow and fragment into the blood have specificities close to 95% [5]. TEE has
stream [5]. increased sensitivity because it circumvents
impediments such as body habitus, pulmonary
disease, and other acoustic interference between
Microbiology the chest wall and heart [1]. With improved spa-
tial resolution in TTE technology, some newer
Positive blood cultures are a hallmark of endo- studies have shown sensitivity for TTE as high as
carditis. Gram positive bacteria account for 80% 89% (Fig. 19.6) [1]. Other imaging studies such
of cases of native infective endocarditis. This as cardiac CT (Fig. 19.2) can also be useful in the
includes Staphylococcus aureus (35–40%), strep- diagnosis of perivalvular extension and embolic
tococci (30–40%), and enterococci (10%) complications. Echocardiography demonstrates
(Table 19.6). Coagulase negative staphylococci the hemodynamic significance of the leaflet
are more common in prosthetic-valve infective destruction and regurgitant lesions in real time
endocarditis [5]. The HACEK organisms (see (Figs. 19.3 and 19.7.
186 A. Stephens et al.

imity to the AV node and proximal intraventricu-

lar conduction system. Specifically, a lesion
involving the right and non-coronary cusps is at
risk of impacting the conduction system. A less
common presentation is a perivalvular extension
or vegetation embolization which affects coro-
nary artery patency resulting in ischemic ECG
changes (ST depression, T wave inversion, or ST
elevation) [1].

Diagnostic Criteria

The Duke Criteria for endocarditis were created

in 1994 to establish the definite or possible diag-
nosis of IE as well as reject the diagnosis.
Fig. 19.2 Cardiac CT showing vegetation of infective Multiple clinical trials have reported sensitivity
endocarditis of the native aortic valve (red arrow) of Duke Criteria to be around 80% with specific-
ity and negative predictive value of approxi-
mately 90% [1]. The Duke criteria incorporate
clinical findings, microbiologic analysis, and
imaging results. Criteria are weighted as major or
minor (see Table 19.5).

Table 19.5 Duke major and minor criteria for IE

Major criteria Minor criteria
Blood culture positivity Fever >38 °C
with an organism
associated with IE on
two separate blood
cultures sets (Tables
19.4 and 19.6)
Evidence of endocardial Predisposing heart condition
involvement seen on (implanted prosthetic
imaging to include material, recent or
mobile vegetation, unrepaired CHD, previous
abscess, and/or IE), or IV drug use
Fig. 19.3 Destruction of the aortic valve leads to severe dehiscence of a
eccentric insufficiency (red arrow) seen on prosthetic valve
echocardiography Vascular phenomena and
evidence of embolic disease
(Janeway spots), Intercranial
hemorrhage
EKG Microbiological evidence
not meeting major criteria
(organism not associated
12-lead EKG is less useful in diagnosis of IE and
with IE, single positive
is usually associated with nonspecific findings. blood culture)
Perivalvular extension of infection at the aortic Immunologic phenomena
root can cause new atrioventricular block (AVB) Rheumatoid F, Osler’s
or bundle branch block (BBB) because of prox- nodes, glomerulonephritis
19 Infective Endocarditis 187

Definite diagnosis requires (a) two major criteria, Antimicrobial Therapy

(b) one major with three minor, or (c) five
minor criteria. The American Heart Association, American
Possible diagnosis requires (a) one major and one College of Cardiology, and American Association
minor or (b) three minor criteria. for Thoracic Surgery have each published guide-
Diagnosis is rejected with (a) no clinical criteria lines on the management of IE. While these
are met or (b) complete resolution of ID syn- guidelines are generally concordant, there are
drome or absence of anatomic evidence for IE minor differences in their recommendations
on antibiotic therapy for no more than 4 days about antimicrobial therapy [2]. Because there
or (c) an alternative diagnosis explains the are continuous changes in antimicrobial sensitiv-
patient presentation [8]. ity over time, as well as regional and site-specific
differences in antimicrobial susceptibility pro-
files, consultation with infectious disease is
Management imperative for treatment [2]. The infectious dis-
ease team is also essential as resistance to many
In general, randomized controlled trials to guide antibiotics is rising and has become one of the
IE are minimal, and none of the recommenda- greatest threats to modern health care [8].
tions in international guidelines on IE are The primary goal of antibiotic treatment is to
backed by Level A evidence [8]. The manage- stabilize vegetations and eventually eradicate
ment of infective endocarditis (IE) includes infections [6]. The penetration of antibiotics is a
prompt diagnosis, treatment with antimicrobial significant challenge in the treatment of IE
therapy, and in some cases of complicated IE, because cardiac vegetations, which are composed
surgical management [9]. Given its ability to of fibrin and platelets, pose a considerable
cause complications both at the cardiac site and mechanical barrier between the antibiotic and the
at extracardiac locations, management of IE embedded targeted microorganisms [6]. These
requires a team approach. In all cases, decisions vegetations create a protective micro-environment
on intervention should be multifactorial and that is poorly accessible to neutrophils and host
include a discussion involving multidisciplinary defense molecules. Vegetations are loaded with
teams including cardiothoracic surgery, cardiol- bacteria at very high densities [5].
ogy, and infectious disease. If a patient has In treating IE, determination of the causative
endured an embolic stroke from their IE, neurol- pathogen is of prime importance, allowing clini-
ogy should be consulted to make recommenda- cians to narrow and target therapy specifically to
tions regarding the timing of surgery. Stroke is the pathogen (Table 19.6) [4]. Empiric antibiotic
an independent risk factor for postoperative therapy should be initiated and continued after
death, especially if the stroke is hemorrhagic. blood cultures (ideally 3 sets) are obtained [2].
Consultation with addiction medicine and dis-
cussion with an ethics team should also be con- Table 19.6 Common organism and antibiotic regimens
sidered in cases regarding IV drug abuse for IE
associated IE, especially for recurrent IE. These Example of common
cases are complicated with longer hospital Common causes of IE antibiotic regimen
stays, higher readmission rates, medical non- Staphylococcus aureus
compliance, and re-infection from continued IV 35–40%
drug abuse. Addiction medicine therapy has MRSA Daptomycin or vancomycin
MSSA Anti-staphylococcal PCN
shown to reduce mortality and morbidity rates (ex: Nafcillin)
in this patient population postoperatively [10]. Streptococci 30–40% Gentamicin plus penicillin or
It is best practice for patients with IE to be man- ceftriaxone
aged in a medical center that offers these differ- Enterococci 10% Ampicillin plus gentamicin
ent specialists [5]. or ceftriaxone
188 A. Stephens et al.

Once these cultures have been obtained, therapy mycin plus ceftriaxone is a reasonable choice for
should be started very quickly [8]. The choice of empirical therapy to cover likely pathogens while
empiric therapy should take into consideration blood cultures are pending [5]. It should be noted
the most likely pathogens. Gram positive bacteria that recommendations for antimicrobial therapy
account for approximately 80% of cases of native for IE are based almost entirely on observational
valve IE. These bacteria include methicillin- studies rather than on randomized controlled tri-
sensitive Staphylococcus Aureus (MSSA) and als [5]. Common antibiotic regimens for specific
methicillin-resistant Staphylococcus Aureus organisms are seen in Table 19.6.
(MRSA) (35–40% of cases), streptococci (30– As mentioned, S. aureus is the most common
40% of cases), and enterococci (10% of cases). S. cause of IE (both native valve and prosthetic
aureus is the leading cause of IE (both native and valve). The rates of S. aureus IE have increased
prosthetic valve) in the United States. More rare over the years and are primarily a consequence of
species include other gram-positive pathogens, healthcare contact (intravascular catheters, surgi-
fungi, polymicrobial infection, and finally gram- cal wounds, indwelling prosthetic devices, and
negative bacilli [5]. Though fungal IE is rare, it hemodialysis) [6]. Antibiotic treatment decisions
has well-recognized associated risk factors for S. aureus IE hinge on the presence or absence
including IV drug use, immunocompromised of antibiotic resistance [4]. Single antibiotic ther-
state, and indwelling devices [6]. After initial apy is usually enough for native valve
blood cultures have been obtained and empiric IE. However, for S. aureus-infected prosthetic
antibiotic therapy started, adjustments in antimi- valves, combination therapy from multiple anti-
crobial selection depend on the blood culture iso- biotic classes is recommended [4]. Daptomycin
late and its antimicrobial susceptibility [5]. The or vancomycin monotherapy is recommended for
expectation is that this empirical therapy will be treatment of native-valve IE caused by MRSA. An
revised once the susceptibility results are anti-staphylococcal penicillin (nafcillin) is the
obtained, as optimal treatment of IE is based on drug of choice for IE caused by MSSA, as these
antimicrobial therapy that is effective against the agents have shown higher cure rates for MSSA
specific infective organism identified [6]. than vancomycin [7]. Despite early diagnosis and
Rarely, IE can occur without associated posi- appropriate therapy, IE after S. aureus bacteremia
tive blood cultures. Most often this is caused by is frequently associated with disabling and life-
recent administration of antibiotics prior to blood threatening sequelae [2].
culture collection or by organisms that grow For streptococcal IE, treatment regimens vary
poorly or not at all in standard blood culture widely based on the microorganism. Two com-
media [5]. Empiric treatment of patients with cul- mon regimens for streptococcal IE are penicillin
ture negative IE should cover both gram positive and gentamicin or ceftriaxone and gentamicin.
and gram-negative organisms, and infectious dis- Single antibiotic therapy (penicillin, ceftriaxone,
ease involvement is imperative in these cases. or vancomycin) alone is also a common treat-
PCR assays are now available for a variety of ment strategy for streptococcal IE.
these less-common microorganisms. Karius For enterococcal IE, combination therapy is
Testing™ can also identify pathogen DNA in recommended. Two common combination regi-
plasma even when blood cultures are negative, mens involve ampicillin and ceftriaxone or ampi-
which can lead to more prompt antibiotic cillin and gentamicin. The use of single-drug vs
therapy. combination drug therapy can vary according to
Because pathogen-specific recommendations the specific pathogen, potential presence of anti-
for antibiotics are often changing and vary geo- biotic resistance, and whether the infection
graphically, organism-specific treatment regi- involves a native or prosthetic valve [4].
mens are outlined in consensus guidelines [9]. In Serial blood cultures should be obtained to
general, for patients with native valve IE, vanco- confirm clearance of bacteria with therapy. While
19 Infective Endocarditis 189

undergoing treatment, these cultures are typically Surgical Management

obtained every 24–48 h until bloodstream infec-
tion is cleared [6]. Antibiotics should generally In many patients with IE, despite antimicrobial
be continued for 4–6 weeks after blood cultures treatment, surgery is needed for effective treat-
convert to negative [5]. Antimicrobial therapy ment. Surgical treatment is typically undertaken
duration must be sufficient to ensure complete in 40–50% of patients with IE [12]. Infection
eradication of microorganisms within vegeta- causes destructive mobile vegetations on the
tions [6]. The duration of antibiotics for native- valve leaflets (Figs. 19.4, and 19.5). These vege-
valve endocarditis typically ranges from tations prevent hemostatic coaptation of the leaf-
4–6 weeks. Factors that compel the extended lets and can produce detrimental tears or
6-week antibiotic course include: left-sided veg- perforations within the valve leaflet (Figs. 19.2,
etations (which tend to have higher bacterial den- 19.3, 19.6, and 19.7). These changes can lead to
sities), the presence of drug-resistant organisms, acute regurgitation requiring urgent surgical
and the use of slowly bactericidal antibiotics such intervention. Paravalvular infection may also
as vancomycin [9]. occur including annular or aortic abscesses which
Most patients with IE become afebrile 3 to are considered life threatening and has a ≥40%
5 days after initiation of appropriate antimicro- mortality rate and increased risk of heart block
bial therapy. Patients with S. aureus IE may (Fig. 19.8) [10]. The main goal of surgical inter-
respond somewhat more slowly, remaining
febrile for up to 5–7 days after initiation of ther-
apy [11]. Patients with right-sided IE and septic
pulmonary emboli may remain febrile for an
even longer duration of time, given the recurrent
embolic events.
Careful serial examinations should be per-
formed to evaluate for heart failure (new or wors-
ening), emboli, or other complications. Patients
who develop new complications while on appro-
priate antimicrobial therapy should have an
urgent repeat echocardiogram [11].
The first year after implantation is a vulnera-
ble period for prosthetic valve endocarditis
because of a greater exposure to healthcare con- Fig. 19.4 Mitral valve endocarditis with multiple
tact along with incomplete endothelialization of vegetations
the prosthetic valve early after implantation.
Mortality with antibiotics alone with the pres-
ence of a prosthetic valve is high (26–75%) [3].
There are some indications for antibiotic therapy
alone in prosthetic valve IE, including hemody-
namically stable patients, improvement on antibi-
otic therapy, early diagnosis of prosthetic valve
IE, and right-sided endocarditis [3]. Treatment of
prosthetic valve IE is typically more difficult than
treatment of native-valve endocarditis and often
requires surgical replacement of the prosthesis in
addition to antibiotic therapy. The typical dura-
tion of therapy in prosthetic valve IE is the full
6 weeks. Fig. 19.5 Mitral valve endocarditis with large vegetation
190 A. Stephens et al.

Fig. 19.6 Vegetation on the posterior of the mitral valve

(red arrow)

Fig. 19.8 Aortic valve endocarditis complicated by

annular abscess. Vegetation in the ascending aorta (red
arrow) in communication with leaflet and hypodense
abscess formation in the aortic annulus (yellow arrow).
Management requires urgent surgical intervention

able, infection is unable to be effectively

debrided, or an abscess is present, valve replace-
ment is warranted. Valve selection is challenging
in IE with the decision between bioprosthetic and
mechanical valve being critical. Prosthetic valves
are at risk for reinfection if active infection per-
sists. However, in the setting of IE secondary to
IVDU, medical compliance is questionable and
mechanical valve placement is not advised. Refer
to Chap. 16 on aortic stenosis for further discus-
sion on valve selection. Homograft or freestyle
aortic valves are utilized when the endocarditis
involves an aortic root abscess and root extrac-
tion is warranted. In patients with relapsing pros-
thetic valve endocarditis after a full course
antibiotic therapy, the prosthetic valve is pre-
Fig. 19.7 Severe mitral regurgitation due to destruction sumed to be the source and should be removed
of the valve leaflet by vegetation
[10].
The timing of valve surgery is not well defined
vention is to remove all damaged and infected tis- and is a highly individualized decision that is best
sue by debridement and restore valve integrity. If made by an experienced multidisciplinary team
salvageable, valve repair is always preferred over [14]. The timing of surgery, criteria for poten-
replacement to avoid placement of prosthetic tially delaying surgery, and predictors of surgical
material into an infected space. This is especially mortality and poor outcomes need to be better
important with right-sided endocarditis associ- defined. However, intervention is recommended
ated with IV drug users (IVDU) as repair is asso- during the initial hospitalization and prior to the
ciated with better late survival and longer freedom completion of the recommended course of antibi-
from recurrent IE [13]. If the valve is unrepair- otics when the below listed indications for early
19 Infective Endocarditis 191

Table 19.7 Indications for early intervention valve sur- length), highly mobile, and located on the mitral
gery for the treatment of IE
valve [12]. Emboli most often involve major arte-
• Patients who present with valve dysfunction resulting rial beds, including the brain, lungs, coronary
in symptoms of HF
arteries, spleen, bowel, and extremities. Up to
• Patients with left-sided IE caused by S. aureus, a
fungal organism, or another highly resistant organism 65% of embolic events involve the CNS, and
• Patients with IE complicated by heart block, annular >90% of CNS emboli lodge in the distribution of
or aortic abscess, or destructive penetrating lesions the middle cerebral artery [16]. The rate of
• Patients with IE and evidence of persistent infection as embolic events decreases dramatically during
manifested by persistent bacteremia or fevers lasting
>5 days after initiation of antimicrobial therapy
and after the first 2–3 weeks of successful antibi-
• For patients with IE and an implanted cardiac otic therapy [16]. In patients with IE and evi-
electronic device, complete removal of the pacemaker, dence of CVA, regardless of the indications for
or defibrillator system is indicated anticoagulation, it is reasonable to temporarily
• Patients with prosthetic valve endocarditis and discontinue anticoagulation [15]. This is because
relapsing infection (defined as bacteremia recurrence
after antibiotic course completion and negative blood anticoagulation therapy may increase the risk of
culture results) an embolic infarct becoming hemorrhagic. Even
• Patients with IE present with recurrent emboli and in most patients with prosthetic valves who expe-
persistent vegetations despite appropriate antibiotic rience a CNS embolic event, all anticoagulation
therapy
therapy should be held for at least 2 weeks. This
Adapted from the American College of Cardiology/ time should allow for thrombus organization and
American Heart Association 2020 Guideline for the
Management of Valvular Heart Disease help to prevent acute hemorrhagic conversion of
embolic lesions [16]. Most guidelines do agree
on delaying valve surgery for at least 4 weeks in
surgery are present (see Table 19.7). In this popu- patients with large embolic CNS lesions or intra-
lation, early intervention has shown improved cranial hemorrhage [14]. Other reasonable rea-
outcomes and decreased mortality [10]. sons to delay early surgery are very high operative
Heart failure caused by valvular regurgitation risk or major neurologic impairment [17].
or obstruction is the most common indication for Indications for surgery in right-sided native
surgery. Outcomes for IE have historically been valve endocarditis differ and include very large
dire without surgery once the patient has devel- vegetations (>20 mm in diameter), recurrent sep-
oped refractory pulmonary edema or cardiogenic tic pulmonary emboli, highly resistant organ-
shock secondary to their IE [12]. Emergent sur- isms, or persistent bacteremia. HF is not a
gery for heart failure unresponsive to medical common indication for early surgery in right-
management is crucial, and swift surgery is also sided NVE since severe TR is better tolerated
recommended even if temporary stabilization of than left-sided regurgitation [17].
the patient with heart failure secondary to IE can Early surgery can also be indicated for certain
be achieved. pathogens (examples including Pseudomonas
Uncontrolled or complex infection is the aeruginosa, Brucella, fungi, enterococci, and S.
second- most common indication for surgery. aureus) as these pathogens can be extremely dif-
Abscesses and paravalvular extension of infec- ficult to cure with medical therapy alone and are
tion often cannot be cured with antibiotic therapy also prone to abscess or fistula formation and
alone. Mortality rate is significantly reduced other cardiac tissue destruction [15].
when early surgery is undertaken in these patients In patients with an implanted cardiac elec-
[15]. tronic device, the entire system, including the
The third-most common indication for sur- generator and leads, should be removed even if
gery is to prevent recurrent emboli from the veg- there is no sign of infection along the device.
etation, a devastating complication that affects This is because blood stream infections can cause
25–50% of patients [12]. Embolism is more a biofilm of infection to coat (seed) the leads,
likely when vegetations are large (>10 mm in thus making the infection impossible to irradicate
192 A. Stephens et al.

with medical therapy alone. Removal can be per- Table 19.8 Patient care during and after completion of
antimicrobial treatment
formed at the time of infected valve surgery or at
a specialized center where laser lead extractions Initiate before or at completion of therapy
• Obtain transthoracic echocardiogram to establish
are performed, for those not undergoing surgical
new baseline
valve management. • Drug rehabilitation referral for patients who use
Surgical risk stratification can be quantified illicit injection drugs
utilizing the Society for Thoracic Surgeon (STS) • Educate regarding signs of endocarditis, need for
risk calculator for mitral or aortic endocarditis, antibiotic prophylaxis for certain dental/surgical/
invasive procedures
but not currently for tricuspid endocarditis. Refer
• Thorough dental evaluation and treatment if not
to Chap. 4 for surgical management of coronary performed earlier in evaluation
artery disease and discussion on risk assessment. • Prompt removal of intravenous catheter at
In all cases, decisions on intervention should be completion of antimicrobial therapy
multifactorial and include discussions with the Short-term follow-up
multidiscipline teams involved with the patient’s • Obtain at least three sets of blood culture
specimens from separate sites for any febrile illness
care. and before initiation of antibiotic therapy
The risk calculator is available on the STS • Physical examination for evidence of congestive
website: heart failure
https://riskcalc.sts.org/stswebriskcalc/ • Evaluate for toxicity resulting from antimicrobial
therapy
calculate
Long-term follow-up
Surgical risk is exceptionally high in patients • Obtain at least three sets of blood cultures from
with active IE; however, in many cases, the separate sites for any febrile illness and before
patient will not improve without surgical inter- initiation of antibiotic therapy
vention. The average mortality risk for patients • Evaluation of valvular and ventricular function
undergoing surgery for IE with associated HF is (echocardiography)
• Scrupulous oral hygiene and frequent dental
21%, however, mortality risk for patients with professional office visits
medical therapy alone is 45% [10].
Adapted from Mann et al. Braunwald’s Heart Disease. A
Textbook of Cardiovascular Medicine, Tenth Edition.
Elsevier
Outpatient Management
and Follow-Up Evaluation
(Table 19.8) from an infectious disease specialist, in certain
patients who are clinically stable with reassuring
Although novel diagnostic and therapeutic strate- TEE results [15].
gies have emerged, the 1-year mortality has not At the completion of antibiotic therapy, a
improved and remains at >30%, which is worse transthoracic echocardiogram should be per-
than many cancers [12]. While on antimicrobial formed to serve as a new baseline reference for
therapy, patients should be monitored for toxic- valve appearance, severity of valvular regurgita-
ity. Weekly lab monitoring (including a complete tion, and quantification of left ventricular func-
blood count and complete metabolic panel) tion [17].
should be performed [18]. Historically, the entire Ongoing monitoring is recommended after
course of antibiotics has been intravenous (typi- hospital discharge, mainly for recurrent infection
cally with a peripherally inserted central catheter (either relapse or reinfection) and progressive
placed to allow home IV antibiotic administra- valve dysfunction [12]. Patients should be
tion). However, recent data have shown that tran- informed that they remain at risk of recurrent IE,
sitioning certain patients to oral antibiotics, after estimated to occur at a rate of 1–3% per year. At
at least 10 days of IV antibiotics, was non- regular medical checkups, patients should be ques-
inferior. This transition to an oral step-down regi- tioned about symptoms of heart failure, and a thor-
men may be a possible course, with direction ough physical exam should be performed [16].
19 Infective Endocarditis 193

Patients should be made aware that relapses Table 19.9 SBE prophylaxis antibiotic regimens
can occur and that new onset of fever, chills, Adult
or other evidence of systemic infection man- Situation Medication dosing
Oral Amoxicillin 2 gm
dates immediate evaluation, including a thor-
Unable to take oral Amoxicillin 2 gm IM/
ough history and physical exam and three sets meds Ampicillin IV
of blood cultures [16]. Prescribing empirical Cefazolin/ 2 gm IM/
antibiotic therapy should be avoided for unde- ceftriaxone IV
fined febrile illness until after blood cultures 1 gm IM/
IV
have been obtained (unless the patient’s clini-
Allergic to PCN or Cephalexin 2 gm
cal condition warrants urgent empirical ther- AMP-oral Azithromycin/ 500 mg
apy) [16]. clarithromycin 100 mg
Measures to prevent IE recurrence, including Doxycycline
good oral hygiene and consideration of antibiotic Allergic to PCN or Cephazolin/ 1 gm IM/
AMP-unable to take ceftriaxone IV
prophylaxis at the time of dental and other inva- oral meds
sive procedures, are important [12]. Oral health
and hygiene is now considered more important
than antibiotic prophylaxis to reduce the risk of health-topics/infective-endocarditis which also
recurrent IE. For ongoing long-term follow up, has printable cards for patients. It is critical to
daily dental hygiene should be stressed, with educate high-risk patients regarding the poten-
serial evaluations by a dentist who is ideally tial symptoms of endocarditis as the associated
familiar with this patient population. Patients morbidity and mortality are high. Note: guide-
should be counseled to discuss with their team lines recently changed to no longer include
the role of antibiotic prophylaxis prior to specific clindamycin for prophylaxis due to potential
types of procedures, including certain types of for severe adverse drug reactions.
dental procedures [17]. The ACC and AHA do
recommend ongoing use of antibiotic prophy- Clinical Pearls
laxis for patients undergoing certain procedures • It is critically important for high-risk patients
who are the highest risk of IE. Patients deemed to know the signs and symptoms of IE.
high risk include those with a history of IE [12]. • Fever and new or worsening murmur are the
SBE prophylaxis is recommended for dental most common findings of IE.
procedures only for patients with cardiac con- • Gram positive bacteria are the most common
ditions at highest risk of adverse outcomes “bug” identified in native IE.
from endocarditis including prosthetic cardiac • The diagnosis is made using the Duke Criteria.
valve, previous endocarditis, congenital heart • Annular and aortic abscesses have an increased
disease with unrepaired cyanotic lesions risk of heart block and death.
(including palliative shunts and conduits), com- • Valve repair is always preferred over replace-
pletely repaired CHD with prosthetic material ment to avoid placement of prosthetic
or device during the first 6 months after place- material.
ment, repaired CHD with residual defects at the • Right-sided endocarditis is often associated
site or adjacent to the site of prosthetic patch or with IV drug use.
device, and/or cardiac transplant patients with • The most common indication for surgery in
cardiac valvular disease. Prophylaxis is no lon- left-sided lesions is heart failure.
ger recommended for gastrointestinal or geni- • Embolic risk is high with large, mobile, MV
tourinary procedures. The antibiotics used for vegetations.
prophylaxis are listed below (Table 19.9) and • If a pacemaker/defibrillator is present, it is
are taken 30–60 min before the procedure start. assumed to be infected with any blood stream
The guidelines are listed on the American Heart infection and removal will need to be
Association website: https://www.heart.org/en/ considered.
194 A. Stephens et al.

References 12. The Society of Thoracic Surgeons; 2022. Available

from: https://www.sts.org/resources/riskcalculator.
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1. Mann, et al. Braunwald’s Heart Disease. A textbook
Siegel RJ. Right-sided infective endocarditis 2020:
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2. Otto CM, et al. ACC/AHA guideline for the man-
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2020;2021(143):e72–e227.
Bavaria JE, Elmariah S, et al. 2019 AATS/ACC/
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SCAI/STS expert consensus systems of care docu-
Cardiovasc Med. 11:869–83.
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4. Wang A, et al. Management considerations in infective
and requirements for transcatheter mitral valve inter-
endocarditis: a review. JAMA. 2018;320(1):72–83.
vention. J Am Coll Cardiol. 2020;76(1):96–117.
5. Chambers, et al. Native-valve infective endocarditis.
15. Lawton JS, Tamis-Holland JE, Bangalore S,
N Engl J Med. 2020;383:567–76.
Bates ER, Beckie TM, Mischoff JM, et al. 2021
6. Baddour LM, et al. Infective endocarditis in adults:
ACC/AHA/SCAI Guideline for Coronary artery
diagnosis, antimicrobial therapy, and management of
Revascularization, A report of the American College
complications. Circulation. 2015;132:1435–86.
of Cardiology/American Heart Association Joint
7. Murdoch DR. Clinical presentation, etiology, and
Committee on Clinical Practice Guidelines. J Am
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tury. Arch Intern Med. 2009;169(5):463. https://doi.
16. Chung J, Shum-Tim D. The current indications and
org/10.1001/archinternmed.2008.603.
options for aortic valve surgery. J Surg. 2014;2(1):6.
8. Cahill TJ, et al. Infective endocarditis. Lancet.
17. Fedak PWM, McCarthy PM, Bonow RO. Evolving
2016;387:882–93.
concepts and technologies in mitral valve repair.
9. UpToDate: overview of management of infective
Circulation. 2008;117(7):963–74.
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18. Watts TMF, Brescia AA, Murray SL, Burn DA,
10. Otto CM, Nishimura RA, Bonow RO, Carabello BA,
Wisniewski A, Romano MA. Degenerative mitral
Erwin JP III, Gentile F. 2020 ACC/AHA guideline for
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11. UpToDate: antimicrobial therapy of left-sided native
valve endocarditis.
Part V
Cardiomyopathies/Congestive Heart
Failure

Joseph Mishkin

Heart failure is a syndrome characterized by shortness of breath and fatigue

and is often associated with evidence of fluid retention. This syndrome can
occur due to a multitude of cardiac insults that lead to either impaired con-
traction or relaxation of the myocardium [1]. In some instances, the primary
etiology can be due to pathology involving the pericardium as described in
Chap. 23. Understanding the instigating cause of heart failure can be impor-
tant in directing appropriate treatment, i.e., identifying ischemic heart disease
and providing appropriate revascularization [2]. The classification of heart
failure based on ejection fraction is important as most clinical trials with posi-
tive results have enrolled patients with systolic dysfunction. Fortunately, in
recent years, new drug therapies have been identified to improve outcomes in
those with heart failure and preserved ejection fraction [3–6]. Furthermore,
advances in the treatment of cardiac amyloidosis have given optimism when
targeted therapies previously did not exist [7]. In many cases, the pathophysi-
ological cascade of neurohormonal activation and cytokine upregulation is
similar regardless of the etiology of heart failure. Therefore, the pharmaco-
logical interventions to treat heart failure follow a common pathway regard-
less of the etiology of the heart failure syndrome [8–11].
The following chapters will define some of the most common causes of
systolic and diastolic heart failure and provide the rationale for guideline
directed medical therapy. Given the expected rise in incidence of heart failure
in the USA and beyond, a solid foundation in identifying and treating this
syndrome is important for a variety of cardiovascular and internal medicine
specialties. Later sections will provide the basis for managing the more ful-
minant form of heart failure—cardiogenic shock.

Joseph Mishkin
Heart Failure and Transplant Services, Atrium Health/Sanger Heart and
Vascular Institute, Charlotte, NC, USA
[email protected]
196 Cardiomyopathies/Congestive Heart Failure

References

1. Braunwald E. Heart failure. JACC Heart Fail. 2013;1(1):1–20.

2. Truby L, Rogers J. Advanced heart failure: epidemiology, diagnosis, and
therapeutic approaches. J Am Coll Cardiol HF. 2020;8:523–36.
3. Bhatt AS, Abraham WT, Lindenfeld J, et al. Treatment of HF in an era of
multiple therapies: statement from the HF collaboratory. J Am Coll
Cardiol HF. 2021;9(1):1–12.
4. Fonarow GC, Stough WG, Abraham WT, et al. Characteristics, treat-
ments, and outcomes of patients with preserved systolic function hospi-
talized for heart failure: a report from the OPTIMIZE-HF Registry. J Am
Coll Cardiol. 2007;50:768.
5. Anker SD, Butler J, Filippatos G, et al. Empagliflozin in heart failure
with a preserved ejection fraction. N Engl J Med. 2021;385:1451–61.
6. Pitt B, Pfeffer MA, Assmann SF, et al. Spironolactone for heart failure
with preserved ejection fraction. N Engl J Med. 2014;370:1383–92.
7. Ruberg FL, Grogan M, Hanna M, Kelly JW, Maurer MS. transthyretin
amyloid cardiomyopathy: JACC state-of-the-art review. J Am Coll
Cardiol. 2019;73:2872–91.
8. Metoprolol CR/XL Randomised Intervention Trial in Congestive Heart
Failure (MERIT-HF). Effect of metoprolol CR/XL in chronic heart fail-
ure. Lancet. 1999;353:2001.
9. Packer M, Fowler MB, Roecker EB, et al. Effect of carvedilol on the
morbidity of patients with severe chronic heart failure: results of the
carvedilol prospective randomized cumulative survival (COPERNICUS)
study. Circulation. 2002;106:2194.
10. Zannad F, McMurray JJ, Krum H, et al. Eplerenone in patients with sys-
tolic heart failure and mild symptoms. N Engl J Med. 2011;364:11.
11. Desai AS, McMurray JJ, Packer M, et al. Effect of the angiotensin-recep-
tor-neprilysin inhibitor LCZ696 compared with enalapril on mode of
death in heart failure patients. Eur Heart J. 2015;36:1990.
Heart Failure with Reduced
Ejection Fraction (HFrEF)
20
Lauren Eyadiel and Bridget Rasmussen

Introduction Anatomy and Physiology

Heart failure is a complex systemic syndrome Heart failure is a complex neurohormonal pro-
where inadequate blood supply due to heart dys- cess that is not completely understood. Simply
function is unable to meet the metabolic demands put, there is an inciting event that results in dam-
of the tissues [1]. This clinical syndrome consists age to the homeostasis of the metabolic system
of symptoms of congestion and/or inadequate resulting in activation of multiple compensatory
cardiac perfusion. Congestive symptoms include mechanisms. These compensatory mechanisms
shortness of breath, lower extremity edema, involve the adrenergic nervous system, renin
abdominal bloating, orthopnea, and/or paroxys- angiotensin aldosterone system (RAAS), and
mal nocturnal dyspnea (PND). Symptoms of cytokine system. This process is initially protec-
inadequate cardiac perfusion include mental sta- tive, but sustained activation of these compensa-
tus changes, cardiac cachexia, renal dysfunction, tory mechanisms results in adverse remodeling
and fatigue due to decreased end organ perfusion. of the left ventricle with associated dilation and
The clinical syndrome is combined with elevated increase in left ventricular volume and mass [4,
natriuretic peptides and objective evidence of 5]. Cardiomyocyte loss leads to the inability of
congestion and/or echocardiographic findings of heart muscle to contract properly and reduces
structural changes to the heart including reduc- cardiac output. A reduction in cardiac output
tion in ejection fraction. Heart failure with causes activation of the sympathetic nervous sys-
reduced ejection fraction (HFrEF) is defined as tem and norepinephrine release, promoting
patients with the clinical syndrome of heart fail- peripheral vasoconstriction, increased heart fail-
ure with a left ventricular ejection fraction of less ure, and increased myocardial contractility.
than 40% [2, 3]. This will be the focus of this Activation of RAAS leads to water and sodium
chapter. Heart failure with preserved ejection retention, increasing circulating volume and pre-
fraction will be covered in Chap. 21. load. The Frank-Starling mechanism states that
cardiac fiber length increases contractile strength
[6] (see Chap. 2). Thus, the increased preload
L. Eyadiel · B. Rasmussen (*) causes increased myocardial contractility. If this
Advanced Heart Failure, Heart Transplant, and
Mechanical Circulatory Support, Cardiology, Atrium process persists, detrimental ventricular remodel-
Health Wake Forest Baptist, ing develops. Figure 20.1 summarizes this pro-
Winston Salem, NC, USA cess. A basic understanding of the
e-mail: [email protected]; pathophysiology of HFrEF is required as
[email protected]

© The Author(s), under exclusive license to Springer Nature Switzerland AG 2023 197
R. Musialowski, K. Allshouse (eds.), Cardiovascular Manual for the Advanced Practice Provider,
https://doi.org/10.1007/978-3-031-35819-7_20
198 L. Eyadiel and B. Rasmussen

Congestion

A B

Adequate Perfusion
Dry-warm Wet-warm

L C
Dry-cold Wet-cold

Fig. 20.2 Hemodynamic profile of heart failure patients

[8]
Fig. 20.1 Neurohormonal influences in HFrEF. (Adapted
from Harrison’s Principles of Internal Medicine)
poor prognostic indicator [9]. Pressing on the
abdomen should cause transient JVP elevation
guideline-
directed medical therapies (GDMT) that can help differentiate the waveform from
target these compensatory mechanisms. There carotid pulsation. This change in abdominal
are multiple etiologies of heart failure including pressure, termed hepatojugular reflux (HJR), is
both ischemic and nonischemic disease which pathologic if a sustained elevation is noted over
are further discussed in the pathology section of 10 seconds of abdominal pressure, suggesting
this chapter. elevated right-sided filling pressure [9].
Likewise, the presence of orthopnea—dyspnea
when lying back or supine—is indicative of ele-
Physical Exam vated left ventricular filling pressures and pul-
monary capillary wedge pressure (PCWP).
Careful clinical examination of patients with Respiratory exam may be notable for crackles or
heart failure is essential. Broadly speaking, heart diminished breath sounds indicative of pleural
failure physical exam components can fall into effusions, but the presence or absence of this is
two categories: volume status and perfusion sta- nonspecific. Cardiac auscultation may be nota-
tus. Combining these assessments provides a ble for S3 gallop sound, a brief third heart sound
clinical profile [7] that can drive decisions in in early diastole indicating increased flow rates
management (Fig. 20.2). or increased ventricular dilation. This is best
heard over the apex when the patient is in a left
lateral position (see Chap. 1). Pulsus alternans,
Volume Status alternating weak and strong pulse pressure, is an
indicator of left ventricular resistance and left-
Jugular vein distention, indicating an elevated sided dysfunction and may suggest decompen-
jugular vein pressure (JVP), is common in sation. While lower extremity edema is
patients who have increased congestion. JVP is frequently present, it is not specific for heart
used to estimate right atrial pressure. Waveform failure etiology. Dry oral mucosa and poor skin
or pulsation is examined, typically at 45°, on turgor without an obvious cause are a sign of
both sides of the neck, which can be calculated intravascular volume depletion (Fig. 20.3).
by measuring elevation and calculating horizon-
tal distance from the sternal angle in centimeters Perfusion Status
(cm) then estimating distance to the right atrium Although a careful review of systems is vital to
by adding 5 cm. Inspiratory increase in JVP is a determining cardiac output or perfusion status,
20 Heart Failure with Reduced Ejection Fraction (HFrEF) 199

Table 20.1 Classification of heart failure

ACCF/AHA stages of NYHA functional
6F classification
Stage A: At high risk I: No limitation of physical
for HF but without activity.
structural heart disease
or symptoms of HF
Stage B: Structural II: Slight limitation of
heart disease but physical activity.
without signs of Comfortable at rest, but
symptoms of HF ordinary activity results in
Fig. 20.3 How to measure JVP. (https://www.renalfel- symptoms of HF
low.org/2011/01/02/jugular-venous-pressuredistention)
Stage C: Structural III: Marked limitation of
heart disease with prior physical activity.
or current symptoms of Comfortable at rest, but less
perfusion can be assessed by clinical exam as
HF than ordinary activity causes
well. A narrow pulse pressure (systolic minus symptoms of HF
diastolic pressure) or low proportional pulse Stage D: Refractory HF IV: Unable to carry on any
pressure (pulse pressure divided by systolic requiring specialized physical activity without
pressure) is a marker of low cardiac output. interventions symptoms of HF, or
symptoms of HF at rest
Cool or tepid extremities are suggestive of low
cardiac output, but sensitivity is low. Prolonged
or sluggish capillary refill time (greater than
2 seconds), if present, is a marker of poor Imaging
perfusion.
Imaging is utilized in heart failure to confirm the
Review of Systems diagnosis, provide information regarding the etiol-
Like physical examination, a thorough review of ogy, monitor for treatment response, and to assist
systems can be instructive. Pertinent positive in prognostication. Depending on the type of
review of system findings connoting elevated imaging, information is given regarding the car-
volume status includes weight changes; new diac chamber size, architecture, global, and
cough, especially when lying supine; orthopnea; regional left ventricular function. Choosing the
paroxysmal nocturnal dyspnea (may be expressed most appropriate imaging modality can be chal-
as change in sleep habit); early satiety; abdomi- lenging and requires careful attention to patient-
nal bloating; and lower extremity edema. specific factors based on history, physical
Findings that suggest poor cardiac perfusion examination, and laboratory testing. Table 20.2
include fatigue or malaise, decreased appetite, provides a comprehensive overview of the imag-
cold intolerance, confusion, decreased urination, ing modalities used for evaluation of patients with
and dizziness/lightheadedness. Early decompen- heart failure. The most common imaging modali-
sated heart failure is often misdiagnosed as a ties will be discussed in further detail below. Of
respiratory ailment. note, routine repeat measurement of left ventricu-
lar function is not indicated in the absence of a
Clinical Classifications clinical status change or treatment intervention.
There are two main tools to classify heart fail-
ure. The ACC/AHA stages of Heart Failure
emphasize the development and progression of Echocardiography
disease, and the New York Heart Association
(NYHA) classes focus on exercise capacity, Two-dimensional echocardiography is consid-
physical examination, and the symptomatic sta- ered the most useful, versatile, and cost-effec-
tus of the HF disease (Table 20.1). tive diagnostic method for patients with heart
200 L. Eyadiel and B. Rasmussen

Table 20.2 Summary of imaging modalities utilized in heart failure

Conditions where
Imaging modality Most useful in defining most helpful Advantages Disadvantages
Coronary Gold standard for Suspected CAD Can intervene at Invasive, radiation
angiogram evaluating coronary time of diagnosis exposure, risk for
artery disease (CAD) contrast-induced
nephropathy
Echocardiography Biventricular function, Suspected CAD, Noninvasive, no Difficult in patient
wall motion, valvular valvular disease, radiation exposure, with poor acoustic
lesions, structural pericardial ventricular function, windows
abnormalities, pericardial tamponade, hemodynamic
effusion, estimation of pulmonary information, good
right atrial and hypertension for initial evaluation,
pulmonary artery and monitoring of
pressures treatment response
in HF
Computed Coronary disease, Suspected CAD, High negative Radiation exposure,
tomography biventricular function adult congenital predictive value for risk for contrast-
(coronary CT) and volumes, congenital disease CAD with reliable induced nephropathy,
heart disease anatomy ejection fraction difficult with rapid
(EF) measurement heart rate
Magnetic resonance Gold standard for EF Ischemic CMP: No radiation Limited to magnet
(CMR) and volume assessment. Viability exposure, best compatible metals,
Etiology (ischemic Nonischemic CMP: noninvasive poor visualization in
versus nonischemic Diagnosis evaluation of the presence of
CMP) and Myocarditis, myocardial tissue pacemakers or
characterization of sarcoidosis, implantable cardiac
nonischemic CMP, amyloidosis, defibrillators,
myocardial viability, arrhythmogenic RV difficult to evaluate
biventricular volumes, cardiomyopathy, LV in arrhythmias
congenital heart disease non-compaction,
anatomy constrictive
pericarditis
Cardiopulmonary Objective measurement Advanced HFrEF, Noninvasive, Orthopedic issues
exercise testing of functional limitation consideration for objective that limit patient
(CPET) in advanced HF advanced HF measurement of ability to ride bike or
therapies, functional status, walk on treadmill,
determining monitoring of can be affected by
pulmonary versus functional decline beta blocker use and
cardiac etiology of over time obesity
dyspnea
Nuclear imaging
Multigated LV function and volumes Determining LVEF Highly reproducible Radiation exposure
acquisition scan in patients with poor measurement of
(MUGA) acoustic windows LVEF
Positive emission Myocardial perfusion Suspected CAD, Allows for Exposure to
tomography (PET) and viability, LV function “hibernating” noninvasive radiation, variable
and volumes, sarcoidosis myocardium, diagnosis of accuracy given
sarcoidosis sarcoidosis specific diet prior to
testing, may miss
three vessel CAD
Single-photon Myocardial perfusion, Suspected CAD, Noninvasive Exposure to
emission computed amyloidosis amyloidosis diagnosis of radiation, may miss
tomography amyloidosis three vessel CAD,
(SPECT) poor assessment of
ejection fraction
Adapted from Heart Failure: A Companion to Braunwald’s Heart Disease [10]. CMP cardiomyopathy
20 Heart Failure with Reduced Ejection Fraction (HFrEF) 201

management [13]. The presence of late gadolin-

ium enhancement is representative of scar in the
myocardium, which is important for treatment
considerations, including placement of implant-
able cardiac defibrillators. The pattern of
enhancement gives information regarding HF
etiology and can differentiate between dilated
cardiomyopathy, ischemia, hypertrophic cardio-
myopathy, myocarditis, as well as more rare car-
diomyopathies [10, 12]. This method is superior
in identification and characterization of left ven-
tricular thrombi when compared with TTE [10].
In ischemic cardiomyopathy, CMR images can
assist in evaluating viability with and without
stress images [10].
Unfortunately, the presence of cardiac devices,
including cardiac resynchronization therapy
devices, can cause artifact, making the images
difficult or impossible to interpret. This may ren-
Fig. 20.4 Cardiac chamber enlargement on echo due to
der the test inadequate; therefore, alternative
HFrEF imaging methods are preferred in these patients.
In addition, CMR is contraindicated in patients
with metallic elements that are not MRI compat-
failure [11]. Transthoracic echocardiography ible. MRI can cause these metals to heat up dur-
(TTE) is readily available, noninvasive, and pro- ing the test, can cause forces on magnetic metals,
vides information regarding the type of ventric- or cause severe image degradation.
ular dysfunction (systolic versus diastolic), left
ventricular ejection fraction (LVEF), assess-
ment of right ventricular function, dimensions Pathology/Description
of the cardiac chambers, valvular function,
structural abnormalities, as well as the presence Ischemic Heart Failure
or absence of a pericardial effusion. This infor-
mation is useful at the time of diagnosis as well Despite advances in revascularization and treat-
as for monitoring treatment response and prog- ment of coronary artery disease, myocardial
nosis over time. Below are images that demon- infarction (MI) is the most common cause of
strate HFrEF based on echocardiography heart failure. Heart failure development at the
(Fig. 20.4). time of MI, during index hospitalization, or fol-
lowing MI may manifest with different clinical
attributes and outcomes. Myocardial compro-
Cardiac Magnetic Resonance Imaging mise secondary to necrosis, stunning, or struc-
tural rupture causes rapid structural changes,
Cardiac MRI (CMR) is considered to provide a myocyte edema, and progressive myocyte death
higher-quality image than TTE and has become within three hours of ischemic time. Even revas-
the noninvasive gold standard for determining cularization causes insult through an oxidative
LV volume, LVEF, and LV mass [10, 12, 13]. stress reaction and embolization of thrombotic
Compared with TTE, it is felt that there is less debris [14]. The incidence of heart failure at the
interrater variability. This imaging modality typ- time of presentation has increased, possibly
ically utilizes gadolinium contrast which assists because of improvement in prehospital care.
in differentiating tissue characteristics to guide Conversely, heart failure development during
202 L. Eyadiel and B. Rasmussen

hospitalization has fallen in the setting of statins within 24 h of MI is associated with a

improvements in revascularization. However, the reduction in heart failure hospitalization and in-
incidence of heart failure with preserved ejection hospital mortality [15]. Patients should be risk
fraction after myocardial infarction has increased. stratified for wearable defibrillator prior to hospi-
Heart failure with reduced ejection fraction tal discharge (see Chap. 13).
(HFrEF) following hospitalization for MI is sec-
ondary to scar formation and cardiomyocyte onischemic Cardiomyopathy (NICM)
N
death triggering activation of neurohormonal and Cardiomyopathy is a myocardial disorder in
sympathetic nervous system processes that initi- which heart muscle structure and/or function is
ate and perpetuate left ventricular remodeling. abnormal in the absence of coronary artery dis-
Infarction size and location impact the risk for ease, hypertension, valvular disease, or congenital
development of HFrEF. Multivessel disease and heart defect [16]. Non Ischemic Cardiomyopathy
anterior MI pose the highest risk [14]. categorization has evolved through advances in
Comorbidities including hypertension, atrial imaging and knowledge. The American Heart
fibrillation, diabetes, and chronic kidney disease Association (AHA) defined cardiomyopathies as
further compound the risk for HFrEF develop- primary, or confined to the heart, or secondary, as
ment post MI. Female gender and older age also part of generalized systemic disorders.
increase the risk of heart failure. Three primary categories exist:
Natriuretic peptide elevation, biphasic pattern
of BNP elevation, and glomerular filtration rate 1. Genetic: channel disorders, arrhythmogenic
are associated with HFrEF development post MI. right ventricular cardiomyopathy (ARVC),
Troponin elevation can correspond to infarct size hypertrophic cardiomyopathy (HCM), left
on CMR, but association with HFrEF develop- ventricular non-compaction (LVNC), and gly-
ment is unclear [14]. cogen storage disorders
Wall motion abnormalities on TTE predict 2. Acquired: inflammatory/myocarditis, stress
mortality in HFrEF more accurately than LV induced (Takotsubo), peripartum,
ejection fraction alone. Right ventricular dys- tachycardia-induced
function seen on TTE also contributes to HFrEF 3. Mixed acquired and genetic (dilated (DCM)
development. Left ventricular enlargement post and restrictive (RCM) cardiomyopathy) [17]
MI is more commonly seen in relation to trans-
mural MI, larger infarct size, intramyocardial The European Society of Cardiology 2008
hemorrhage, microvascular obstruction, and position paper on cardiomyopathy classification
advanced age and confers an increased risk of sought to group cardiomyopathies according to
HFrEF hospitalization [14]. CMR is the gold functional and morphological phenotypes which
standard imaging modality to define infarct size could be used to guide clinical practice [18].
and scar formation. Cardiomyopathies were divided into five catego-
Guideline-directed medical therapy including ries which could have either familial or nonfamil-
beta blockers, ACEIs/ARBs, and mineralocorti- ial subclassifications: HCM, DCM, ARVC,
coid receptor antagonists has shown mortality RCM, and unclassified cardiomyopathies
benefit following MI. Early administration of (Fig. 20.5).
20 Heart Failure with Reduced Ejection Fraction (HFrEF) 203

Heart Muscle
Diseases Myocarditis

Inflammation of
heart muscle

Hypertrophic cardiomyopathy Dilated cardiomyopathy

Thickened
Weakened
heart muscle
heart
musc

Enlarged
ventricle

Fig. 20.5 ESC classification of myocarditis, dilated cardiomyopathy, and hypertrophic cardiomyopathy. (Used with
permission, Shutterstock)

Hypertrophic Cardiomyopathy (particularly associated with exertion or dehydra-

(HCM) tion) and SCD. Evaluation of family history for
unexplained SCD is imperative. A systolic mur-
HCM is an autosomal dominant sarcomere pro- mur that increases with intensity during Valsalva
tein mutation cardiomyopathy in which non- maneuver may be present [20].
dilated left ventricular hypertrophy (LVH) is Electrocardiographic T wave inversions, gener-
present in the absence of a systemic or valvular ally in the lateral leads, are the most common
disease [16, 17]. There are greater than 30 genes electrocardiogram abnormality; ST segment
known that can be evaluated for by genetic test- depression, pathological Q waves, and ventricu-
ing for prognostic education of family members. lar arrhythmias have also been observed, particu-
It is the most common cause of sudden cardiac larly after exercise [19, 20]. On TTE, small
death (SCD) in athletes younger than 35 years of ventricular chamber size with LVH is noted with
age [19]. It can be associated with congenital an irregular localization of septal or apical hyper-
syndromes and glycogen storage disease disor- trophy (Fig. 20.6), which can result in left ven-
ders or metabolic disorders such as tricular outflow tract obstruction (LVOTO) or
Anderson-
Fabry disease. Presenting symptoms mitral valve dysfunction (Fig. 20.7) (systolic
characteristic of HCM include atypical chest pain anterior motion of the mitral valve against the
204 L. Eyadiel and B. Rasmussen

intraventricular septum causing dynamic which is associated with increased risk of ven-
LVOTO) (Fig. 20.8). In cases of mild LVH in ath- tricular arrhythmias [21].
letes, CMR can help differentiate pathologic and Beta blockers are the initial therapy for symp-
physiologic LVH [19]. Contrasted CMR studies tomatic HCM, with non-dihydropyridine calcium
differentiate the extent of myocardial fibrosis channel blockers used if beta blockers are not
well tolerated. These medications decrease myo-
cardial oxygen demand of the hypertrophied
muscle, decrease the rate of fibrosis formation,
and reduce the severity of the obstruction. They
also can help prevent and treat potential arrhyth-
mias. Reduction of symptoms and improvement
of the murmur is the goal of therapy. If LVOTO is
refractory to maximally tolerated medical ther-
apy or hemodynamics are compromised, septal
reduction procedures such as surgical myomec-
tomy or alcohol ablation should be considered.
Cardiac transplantation is reserved for end-stage
systolic dysfunction [21]. Regardless of medical
course, moderate or high intensity competitive
sports are prohibited. Shared decision-making
Fig. 20.6 Echocardiography of HCM. Arrow points to between the patient and physician is critical
asymmetric septal hypertrophy of HCM

Fig. 20.7 Dynamic outflow tract gradient-induced MR. demonstrates eccentric MR caused by abnormal anterior
Red arrow shows turbulent flow below the aortic valve leaflet function
from a dynamic LVOT obstruction. The yellow arrow
20 Heart Failure with Reduced Ejection Fraction (HFrEF) 205

Normal Hypertrophic Cardiomyopathy

arch of aorta
blood flows easily
through vessels
left atrium
aortic valve
right atrium mitral valve
ventricular septum left ventricle thickened ventricular septum
tricuspid valve small left ventricle
right ventricle

heart pumping
normally

Fig. 20.8 Structural differences in normal and hypertrophic heart. (Used with permission, Journal of Imaging, 8(4),
102. https://doi.org/10.3390/jimaging8040102)

regarding activity restriction. Patients should be observed. A right-sided S3 or left ventricular S4

risk stratified for SCD and evaluated for implant- sound may be present, indicating rapid filling
able cardioverter-defibrillator (ICD) placement. within a stiffened ventricle [23] (see Chap. 1).
This evaluation considers percentage of scar bur- Diffuse reduced QRS voltage or prolonged PR
den seen on MRI (>12–15%), frequency of non- interval can be seen on electrocardiogram,
sustained ventricular tachycardia on ambulatory although their presence is unnecessary for diag-
monitoring, the specific genetic defect, and fam- nosis. Bi-atrial enlargement is often present with
ily history of SCD. restrictive physiology and is reflected in widened
more prominent P waves on EKG. Atrial or ven-
tricular dysrhythmia may also be present [23].
Restrictive Cardiomyopathy (RCM) Common TTE findings are bi-atrial enlargement
and diastolic dysfunction. Further imaging is
Unlike the anatomic basis for HCM, restrictive guided by disease suspicion. Laboratory finding
cardiomyopathies are characterized by a func- of elevated B-type natriuretic peptide (BNP)
tional pattern in which impaired myocardial marker is common.
compliance results in reduced ventricular filling
and increased ventricular pressure, diastolic dys-
function, and preserved ejection fraction [16]. Amyloidosis
Heterogeneity of culprit pathologies makes defin-
ing RCM difficult. RCM can be idiopathic, famil- Amyloidosis is an infiltrative RCM in which
ial, or secondary to systemic disorders. It can amyloid, an abnormal fibrillar protein made up of
involve infiltration of the myocardium with unstable precursor proteins, deposits in the heart
abnormal proteins, glycogen, minerals, or other (or other organs) leading to functional organ loss
substances or demonstrate restrictive physiology [24]. The most common types are immunoglobu-
without infiltration. Common causes of RCM in lin light chain amyloidosis (AL) or transthyretin
adults are amyloidosis, sarcoidosis, hemochro- amyloidosis, further divided into “wild type”
matosis, and sequelae of radiation therapy [22]. (ATTR-wt) and mutant (ATTR-m) subtypes.
Diagnosis of RCM is based on clinical, labo- Patients present with differing organ involvement
ratory, and imaging findings. The primary clini- patterns with disease course dependent on the
cal presentation is heart failure, particularly right involved organs. In general, cardiac involvement
heart failure, with dyspnea on exertion and increases mortality [22]. History of bilateral car-
fatigue being most common. Signs of right heart pal tunnel syndrome, peripheral neuropathy, or
failure, such as elevated jugular vein distention, syncope raises suspicion of disease presence.
peripheral edema, and ascites are commonly Physical exam may be notable for macroglossia
206 L. Eyadiel and B. Rasmussen

and periorbital purpura. Orthostatic hypotension sition pattern. If EMB is pursued, Congo red
or baseline hypotension is often present. staining identifies amyloid presence. A less inva-
In addition to the restrictive pattern findings sive biopsy test is fat pad biopsy, which has a
above, TTE imaging is also significant for LV, higher yield in AL amyloid [22].
right ventricular, and intra-atrial thickening, pos- Heart failure treatment involves addressing
sibly with a “speckled” pattern seen on ultra- conduction blocks and managing volume over-
sound imaging due to amyloid fibrils in the load with diuretics or aldosterone antagonists
myocardium. Pericardial effusion can be present. [20]. AL amyloid is treated systemically with
Longitudinal strain imaging shows more signifi- chemotherapeutic agents and potentially stem
cant impairment in the left ventricular basal ver- cell transplant. ATTR amyloid (both wild type
sus apical segments, producing a “cherry on top” and mutant) can be treated with early initia-
pattern [23] (Fig. 20.9). On CMR, amyloid tion of tafamidis, which binds to transthyretin
deposits produce a unique subendocardial late and slows amyloid formation. Beta blockers
gadolinium enhancement in the ventricles and should be used cautiously since the cardiac
atria [22]. Nuclear imaging tracers (pyrophos- output in amyloid patients is often heart rate
phate scan) can detect ATTR with high sensitivity dependent.
and specificity differentiate between AL and
ATTR types.
High sensitivity cardiac troponin and BNP are Cardiac Sarcoidosis
useful markers of disease progression but not
specific. After TTE, electrocardiogram, and clini- Sarcoidosis is a multi-organ granulomatous dis-
cal evaluation, laboratory markers of AL amyloi- ease in which noncaseating granulomatous
dosis should be considered. These include serum inflammation can lead to fibrosis in affected
free light chains, serum, and urine immunofixa- organs. Cardiac sarcoidosis (CS) most commonly
tion electrophoresis. While endomyocardial presents as conduction abnormalities (including
biopsy (EMB) is the gold standard for cardiac ventricular abnormalities and atrioventricular
amyloidosis, it is invasive and not without com- (AV) node blocks) and heart failure symptoms.
plication risk. A negative biopsy cannot rule out Patients may complain of palpitations, syncope,
disease process because of patchy amyloid depo- presyncope, or even have SCD [25]. In clinically

a b

Fig. 20.9 (a) Typical echogenic findings of cardiac amyloidosis with LV and septal thickening and (b) strain imaging.
(Used with permission, Biomedicines, 10 (4), 903. https://doi.org/10.3390/biomedicines10040903)
20 Heart Failure with Reduced Ejection Fraction (HFrEF) 207

Fig. 20.10 Late gadolinium enhancement in a patient LGE areas with infiltration (arrows) in a variable pattern
with pulmonary sarcoidosis and extensive cardiac involve- of transmural distribution
ment. There are several focal non-subendocardial based

evident disease, electrocardiogram abnormalities Corticosteroids are the treatment of choice in

in addition to conduction blocks can include QRS active disease, with methotrexate as a second-line
complex fragmentation, pathological Q waves, agent. Antiarrhythmic medication and possible
and ST changes. TTE findings are not pathogno- transcatheter ablation may be necessary in cases
monic but may show basal interventricular thin- of ventricular arrhythmia. Patients should be
ning [26] (Fig. 20.10). Endomyocardial biopsy is risk-stratified for SCD and implantable cardiac
felt to be low yield secondary to the patchy nature defibrillator discussed. Cardiac resynchroniza-
of the CS. tion defibrillator therapy is indicated for high-
CMR is the optimal study to determine the grade heart blocks.
presence of cardiac sarcoidosis. Late gadolinium
enhancement, seen in basal segments of the sep-
tal and lateral wall in a non-infarct pattern, com- Dilated Cardiomyopathy (DCM)
monly represents fibrosis although can also
indicate inflammation. In active disease, inflam- Dilated cardiomyopathy is defined as an enlarge-
mation can be seen with fluorodeoxyglucose ment of the left ventricle with contractile dys-
positron emission tomography (FDG-PET), with function. It is a common form of heart muscle
FDG uptake patterns indicating active CS inflam- disease and the most frequent cause of heart
mation [25], guiding treatment. These two transplantation [17]. Familial cases account for
imaging modalities are complementary in the
up to 35% of DCM [27]. Presentation can be
diagnosis and management of CS. accompanied by thromboembolic events and
208 L. Eyadiel and B. Rasmussen

arrhythmias. Pathophysiologic changes of ven- Myocarditis

tricular remodeling and ventricular dilation are
discussed in detail above. Myocarditis is an inflammatory disease of the
While heterogeneous in etiology (see heart which can be a consequence of infection,
Table 20.3), initial heart failure symptoms (lower toxic substance exposure, or immune system
extremity swelling, orthopnea, fatigue after mild activation. It can exist along a continuum from
exertion) are typically present and may be accom- acute to chronic and is characterized by those
panied by nausea, abdominal fullness, early sati- stages as well as etiology and severity. The initial
ety, and anorexia. Physical exam can reveal presentation can range from prodromal symp-
peripheral and generalized edema, elevated jugu- toms to fulminant myocarditis with circulatory
lar vein pulsation, tachycardia, inferolateral dis- collapse [28, 29]. Myocarditis progresses from
placement of apical pulse, S3 gallop, delayed acute inflammation to interstitial edema to myo-
capillary refill, and crackles in lung field cyte necrosis to fibrosis. Ventricular size may be
auscultation. preserved in the early phase, but damage to the
Electrocardiography is nonspecific but can myocardium over time leads to LV dilation [17].
include tachyarrhythmias and bundle branch Patients with acute myocarditis present with a
blocks. Chest X-ray imaging will show cardio- variety of signs and symptoms as seen in
megaly, often with pulmonary venous c ongestion. Table 20.4 [17, 28].
Diagnosis is confirmed with echocardiography Over a quarter of presentations represent ful-
which may include wall motion abnormalities, minant myocarditis presenting with ventricular
right ventricular involvement, and functional arrhythmias and cardiogenic shock (Table 20.5).
mitral regurgitation [27]. More commonly, symptoms are accompanied by
abnormal electrocardiogram with ST elevation,
Table 20.3 Common causes of dilated cardiomyopathy frequently in the inferior and lateral leads [28].
Endomyocardial biopsy is necessary in
Genetic/familial Syndromic disease/inborn
errors of metabolism arrhythmogenic or fulminant presentation with
Neuromuscular Drugs cardiogenic shock [29]. EMB is recommended in
disorders the following settings:
Duchenne muscular Antineoplastic agents
dystrophy Psychiatric drugs
Becker muscular
• Other causes of HF have been excluded or
dystrophy when it may influence treatment (Table 20.5).
Infection (myocarditis) Endocrine disorders • For patients with unexplained fulminant HF
Viral Hypothyroidism (new-onset HF of less than 2 weeks duration
Bacterial Hyperthyroidism associated with hemodynamic compromise).
Fungal Cushing’s disease
Parasitic Addison’s disease
• Unexplained new-onset HF of 2 weeks to
Protozoal Diabetes mellitus 3 months duration associated with a dilated
Rickettsia Acromegaly LV and new ventricular arrhythmias, Mobitz
Autoimmune disorders Nutritional deficiency type II second-degree AV block, third-degree
Giant cell myocarditis Selenium AV block, or failure to respond to usual care
Dermatomyositis Thiamine
Systemic lupus Zinc within 1–2 weeks.
erythematosus Copper
Peripartum CMR is recommended in clinically suspected
Toxicity and overload acute myocarditis within 2–3 weeks from onset of
Ethanol symptoms to evaluate for myocardial inflamma-
Cocaine
Amphetamines tion. Hyperemia is suggested with early gadolin-
Anabolic steroids ium enhancement, tissue edema seen with increased
Table adapted from Weintraub, R. et al. (2017). Dilated T2-weighted imaging, and necrosis/fibrosis seen
Cardiomyopathy. The Lancet, 390(10092), 401–402 [27] with late gadolinium enhancement. These are the
20 Heart Failure with Reduced Ejection Fraction (HFrEF) 209

Table 20.4 Presentation of myocarditis

Signs and symptoms Clinical features Differential cause
New or worsening heart failure/ Excessive fatigue or exercise intolerance All causes
cardiomegaly Pulmonary edema, S3 gallop
Chest pain/ACS-like presentation Ischemic features on EKG such ST depression or All causes
elevation/T-wave inversion
Acute pericarditis Pleuritic chest pain. PR depression/diffuse ST elevation
Cardiac arrhythmias or EKG Sinus tachycardia. Atrial or ventricular arrhythmia; new Giant cell
changes bundle branch block, heart block myocarditis
Cardiac sarcoidosis
Cardiogenic shock May see rapid decompensation with or without associated Giant cell
multisystem organ failure myocarditis
Cardiac sarcoidosis
Nonspecific myalgias or recent Viral myocarditis
viral illness/URI Eosinophilic
myocarditis
Sudden cardiac death All causes

established cardinal findings to support myocardi-

Table 20.5 Clinical criteria for myocarditis tis. PET imaging can be considered as alternative
imaging if CMR is not possible or if other organs or
Clinical
presentation: at a systemic process is suspected [28].
least one or Diagnostic criteria: Ancillary One specific consideration is giant cell myo-
more of the at least one or more supportive carditis. This disease presents as a rapidly pro-
following of the following findings
gressive necrotizing myocarditis with generally
Acute chest New EKG findings Fever ≥38.0 °C
pain of any of the at presentation
fulminant presentation and involving refractory
(pericarditis) following: or within prior ventricular arrhythmias. It should be diagnosed
First-third degree 30 days promptly with endomyocardial biopsy, and
AV block or BBB; +/− associated immunosuppressive therapy should be initiated
ST/T wave changes; symptoms such
sinus arrest; VT; as chills,
as soon as possible. Even with early and aggres-
VF; asystole; Afib; myalgias, HA, sive therapy, mortality and need for cardiac trans-
IVCD; low voltage; N/V/D plantation are very high in this cohort of critically
SVT ill patients. There should be early consideration
New onset or Elevated troponin Prior clinical
worsening suspected or
of extracorporeal membrane oxygenation and
dyspnea at rest definite mechanical support.
or exercise, myocarditis Immune checkpoint inhibitor inflammation is
and/or fatigue, another specific disease. Patients on this class of
with or without
left and/or right
chemotherapeutic agents can have a rapidly pro-
HF signs gressive decompensation resulting in death. This
Palpitations or LV or RV Exposure to type of myocarditis needs an early diagnosis, and
unexplained dysfunction toxic agents high-dose corticosteroids are necessary to avoid
arrhythmia
cardiogenic shock and death. Fortunately, early
symptoms and/
or syncope and/ intervention results in normalization of the ven-
or sudden tricular function.
cardiac death Treatment is directed at underlying cause and
Unexplained Tissue Extra-cardiac therapies aimed at clinical presentation. Inotropic
cardiogenic characterization by autoimmune
shock CMR disease and advanced mechanical support may be needed
in severe disease. The immune modulation thera-
Adapted from Cooper, Leslie. Up to date. Clinical mani-
festations and diagnosis of myocarditis in adults. Jul 13, pies are reserved for a small subset of acute myo-
2021 carditis (Table 20.6).
210 L. Eyadiel and B. Rasmussen

Table 20.6 Myocarditis etiologies to consider early out LV dysfunction, with histological and/or
biopsy and immune modulating agents
electrocardiographic abnormalities present [16].
Giant cell myocarditis-related shock and arrhythmias The disease process may have immunologic
Immune checkpoint inhibitor inflammation
mediation since inflammatory infiltrate is fre-
Acute sarcoidosis shock and related arrhythmias
quently present. Presentation with arrhythmias
(ventricular ectopy or ventricular tachycardia
Peripartum Cardiomyopathy with left bundle branch morphology), exercise-
induced syncope, or sudden cardiac death is com-
Peripartum cardiomyopathy is left ventricular mon [17, 31]. The electrocardiogram commonly
systolic dysfunction associated with pregnancy, exhibits T-wave inversions in V1-V3, and pro-
most commonly presenting in the peripartum or gression beyond V3 is associated with advanced
postpartum period. Risk factors include increased disease [31]. Additionally, a right bundle branch
age, African American race, hypertension and block can be seen in severe structural disease.
preeclampsia, multiple gestations, prior cardio- Likewise, the presence of an epsilon wave, a
myopathy during pregnancy, and obesity [17, deflection at the end of the QRS complex and
20]. In addition to the hemodynamic stress of before the T wave, connotes significant disease
pregnancy, genetics, nutritional deficiencies, and [31] (Fig. 20.11). Other conduction criteria and
autoimmune processes have been implicated family history are important considerations in
[30]. Because symptoms of heart failure such as diagnosis and therapy options. TTE findings
fatigue, dyspnea, or lower extremity edema can include right ventricular hypertrophy, dilation of
be mistaken for common pregnancy symptoms, right ventricular outflow tract and ventricle, and
diagnosis may be delayed. TTE imaging is non- most frequently right ventricular global or seg-
specific and notable for LV systolic dysfunction mental abnormalities [31]. CMR is the image
and dilation [20]. Peripartum cardiomyopathy is modality of choice to show functional and mor-
treated with guideline-directed medical therapy phological abnormalities associated with ARVC
(GDMT) aimed at preventing further LV remod-
eling, with the caveat that angiotensin receptor
blockers and angiotensin-converting enzyme
inhibitors are contraindicated during pregnancy
and diuretics should be used carefully to avoid
hypotension and poor uterine perfusion. Planned
delivery with a cardio-obstetrics team is impor-
tant, as is risk stratification for SCD and careful
contraceptive measures postdelivery [30] (see
Part XI).

Arrhythmogenic Right Ventricular

Cardiomyopathy (ARVC)

ARVC is a familial disease process of the heart

muscle, predominantly impacting the right ven-
tricle in which myocardial tissue is replaced with
adipose and fibrous tissue. Subepicardial RV free
wall segments impacted by mechanical stress
Fig. 20.11 Post excitation epsilon waves in right precor-
during cardiac contraction are most frequently dial leads. (Used with permission, Orphanet Journal of
impacted [16, 31]. It is defined by right ventricu- Rare Diseases, 2 (1), 45. https://doi.
lar regional or global dysfunction, with or with- org/10.1186/1750-1172-2-45)
20 Heart Failure with Reduced Ejection Fraction (HFrEF) 211

including intramyocardial fat infiltration and RV increases the risk of subsequent stress-induced
dilation. recurrence.
Treatment involves risk stratification for ICD
consideration, as well as treatment with antiar-
rhythmic medications, beta blockers, and stan- Management
dard heart failure therapies. Anticoagulation may
be warranted. Finally, ARVC diagnosis precludes Guideline-Directed Medical Therapy
patients from participating in competitive or (GDMT)
resistance sports [31].
Based on the guidelines, patients with HFrEF
should be maintained on beta blockers, RAAS
Unclassified inhibition (angiotensin-converting enzyme inhib-
itors (ACEi)), angiotensin receptor blockers
Takotsubo Cardiomyopathy (ARB), or angiotensin-neprilysin inhibitors
(ARNi), and a mineralocorticoid receptor antag-
Stress cardiomyopathy or “broken heart syn- onist (MRA) [32] (Fig. 20.11). However, since
drome” is defined by acute decline in LVEF in publication of the 2017 American Heart
response to profound stress, primarily affecting Association and American College of Cardiology
older/postmenopausal women. Presentation of comprehensive heart failure guidelines, ongoing
acute chest pain is common. Diffuse T-wave clinical trial data has indicated reduction of mor-
inversions, possibly with ST elevations, are seen tality and benefit with four specific groups of
on electrocardiogram, and cardiac biomarkers medications which are now known as the “four
may be mildly elevated. The echocardiography pillars of heart failure therapy” [33] (Fig. 20.12).
findings of regional wall motion abnormalities The four pillars of heart failure therapy include a
impacting the LV apex (“apical ballooning”) in beta blocker, ARNI, MRA, and sodium-glucose
the absence of obstructive coronary disease are cotransporter 2 inhibition (SGLT2i). Isosorbide
pathognomonic for Takotsubo cardiomyopathy dinitrate and hydralazine have mortality benefit
[16]. This apical ballooning is the most common but are often second-line agents. There are addi-
form (85%), but isolated mid-wall and basal tional medical therapies that improve morbidity
wall motion abnormalities may occur (15%). but not mortality, including loop and thiazide
With supportive medical management, LV func- diuretics, ivabradine, digoxin, and vericiguat.
tion is rapidly reversible in days to weeks [17]. The focus of this section will be on the four pil-
A previous stress-induced cardiomyopathy lars of heart failure therapies and diuretics for

Fig. 20.12 Adapted The Four Pillars of Heart Failure Therapy

from Sam Straw et al.
Open Heart
ARNi Beta MRA SGLT2i
2021;8:e001585
Blockers

Consider alternative therapies

212 L. Eyadiel and B. Rasmussen

relief of congestion. Target doses of these medi- regard to rapid initiation and up-titration of the
cations and data-driven agents within each cate- four pillars of heart failure therapy to further
gory are summarized in Table 20.7. The mortality reduce morbidity and mortality for patients with
benefit of these agents has been shown to be dose HFrEF [34] (Fig. 20.13). A recommended rapid
dependent. There is a newer concept in manage- sequencing for initiation of GDMT is shown in
ment of HFrEF of the “need for speed” with the figure below [35].

Table 20.7 Target doses of the four pillars of heart failure guideline-directed medical therapies
Starting dose Target dose
Beta blockers
Bisoprolol 1.25 mg once daily 10 mg once daily
Carvedilol 3.125 mg twice daily 25 mg twice daily for weight <85 kg and 50 mg
twice daily for weight ≥85 kg
Metoprolol succinate 12.5–25 mg daily 200 mg daily
ARNI
Sacubitril/valsartan 24/26 mg twice daily 97/103 mg twice daily
ACEis
Captopril 6.25 mg three times daily 50 mg three times daily
Enalapril 2.5 mg twice daily 10–20 mg twice daily
Lisinopril 2.5 mg daily 40 mg daily
Ramipril 1.25 mg daily 10 mg daily
ARBs
Candesartan 4 mg daily 32 mg daily
Losartan 25 mg daily 150 mg daily
Valsartan 40 mg twice daily 160 mg twice daily
Mineralocorticoid receptor antagonists
Eplerenone 25 mg daily 50 mg daily
Spironolactone 25 mg daily 50 mg daily
SGLT2i
Dapagliflozin 10 mg daily 10 mg daily
Empagliflozin 10 mg daily 10 mg daily
Adapted from: https://www.jacc.org/doi/pdf/10.1016/j.jacc.2020.11.022

Conventional Sequencing Rapid Sequencing

ACEi/ARB
Beta blocker + SGLT2i

Beta blocker

Mineralocorticoid receptor antagonist ARNi

ARNi

Mineralocorticoid receptor antagonist

SGLT2i

Takes approximately 6 months to get on all Goal is patient on all 4 pillars of heart
4 pillars of therapy while maximizing the failure therapy within 4 weeks, then
dose before adding an additional agent. maximize to highest tolerated doses.

Fig. 20.13 Adapted from Packer and McMurray (2021), European Journal of Heart Failure [35]
20 Heart Failure with Reduced Ejection Fraction (HFrEF) 213

Beta Blockers ngiotension Receptor Blockers: ARBs

A
ARBs are an alternative agent to ACEIs with sim-
Beta blockers are utilized to decrease sympa- ilar mortality benefits in patients with heart fail-
thetic stimulation resulting in improved progno- ure with fewer adverse effects. These medications
sis in patients with HF. These medications are block the angiotensin receptor as the name indi-
considered the cornerstone of HFrEF therapy. cates. These medications do not cause cough and
While many beta blockers exist, only bisopro- are generally better tolerated than ACEIs. Patients
lol, metoprolol succinate, and carvedilol have who have had angioedema with ACEIs can be
shown a mortality benefit in patients with carefully challenged with an ARB as cross reac-
HFrEF. Initiation of beta blockade should be tivity is rare. Monitoring for ARBs is the same as
done with caution as they may worsen volume with ACEIs.
overload and precipitate cardiogenic shock if
initiated or up-titrated during acute decompen- Angiotensin Receptor-Neprilysin
sation. Withdrawal or dose reduction of beta Inhibitor: ARNIs
blockade in patients who are acutely decompen- ARNIs are superior regarding reduction in mor-
sated and in those at baseline has been shown to tality and HF hospitalizations when compared
increase mortality. Therefore, these should be with ACEIs or ARBs making these medications
continued, if possible, on admission. In a stable, one of the four pillars of heart failure therapy and
compensated patient, the goal is to increase to the drug of choice for RAAS inhibition. RAAS
the target dose as noted in Table 20.7. A good inhibition is achieved by blocking both angioten-
rule of thumb with beta blockers in heart failure sin and neprilysin. Neprilysin is an enzyme that
is to “start low and titrate slow.” Common side breaks down endogenous brain natriuretic pep-
effects of beta blockers include fatigue, exercise tide (BNP). BNP causes a natriuresis and diuresis
intolerance, erectile dysfunction, and via the kidney. ARNIs inhibit the breakdown of
bradycardia. BNP and improve sodium and fluid excretion.
These medications are indicated for patients with
chronic symptomatic HFrEF with any ejection
RAAS Inhibition fraction and NYHA Class II-IV symptoms. These
medications are more blood pressure lowering
CE Inhibitors (ACEIs)
A than ACEIs or ARBs thus should be used with
Angiotensin-converting enzyme inhibitors caution in patients with hypotension. The use of
(ACEIs) were the initial drug utilized in early ARNIs causes a transient elevation in BNP levels
trials showing a reduction in mortality for due to neprilysin inhibition but not in NT-pro
patients with heart failure. These medications BNP levels. ARNIs are contraindicated in patients
inhibit RAAS by inhibiting angiotensin-con- who have had angioedema to ACEIs. In addition,
verting enzymes. While on these medications, due to cross-reactivity, a 36-h washout period is
renal function and potassium levels should be required when transitioning from ACEI to ARNI
monitored as these can cause acute kidney but not when transitioning from ARB to ARNI.
injury and hyperkalemia. Because of this,
ACEIs should not be started in patients with
rapidly changing renal function. Patients on Mineralocorticoid Receptor
these medications can have a side effect of Antagonists
cough which can be mitigated by changing to
an ARB or ARNI. Rare, more serious side These medications work by blocking the RAAS
effects include severe allergic reactions includ- through inhibition of aldosterone production.
ing anaphylaxis and angioedema. ACEIs and MRAs are indicated in patients with symptom-
ARBs should not be administered as part of the atic heart failure with NYHA Class II-IV symp-
same HfrEF regimen. toms. The two agents include spironolactone and
214 L. Eyadiel and B. Rasmussen

eplerenone, both of which have a proven mortal- Diuretics

ity benefit in patients with HFrEF. Due to RAAS
inhibition, renal function must be monitored. Loop diuretics are the cornerstone of manage-
These agents are potassium-sparing diuretics, ment of congestion in patients with HF. That
and while their diuretic effect is weak, caution said, these medications have never shown a mor-
should be used in patients with hyperkalemia or tality benefit for patients with heart failure and
baseline potassium levels of thus are not considered one of the pillars of heart
>5.0 mmol/L. Gynecomastia is a common side failure therapy. The ideal dose is the lowest dose
effect of spironolactone, and patients can be the patient needs to achieve and maintain
changed to eplerenone. Newer literature indicates euvolemia. If this is not possible with loop diuret-
this agent reduces blood pressure in patients who ics alone, the use of thiazide diuretics for aug-
are hypertensive but does not have a significant mentation can be considered. Diuretics are best
effect on blood pressure in patients who are nor- given in the morning due to frequent urination.
motensive at baseline. Twice daily dosing can be considered with a sec-
ond dose midday to prevent nocturia if once daily
dosing is insufficient. Table 20.8 shows loop and
odium-Glucose Cotransporter 2
S thiazide diuretic agents and dosing options.
Inhibition (SGLT2i) Furosemide is the initial loop diuretic of
choice due to cost but overall has variable oral
SGLT2i works by blocking the sodium-glucose bioavailability. In the setting of diuretic resis-
cotransporter in the kidney, but the exact tance, or lack of diuresis with optimal dosing,
mechanism of benefit in patients with HFrEF is transitioning to an alternative loop diuretic with
unknown [33]. However, SGLT2 inhibition better oral bioavailability such as torsemide or
leads to osmotic diuresis and natriuresis result- bumetanide should be considered.
ing in decreased arterial pressure and stiffness When considering equivalent diuretic dos-
[36]. This, in turn, reduces preload and after- ages, 40 mg of oral furosemide = 20 mg of oral
load which results in reduction of adverse car- torsemide = 1 mg of oral bumetanide = 20 mg of
diac remodeling. These medications have been IV furosemide.
shown to reduce all-cause mortality in patients
with HFrEF which is likely driven by the statis-
tically significant reduction in heart failure hos- Device Therapy
pitalizations in patients with and without
diabetes. The medications which have been I mplantable Cardiac Defibrillators
studied for use in HFrEF include dapagliflozin (ICDs)
and empagliflozin. Common adverse effects About 50% of patients with HFrEF have ventric-
include dehydration, renal dysfunction, and ular arrhythmias resulting in sudden cardiac
yeast infections. When used in conjunction
with loop diuretics, the dose of loop diuretics Table 20.8 Diuretic dose ranges
should be decreased in anticipation of natriure- Diuretics Dose range
sis with initiation of SGLT2i. However, the Loop diuretics
exact dose adjustment of loop diuretics has not Furosemide 20–240 mg
yet been investigated. Like ACEIs, ARBs, and Bumetanide 0.5–5 mg
ARNIs, SGLT2is have been shown to be renal Torsemide 20–200 mg
Thiazide diuretics
protective in patients with chronic kidney
Metolazone 2.5–10 mg
disease. Hydrochlorothiazide 25–100 mg
20 Heart Failure with Reduced Ejection Fraction (HFrEF) 215

death [37]. Therefore, ICDs are indicated in

NYHA II/III patients with an LV ejection frac-
tion of ≤35% on optimal GDMT for 3 months for
prevention of sudden cardiac death [36].
Interestingly, patients who have a higher
New York Heart Association (NYHA) functional
class have a higher risk for sudden cardiac death.
While GDMT reduces the risk of sudden cardiac
death, this is not eliminated. Antiarrhythmic drug
therapies increase the sudden death risk. ICDs
are not indicated in patients who have a life
expectancy of less than 12 months. It is important
to note that ICDs do not provide any direct thera-
peutic benefit for HFrEF but instead act solely to
prevent sudden cardiac death from ventricular
arrhythmias.

Cardiac Resynchronization Therapy

(CRT)
CRT is indicated in patients who have a left bun-
dle branch block with a QRS of ≥150 ms
(Fig. 20.14), NYHA class II-IV symptoms, with
an LV ejection fraction of ≤35% on maximally
tolerated GDMT for 3–6 months. There are two
forms of CRT—one where this device acts solely
as a biventricular pacemaker (CRT-P) and the
other where a defibrillator lead is added to the Fig. 20.14 Findings of left bundle branch block mor-
right ventricle (CRT-D). Unlike ICDs, CRT has phology on EKG. (Used with permission, The American
Journal of Cardiology, 111 (2), 291–300 https://doi.
been shown to reduce mortality in patients with org/10.1016/j.amjcard.2012.09.029)
HFrEF by reducing heart failure events and
improving LVEF [38]. CRT-D is a three-lead
device with a lead in the right atrium, defibrillator when indicated, one should consider referral to
coil in the right ventricle, and a left ventricular an advanced heart failure specialist for consider-
lead which is placed in the coronary sinus. An ation of advanced heart failure therapies. The
alternative indication for CRT-D is high right high-risk features which indicate appropriateness
ventricular pacing burden in patients with dual- of referral are summarized in the acronym
chamber ICDs. The EKG of a standard RV apical I-NEED-HELP [33].
pacemaker is a LBBB morphology in lead V1.
CRT will have a more RBBB morphology in lead I: IV inotropes
V1. The higher the biventricular pacing percent- N: NYHA IIIB/IV or persistently elevated natri-
age, the more likely the patient is to have effec- uretic peptides
tive CRT. Higher dose of beta blockers may be E: End-organ dysfunction
used to optimize pacing as well. E: Ejection fraction ≤35
D: Defibrillator shocks
H: Hospitalizations >1
Advanced Heart Failure Therapies E: Edema despite escalating diuretics
L: Low blood pressure, high heart rate
If patients do not have improvement in LVEF and P: Prognostic medication: progressive intoler-
functional status with GDMT or addition of CRT ance or down-titration of GDMT
216 L. Eyadiel and B. Rasmussen

Advanced heart failure therapies include left cium channel blockers and alpha-adrenergic
ventricular assist devices and cardiac transplanta- blockers are recommended [39].
tion. Cardiac transplantation is considered for
patients with advanced heart failure who have an leep-Disordered Breathing (SDB)
S
acceptable BMI, are compliant with medications There is a strong association of both central
and follow-up, do not have substance abuse sleep apnea and obstructive sleep apnea with
including current tobacco use, and are 70 years of worse heart failure outcomes. Sleep-disordered
age or younger. breathing leads to increased inflammation, oxi-
dative stress-induced endothelial dysfunction,
increased sympathetic nervous system activa-
Management of Comorbidities tion, and increased intrathoracic pressure fluc-
tuations. This in turn causes an increase in LV
The 2017 American College of Cardiology afterload and possibly contributes to atrial
(ACC) consensus statement identified cardiovas- fibrillation which is strongly associated with
cular and non-cardiovascular heart failure comor- SDB [40]. Addressing and treating SDB
bidities: coronary artery disease, atrial through oxygen therapy or positive airway
dysrhythmias, mitral regurgitation, aortic steno- pressure therapy are imperative in heart failure
sis, hypertension, dyslipidemia, peripheral vas- management.
cular disease, cerebrovascular disease, obesity,
chronic lung disease, chronic renal disease, Iron Deficiency
anemia, iron deficiency, thyroid disorders, and Iron deficiency, even in the absence of anemia, is
sleep-disordered breathing [32]. prevalent among heart failure patients and associ-
ated with decreased functional capacity and sur-
Mitral Regurgitation vival [41]. The ACC guidelines recommend that
Recent trials (Coapt) in patients after optimiza- patients with iron deficiency defined as ferritin
tion of GDMT and at least moderate residual sec- <100 ng/L or ferritin 100–300 ng/L if transferrin
ondary mitral regurgitation have shown mortality saturation is less than 20% be considered for
benefit with intervention on the mitral valve. intravenous iron therapy to improve functional
Transcatheter edge-to-edge mitral repair (TEER) status [41].
has been shown to confer additional mortality
benefit. Consideration of intervention upon the Clinical Pearls
valve should be considered (see Chap. 17). • Never forget, there is no substitute for a good
history and physical exam. Heart failure is a
Hypertension clinical diagnosis which is confirmed with
While no clinical trials evaluating optimal blood imaging and laboratory testing.
pressure lowering agents and blood pressure • Physical exam: Jugular venous pressure
reduction in the setting of HFrEF and hyperten- assessment is an important skill learned over
sion are available, ACC guidelines recommend time.
management of HFrEF with concurrent hyper- • Ischemic evaluation: All patients with a new
tension with GDMT to a goal threshold associ- diagnosis of heart failure or a new decline in
ated with improved clinical outcomes in other LV ejection fraction need an ischemic evalua-
high-risk populations: less than 130/80 mmHg. tion to rule out a reversible cause or a contrib-
In clinical practice, the goal is to reduce patients’ uting factor to the reduction in ejection
blood pressure in HFrEF to as low as a patient fraction.
will tolerate without symptoms of orthostasis. In • GDMT: Do not repeat imaging until your
addition to GDMT, diuretics can be used in patient is on maximally tolerated GDMT to
patients with volume overload to control blood determine ICD candidacy or advanced ther-
pressure. Avoidance of non-dihydropyridine cal- apy. Maximal GDMT means the highest doses
20 Heart Failure with Reduced Ejection Fraction (HFrEF) 217

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Orphanet J Rare Dis. 2007;2(1):45. https://doi. dosis. Biomedicines. 2022;10(4):903. https://doi.
org/10.1186/1750-1172-2-45. org/10.3390/biomedicines10040903.
Heart Failure with Preserved
Ejection Fraction (HFpEF)
21
Carolina D. Tennyson

Anatomy and Physiology Table 21.1 Risk factors for HFpEF

Risk factors for heart failure [1]
Heart failure (HF) is a complex clinical syndrome Sedentary lifestyle
that results from any structural or functional Cigarette smoking
Obesity
impairment of cardiac output. Heart failure with
Excessive alcohol intake
preserved ejection fraction (HFpEF) is a chronic Influenza
HF syndrome in the setting of an EF > 50%. It is Cardiotoxic drugs
estimated that HFpEF accounts for at least one- Chest radiation
half of all HF cases. The initial diagnosis of Hypertension
HFpEF frequently progresses to a chronic clini- Dyslipidemia
cal course of HFrEF (see Tables 21.1 and 21.2). Diabetes mellitus
Coronary artery disease
Patients with HFpEF typically have one or
more of the following underlying pathophysio-
logic processes acting together: (1) diastolic dys-
function due to impaired left ventricular (LV) tor for cardiorenal and cardio-hepatic syndromes
relaxation, or LV diastolic stiffness; (2) LV in all forms of clinical heart failure.
remodeling; (3) increased ventricular and arterial Acute HF can result in rapid decompensation
stiffness; (4) right HF due to pulmonary venous and can be attributed to neurohormonal activa-
hypertension; (5) chronotropic incompetence; tion, venous congestion, endothelial dysfunction,
and (6) endothelial dysfunction. Underlying myocardial injury, and renal dysfunction [3].
comorbidities like chronic kidney disease, hyper- This constellation of physiological changes
tension, and diabetes mellitus contribute to a sys- causes the patient symptoms of dyspnea, fatigue,
temic proinflammatory state. This activates the peripheral pitting edema, and jugular vein disten-
renin-angiotensin-aldosterone system (RAAS), tion. Exercise intolerance, weight gain, early sati-
which is a critical regulator of blood volume and ety, and dyspnea are common presentations of
systemic vascular resistance. The activation of HFpEF exacerbation.
the RAAS system and altered perfusion affects
end-organ function, and clinicians should moni-

C. D. Tennyson (*)
Duke University School of Nursing,
Durham, NC, USA
e-mail: [email protected]

© The Author(s), under exclusive license to Springer Nature Switzerland AG 2023 221
R. Musialowski, K. Allshouse (eds.), Cardiovascular Manual for the Advanced Practice Provider,
https://doi.org/10.1007/978-3-031-35819-7_21
222 C. D. Tennyson

Table 21.2 Some etiologies of HFpEF Classification (See Chap. 20)

Hypertensive heart disease [2]
Coronary artery disease Imaging (See Chap. 20)
Ischemic cardiomyopathy
Severe, chronic, stable coronary disease
Restrictive cardiomyopathy Diagnosis
Infiltrative diseases (amyloidosis, sarcoidosis, The diagnosis of HFpEF can be challenging
hemochromatosis) because it requires exclusion of other potential
Primary diabetic cardiomyopathy noncardiac causes of symptoms suggestive of
Idiopathic
HF. There is no single diagnostic test for HF
Hypertrophic cardiomyopathy
Obstructive or nonobstructive because it is largely a clinical diagnosis based on
Primary valvular heart disease a careful history and physical exam. The
Aortic stenosis European Society of Cardiology recommends a
Aortic regurgitation simple diagnostic approach that includes all of
Mitral stenosis
Mitral regurgitation the following:
Pericardial disease
Constrictive pericarditis 1. Symptoms and signs of HF
Cardiac tamponade 2. Evidence of an LVEF ≥50%
Primary right ventricular dysfunction
3. Objective evidence of cardiac structural and/
Pulmonary arterial hypertension
Arrhythmogenic right ventricular dysplasia or functional abnormalities consistent with
Congenital heart disease the presence of LV diastolic dysfunction/
High-output cardiac failure (uncommon) raised LV filling pressures, including raised
Severe anemia natriuretic peptides [2]
Thyrotoxicosis
Cirrhosis
Shunt due to large arteriovenous fistulae In patients presenting with dyspnea, measure-
ment of natriuretic peptide biomarkers is useful
to support a diagnosis or exclusion of HF but is
Physical Exam (See Chap. 20) not diagnostic itself [1].

A full physical exam should be completed.

Special attention should be paid to: Management

• Lung fields should be assessed for crackles/ Medical Therapy

rales that may indicate pulmonary edema
• Jugular venous distension +/ hepatojugular There are fewer medications with demonstrated
reflex benefit for HFpEF as compared to HFrEF. For
• Edema in the legs, hips, and abdomen patients with HFpEF, the diagnosis and treatment
• Heart sounds: rate, rhythm, S3 and/or S4 of contributing factors such as atrial fibrillation,
sound may indicate volume overload hypertension, coronary artery disease, diabetes,
• Signs of low cardiac output (cool and/or dia- and chronic kidney disease are essential to pre-
phoretic skin, weak pulses) vent the progression of HF. Beta blockers should
be used cautiously in patients with amyloidosis
Volume status and vital signs should be as the cardiac output is very heart rate
assessed at each patient encounter. This includes dependent.
serial assessment of body weight, as volume Patients with HFpEF and persistent hyperten-
overload will result in weight gain. sion should be treated to attain a systolic blood
21 Heart Failure with Preserved Ejection Fraction (HFpEF) 223

pressure less than 130 mmHg. There are limited evaluations for either of these two volume states.
data to guide the choice of antihypertensive ther- Loop diuretics like torsemide, furosemide, and
apy in HFpEF, but medications that inhibit the bumetanide have not been found to improve sur-
renin-angiotensin-aldosterone system are pre- vival but are the main agent for symptom man-
ferred (i.e., mineralocorticoid receptor antago- agement and decongestion. Intravenous delivery
nist, angiotensin receptor neprilysin inhibitor) should be used for patients needing immediate
[1]. relief or who are decompensated.
Patients with HFpEF are more likely than the Periodically, all HF patients should be
general population to have atrial fibrillation. screened for iron deficiency anemia.
Heart rhythm and rate control are important Symptomatic, ambulatory HF patients with iron
mainstays of HFpEF treatment. It is very impor- deficiency anemia and EF ≤45% or hospitalized
tant to consider occult unrecognized paroxysmal HF patients with EF ≤50% should be supple-
atrial fibrillation as a cause of decompensation mented with ferric carboxymaltose.
and recurrent hospitalization, even if the patient
presents through ED in normal sinus rhythm.
Management of atrial fibrillation is reasonable to Nonmedical Management
improve symptomatic HF. Beta blockers are the
preferred agent for achieving rate control, and Patients who are admitted to the hospital for the
digoxin may be an effective adjunct therapy. primary problem of heart failure exacerbation
Diltiazem has a mild negative inotropic effect should have a follow-up appointment within
and should be used with caution. When rate or 1 week to evaluate fluid volume status, review any
rhythm control is not achievable, AV nodal abla- changes made in medication regimen, and provide
tion and resynchronization therapy device place- patient education. Fluid restriction is beneficial to
ment can be useful [4]. minimize readmissions, and dietary salt restriction
The SGLT2 inhibitor empagliflozin is the is recommended, but this recommendation is cur-
agent approved for reducing the risk of cardio- rently being reevaluated in clinical trials.
vascular death and hospitalization for HF in
patients with HFpEF. Multiple mechanisms of Clinical Pearls
action are thought to contribute to this cardio- • The evidence-based medication to treat
vascular benefit including the lowering of glu- HFpEF is an SGLT2 inhibitor.
cose, blood pressure, and body weight. SGLT2 • Treating comorbidities like hypertension, obe-
inhibits also induce a mild diuretic effect, reduc- sity, and atrial fibrillation can help mitigate the
tion of uric acid, and higher red cell mass [5]. progression and exacerbation of HF.
Empagliflozin does not need to be titrated for • Volume status can sometimes be tenuous in
HF benefit. Reduction of a patient’s insulin regi- the HFpEF population. Use the lowest dose of
men should be considered when initiating an effective loop diuretic in conjunction with
SGLT2 inhibitor. Additionally, evidence is SGLT2 inhibitors to maintain euvolemia.
mounting that the prescription of SGLT2 inhibi- Educate the patient regarding daily weights
tors even during hospitalization for acute heart and PRN dosing to avoid hospitalization.
failure can also provide clinical benefit within • Preferred treatment of HTN for patients with
90 days [6]. HFpEF is medications that work to modify the
HFpEF is a preload driven diagnosis. The dia- RAS system (ACE-I/ARB/ARNI, MRA).
stolic filling curve is very steep. Thus, the ven- • When patients with HFpEF have persistent
tricle progresses rapidly from volume depletion symptoms and/or HF hospitalizations despite
to pulmonary edema. This pathology leads to the optimal medical therapy, refer to an advanced
frequent and recurrent emergency department HF program.
224 C. D. Tennyson

References 4. Yancy CW, Jessup M, Bozkurt B, Butler J, Casey DE,

Drazner MH, et al. 2013 ACCF/AHA guideline for
the management of heart failure. J Am Coll Cardiol.
1. Yancy CW, Jessup M, Bozkurt B, Butler J, Casey DE,
2013;62(16):e147–239.
Colvin MM, et al. 2017 ACC/AHA/HFSA focused
5. Rangaswami J, Bhalla V, de Boer IH, Staruschenko A,
update of the 2013 ACCF/AHA guideline for the
Sharp JA, Singh RR, et al. Cardiorenal protection with
management of heart failure. J Am Coll Cardiol.
the newer antidiabetic agents in patients with diabe-
2017;70(6):776–803.
tes and chronic kidney disease: a scientific statement
2. McDonagh TA, Metra M, Adamo M, Gardner RS,
from the American Heart Association. Circulation.
Baumbach A, Böhm M, et al. 2021 ESC guidelines for
2020;142(17):e265–86.
the diagnosis and treatment of acute and chronic heart
6. Voors AA, Angermann CE, Teerlink JR, Collins SP,
failure: developed by the task force for the diagnosis
Kosiborod M, Biegus J, et al. The SGLT2 inhibitor
and treatment of acute and chronic heart failure of the
empagliflozin in patients hospitalized for acute heart
European Society of Cardiology (ESC) with the special
failure: a multinational randomized trial. Nat Med.
contribution of the Heart Failure Association (HFA) of
2022;28:1–7.
the ESC. Eur Heart J. 2021;42(36):3599–726.
3. Mentz RJ, O’Connor CM. Pathophysiology and clini-
cal evaluation of acute heart failure. Nat Rev Cardiol.
2016;13(1):28–35.
Pulmonary Vascular Disease
22
Lyn Shelton and Joe Mishkin

Introduction Sixth World Symposium on Pulmonary

Hypertension further defines PH in updated terms
Pulmonary hypertension, in its basic definition, is of Pre- and Post-capillary pulmonary hyperten-
the elevation of pulmonary artery pressures. The sion. Patients may also have a combination of
elevated pulmonary artery pressures result both forms of pulmonary hypertension. These
from pulmonary vasculature remodeling due to designations require hemodynamic assessment
an underlying disease process. Over time the via right heart catheterization for pulmonary
resultant progressive workload imposed via the artery pressures and pulmonary capillary wedge
pulmonary vasculature overworks the right ven- pressure measurements, respectively.
tricle. PAH without intervention may be progres- Precapillary pulmonary hypertension is
sive, leading to right heart failure and death. defined as a mean pulmonary artery pressure
Regarding formal diagnostic criteria, how- (mPAP) greater than 20 mmHg at rest in addition
ever, pulmonary hypertension consists of a mean to pulmonary capillary wedge pressure (mPCWP)
pulmonary artery pressure greater than 20 mmHg. less than or equal to 15 mmHg and a pulmonary
Previously, the cutoff was a mean PA pressure vascular resistance (PVR) greater than or equal to
greater than or equal to 25 mmHg based upon an 3 Wood units. PVR is a function of mean pulmo-
arbitrary number. Evidence suggested that nary artery pressure minus mean wedge giving us
patients in the borderline range of a mean PA transpulmonary gradient. (TPG). The TPG
pressure 21–24 mmHg had suffered worse out- divided by cardiac output equals PVR.
comes which prompted the guideline update. The

TPG = Mean PApressure − Mean pulmonary capillary wedge pressure

PVR = TPG / cardiac output ( COL / min )

L. Shelton (*) J. Mishkin

Atrium Health/SHVI Heart Failure/Transplant Clinic, Atrium Health/SHVI Heart Failure/Transplant Clinic,
Pulmonary Hypertension Clinic, Pulmonary Hypertension Clinic, Charlotte, NC, USA
Charlotte, NC, USA
Atrium Health/Sanger Heart and Vascular Institute,
Asheville Cardiology, Asheville, NC, USA Charlotte, NC, USA
e-mail: [email protected] e-mail: [email protected]

© The Author(s), under exclusive license to Springer Nature Switzerland AG 2023 225
R. Musialowski, K. Allshouse (eds.), Cardiovascular Manual for the Advanced Practice Provider,
https://doi.org/10.1007/978-3-031-35819-7_22
226 L. Shelton and J. Mishkin

As you can see from the above equations, spe- Table 22.1 WHO group classifications of pulmonary
hypertension
cific factors can drive pulmonary vascular resis-
tance. The higher the PA pressure versus the I. PAH Idiopathic
Drug and toxin-induced
mean wedge pressure, the higher the PVR. PVR Heritable
is augmented when there is lower cardiac output. Associated with PAH: Examples
Try to think of PVR as a factor of the difficulty of include connective tissue
moving blood from the right heart through the disorders, portal hypertension,
congenital heart disease, HIV
lungs to reach our left heart circulation. infection, Pulmonary venous
Precapillary PH entails elevated pulmonary occlusive disease (PVOD)
pressures in the absence of left-sided heart disease/ II. Pulmonary LV systolic or diastolic
volume overload (i.e., therefore excludes WHO hypertension due to dysfunction, valvular heart
left-sided heart disease
Group II PH). Isolated post-capillary pulmonary
disease
hypertension is defined as mPAP greater than III. Pulmonary Examples include COPD, ILD,
20 mmHg with mPCWP greater than 15 mmHg and hypertension due to OSA
a PVR <3 Wood units. This is consistent with higher lung disease and/or
filling pressures secondary to left-sided heart dis- hypoxia
IV. Chronic Pulmonary embolism
ease (WHO Group II or also can include WHO thromboembolic
Group V). There is also combined pre- and post- pulmonary
capillary pulmonary hypertension where mPCWP hypertension
is greater than 15 mmHg and, PVR is greater than 3 (CETPH).
Wood units. Typically, the pulmonary vascular bed V. Pulmonary Examples include end-stage
hypertension with renal disease on dialysis,
can vasodilate in response to enhanced flow. unclear or myeloproliferative disorders,
However, if we examine PAH histologically, we multifactorial sarcoidosis
find remodeling of the distal pulmonary vasculature mechanisms
with the growth of endothelial and smooth muscle
cells as well as infiltration of inflammatory cells
[1–3]. This is manifested by constriction via vascu- of underlying etiologies, placing them in more
lar remodeling with fibrosis and stiffness. In addi- than one WHO group. Pharmacological treat-
tion, there is in situ thrombosis [4]. Factors in PH ment strategies will be outlined in further detail
patients that lead to these changes include decreased later but focus on WHO group I PAH as well as a
nitric oxide (NO) levels and increased endothelial pharmacological indication for WHO group IV.
levels. NO is an antiproliferative and a vasodilator, The Global prevalence of PAH is often diffi-
while endothelin is a vasoconstrictor. Prostacyclin cult to assess. European registries have reported
levels are also decreased. Prostacyclin is antiprolif- rates of 5–52 per million people. Regarding WHO
erative, inhibits platelet function, and is a vasodila- Group I, statistics note an annual incidence of
tor. The pathophysiology of PAH has led to the 2–5 cases per million people and affects 25 per-
development of medications that affect these path- sons per one million population in Western coun-
ways and are targets for treatments [5]. tries. Contrasting this with WHO group 2,
valvular left-sided heart disease accounts for
more than 100 million persons [6, 7].
Classifications

We need to further categorize pulmonary hyper- Presentation/Physical Exam

tension based upon the underlying disease pro- Findings
cess. The World Health Organization (WHO)
designates five classification groups of pulmo- As an APP, you will be required to evaluate and
nary hypertension (Table 22.1). It should be treat patients with primary cardiac issues, but
noted that although patients may have a diagnosis often they possess concomitant comorbidities.
of PH, often these patients possess a combination Patients frequently present with complaints of
22 Pulmonary Vascular Disease 227

Table 22.2 Physical exam findings that may be suggestive of pulmonary hypertension
An increased pulmonic High-pitched early diastolic Abnormal pulmonary exam may be associated
component of the second murmur of pulmonic with underlying pulmonary diseases such as
heart sound [11]. regurgitation interstitial lung disease (ILD), COPD/
emphysema. These include velcro-like dry
crackles, wheezing, or severely diminished
airflow
Holosystolic murmur of Elevated jugular venous The examination may also include a large A wave
tricuspid regurgitation distention corresponding to right in the jugular venous pulse or may also have
ventricular fluid overload as well prominent V waves in the jugular venous pulse
as tricuspid regurgitation secondary to tricuspid regurgitation
Liver tenderness or Right heart failure signs may Patients may have a palpable RV heave given
enlargement on exam include peripheral edema or right ventricular hypertrophy/dilation
ascites
Cyanosis and evidence of Scleroderma patients may have
clubbing may be present associated skin changes,
in patients with underlying telangiectasias, digital
shunts or congenital heart ulcerations.
disease

dyspnea, fatigue and progressive functional limi- by left main coronary artery compression sec-
tations. This presentation may be consistent with ondary to an enlarged pulmonary artery [9].
pulmonary HTN, but the differential diagnosis is Syncope in patients with underlying pulmonary
lengthy. Given that presenting symptoms can arterial hypertension is highly concerning for
often be attributed to other comorbidities, PH poor cardiac output with RV dysfunction,
patients may have a delay in diagnosis and subse- reduced forward flow, and high pulmonary vas-
quent treatment. cular resistance. Patients with right heart failure
REVEAL (Registry to Evaluate Early and and strain may present with prominent abdomi-
Long-Term PAH Disease Management) data nal distention/ascites as well as lower extremity
review in 2011 noted 21.1% of patients experi- edema and JVD (see discussion on cor pulmo-
enced symptoms greater than 2 years before PAH nale). Rare findings may include hoarseness via
was recognized. Patients less than 36 years of age Ortner’s syndrome, in which the left laryngeal
showed the highest likelihood of delayed disease nerve becomes paralyzed secondary to com-
recognition as well as those patients with a docu- pression by dilated pulmonary artery [10].
mented history of common respiratory diseases Work-up and subsequent treatment options will
with obstructive sleep apnea/obstructive airways be based on the type of diagnosed pulmonary
disease [8]. Therefore, a detailed history and hypertension and associated comorbidities. A
proper examination combined with appropriate detailed physical exam is an essential compo-
diagnostic testing are paramount. Higher risk nent of assessing the pulmonary hypertension
comorbidities, such as a history of connective tis- patient (Table 22.2).
sue disorder, liver disease, HIV disease, throm-
boembolic history, or methamphetamine abuse,
should imply a higher suspicion for pulmonary Diagnostic Modalities/Imaging
arterial hypertension [1]. This should also include
those with a history of congenital heart disease. Diagnostic testing is necessary to assist in eluci-
More advanced PAH may present with chest dating the form of pulmonary hypertension to
pain, syncope, and evidence of right heart fail- guide your treatment strategy. Testing should aid
ure/strain. Chest pain can be seen due to reduced in confirming or excluding forms of pulmonary
cardiac output as a factor of RV strain and over- hypertension, for which the management strategy
load in combination with higher pulmonary vas- should be focused on the underlying disease pro-
cular resistance. Chest pain may also be caused cess versus PAH. Examples include PH second-
228 L. Shelton and J. Mishkin

ary to obstructive sleep apnea, chronic pulmonary TTE has been used to estimate pulmonary
disease, systolic and diastolic heart failure. artery systolic pressure (PASP) or right ventricu-
lar systolic pressure (RVSP) at times. It is not
recommended to use estimated pulmonary artery
Echocardiography pressure, however, via echo for diagnosis. This
given potential inaccuracies of estimated right
Transthoracic echo (TTE) is one of the hallmarks atrial pressure as well as suboptimal tricuspid
of pulmonary hypertension screening tests. One regurgitation signal or interpretation, which are
benefit is that's it's noninvasive and widely avail- used to estimate PA pressures [12]. Furthermore,
able. It can be a useful initial screening study in TTE findings should never be utilized in the place
the setting of presenting subjective symptoms. of right heart catheterization for documenting
TTE is effective at identifying structural changes definitive pulmonary artery systolic pressure for
that may be associated with pulmonary hyperten- initiation or alteration of therapies for PAH.
sion. These include right ventricular size and sys- However, tricuspid regurgitation velocity
tolic function, presence of pericardial effusion, (TRV) has been utilized for assigning the echo-
and presence and severity of tricuspid regurgita- cardiographic probability of pulmonary hyper-
tion. It can assess for flattening of the interven- tension in patients suspected of having pulmonary
tricular septum (D-shaped LV) associated with hypertension. TRV greater than 3.4 m/sec con-
right ventricular pressure and/or volume overload fers a high risk of pulmonary hypertension,
(Fig. 22.1). In addition, an echocardiogram can whereas below 2.8 m/sec without other signs of
identify other potential contributing factors to pulmonary hypertension changes on echo con-
pulmonary hypertension including diastolic dys- fers a low probability if no other parameters of
function, valvular heart disease, and left ventricu- PH findings on echo are met [13]. A TRV of less
lar systolic dysfunction. than 2.8 m/sec without other presence of pulmo-
nary hypertension signs on echo confers a low
probability.

Computerized Tomographic
Angiography (CTA) of the Chest

CTA is used to assess for acute pulmonary embo-

lism given concern for thromboembolic phenom-
enon as acute potential cause for pulmonary
hypertension and right ventricular systolic dys-
function. It should be noted that CTA is an appro-
priate modality for the evaluation of underlying
acute pulmonary emboli. However, its sensitivity
may be suboptimal for defining chronic thrombo-
embolic phenomenon in WHO IV. (Please see
V/Q scan discussion below).

CT of the Chest

Fig. 22.1 D-shaped interventricular septum of PH and
Obtained for parenchymal lung disease, assess
RV enlargement. The RV is severely dilated and larger
than the LV. High RV pressures flatten the septum into a for RV dilation, assess enlarged main pulmonary
D-shape artery.
22 Pulmonary Vascular Disease 229

Ventilation Perfusion Scan PAH therapy and subsequent titrations based on

follow-up hemodynamics after therapy is initi-
This scan can identify potential chronic thrombo- ated. (See Chap. 2).
embolic phenomenon as CTA chest has dimin-
ished sensitivity in identifying chronic
thromboembolic pulmonary disease. Even if a Chest X-ray
patient has a negative CTA chest for pulmonary
embolism, this does not exclude the potential for May show enlargement of the pulmonary arter-
chronic thromboembolic disease. ies/RV enlargement.
V-Q scan utilizes an inhaled radiolabeled
aerosol and injectable radioactive tracer to assess
lung ventilation/perfusion. A nuclear camera is 12 Lead ECG
utilized to register distribution of the radioactive
material on the alveoli and pulmonary arteries, EKG Findings in pulmonary hypertension may
looking for mismatches. Results are noted as include right axis deviation, p pulmonale c/w
high, intermediate, or low probability and non- right atrial enlargement, signs of RV hypertro-
diagnostic [14]. phy, RV strain, RBBB, and in some cases QTc
prolongation [15].

PFTs: Pulmonary Function Studies

OSA Evaluation
This functional test helps identify pulmonary
hypertension attributed to WHO group III with Sleep apnea may be a contributing factor to WHO
the suggestion of underlying restrictive or Group III pulmonary hypertension which, can be
obstructive lung disease. PFTs also utilize DLCO readily diagnosed and treated. We will discuss
(diffusion capacity), which can be noted to be sleep apnea in further detail later.
decreased in pulmonary arterial hypertension and
concern for PVOD (pulmonary venous occlusive
disease.) Vasoreactivity Study

This study is done at the time of the initial right

Cardiac MRI heart cath. This involves assessing pulmonary
pressure changes with a Vaso-reactive agent: typ-
CMRI is the gold standard for right ventricular ically, this is inhaled nitric oxide. Vaso-reactive
assessment as it can give accurate measurements patients demonstrate a reduction in mean pulmo-
of anatomy, ejection fraction, flow, and even nary artery pressure of ≥10 mmHg to an absolute
assess for myocardial perfusion. value of ≤40 mmHg with either an increase or no
change in cardiac output (CO). Treatment of Vaso
reactive patients will be discussed under treat-
Right Heart Catheterization ment options.

This invasive study is required for the diagnosis

of pulmonary arterial hypertension as it provides 6-min Walk
direct hemodynamic assessment. It is mandatory
to confirm the presence of and help delineate This easy evaluation is the measurement of dis-
the type of pulmonary hypertension (pre/post/ tance walked in 6 min but is a vital data point
combined), and assist with risk stratification. It linked to survival rates. This must be measured in
also provides the hemodynamic data to initiate a consistently.
230 L. Shelton and J. Mishkin

Pulmonary Artery (PA) Angiogram ive treatments for PAH are an essential compo-
nent of the treatment paradigm. Basic supportive
A PA angiogram is a catheterization-based proce- treatments should be indicated in the treatment of
dure to assess for pulmonary emboli. It is typi- an underlying disease process (Table 22.3).
cally indicated if abnormal VQ Scan or high Patients with confirmed WHO Group 4 PH
suspicion for chronic thromboembolic disease secondary to thromboembolic disease should be
(WHO Group IV PH). referred early to a specialty center for pulmonary
endarterectomy. If they are not candidates for
surgery, balloon pulmonary angioplasty (BPA)
Initial Routine Lab Work and medical therapy should be considered.

1. Complete blood count. Rule out anemia or

potential for possible blood dyscrasias.
Table 22.3 Supportive treatment options
2. Complete metabolic panel for assessment of
Treatment Recommendations
renal function, liver function studies (porto-
Supervised Avoid over-strenuous exertion/
pulmonary HTN). exercise symptomatic exercise
3. Hepatitis panel. Supplemental When required to maintain
4. Thyroid panel. oxygen appropriate oxygen sats with rest,
5. HIV serologic testing. exercise, or sleep
Anticoagulation As indicated in WHO Group IV
6. Genetic testing: BMPR2. BMPR2 mutation
(CTEPH)
accounts for 80% of heritable and 20% of In idiopathic PAH-must be
idiopathic pulmonary hypertension [16]. determined on an individual basis
7. Assessment for connective tissue disorders. Diuretics Cautious use for right heart failure
For example: ANA. as it can cause reduced right heart
preload
8. Cardiac BNP or NTProBNP.
Diuretics for patients with high
left-sided filling pressures (WHO
Group II)
Treatment Arrhythmias Aggressive treatment of SVTs.
Often poorly tolerated in severe
PAH
In terms of pulmonary hypertension manage- Typically try to avoid negative
ment, it is important to verify the type/types of inotropic medications with right
pulmonary hypertension and risk stratify patients. heart failure
Tools are readily available to clinicians to risk Avoidance of High mortality risk in PAH and
stratify pulmonary hypertension patients into pregnancy pregnancy. Necessity for
appropriate contraception
low, intermediate, and high-risk groups. These Underlying Needs appropriate treatment of
classifications are based on functional, clinical, pulmonary underlying pulmonary disease
and hemodynamic measurements. There are disease
many comprehensive risk stratification tools Smoking
cessation
available. The following parameters appear to
Immunizations Including PNA/pneumococcal
have the greatest predictive accuracy: 6-min walk vaccinations
distance, BNP/NTproBNP, right atrial pressure, Psychosocial support
cardiac index, and mixed venous oxygen satura- Hematology Correction of iron deficiencies
tion [17]. given increased metabolic demand
with anemia/iron deficiency
The REVEAL registry uses variables to calcu-
WHO Group IV Early referral to a special center for
late 1-year mortality and is predictive of survival (CTEPH) potential pulmonary
at baseline, 1-year follow-up, and 5-year follow- thromboendarterectomy or balloon
up. In the absence of or in conjunction with PAH pulmonary angioplasty (BPA) if a
pharmacologic therapy when indicated, support- candidate
22 Pulmonary Vascular Disease 231

Pharmacological therapy has been shown via Prostacyclin Pathway

clinical trial results to be indicated in pulmonary
arterial hypertension (WHO Group I) and WHO Prostacyclin induces potent vasodilatation of all
Group 4. Patients with WHO Group 2 and 3 PH vascular beds. This decreases pulmonary vascular
should not be treated with PAH- specific therapy resistance and reduces pressure. It inhibits platelet
due to the high risk of complications. The excep- aggregation and appears to have both cytoprotective
tion is pulmonary hypertension associated with and antiproliferative activities [20]. It can be deliv-
interstitial lung disease (WHO Group III), with ered orally, via IV or subcutaneously, or inhaled.
recent data demonstrating the benefits of inhaled Common side effects include local site pain
prostacyclin, Treprostinil [18]. Goals of therapy (SQ route), vasodilatory side effects such as head-
and factors associated with better prognosis ache, flushing, and GI upset. The side effects can
include functional class I–2, 6-min walk distance be dose-dependent. IV or SQ is initiated at a low
greater than 400 m, and normal right ventricular dose (usually 1–2 ng/kg/min) and titrated upward
function per echocardiogram and hemodynamic slowly over time to achieve clinical improvement
parameters (Table 22.4). or occasionally limited due to side effects. IV
Current treatment recommendations call for requires an indwelling catheter which can increase
upfront oral combination therapy for low to the risk of line-associated infections. Therefore,
intermediate-risk patients with PAH and upper appropriate hygiene measures are necessary. In
combination therapy that should include pros- addition, we always recommend IV prostacyclin
tacyclin therapy for patients with high-risk fea- infuse via a single-lumen catheter. You must avoid
tures. Patients should be reevaluated 3–6 flushing the line containing the prostacyclin,
months from the start of combination therapy, which, if given as a bolus, can induce profound
and if goals are not met, sequential triple ther- hypotension, GI side effects, or even reports of
apy or escalation of therapy from oral to paren- deaths associated with boluses. See Table 22.5.
teral prostacyclin is most likely to be considered
[19]. Table 22.5 Prostacyclins
Vasoreactivity testing is recommended to Prostacyclin Utilization/description
evaluate the response to calcium channel blocker IV Prostacyclin analog
only for patients with idiopathic PAH, heritable Epoprostenol Demonstrated survival benefit in
PAH, and PAH associated with drugs and toxins. randomized clinical trials
If positive, then high-dose calcium channel Half-life few minutes: Potential for
rebound effects if interruptions in
blocker is used, If goals of therapy are not therapy
achieved after 3–6 months, it is recommended to Common side effects: Diarrhea, jaw
start specific PAH therapy. pain, muscle pain, flushing, headache
Regarding pharmacologic therapy for PAH, Iloprost Inhaled prostacyclin therapy
there are three main pathways typically targeted. Short half-life, therefore, must be given
6x a day
These include the prostacyclin pathway, endothe-
Common side effects: Cough,
lium pathway, and nitric oxide. headache, flushing
Treprostinil Longer half-life than Epoprostentol
Available via IV, subcutaneous route
Subcutaneous route may experience
infusion site pain, swelling, redness
Selexipag Selective prostacyclin receptor agonist.
Table 22.4 Goals of therapy/factors associated with bet- Orally dosed
ter prognosis Starts 200 mcg bid and titrate up to
Functional class NYHA class 1–2 1600 mcg bid if tolerating
6-minute walk distance Greater than 400 meters Similar side effects to others with
Right ventricular function Normal headache, flushing, arthralgias, jaw
Treatment regimen Combination therapy pain, and GI side effects with nausea/
diarrhea. SEs may be dose-dependent
232 L. Shelton and J. Mishkin

Table 22.6 Endothelin Receptor Antagonists

ERA generic Brand Dosing Monitoring
Ambrisentan Letairis® 5, 10 mg Selective ETA receptor antagonist, low risk of liver injury
Risk of edema (class effect)
Macitentan Opsumit® 10 mg Risk of edema. Potential for anemia
Bosentan Tracleer® 62.5 mg,125 mg Liver toxicity potential so close monitoring required
Pre/post-initiation/ongoing treatment
<40 kg: start with 62.5 mg bid >40 kg: Start 62.5 mg bid and then
increase to 125 mg bid in 4 weeks

Endothelin Receptor Antagonists Table 22.7 PDE-5 Inhibitors

PDE-5i generic Brand Dosing
Endothelial -1 is a vasoconstrictor and has Type Sildenafil Revatio® 20 mg three times a day
A and B receptors. Binding to these receptors is Tadalafil Adcirca® 20 mg, 40 mg once daily
utilized to reduce pulmonary vascular resistance.
Dependent upon the ERA used, it may bind to PDE-5 Inhibitors
type A only (Ambrisentan) or to type A and B (Phosphodiesterase-5 Inhibitors)
(Bosentan and Macitentan). See Table 22.6. Clinical Pearls

• They are contraindicated in the setting of

ERA Clinical Points baseline nitrates, given the potential for prom-
inent hypotension.
• PAH patients may often require low-dose • Common side effects include the following:
diuretics with mild symptoms of edema. Headache, nasal congestion, epistaxis, flush-
• ERA should not be utilized in patients with ing, joint pain, GI side effects.
diastolic dysfunction or PAH patients with • May lower blood pressure.
elevated capillary wedge pressure on right • Contraindicated with Riociguat.
heart cath.
• ERA’s are potentially teratogenic. Therefore, it oluble Guanylate Cyclase Stimulator
S
is imperative that women patients of childbear- Riociguat (Adempas®): Works by enhancing
ing age use appropriate contraception and obtain cGMP production, which is a vasodilator.
monthly pregnancy tests while on therapy. Indications:
• Common side effects other than edema include
nasal congestion, and headache. • It is indicated for PAH and PAH secondary to
chronic thromboembolic etiology.

Nitric Oxide Pathway Potential Side effects:

DE-5 Inhibitors (Phosphodiesterase-5

P • Hypotension.
Inhibitors) • Syncope potential.
PDE-5 inhibiton results in vasoldilation of the • Bleeding.
pulmonary arteries via the nitric oxide pathway. • It has demonstrated antiproliferative/anti-
This class is utilized in the treatment of PAH as our remodeling properties in animals [18].
pulmonary vasculature contains phosphodiesterase
5. It should be noted that these drugs are used to Dosing
treat erectile dysfunction but have different indica-
tions and dosing with regard to pulmonary hyper- • Dosing is typically 0.5–1.0 mg TID and moni-
tension. See Table 22.7. tor for hypotension.
22 Pulmonary Vascular Disease 233

• It can be titrated up to a max dose of 2.5 mg or may have to be verified via their specialty
tid. pharmacy.
• If they are on IV or SQ prostacyclin therapy,
Major Contraindication always verify their current weight and dosing
weight. Often their prescribing pharmacy or
• Concurrent use with PDE 5 inhibitors is con- info may be detailed on their infusion pump.
traindicated, given potential for hypotension. Occasionally adjustments need to be made for
prominent weight changes to make sure they
Most patients with PAH are treated initially are on the appropriate dosing.
with combination therapy consisting of two • A combination of Riociguat (Adempas) and a
agents. Select patients may be candidates for PDE-5 inhibitor is contraindicated due to
monotherapy as per the outline. PAH requires ®
hypotension.
ideally early disease detection and proactive • Not all pulmonary hypertension is pulmonary
treatment with multiple classes of drugs targeting arterial hypertension.
multiple pathogenic pathways [2]. Treatment
combinations have been shown to demonstrate
improved 6-min walk distance and delay in time Pulmonary Embolism
to clinical worsening. In patients whom medical
therapy fails to reduce their risk to low or inter- Introduction
mediate level, referral for lung transplation is rec-
ommended. [21]. Atrial septostomy may be Acute pulmonary embolism remains one of the
considered in end-stage PAH or those awaiting most challenging cardiovascular disorders to
lung transplant. It unloads the right atrium and manage. The heterogeneity in presentation, com-
right ventricle and delays right ventricular fail- plex nomenclature for risk stratification and mul-
ure. This in turn improves left ventricular preload tiple treatment modalities now available create a
but at the price of reduced oxygenation given need for a multidisciplinary approach to the man-
right to left shunting [21]. agement of this disease process. Despite advances
in technology, mortality for acute PE remains
Clinical Pearls high [22]. The following section reviews the con-
temporary approach to diagnosis, risk stratifica-
• Patients on IV prostacyclin therapy: DO NOT tion, and treatment of acute pulmonary
flush the line infusing the prostacyclin agent. thromboembolic disease. The evaluation and
This can accidentally bolus the patient and management of chronic thromboembolic will be
lead to significant consequences not limited to addressed in pulmonary hypertension section of
hypotension, prominent flushing, and even this chapter.
death.
• Always make sure patients are not on active
nitrate medications if you are prescribing a Physiology
PDE-5 inhibitor. The combination can cause
prominent hypotension. Acute PE results in sudden increase in pulmo-
• Care with aggressive diuresis in true PAH nary vascular resistance (PVR) which can cause
patients as they can be right heart preload right ventricular (RV) dilation, tricuspid regurgi-
dependent and you can cause hypotension, tation, and subsequent RV failure. This can rap-
worsening of cardiac output if they become idly escalate to systemic hypotension and
volume depleted. cardiogenic shock. The mechanism of this dete-
• Always verify names and dosages of PAH rioration is multifactorial including shifting of
medications—this may be through the patient the interventricular septum toward the left ven-
tricle (LV) causing decreased LV filling as well
234 L. Shelton and J. Mishkin

as increased RV wall stress and causing myocar- subclassified into intermediate-low and
dial ischemia (Fig. 22.1). Acute PE can lead to intermediate-high risk depending on presence or
severe ventilation-perfusion mismatching and absence of both RV dysfunction in conjunction
subsequent hypoxemia. Patients may also with a positive troponin or elevated brain natri-
develop a respiratory alkalosis due to uretic peptide (BNP) level.
hyperventilation. Scoring systems exist to help characterize the
severity of acute PE to help guide therapeutic
decision-making. The PESI (Pulmonary
Classification and Risk Stratification Embolism Severity Index) and simplified PESI
(sPESI) scores are common tools used to identify
Classification and risk stratification in acute PE patients with increased 30-day mortality risk [25,
incorporates clinical indicators, imaging find- 26]. In addition to these risk scores, an increased
ings, and biomarkers to help determine severity RV-to-LV ratio on computed tomography (CT)
of disease and best interventions [23]. The clas- imaging is associated with high 30-day mortality
sification has differing risk and therapeutic risk as well.
options (Table 22.8). Most patients who present
with PE are normotensive without imaging or
biomarker evidence of RV strain or dysfunction. History and Presentation
PE with signs of RV dysfunction but normoten-
sion is termed intermediate-risk PE, while the The presentation of pulmonary embolus is diverse.
presence of hemodynamic instability is indica- Patients may be asymptomatic with an embolus
tive of high-risk PE [24]. High-risk PE is also seen as an incidental finding on imaging. This
termed massive PE. These patients may present diagnosis should be considered in patients with
with syncope, systemic arterial hypotension, car- the common findings in Table 22.9. Most often
diogenic shock, or cardiac arrest. The term patients will present with chest pain that is pleu-
“supermassive” or catastrophic PE is used to ritic in nature accompanied by shortness of breath.
describe patients with fulminant cardiopulmo- In some cases, presenting symptoms can be vague
nary collapse that require cardiopulmonary and nonspecific and attributed to anxiety. In
resuscitation. severe cases, acute PE may present as sudden car-
Intermediate-risk PE patients represent a con- diac death. Risk factors for PE include recent sur-
siderable challenge as they can experience a sud- gery, trauma, immobilization or active malignancy.
den decline in clinical status despite early In some instances, patients may harbor a genetic
identification and institution of anticoagulation predisposition to thrombus formation.
therapy. The significant heterogeneity of this
patient population can lead to confusion regard-
ing appropriate treatment strategies. Intermediate- Physical Findings
risk PE patients are sometimes further
Physical exam findings for acute PE can range
Table 22.8 Classification of Pulmonary embolus from normal vital signs to tachycardia and hypo-
Risk Hemodynamics tension. In cases of massive PE, patients may
Intermediate low RV dysfunction with normotension
with negative troponin and BNP
Table 22.9 Common presenting signs and symptoms of
Intermediate high RV dysfunction with normotension PE
with elevated troponin and BNP
High risk/massive Hemodynamic instability Unexplained tachycardia
Catastrophic/ Cardiovascular collapse Dyspnea on exertion
super massive Pleuritic and localized chest pain
Syncope
Adapted from Piazza G. Submassive pulmonary embo-
lism. JAMA 2013;309:171–80 Cardiac arrest
22 Pulmonary Vascular Disease 235

present with syncope or fulminant cardiogenic where a team-based approach to care has been
shock. successful in improving outcomes. The goal of
There can be evidence of right heart strain the PERT is to improve access to care, reduce
including elevated jugular venous pressure and a variability in treatment strategies and identify
third heart sound. Evidence of malperfusion may best practices [27, 28].
include altered mental status and cool extremities
in conjunction with cyanosis.
Pharmacologic Therapies

Imaging Anticoagulation remains the cornerstone for

treatment of PE. Regimens include intravenous
An EKG most commonly shows sinus tachycar- unfractionated heparin, subcutaneous low molec-
dia, but atrial arrhythmias may occur. The classic ular weight heparin, fondaparinux, or direct oral
EKG is described as S1Q3T3. This describes a anticoagulants.
new S wave in lead I with a new Q wave and Systemic fibrinolysis is utilized to attempt
inverted T wave in lead III. These findings are immediate reversal of RV dysfunction and pre-
consistent with acute RV dilatation and strain. vent deterioration into hemodynamic collapse
CTA of the chest is the best diagnostic modal- and improve mortality [29, 30]. In a large,
ity to image acute PE (Fig. 22.2). The rapid avail randomized-control trial full-dose systemic fibri-
ability of CT is essential in these patients as nolysis consisting of 100 mg tissue plasminogen
hemodynamic collapse may occur suddenly. activator (t-PA), reduced the risk of hemody-
namic collapse in intermediate-risk PE, though
with an associated increased risk of bleeding in
Treatment and Management the form of intracranial hemorrhage [31].
Subsequent clinical trials investigating half-dose
Multidisciplinary PE response teams (PERT) t-PA did not demonstrate improvement in mortal-
have emerged to help standardize the approach to ity or reduction in adverse bleeding events. There
treatment of PE, particularly cases where the was also an increased need for escalation of ther-
quality of evidence is limited or in the presence apy with this strategy [32, 33].
of conflicting recommendations. The utilization Pharmacologic hemodynamic support is
of the PERT is like what has been done in important for the initial stabilization of patients
response to other common cardiovascular condi- and to maintain end organ perfusion while insti-
tions, such as myocardial infarction, stroke, and tuting more definitive therapy for PE. Epinephrine
acute aortic syndromes. As previously stated, and norepinephrine are drugs of choice due to
acute PE can lead to cardiogenic shock, an area their ability to enhance RV contractility without
promoting systemic vasodilation. Avoidance of
excessive volume loading is critical in the setting
of RV dysfunction and should be avoided when
central venous pressure exceeds 15 mmHg.
Although pulmonary vasodilator therapy can
reduce pulmonary vascular resistance and RV
afterload, the use of inhaled nitric oxide has not
been shown to improve outcomes in intermediate-
risk PE [34].

Advanced Therapies
Fig. 22.2 CTA chest showing PE. Red arrows point to Advanced therapies for PE include catheter-
bilateral thrombus in the right and left pulmonary arteries based Intervention, surgical pulmonary embolec-
236 L. Shelton and J. Mishkin

tomy, and mechanical circulatory support [35].

Catheter-based therapy includes catheter-directed
fibrinolysis and mechanical embolectomy. These
modalities can also be employed in combination.
While the frequency of catheter-based therapy
utilization has increased, the overall efficacy of
this approach with respect to mortality has not
been studied in large, randomized-control trials.
Ultrasound-facilitated, catheter-directed fibrino-
lysis (EkoSonic Endovascular System™) has
been FDA approved in the USA for the treatment
of intermediate and high-risk PE. The main end-
point noted in trials utilizing ultrasound- Fig. 22.3 TEE image showing Clot (yellow arrow) in
transit across a PFO
facilitated, catheter-directed fibrinolysis has been
improvement in RV-LV ratio [36, 37]. Ultrasound
waves are pulsed into the thrombus to break up Extracorporeal membrane oxygen (ECMO)
the clot and facilitate the effect of thrombolytics. has been increasingly utilized for management of
Percutaneous mechanical thrombectomy is high-risk PE. Patient selection and timing of
another catheter-based technique that does not deployment are critical aspects that have yet to be
utilize thrombolysis therapy. The FlowTriever™ well-defined. Like other forms of cardiogenic
system (Inari Medical, Irvine, California) and the shock, utilization of temporary mechanical circu-
Indigo Thrombectomy System™ (Penumbra, latory support demonstrates improved outcomes
Inc., Alameda, California) are two such devices when employed prior to onset of severe multisys-
that have been undergone single-arm studies, tem organ failure. While ECMO has been utilized
both demonstrating improvement in imaging out- as an adjunctive measure in PE, recently it has
comes. Further research is needed to determine been shown that some patients may recover on
the best utilization of these catheter-based tech- ECMO without the addition of fibrinolysis or
nologies along with timing of their deployment. mechanical thrombectomy (Chap. 25) [40].
These devices mechanically remove the throm-
bus from the pulmonary artery. They work best
on proximal thrombus. Conclusion and Future
Surgical pulmonary embolectomy should be Considerations
considered in patients with intermediate–high- or
high-risk PE when fibrinolysis has failed or is The management of acute PE depends not only
contraindicated [38, 39]. Surgical intervention on timely diagnosis, but also appropriate and
should also be considered when “clot-in-transit” accurate risk stratification to guide the utilization
is present (Fig. 22.3), patients experience hemo- of pharmacologic therapies. Furthermore, accu-
dynamic collapse or respiratory failure requiring rate risk assessment can help identify those
cardiopulmonary resuscitation. It is most effec- patients that may benefit from a broadening avail-
tive in patients with large centrally located PE ability of catheter-based interventions.
and when performed before onset of multisystem Intermediate-risk PE patients remain a signifi-
organ failure and high vasoactive medication cant challenge as many data points need to be
requirement. In this scenario, a Cardiothoracic assimilated in a timely fashion to balance the
surgeon will mechanically remove thrombus risk-benefit ratio of various treatment modalities.
from inside the pulmonary arteries via a median High-risk and catastrophic PE patients who pre-
sternotomy approach. Most often these patients viously experienced dismal outcomes, may have
require temporary mechanical circulatory sup- better opportunity for survival with mechanical
port after the procedure. circulatory support and deployment of catheter-
22 Pulmonary Vascular Disease 237

based technology or surgical thrombectomy in for PH prior [41]. This leads to hyper viscosity
selected patients. There is optimism that utiliza- from pulmonary vasoconstriction and polycythe-
tion of multidisciplinary PERT will help improve mia. Subsequently, the pulmonary vasculature
outcomes moving forward. does not allow increases in cardiac output with-
out significant increases in pulmonary artery
Clinical Pearls pressure [42]. The cascade ultimately results in
RV systolic dysfunction with limitations in car-
• The management of acute PE depends not diac output in response to exercise.
only on timely diagnosis, but also appropriate Cor pulmonale can be further defined as acute
and accurate risk stratification to guide the uti- or chronic. Chronic cor pulmonale can be seen in
lization of pharmacologic therapies. the setting of pulmonary hypertension etiologies
• Anticoagulation remains the cornerstone for outlined prior for WHO Groups from PH discus-
treatment of PE. sion earlier. These include diseases such as
• Intermediate-risk PE patients remain a signifi- COPD and interstitial lung disease. It may also
cant challenge as many data points need to be occur in upper airway obstruction/sleep apnea,
assimilated in a timely fashion to balance the and chest wall changes with kyphoscoliosis or
risk-benefit ratio of various treatment pulmonary vasculature with pulmonary arterial
modalities. hypertension [41]. Other findings include auto-
• High-risk and catastrophic PE patients who immune diseases such as scleroderma, cystic
previously experienced dismal outcomes, may fibrosis, and obesity hypoventilation syndrome
have better opportunity for survival with [41].
mechanical circulatory support and deploy- Acute cor pulmonale, on the other hand, is
ment of catheter-based technology or surgical most commonly due to acute pulmonary embo-
thrombectomy in selected patients. lism. The right heart is better equipped to handle
• There is optimism that utilization of multidis- volume load as opposed to a pressure load.
ciplinary PERT will help improve outcomes Therefore, even small increases in pulmonary
moving forward. artery pressure may result in large increases in
right ventricular work and right ventricular
hypertrophy [43].
Cor Pulmonale Presenting symptoms are like those of pul-
monary hypertension and are often related to the
We will briefly outline Cor Pulmonale in con- underlying disorder. Common symptoms include
junction with our pulmonary hypertension sec- dyspnea on exertion as well as exertional fatigue.
tion. Cor Pulmonale is defined by alteration in Also, RV failure signs with abdominal distention
the structure and function of the right ventricle and lower extremity edema may be seen.
caused by a primary respiratory system disease
[41]. It refers to the combination of hypertrophy,
pressure overload, and dilation of the right ven- Physical Exam
tricle in the face of pulmonary hypertension [42].
It is the result of pulmonary hypertension devel- See the Pulmonary hypertension exam above
oped from any underlying process. In the pres- given similarities.
ence of an underlying pulmonary disease, there
can be alveolar hypoxia which can be a main
cause of pulmonary vasoconstriction, as dis- Evaluation
cussed in the PH section prior. Hypoxemia also
leads to smooth muscle cell proliferation of small Evaluation for cor pulmonale is consistent with
pulmonary arteries with vascular mediated pulmonary hypertension evaluation. Assessment
changes in nitric oxide, endothelin 1 as outlined for acute or chronic PE, underlying pulmonary
238 L. Shelton and J. Mishkin

disease with cxr/pulmonary function test/paren- tion while sleeping [45]. Central sleep apnea
chymal lung disease should be considered. Echo results from the removal of wakefulness stimulus
can assess for structural changes of the right heart to breathe in patients with compromised neuro-
and estimated pulmonary pressures. Cardiac muscular ventilatory control [46]. These include
MRI can further assess right heart morphology patients with neuromuscular disease or chest wall
and include right heart ejection fraction/volumet- disease. They may have central nervous system
ric indices. Assess EKG for signs of right ven- disease, neuromuscular disease or severe abnor-
tricular hypertrophy, P pulmonale, and right malities in pulmonary mechanics such as kypho-
bundle branch block. scoliosis. Central sleep apnea is felt to be
secondary to mechanisms that trigger central
respiratory events, including post hyperventila-
Treatment tion central apnea or central apnea secondary to
hypoventilation, as can be seen with opioid use
Cor pulmonale treatment should be aimed at [46].
treating the underlying condition. This includes
the correction of hypoxia to improve pulmonary
vasoconstriction. In patients with evidence of Presentation
right ventricular failure, diuretics may also be
utilized for decongestion. Treatment of the under- Presenting symptoms of OSA often include
lying pulmonary process is indicated. Examples patient complaints of waking up gasping for air
include treatment of pulmonary arterial hyperten- or choking. Partners or family members may also
sion, OSA, and pulmonary emboli if indicated. reiterate the patient frequently snores or may
Smoking cessation is imperative. have witnessed apneic periods. Patient may have
If COPD is diagnosed, advise appropriate daytime somnolence, dyspnea on exertion, and
treatment of the disease, which may include easy fatigability. Complaints of restless sleep,
bronchodilators and avoidance of pulmonary nocturia, headache on awakening, and sore throat
irritations. can be common. Sleep apnea often goes undiag-
nosed and untreated as the symptoms may not be
Clinical Pearls readily noticeable or not attributed to sleep apnea.

• Smoking cessation!
• Assess and treat the underlying etiology. Physical Exam
• Diuretics for symptomatic relief of right-sided
congestion. Physical exam typically focuses on the assess-
• Hypotension and renal failure are poor prog- ment of risk factors and limited exam with oral
nostic indicators. assessment, BMI, and neck measurements (see
Table 22.10).
Approximately 30% of patients with BMI > 30
leep Apnea and Cardiovascular
S and 50% of those with BMI > 40 have OSA [47].
Disorders Mallampati score provides a score of 1–4
based upon anatomic features of the airway when
Obstructive sleep apnea (OSA) is a disorder char- patients have their mouth open, and their tongue
acterized by obstructive apnea, hypopnea, and/or
respiratory effort-related arousals caused by Table 22.10 Risk Factors for OSA
repetitive collapse of the upper airway [44]. It is Obesity with BMI greater than 30
the most common sleep-related breathing disor- Large neck circumference: Greater than 17 in. in men
der. It can be characterized by hypoxia and (43 cm), 15 inches in women (37 cm)
hypercapnia with full or partial airway constric- Increased Mallampati score
22 Pulmonary Vascular Disease 239

Fig. 22.4 Anatomy of

the Mallampati score

Class I Class II Class III Class IV

Table 22.11 STOP-bang questionnaire

S: “Do you snore loudly, loud enough to be heard
(Table 22.11). (AHI defined as an average num-
through a close door?” ber of episodes of apnea and hypopnea per hour.)
T: “Do you feel tired or fatigued during the daytime Patients with scores of 0–2 on STOP-BANG
almost every day?” are at low risk for moderate to severe OSA
O: “Has anyone observed that you stop breathing and with scores 5–8 are considered high risk
during sleep?”
P: “Do you have a history of high blood pressure with
for OSA. Patients with scores of 3–4 require fur-
or without treatment?” ther criteria for classification as having a higher
B: BMI greater than 35 risk for moderate to severe OSA [49]. Typically,
A: Age older than 50 years they are considered higher risk if they have one
N: Neck circumference greater than 17 in (43 cm) additional risk factor to include BMI >35, male
G: Gender, male gender, neck circumference >16 in (40 cm), or a
SCORE 0–2 3–4 5–8 serum bicarbonate level > or equal to 28 mmol/L
OSA risk for moderate to Low Assess risk High [49].
severe OSA factors

protruded. The score is calculated based on the Physiology

physical exam of the soft palate in relationship to
the tongue. Less visualization of the uvula is Sleep apnea can lead to a cascade of changes
scored higher and has a higher likelihood of OSA from the pathophysiology standpoint.
(Fig. 22.4). For every one-point increase in the Parasympathetic activity increases during our
Mallampati score, the odds of having obstructive sleep cycle. However, during periods of apnea
sleep apnea increased more than twofold, inde- with airway obstruction, hypoxia, and increased
pendent of more than 30 variables that reflected CO2 leads to an increase in sympathetic output.
body habitus, airway anatomy, symptoms, and Other potential changes include the activation of
medical history [48]. the renin angiotensin-aldosterone system
Screening tools at the time of assessment may (RAAS) in the setting of sympathetic activation.
also be used to further stratify potential risk for Sleep apnea patients often have elevated angio-
OSA and the necessity for a referral. tensin II and aldosterone levels. These cause
The STOP-BANG screening tool is outlined water retention of the kidneys and vasoconstric-
below and widely utilized, given its ease of use/ tion of the peripheral vasculature, which can lead
limited time required. Chung et al. developed ini- to hypertension [50]. OSA may also lead to endo-
tially as pre-surgery screening tool for OSA and thelial dysfunction. Nitric oxide, a vasodilator,
is easily completed for risk stratification. The can be impaired with obstructive sleep apnea but
score is from 0 to 8. Sensitivity to detect OSA can improve with treatment [51].
based upon score of ≥3 to detect moderate to Obstructive sleep apnea may also increase
severe OSA (AHI > 15) and severe OSA inflammatory markers and reactive oxygen spe-
(AHI > 30) was 93% and 100%, respectively cies, which is postulated as a possible mecha-
240 L. Shelton and J. Mishkin

nism by which OSA increases the risk of AHI or RDI greater than or equal to 15 events
cardiovascular disease and overall mortality per hour
[52]. Patients with untreated sleep apnea are at AHI or RDI greater than or equal to 5 and less
higher risk of hypertension or difficult to control than or equal to 14 events per hour with docu-
hypertension. Other potential complications mented symptoms of excessive daytime sleepi-
include an increased risk of arrhythmia given ness, impaired cognition, mood disorders,
hypoxic induced events. Patient may have atrial insomnia, or documented hypertension, ischemic
arrhythmias/bradycardia arrhythmias, Increased heart disease, or history of stroke [47].
risk of heart failure, myocardial infarction, Patients with a higher risk PSG during the first
stroke, and pulmonary hypertension. Sleep 2 h of diagnostic PSG may undergo a split-night
apnea occurs in obese population which have PSG study. The second portion of the testing
other concomitant comorbidities associated with involves titrating a CPAP device [47].
obesity, including diabetes, dyslipidemia, Alternatively, home sleep study evaluations are
and underlying CAD. becoming popular and more cost-effective.
Typical risk factors for sleep apnea include
obesity. Obesity leads to mechanical obstruction
from adipose tissue causing airway collapse. Management

Non-surgical treatment options include CPAP (con-

Diagnosis tinuous positive airway pressure) or BiPAP (bilevel
positive airway pressure in which the inhaled/
In patients with risk factors or symptoms con- exhaled pressures are adjusted independently.)
cerning for obstructive sleep apnea, prompt refer- These devices provide airflow into the airway
ral should be entertained to sleep medicine via a facemask/nasal covering. It is considered a
physicians. These specialized physicians can first-line intervention for sleep apnea and
then determine the appropriateness for further decreases symptoms. Benefits of therapy include
testing, including polysomnography. improvement in blood pressure, improvement in
right heart function, pulmonary hypertension,
daytime sleepiness, and cognition.
Sleep Study The treatment process for sleep apnea also
includes general and behavioral measures,
Polysomnography (PSG) is performed in the lab- including:
oratory with technicians. This study is beneficial
as it provides an opportunity to directly assess • Weight loss which has been shown to improve
potential for obstructive sleep apnea and directly obstructive sleep apnea symptoms and
observed rapid eye movements, sleep-associated severity.
disturbances such as periodic leg movements, • Avoidance of sleeping in the supine position
apneas, and seizures [47]. Nocturnal seizure- to reduce airway collapse.
sare are an ominous sign which may lead to sud- • Sleep hygiene: consistent sleep/wake cycle
den death during sleep if treatment is not rapidly and avoidance of device/light stimulation at
initiated. AASM guidelines require EEG or bedtime.
EMG, heart rhythm monitoring, monitoring of • Avoidance of sedating pharmacologic agents,
leg movements, breathing with monitoring air- including alcohol, 4–6 h before bedtime.
flow at the nose and mouth. • Compliance with CPAP or BiPAP, including
The Centers for Med”care and Medicaid nocturnal oxygen if utilized.
Services criteria recognize a positive polysom-
nography study for OSA as: Potential surgical treatments for OSA also
exist. Options include Uvulopalatopharyngo-
22 Pulmonary Vascular Disease 241

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Pericardial Disease
23
Ashley McDaniel and Richard Musialowski

Pericardial Disease diseases and neoplastic disease with pericardial

involvement (Table 23.1) [2]. The clinical diag-
The heart is protected by tissue layers that make nosis is made when two of the four criteria listed
up the pericardial sac. The parietal pericardium is in Table 23.2 are present. Commonly, a patient
a thick fibrous structure that can be congenitally will present with inability to lay flat due to sharp
absent without clinical significance. The visceral and stabbing chest pain. The pain is usually sud-
pericardium is adherent to the epicardial layer of den in onset and often described as centrally
the heart. The potential space between the two located, worse with deep inspiration, and pleu-
layers contains a small amount of serous pericar- ritic in nature. Pain frequently improves when sit-
dial fluid to cushion and protect the heart, allow- ting forward. Patients may describe radiation to
ing it to move freely within the pericardial sac. It the trapezius ridge, the area from the neck to the
is important to recognize that the parietal pericar- shoulder region. Recurrence of inflammation will
dium extends up to and includes the ascending have very similar symptoms to initial presenta-
root of the aorta (Fig. 23.1). This becomes clini- tion. Many also complain of associated fatigue,
cally relevant with aortic dissection. Blood track- shortness of breath, orthopnea, or PND.
ing outside the aorta will collect in the pericardial The classification of pericarditis is related to
space with resultant hemodynamically signifi- the duration and recurrence of symptoms
cant effusion and clinical tamponade (Chap. 28). (Table 23.3).

Pericarditis Physical Exam

Pericarditis is inflammation of the pericardial sac Commonly, the physical exam is unremarkable.
surrounding the heart. Acute pericarditis is the Occasionally, a pericardial rub may be heard with
most common disorder involving the pericardium the patient leaning forward, during expiration at
and is often secondary to a viral process [1]. the left lower sternal edge. It may have one, two,
Other common causes are systemic autoimmune or three components. Usually, a single sound dur-
ing ventricular systole can be heard intermit-
A. McDaniel (*) · R. Musialowski tently. It has been described sounding like the
Sanger Heart and Vascular Institute, Atrium Health, separation of Velcro™ and can be mistaken for a
Charlotte, NC, USA systolic murmur. The presence of a pericardial
e-mail: [email protected]; effusion often negates the presence of the rub as
[email protected]

© The Author(s), under exclusive license to Springer Nature Switzerland AG 2023 245
R. Musialowski, K. Allshouse (eds.), Cardiovascular Manual for the Advanced Practice Provider,
https://doi.org/10.1007/978-3-031-35819-7_23
246 A. McDaniel and R. Musialowski

Fig. 23.1 Anatomy of

pericardium. (Adapted
from Poorsattar, S.P.,
Maus, T.M. (2022).
Pericardium. In: Maus,
T.M., Tainter, C.R. (eds) Parietal
Essential pericardium
Echocardiography. Visceral
Springer, Cham. https:// pericardium
doi.org/10.1007/978-3-
030-84349-6_14)

Pericardial
fluid

Pericardium

Table 23.1 Causes of pericarditis

Table 23.3 Classification of pericarditis
Etiologies Examples
Infectious Viral: Idiopathic. Acute Criteria present in Table 23.2, CRP and
COVID-19-common sedimentation rate elevation,
Bacterial: TB—more CT or MR imaging showing pericardial
common in underdeveloped inflammation
countries Incessant Symptoms lasting >4–6 weeks and less than
Fungal-rare 3 months
Uremic pericarditis ESRD patients Recurrent Symptom recurrence after 4–6 weeks or
Post-myocardial Less commonly seen due to longer of a symptom-free interval
infarction (Dressler’s early MI intervention Chronic Symptoms greater than 3 months
syndrome) Adapted from Yehuda Adler, Philippe Charron, Massimo
Autoimmune disease RA, SLE serositis—common Imazio, Luigi Badano, Gonzalo Barón-Esquivias, Jan
Malignancies Metastatic cancer-lung, Bogaert, Antonio Brucato, Pascal Gueret, Karin Klingel,
melanoma, Christos Lionis, Bernhard Maisch, Bongani Mayosi,
and breast—common Alain Pavie, Arsen D Ristić, Manel Sabaté Tenas, Petar
Seferovic, Karl Swedberg, Witold Tomkowski, ESC
Scientific Document Group, 2015 ESC Guidelines for the
Table 23.2 Diagnostic criteria by the American College diagnosis and management of pericardial diseases: The
of Cardiology requires two of four criteria Task Force for the Diagnosis and Management of
Chest pain that is positional and pleuritic Pericardial Diseases of the European Society of
Physical exam finding of friction rub Cardiology (ESC) Endorsed by: The European Association
for Cardio-Thoracic Surgery (EACTS), European Heart
EKG changes characteristic of pericarditis
Journal, Volume 36, Issue 42, 7 November 2015, Pages
New or worsening pericardial effusion 2921–2964, https://doi.org/10.1093/eurheartj/ehv318
23 Pericardial Disease 247

the fluid lubricates the inflamed pericardial lay- Labs: Inflammatory markers may be elevated
ers. A current or recent fever may be associated if including white blood cell count, C-reactive pro-
infectious process is present. tein, and sedimentation rate. High sensitivity tro-
ponin is used to assess for myocardial damage
and associated myocarditis or ischemic etiology.
Diagnostic Testing If there is a classic presentation of positional
chest pain with other clinical signs of pericardi-
EKG may show diffuse concave or saddle-shaped tis, an elevation of troponins suggests myoperi-
ST elevation in multiple vascular distributions. If carditis (Table 23.6).
these changes were all true STEMI, hemody- Cardiac MRI (cMRI) may be useful to assess
namic collapse and cardiogenic shock would be for pericardial inflammation and to evaluate asso-
clinically present. Diffuse PR segment depres- ciated myocarditis (Fig. 23.3).
sion with isolated PR segment elevation in aVR
is usually present simultaneous with the ST seg-
ment changes (Fig. 23.2). Management of Acute Pericarditis
Transthoracic Echocardiogram: Since peri-
carditis is a clinical diagnosis, there are no spe- Uncomplicated pericarditis should be managed
cific echocardiographic findings in acute in the ambulatory setting (Table 23.4). High-risk
pericarditis. The imaging modality may be a features including an effusion with hemody-
helpful diagnostic tool to assess for pericardial namic compromise necessitating admission for
effusion and tamponade physiology. Assessment inpatient management (Fig. 23.4). Acute inpa-
for a focal wall motion abnormality should be tient management includes Ketorolac 15–30 mg
undertaken potentially indicating post-infarct IV for 1–2 doses for initial pain management and
pericarditis or myocarditis. immediate initiation of colchicine.

Fig. 23.2 EKG suggestive of acute pericarditis

248 A. McDaniel and R. Musialowski

High-risk
Features
• Fever > 38°C
• Subacute onset
• Anticoagulated
• Immunocompromised Yes
• Hypotension
• Jugular venous
distension
• Large effusion
Admit to
Hospital

No
Fig. 23.3 MRI of pericarditis and effusion. Yellow
arrows indicate pericardial effusion. Red arrows are gado-
linium enhancement of inflamed pericardium Outpatient Management
• NSAID x 2 weeks
• ± Colchicine x 3 months
Table 23.4 Treatment options for acute pericarditis
Duration of
Drug Usual dosing therapy Tapering Fig. 23.4 Pathway for treatment of acute pericarditis.
(Adapted from Lilly, L., 2013. Treatment of Acute and
High-dose 750– 1–2 weeks Decrease by
Recurrent Idiopathic Pericarditis. Circulation, 127(16),
aspirin 1000 mg 250–500 mg
pp.1723–1726)
every 8 h every
1–2 weeks
Ibuprofen 600 mg 1–2 weeks Decrease by high-dose ASA should be continued until the
every 8 h 200–400 relief of symptoms occurs [4]. Cardiac MRI is
every now recommended in cases of recurrent pericar-
1–2 weeks
Colchicine 0.5 mg daily 3 months Continue for
ditis. Corticosteroids are considered to treat
(<70 kg) or duration recurrence if the serum CRP is low and the
0.5 mg twice patient is without cardiac MRI abnormalities.
daily Recently, a new agent, rilonacept, was approved
(≥70 kg)
to treat recurrent pericarditis, especially if abnor-
Adapted from Yehuda Adler, Philippe Charron, Massimo
mal MRI findings of late gadolinium enhance-
Imazio, Luigi Badano, Gonzalo Barón-Esquivias, Jan
Bogaert, Antonio Brucato, Pascal Gueret, Karin Klingel, ment are seen within the pericardium. This
Christos Lionis, Bernhard Maisch, Bongani Mayosi, Alain injectable agent inhibits IL-1 alpha and IL-1 beta
Pavie, Arsen D Ristić, Manel Sabaté Tenas, Petar Seferovic, and thus alters the autoinflammatory pathway
Karl Swedberg, Witold Tomkowski, ESC Scientific
associated with recurrent pericarditis.
Document Group, 2015 ESC Guidelines for the diagnosis
and management of pericardial diseases: The Task Force
for the Diagnosis and Management of Pericardial Diseases Clinical Pearls
of the European Society of Cardiology (ESC) • Pericarditis is a clinical diagnosis. A good his-
tory of present illness is all that is needed.
Corticosteroids should be avoided as initial • Inquire about recent cold symptoms or fever
treatment since corticosteroids could suppress as recent viral illness is a very common cause
the patient’s immune response to a virus and of pericarditis.
therefore maintain the trigger for inflammation • Always obtain an EKG to rule out ischemia as
[3]. This may lead to increased risk of chronic an etiology.
pericarditis and constrictive pericardial physiol- • If hemodynamically unstable, echocardiogra-
ogy. If recurrent pericarditis does occur, colchi- phy and clinical bedside assessment to evalu-
cine for 6 months along with NSAIDs or ate for tamponade.
23 Pericardial Disease 249

• Avoid corticosteroids as they can often lead to Table 23.5 Common causes of constrictive pericardial
disease
recurrent pericarditis.
• Exercise restriction for 3 months or until reso- Acute or relapsing viral or idiopathic pericarditis
Any type of cardiac surgery
lution of symptoms and normalization of CRP,
Trauma with organized blood within pericardial space
ECG, MRI, and echocardiogram. Mediastinal irradiation
Neoplastic disease
Rheumatoid arthritis
Myocarditis Systemic lupus erythematosus
ESRD/chronic dialysis patients
Myocarditis is inflammation of the heart muscle Adapted from Hoit, B., 2022. UpToDate. [online]
tissue. Clinically, myocarditis and pericarditis Uptodate.com
can present at the same time. Similar to pericardi-
tis, viral infection and replication in myocarditis tional obstruction if an effusion is present, but the
can cause myocardial injury and cell death. The underlying constriction will still cause clinical
injury occurs through direct invasion, production cor pulmonale.
of cardiotoxic substances, or chronic inflamma- Normally, LV filling is independent of respira-
tion [5]. Clinical pericarditis with significant tro- tory variation. In constrictive pericarditis, ele-
ponin elevation and LV dysfunction suggests vated pericardial pressures impede diastolic
myocarditis (see Chap. 20). This diagnosis should filling of the RV and eventually the LV. As respi-
be suspected in patients who present with or ration occurs, there is increased blood return to
without new cardiac symptoms with a rise in car- the fixed RV. The pressures equilibrate due to
diac biomarkers, abnormal LV function, or constriction or an effusion, and the septum pushes
change in EKG [6]. into the LV. The abnormal septal motion will
impede LV filling and results in lower stroke vol-
ume and cardiac output. When this occurs, the
Constrictive Pericarditis ventricles become interdependent. This interde-
pendence causes variation of LV filling associ-
Constrictive pericarditis is typically a chronic ated with respiration. Echocardiography can
condition that results when granulation tissue image this interdependence, and the abnormal
forms scar/fibrosis that encases the heart. This septal motion with inspiration is easily seen.
causes a loss of elasticity of the pericardial sac. Constriction is a clinical diagnosis supported by
Scarring can become calcified and lead to a cardiac imaging. Occasionally, cardiac catheter-
compressive syndrome where the ventricles are ization is necessary to confirm equalization of
unable to adequately fill [7]. The disease is often diastolic pressures.
progressive in nature, and nonspecific early Constriction and restrictive cardiomyopathy
signs of cor pulmonale often delay the diagno- can be a clinical dilemma. The main difference is
sis. Traditional treatment often is not successful, the presence of pericardial abnormalities with
and this diagnosis must be considered if there ventricular interdependence on imaging in con-
are risk factors for constriction (Table 23.5). strictive disease. Restriction has abnormalities of
the myocardium with evidence of pulmonary
hypertension due to chronic HFpEF [8].
Physiological Characteristics

Constriction causes hemodynamic compromise Physical Exam

due to the fixed obstruction to rapid early dia-
stolic filling. An effusion does not need to be The examination is very similar to pericardial
present for constrictive pericardial disease. If it is tamponade. The chronicity of the constriction
present, it is referred to as constrictive-effusive results in more extensive signs of cor pulmonale
disease. Pericardiocentesis can alleviate the addi- as seen in Table 23.6.
250 A. McDaniel and R. Musialowski

Table 23.6 Clinical examination findings of constrictive

pericarditis
Elevated JVP with a deep, steep Y descent
Kussmaul sign—lack of an inspiratory decline in JVP
Peripheral edema
Ascites and hepatomegaly
Pleural effusion
Pericardial knock—slightly earlier than a third heart
sound
Pulsus paradoxus—uncommon without effusion
Adapted from Hoit, B., 2022. UpToDate. [online]
Uptodate.com

Fig. 23.6 CT of pericardium. Red arrow shows calcifica-

tion of the pericardium. Yellow arrow shows marked
thickening of the pericardium. Both finding suggest con-
strictive pericardial disease. Note the absence of a signifi-
cant effusion

Treatment

Constrictive pericardial disease is difficult to

diagnose and treat. Diuretic therapy to manage
symptoms of cor pulmonale is the cornerstone of
treatment. Often, this becomes inadequate and
signs of intravascular volume depletion and end-
organ hypoperfusion become problematic.
Surgical pericardial stripping can be performed
Fig. 23.5 Constrictive effusive pericarditis. The yellow
arrows show the thickened parietal pericardium with but only after the failure of conservative manage-
fibrinous exudate attached suggestive of a chronic disease. ment. This is a high-risk procedure that has high
The red arrow shows the pericardial effusion surgical mortality but can significantly improve
this disease. During this procedure, parietal peri-
Noninvasive Testing cardium is removed allowing passive filling of
the ventricles. If the disease has progressed sig-
Echocardiography is the initial test of choice. nificantly, the visceral pericardium may be
Signs of chronic effusion with thickening of the involved, and the patient may have minimal
visceral and parietal pericardium are often noted. improvement postoperatively. Appropriate
Abnormal septal bounce (ventricular interdepen- patient selection is essential prior to this
dence) is seen with ventricular contraction and procedure.
varies with respiration (Fig. 23.5).
Cardiac CT is a very good test to evaluate for Clinical Pearls
pericardial thickening as is MRI. CT imaging is • Consider constriction in patients with risk fac-
more readily available and has excellent tors and treatment-resistant cor pulmonale
diagnostic accuracy. An effusion does not have • Diuretics are used aggressively before high-
to be present for constriction physiology risk surgery is considered
(Fig. 23.6).
23 Pericardial Disease 251

Pericardial Effusion slowly released from the cuff until sounds are
intermittently heard. The cuff is deflated until
The normal pericardial sac contains 10–50 ml of the sounds are present continuously. The differ-
serous fluid. This fluid is designed to lubricate the ence in numbers from beginning of intermittent
heart during contraction. Certain disease states and continuous is calculated. You should also
result in an increased production of this physio- palpate the radial pulse, and if you note the
logic fluid. A pericardial effusion may be present pulse weakens or disappears during inspiration,
and asymptomatic. The effusion is often an inci- this is also a positive sign [5]. Normal is less
dental finding on other imaging studies and only than 10 mmHg. Hemodynamic significance is
significant if its size causes hemodynamic insta- seen at 30 mmHg.
bility. A pericardiocentesis may be performed to
rapidly treat hemodynamic instability or may be
performed for diagnostic evaluation to determine Diagnosis
the etiology (Table 23.7).
The gold standard for diagnosis of a pericardial
effusion is with echocardiography (Fig. 23.7). It
Physical Examination is rapidly available and simple test to evaluate
hemodynamic stability. Stable pericardial effu-
Heart sounds may be faint due to increased dis- sion can be appreciated on a CT scan or
tance between the chest and the heart. Clinically, MRI. Hemodynamic abnormalities can be seen
the measurement of pulsus paradoxus is the on these imaging modalities, but echocardiogra-
bedside examination finding of ventricular phy is more readily available. CT can sometimes
interdependence. Pulses paradoxus is a clinical overestimate the size of effusion, and the size
clue to tamponade and consists of a greater than should be confirmed with echocardiography.
10 mmHg inspiratory decline in systolic arterial EKG findings are nonspecific. When a peri-
pressure. This evaluation is performed by cardial effusion is present and large, you may see
increasing the pressure of sphygmomanometer electrical alternans on the EKG. This is caused
cuff until there are no Korotkoff sounds. Air is by the heart “floating” in the fluid and moving
with respiration and contraction toward and away
Table 23.7 Common causes of pericardial effusion from the EKG leads.
Common causes of Uncommon causes of cardiac The cardiac silhouette may be enlarged on
cardiac tamponade tamponade chest X-ray due to the presence of fluid.
Pericarditis Collagen vascular disease
(SLE, RA, scleroderma)
Tuberculosis Radiation induced
Iatrogenic/procedure Post myocardial infarction
Trauma Uremia
Neoplasm/malignancy Aortic dissection
Bacterial infection
Pneumopericardium
Adapted from Yehuda Adler, Philippe Charron, Massimo
Imazio, Luigi Badano, Gonzalo Barón-Esquivias, Jan
Bogaert, Antonio Brucato, Pascal Gueret, Karin Klingel,
Christos Lionis, Bernhard Maisch, Bongani Mayosi,
Alain Pavie, Arsen D Ristić, Manel Sabaté Tenas, Petar
Seferovic, Karl Swedberg, Witold Tomkowski, ESC
Scientific Document Group, 2015 ESC Guidelines for the
diagnosis and management of pericardial diseases: The
Task Force for the Diagnosis and Management of Fig. 23.7 Pericardial effusion on echocardiography.
Pericardial Diseases of the European Society of White arrows point to large circumferential pericardial
Cardiology (ESC) effusion
252 A. McDaniel and R. Musialowski

Treatment Treatment
Pericardiocentesis is indicated if there is hemo-
Asymptomatic effusions are usually observed dynamic compromise with tamponade physiol-
without treatment. If the etiology is unclear and ogy. If immediate removal of fluid is not possible,
enough fluid is present, pericardiocentesis may aggressive fluid resuscitation should be adminis-
be used as a diagnostic test. Treatment of an tered to optimize preload. Occasionally, recurrent
underlying disease is often indicated. Rarely, significant effusions may require surgical
empiric anti-inflammatory agents are given if the removal of a section of pericardium (pericardial
sed rate and CRP are elevated (Table 23.4). window) to avoid recurrent tamponade, often
seen with malignant effusions and is usually pal-
liative in nature [9].
Cardiac Tamponade

Cardiac tamponade is a life-threatening condition Clinical Pearls

that occurs when the accumulation of fluid in the • CT scan can sometimes overestimate the size
pericardial space compresses the ventricle result- of effusion. Always confirm size and hemody-
ing in obstruction to ventricular filling. The quan- namic significance with echocardiography
tity of fluid is of less concern but more so how • Tamponade is an emergency and requires
rapidly it accumulates. The amount of fluid immediate action
needed to cause tamponade could be as small as • Never give beta blockers to a patient in
200 ml if it develops rapidly. When pericardial tamponade
effusions are chronic or develop more slowly, the
pericardium has time to adapt, and there is less
chance of hemodynamic compromise.
References
1. Imazio M. Acute pericarditis: clinical presenta-
Clinical Signs tion and diagnosis. UpToDate. [online] Uptodate.
com. 2022. Available at: https://www.uptodate.
Three principal clinical features of tamponade are com/contents/acute-pericarditis-clinical-presen-
tation-and-diagnosis?search=pericarditis%20
hypotension, soft or absent heart sounds, and jug- adult&source=search_result&selectedTitle=1~150&
ular venous distention with a prominent descent usage_type=default&display_rank=1.
during systole. These three clinical features are 2. Bach DS. American College of Cardiology: 2015
known as Beck’s triad. Since the main issue is ESC guidelines for pericardial disease. 2015.
3. Ismail TF. Acute pericarditis: update on diagnosis and
reduced preload to the ventricles from external management. Clin Med (Lond). 2020;20(1):48–51.
compression, the heart rate increases to maintain https://doi.org/10.7861/clinmed.cme.20.1.4.
a cardiac output. The SVR increases to maintain 4. Lilly L. Treatment of acute and recurrent idiopathic
blood pressure. The patient in tamponade presents pericarditis. Circulation. 2013;127(16):1723–6.
5. Jameson JL, Fauci A, Kasper D, Hauser S, Longo D,
cool, diaphoretic, tachycardic, and hypotensive. Loscalzo J. Harrison’s principles of internal medicine,
Never give beta blockers to reduce the heart rate 20th ed.
as this will result in cardiovascular collapse. 6. Cooper, L. Up to date. Treatment and prognosis of
myocarditis in adults.
7. Hoit B. UpToDate. [online] Uptodate.com. 2022.
Diagnosis Available at: https://www.uptodate.com/contents/
Echocardiography will show collapse of the RA constrictive-pericarditis?search=constrictive%20
and RV walls during diastole. The collapse con- pericarditis&source=search_result&selectedTitle=1~
firms impaired filling of the ventricle. Blood flow 110&usage_type=default&display_rank=1. Accessed
16 Aug 2022.
across the mitral valve is also assessed to deter- 8. Sorajja P, Hoit B. UpToDate. [online] Uptodate.
mine if there is variation with respiration. These com. 2022. Available at: https://www.uptodate.com/
signs together confirm tamponade. contents/differentiating-constrictive-pericarditis-and-
23 Pericardial Disease 253

restrictive-cardiomyopathy?source=history_widget. cardial diseases: the Task Force for the Diagnosis and
Accessed 12 Aug 2022. Management of Pericardial Diseases of the European
9. Adler Y, Charron P, Imazio M, Badano L, Barón- Society of Cardiology (ESC) Endorsed by: the
Esquivias G, Bogaert J, Brucato A, Gueret P, Klingel European Association for Cardio-Thoracic Surgery
K, Lionis C, Maisch B, Mayosi B, Pavie A, Ristić (EACTS). Eur Heart J. 2015;36(42):2921–64. https://
AD, Tenas MS, Seferovic P, Swedberg K, Tomkowski doi.org/10.1093/eurheartj/ehv318.
W, ESC Scientific Document Group. 2015 ESC
Guidelines for the diagnosis and management of peri-
Part VI
Shock
Cardiogenic Shock
24
Courtney Bennett and Amanda Solberg

Introduction the cardiac intensive care unit (CICU) setting

around the country [1, 3].
Cardiogenic shock (CS) is a life-threatening state
of end-organ hypoperfusion secondary to low
cardiac output (CO). CS is associated with sig- Differentiating Shock
nificant in-hospital mortality and significant
healthcare cost. Mortality rates have been docu- Shock is a state of circulatory failure, which leads
mented in excess of 80% despite modern thera- to cellular and tissue hypoxia. There are multiple
pies [1, 2]. underlying etiologies of shock based on the
Over the last several years, there has been a mechanism of hypoperfusion. The classifications
subtle shift in etiology of CS as early identifica- include cardiogenic, distributive, obstructive,
tion and treatment of acute coronary syndrome hypovolemic, and neurogenic (Table 24.1). In
(ACS) have become the standard of care. this chapter, we will focus on cardiogenic shock,
Myocardial infarction (MI) remains the most but it is important to recognize the other causes
prevalent etiology with mortality reported as and that patients may have a combination of more
greater than 35% [1], but CS secondary to than one type of shock.
advanced heart failure is now commonly seen in

C. Bennett · A. Solberg (*)

Mayo Clinic, Rochester, MN, USA
e-mail: [email protected];
[email protected]

© The Author(s), under exclusive license to Springer Nature Switzerland AG 2023 257
R. Musialowski, K. Allshouse (eds.), Cardiovascular Manual for the Advanced Practice Provider,
https://doi.org/10.1007/978-3-031-35819-7_24
258 C. Bennett and A. Solberg

Table 24.1 Classification of shock and expected hemodynamic responses

Classification of Shock

Cardiac
Heart Rate CVP PCWP SVR
Output

Cardiogenic

Distributive
-Septic
-Anaphylactic

Obstructive
-Tamponade
-PE
-Pneumothorax

Hypovolemia

Neurogenic

Pathophysiology Catecholamines are released by the sympa-

thetic nervous system in an attempt to increase
Cardiogenic shock is a condition of decreased stroke volume by raising the heart rate and con-
myocardial contractility secondary to underlying stricting blood vessels. Simultaneously, the
cardiac dysfunction and hypotension causing renin-angiotensin-aldosterone system is activated
hypoperfusion of the myocardium and other end when the renal system is poorly perfused and
organs. This hypoperfusion causes even more attempts to increase blood volume. Fluid is then
ischemia to cardiac tissue, which further reduces retained in an attempt to raise blood pressure,
low stroke volume and worsens diastolic filling. which increases both preload and afterload. As
This cycle can progress rapidly leading to patient the myocardium is stretched, brain natriuretic
death if not treated. peptide (BNP) is released and further contributes
As cardiac output decreases, intrinsic com- to the physiologic cycle.
pensatory mechanisms designed to raise blood The goal of these intrinsic mechanisms is to
pressure cause vasoconstriction and fluid reten- increase cardiac output by raising preload, stroke
tion. This is reflected as increased systemic vas- volume, and heart rate. However, if left
cular resistance (SVR) and elevated pulmonary unchecked, they increase the myocardial work-
capillary wedge pressure (PCWP). In CS, these load leading to worsening cardiac output,
mechanisms become maladaptive and cause an decreased tissue perfusion, hypotension,
increase in myocardial oxygen requirements, fur- ischemia, and ultimately myocardial dysfunction
ther worsening myocardial dysfunction. with remodeling [4].
24 Cardiogenic Shock 259

End-organ dysfunction occurs secondary to Patients with CS may present with symptoms
tissue hypoperfusion. When systemic tissue is consistent with their underlying pathology, and
hypoperfused, an inflammatory process is trig- the physical exam will be dictated by the CS phe-
gered. This inflammatory process leads to the notype [2]. Three phenotypes of CS exist. These
release of cytokines and nitric oxide, which cause phenotypes are categorized according to volume
vasodilation in the microcirculation, further status and cardiac output or peripheral exam.
affecting blood pressure and worsening hypoper- Clinically, phenotypes can be broken down into
fusion. As vasodilation occurs, oxygen delivery warm or cold and wet or dry (Table 24.2). The
decreases and ischemia develops [5, 6]. Poor tis- first phenotype is described as classic CS. Patients
sue perfusion and hypoxia lead to the develop- will have evidence of decreased CO, increased
ment of lactic acidosis. SVR, and evidence of increased preload.
Euvolemic CS also has evidence of decreased
cardiac output and increased SVR, but preload is
Clinical Presentation normal. Mixed or vasodilatory CS is a decrease
in CO and increase in preload, but the SVR is
History and Physical normal to low. Lastly, vasodilatory shock which
is non-cardiogenic is described as an increase in
Past medical history is key to the workup of CO, with decreased preload and afterload.
CS. Myocardial infarction, particularly When there is clinical evidence for CS, assess-
ST-elevation MI, is the most common cause of CS, ment of the severity is crucial to understanding
and anterior MI is the most likely to develop the patient’s risk for deterioration and overall
CS. Any primary cardiac diagnosis that causes prognosis. Clinical evidence of CS may include
myocardial dysfunction can deteriorate to ashen or mottled appearance, cold and clammy to
CS. Chronic heart failure (HF) can deteriorate into the touch, elevated lactate (>2.0), rales on physi-
an acute decompensated state and now accounts cal exam, evidence of organ involvement includ-
for as much as 30% of CS presentations [2]. Other ing transaminitis or rise in creatinine (double in
causes of CS include cardiac arrest, valvular heart creatine or 50% decrease of GFR), hypotension
disease, tamponade, myocarditis, congenital heart (systolic BP <90, MAP <60), and altered mental
disease, hypertrophic cardiomyopathy, refractory status [7].
ventricular tachycardia, apical ballooning, pulmo- The Killip classification assessment can be of
nary hypertension, and PE [3, 5, 6]. value when attempting to determine the patient’s
Patients may present with a variety of symp- overall clinical picture and mortality risk [8].
toms and/or feelings that include chest pain, dys- This system relies on the physical exam for
pnea, PND/orthopnea, syncope, presyncope, appropriate classification. Killip Class I was
progressive fatigue, and palpitations. Physical defined as no evidence of heart failure. Class II
exam findings may include pallor, cyanosis, or was defined as heart failure with the presence of
mottling of the skin. Assessment of the extremi- an S3 and rales on physical exam. Class III was
ties for strength of pulses and temperature can defined as severe heart failure which included the
provide an understanding of the patient’s presence of significant pulmonary edema. Class
perfusion status. Cardiac auscultation may reveal IV was defined as frank cardiogenic shock.
extra heart sounds, particularly an S3 being
indicative of HF, or murmurs. Evaluation of ele- Table 24.2 Clinical presentation of CS
vated jugular venous pressure, pulsatile liver, sig-
Volume status
nificant hepatojugular reflex, ascites, and lower Wet Dry
extremity edema may be helpful in determining Peripheral Cold Cardiogenic Euvolemic
the patient’s volume status, as well as assessment exam shock cardiogenic shock
of the lungs for rales suggestive of pulmonary Warm Mixed shock Vasodilatory
edema. shock (not CS)
260 C. Bennett and A. Solberg

Identification and management of early stages of ST-segments and T-wave abnormalities is cru-
of CS can prevent further deterioration. The cial. In addition, ECG can determine rhythm and
Society for Cardiovascular Angiography and underlying conduction.
Intervention (SCAI) has developed a classifica- Laboratory workup is a crucial part of evaluat-
tion for CS (Fig. 24.1) [7]. The SCAI classifica- ing end-organ involvement. Troponins should be
tion includes five stages of increased CS severity. drawn at baseline. Troponin I or T is acceptable,
Stage A identifies patients at risk. Stage B identi- although recently institutions have transitioned to
fies patients beginning to show signs of deteriora- high sensitivity troponins. Isolated troponin ele-
tion. These patients develop hypotension and/or vation in the absence of ACS is not specific but is
tachycardia without evidence of hypoperfusion a strong predictor of mortality when significantly
but require intervention to prevent the develop- elevated. A complete blood count to include
ment of end-organ damage. Stage C is classic hemoglobin and white blood cell count will be
CS. The patient has frank evidence of hypoperfu- important to assess for underlying signs of ane-
sion and requires hemodynamic intervention. mia and infection. Electrolytes, creatinine, and
Stage D is CS that continues to worsen despite cystatin C for kidney function assessment, liver
intervention and escalation of therapy. Stage E is function tests with INR, LDH, and lactate.
refractory CS [7]. Elevated lactate levels are associated with
increased mortality in patients with CS [4].
NT proBNP can be helpful for differentiating
Diagnostic Studies the etiology of shortness of breath and for prog-
nosis. ACS patients with increased BNP levels
An electrocardiogram (ECG) should be per- are at increased risk of mortality [4].
formed within 10 min of patient arrival [4, 5]. As A point-of-care ultrasound (POCUS) exam of
MI is the most common cause of CS, assessment the heart, lungs, and IVC can add valuable infor-

EXTREMIS

(A) Modifier: A patient with refractory shock or actual/impending

CA with concern for circulatory collapse.
anoxic brain injury
DETERIORATING

A patient who has clinical evidence of shock that worsens or

fails to improve despite escalation of therapy.

CLASSIC

A patient who has clinical evidence of hypoperfusion

that initially requires pharmacologic or mechanical support.
Hypotension is usually present.
BEGINNING

A patient who has clinical evidence of hemodynamic

instability (including hypotension, tachycardia or abnormal
systemic hemodynamics) without hypoperfusion.
AT RISK

A hemodynamically stable patient who is NOT experiencing

signs or symptoms of CS, but is at risk for its development (i.e.
large AMI or decompensated HF).

©2021 Society for Cardiovascular Angiography and Interventions

Fig. 24.1 SCAI cardiogenic shock stages classifies patients in or at risk for CS according to clinical status. (Permission
granted by Naidu et al. [9])
24 Cardiogenic Shock 261

a b

Fig. 24.2 (a) B-lines consistent with pulmonary edema present on lung imaging, (b) dilated IVC consistent with
increased preload, and (c) dilated left ventricle with a small circumferential pericardial effusion

mation to your physical exam. POCUS is a goal- The cornerstone of treating patients with con-
directed ultrasound and does not take the place of firmed or suspected CS is getting the patient to
a formal transthoracic echocardiogram (TTE). the correct level of care. Patients with CS should
Figure 24.2 demonstrates an example of the con- be triaged to a setting that offers percutaneous
stellation of finding on POCUS in a patient with coronary intervention (PCI), mechanical circula-
CS. Formal TTE should be a standard of care and tory support (MCS), a Cardiac Intensive Care
be performed as part of the CS repertoire. A TTE Unit (CICU), and cardiac transplant capabilities
adds valuable information about cardiac structure [10].
and function and will further define the direction As patients with CS are commonly volume
of care. overloaded and develop pulmonary edema,
Chest X-ray should also be performed and can ensuring an adequate airway and oxygenation is
help differentiate infection from pulmonary crucial. In the setting of acute decompensated
edema or other etiology during evaluation for CS. heart failure and CS, noninvasive positive pres-
sure ventilation (NIPPV) is required to optimize
ventilation and oxygenation. NIPPV recruits
Management lung tissue resulting in an increase in oxygen-
ation and a decrease in work of breathing. If non-
Once CS has been identified, the goal of therapy is invasive positive pressure ventilation is felt to be
to maintain adequate tissue perfusion. Management inadequate, then consider mechanical ventilation
should be geared toward circulatory support, ven- with the goal of lung protection ventilation and
tricular unloading, and myocardial perfusion. The oxygenation [10, 11].
underlying cause of CS must be identified and Continuous hemodynamic monitoring is an
managed while simultaneously providing support- important aspect of managing CS. Using arte-
ive care. As the most common cause of CS remains rial lines for continuous blood pressure man-
ACS, early consideration for reperfusion therapy agement and pulmonary artery catheters (PAC)
will be of utmost importance [5]. to titrate medications and guide additional ther-
262 C. Bennett and A. Solberg

apy can be helpful. If a PAC is unavailable or VO 2

CO
there is a contraindication, then a central line or SaO 2 SvO 2 hgb 13.4
a PICC line can also provide the ability to mon-
CO
itor hemodynamics and give central access for CI
vasoactive medications. There are also mini- BSA
mally invasive hemodynamic monitors avail- To maintain tissue perfusion, CS management
able, and noninvasive measures of hemodynamic should be focused on increasing CO. CO is
parameters can be obtained with improved by increasing the heart rate and the
echocardiography. stroke volume. Inotrope support is the first line
Historically, PAC were used regularly in post for increasing stroke volume, improving contrac-
MI patients. Subsequent literature demonstrated tility, and off-loading pressures working against
a correlation between PA catheter use and failing ventricles. In the CICU, there are common
increase in mortality, and routine PAC use is no IV inotropes used regularly for the treatment of
longer recommended for MI. Despite decline in CS (Tables 24.3 and 24.4). Each has pros and
use, PAC remain the standard for hemodynamic cons for use, and each should be chosen carefully
monitoring in the setting of moderate to severe based on the patient’s clinical picture. Monitoring
CS. Careful patient assessment and risk evalua- should be based on signs of end-organ function
tion should continue when deciding on monitor- including lactate, creatinine, urine output, skin
ing. Complications include bleeding, embolism, temperature, and mottling.
infection, pulmonary infarct or hemorrhage, and Dobutamine is a fast-acting beta receptor ago-
inaccurate data collection. nist with strong beta-1 stimulation and some
Continuous hemodynamic monitoring with beta-2 stimulation. It is a typical first-line IV
PAC can provide real-time feedback for care agent for inotropic support in the treatment of CS
teams to react and adjust treatments. PAC consist [13]. In addition to inotropy, dobutamine causes
of ports enabled to transduce right atrial pressure, vasodilation and therefore has some afterload
pulmonary arterial pressure with the ability to reduction effect. The combination of increased
measure a PCWP tracing, and mixed venous oxy- cardiac contractility and decreased afterload
gen saturation. From these measurements, CO, improves stroke volume and therefore increases
SVR, PVR, cardio power output (CPO), and pul- CO. Dobutamine has side effects including
monary artery pulsatility index (PAPi) can be increased heart rate and is known to be proar-
calculated. rhythmic. The onset of action of dobutamine can
CO and cardiac index (CI) can be obtained via be seen within minutes of initiation. Dosing
thermodilution, which is considered the most should be started low and increased as needed.
accurate, or by Fick calculation. Thermodilution Typical dose initiation is 2.5 μg/kg/min.
is a procedure performed at the bedside ideally Milrinone is a phosphodiesterase inhibitor,
using a dedicated rapid injector. Normal saline is which helps to activate beta receptors. This
rapidly injected into the RA port of the PAC, and results in an inotropic effect in the heart with
a thermistor monitors the temperature from the beta-1 receptor activation and pulmonary and
RA to the PA. Limitations to the thermodilution
method include less reliable readings associated Table 24.3 Differentiating SVO2 and ScVO2 when
with tricuspid valve regurgitation and ventricular trending in CS
septal defects [12]. SVO2 vs ScVO2
A CO and CI calculated by Fick can be done • SVO2 is a true mixed venous sample from the
as an alternative. The Fick calculation takes into distal port of PAC
• ScVO2 can be used as a substitute and is obtained
account oxygen consumption (VO2), height, from a central line, or proximal port of PAC. Central
weight, SaO2 from an ABG, SvO2 from a PAC, venous saturation is higher because the low oxygen
hemoglobin, heart rate, and age. content from the coronary sinus is not included
24 Cardiogenic Shock 263

Table 24.4 Common inotropes and vasopressors used for management of CS

Inotropes and vasopressors
Mechanism Half-life Dose range Considerations
Milrinone Phosphodiesterase inhibitor 2.3 h 0.1–0.5 μg/ – Can accumulate in renal
kg/min failure
Dobutamine Strong beta receptor agonist <2 min 2–10 μg/kg/ – Proarrhythmic
min
Dopamine Dopaminergic receptor agonist, alpha <2 min 2–10 μg/kg/ – Known to be
and beta agonist at higher doses min proarrhythmic
– Associated with higher
mortality
– First choice when heart
rate is low
Epinephrine Strong alpha and beta agonist <5 min 0.01–0.3 μg/ – Proarrhythmic
kg/min – Associated with high
lactate levels
Norepinephrine Strong alpha agonist, weaker beta 1–2 min 0.01–0.3 μg/ – Offers some mild inotrope
agonist kg/min effect
– Associated with less
arrhythmia side effects
Vasopressin Vasopressin receptor agonist in vascular 10–20 min 0.03–0.06 μg – Pure vasoconstrictor
smooth muscle

systemic vasodilation with beta-2 receptor Vasopressor support in the setting of hypoten-
activation. Milrinone has a slower onset of sion should be used to support tissue perfusion
action than dobutamine. In addition, because with the goal to maintain MAP greater than
milrinone is renally cleared, accumulation of 65 mmHg in conjunction with other therapies.
the drug can occur and cause worsening side Norepinephrine has been a standard first-line
effects including arrhythmias and vasopressor agent commonly used to treat hypo-
hypotension. tensive states like septic shock. Norepinephrine
Studies suggest increased mortality with the offers vasoconstriction and mild inotrope effect.
use of dopamine in patients with CS [2]. It has Afterload reduction should be considered if
both inotropic and vasopressor activity. At low tolerated by blood pressure. Afterload reduction
doses (0.5–2 μg/kg/min), the effects are primarily can assist with improving CO by decreasing car-
dopaminergic with peripheral vasodilation. diac oxygen demands. If IV afterload reduction is
Intermediate doses (2–10 μg/kg/min) have pri- necessary, consider nitroglycerin, clevidipine, or
marily beta-1-adrenergic effect with increased nitroprusside for short-term therapy with plans to
cardiac contractility, heart rate, and blood pres- transition to an oral agent based on clinical pic-
sure. Doses >10 μg/kg/min have alpha-adrenergic ture including kidney function.
effect with primary vasoconstriction and
increased blood pressure.
Epinephrine is considered a second-line medi- Long-Term Care
cation that acts as both inotrope and vasopressor.
At lower doses, epinephrine acts more as an ino- Although mortality is high, patients can recover.
trope given strong beta receptor agonist proper- The patient should be supported while decom-
ties. Epinephrine is proarrhythmic and can pensated with plans to intervene and treat their
therefore be problematic in the setting of under- underlying cardiac dysfunction.
lying cardiac dysfunction. In addition, epineph- Guideline-directed medical therapy (GDMT)
rine is associated with high lactate levels. Dose for the treatment of heart failure should be con-
range is similar to norepinephrine ranging from sidered in patients who have recovered from
0.01 to 0.3 μg/kg/min. CS. Beta blockers, ACE inhibitors, and other
264 C. Bennett and A. Solberg

evidence-based therapies can be initiated when hypoxia, and mitochondrial function. Can J Cardiol.
2020;36(2):184–96.
the patient is close to a euvolemic state and wean- 2. van Diepen S, Katz JN, Albert NM, Henry TD,
ing off IV inotrope and vasopressor agents. Jacobs AK, Kapur NK, et al. Contemporary man-
Afterload reduction can be transitioned to an oral agement of cardiogenic shock: a scientific statement
regimen based on kidney function and diagnosis. from the American Heart Association. Circulation.
2017;136(16):e232–e68.
Inotrope support may continue. Some patients 3. Brener MI, Rosenblum HR, Burkhoff
remain on long-term inotropes in the outpatient D. Pathophysiology and advanced hemodynamic
setting as a bridge to transplant or as palliative assessment of cardiogenic shock. Methodist Debakey
support for quality of life. Cardiovasc J. 2020;16(1):7–15.
4. Vahdatpour C, Collins D, Goldberg S. Cardiogenic
shock. J Am Heart Assoc. 2019;8(8):e011991.
Clinical Pearls 5. Bertini P, Guarracino F. Pathophysiology of cardio-
• Patients with confirmed or suspected CS genic shock. Curr Opin Crit Care. 2021;27(4):409–15.
should be triaged to a setting that offers PCI 6. Lim HS. Cardiogenic shock: failure of oxygen
delivery and oxygen utilization. Clin Cardiol.
capabilities and a CICU. 2016;39(8):477–83.
• Evaluation and treatment of underlying car- 7. Baran DA, Grines CL, Bailey S, Burkhoff D, Hall
diac dysfunction should continue while sup- SA, Henry TD, et al. SCAI clinical expert consen-
porting patients in CS. ACS is the most sus statement on the classification of cardiogenic
shock: this document was endorsed by the American
common etiology of CS and should be ruled College of Cardiology (ACC), the American Heart
out immediately upon presentation. Association (AHA), the Society of Critical Care
• To maintain tissue perfusion, CS management Medicine (SCCM), and the Society of Thoracic
should be focused on increasing CO. Inotrope Surgeons (STS) in April 2019. Catheter Cardiovasc
Interv. 2019;94(1):29–37.
support is the first line for increasing stroke 8. Killip T III, Kimball JT. Treatment of myocar-
volume, improving contractility, and off- dial infarction in a coronary care unit. A two
loading pressures working against failing year experience with 250 patients. Am J Cardiol.
ventricles. 1967;20(4):457–64.
9. Naidu SS, Baran DA, Jentzer JC, Hollenberg SM,
• Ongoing risk assessment in the setting of CS van Diepen S, Basir MB, et al. SCAI SHOCK stage
is crucial. Risk assessment tools including the classification expert consensus update: a review and
SCAI shock stages and Killip classification incorporation of validation studies: this statement
should be considered for mortality prediction. was endorsed by the American College of Cardiology
(ACC), American College of Emergency Physicians
• MCS consideration and cardiac transplant (ACEP), American Heart Association (AHA),
evaluation are warranted in patients with European Society of Cardiology (ESC) Association
refractory CS. for Acute Cardiovascular Care (ACVC), International
• Early involvement of palliative care can assist Society for Heart and Lung Transplantation (ISHLT),
Society of Critical Care Medicine (SCCM), and
with goals of care discussions and symptom Society of Thoracic Surgeons (STS) in December
management and can be particularly useful in 2021. J Am Coll Cardiol. 2022;79(9):933–46.
the setting of chronic end-stage heart failure. 10. Jentzer JC, Tabi M, Burstein B. Managing the first
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diagnosis. Curr Opin Crit Care. 2021;27(4):416–25.
should be considered in patients who have 11. Alviar CL, Miller PE, McAreavey D, Katz JN, Lee
recovered from CS. B, Moriyama B, et al. Positive pressure ventilation
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Introduction to Mechanical
Support
25
Courtney Bennett and Amanda Solberg

Intro to Support Devices cally or percutaneously. The main MCS devices

used today include intra-aortic balloon pump
Mechanical circulatory support (MCS) devices (IABP), percutaneous ventricular assist device
are designed to support patients, while they are (pVAD), extracorporeal membrane oxygenation
acutely decompensated, or to support them (ECMO), and implanted ventricular assist devices
through high-risk procedures to prevent decom- (VAD).
pensation. MCS devices are designed to augment Complications include death, infection, limb
vasopressor and inotrope therapy as a way to ischemia, embolic events, bleeding, hemolysis,
decrease preload, afterload, and oxygen con- and malposition [1]. These complications may be
sumption by the heart. Long-term mechanical worsened depending on patient comorbidities.
support devices are also available and are used as Careful patient selection for MCS is warranted.
a bridge to transplantation, bridge to decision, Each patient should undergo a robust multidisci-
destination therapy, or bridge to recovery. plinary evaluation to determine candidacy if able.
There are several MCS options, each with It is also recommended that prompt evaluation by
varying evidence supporting their use the MCS team should be made in patients with
(Table 25.1). MCS devices can be placed surgi- CS to facilitate recovery [1].

C. Bennett · A. Solberg (*)

Mayo Clinic, Rochester, MN, USA
e-mail: [email protected];
[email protected]

© The Author(s), under exclusive license to Springer Nature Switzerland AG 2023 265
R. Musialowski, K. Allshouse (eds.), Cardiovascular Manual for the Advanced Practice Provider,
https://doi.org/10.1007/978-3-031-35819-7_25
266 C. Bennett and A. Solberg

Table 25.1 MCS devices, their level of support, mechanism of action, and helpful information for each
Level of Indication/
support contraindication
Device Description (CO) Placement Mechanism of action Pros/cons
IABP – Increase SV 0.5–1 L/min – Femoral access – Timed balloon – Risk for limb and
(temporary) – Decrease – Sits in inflation during organ ischemia,
afterload descending aorta diastole increases atherosclerotic
– Perfuse coronary artery embolization, and
coronary perfusion, and rapid hemolysis
arteries deflation during systole – Monitor distal
reduces afterload pulses, device
placement with CXR,
CBC, and renal
function
– Used as first-line
MCS despite mixed
evidence
– Patient is limited
to best rest with
maximum HOB
elevation to 30°
– Recent ability to
place axillary to allow
patient ambulation at
some institutions
pVAD – Reduce 2.5–5.5 L/ – Femoral access – An axillary flow – High risk for
(temporary) oxygen min – Sits in the catheter pulls blood hemolysis and leg
consumption of depending ventricle, flows into from the ventricle and ischemia
LV on the aorta pushes blood to aorta – Monitor distal
– Decrease device pulses, CBC, LDH,
diastolic plasma-free
volume of LV hemoglobin
V-A – Provides Up to 6 L/ – Peripheral or – Blood is pumped to – High risk for limb
ECMO both respiratory min central cannulation an extracorporal ischemia with
(temporary) and circulatory – Venous cannula machine, blood is peripheral cannulation
support at the level of the oxygenated, and – The left
right atrium, and carbon dioxide is ventricular may
arterial cannula in removed requiring venting
the aorta or femoral
artery
LVAD – Reduce Up to 8 L/ – Placed via – Blood is removed – Destination
(long term) oxygen min sternotomy from left ventricle and therapy bridge to
consumption of returned to the aorta decision, bridge to
LV transplant, or bridge
– Decrease to recovery
diastolic – No pulses will be
volume of LV auscultated in
continuous flow
devices
– High risk of
thrombotic events, GI
bleed, and infection
25 Introduction to Mechanical Support 267

Reference
1. van Diepen S, Katz JN, Albert NM, Henry TD,
Jacobs AK, Kapur NK, et al. Contemporary man-
agement of cardiogenic shock: a scientific statement
from the American Heart Association. Circulation.
2017;136(16):e232–68.
Part VII
Peripheral Vascular Disease

Frank R. Arko III

Introduction

Vascular disease encompasses a wide span of disease processes involving the

arterial and venous systems. Much of the pathology in vascular surgery is
chronic in nature but each disease process can present in the acute setting and
when this occurs, we see high incidences of morbidity and mortality. In this
chapter, we will define the common diagnoses seen in the vascular surgery
scope to include aortic dissection and aneurysms, peripheral arterial disease
(PAD), carotid artery disease, and deep vein thrombosis (DVT).
Aortic pathology can be life threatening if not appropriately managed and
regularly followed in the outpatient setting. Therefore, it is imperative that we
discuss in detail the acute management of aortic disease as well as the long-
term goals of therapy for our patients. Complicated acute type B aortic dis-
section (TBAD) can present with life threatening end organ ischemia, aortic
rupture, spinal cord ischemia, or limb ischemia. Chronic aortic dissections
can present with aneurysmal degeneration, arterial stenosis, compressive
symptoms, and risk of aortic rupture. A mainstay of treatment in aortic dis-
ease centers around adequate blood pressure control and regular vascular sur-
gery follow-up with imaging to survey aortic size.
PAD is a chronic process that develops over time due to atherosclerosis of
the arteries related to common risk factors including age, cholesterol, smok-
ing history, diabetes, and hypertension. Atherosclerotic disease is important
to discuss and understand as patients present with a wide scope of symptoms
from asymptomatic, to lifestyle limiting claudication and in severe cases of
PAD, rest pain and even limb loss. PAD can affect the great vessels of the
aortic arch, the aorta, iliac arteries, arteries of the lower extremities and is
commonly seen in areas of arterial bifurcations. The mainstay of treatment is

F. R. ArkoIII
Vascular and Endovascular Surgery, Atrium Health/Sanger Heart and Vascular
Institute, Charlotte, NC, USA
e-mail: [email protected]
270 Peripheral Vascular Disease

medical therapy and modification of risk factors and interventional therapy is

usually guided based on the patient’s quality of life with the goal of reducing
symptoms.
Initially a DVT is an acute thrombotic event that over time will develop
into chronic thrombus and scarring within the venous system. Many patients
presenting with DVT can be treated with anticoagulation alone but in the
select group of patients with proximal DVT, interventional therapy can be
recommended to reduce the long-term effects of thrombus burden. A major
goal in the treatment of DVT is to reduce post-thrombotic syndrome and
venous hypertension which can lead to chronic swelling, heaviness, leg
fatigue, hemosiderin deposition, and lastly venous ulceration.
Carotid Artery Stenosis (CAS)
26
Trent Gabriel and Frank R. Arko III

Anatomy and Physiology which is a fibrinous connective tissue that also con-
tains the internal jugular veins and the vagus nerve.
The carotid arteries are the predominate vessels For most patients, the bifurcation of the CCAs into
that supply blood to the head and neck. The right the ECAs and ICAs occurs at the level of the upper
common carotid artery (RCCA) originates from border of the thyroid cartilage and roughly the level
the brachiocephalic artery, whereas the left com- of the fourth or fifth cervical vertebrae. At the bifur-
mon carotid artery (LCCA) originates directly cation, there is the carotid body as well as the
from the aortic arch. Both CCAs bifurcate in the carotid sinus. The carotid body is a chemoreceptor
neck at the level of the carotid sinus into two that works to detect the levels of PO2, PCO2, and
branches. The external carotid arteries (ECAs) sup- pH of the blood that passes through the bifurcation
ply the neck and face with arterial blood, whereas into the brain and face. This mainly works to alert
the internal carotid arteries (ICAs) supply the brain. the brain of the need to increase respiratory rate.
To further specify location, the carotid arteries are The carotid sinus is a baroreceptor that responds to
located posterior to the sternoclavicular joints and changes in the stretch of the blood vessel and helps
are protected as they lie within the carotid sheath, to maintain blood pressure (Fig. 26.1).

T. Gabriel (*)
Atrium Health/Sanger Heart and Vascular Institute,
Charlotte, NC, USA
e-mail: [email protected]
F. R. Arko III
Vascular and Endovascular Surgery,
Atrium Health/Sanger Heart and Vascular Institute,
Charlotte, NC, USA
e-mail: [email protected]

© The Author(s), under exclusive license to Springer Nature Switzerland AG 2023 271
R. Musialowski, K. Allshouse (eds.), Cardiovascular Manual for the Advanced Practice Provider,
https://doi.org/10.1007/978-3-031-35819-7_26
272 T. Gabriel and F. R. Arko III

1. Brachiocephalic artery
2. Right subclavian
3. Right common carotid
artery
4. Right internal carotid
artery
5. Right external carotid
artery
6. Left common carotid
artery
7. Left internal carotid
artery
8. Left external carotid
artery
9. Left subclavian artery

Fig. 26.1 Carotid anatomy

Pathology/Pathophysiology sclerosis can specifically affect the CCAs is the

of Carotid Artery Stenosis anatomy of the arterial bifurcation. The hemody-
namics of the blood flow through this channel
There are several potential causes of CAS with with associated fluctuations of shear stress can
the most common being the development of ath- predispose regions with lower flow velocity (i.e.,
erosclerosis, fibromuscular dysplasia, anatomical the carotid bifurcation) to development of ath-
variances, carotid artery aneurysms, Takayasu’s erosclerotic plaques. The hemodynamics of arte-
arteritis, radiation therapy injuries, and carotid rial flow at the carotid bifurcation can
body tumors. significantly increase the likelihood of athero-
Far and away the most common cause of CAS sclerotic plaque, reducing vessel lumen diame-
is the development of atherosclerosis. One of the ter, and increasing risk of thrombotic or embolic
prominent reasons the development of athero- event (Fig. 26.2).
26 Carotid Artery Stenosis (CAS) 273

Fig. 26.2 Turbulent Laminar

flow in CAS blood flow
development ([1],
Figure 1)

Disturbed
blood flow

Arterial
blood vessel ↓YAP
Endothelial
↓TAZ
cell

↑YAP
↑TAZ Plaque deposit

Plaques form in part due to the inflamma- Table 26.1 Common historical features to consider with
tory response (platelet deposition, smooth CAS
muscle cell proliferation, and slow accumula- Suggestive of symptomatic Commonly not
tion of lipoproteins) involved in the repair pro- CAS associated with CAS
cess. The atherosclerotic plaques form due to Amaurosis fugax—loss of Dizziness/vertigo
vision in one eye without loss of balance
several reasons, including elevated blood cho-
Difficulty speaking or Syncope or near
lesterol, long-term damage from smoking on understanding syncope
the intima of the vessel wall, chronically ele- Loss of strength on Muscle tension
vated blood glucose, and genetic predisposi- contralateral side headache
tion (Chap. 27). Numbness and sensory loss Tinnitus
on contralateral side
Facial droop
Slurred speech
Presentation of CAS Sudden severe headache

Patients with carotid artery disease can present

with or without neurological symptoms. rological symptoms (Table 26.1) and may be
Symptomatology and degree of stenosis are both revascularized at a lower degree of stenosis,
considered when evaluating for surgical revascu- whereas patients with asymptomatic carotid
larization. Patients with symptomatic carotid artery disease may be revascularized at a higher
artery disease may present with a myriad of neu- degree of stenosis.
274 T. Gabriel and F. R. Arko III

Physical Examination duplex ultrasound (DUS), magnetic resonance

angiography, and computed tomographic angi-
It is common to see referrals from providers for ography. Also, there are three main methods of
patients that have been found to have a carotid measuring the degree of stenosis: NASCET,
bruit. Bruits can be heard when there is turbulent ECST, and CC.
blood flow that must flow around an atheroscle- The first method of measuring carotid artery
rotic plaque (stenosis) within the vessel wall. stenosis, the North American Symptomatic
For best clinical practice, the patient should be Carotid Endarterectomy Trial (NASCET),
evaluated with their head secure and slightly tilted measures the residual lumen diameter at the
back with the chin elevated. Stand or sit next to most stenotic portion of the vessel and com-
the patient on the right when auscultating the right pares this with the lumen diameter in the nor-
ICA and ask them to look to their left. Repeat the mal ICA distal to the stenosis. This differs
same technique on the left (sit or stand to their left from the European Carotid Surgery Trial
and have them look right). Stethoscope should be (ECST) which measures the lumen diameter at
placed approximately 2–3 cm above the clavicle, the most stenotic portion and compares this
and patient asked to briefly hold their breath as with the estimated probable original diameter
they are expiring. Reposition the stethoscope two at the site of maximum stenosis (Fig. 26.3).
to three times moving caudally toward the level of Lastly, the third most common method to mea-
the bifurcation on both sides [2]. sure carotid artery stenosis is the common
The presence or absence of a carotid bruit is carotid (CC) method which measures the resid-
not diagnostic for whether the patient has signifi- ual lumen diameter at the most stenotic portion
cant carotid artery stenosis. Additionally, carotid of the vessel and compares it to the lumen
artery bruits are most often found to be benign. diameter in the proximal CCA.
Multiple studies have shown varying degrees of
specificity and sensitivity, with a consistent trend Conventional Cerebral Angiography Pros of
showing a positive bruit to be more specific than this diagnostic modality includes being able to
sensitive. evaluate the entire carotid artery system while
also showing information about atherosclerotic
disease, plaque morphology, and collateral circu-
Imaging/Diagnostic Testing lation as well. However, the downside to this
diagnostic imaging and the main reasons that it is
There are four main diagnostic tests that are rarely used are that it is invasive, quite expensive,
used to evaluate the degree of stenosis within and places patients at a slightly increased risk of
carotid arteries: cerebral angiography, carotid morbidity (due to CVA) and mortality.

Fig. 26.3 Assessing NASCET ECST

External Internal
carotid stenosis severity carotid carotid 30 65
([3], Fig 4) artery artery
A
40 70

B 50 75
60 80
C
70 85
Estimated
position of 80 91
carotid wall 90 97
Approximate equivalent
degrees of internal carotid
Common carotid artery artery stenosis used in
A–B C–B NASCET and ESCT according
NASCET ECST to recent direct comparisons
A C
26 Carotid Artery Stenosis (CAS) 275

Fig. 26.4 Carotid duplex ultrasound with high-grade

stenosis of the proximal ICA. PS peak systolic, ED
end diastolic

Table 26.2 Duplex ultrasound evaluation for carotid severity: Atrium health vascular laboratory standardization
values
Stenosis ICA PSV (cm/s) Plaque ICA EDV (cm/s) ICA/CCA PSV ratio
Normal <125 None <40 <2.0
<50% <125 <50% diameter reduction <40 <2.0
50–69% ≥125–230 >50% diameter reduction ≥40– ≤100 2.0–4.0
> 70% >230 >50% diameter reduction >100 >4.0
Near occlusion High, low, or undetectable Visible Variable Variable
Occlusion Undetectable Visible, no detection Not applicable Not applicable
CCA common carotid, ICA internal carotid, EDV end-diastolic velocity, PSV peak systolic velocity, PSV ratio carotid
index

Carotid Artery Duplex Ultrasound (US) This Magnetic Resonance Angiography This diag-
imaging modality (Fig. 26.4) utilizes B-mode nostic image shows a 3D image of the carotid
and Doppler US techniques to find focal increases bifurcation with good sensitivity for detecting
in blood flow velocity which can be indicative of high-grade stenosis but less accurate for detect-
carotid artery stenosis. It combines data from the ing moderate stenosis. Contraindications to
peak systolic velocity (PSV), end-diastolic veloc- potentially utilizing this modality are that MRA
ity (EDV), spectral configuration, and the carotid is more expensive, time-consuming, and less
index (ICA PSV to CCA PSV ratio). This imag- readily available. In addition, MRA is not a safe
ing modality has been shown to be highly spe- option for patients with significantly reduced kid-
cific or highly sensitive for detecting a residual ney function.
lumen diameter of <1.5 mm (Table 26.2). The
benefits of this imaging modality include that it is Computed Tomography Angiography This
noninvasive, safe, and relatively inexpensive. The imaging modality shows an in-depth anatomic
downside to this specific imaging modality depiction of the lumen, adjacent soft tissues, and
includes that near occlusions can be missed, the bony structures (Fig. 26.5). It can be particularly
degree of stenosis can be overestimated, and the useful when carotid duplex is not reliable. CTA is
cervical portion of the ICA is best seen. The natu- more readily available than MRA but still expen-
ral anatomic variances of patients make it diffi- sive. Lastly, impaired renal function is a relative
cult to obtain accurate results as well. contraindication.
276 T. Gabriel and F. R. Arko III

Fig. 26.5 CT angiography of the neck with 90% ICA stenosis (coronal and orbital views)

anagement of Carotid Artery

M efficacious as high potency statins. Dual
Stenosis antiplatelet therapy may be recommended.
Modifiable risk factors that are encouraged
If the patient is asymptomatic, and there is include smoking cessation, routine exercise,
less than <70% ICA stenosis, conservative adequate blood pressure control, blood glu-
management is the best option. Optimal cose control, and adherence to medical
medical therapy includes aspirin 81 mg and regimen.
statin therapy. Statin medications have been Surgical options for carotid revascularization
proven through many studies to be very ben- include TCAR (transcarotid artery revasculariza-
eficial at reducing atherosclerotic plaque tion), transfemoral carotid artery stenting, CEA
buildup as well as stabilizing existing plaque. (carotid endarterectomy), and carotid artery
Atorvastatin and rosuvastatin are most com- bypass. These modalities are usually considered
mon as they have been shown to be the most in symptomatic patients with stenotic disease.
26 Carotid Artery Stenosis (CAS) 277

Table 26.3 Qualifying characteristics for TCAR ease. Restenosis can occur after revascularizations
>75 years of age due to in-stent restenosis or thrombosis in TCAR,
HFrEF <35% intimal hyperplasia, thrombosis, or recurrent ath-
CAD with >75% stenosis erosclerotic disease after CEA.
Abnormal stress testing
Severe pulmonary disease
Prior head and neck radiation Clinical Pearls
Prior CEA with restenosis • The presence or absence of a carotid bruit
Surgically inaccessible lesion does not correlate with the severity of extra-
Contralateral occlusion cranial carotid disease.
Able to use clopidogrel for 60 days • Patients with risk factors, or known coronary,
neurovascular, or peripheral arterial disease,
CEA This surgery is an open surgical procedure should be screened for carotid artery disease.
where the carotid artery is opened and the plaque • Symptomatology in conjunction with degree
within the vessel is removed, and the artery is of stenosis will determine the need for carotid
repaired. revascularization.
• TCAR may be a good surgical option for high-
TCAR This surgery can be ideal for many high- risk surgical patient meeting TCAR criteria.
risk surgical patients. Direct visualization of the dis- • Ultrasound surveillance is needed after carotid
eased carotid and a reversal of flow away from the intervention to assess for restenosis.
brain are established with a small pump removing
debris and reducing embolic potential. A filter is uti-
lized, and the blood is removed from the carotid
artery and returned to the femoral vein. Once this References
reversed flow is safely established, stenting of the
1. Mehta V, Tzima E. A turbulent path to plaque
carotid lesion is undertaken with a reduction in the
formation. Nature. 2016;540:531–2. https://doi.
risk of neurologic injury. There are several qualify- org/10.1038/nature20489.
ing factors for patients (Table 26.3). 2. Kass J, Krishnamohan P. Clinical overview: carotid
artery stenosis. Elsevier. 1 Jan 2022. ClinicalKey.
Accessed 14 Mar 2022.
3. Saxena A, Ng EYK, Lim ST. Imaging modalities to
diagnose carotid artery stenosis: progress and pros-
Surveillance pect. Biomed Eng OnLine. 2019;18:66. https://doi.
org/10.1186/s12938-019-0685-7.
Doppler ultrasound imaging is traditionally used
for postoperative surveillance after carotid revas-
cularization to evaluate patency or recurrent dis-
Peripheral Arterial Disease (PAD)
27
Trent Gabriel, Amber Amick, and Frank R. Arko III

Anatomy made up of long fibrinous collagen chains, auto-

nomic nerves, and vasa vasorum (perfuse exter-
The body’s circulatory system is made of an nal walls of larger vessels) [1] (see Fig. 28.1).
amazing network of vessels. Systemic arteries When evaluating the total arterial anatomy
bring oxygenated blood flow from the heart to all (Fig. 27.1), it may be easiest to start from the
the tissues and organs throughout the body, heart and follow the aortic arch into the brachio-
through tiny capillaries, and back to the heart via cephalic, common carotids, and subclavian arter-
the venous system. The arterial system is contin- ies and continue into the head/neck/chest. These
uous from the heart and structured to accommo- arteries are also called the great vessels. From the
date the high pressures of blood being ejected subclavian arteries, the arm will further perfuse
from the heart with each heartbeat. Arteries have via the axillary, brachial, radial, and ulnar arteries
three layers, the innermost being the intima, into the palmar arch and smaller arteries of the
which is lined with endothelium. This single- hands. Blood flow also continues from the arch to
celled layer is a continuous layer present through- the descending aorta just left of the left subcla-
out the arteries, capillaries, veins, heart valves, vian artery and follows the thoracic aorta through
and endocardial surfaces. The intima secretes the chest and past the diaphragm where the
multiple factors that adjust vessel tone (vasodila- abdominal aorta will lead you to the visceral seg-
tion) and affect platelet aggregation and forma- ment. Here you will find the celiac, superior mes-
tion of thrombus. The middle layer, or media, of enteric, bilateral renal, and inferior mesenteric
arteries is made of smooth muscles, elastin, and arteries that supply blood flow to structures and
collagen and responds to signals along the intima. organs of the abdomen. Proceed distally, and you
The outermost wall of arteries is the adventitia, will reach the common iliac arteries, where the
aorta bifurcates into smaller arteries of the pelvis
and provides inflow to the bilateral lower extrem-
T. Gabriel · A. Amick (*) ities. The iliac arteries will bifurcate into internal
Atrium Health/Sanger Heart and Vascular Institute, and external iliac arteries and then continue to the
Charlotte, NC, USA
e-mail: [email protected]; femoral arteries. The common femoral arteries
[email protected] will bifurcate into the profunda and superficial
F. R. Arko III femoral arteries. The superficial femoral arteries
Vascular and Endovascular Surgery, Atrium Health/ will travel along the medial thighs posteriorly
Sanger Heart and Vascular Institute, behind the knee where the popliteal artery will
Charlotte, NC, USA lead to the tibioperoneal trunk, peroneal artery,
e-mail: [email protected]

© The Author(s), under exclusive license to Springer Nature Switzerland AG 2023 279
R. Musialowski, K. Allshouse (eds.), Cardiovascular Manual for the Advanced Practice Provider,
https://doi.org/10.1007/978-3-031-35819-7_27
280 T. Gabriel et al.

Internal carotid artery

External carotid artery
Internal jugular vein
Common carotid artery
External jugular vein
Subclavian artery
Subclavian vein
Pulmonary artery
Superior vena cava Aorta
Cephalic vein Pulmonary vein
Inferior vena cava Axillary artery
Axillary vein
Heart
Hepatic vein
Renal vein Descending aorta
Hepatic portal vein Gastric artery
Basilic vein Brachial artery
Renal artery
Mesenteric artery
Median cubital vein
Common iliac artery
Common iliac vein
Radial artery
Ulnar artery
Arterial palmar arch

Digital arteries
Palmar digital veins Femoral artery
Great saphenous vein
Femoral vein

Anterior tibial artery

Small saphenous vein
Anterior tibial vein Posterior tibial artery
Posterior tibial vein Peroneal artery

Arcuate artery
Dorsal venous arch
Dorsal digital vein Dorsal digital arteries

Fig. 27.1 Human circulatory system

27 Peripheral Arterial Disease (PAD) 281

posterior tibial artery, and the anterior tibial Pathology/Pathophysiology

artery. These distal arteries will then perfuse the
arteries of the foot. Peripheral arterial disease (PAD) is a condition
which is caused by atherosclerosis which reduces
tissue perfusion over time. Atherosclerosis is the
Physical Examination pathophysiologic process of accumulation of lip-
ids and fibrous materials between the layers of
A clinician’s physical exam should be thorough to the arterial wall, reducing the diameter of the
best evaluate for PAD as well as to determine arterial lumen, thereby limiting arterial blood
potential need for intervention. Upon inspection, a flow to tissue [2]. This development of athero-
clinician may appreciate muscle atrophy, hair loss, sclerosis over time leads to the formation of
color changes (cyanosis or pallor), ischemic tissue plaque which can eventually thrombose or rup-
changes, wounds, or decreased motor function of ture, causing occlusion of distal vessels
an area affected by arterial insufficiency. When (Fig. 27.2). PAD effects the lower extremities
palpating, the clinician may note cooler tempera- more often than the upper; however, PAD may
tures along the skin which may correspond with occur anywhere in the body and manifests
the level of disease. The clinician should evaluate through varying degrees of symptoms based on
motion and sensation along the extremities, includ- the severity of disease, as well as collateralized
ing hands, fingers, feet, and toes where the most blood flow. PAD is a chronic and progressive dis-
distal arteries may be compromised. A clinician ease in which the severity of symptoms will
should evaluate their patient for palpable pulses worsen with time if not appropriately managed.
(brachial, radial, ulnar, femoral, popliteal, poste- In its mildest form, patients may present with
rior tibial, and dorsalis pedis), their quality, as well abnormal test results but without symptoms. In
as if there is variation in laterality. mild to moderate disease, patients may experi-
Pulse may be qualified as 0, absent; 1, dimin- ence symptoms such as nonlimiting or limiting
ished; 2, normal; and 3, bounding. claudication. The Rutherford Classification
If pulses are nonpalpable, a clinician can fur- System is the gold standard among most vascular
ther evaluate with a handheld Doppler while lis- practices within the United States to aid in clas-
tening to the quality of arterial signals in the sifying severity of claudication (Fig. 27.3).
same anatomical locations – these may be Patients who suffer from severe disease may
described as triphasic, biphasic, monophasic, or develop tissue injury, nonhealing wounds, or
absent arterial signals. In addition to auscultation ischemic pain. Patients who suffer from rup-
via Doppler, a clinician may apply the bell of a tured atherosclerotic plaque may present with
stethoscope to evaluate for turbulent blood flow acute limb ischemia and need to be revascular-
(i.e., bruit), which could indicate stenosis, fistula, ized quickly to minimize irreversible ischemic
and other vascular pathologies. injury—please refer to The Rutherford

ATHEROSCLEROSIS

1. 2. 3. 4. 5.
NORMAL ARTERY ENDOTHELIAL FATTY STREAK STABLE (FIBROUS) UNSTABLE
DISFUNCTION FORMATION PLAQUE FORMATION PLAQUE FORMATION

Fig. 27.2 PAD progression of arterial disease

282 T. Gabriel et al.

Grade Category Sensory loss Motor deficit Prognosis Doppler signals

Arterial Venous
I Viable None None No immediate threat Audible Audible
IIA Marginally threatened None or minimal (toes) None Salvageable if promptly Inaudible Audible
treated
IIB Immediately threatened More than toes Mild/moderate Salvageable if promptly Inaudible Audible
revascularised
III Irreversible Profound, anaesthetic Profound, paralysis Major tissue loss amputation. Inaudible Inaudible
(rigor*) Permanent nerve damage
inevitable
This is an identical replica of the table in the 1997 publication by Rutherford et al.,2 with the exception of the asterisks (*).
*In the original 1997 classification it was stated that arterial Doppler sounds are never present in Stage IIA, and that rigor (mortis) is always
present in Stage III. However, it is the opinion of the Writing Committee that exceptions to these rules do exist, and a slight modification of
the Rutherford classification from 1997 may be appropriate in the future.

Fig. 27.4 Rutherford classification of acute limb ischemia

Classification of Acute Limb Ischemia ankle, divided by the highest brachial systolic
(Fig. 27.4). blood pressure.
A normal ABI is ≥1 as the systolic blood pres-
sure in the ankle is typically higher than in the
Imaging/Diagnostic Testing arm. An ABI of ≤0.9 is diagnostic of the presence
of PAD. An ABI of 0.4–0.9 is suggestive of a
Ankle Brachial Index degree of arterial obstruction often associated
with claudication. An ABI of less than 0.4 repre-
Physiologic testing is used to establish the diag- sents severe, multilevel, disease that risks non-
nosis of PAD. Depending on the specific type of healing ulcerations, ischemic rest pain, and pedal
testing, this can assist in defining the severity and gangrene (Fig. 27.4). ABI results of >1.3 are
extent of disease in patients with risk factors or falsely/artificially elevated which signifies that
suspicion for PAD. A cost-effective, easily avail- the lower extremity ankle arteries are calcified
able, and appropriate diagnostic tool to first eval- and/or noncompressible. In this case, the values
uate a patient for PAD is by obtaining an recorded are considered nondiagnostic. If the val-
ankle-brachial index (ABI). This simple and non- ues are nondiagnostic, then the use of toe-brachial
invasive test can determine the presence and indices (TBI) and toe pressures (TP) becomes
extent of PAD. An ABI can be calculated on each even more valuable in predicting the ability to
leg by using the systolic blood pressure at the heal a current wound. TBIs are obtained by plac-
27 Peripheral Arterial Disease (PAD) 283

Table 27.1 Toe pressure utilization for nondiagnostic statin therapy is recommended for all patients
ABI >1.3
with atherosclerotic disease regardless of base-
Toe-brachial index 0.7–0.8 normal line LDL level [2]. Hypertension impacts plaque
Toe pressure >30 mmHg in diabetic favorable wound
formation; thus, adequate blood pressure man-
healing
Toe pressure >50 mmHg nondiabetic favorable wound agement according to guidelines is important.
healing Glucose management in diabetics is important
for long-term vascular health, as well as mini-
mizing risk of lower extremity wounds. Tobacco
ing a pneumatic cuff on one of the toes (usually cessation is important for overall cardiovascular
the great toe) (Table 27.1). health, as well as maintaining patency of prior
vascular interventions. Lifestyle modification
should also include regular exercise or imple-
Arterial Duplex Ultrasound menting a regular walking program. Many
patients can avoid (or at least delay) the need for
Arterial duplex ultrasound is considered the endovascular or surgical intervention by adhering
mainstay and often the initial noninvasive vascu- to a walking program and successfully modifying
lar imaging obtained when PAD is suspected. risk factors.
Duplex evaluation visualizes perfusion through Currently, there is no definitive evidence for
the arteries in real time and measures peak sys- the efficacy of aspirin in patients with asymptom-
tolic velocities (PSV) of arterial blood flow. atic PAD. The guidelines vary in their treatment
Ratios are then determined from the change in recommendations for patients with asymptom-
PSV, which indicate a particular degree of atic PAD. The American Heart Association/
stenosis. American College of Cardiology PAD guideline
recommends antiplatelet therapy as reasonable if
the ankle-brachial index is ≤0.90; the European
Computed Tomography Angiography Society of Cardiology guideline recommends
(CTA) against routine antiplatelet therapy in asymptom-
atic patients; and the Society for Vascular Surgery
CT imaging uses contrast to obtain large series of guideline provides no specific recommendations
still images to better visualize and evaluate arte- for this. Patients with symptomatic PAD should
rial blood flow. CTA can be used when consider- be treated with antithrombotic therapy to reduce
ing open operative approach or concern for cardiovascular risk. Single antiplatelet therapy
inability to cannulate for endovascular interven- with either aspirin or clopidogrel is recom-
tion. CT evaluation requires intravenous contrast mended. Patients who undergo revascularization
for adequate visualization of vessels, thus con- for PAD should be prescribed lifelong antithrom-
sider risk of contrast exposure in renal patients. botic therapy. With respect to surgical revascular-
ization, aspirin, clopidogrel, and rivaroxaban are
all reasonable strategies [3].
Management Revascularization management and procedures
of the lower extremities include a variety of endo-
Medical management and risk factor modifica- vascular and open surgical techniques. Age, risk
tion are crucial in maintaining vascular wellness, factors, acute vs. chronic disease, and a multitude
reducing complication and recurrent ischemic of variables are considered in a patient’s plan of
events, minimizing atherosclerotic progression, care. Generally, endovascular approach is preferred
and achieving limb salvage. Medical therapies to an open surgery procedure. An endovascular
may include antiplatelet therapy, lipid-lowering approach consists of a surgeon evaluating and
agents (statins), and full anticoagulation when treating arterial blockages from within the lumen
deemed appropriate. High-dose/high-potency of an artery. After accessing the artery, an angio-
284 T. Gabriel et al.

gram will be performed to visualize disease along Clinical Pearls

the vessel, and then interventions such as angio- • Critical limb ischemia (CLI) is a classification
plasty, atherectomy, thrombectomy, drug-coated of severe peripheral arterial disease. These
balloon angioplasty, stenting, and administration of patients suffer ischemic rest pain and/or tissue
medications (i.e., nitroglycerin, thrombolytics) loss. If revascularization is unsuccessful,
may be performed. amputation may be needed.
There are multiple open revascularization • Patients with severe PAD as evidenced by test-
options depending on a patient’s extent of dis- ing may not require surgical intervention if
ease. Some examples of open surgical revascular- asymptomatic but warrant medical manage-
ization are provided below: ment and a regular walking program.
• Patients with severe peripheral arterial disease
• Aortobifemoral bypass—performed to treat should be considered for screening of disease
aortoiliac occlusive disease or aneurysmal dis- in other vascular beds (neurovascular, coro-
ease. A bypass is placed from the aorta to both nary, carotid).
femoral arteries. • After revascularization in patient with acute
• Iliofemoral bypass—used to treat iliofemoral limb ischemia, evaluate for compartment syn-
occlusive disease. A bypass is placed from the drome, an acute process that leads to repeat
iliac to femoral artery. occlusion of arterial perfusion and potential
• Axillofemoral bypass—extra-anatomic nerve damage.
bypass performed axillary artery to the femo-
ral artery. Lower patency rates long term.
Deep Vein Thrombosis
Revascularization may be performed using
autologous vein harvest, synthetic material, or Anatomy and Physiology
donor vessel.
Autogenous vein conduit bypass generally is Deep vein thrombosis (DVT) is when thrombus
preferred over synthetic grafts. forms within a deep vein of the leg. Deep veins
Prosthetic conduit bypass has an increased are identified as they have corresponding arterial
risk of needing graft explantation in the setting of vessels, whereas superficial veins do not
infection. (Fig. 27.5).
Superficial veins can be found in the subcu-
taneous tissues, while deep veins travel among
Surveillance muscles and bones below the fascia [1].
Perforator veins drain superficial venous blood
Patients having undergone vascular intervention flow into the deep vein system. Veins differ
will need lifelong management and surveillance. from arteries in that they are a low flow system
This is often done with duplex ultrasound fol- and have a thin muscular wall, and blood is
low-up at least annually. CTA may be more traveling against gravity. Veins have one-way
appropriate for certain patients. Ankle- and toe- valves which prevent regurgitation of blood
brachial index pressures are typically followed flow back down the leg, while it travels back to
long term for reassessment of trending patient’s the heart for recirculation [12]. Skeletal muscle
baseline arterial flow. At every follow-up, symp- contraction of the lower extremities also aids
toms are evaluated in conjunction with testing in propulsion of blood flow up through the low
results to determine potential need for reinter- flow venous system. DVTs are more common
vention. It is important to maintain close follow- in the lower extremities due to this flow against
up as the patient will require lifelong medical gravity.
therapy and potentially require repeat DVTs should be classified as either provoked
intervention. or unprovoked, which guides management.
27 Peripheral Arterial Disease (PAD) 285

Fig. 27.5 Deep veins of Inferior vena cava

lower extremity
Common iliac

External iliac

Common femoral
Deep femoral

Superficial femoral

Popliteal

Posterior tibial
Peroneal

Anterior tibial

Anatomical location of DVT also helps guide Table 27.2 DVT location and risk [13]
management, taking into consideration proximal Proximal—higher risk of PE and Distal—lower
or distal involvement in the extremities [5] mortality risk
(Table 27.2). Iliac Peroneal
Femoral Posterior Tibial
A myriad of other complications may arise
Popliteal Anterior Tibial
from DVT, including post-thrombotic syndrome
(PTS), venous insufficiency, venous wound
development (venous stasis ulceration), and Table 27.3 Risk factors for post-thrombotic syndrome
(PTS)
potential limb loss.
Post-thrombotic syndrome (PTS) occurs in DVT above the knee
Recurrent DVT in the ipsilateral limb
20–50% of patients with DVT, with 5% develop-
Persistent symptoms beyond 1 month of therapy
ing severe PTS. [7] Patients can develop chronic Therapy noncompliance/subtherapeutic AC levels
leg pain, itching, neuropathy, erythema, edema, Obesity
ulcers, and limited activity tolerance (Table 27.3). Residual thrombus
PTS is managed with compression garments
(usually 30–40 mmHg), wound care, and medical
therapy (i.e., moisturizer, topical steroids, anti-
inflammatories) [8].
286 T. Gabriel et al.

Physical Exam Imaging and Diagnosis

Patients with DVT may exhibit swelling, tender- D-dimer can be tested, but it is not recommended
ness, erythema, firmness along the leg, as well as given low specificity. Diagnosis of DVT is
a positive Homan’s sign. Patients with Homan’s obtained via visualization of thrombus in the
sign experience increased calf pain with dorsi- vein. Venous duplex for evaluation of DVT is the
flexion of the foot; however, this is a poor predic- gold standard (Fig. 27.6); however, computed
tor of DVT. tomography venography (CTV) can also be
obtained (Fig. 27.7). Interventional venogram
can be diagnostic as well therapeutic. Patients
Pathology/Description

DVTs can develop due to stasis of blood flow

within the deep vein system, endothelial injury,
or because of a hypercoagulable state, known as
Virchow’s Triad [9]. DVTs occur in 300,000–
600,000 people in the United States per year [7].
For common risk factors, see Table 27.4.
Symptoms will develop in the affected limb.
Most patients will experience pain, swelling,
warmth, erythema, hyperpigmentation, aching,
throbbing, and limb heaviness. If patients experi-
ence chest pain, shortness of breath, tachypnea,
tachycardia, or unexplained cough with DVT,
they should be screened for pulmonary embolus
[10] (Chap. 22).

Table 27.4 Risk factors for DVT

Family history/genetics History of prior
thrombotic event
Malignancy Spinal cord injury/
paralysis
African American race Tobacco use
Oral contraceptives Pregnancy (6 weeks
postpartum)
Surgery within 3 months Venous catheters
Prolonged immobility-travel, Hospitalization
cast
Age >40 years and risk Hypertension
doubles with every 10 years
Congestive heart failure Sickle cell disease Fig. 27.6 Femoral vein that does not collapse with pres-
Autoimmune disorders Hypercoagulable states sure. The lack of compression is suggestive of thrombus
and DVT at the yellow arrow
27 Peripheral Arterial Disease (PAD) 287

recommend if thrombus has propagated (even if

remaining in the distal veins).
CHEST recommends AC for patients with iso-
lated DVTs who are experiencing severe symp-
toms. Apixaban, dabigatran, edoxaban, or
rivaroxaban over VKA is recommended in the
first 3 months (treatment phase), and AC alone
over interventional therapies (thrombolytic,
mechanical, or pharmacochemical) for acute
DVTs. Oral Xa inhibitor (apixaban, edoxaban,
rivaroxaban) over LMWH is recommended for
initiation and treatment phases for patients with
Fig. 27.7 CTV to evaluate IVC stented segment. Dark
thrombus formation is seen on the right side of the stented
cancer. VKA (with INR target 2.5) is recom-
IVC segment mended for patients diagnosed with triple
antiphospholipid syndrome.
The CHEST guidelines also provide recom-
who have unprovoked DVT should undergo mendations on duration of treatment. Patients
hypercoagulable workup. EKG, echocardiogram with acute DVT without contraindication for AC
(to evaluate for right heart strain), CT angiogra- should begin a treatment phase of 3 months of
phy of the chest, or ventilation-perfusion (VQ) AC. At the completion of 3 months, patients
scan may be used to evaluate for pulmonary should be assessed for extended therapy. Therapy
embolism. should be extended for patients if the VTE was
unprovoked or provoked by a persistent risk fac-
tor (prefer DOAC over VKA).
Management Surgical interventions for management of
DVT include thrombolysis, catheter-directed
The aim of DVT management is to reduce risk of therapy, and thrombectomy. Thrombolysis,
thrombus propagation and embolization, relieve catheter-directed thrombolysis, and surgical
acute symptoms, and reduce risk of lasting com- thrombectomy are reserved for extensive proxi-
plications [11]. DVTs are managed with antico- mal lower extremity DVT (iliofemoral) for those
agulation (AC). Intravenous options for this with severe symptoms, threatened limb (phleg-
include systemic regular dose unfractionated masia), and with thrombus burden for <14 days
heparin in the acute setting. Therapeutic low- [11] (see Table 27.5). For these patients, the ben-
molecular- weight heparin (enoxaparin) or oral efit of more aggressive intervention may out-
anticoagulation can be used in the acute, sub- weigh the associated risks [13]. The 2016 AC
acute, or chronic phase. Oral anticoagulants Forum and 2020 NICE recommend individual
include direct-acting oral anticoagulants risk-to-benefit analysis for catheter-directed ther-
(DOACs) (apixaban, dabigatran, edoxaban, rivar- apy (CDT) and that patients with iliofemoral
oxaban) or warfarin (vitamin k DVT who have symptoms for <14 days, good
antagonists-VKA). functional status, life expectancy of 1+ years, and
The CHEST Guidelines can help aid clinician low risk for bleeding be considered for CDT [13].
decision-making based on DVT classification. Patients should undergo repeat venous ultra-
CHEST recommends serial imaging (weekly sound to evaluate DVT if symptoms worsen—
venous ultrasound) for 2 weeks instead of this will evaluate for thrombus propagation.
anticoagulation in patients with isolated distal Swelling and leg heaviness may persist for
DVT of the leg without severe symptoms or risk those with extensive DVTs, despite surgical
factors for extension. Upon repeat imaging, AC is intervention and post intervention therapies.
not recommended if no extension is seen and is This can be alleviated by consistent use of com-
288 T. Gabriel et al.

Table 27.5 Contraindication to thrombolysis and DVT tiation and treatment phases for patients with
[12]
cancer.
Absolute Relative • Clinicians should weigh risk of bleeding when
Recent intracranial History of uncontrolled HTN considering anticoagulation. Risk factors for
hemorrhage (ICH)
Severely uncontrolled Severe hypertension at
major bleeding while taking AC include age
HTN presentation (SBP >180, DBP >65, alcohol use, liver failure, renal failure,
>110) anemia, antiplatelet therapy, cancer, reduced
Cerebral vascular CPR >10 min within last functional capacity, frequent falls, prior bleed-
lesion-neoplasm 3 weeks
ing issues, prior stroke, and recent surgery
Ischemic stroke within Remote ischemic stroke
3 months [11].
Possible aortic Dementia • An inferior vena cava (IVC) filter may be
dissection placed in patients with acute proximal DVT of
Head trauma or facial Pregnancy the leg who have contraindication to AC.
trauma within
• It is important to educate patients on modifi-
3 months
Recent intracranial or Major surgery within 3 weeks able risk factors to prevent new or recurrent
spinal surgery thrombotic events. These risk factors include
Active bleeding Internal bleeding within medication compliance, smoking cessation,
(except menses) 2–4 weeks heart healthy diet, regular exercise, weight
Streptokinase within Active peptic ulcer disease management, and surgical prophylaxis.
6 months
Noncompressible vascular
• Phlegmasia dolens is a rare and life-threatening
puncture complication of extensive, acute DVT
[14]. Surgical intervention due to arterial per-
fusion compromise and risk of limb loss may
be needed.
pression garments, leg elevation, and regular
exercise. Patients can begin wearing compres-
sion garments once a DVT is deemed stable,
and not propagating. Compression garments References
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DVT diagnosis while starting anticoagulation ity peripheral arterial disease. UpToDate. 2021.
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extremity-peripheral-artery-disease?source=history_
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• Aside from patient with asymptomatic distal SS, Verma S, Bhatt DL. Antithrombotic therapy for
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Diseases of the Aorta
28
Tracy Totten and Frank R. Arko III

Aneurysm Pathology/Description

Anatomy and Physiology Aneurysmal degeneration of the aorta is a multi-

factorial, systemic process generally felt to be
The term aneurysm describes dilatation of any due to alterations in vascular wall biology lead-
blood vessel greater than 1.5× increase in diam- ing to a loss of vascular structural proteins (viz.,
eter compared with expected normal diameter. collagen) and wall strength. Biomechanical
Excluding intracranial vessels, arterial aneu- forces, including stress across the arterial wall,
rysms are most prevalent in the infrarenal aorta are also felt to play a role [3]. As the aorta
[1]. Aortic aneurysms are commonly associated enlarges, turbulent flow develops within the
with concomitant aneurysm of the ascending aneurysm due to the flow dynamics and can lead
aorta, thoracic aorta, iliac, femoral, or popliteal to thrombus formation along the aortic wall [4].
arteries. This can lead to distal embolization.
Arterial walls are made up of three layers:
tunica intima, media, and adventitia. A true aneu-
rysm involves dilation of all intact layers of the Classification
arterial wall due to remodeling of the extracellu-
lar matrix (ECM) (Fig. 28.1). The shape of aneurysms is defined as fusiform or
saccular. A fusiform aneurysm is a ballooning on
all sides of the aorta, whereas a saccular aneu-
rysm is a focal enlargement which is one sided. A
false aneurysm (pseudoaneurysm) develops from
arterial injury with subsequent hematoma forma-
tion and does not involve all three layers of the
arterial wall (Fig. 28.2).
T. Totten (*) Aneurysms can occur throughout the entirety
Atrium Health/Sanger Hearth and Vascular Institute,
Charlotte, NC, USA of the aorta. Location of aneurysms includes the
e-mail: [email protected] aortic root, ascending aorta, aortic arch, thora-
F. R. Arko III coabdominal aorta (Type I, II, III, IV), suprarenal
Vascular and Endovascular Surgery, Atrium Health/ aorta, juxtarenal, and infrarenal aorta. Abdominal
Sanger Heart and Vascular Institute, aortic aneurysms (AAAs) are a leading cause of
Charlotte, NC, USA death in the United States [1]. AAAs are classi-
e-mail: [email protected]

© The Author(s), under exclusive license to Springer Nature Switzerland AG 2023 291
R. Musialowski, K. Allshouse (eds.), Cardiovascular Manual for the Advanced Practice Provider,
https://doi.org/10.1007/978-3-031-35819-7_28
292 T. Totten and F. R. Arko III

Internal Elastic Lamina

Tunica Intima
External Elastic Lamina
Tunica Media
Tunica Adventitia

Adverse ECM
Physiological
remodeling
ECM
leading to
remodeling
aortic aneurysm

smooth muscle cell Proteoglycan

fibroblast MMPs
collagen TIMPs
Glycosaminoglycans (GAGs) Macrophages
Neutrophils

Fig. 28.1 Extracellular matrix, regional heterogeneity of the aorta, and aortic aneurysm [2]

diameter and length, with diameter being the

important risk factor for rupture (Table 28.1).

Risk Factors

Aortic aneurysms often occur in the setting of

other concomitant diseases. Most AAAs are
related to atherosclerotic disease (Table 28.2).
Incidence of AAA increases in males age
greater than 60 years and females greater than
Fusiform Saccular Saccular and Pseudo
aneurysm aneurysm fusiform
70 years of age. Males are more likely to develop
aneurysm
aneurysm AAA than females. However, females are more
likely to rupture at a smaller size than males [5].
Fig. 28.2 Types of aneurysm
Genetic conditions that are known to be associ-
ated with developing aortic aneurysms include
fied based on anatomical location, shape, and Ehlers-Danlos syndrome (EDS) and Marfan’s
size (Fig. 28.3). syndrome. These conditions are more concerning
Depending on the location and size of the in patients who present with aneurysms at a
aneurysmal segment, the management and clas- younger age. There is high association between
sification can vary. Aneurysm size is described by smoking and development of aneurysm.
28 Diseases of the Aorta 293

AORTIC ANEURYSMS
THORACIC AORTIC ANEURYSMS

THORACIC AORTIC
ANEURYSMS

NORMAL AORTA DESCENDING THORACIC AORTIC ROOT AORTIC ARCH ASCENDING THORACIC
AORTIC ANEURYSM ANEURYSM ANEURYSM AORTIC ANEURYSM

ABDOMINAL AORTIC ANEURYSM

ABDOMINAL
AORTIC ANEURYSM

NORMAL AORTA SUPRARENAL PARARENAL JUXTARENAL INFRARENAL

ABDOMINAL ABDOMINAL ABDOMINAL ABDOMINAL
AORTIC ANEURYSM AORTIC ANEURYSM AORTIC ANEURYSM AORTIC ANEURYSM

Fig. 28.3 Aortic aneurysm morphology and location

Table 28.1 Size and rupture risk [5] Asymptomatic screening is recommended in
Size of aneurysm Annual risk of rupture patients with tobacco use.
Small (3–3.9 cm) No increased risk
Medium (4–4.9 cm) 1%
Large (5–5.9 cm) 5–10% Signs and Symptoms
Very large (6–6.9 cm) 10–20%
Giant (7–7.9 cm) 20–40%
AAAs are commonly asymptomatic and found
>8 cm 30–50%
incidentally during workup for other disease pro-
cesses or on an age-related screening exam.
Table 28.2 Risk factors for aneurysm development Symptomatic patients can present with a wide
Atherosclerotic disease Any tobacco use array of symptoms. This may include abdominal,
Family history Male sex back, or flank pain. If there is evidence of a large
Genetic predisposition PAD/PVD
AAA, the patient can present with obstructive
Autoimmune/inflammatory Remote aortic
process surgery symptoms such as gastric outlet obstruction
Infection Hypertension (GOO), nausea/vomiting, urinary symptoms due
Age >60 years Caucasian race to obstruction of ureters, and inferior vena cava
Obesity Trauma compression and deep vein thrombosis (DVT). If
294 T. Totten and F. R. Arko III

an AAA has evidence of thrombus along the aor- and surveillance of AAA and lower extremity
tic wall, a patient may present with embolic aneurysms [5]. This is also the cheapest and least
changes (i.e., claudication, discoloration of toes, invasive. It is not uncommon that an abdominal
and feet). CT scan will be ordered for a patient during
workup of abdominal pain revealing an inciden-
tal finding of AAA. Non-contrasted abdominal
Physical Exam CT scans can help to identify AAAs but are not
an ideal study for surgical planning. A CT angi-
When examining the vascular patient for a con- ography of the abdomen and pelvis is the most
cern of aortic aneurysm, it is important to com- accurate modality for preoperative workup or
plete a full vascular exam. This includes a full concern for ruptured AAA. A CTA chest/abdo-
abdominal examination, lower extremity, and men/pelvis should be considered for any thoracic
peripheral pulse examination including palpation or thoracoabdominal aortic aneurysm. MRI of
of the popliteal fossa for pulsatile masses, auscul- the lumbar spine can also help to identify AAA
tation of carotid bruits, and cardiac auscultation. but are not ideal studies for AAA and are not
The provider must keep in mind the following list appropriate for surgical planning (Fig. 28.4).
of physical exam findings as the patient may
present with any of the following (Table 28.3).
Do not rely on a physical exam to diagnose a Management
AAA since it is a difficult clinical diagnosis.
Always check distal pulses due to risk of embolic Aortic aneurysms are managed medically with
disease and concomitant PAD. regular imaging surveillance until they reach size
criteria for surgical intervention. A goal of aneu-

Imaging Table 28.3 Physical findings consistent with AAA

Abdominal pulsatile mass Enlarged popliteal pulse
When working up an AAA, there are many dif- Aortic bruit Painful aortic palpation
ferent imaging modalities. Duplex ultrasound Abdominal, inguinal, or Embolic changes in lower
(DUS) is the modality of choice for screening flank pain extremity

Fig. 28.4 Infrarenal AAA pre-EVAR with heavy thrombus (DARK) and atherosclerotic burden (calcification in wall
of aorta) on CT imaging
28 Diseases of the Aorta 295

rysmal disease is early detection, surveillance, Surgical intervention is then further defined
and elective repair to prevent complications of based on endovascular repair versus open repair.
rupture, thrombosis, or embolism. The diagnosis EVAR is the most common repair, but there are
and treatment will depend on stability of the still cases in which open repair is preferred.
aneurysm [5]. Vascular surgery referral can be Endovascular repair is defined as EVAR (endo-
placed for any aortic aneurysm. Any incidence of vascular aortic repair), TEVAR (thoracic endo-
ruptured aortic aneurysms requires emergent vascular repair), and FEVAR (fenestrated
operative repair. endovascular aortic repair).
Medical management is indicated for stable Open aortic repair is completed with aortic
aortic aneurysms of less than 5.5 cm in males and bypass grafting with either aortoiliac, aortobi-
less than 5.0 cm in women. Modifiable risk fac- femoral bypass graft, or straight aortic tube graft
tors in the medical management of aortic aneu- for patients without iliac artery involvement.
rysms include smoking cessation, management Open repair may be indicated in younger patients
of hypertension, cholesterol, obesity, and athero- who are otherwise healthy; patients with anatomy
sclerotic disease. Medical therapy includes anti- not conducive to EVAR, including short or angu-
platelet therapy, statin drugs, and blood pressure lated infrarenal aortic neck; and multiple branch
management with a goal of normotension. Beta- vessels increasing risk for endoleak. Patients
blocker therapy is preferred as first-line agent. with connective tissue disorders may be favored
Full anticoagulation is needed if thromboembolic for open repair.
disease distal to an aneurysm is identified with Endovascular aortic repair is completed via
mural thrombus within the aneurysm. Avoid the percutaneous or open arterial access.
use of fluoroquinolones as they have been shown Straightforward EVAR can be completed with
to increase size of AAA and complications asso- procedural sedation versus general sedation.
ciated with rupture or dissection. Open access may be indicated in patients with
Once an aneurysm is diagnosed, DUS surveil- concomitant peripheral arterial disease, small
lance is obtained and is based on size and loca- access vessels, or prior surgical interventions.
tion (Table 28.4). Depending on the complexity of the repair,
The timing of surgical intervention is often alternative access sites may also be indicated

guided by size of the aneurysm (Table 28.5). including brachial artery or open axillary artery
conduit. Repair is completed by placing a bifur-
cated endograft within the aorta thereby exclud-
Table 28.4 Aneurysm surveillance AAA ing the aneurysm sac (Fig. 28.5). Prior to
Aneurysm size Duplex imaging frequency completion, a final angiogram is imaged to ensure
<4.0 cm Annually no evidence of endoleak at the remainder of the
4.0–5.0 cm Every 6 months case. Occasionally, assistive devices are used to
>5.0 CTA aid with the seal zone including fixation devices,
coiling, or onyx glue in patients with a short
Table 28.5 Aneurysm size and indication for surgical neck.
intervention Open aortic repair is completed via midline
Rapid growth 0.5 cm over 6 months or retroperitoneal incision (Fig. 28.6). The
Ascending and abdominal >5.5 cm males, >5.0 cm extent of repair is based on anatomical involve-
females ment of iliac and femoral arteries or concomi-
Ascending and abdominal Marfan’s >5.0 cm male,
4.5 cm female
tant PAD. The incision is carried down to the
>4.5 cm ascending root if aortic valve disease abdominal cavity exposing the aorta. A retro-
involvement peritoneal approach is performed with the
Isolated aortic arch >5.5 cm patient in right lateral decubitus position through
Popliteal >2.5 cm asymptomatic a left flank incision. The proximal and distal
Common iliac >3.5 cm asymptomatic arteries are then clamped, repair is completed
296 T. Totten and F. R. Arko III

Fig. 28.5 EVAR treatment of AAA with exclusion of residual thrombus

Table 28.6 Types of endoleaks (EL)

1 Proximal (a) distal (b) graft attachment site leaks
ab
2 Retrograde flow into the sac via aortic side
branches (i.e., lumbar, mesenteric)
3 Defect in the graft either d/t fabric tear or
disconnection of modular overlap
4 Graft wall porosity
5 Increase in maximum aneurysm diameter with no
identifiable endoleak; endotension
a
Intervention is indicated for Types 1, 3, and 2 when EL
sac with increasing aortic size [6]

within the remaining AAA sac, risking continued

aneurysm growth (Table 28.6).

Clinical Pearls
• Consider screening patients with risk factors
for AAA given they are commonly
asymptomatic.
• Fluoroquinolones are contraindicated in
patients with history of aortic aneurysm or
dissection as there is an increased risk of
Fig. 28.6 Open aorto-bi-iliac bypass with Dacron graft aneurysm and dissection with this drug
class.
by replacing the aneurysmal segment with syn- • Consider TTE screening for ascending aortic
thetic graft, the aneurysm is then oversewn, and aneurysm with new diagnosis of AAA and
the abdomen is closed. vice versa.
Postoperative surveillance of EVAR of the • Endocarditis prophylaxis should be recom-
infrarenal segment can be completed with aortic mended with any patient s/p aortic graft.
duplex in the vascular surgery clinic. An endoleak • There is risk for genetic inheritance of aneu-
is defined as flow outside of the endograft and rysms, thus recommend family screening.
28 Diseases of the Aorta 297

Aortic Dissection DeBakey

Type 1. Dissection originates in the ascending
Anatomy and Physiology aorta, extending to descending and abdominal
aorta
An aortic dissection is a tear within the layers of Type 2. Dissection originates and is confined to
the aorta. The tear occurs within the intima which the ascending alone
causes a separation of the media, creating a new Type 3. Dissection originates in the descending
channel which is defined as the false lumen. The aorta
native channel is defined as the true lumen. 3a = Supra-diaphragm
Throughout the aortic dissection, there are many 3b = Below diaphragm
communications between the true and false
lumen defined as fenestrations. The presence of The newest classification system as defined by
an “intimal flap,” representing the intimomedial the Society for Vascular Surgery (SVS) in 2020
septum between the true and false lumen, is the helps to overcome previous limitations and fur-
most characteristic pathology in acute aortic dis- ther develop more accurate communication when
section [7] (Fig. 28.7). Aortic dissections are describing the complex aortic dissection patient.
classified as acute versus chronic based onset Within the new SVS classification scheme for
timing and on the location of the entry tear. An aortic dissection, the distinction between Type A
acute aortic dissection is defined as onset of and Type B is predicated on entry tear location
symptoms within 2 weeks, subacute >14 days to alone and defined in zones [8].
90 days, and chronic >90 days. When discussing aortic syndromes, intramu-
Historically, there were two classification sys- ral hematoma (IMH) as well as the penetrating
tems: Debakey (1965) and Stanford (1970). The aortic ulcer (PAU) should also be included. IMH
Debakey classification defines the intimal tear does not have a clear tear or communication as an
and the extent of aortic dissection. The standard aortic dissection but rather appears as hemor-
Stanford classification describes only the tear and rhage within the aortic wall [8]. A PAU is defined
defines a type A as involving the proximal aorta as atherosclerotic plaque that penetrates the aor-
or type B (TBAD) which is distal to the left sub- tic wall. PAU rupture risk is directly associated
clavian artery [7] (Fig. 28.8). with the ulcer depth [8].

AORTIC DISSECTION
True lumen
False lumen

Outer layer

Middle layer

Inner layer

Blood flow

Fig. 28.7 Development and progression of aortic dissection

298 T. Totten and F. R. Arko III

Classification of Aortic Dissection

Stanford Classification

Type A Type B
Aortic arch
Ascending
aorta

Aortic
root

Descending
Thoracic
aorta

Suprarenal
artery Diaphragm

Renal artery

Abdominal
aorta

Healthy aorta Type I Type II Type III a Type III b

DeBakey Classification

Fig. 28.8 Dissection classification: Stanford and Debakey

Table 28.7 Risk factors for dissection

Pathology/Description
Uncontrolled and sudden variation in blood pressure
Cocaine
The process of an aortic dissection is dynamic,
Pregnancy
therefore can occur anywhere along the aorta and Genetic predisposition (Marfan, Ehlers-Danlos
present with an array of symptoms. The entry tear syndrome (EDS), Loeys-Dietz syndrome (LD)
occurs within the intima and media layers of the Blunt force trauma
aortic wall, creating an intimal flap in which blood Bicuspid aortic valve
rushes into the space both proximal and distal with Inflammatory conditions of Giant cell arteritis (GCA),
Takayasu arteritis
multiple fenestrations between layers [7]. Rupture
of the intima and media is the initial event in most
cases of aortic dissection. The violation of the inti- organs, true lumen compression, aneurysmal
mal surface results in formation of a cleavage degeneration, uncontrolled pain, or aortic
plane into the outer media and subsequent propa- rupture.
gation for a varying distance in this plane, either
antegrade or retrograde [7] (Fig. 28.7).
Aortic dissections are classified as compli- Risk Factors for Dissection
cated versus uncomplicated. Complicated
dissections are defined by malperfusion of end See Table 28.7.
28 Diseases of the Aorta 299

Physical Exam chronic dissection which will appear as a clearly

defined dissection flap that usually is thicker and
The patient may present with a wide array of more dense [8]. IMH will appear as a hyper-
symptoms. The classic description is described as density within the aortic wall. PAU will appear as
a ripping, tearing, sharp, “worst ever” anterior an atherosclerotic lesion with ulcer-like projec-
chest or back pain. There may be evidence of an tion within the aortic wall. A chest X-ray can
anxious appearing patient with tachycardia and reveal widening of the cardiac or aortic silhouette
tachypnea. If there is a flow-limiting dissection, with widened mediastinum. A TTE or TEE can
the patient can present with hypoperfusion symp- be used to evaluate for any evidence of cardiac
toms and commonly abdominal pain. The medi- tamponade or aortic insufficiency in the setting of
cal provider should always obtain blood pressure a type A aortic dissection. A TTE should be
readings in both upper extremities as the patient ordered with diagnosis of acute aortic dissection.
may present with loss of pulses to extremities MR angiograms are not recommended. An EKG
which could represent ischemia. Always com- should always be obtained in the setting of acute
plete a thorough cardiac exam and auscultate for type A aortic dissection. Proximal dissection into
cardiac murmur. If the dissection involves the a coronary artery (RCA) can create STEMI in
intracranial vessel, there could be evidence of addition to aortic dissection.
neurologic changes presenting with stroke,
Horner’s syndrome, voice hoarseness, and spinal
cord ischemia. Management

Prompt diagnosis and management are key, and

Imaging aortic dissections are associated with high mor-
bidity and mortality. Type B aortic dissections are
When working up, aortic dissections consider the either managed medically or occasionally surgi-
following imaging modalities. The gold standard cally. The cornerstone of medical therapy is
imaging is a CT angiogram of the chest, abdo- reduction of arterial blood pressure [7]. Acute
men, and pelvis. An acute dissection flap aortic dissection patients will be admitted to ICU
(Fig. 28.9) is thin in appearance compared with a for anti-impulse therapy and vasodilator therapy.

Fig. 28.9 CTA with acute thoracic aortic dissection

300 T. Totten and F. R. Arko III

Beta blockade (labetalol or esmolol) is always fusion or disease progression. TEVAR or surgical
initiated first as vasodilators can cause a reflex intervention may be warranted in TBAD with
tachycardia, which can worsen the dissection. persistent/recurring pain, uncontrolled hyperten-
Intravenous nicardipine is commonly used as a sion despite medical therapies, advancing aortic
vasodilator. The goal is prompt control of heart expansion, or any evidence of malperfusion. A
rate and systolic blood pressure goal <120 mmHg TEVAR may be performed to prevent late com-
or HR <70 bpm. plications and promote aortic remodeling as well.
Urgent surgical repair is indicated of acute During this procedure, a stent graft is deployed in
type A aortic dissections because medical treat- the true lumen to cover the entry tear with the
ment is associated with 60% in-hospital death goal of improved aortic perfusion and encourag-
rate [7]. The anatomic goal is resection of the ing thrombosis of the false lumen (Fig. 28.10).
aortic intimal tear to eliminate the threat of rup-
ture and to reconstruct the aortic wall layers.
Type A dissection may require aortic valve repair/ Surveillance
replacement, aortic root/aortic arch/hemiarch
repair/replacement. Acute tamponade may The principal late complication of aortic dis-
develop with dissection into the pericardium. section is aneurysmal dilatation of the outer
This is a surgical emergency, and pericardial tap wall of the false lumen [7]. Regular follow-up
should be avoided as this may worsen hemody- with serial imaging for routine surveillance is
namic collapse and delay emergent surgical recommended lifelong with a vascular surgery
intervention. clinic. False lumen patency or thrombosis is an
In patients with uncomplicated type B dissec- important predictor of regional luminal growth
tion (TBAD), surgical therapy has not shown and reintervention rate [8]. In follow-up, maxi-
superiority over medical therapy [7]. Therefore, mal aortic diameter is documented and fol-
most TBAD are managed medically if uncompli- lowed over time. Patients with aortic dissection
cated. The goal of medical therapy is anti-impulse undergo at least annual surveillance with CT
control, pain control, and evaluating for malper- angiogram.

Fig. 28.10 TEVAR within true lumen excluding thrombus in false lumen
28 Diseases of the Aorta 301

Clinical Pearls 2. Jana S, Hu M, Shen M, Kassiri Z. Extracellular

matrix, regional heterogeneity of the aorta, and aortic
• Patients diagnosed with aortic dissection aneurysm. Exp Mol Med. 2019;51:1–15.
should be referred to an aortic center when 3. Dalman R, Mell M. Overview of abdominal aortic
possible. aneurysm. 2022. https://www.uptodate.com/contents/
• Anti-impulse therapy is the mainstay of treat- overview-of-abdominal-aortic-aneurysm#!.
4. Schermerhorn M, Cronenwett JL. Arterial aneurysms:
ment for heart rate and blood pressure in abdominal and iliac aneurysms. Rutherford vascular
patients with aortic dissection. surgery. 6th ed. Elsevier; 2005.
• A bicuspid aortic valve is associated with 5. Abdominal aortic aneurysm. Elsevier BV; 2021.
increased risk of aortic dissection and thoracic https://www-c linicalkey-c om.ahecproxy.nca-
hec.net/#!/content/67-s 2.0-7 c5e261c-e a6f-4 cab-
aortic aneurysm. aae7-cb8155587799.
• Genetic referral for screening should be con- 6. White SB, Stavropoulos SW. Management of
sidered in patients with acute aortic dissec- Endoleaks following Endovascular Aneurysm
tions, especially in the younger population. Repair. Semin Intervent Radiol. 2009 Mar;26(1):33-
8. https://doi.org/10.1055/s-0029-1208381. PMID:
21326529; PMCID: PMC3036461.
7. Black J, Cambria RP. Aortic dissection: perspectives
References for the vascular/endovascular surgeon. Rutherford’s
vascular surgery. 2005. p. 1512–31.
1. Lawrence PF, Rigberg DA. Arterial aneurysms, 8. Lombardi JV, Hughes GC, Appoo JJ, et al. Society
epidemiology, and natural history. Rutherford’s for Vascular Surgery (SVS) and Society of Thoracic
vascular surgery and endovascular therapy. Surgeons (STS) reporting standards for type B aortic
2019. p. 875–83. https://www-clinicalkey-com. dissections. 2020. https://www.jvascsurg.org/article/
ahecproxy.ncahec.net/#!/content/book/3-s 2.0- S0741-5214(19)32649-7/fulltext.
B9780323427913000694?scrollTo=hl0000575.
Part VIII
Adult Congenital Heart Disease (ACHD)

Jana Reid Arwa Saidi

1.1 Introduction

Congenital heart disease is a rapidly growing subspecialty of cardiology.

Nearly 1% of infants born in the USA have congenital heart disease [1–4].
Initially considered a disease of the pediatric population, many advances in
the field have led to more adults now living with congenital heart disease than
children. Prior to 1940, in the absence of any meaningful treatment options,
90% of infants born with complex congenital heart disease died before adult-
hood [2]. Following major advancements in diagnosis and treatment, a major-
ity of infants now live into adulthood. As such, there are currently well over
one million adults living with congenital heart disease [4, 5].
The evolution of treatment of congenital heart disease has been dramatic
over the last 60 years. The development and advances in surgical, interven-
tional, and diagnostic tools have changed the landscape of management and
have profoundly affected outcomes. The first PDA ligation was performed in
1938. In 1944, Dr. Blalock, Dr. Taussig and Mr. Thomas devised the first
shunt to improve pulmonary blood flow in a patient with Tetralogy of Fallot.
The invention of the heart-lung bypass machine in 1955 led to the first repair
of an ASD, which was the start of decades of advancement in congenital heart
surgery. Catheter based procedures were developed in the 1960s and initially
treated lesions such as PDAs and ASDs and are now used in complex disease.
The first Fontan procedure was performed in 1968, allowing children born
with a single functional ventricle to live past one year of age. The advent of
2D echocardiography in the 1970s permitted a major step forward in the diag-

J. Reid · A. Saidi
UF Health Congenital Heart Center, University of FL, Gainesville, FL, USA
e-mail: [email protected]; [email protected]
304 Adult Congenital Heart Disease (ACHD)

nosis and management of congenital heart disease. Transposition of the Great

Arteries was treated with the first arterial switch procedure in 1975, eventu-
ally replacing the previously performed atrial switch procedure and
dramatically altering the long-term course for patients with TGA. The first
minimally invasive heart valve replacement was performed in 2000, leading
the way for non-surgical options for a variety of congenital heart defects. 3D
imaging is now being used to help map out complex anatomy in advance of
intricate surgical interventions and stem cell therapy is an emerging field that
is the source of many exciting research studies [6].
Hundreds of thousands of infants and children have benefitted from these
advances in diagnosis, intervention, and clinical care, such that they are living
well into adulthood. While initially thought to be curative, it has been recog-
nized over time that many of these interventions allowed children to grow up
without severe limitations, but with increased long-term morbidity and mor-
tality, often becoming evident in the adult years. The need for uninterrupted
specialized care in an ACHD center cannot be overstated, as outcomes for
adults who have been lost to follow-up are notably worse than those who have
consistent access to care. As childhood palliative interventions reach the end
of their lifespan, adults with congenital heart disease are prone to atrial and
ventricular arrhythmias, infective endocarditis, heart failure, pulmonary
hypertension, and the need for pacemakers and/or defibrillators [3, 4, 7].
They may require additional interventions for their congenital heart disease,
either via surgical or transcatheter intervention. For those with advanced dis-
ease processes that cannot be otherwise salvaged, advanced therapies includ-
ing mechanical circulatory support and transplantation, sometimes
multi-organ, may be considered. Additional factors for adults with congenital
heart disease include contraception, pregnancy risk and delivery consider-
ations, perioperative care for non-cardiac surgery and the management of
acquired cardiac and non-cardiac co-morbidities [4–7]. A multidisciplinary
model of care for adult congenital heart disease is critical to long-term health
and wellness.
Adults with congenital heart disease make up an ever growing and intrigu-
ing subset of general cardiology. Whether a simple or complex lesion, these
patients have special considerations for management. There have been many
advances in care over the last 60 years and certainly the future is full of more
revolutionary innovations for those living with congenital heart defects.

References

1. Allen HD, Penny DJ, Feltes TF, Cetta F. Moss and Adams’ heart disease
in infants, children, and adolescents including the fetus and young adult.
9th ed. Wolters Kluwer; 2016.
2. Tennant PW, Pearce MS, Bythell M, Rankin J. 20-year survival of children
born with congenital anomalies: a population-based study. Lancet.
2010;375(9715):649–56. https://doi.org/10.1016/S0140-6736(09)
61922-X.
Adult Congenital Heart Disease (ACHD) 305

3. Gurvitz M, Dunn JE, Bhatt A, et al. Characteristics of adults with congeni-

tal heart defects in the United States. J Am Coll Cardiol.
2020;76(2):175–82.
4. Stout KK, Daniels CJ, Aboulhosn JA, et al. 2018 AHA/ACC Guideline for
the Management of Adults With Congenital Heart Disease: a report of the
American College of Cardiology/American Heart Association Task Force
on Clinical Practice Guidelines [published correction appears in J Am Coll
Cardiol. 2019 May 14;73(18):2361–2362]. J Am Coll Cardiol.
2019;73(12):e81–e192.
5. Baumgartner H, De Backer J, Babu-Narayan SV, et al. 2020 ESC guide-
lines for the management of adult congenital heart disease. Eur Heart J.
2021;42:563–645.
6. Kiess M. History and evolution of the treatment of adult congenital heart
disease. BCMJ. 2016;58(7):368–72.
7. Warnes CA. Adult congenital heart disease: the challenges of a lifetime.
Eur Heart J. 2017;38(26):2041–7. https://doi.org/10.1093/eurheartj/
ehw529.
ACHD
29
Amanda Green and Jorge Alegria

Simple Defects of left ventricular diastolic dysfunction with sub-

sequent increase in left atrial pressure may result
Atrial Septal Defect (ASD) A communication in an increase left to right shunt in adults, espe-
between the atria, allowing blood flow between cially in the presence of hypertension or coronary
the systemic and pulmonary circulations [1]. artery disease.
These can occur in isolation or as a part of a more
complex diagnosis/constellation of defects.
Types of ASD

Anatomy and Physiology Secundum ASD: Located in septum primum, in

the region of the fossa ovalis. This is more com-
Defect in the atrial septum. These can be in the mon in females who make up 65–75% of the
septum primum, secundum, or associated with patient population with secundum ASD [3].
anomalous pulmonary veins in the case of a sinus Depending on the defect size and pulmonary vas-
venosus defect (superior or inferior location). cular resistance, it can often be closed by trans-
The degree of shunting across the ASD is catheter techniques.
determined by the size of the defect as well as the Primum ASD: Also known as endocardial
degree of ventricular compliance. In older adults cushion or AV septal defects and are associated
who have decreased ventricular compliance and a with abnormalities of the atrioventricular valves
stiffer ventricle, there is a greater risk of transient [3]. Anatomically located in the septum secun-
heart failure after closure of the atrial defect, dum, these ASDs usually require surgical repair.
given that the stiff ventricle now must accept a In the electrocardiogram a first-degree atrioven-
greater volume load and no longer has the “pop tricular block and left axis deviation can be
off” of the atrial septum [1, 2]. The development found. Left ventricular outflow tract obstruction
can be present. Long-term complications in
adults may result in need of permanent pace-
A. Green maker, left sided atrio-ventricular valve
Atrium Health/Sanger Heart and Vascular Institute,
Greenville, SC, USA replacement.
e-mail: [email protected] Sinus Venosus ASD: These are located along
J. Alegria (*) the superior or inferior portion of the atrial
Atrium Health/Sanger Heart and Vascular, Congenital septum near the junction of the SVC or

Heart Center, Charlotte, NC, USA IVC. They are often associated with partial
e-mail: [email protected]

© The Author(s), under exclusive license to Springer Nature Switzerland AG 2023 307
R. Musialowski, K. Allshouse (eds.), Cardiovascular Manual for the Advanced Practice Provider,
https://doi.org/10.1007/978-3-031-35819-7_29
308 A. Green and J. Alegria

anomalous pulmonary venous return. Superior Coronary Sinus Septal Defect: This is a defect
sinus venosus is the most common form of the in the wall of the coronary sinus also known as an
two, and accounts for 5–10% of all ASDs [3]. “unroofed coronary sinus,” which can result in
These commonly requires surgical repair of left to right shunting (LA CS defect RA) [3]. This
defect and baffling of the pulmonary veins to the is also commonly associated with a persistent left
left atrium. superior vena cava.

Secundum
Sinus venosus
superior and Primum
inferior

Physical Exam Correlations EKG may demonstrate a right bundle branch

block or rSr’ pattern in secundum atrial septal
On physical exam, there may or may not be a defect [1, 3].
murmur if the ASD is small with a low degree of
shunting. If a higher degree of left to right shunt
is present, there may be a soft systolic ejection Pathology/Description
murmur given the increased blood flow across
the pulmonary valve annulus. S2 may have fixed This defect may be associated with Down
splitting but this finding is not always present [3]. Syndrome, Holt Oram syndrome, DiGeorge syn-
In patients with pulmonary hypertension, P2 may drome, and Ellis Van Creveld syndrome [2].
be loud or “snappy” [3]. There is an approximate 10% inheritance risk
Adults with undiagnosed ASDs may present from a parent with an ASD to their child [2].
with a chief complaint of fatigue, exercise intol- Imaging: CMR, Cardiac CT, and/or TEE are
erance, and/or palpitations [1]. Paradoxical useful to evaluate ASD size, shape, rim tissue,
embolism may also occur. and pulmonary venous connections in adults with
29 ACHD 309

ASD. These imaging modalities are helpful in the tional cardiology procedures including EP pro-
decision-making regarding ASD closure type and cedures [4].
timing [3].
Pearls
• Approximately 34% of adults with unre-
Management paired ASD have complaints of palpitations,
which typically is sinus tachycardia [1]. In
Management of the ASD depends on the type and patients aged 40–60 years, 15% may have
location of the defect. Secundum ASDs can often atrial flutter [1].
be closed with transcatheter techniques and • ASD may have fixed splitting of S2, more
devices, while primum ASDs, coronary sinus common in defects with greater shunting
septal defects, and sinus venosus ASDs require (higher Qp:Qs) [3].
surgical repair. • If pulmonary hypertension is present, may
The ACC/AHA guidelines recommend that have loud P2 [3].
adults with an unrepaired ASD or a repaired ASD • RV lift may be felt in the subxiphoid area on
with residual shunt have pulse oximetry at rest deep inspiration [3].
and during exercise performed. This will help • EKG may show a rSr’ pattern in the right pre-
assess for systemic desaturation, which would cordial leads, and right bundle branch block
indicate the presence of right to left shunting may also be seen [1, 3].
across the defect.
Indications for Repair [4]:
Ventricular Septal Defect (VSD)
• Qp:Qs (pulmonary: systemic blood flow) of
>/= 1.5:1 and/or right heart enlargement. Anatomy and Physiology
• ASDs should not be closed in adults where the
pulmonary arterial systolic pressure is >2/3 of A VSD is a hole/communication between the
systemic, PVR greater than 2.3 systemic, and/ ventricular septum (wall that separates right and
or there is a net right to left shunt. left ventricles) that allows for blood communi-
cation from the left sided systemic circulation to
Long-term surveillance for ASD depends on the right sided circulation or pulmonary circula-
the type of ASD and repair needed and are speci- tion. Ventricular septal defects can occur in vari-
fied in the AHA/ACC Guidelines for the ous parts of the ventricular septum and are
Management of Adults with Congenital Heart classified based on their location [5]. In both
Disease. children and adults (excluding bicuspid aortic
Simple (I): a small, isolated ASD. This includes valve in the adult population), VSDs are the
a native isolated small ASD, or repaired secundum most common congenital heart defect [5]. In
ASD or sinus venosus defect without significant many cases the VSD may close spontaneously
residual shunt or chamber enlargement. from either muscle occlusion in muscular
Moderate Complexity (II): Primum ASD, defects, or closure from aneurysmal tricuspid
moderate to large unrepaired secundum ASD. valve tissue in perimembranous defects. With
ACHD expertise may improve outcomes in reduction in size, the burden of shunt is also
procedures such as diagnostic and interven- decreased [5].
310 A. Green and J. Alegria

Subpulmonic

Membranous

AV canal type/
inlet Muscular

Physical Exam Correlations patients can develop Eisenmenger syn-

• Systolic Murmur typically present. drome which is classified as irreversible
–– Very small Muscular VSD - Murmur can pulmonary hypertension with cyanosis.
be a short “squeaky” type murmur as the These patients may have a left to right
defect may close part way through systole. shunting at rest with reversal to right to left
–– Muscular VSD: This will be a pansystolic shunting with ambulation. Consider ambu-
murmur, usually harsh in quality, along the latory saturation testing to evaluate for
second to third left intercostal spaces. desaturation with activity [7].
Patient may have an associated thrill, so the
provider should always palpate precordium Pathology/Description
to determine if this is present [6].
The louder the murmur, typically the VSD is a defect located in the ventricular septum
more restrictive the defect (greater drop which initially creates a volume load on the left
in pressure across the defect = louder heart. Long-standing VSDs can ultimately lead to
murmur). elevation in pulmonary artery pressures and pul-
–– Large VSD: Systolic murmur may not be monary hypertension.
as loud if there is not a dramatic pressure
gradient change across the ventricular sep- Imaging
tum. If the VSD is large, patient will have a
soft murmur, may have fixed splitting of S2 VSD can be evaluated by echocardiogram.
or “snappy” P2 component of S2 given the Modalities such as Cardiac MRI may also be
elevated pulmonary arterial pressures [7]. helpful as this will give you detailed anatomic
If there is significant volume overload information as well as information regarding the
from left to right shunting, patient may degree of shunting. Cardiac CT can be used to
also have a diastolic rumble. obtain information regarding anatomy (size and
–– Nonrestrictive VSD: Typically, this is a location) of the defect [5, 7].
large VSD with equalization of pressures If there is a concern for cyanosis, ambulatory
in both ventricles and associated pulmo- saturation monitoring with a hall walk test is
nary hypertension. If this is longstanding, helpful.
29 ACHD 311

Right heart catheterization is helpful to gather • The majority of small restrictive VSDs located
information regarding the degree of pulmonary in the membranous or muscular septum can be
hypertension, PH reversibility testing, as well as observed and do not need intervention [4]. For
degree of shunting (Qp:Qs) [5, 7]. the small number of patients who develop pro-
gressive aortic insufficiency related to their
Management perimembranous VSD, surgical repair may be
indicated [4, 8].
• Most isolated muscular and Perimembranous • Patients with unrepaired VSDs, that are mod-
VSDs close spontaneously. erately restrictive, may have mild-moderate
• If repair is indicated: pulmonary hypertension. Some patients with
• Membranous, Inlet, Subpulmonary, all require large nonrestrictive defects may develop
surgical repair if hemodynamically Eisenmenger syndrome, and have shunt rever-
significant. sal and systemic desaturation [4, 8].
–– Clinically symptomatic • Patients with previous closure of their VSD
–– Qp:Qs ≥ 1.5:1 may have patch leak or residual VSD [4].
–– Chamber enlargement (left heart)
• Muscular VSD can be repaired in the cath lab
or surgically depending on anatomy/size. Bicuspid Aortic Valve (BAV)
• Closure of a large VSD with associated pul-
monary hypertension may not be recom- Bicuspid AV is the most common congenital
mended if pulmonary vascular bed not heart defect with incidence of 4.6 per 1000 live
responsive or if there is a concern that the births. It is 1.5 times more prevalent in males
pulmonary vascular resistance is too high, than females. It has a high degree of disease pro-
although in some cases a “fenestrated” gression leading to aortic stenosis and/or regurgi-
patch or device can decompress the right tation, as well as association with aortic root
heart [4]. dilation, aortic dissection, and thoracic aortic
aneurysm [4, 10].
Pearls
• In patients with unrepaired VSD, there is an Anatomy and Physiology
increased risk of infective endocarditis. This
will typically affect the tricuspid and pulmo- Bicuspid AV is caused by fusion of the aortic
nary valves [4, 8]. valve leaflet commissure creating a two-leaflet
• Survival in Unoperated VSD: valve instead of a three-leaflet valve. This results
–– Small restrictive defects have a high in a “fish mouth”- appearing opening of the aortic
25-year survival of 87% [4, 8]. In patients valve rather than a round unobstructed opening.
with a small VSD, low Qp:Qs <1.5:1 and The most common anatomic forms of bicuspid
low pulmonary vascular resistance had sur- aortic valve include fusion of the right and left
vival rate of 96% [9]. coronary commissures or right and non-coronary
–– Moderate and large defects have a lower commissures. Fusion of the right and non-
25-year survival of 86 and 61%, respec- coronary commissure is associated with a more
tively [4]. rapid deterioration of the valve leading to steno-
–– Patients with large shunt and Eisenmenger sis or insufficiency, whereas fusion of the right
syndrome had even lower 25-year survival and left coronary commissure has a greater inci-
at 42% [4]. dence of association with coarctation of the aorta
• Survival in repaired VSD: Significantly [10, 11].
improved but remains abnormal [4].
312 A. Green and J. Alegria

Bicuspid valve with

fusion of leaflets

Closed Valve Open Valve

Normal

Physical Exam Correlations Imaging

Patients may have an audible click (systolic ejec- Evaluation of bicuspid aortic valve is with trans-
tion noise) [12]. Murmur may only be present if thoracic echocardiogram. The valve can be eval-
there are other associated diagnoses such as uated in more detail with TEE, Cardiac MRI
coarctation of the aorta, or valvular disease with and Cardiac CT to look at valve morphology
obstruction or insufficiency [12]. Providers need and evaluate degree of aortic stenosis and
to assess for coarctation of the aorta. Coarctation regurgitation.
of the aorta and bicuspid valve are commonly If AS or AI is present, stress testing can also
associated [10, 11]. be used to evaluate and risk stratify the patient’s
need for intervention, either transcatheter or sur-
Pathology/Description gical [4, 12].

BAV has aortic valve morphology but with two Management

functional leaflets of unequal size, instead of
three, due to incomplete commissural separation Surgical and/or transcatheter management of
during fetal development [3, 5]. There is a famil- bicuspid valves can be considered in patients
ial heritability in an autosomal dominant pattern. with severe obstruction or regurgitation. In the
In one study, the incidence of asymptomatic younger population, balloon aortic valvuloplasty
bicuspid aortic valve in first-degree relatives is in the cath lab is more common; however, in
9% with a 32% incidence of those first-degree adults, transcatheter valve therapies or surgical
relatives having an abnormal aorta [4, 12]. valve repair/replacement is more common [12,
Given the abnormal flow pattern of blood 13].
across the aortic valve leaflets in bicuspid aortic
valve, there may be calcification or obstruction of Clinical Pearls
the leaflets, which can happen at a higher rate • Bicuspid aortic valves can often be asymp-
than for those with a tricuspid aortic valve [10]. tomatic but can also present with aortic steno-
There may also be incomplete coaptation of the sis or insufficiency earlier in life. One study
valve leaflets resulting in aortic insufficiency. found that patients with bicuspid aortic valve
29 ACHD 313

presented at age 40 ± 20 years vs. 67 ± 16 years the right ventricle and pulmonary arteries with
for patients with tricuspid valve [12]. obstruction at the level of the valve, results in
• If a Bicuspid valve found, assessment for hypertension of the right ventricle [14].
coarctation of the aorta (supine 4 extremity
BPs and imaging) and other aortopathies Anatomy and Physiology
(ascending aorta/aortic root, thoracic aorta)
should be undertaken [10–12]. Valvar PS occurs in approximately 7% of chil-
• First-degree relatives of patients with bicuspid dren born with CHD. PS can be isolated or can
valve should have routine screening echocar- occur in combination with other defects, such as
diograms [4]. in Tetralogy of Fallot [14]. Pulmonary stenosis is
associated with Noonan syndrome, Alagille syn-
drome, Williams syndrome, and congenital
Valvar Pulmonary Stenosis (PS) rubella [14]. Isolated valvar PS can be associated
with a dilated main PA and dysplastic valve leaf-
PS is typically associated with a conical or dome- lets [4]. Valvar PS results in RV hypertrophy and
shaped pulmonary valve or can be a result of hypertension, which varies based on the degree
thickening of the pulmonary valve leaflets. The of obstruction [14].
narrowing of the opening of the valve between

Valvar pulmonary stenosis with dysplastic /thickened

leaflets of the pulmonary valve, and right ventricular
hypertrophy, as well as dilation of the main and
branch pulmonary arteries which can be secondary
to the high velocity jet across the pulmonary valve
leaflets.

Physical Exam Correlations in intensity and can have associated thrill [14]. If
the patient has pulmonary insufficiency, you may
Physical exam findings may include a crescendo- also hear a diastolic murmur or a “to-fro”
decrescendo systolic murmur which radiates out murmur.
into the axillae or to the back. The murmur varies
314 A. Green and J. Alegria

Pathology/Description • Patients with PS (mild, moderate, and

severe)—usually have a good long-term out-
Pulmonary valve stenosis is primarily a congeni- come. Some will require intervention in
tal diagnosis and includes pulmonary valve adulthood either for progressive PS or sig-
abnormalities such as uni-commissural, dome- nificant pulmonary insufficiency due to prior
shaped, dysplastic, and bicuspid [4, 14] valves. intervention (Transcatheter or surgical) [4,
Pulmonary stenosis can be seen in Noonan, 14].
Alagille, and Williams syndromes, and with con-
genital rubella [4, 14].
Tetralogy of Fallot (TOF)
Imaging
The most common cyanotic congenital heart
Echocardiograms are done for routine surveil- defect is Tetralogy of Fallot (TOF), and it
lance of the degree of obstruction and/or insuffi- accounts for 7% to 10% of congenital heart
ciency. Cardiac MRI can be helpful to evaluate defects [15].
RV size and volumes as well as the dimensions of
the pulmonary valve and main pulmonary artery Anatomy and Physiology
if interventions are being considered [4]. EKG is
also recommended [4]. Tetralogy of Fallot (TOF) is comprised of four
defects including a large VSD, overriding
Management aorta, pulmonary stenosis, and RV hypertro-
phy. Unrepaired TOF can either be “pink”
Intervention for valvar pulmonary stenosis can (acyanotic) or “blue” (cyanotic) depending on
often be done by transcatheter techniques, bal- the degree of pulmonary stenosis and amount
loon pulmonary valvuloplasty. If failure of bal- of pulmonary blood flow/right to left shunting
loon pulmonary valvuloplasty occurs or there is across the VSD. Repair of TOF is typically
progressive insufficiency, surgical intervention done when the patient is an infant, and con-
may be considered [4]. sists of VSD closure, transannular patch, and
resection of RV muscle bundles [4]. This
Clinical Pearls repair typically leaves the patient with little to
• Adults with the history of pulmonary stenosis no PS and free pulmonary insufficiency. In the
require ongoing cardiac follow-up and moni- present day, TOF is repaired in infancy.
toring for evidence of progressive valve steno- However, there may be adult patients that have
sis or regurgitation, RV hypertrophy, heart not had complete repair given when/where
failure, and arrhythmias [4, 14]. they were born.
29 ACHD 315

Unrepaired Tetralogy of Fallot

Overriding aorta
Pulmonary stenosis/
small main PA Ventricular septal
defect (VSD)

Right ventricular
hypertrophy

Physical Exam Correlations Imaging

In repaired TOF, the physical exam may consist EKG, Echo, Cardiac MRI, and stress testing are
of a to-fro systolic murmur. This is secondary to recommended at certain intervals. Cardiac MRI
the movement of blood back and forth across the is helpful for quantification of RV size and func-
RVOT (systolic murmur secondary to pulmonary tion, especially when considering the timing of
stenosis) and diastolic murmur from the pulmo- pulmonary valve replacement [4].
nary insufficiency.
Management
Pathology/Description
Repair of tetralogy of Fallot usually consists of
In tetralogy of Fallot, the aorta overrides the resection of RV muscle bundles, and use of a patch
ventricular septum, which “crowds out” the to enlarge the main pulmonary artery and branch
pulmonary artery and subpulmonic area, pulmonary arteries. The VSD is closed with a patch
resulting in a small MPA, potentially small and any residual ASD is closed [4]. Adults with
branch PA’s, valvar, and subvalvar pulmonary repaired tetralogy of Fallot may often require pul-
stenosis [15]. Adults with tetralogy of Fallot monary valve replacement. This can either be done
who have undergone complete repair may via surgical techniques or in the cath lab via trans-
require pulmonary valve replacement in adult- catheter techniques. There are now FDA approved
hood given ongoing PS/PI and RV dilation and transcatheter valve therapies for replacement of pul-
dysfunction [4]. monary valve in the native RVOT [4].
316 A. Green and J. Alegria

Surgical repair of tetralogy of Fallot (TOF)

Transannular patch
with resection of
sub-pulmonary VSD patch
stenosis closure

Clinical Pearls Coarctation of the Aorta

• Cardiac MRI is the gold standard for evalua-
tion of RV size, function, and valve regurgita- Anatomy and Physiology
tion in patients with repaired TOF [4].
• Prior to any intervention, the proximal coro- Coarctation is a narrowing or stricture in the
naries and their origins need to be outlined aorta. This most commonly occurs near the duc-
[4]. tal remnant and takeoff of the left subclavian
• Leading causes of mortality in adults with artery (proximal descending aorta) [4, 16]. It is
repaired TOF are arrhythmia, heart failure, frequently associated with a bicuspid aortic valve
and complications from reoperations [15]. and may be seen in Turner’s Syndrome. First-
• In adults with TOF, inducible VT is associated degree relatives of patients diagnosed with
with increased risk of clinical VT or obstructive left heart disease are at a significantly
SCD. Programmed ventricular stimulation is higher risk (as high as 10%) for coarctation and
useful in risk-stratifying patients who are at other left heart lesions [16].
moderate risk of SCD, rather than as a routine
surveillance tool in low-risk patients [4]. Physical Exam Correlations
• Bundle Branch Block >180 ms is associated
with higher risk of sudden death. Hypertension is common in both repaired and
• Syncope in a repaired TOF must be consid- unrepaired patients with coarctation of the aorta
ered VT until proven otherwise. [4, 16]. If a patient has recurrent obstruction, four
• Pulmonary hypertension can occur in repaired extremity blood pressures, done with the patient
TOF. laying supine, may reveal decreased BP in the
29 ACHD 317

lower extremities. A systolic murmur may be undergone surgical patch repair are at a higher
heard at the left mid-clavicular line and/or poste- risk of developing aneurysms [4, 18].
riorly along the spine. Brachial femoral pulse
delay may be present if there is obstruction [4]. Clinical Pearls
• Recurrent obstruction is defined as an upper
Pathology/Description extremity to lower extremity resting pressure
gradient of >20 mmHg (i.e., right arm Systolic
There are several theories of why coarctation BP of 150 mmHg and left leg systolic BP of
occurs: 110 mmHg—in this example the peak to peak
1. Ductal tissue extends into the aortic arch and gradient is 40 mmHg), and/or mean Doppler
as the ductus closes and becomes a ligament systolic gradient >20 mmHg [4].
the aorta is also constricted. • Recurrent obstruction may be amenable to
2. Flow: poor flow through the aortic arch during balloon aortoplasty.
fetal development secondary to other left • If LV systolic function is decreased or aortic
heart lesions resulting in poor growth of the regurgitation is present, recurrent obstruction
aorta this is often associated with hypoplasia is defined as an upper extremity to lower
of the aortic arch, not just coarctation. extremity gradient of >10 mmHg or mean
Doppler gradient >10 mmHg with collateral
Post-repair of coarctation, aneurysm forma-
flow. (CMR or CT is used to help assess for
tion in the proximal descending aorta at the site
anatomic evidence of recurrent Coarctation of
of repair can occur. Dissection can also occur,
the aorta) [4].
primarily in the setting of uncontrolled hyperten-
• Cerebral aneurysm can be present in up to
sion [4]. Ascending aortic aneurysm can occur in
10% of patients with coarctation of the aorta
those patients with bicuspid aortic valve.
[4, 19].
Imaging

Transthoracic echocardiogram, Cardiac CT and L-TGA

MRI can all be helpful for evaluating the struc-
ture of the aortic arch and gradient across the Anatomy and Physiology
coarctation. Upper and lower extremity BPs are
also helpful in evaluating gradient (using the Congenitally corrected transposition of the great
right arm for upper extremity measurement). arteries (CCTGA) or L-TGA describes the condi-
EKG and stress testing are used in evaluation tion in which the right sided (subpulmonary) ven-
with the EKG evaluating for LVH and stress test- tricle has the shape of the anatomic left ventricle
ing is used to evaluate BP measurements with (morphologic LV), and the left sided (sub aortic)
exercise as well as look for any evidence of isch- ventricle has the shape of the anatomic right ven-
emia [4]. tricle (morphologic RV). This physiology results
in the patient having a systemic right ventricle.
Management This defect can occur in isolation or can be asso-
ciated with other defects such as atrial or ven-
Surgical repair or stent angioplasty in the cath lab tricular septal defects or pulmonary stenosis.
is recommended for adults with hypertension and There is also a high incidence of Ebstein-like
significant native or recurrent coarctation of the malformation of the left sided AV-valve, which is
aorta [4, 17]. Hypertension management is criti- the anatomic tricuspid valve. This incidence is
cal. Complications of coarctation repair include felt to be as high as 90%. This malformation can
re-coarctation, pseudoaneurysm, dissection. 11% lead to progressive tricuspid (systemic) valve
of patients may require reintervention for reste- regurgitation [4, 20]. There is a 1% per year or
nosis seen by CMR or CTA and supported by 10% per decade risk of complete heart block [4,
physical exam findings [4]. Patients who have 21] with this condition.
318 A. Green and J. Alegria

Morphologic RV Morphologic RV

Morphologic LV
Morphologic LV

L-TGA with VSD L-TGA with no other defects

Physical Exam Correlations tion, AV-valve regurgitation, as well as any other

intracardiac lesions or anatomic repairs/pallia-
Physical exam findings depend on other lesions tions [4]. Given the likelihood for conduction
present or prior surgery/palliation. If no other lesions, abnormalities, patients will also need routine
physical exam may be normal. Abnormalities in EKG monitoring as well as Holter monitoring
physical exam may show the presence of a systolic [4].
murmur in patients with PS and/or VSD.
Management
Pathology/Description
Surgical management of patients with L-TGA
Isolated L-TGA without other defects may present varies based on the additional defects involved.
in the third or fourth decade with a new diagnosis One operation that can be done for patients
of heart failure. More than 1/3 of patients with with L-TGA with or without VSD is called a
L-TGA and no other significant defects presents “double switch.” This operation consists of an
by the fifth decade with significant heart failure atrial switch (Senning or Mustard procedure)
(systemic RV) or may present in complete heart to re-route the venous return to the appropriate
block with a 10% per decade risk (i.e., 40% risk by ventricle, and then arterial switch to switch the
age 40 years) [22, 23]. Patients with L-TGA with great vessels so that they are then aligned with
other significant associated defects and history of the re-routed systemic venous return to the
prior heart surgery have a significant risk of sys- appropriately shaped ventricle [4, 23].
temic ventricular failure, with 2/3 of these patients Progressive systemic atrioventricular valve
presenting by age 45 with heart failure [23]. regurgitation (tricuspid valve) is common and
tricuspid valve replacement should be consid-
Imaging ered early when there is severe tricuspid valve
regurgitation to prevent further decline in sys-
Cardiac MRI or Cardiac CT, and echocardiogra- temic ventricular dysfunction (right
phy are all used to evaluate the ventricular func- ventricle).
29 ACHD 319

Double Switch Surgical Procedure:

Atrial switch with Mustard/Senning to re-route systemic
venous return to the left sided tricuspid valve and
morphologic RV; and pulmonary venous return to the
mitral valve and morphologic right sided LV
Jatene/Arterial Switch with switch of the great vessels
so that they are then aligned with the appropriate
venous return and morphologic ventricle.
If VSD present, VSD closure can also be performed
during this operation

Clinical Pearls D-TGA

• Disease progression and clinical course is pri-
marily related to the presence and type of Anatomy and Physiology
other defects and their severity. The presence
of other defects also determines the type and In d-TGA (dextro-transposition of the great arter-
complexity of the surgical repair/palliations ies) the pulmonary artery and aorta are
needed. “switched,” with the pulmonary artery arising
• Tricuspid valve replacement in L-TGA should from the left ventricle and the aorta arising from
be considered at the earliest sign of RV the right ventricle. This defect is often accompa-
dysfunction. nied by an atrial septal defect and/or PFO. It may
• These patients have a high risk of heart block also have associated ventricular septal defect and
as well as atrial arrhythmias. coronary artery abnormalities [23, 24].
• Failure of the systemic ventricle is higher with
concomitant tricuspid regurgitation [23].
• May present later in life after asymptomatic
period after birth.
320 A. Green and J. Alegria

d-TGA with VSD and PFO

Aorta arises off the

right ventricle
Pulmonary artery
arises off the left
ventricle

Physical Exam Correlations Pathology/Description

A patient with repaired transposition, either with In unrepaired d-TGA, there are two parallel
an arterial switch or an atrial switch, may have a circuits in which the deoxygenated systemic
normal physical exam. However, exam findings venous return is recirculated in the systemic
may include a single S2 (A2) (given anterior circuit and oxygenated pulmonary venous
location of the aorta), and a systolic murmur if return is recirculated in the pulmonary circuit.
there is associated main or branch pulmonary These parallel circuits are not compatible with
artery stenosis [24]. Other physical exam find- life unless there is mixing, which can occur
ings are based on residual defects. In patients across an atrial defect, a VSD or PDA [23, 24].
with atrial switch, assess ambulatory saturations The patent ductus arteriosus (PDA) needs to
to assess for baffle leaks and possible right to left remain open in the neonatal period, which can
shunting and desaturation [23]. be accomplished by an infusion of prostaglan-
29 ACHD 321

din. Additionally, creation of an atrial defect of additional testing such as Holter monitors,
with a balloon atrial septostomy procedure pulse oximetry vary between the two repair
may need to be done if there is inadequate types [4].
mixing prior to surgical repair [24].
Management
Imaging
There are two common surgical repairs seen in
Echo, EKG, Cardiac MRI, Cardiac CT, and adults who underwent repair as a child—the
exercise testing are all used at routine inter- Arterial switch (Jatene switch with LeCompte
vals to evaluate patients with both arterial and Maneuver) and Atrial switch (also known as a
atrial switch for d-TGA. The timing and type Mustard or Senning operation) [4, 23].

Arterial (Jatene) switch and VSD closure

Present day Surgical Repair – arterial switch
(Jatene switch) done around 3-5 days of age.

Jatene switch was developed and 1st done successfully

in 1975, gained popularity and widespread use for d-TGA
repair in the 1980’s
VSD/ASD/PFO closed (if present)
Aorta and pulmonary artery transected above the sinus.
Coronary buttons taken off and re-implanted on the neo-aorta.
Pulmonary arteries are brought anterior to the aorta,
and draped over the ascending (LeCompte Maneuver)

Long Term Consequences of the Arterial Switch

Stenosis at the arterial anastomotic sites,

most commonly supravalvular PS
Branch pulmonary artery stenosis
Neoaortic root dilation
Neoaortic valve regurgitation (native pulmonary valve)
Coronary ostial stenosis/occlusion

Clinical Pearls plasty, which is often done in the cardiac cath

• Some patients with d-TGA s/p arterial switch lab using stent angioplasty technique [4].
who have early problems with pulmonary ste- • Patients post-arterial switch can develop coro-
nosis undergo RV to PA conduit placement nary artery stenosis or occlusion given that the
(Rastelli), and can need further surgical revi- coronary arteries are moved as buttons in the
sion of this conduit either in an open or trans- arterial switch procedure [4].
catheter procedure [4, 24]. • Patients undergoing arterial switch are at
• Patients post Le-Compte maneuver as a part higher risk for neurodevelopmental problems
of the arterial switch may need branch PA and ADHD [24, 25].
322 A. Green and J. Alegria

Atrial Switch (Mustard/Senning)

Senning: Developed by Dr. Ake Senning in 1957. Uses a

complex reconstruction utilizing flaps from the atrial
septum and atrial tissue to create the baffles

Mustard: Developed in 1963 by Dr. William Mustard.

Resects the atrial septum and uses pericardial patch to
create the baffles

Long Term Consequences of the Atrial Switch

(Mustard/Senning)

Baffle leaks
Obstruction of the venous pathways
Arrhythmias
Need for pacemakers/defibrillators
Systolic dysfunction of the systemic right ventricle.

Clinical Pearls systemic RV and require transplant evalua-

• Patients post-atrial switch can develop leak or tion [4].
obstruction of their systemic venous or pulmo-
nary venous baffles. If systemic SVC venous
baffle obstruction occurs, they may present Ebstein’s Anomaly
with SVC type syndrome—JVD, prominent
veins on upper limbs and chest. Systemic IVC Anatomy and Physiology
baffle obstruction may present with abdominal
distension/ascites, prominent veins on abdo- Ebstein’s anomaly of the tricuspid valve is an
men, lower extremity edema, and no significant uncommon congenital heart defect occurring
upper extremity symptoms. Baffle leak may in about 0.005% of live births [4]. It is a mal-
present with systemic desaturation. Assessment formation of the tricuspid valve and right ven-
for baffle leak can be done with agitated saline tricle with varying severity. This defect is
injection but must be done from upper and classically described as apical displacement of
lower extremities to rule out upper (SVC) and the septal and posterior tricuspid valve leaflets,
lower (IVC) baffle leaks [4, 26]. leading to “atrialization” of the right ventricle
• These patients can have a significant burden of [27]. It is associated with an ASD in more than
atrial arrhythmias given multiple atrial suture 80% of patients [28]. Ebstein malformation of
lines [4, 26]. the tricuspid valve is often found in patients
• Patients with d-TGA post Atrial switch may who also have L-TGA (congenitally corrected
present in heart failure given failure of the TGA).
29 ACHD 323

Ebstein Anomaly

Apical displacement of the tricuspid valve leaflets with

atrialization of the right ventricle

Physical Exam Correlations 1/3 of patients with Ebstein anomaly have more
than one accessory pathway. 5–25% of patients
The exam in these patients varies based on sever- with Ebstein anomaly have Wolff Parkinson
ity of the anatomy. Exam may include systolic White syndrome [28, 29].
AV-valve murmur secondary to the tricuspid
regurgitation. The patient may have cyanosis sec- Imaging
ondary to right to left shunting across the atrial
septum, if ASD/PFO present. EKG, Holter, Cardiac MRI, 2D, and 3D echocar-
diogram including TEE may all be helpful.
Pathology/Description
Management
Ebstein’s anomaly has apical displacement of the
septal and posterior tricuspid valve leaflets. The Management for Ebstein Anomaly depends on
valve may be tethered/have restricted motion or the severity of the lesion. Intervention may
have a sail like appearance with abnormal chordal include ablation of accessory pathways, or surgi-
attachments, which can contribute to inappropri- cal management of these pathways at the time of
ate coaptation leading to significant regurgitation surgery. Surgical repair can include tricuspid
[27]. The functional right ventricle can be very valve repair or replacement, plication of the atri-
small and consist only of the RVOT in cases of alized right ventricle (Cone procedure), reduc-
severe apical displacement [27]. Conduction sys- tion atrioplasty, closure of atrial defect, and
tem abnormalities are common, and as many as arrhythmia management [4]. Poorer outcomes
324 A. Green and J. Alegria

are associated with delay of surgery until presen- 1. Defects include, but are not limited to:
tation of HF symptoms or RV systolic dysfunc- (a) Hypoplastic left heart syndrome (HLHS)
tion [4]. (b) Double inlet left ventricle (DILV)
(c) Tricuspid atresia
Pearls (d) Double outlet right ventricle (DORV)
• Over half of the adult patients’ initial present- (e) Pulmonary atresia with intact ventricular
ing symptom is palpitations or arrhythmia septum (PA/IVS)
[29]. (f) Ebstein anomaly
• Patients can present with cyanosis, fatigue, (g) AV canal (unbalanced)
dyspnea, arrhythmia, and/or symptoms of 2. Fontan palliation is typically a three-stage
right heart failure [27]. operation over the first few years of life.
• There is an association with accessory path- (a) Stage I is typically creation of a shunt—
way tachycardia (WPW). either Blalock-Taussig (BT) or Sano to
the pulmonary arteries.
(b) Stage II is a bidirectional Glenn operation
Single Ventricle/Fontan Physiology in which the SVC is disarticulated from
the RA and sewn directly into the pulmo-
Anatomy and Physiology nary arteries. The shunt, which was
placed in stage I is taken down.
The term single ventricle physiology or Fontan (c) Stage III—or Fontan Completion—is the
physiology refers to complex intracardiac anat- baffling of the IVC return to the pulmo-
omy that is not amenable to 2-ventricule circula- nary arteries via a conduit. There are
tion, thus leaving the patient with a “single many variations of this with the most
ventricle” for systemic circulation. This may be common including: Classic Fontan,
either a systemic right ventricle or systemic left Lateral Tunnel, and extra-cardiac.
ventricle.

Hypoplastic Right ventricle with Tricuspid atresia,

severe pulmonary stenosis, and VSD – s/p
Bidirectional Glenn and Extra-cardiac Fontan
completion
29 ACHD 325

Hypoplastic Left ventricle with Aortic and mitral

atresia – s/p Norwood, Bidirectional Glenn and
Extra-cardiac Fontan completion

Physical Exam Correlations Pathology/Description

In a well-functioning Fontan, the patient may In the unoperated patient, stage I or II single ven-
have normal physical exam findings with normal tricle physiology, there is mixed blood circula-
oxygen saturation. Alternatively, there may be a tion (mixed systemic venous and systemic arterial
murmur if there is significant valve disease, blood) through the body. This mixing occurs
recurrent coarctation of the aorta, or a significant depending on structural abnormality but is typi-
burden of aorto-pulmonary collaterals. Oxygen cally across an atrial septal defect (ASD), ven-
saturation may not be normal and may range tricular septal defect (VSD) or patent ductus
between 88% and 92%, in the absence of signifi- arteriosus (PDA). This mixing of the blood is
cant venous abnormalities, depending on the necessary to maintain cardiac output [30]. Over
physiology. Prominent abdominal vessels, dis- the three palliative surgeries, the circulation is
tended abdomen, or lower extremity edema may separated such that the venous blood is routed to
be present if the Fontan pressures are elevated or the lungs by passive/gravitational flow and arte-
if there is obstruction in the Fontan circuit. If a rial blood is pumped to the body without mixing,
fenestration is present, the oxygen saturations allowing for the patient to have a relatively nor-
may drop with ambulation. mal oxygen saturation. Adults with Fontan physi-
326 A. Green and J. Alegria

ology have chronically low cardiac output given PLE are decreased serum albumin <3.5 g/
the passive cavo-pulmonary flow of the Fontan dL and Total protein <6.0–6.3 g/dL, as well
circuit. The Fontan circuit is not able to deliver as augmented enteric protein loss with
normal amount of volume across the pulmonary Fecal alpha-1-antitrypsin clearance
vascular bed, which results in reduced ventricular >56 ml/24H (with diarrhea) and
filling and low stroke volume. This physiologic >27 ml/24 h (without diarrhea) [31].
state is not able to augment stroke volume nor- Management: decrease resistance in the
mally with exercise or other states of increased Fontan circuit by alleviating any
demand [31, 32]. Atrial tachycardias occur in obstruction, reducing PVR, unfraction-
60% of adults with Fontan palliation. They are ated heparin or budesonide to reduce
poorly tolerated and can be difficult to manage, enteric inflammation. Other medica-
thus they should be addressed promptly [4]. tions that can help improve endothelial
Sinus node dysfunction occurs in up to 45% of cell function and reduce inflammation
adults with Fontan palliation [4]. such as Spironolactone and Octreotide
(limited evidence) [31, 33].
Imaging –– Hepatic dysfunction: Elevated central
venous pressure and systemic hypoperfu-
EKG, transthoracic, Cardiac MRI, Cardiac CT, sion lead to congestive hepatopathy, liver
and stress testing are all used to evaluate the fibrosis to cirrhosis and even hepatocellular
patient with a Fontan. Holter monitoring for carcinoma [31].
arrhythmias is also used for evaluation. –– Screening for hepatocellular carcinoma
should be done with Alpha fetoprotein
Clinical Pearls (AFP) and liver imaging (Ultrasound, liver
• Cardiac output for patients with Fontan physi- MRI with Evoist or CT).
ology is not normal. They are limited by the –– Thromboembolic complications: Risk of
passive flow to the lungs and the abnormal thromboembolism as high as 20% in
blood throughput in the pulmonary circuit. patients with Fontan physiology. This is
Over time the chronic volume depletion felt to be caused by lack of pulsatile flow in
causes progressive decline in ventricular func- the pulmonary circuit and ensuing venous
tion, resulting in a cycle of increased end- stasis leading to a hypercoagulable state
diastolic pressure, systemic venous which is made worse by deficiency of pro-
congestion, and low cardiac output [31, 32]. tein C, S, antithrombin III and increased
• Failing Fontan physiology: platelet reactivity [31, 34].
–– Cyanosis: Patients with Fontan physiology
are often mildly hypoxemic. This is caused
by the presence of a surgically created fen- Infective Endocarditis Prophylaxis
estration or leaks in the fontan baffle itself,
coronary sinus venous return to the atrium, It should be discussed in detail with the patient
pulmonary AV-malformations, and veno- the importance of infective endocarditis preven-
venous collaterals which can drain into the tion. Infective endocarditis can be a potentially
pulmonary veins or directly into the left life-threatening condition with 10–20% mortal-
atrium [31]. ity and prevention along antibiotic prophylaxis
–– Protein losing enteropathy (PLE) occurs in when indicated and early diagnosis is of para-
5–15% of patients with Fontan physiology. mount relevance. Recommendations of proper
This refers to the loss of serum proteins dental hygiene including teeth brushing three
into the lumen of the gut leading to chronic times a day, flossing once a day, visiting the
diarrhea, abdominal discomfort, and dentist twice a year and following infective
peripheral edema. Lab values indicative of endocarditis prophylaxis guidelines with antibi-
29 ACHD 327

otics when indicated. Also, for other procedures, 7. Dakkak W, Oliver TI. Ventricular septal defect.
infective endocarditis prophylaxis may need to [Updated 2022 May 10]. In: StatPearls [Internet].
Treasure Island, FL: StatPearls Publishing; 2022.
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endocarditis that may include fever, myalgias, 8. Corone P, Doyon F, Gaudeau S, et al. Natural history
headache, arthralgias, or other symptoms. The of ventricular septal defect. A study involving 790
cases. Circulation. 1977;55:908–15.
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COVID. Also, a low threshold for blood cul- of ventricular septal defect in adults. Scand J Thorac
tures in the absence of a clear diagnosis with Cardiovasc Surg. 1985;19:29–31.
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Pibarot P, Michelena HI, Limongelli G, Boulanger
collaboration with primary care providers to MC, Evangelista A, Bédard E, Citro R, Body SC,
facilitate diagnostic and care pathways as Nemer M, Schoen FJ. The pathology and patho-
needed. AHA infective endocarditis prophylaxis biology of bicuspid aortic valve: state of the art
card must be given. and novel research perspectives. J Pathol Clin Res.
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Part IX
Ambulatory/Preventative Cardiology
Prevention of Cardiometabolic
Disease
30
Allison W. Dimsdale and Christopher Kelly

Introduction i.e., they tend to judge their own risk as lower

than predicted [2].
Atherosclerotic cardiovascular disease (ASCVD) Although it is impossible to precisely quantify
is a progressive, systemic disorder that affects risk at the individual level, given the large num-
vascular systems throughout the body and can ber of pro-atherogenic genetic and other factors
lead to devastating complications such as myo- that remain poorly understood, it is possible to
cardial infarction, stroke, and limb amputation. estimate risk by comparing an individual to a
In the United States, ASCVD is the leading cause matched population from which longitudinal data
of death and generates >$200 billion per year in have already been collected. Multiple screening
annual healthcare costs and lost productivity. A tools exist to fuel and inform this critical conver-
large share of the disease burden occurs because sation, so the clinician should be facile with the
of failure to implement appropriate prevention research and evidence as it changes.
strategies and control known risk factors in the It is important to recall that even though clini-
general adult population [1]. This chapter will cians think frequently about risk and view most
discuss the assessment and management of risk-reducing intervention favorably, patients
ASCVD risk, with a particular focus on coronary have a wide range of attitudes toward risk and
artery disease (CAD). often have negative views of medications, espe-
cially when they do not treat a symptom or offer
some other immediate benefit. Therefore, any
Assessment of Risk discussion of risk should include an overview of
how the risk has been determined, what the risk
All adults should be regularly assessed for their actually means, and the lifestyle changes or ther-
risk of developing ASCVD and, among those at apies available to reduce that risk (Fig. 30.1).
increased risk, questioned regarding symptoms Afterward, the clinician should learn about the
that would indicate such disease is already estab- patient’s overall impression of that risk and assess
lished. Most patients have an optimistic bias— their willingness to make changes, as well as the
real and perceived costs of any medical interven-
A. W. Dimsdale (*) tions (e.g., statin therapy).
Duke University Health System, Durham, NC, USA When discussing the concept of risk, one
e-mail: [email protected] effective strategy to present this information is to
C. Kelly state, “Eight out of 100 people like you will have
UNC Rex Hospital, UNC Health, Raleigh, NC, USA a heart attack or stroke in the next ten years.” Or,
e-mail: [email protected]

© The Author(s), under exclusive license to Springer Nature Switzerland AG 2023 331
R. Musialowski, K. Allshouse (eds.), Cardiovascular Manual for the Advanced Practice Provider,
https://doi.org/10.1007/978-3-031-35819-7_30
332 A. W. Dimsdale and C. Kelly

Provide easy-to-
Explain benefit vs
understand Explain any present
Create trusting risk for lifestyle
explanation of the risk-enhancing
relationship changes and
patient’s estimated factors
medications
10-year ASCVD risk

Baseline If patient remains

laboratories, Assurance of uncertain about
Address concerns
assessment of clinician availability statin therapy, offer
about cost
predisposing factors for patient concerns coronary calcium
for SE scoring test

Fig. 30.1 Clinician-patient risk discussion

conversely, “92 out of 100 people like you will tool can serve as a useful starting point for dis-
not have a heart attack or stroke in the next ten cussions about risk and can help forecast the
years.” When the 10-year estimates are not com- potential impact of interventions such as statin
pelling enough to motivate change, the lifetime therapy or smoking cessation. In addition, risk
estimates of risk can be more motivational. Of can be reassessed at follow-up visits. This infor-
note, creative display of risk information such as mation can increase patient engagement in
pictograms does not necessarily improve patient guideline-directed changes in lifestyle and medi-
understanding and, in one study, was actually cation strategies by allowing them to witness the
shown to decrease the perception of risk [2]. impact of their choices on their risk estimate.
It is important to clarify that a seemingly low Several alternatives to the PCE are also avail-
risk of ASCVD—such as 8% over 10 years—is able, including the Framingham [4] and Reynolds
actually characterized as intermediate. Likewise, [5] scores. In general, however, most patients in
it can be useful to discuss relative rather than contemporary practice are evaluated using the
absolute risk reduction while discussing the PCE and then further assessed to determine if
implications of proposed therapies. A reduction other risk-enhancing factors are present.
in 10-year risk from 20% to 16% may not sound
impressive to a patient, whereas a 20% reduction
in their overall risk could be more compelling. Risk-Enhancing Factors
The risk score most often used in clinical
practice is the pooled cohort equation (PCE) [3]. When a patient’s 10-year risk is borderline (5%
This calculator is used to estimate the 10-year to <7.5%) or intermediate (>7.5% to <20%), the
risk of myocardial infarction and stroke, and it presence or absence of risk-enhancing factors
can be applied to adults age 40–75 years. can help further refine the estimation [1]. Such
Variables in this model include age, gender, race, factors include family history of early-onset
systolic and diastolic blood pressure, total cho- ASCVD, familial hypercholesterolemia, meta-
lesterol, HDL and LDL cholesterol, diabetes sta- bolic syndrome, chronic kidney disease, inflam-
tus, smoking status, and the presence or absence matory conditions (such as rheumatoid arthritis),
of hypertension treatment, lipid-lowering treat- premature menopause, history of pregnancy-
ment, and aspirin therapy. Notably, the equation associated conditions such as preeclampsia,
does not consider a family history of ASCVD, high-risk race/ethnicity such as South Asian
novel risk markers such as lipoprotein(a), or the ancestry, abnormal ankle-brachial index (<0.9),
severity of diabetes. In addition, it performs best and lipid biomarkers associated with increased
among non-Hispanic whites and blacks, and less ASCVD risk including lipoprotein(a) and apoli-
accurately for other race groups. Nonetheless, the poprotein B (Fig. 30.2a, b).
30 Prevention of Cardiometabolic Disease 333

a Risk Enhancing factors for Clinician-Patient Risk Discussion

Risk-Enhancing Factors

Family history of premeture ASCVD (males, age <55; females age <65)

Primary hypercholesterolemia (LDL-C, 160-189 mg/dl (4.1-4.8 mmol/L), non HDL-C 190-219 mg/dl (4.9-5.6
mmol/L))

Metabolic syndrome (incrased waist circumference,elevated triglycerides (>150 mg/dL, nonfasting), elevated
blood pressure, elevated glucose, and low HDL-C(<40 mg/dL in men; <50 md/dL in women) are factors; a tally
of 3 makes the diagnosis

Chronic kidney disease (eGFR 15-59 mL/min/1.73 m2 with or without albumineuria; not treated with dialysis or
kidney transplantation

History of premature menopause (before age 40) and history of pregnancy-associated conditions that increase
later ASCVD risk, such as preeclampsia

High-risk race/ethnicity (eg, South Asian ancestry)

Lipids/biomakers: associated with increased ASCVD risk

Persistently elevated primary hypertriglyceridemia (>175 mg/dL, nonfasting)

If measured:

Elevated high-sensitivity C-reactive protein (>2.0 mg/L)

Elevated Lp(a): A relative indication for its measurement is family history of premature ASCVD. An Lp(a)
>50 mg/dL or >125 nmol/L cinstitutes a risk-enhancing factor, especially at higher levels of Lp(a)

Elevated apoB (>130 mg;dL): A relative indication for its measurement would be triglyceride>200 mg/dL
A level >130 mg/dL corresponds to an LDL-C<160 mg/dL and constitutes a risk-enhancing factor

ABI (<0.9)

Fig. 30.2 (a) Risk-enhancing factors for clinician-patient risk discussion. (b) Risk enhancing factors
334 A. W. Dimsdale and C. Kelly

Fig. 30.2 (continued) b Family history of

1 premature ASCVD

Primary
2
hypercholesterolemia

3 Metabolic syndrome

4 Chronic kidney disease

h/o preeclampsia or
Risk 5 premature menopause
Enhancing
Factors
6 High risk race or ethnicity

7 Lipids/biomarkers

8 Elevated triglycerides

9 Elevated Lp(a)

10 Elevated ApoB

Risk-Enhancing Factors non-contrast CT scan of the chest gated to the

ECG. Because calcium hyperattenuates and is
When a patient’s 10-year risk is borderline (5% easily seen on a CT scan, the degree of coronary
to <7.5%) or intermediate (>7.5% to <20%), the calcification correlates fairly well with the total
presence or absence of risk-enhancing factors amount of atherosclerosis. The calcium score is
can help further refine the estimation [1]. Such quantified using the Agatston method and
factors include family history of early-onset reported both as a total number and as subtotals
ASCVD, familial hypercholesterolemia, meta- for each coronary artery.
bolic syndrome, chronic kidney disease, inflam- CAC is particularly helpful when deciding
matory conditions (such as rheumatoid arthritis), whether to initiate preventive medical therapies
premature menopause, history of pregnancy- such as a statin or aspirin. Moreover, this test
associated conditions such as preeclampsia, converts the abstract concept of risk into the more
high-risk race/ethnicity such as South Asian concrete concept of coronary plaque burden and
ancestry, abnormal ankle-brachial index (<0.9), the risk of a clinical event. If the CAC is zero, the
and lipid biomarkers associated with increased patient is unlikely to derive any benefit from
ASCVD risk, including lipoprotein(a) and apoli- statin therapy, and the risk can be reassessed after
poprotein B (Figs. 30.2a, b). 10 years. In contrast, if the score is greater than
400, stress testing may be warranted for an inac-
tive patient to ensure there is no obstructive dis-
Calcium Scoring ease. A calcium score of any value can be entered
alongside other patient characteristics in the
When an asymptomatic patient’s risk estimate MESA risk estimator to assess its impact on the
remains uncertain or is in the intermediate range, 10-year risk [6–8].
a coronary artery calcium (CAC) score often The CAC is easily available, often without a
helps inform the discussion by providing a snap- prescription. As such, people may obtain this
shot of the patient’s existing burden of coronary score out of interest and then present to their pro-
atherosclerosis. This score is calculated from a vider with the score to discuss how to manage
30 Prevention of Cardiometabolic Disease 335

further preventive efforts [6, 9]. The average cost second-hand smoke are also essential to consider
of a CAC is $43.00–$246.00 [10]. in all patients.
Additional patient groups that may benefit
from learning their calcium score include those
who are reluctant to initiate statin therapy as well Nutrition and Diet
as those who have discontinued statins because
of side effects and are concerned about reat- There are innumerable diets and dietary fads in
tempting lipid-lowering therapy. popular culture, most of which have never been
shown to improve cardiovascular health. The
shift over time from high-carbohydrate/low-fat
Modification of Risk diets to low-carbohydrate/high-fat diets—and
now, even zero carb, ketogenic diets—has left
Social Determinants of Health many patients confused and frustrated [13].
In contrast, the current recommendations from
In 2008, the World Health Organization’s the American College of Cardiology and
Commission on the Social Determinants of American Heart Association and (ACC-AHA)
Health defined such determinants as the “condi- incorporate simple and clear guidelines based on
tions in which people are born, grow, live, work data whenever possible. Although there are not
and age.” The Healthy People 2030 initiative [11] many randomized clinical trials of diets that have
further classified these determinants into five included clinically meaningful endpoints, multi-
groups: economic stability, education access/ ple observational studies have associated
quality, healthcare access/quality, neighborhood increased CVD risk with the consumption of
and built environment, and social and community refined grains, trans- and saturated fats, sodium,
context. red meats, processed meats, and sugar [14, 15].
A discussion of the patient’s social determi- Meanwhile, the Adventist Health Study [16]
nants of health is a useful starting point for the demonstrated that replacing meat with seeds and
conversation about how to modify risk [1]. The nuts was associated with a significant reduction
CDC has developed a framework to be used as a in cardiovascular risk, while the PREDIMED
screening tool to assess housing instability, food Mediterranean diet study [17] demonstrated
insecurity, transportation difficulties, utility reduced mortality among patients assigned to a
assistance needs, and interpersonal safety [12]. Mediterranean-style diet rich with olive oil and
Of course, if a patient lacks transportation to nuts. There is an ever-growing body of evidence
appointments or the grocery store, cannot afford showing that plant-based and whole food diets
(or identify) healthy fresh food, or cannot afford are associated with decreased mortality [18].
medications, discussions regarding lifestyle The current ACC-AHA recommendations
changes and medications are likely futile. include the following five diet strategies:
Even among patients not facing such funda-
mental barriers, additional determinants may 1. Eating a diet which emphasizes eating vegeta-
compromise efforts to modify risk. Barriers to bles, fruits, legumes, nuts, whole grains, and
heart-healthy diets include access to fresh food, fish.
living in an inner-city or rural environment, 2. Replacing saturated fat—which is solid at
socioeconomically disadvantaged status, cultural room temperature and found in meat, coconut
practices and traditions, and advanced age. oil, and cheese—with dietary monounsatu-
Exercise may be limited if individuals do not rated and polyunsaturated fat.
have access to appropriate venues such as side- 3. Reducing intake of dietary cholesterol and
walks, malls, or gyms. Issues such as sleep sodium (<2000 mg daily).
hygiene, work hours, psychosocial stressors and 4. Minimizing the intake of processed meats
support, financial well-being, and exposure to (e.g., deli meats, hot dogs), refined carbohy-
336 A. W. Dimsdale and C. Kelly

drates (e.g., high fructose corn syrup), and (musculoskeletal pain, low vision, lack of safe
sweetened beverages. places to exercise) be addressed before starting
5. Reducing trans fats, which are found in pre- an exercise program.
pared foods and occur naturally, albeit to a The current ACC/AHA guidelines recom-
small degree, in meat and dairy. mend that the average adult engage in 150 min-
utes weekly of moderate-intensity exercise, or
75 min weekly of vigorous-intensity physical
Physical Activity and Obesity activity. If an adult cannot meet these goals,
engaging in even some moderate- or lower-
Physical activity and exercise are essential for intensity activity can still reduce the risk of
maintaining or improving cardiovascular health. ASCVD. Defining high and low intensity for
Multiple clinical trials have shown that regular patients can help them assess their own life-
physical activity can increase life expectancy by style. It can be helpful to share the definition of
0.4 to 6.9 years [19]. Aerobic and resistance exer- METs and their associated values (Fig. 30.3).
cise can also improve glycemic control, decrease The take-home message for these patients is
weight, and lower blood pressure [15]. When dis- that any improvement upon a sedentary life-
cussing an exercise prescription, it is essential to style is likely to reduce ASCVD risk [15].
understand the patient’s current baseline. A sed- Annual assessment of BMI and waist circum-
entary or obese individual should begin with low- ference may help patients see the results of
intensity exercise such as slow walking and then their intentions and actions, creating a positive
gradually increase to recommended levels. It is feedback cycle that encourages further
also essential that any functional impairment progress.

Fig. 30.3 Definitions of varying intensity of physical 2.0 “2017-08-08-Matt_Duboff-Men’s Swimming-47” by

activity. (Adapted from: “Leather Recliner #723” by 2017 Canada Games //Jeux du Canada 2017 is licensed
DesignFolly.com is licensed under CC BY-SA 2.0 “Person under CC BY 2.0 “Carrera Regency” by @jluisro is
Walking Through Fall Leaves Foreground in focus, per- licensed under CC BY-NC-SA 2.0)
son soft focus” by ShebleyCL is licensed under CC BY
30 Prevention of Cardiometabolic Disease 337

Type 2 Diabetes Mellitus cholesterol goals for all patients is essential. The
concept of a single “normal” cholesterol threshold
Type 2 diabetes mellitus (T2DM) is a metabolic remains popular among patients but is no longer
disorder defined by insulin resistance leading to used in contemporary practice. Instead, an indi-
hyperglycemia. This condition is highly preva- vidual’s target cholesterol values are determined
lent in the United States, affecting nearly one in based on their global risk of either developing
eight adults. More than one third of American clinical ASCVD or experiencing a recurrence. The
adults have prediabetes and are at high risk of current guidelines for setting and then achieving
developing T2DM. Moreover, adults with diabe- such goals were established in the “2018
tes are two to four times more likely to die of Cholesterol Clinical Practice Guidelines.” [1]
heart disease than adults without diabetes [20]. For the purposes of primary prevention, the
Important interventions in treating and managing clinician will typically determine the need for
T2DM include diet, exercise, weight loss, and phar- lipid lowering with the 10-year ASCVD risk as
macotherapies such as metformin. Mediterranean, calculated using the PCE. If the risk is intermedi-
low sodium, and vegetarian diets have all been ate or higher, and the LDL is ≥70 mg/dl, lipid-
shown to improve glycemic control [15]. Clinicians lowering therapy is recommend to reduce the
can take a multidisciplinary approach with diabetic LDL by at least 30–50%. Of note, however, lipid-
patients to provide education, exercise prescriptions lowering therapy is also recommended in all
including aerobic and resistance strategies, diet over- adults with an LDL > 190 mg/dl regardless of the
sight, medication management, and assessment of overall ASCVD risk score, as well as adults with
social determinants in order to decrease the risk of T2DM. Among those with diabetes, an LDL goal
developing clinical ASCVD. of <70 mg/dl is appropriate (Fig. 30.4).
Among lipid-lowering drugs, statins have the
strongest evidence for reducing the incidence of a
Management of Blood Cholesterol first clinical ASCVD event. The various agents
and available doses are generally divided into
Several cholesterol markers—including LDL, “moderate-” and “high-” intensity regimens, with
lipoprotein B, and lipoprotein(a)—strongly pre- the latter recommended for those with the highest
dict ASCVD risk. Therefore, defining and targeting LDL levels or highest risk (e.g., those with

Four Statin Benefit Groups

Patients age 40-75 Patients age 40-79

Patients with clinical Patients with LDL-C
with DM and LDL-C without DM and
ASCVD >190 mg/dl
70-189 mg/dl LDL-C 80-189 mg/dl

Statin Recommended

Assess 10Y ASCVD Assess 10Y ASCVD

risk with pooled risk with pooled
cohort calculator cohort calculator

Moderte intensity Risk > 7.5% - high

statin or if risk intensity statin
High Intensity Statin High Intensity Statin
>7.5%, high Risk 5-7% - consider
intensity statin moderate intensity
statin if other risk
factors present

Fig. 30.4 Management of blood cholesterol

338 A. W. Dimsdale and C. Kelly

High Intensity Moderate Intensity Low Intensity

Statin Therapy Statin Therapy Statin Therapy

Daily dose lowers LDL-C on average Daily dose lowers LDL-C on average Daily dose lowers LDL-C on average
by approximately >50% by approximately 30<50% by <30%

Atorvastatin 40-80 mg Atorvastatin 10-20 mg Simvastatin 10 mg

Rosuvastatin 20-40 mg Rosuvastatin 5-10 mg Pravastatin 10-20 mg

Simvastatin 20-40 mg Lovastatin 20 mg

Pravastatin 40-80 mg Fluvastatin 20-40 mg BID

Lovastatin 40 mg Pitavastatin 1 mg

Fluvastatin XL 80 mg

Fluvastatin 40 mg BID

Pitavastatin 20 mg

Fig. 30.5 Intensity of statin medications. (Adapted from Grundy et al. [1])

T2DM) (Fig. 30.5). Other agents—such as ezeti- The clinician may also evaluate other reasons for
mibe, bempedoic acid, and PCSK9 inhibitors— myalgias in order to establish a causal relation-
are currently used only when patients are unable ship. These may include hypothyroidism, low
to achieve adequate lipid lowering with statins, vitamin D, recent exercise, or alcohol/drug abuse
either because of inefficacy or intolerable side [21]. Note that there is no evidence that statins
effects. adversely affect cognition. If a patient develops
When initiating lipid-lowering therapy, it is confusion or memory impairment while on statin,
important to discuss the potential risk reduction, consider all causes.
possible adverse effects, drug-drug interactions, Randomized clinical trials have repeatedly
and cost. Adherence to the prescribed regimen demonstrated that the benefits of moderate- or
should be assessed at each visit. Myalgia is the high-intensity statin outweigh the risks in nearly
most common side effect of statin therapy and all patients, excepting those with significant
can affect adherence. Prior to initiating statin adverse effects such as myositis. Regardless,
therapy, baseline CK and myalgia assessment patients tend to focus on potential side effects—
should be completed. Review of systems will the most common of which include myalgias,
include muscle aching, pain, stiffness, tender- dysglycemia, and cognitive impairment. A patient
ness, weakness, fatigue, or cramps (Fig. 30.6). experiencing side effects with one statin should
30 Prevention of Cardiometabolic Disease 339

Fig. 30.6 How to Assessing for myalgia

evaluate for myalgias in
patients on statins • Prior to initiating and during statin therapy
• Baseline CK for increased risk (elderly, meds that increase myopathy
risk
• No routine assessment
• ROS:
• Muscle aching
• Pain
• Stiffness
• Tenderness
• Weakness
• Fatigue
• Cramps
• Evaluate other reasons for myalgias-establish causal relationship
• Hypothyroidism
• Low vitamin D
• Recent exercise
• Alcohol/drug abuse

generally be transitioned to a different statin, The definition of hypertension has evolved

often at a lower intensity, and then retitrated. over the past several decades, and many profes-
Patients should generally not be labeled as statin sional organizations continue to offer slightly dif-
intolerant until they have failed at least three differing thresholds and goals. Unlike cholesterol,
ferent agents. For the clinician, it can be difficult where lower values are almost always better, the
to convince a patient to accept a medication that relationship between mortality and blood pres-
causes adverse effects, even if only perceived, in sure is clearly U-shaped, and overtreatment is a
order to prevent a theoretical future risk. common challenge.
The current guidelines categorize blood pres-
sure as normal, elevated, or hypertension, which is
Blood Pressure then further divided into stages 1 and 2 (Fig. 30.7).
Previously, a blood pressure of <130/80 was con-
Hypertension accounts for more ASCVD fatali- sidered normal, and clinicians may find patients
ties than any other modifiable risk factor, largely are confused by the newer, lower goals.
because of its high and rising prevalence [22]. In For most patients, the diagnosis of hyperten-
a meta-analysis of 61 studies, a log-linear asso- sion requires abnormal readings on two separate
ciation was observed between SBP levels <115 to occasions [15]. An exception may be made for
>180 mmHg and DBP levels <75 to 105 mmHg patients with especially high blood pressure (e.g.,
and the risk of ASCVD across an age spectrum of SBP greater than 160 mm Hg or DBP > 100 mm
30–80 years. Thus, all clinicians must diligently Hg) on a single occasion, provided the measure-
help patients achieve target blood pressure levels ment has been repeated under appropriate condi-
to decrease their cardiac risk. tions and after an adequate period of rest.
340 A. W. Dimsdale and C. Kelly

BP Category SBP DBP

Normal <120 mm Hg and <80 mm Hg
> readings
120-129 mm Hg <80 mm Hg on
Elevated and
>2 occasions

Hypertension

Stage 1 130-139 mm Hg or 80-89 mm Hg

Stage 2 >140 mm Hg or <90 mm Hg

Guideline now defines hypertension to be above 130 mmHg systolic, or 80 mmHg diastolic
More patients (46% vs 32% based on JNC7) will be diagnosed with hypertension

Fig. 30.7 Blood pressure definitions

Patients with normal BP (<120/80 mmHg) The antihypertensive medications currently

should continue to pursue healthy lifestyle habits. available for use include ACE inhibitors or angio-
Patients with elevated BP (120–129/<80 mmHg) tensin receptor blockers, diuretics (loop, potas-
or stage I hypertension (BP 130–139/80– sium sparing, aldosterone antagonists), calcium
89 mmHg) with an estimated 10-year ASCVD channel blockers, beta blockers (cardioselective,
risk <10% should consider lifestyle changes and vasodilatory, combined), direct renin inhibitors,
nonpharmacological therapies. Patients with and alpha blockers. The clinician should choose
stage 2 hypertension (>140/90 mmHg), as well as therapies based on the amount of blood pressure
those with stage 1 hypertension and a 10-year lowering that is required, the patient’s other
risk >10%, should pursue both nonpharmacolog- comorbidities, dosing frequency, side effects, and
ical and pharmacological therapies [23]. cost (Fig. 30.8).
Nonpharmacologic approaches to blood pres- Every hypertensive patient should have a clear
sure management can be very effective, though and detailed plan of care that outlines their treat-
long-term adherence is challenging [15]. The ments and their personalized, achievable goals.
most effective interventions include weight loss, They should know how to measure their blood
a plant-based diet, reduced dietary sodium intake, pressure at home, how to record it, and whom to
increased dietary potassium intake, physical contact when questions arise. An interprofes-
activity, and reduction of alcohol consumption. sional collaborative care team including a clini-
In addition, patients may need to reduce or avoid cian (physician, nurse practitioner, or physician
the use of certain medications and supplements assistant), nurse, medical assistant, pharmacist,
that can raise blood pressure, including decon- and perhaps trainer or exercise physiologist
gestants, antidepressants, caffeine, oral contra- should assume shared responsibility for this
ceptives, nonsteroidal anti-inflammatory drugs effort. The reassessment frequency should
(NSAIDs), corticosteroids, licorice, anise, black depend on the level and stability of control, and
cohosh, ginger, ma huang, ginseng, and St. John’s the patient should always leave the office with a
wort. follow-up appointment scheduled.
30 Prevention of Cardiometabolic Disease 341

Thiazide diuretics Chlorthalidone, • Monitor for hyponatremia and hypokalemia, uric

hydrochlorothiazide, Acid and calcium, careful with gout
metolazone, indapamide • chlorthalidone is preferred diuretic due to long half
life and proven risk reduction
Ace Inhibitors Benazepril, enalapril, • May cause ARF in patients with bilateral renal
lisinopril, ramipril etc. artery stenosis, watch for angioedema at any time
• Do not combine with ARB or direct renin
inhibitor, increased risk of hyperkalemia in CKD
• Do not use in pregnancy
Angiotensin Receptor Candesartan, irbesartan, • Do not combine with ACEi
Blocker olmesartan, valsartan, etc.
CCB – dihydropyridine Amlodipine, felodipine, • Avoid in HFrEF
nifedipine, nisoldipine • More common in women
• Associated with dose-related pedal edema
CCB – Diltiazem, verapamil • Avoid routine use with BB drug interactions with
nondihydropyridine diltiazem and verapamil
• Associated with bradycardia and heart block
• Avoid in HFrEF
Diuretics – loop Bumetanide, furosemide, • Preferred diuretic in patient with symptomatic HF
torsemide • Preferred over thiazides in patients with moderate
to severe CKD (GFR <30ml/min)
Diuretics – aldosterone Eplerenone, spironolactone • Spironolactone associated with increased
antagonists gynecomastia and impotence
• Common add-on in resistant htn
• Avoid use with K+ supplements
• Eplerenone often requires BID dosing
• Preferred in primary aldosteronism and resistant
hypertension
Beta blockers – Atenolol, bisoprolol, • Not recommended as first line agents unless
cardioselective metoprolol patient has CAD or HFrEF
• Bisoprolol preferred to treat HTN +
bronchospastic airway disease
• Bisoprolol and metoprolol succinate preferred in
HTN with HFrEF
• Avoid abrupt cessation
Beta blockers – Nebivolol • Induces nitric oxide-induced vasodilation
cardioselective and • Avoid abrupt cessation
vasodilatory
Beta blockers – non Nadolol, propranolol • Avoid with reactive airway disease
cardioselective • Avoid abrupt cessation
Beta blockers – Carvedilol, labetalol • Preferred in patients with HFrEF
combined alpha and
beta receptor
Direct renin inhibitor Aliskaren • Long acting
• Increased risk of hyperkalemia
• Watch for acute renal failure with renal artery
stenosis
• Avoid in pregnancy
• Targets renin angiotensis sytem
• Do not combine with ACEi/ARB
Alpha-1 blockers Doxazosin, prazosin, terazosin • May consider as second line agent with
concomitant BPH
• Associated with orthostatic hypotension
Central alpha2-agonist Clonidine, methyldopa, • Reserved as last line due to CNS adverse effects
and other centrally guanfacine especially in older adults
acting drugs • Avoid abrupt discontinuation of clonidine which
may induce hypertensive crisis, must be tapered
Direct vasodilators Hydralazine, minoxidil • Associated with sodium and water retention, and
reflex tachydardia
• Minoxidil associated with hirsutism – use with
loop diuretic, can induce pericardial effusion
• Must be used with diuretic and beta blocker

Fig. 30.8 Classes of oral antihypertensives

342 A. W. Dimsdale and C. Kelly

Tobacco Use Aspirin Use

Tobacco use is the leading preventable cause of Aspirin has long been recommended for the pre-
death, disease and disability in the United States, vention of ASCVD. Aspirin reduces the risk of
and even secondhand smoke contributes to the atherosclerosis by inhibiting platelet function,
risk of ASCVD and stroke. Although the risks of but this also increases the risk of bleeding [26].
cigarettes are now well-known, newer, electronic Its importance for secondary prevention remains
nicotine delivery systems (e-cigarettes) also emit unchallenged, but its role in primary prevention
aerosols containing particulates, nicotine, and has become more controversial. Historically,
noxious gases that can increase the risk of cardio- low-dose aspirin was recommended for primary
vascular and pulmonary diseases [24]. prevention among adults aged 40–70 years at
Many clinicians are daunted by the challenge increased risk of ASCVD and low risk of
of delivering effective tobacco cessation therapy, bleeding.
given the chronic and relapsing nature of tobacco In current practice, however, most guidelines
addiction. The assessment should cover frequency favor the use of low-dose aspirin only in a small
of use, lifelong exposure, and readiness to quit, cohort of patients [27]. Aspirin use for prevention
often at each ambulatory encounter. Appropriate in adults aged 40–59 years who have a 10% or
questions to ask the patient include: “Have you greater 10-year CVD risk has a small net benefit.
smoked any tobacco products in the past 30 days? The use of aspirin for primary prevention of CVD
Have you vaped or Juul’ed in the past 30 days? events should be avoided in adults 60 years or
Have you used any tobacco products in the past older, adults with an increased risk of bleeding,
30 days, even a puff?” Such questions are far and adults younger than 59 with a <10% 10-year
more effective than, “Do you smoke?”. ASCVD risk estimate [27].
The pharmacologic arsenal for helping Factors consistent with an increased risk of
patients defeat tobacco addiction includes FDA- bleeding include a history of GI bleed, peptic
approved pharmacotherapies—including vareni- ulcer disease, bleeding at other sites, thrombocy-
cline, bupropion, nortriptyline—and several topenia, coagulopathy, chronic kidney disease, or
approved forms of nicotine replacement, such as concurrent use of other medications that may
patches, gums, lozenges, and inhalers [25]. These increase bleeding (NSAIDS, steroids, anticoagu-
interventions should always be combined with lants, warfarin, or fish oil) (Fig. 30.9). In the
cognitive behavioral skills training and appropri- future, precision medicine may help clinicians
ate encouragement and incentives. Formal understand a patient’s platelet phenotype, and
tobacco cessation clinic referrals should be con- relative risk versus benefit, when making deci-
sidered if available. sions about antiplatelet use [27].

Fig. 30.9
Contraindications to
aspirin use in primary
prevention
30 Prevention of Cardiometabolic Disease 343

Conclusion 5. Ridker PM, Buring JE, Rifai N, Cook

NR. Development and validation of improved
algorithms for the assessment of global cardio-
Many ASCVD events are avoidable with effec- vascular risk in women: the Reynolds risk score.
tive primary prevention. The best way to prevent JAMA. 2007;297(6):611. https://doi.org/10.1001/
ASCVD is to promote a lifelong, healthy life- jama.297.6.611.
6. Miedema MD, Duprez DA, Misialek JR, et al. Use
style. Tobacco avoidance is critical, and all adults of coronary artery calcium testing to guide aspirin
should seek to engage in brisk physical activity utilization for primary prevention: estimates from the
as often as possible. A diet high in fruits, vegeta- multi-ethnic study of atherosclerosis. Cardiovascul
bles, and whole grains is preferred. Although a Qual Outcom. 2014;7(3):453–60. https://doi.
org/10.1161/CIRCOUTCOMES.113.000690.
plant-based diet is preferred, fish and poultry are 7. Mitchell JD, Fergestrom N, Gage BF, et al. Impact
the preferred sources of protein among meat eat- of statins on cardiovascular outcomes following
ers. It is important to minimize trans fats, added coronary artery calcium scoring. J Am Coll Cardiol.
sugars, red and processed meats, and excessive 2018;72(25):3233–42. https://doi.org/10.1016/j.
jacc.2018.09.051.
sodium. 8. Explaining ASCVD risk scores for primary preven-
Clinicians should work with patients to assess tion. https://www.acc.org/-/media/Non-Clinical/
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to assess and understand their personal risk fac- Support/Risk-C ommunications/3-E xplaining-
ASCVD-Risk-Scores-for-Primary-Prevention.pdf?la
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include an interprofessional team working 8C462FDCC23. Accessed 5 Apr 2022.
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Lastly, awareness of the social determinants of M. Coronary artery calcium scoring: its practi-
cality and clinical utility in primary care. CCJM.
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jamacardio.2018.3680.
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3. American College of Cardiology, American Heart
https://doi.org/10.1161/CIR.0000000000001031.
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14. Reedy J, Krebs-Smith SM, Miller PE, et al. Higher
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Part X
Emergency Department Evaluation
of Chest Pain

Musialowsk Musialowski

There are approximately 130 million emergency department (ED) visits

annually, many of which are due to a cardiovascular cause [1]. Cardiovascular
complaints frequently require hospital admission. Congestive heart failure is
the second leading cause of emergency department (ED) visits requiring hos-
pital admission, comprising 4.1% of all hospital admission [2]. Acute myo-
cardial infarction (AMI) and cardiac dysrhythmias are also among the top ten
admission diagnoses with 2.5% and 2.2% of all hospital admissions, respec-
tively [2]. Cardiac disease remains the leading cause of death in the USA,
accounting for 211.5 deaths per 100,000.
Patients presenting with chest pain may have a wide array of potential
diagnoses with varying severity and urgency. This spectrum can range from a
non-cardiovascular etiology of symptoms to a life-threatening emergency
requiring immediate diagnosis and intervention. A provider in the ED must
exclude life-threatening diagnoses via a rapid and thorough evaluation prior
to the consideration of more benign etiologies. The high prevalence of cardio-
vascular disease in patients presenting to the ED has prompted many
guideline-directed care pathways. These guidelines and pathways are essen-
tial to rapidly evaluate and triage the acuity of the patient.
Patients can present to healthcare locations other than an ED. Patients with
STEMI may present to the office or any ambulatory setting. The same prin-
ciples apply to the evaluation of patient complaints in any setting. The follow-
ing chapter will evaluate the common presenting complaint of cardiovascular
disease: chest pain. The common theme will be focusing on pertinent ele-
ments of patient history, physical examination, laboratory, and diagnostic
testing which will guide rapid diagnosis and treatment. Always remember to
exclude the most dangerous and life-threatening etiologies before consider-
ing a less severe or even noncardiovascular etiology.

M. Musialowski
Sanger Heart and Vascular Institute, Atrium Health, Charlotte, NC, USA
e-mail: [email protected]
346 Emergency Department Evaluation of Chest Pain

References

1. https://www.cdc.gov/nchs/fastats/emergency-department.htm
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Hospital-Stays-2018.pdf#:~:text=%E2%96%A0%20The%20most%20fre-
quent%20principal%20diagnoses%20for%20hospitalizations,stays%29%20
and%20the%20costliest%20%28%2441.5%20billion%20in%20
aggregate%29
Acute Evaluation of Chest Pain
31
Devin Stives and Richard Musialowski

Introduction used today due to the numerous superior medical

and invasive treatment options (see Part II).
Chest pain accounts for approximately 5% of all
ED visits. Noncardiac chest pain will be identi-
fied in over 50% of these patients [1]. ED clini- Etiologies of Chest Pain
cians should always consider cardiovascular
pathologies when evaluating a patient complain- We recommend an anatomic approach to estab-
ing of chest pain. However, several pathologies lishing a differential diagnosis for chest pain as
involving the pulmonary, musculoskeletal, and outlined in Table 31.1. Besides cardiovascular
gastrointestinal systems share similar symptoms causes, there are numerous noncardiac etiologies
with cardiovascular disease. Afferent pain fibers including pulmonary, gastrointestinal, and mus-
originating from intrathoracic organs course with culoskeletal diseases. ED providers will need to
afferent sympathetic nerves to paravertebral gan- evaluate for any life-threatening causes in a
glion before entering the spinal cord. The desti- timely manner prior to consideration of a more
nation for visceral pain sensation is the thalamus. benign diagnosis. Patient history and examina-
No area within the cerebral cortex localizes vis- tion is insufficient to establish a diagnosis and
ceral pain. The lack of brain stem localization typically requires further testing.
results in patients unable to localize a specific
origin of their visceral pain and symptoms can
overlap between different organ systems [2]. The Myocardial Ischemia
involvement of sympathetic nerves in cardiac
pain sensation was known as early as 1921, when Cardiac causes of chest pain can be due to isch-
angina pectoris was successfully treated with emia attributable to coronary disease such as
sympathectomy [3]. This practice is no longer acute coronary syndrome, coronary vasospasm,
spontaneous coronary artery dissection, or
increased myocardial demand in the setting of a
D. Stives (*)
Cardiovascular Disease Fellow, Aurora St. Lukes flow limiting lesion. Noncoronary cardiovascular
Medical Center, Milwaukee, WI, USA etiologies such as aortic dissection, heart failure,
e-mail: [email protected] or myopericarditis should also be considered [4].
R. Musialowski There are several mechanisms of myocardial
Sanger Heart and Vascular Institute, Atrium Health, injury and elevated troponin. Type I MI refers to
Charlotte, NC, USA coronary occlusion due to acute atherosclerotic
e-mail: [email protected]

© The Author(s), under exclusive license to Springer Nature Switzerland AG 2023 347
R. Musialowski, K. Allshouse (eds.), Cardiovascular Manual for the Advanced Practice Provider,
https://doi.org/10.1007/978-3-031-35819-7_31
348 D. Stives and R. Musialowski

Table 31.1 Differential diagnosis of chest pain cally taught as diagnostic for angina. However,
Cardiovascular – Acute myocardial infarction (type newer data suggests that response to nitroglyc-
I MI) erin does not provide diagnostic accuracy and
– Acute coronary ischemia (type II
MI)
should not weigh heavily as a predictor of
– Aortic dissection coronary-related chest pain [6]. Current guide-
– Cardiac tamponade lines for chest pain recommend distinguishing
– Pericarditis chest pain as “cardiac,” “possible cardiac,” and
– Coronary vasospasm/spontaneous
coronary artery dissection (SCAD)
“noncardiac” to describe the suspected cause of a
– Valvular heart disease patient’s chest pain and recommend against the
– Hypertrophic cardiomyopathy use of “atypical” [7]. Attention should be given to
– Stress cardiomyopathy the uniqueness of the ischemic presentation in
Respiratory – Pulmonary embolus
women, diabetics, elderly patients. This cohort is
– Tension pneumothorax
– Pneumonia more likely to experience associated symptoms
– Malignancy such as shortness of breath, nausea or vomiting,
Gastrointestinal – Esophageal rupture lightheadedness, confusion, presyncope, syn-
– Esophageal spasm cope, or vague abdominal symptoms. Women
– Gastroesophageal reflux disease
– Peptic ulcer with AMI are more likely to present with “typical
– Hiatal hernia symptoms” compared to men but also have a
– Pancreatitis higher frequency of associated symptoms such as
– Cholecystitis nausea, vomiting, and palpitations [8].
Chest wall – Costochondritis
– Chest wall trauma
– Herpes zoster
– Musculoskeletal strain Pericardial Disease
Psychiatric – Anxiety
– Panic disorder Pericarditis is a common cause of chest pain in
Disease processes that require urgent or immediate evalu- the emergency department and occurs due to
ation and intervention are underlined
inflammation of the pericardial layers due to sys-
plaque rupture, and type 2 MI refers to myocar- temic inflammatory or infectious processes.
dial oxygen supply/demand mismatch [5]. Type I However, the most common cause is idiopathic
MI is due to an acute coronary syndrome that as seen in about 90% of patients. Pericarditis is
often necessitates invasive angiography and per- typically a benign etiology of chest pain.
cutaneous coronary intervention (PCI) or coro- However, complications such as pericardial effu-
nary artery bypass grafting (CABG) if indicated. sion with tamponade and/or pericardial constric-
For full details, see Part II on CAD. tion warrant further investigation [9]. See Chap.
A detailed history including prior coronary 23 for full discussion on pericarditis.
evaluation, family history of early myocardial
infarction as defined as age in men <45 or women
<55, and risk factors for CAD should be obtained. Vascular Causes
“Typical” chest pain will be described as subster-
nal chest pain provoked by exertion or emotional An acute aortic dissection is an uncommon but
stress and relived by rest. Patients will describe life-threatening cause of chest pain in the
chest pain as a heaviness, pressure, or squeezing ED. Aortic dissections occur due to a tear within
sensation that originates retrosternal and may the tunica intima and formation of a false lumen
radiate to the left arm or jaw. Pain described as due to shear stress on the intimal wall, most com-
sharp or worsening with inspiration decreases monly due to underlying hypertension and ath-
your likelihood of myocardial ischemia as the erosclerosis. Other risk factors including
origin for their pain. Improvement of a patient’s underlying connective tissue disorders (Marfan
chest pain in response to nitroglycerin was classi- syndrome or Ehlers-Danlos syndromes), cocaine
31 Acute Evaluation of Chest Pain 349

use, pregnancy, and known aortic aneurysm also hemodynamic collapse. Patients with an acute PE
increase risk of aortic dissection as an etiology may report chest pain, dyspnea, hemoptysis, or
[10]. Aortic dissections are classified by the presyncope. These are nonspecific findings, and
Stanford classification, with type A involving the their absence does not exclude PE. Risk factor
ascending aorta and type B without ascending assessment is a crucial element in patients with
aortic involvement. This distinction is crucial as suspected PE. Recent fracture of a lower limb, hip,
it drives management. or knee replacement; major trauma or surgery; and
Patients will classically describe pain as a prior spinal cord injury has an odds ratio of >10 for
severe “tearing,” “ripping,” or “stabbing” sensa- venous thromboembolism [15]. Prior VTE, malig-
tion. Pain is often sudden onset. According to the nancy, and oral contraceptives are also significant
International Registry of Acute Aortic Dissection risk factors for VTE (see Chap. 22).
(IRAD), “tearing” or “ripping” was found to not
be as reliable descriptor as previously thought
[11]. Examination may reveal an uncomfortable Gastrointestinal
appearing, hypertensive patient. A diastolic mur-
mur may be heard in up to 40% of patients with a Gastrointestinal causes of chest pain can mimic
type A aortic dissection. Asymmetric pulses were cardiovascular chest pain but are often due to
only present in 30% of type A aortic dissections benign etiologies. Esophageal perforation or per-
and 20% of type B aortic dissections [11]. See forated peptic ulcer can be life-threatening.
Chap. 28 for full discussion on aortic dissection. Nitroglycerin is often used for patients with sus-
pected chest pain due to cardiac ischemia, and
the medication may be helpful for patients with
Pulmonary Causes esophageal spasm. Attention to precipitating fac-
tors such as relation to meals or associated dys-
Several pulmonary pathologies can result in chest phagia may be an indicator that a patient’s pain is
pain. Pain will commonly be described as pleu- due to a gastrointestinal etiology. Eructation and
ritic and worsens with inspiration. Associated flatus improving the symptoms suggest a GI eti-
dyspnea or cough may be seen. Tension pneumo- ology as well. Symptoms such as odynophagia,
thorax is an uncommon but life-threatening cause GI bleeding, unintentional weight loss, or vomit-
of chest pain to the ED due to air within the intra- ing may warrant further esophageal evaluation.
pleural space. Patients with tension pneumotho-
rax are typically hypoxic and may progress to
respiratory and hemodynamic failure. Signs on History
physical exam of a tension pneumothorax may
include tracheal deviation away from the pneu- Detailed history is commonly insufficient to estab-
mothorax, absent or diminished lung sounds ipsi- lish a clear diagnosis. Attention should also be
laterally, and subcutaneous emphysema [12]. given to a patient’s past medical history and under-
This is a surgical emergency requiring urgent lying risk factors (Table 31.2). Features of chest
decompression of the trapped air. pain carry significant overlap, although history and
Pulmonary embolism (PE) is a common con- physical examination will likely drive additional
sideration for patients presenting with chest pain testing and evaluation. History should be obtained
in the emergency department and significant con- in a standardized format with a focus on high yield
tributor to global disease burden [13]. Commonly, questioning based on most likely etiology.
pulmonary emboli originate from a deep vein
thrombosis in the lower extremities with emboli- 1. Onset: The events leading up to the onset of
zation to the pulmonary arteries [14]. Patients with pain can provide helpful indicators for an eti-
a pulmonary embolism are at risk for acute respi- ology. Pain that started during physical or
ratory and right ventricular failure resulting in emotional stress and builds gradually is typi-
350 D. Stives and R. Musialowski

Table 31.2 Risk factors for common causes of chest pain

Acute coronary Pulmonary
syndrome Aortic dissection embolism Pericarditis Pneumothorax
Coronary artery Hypertension Hypercoagulable Prior Prior
disease Atherosclerosis state pericarditis pneumothorax
Diabetes mellitus Pregnancy Malignancy Autoimmune Chronic lung
Tobacco use Bicuspid aortic valve Lower limb fracture disease disease
Hypertension Connective tissue disease (Marfan Hip replacement Recent type I Tobacco use
Advanced age syndrome, Ehlers-Danlos syndrome) Knee replacement MI
Aortic aneurysm Spinal cord injury Uremia
Tobacco use Major trauma or Radiation
Cocaine use surgery therapy
Oral contraceptives
Prolonged
immobility

cal for ischemic heart disease. Pain that began with change of position may be musculoskel-
abruptly may indicate an acute aortic dissec- etal in origin.
tion, pneumothorax, or PE. Chest pain that 6. Associated symptoms: Symptoms that may
began after eating or drinking is more com- be associated with ACS include dyspnea, pal-
monly due to a gastrointestinal cause. pitations, diaphoresis, presyncope, or abdom-
2. Nature: Angina symptoms can be described inal pain. Hemoptysis may be a sign of PE,
in many ways such as pain, discomfort, pres- although this is not a common complaint.
sure, or squeezing like sensation. A sharp or
stabbing pain may indicate pneumothorax or
acute pericarditis. A “ripping” or “tearing” Physical Examination
sensation is classic for aortic dissection,
although these features lack sensitivity to be Physical exam rarely leads to a solidified type I
used reliably. MI diagnosis without additional testing. Patients
3. Location and radiation: Pain due to isch- may be diaphoretic and either tachycardic or bra-
emic heart disease is most likely retrosternal. dycardic. A new murmur may represent a mechan-
Patients may report radiation to the arm or ical complication of MI. Signs of volume overload
jaw. Associated back pain may be seen in aor- such as jugular venous distention, S3 gallop, rales,
tic dissection. Pain involving the trapezius or peripheral edema suggest depressed LV func-
muscle may be due to phrenic nerve irritation tion as a cause of their symptoms.
and pericarditis. Patients with an aortic dissection typically
4. Precipitating factors: Chest pain that wors- appear distressed and are often tachycardic and
ens with exertion or emotion is most likely hypertensive. Assessment of upper extremity
due to myocardial ischemia. Pain that worsens peripheral pulses bilaterally should be performed
with lying flat usually occurs with acute peri- and assessed for differences. This pulse difference
carditis. Pain that worsens with positional was only present in 30% of patients with aortic
changes or worsening of pain with chest wall dissection and should not be used to exclude aor-
palpation may be seen in musculoskeletal eti- tic dissection. A new diastolic murmur may be
ologies. Symptoms after eating are often not heard indicating aortic insufficiency.
cardiovascular and suggest a GI etiology. In acute pulmonary embolism, patients are
5. Palliating factors: Resolution of the symp- commonly tachycardic and short of breath. A
toms with cessation of an activity is very sug- low-grade fever may be present. Despite the
gestive of coronary ischemia. Newer data patient’s shortness of breath, lung auscultation
suggests that relief from nitroglycerin is not typically reveals clear lungs. A pleural rub may
as reliable as previously thought and should be heard. JVD may be a sign of more severe
not be used as diagnostic criteria. Improvement disease.
31 Acute Evaluation of Chest Pain 351

In acute pericarditis, a pericardial friction rub all patients complaining of chest pain (Fig. 31.1).
is one of four diagnostic criteria. Tachycardia and The ECG is crucial for the identification of
low-grade fever are common. If a pericardial STEMI to facilitate timely coronary reperfusion
effusion is large enough, it may produce pericar- in type I MI. If an initial EKG is nondiagnostic
dial tamponade which will present as tachycar- but clinical suspicion remains high for ACS,
dia, hypotension, and JVD. serial ECGs may increase the sensitivity in
Pneumothorax can be identified with absent detecting potential candidates for coronary reper-
lung sounds unilaterally, tracheal deviation, and fusion [16]. The universal definition of myocar-
respiratory distress. Tension pneumothorax may dial infarction defines STEMI as new ST
produce obstructive shock and JVD on exam. elevation at the J point in at least two contiguous
With gastrointestinal causes of chest pain, there leads of ≥2 mm (0.2 mV) in men or ≥1.5 mm
may also be epigastric tenderness. Clinicians (0.15 mV) in women in leads V2-V3 and/or of
should not neglect direct visualization of the ≥1 mm (0.1 mV) in other contiguous chest leads
patient’s skin to look for vesicles, erythema as or the limb leads in the absence of left ventricular
signs of herpes zoster infection. hypertrophy or left bundle-branch block (LBBB)
[17]. Paced rhythm and underlying LBBB make
the ECG difficult to evaluate for STEMI. ST
iagnostic Testing During the Acute
D depressions in V1-V4 may prompt a clinician to
Presentation perform a repeat ECG including leads V7-V9 to
evaluate for posterior STEMI (see Part II CAD).
Electrocardiogram The ECG will provide additional information
in the setting of acute PE. The most common
An electrocardiogram (ECG) should be per- ECG finding in PE is sinus tachycardia. Patients
formed within 10 min of patient presentation for with “S1Q3T3” are threefold more likely to have

Chest Pain

History
+
physical examination

ECG (1)

Diffuse ST-
ST-depression
elevation Nondiagnostic
STEMI New T-wave New arrhythmia
consistent with or normal ECG
inversions
pericarditis

Repeat ECG if
symptoms Leads V7-V9
Follow
Follow STEMI Follow NSTE- persist or are reasonable
Manage arrhythmia-
guidelines ACS guidelines change or if posterior MI
pericarditis specific
(1) (1) if troponins suspected
positive
guidelines
(2a)
(1)

ECG indicates electrocardiogram; NSTE-ACS, non ST-segment-elevation acute coronary syndrome; MI, myocardial infarction; and STEMI, ST-segment-
elevation myocardial infarction

Fig. 31.1 Ekg and chest pain decision tool. (Adapted Chest Pain: A Report of the American College of
from 2021 AHA/ACC/ASE/CHEST/SAEM/SCCT/ Cardiology/American Heart Association Joint Committee
SCMR Guideline for the Evaluation and Diagnosis of on Clinical Practice Guidelines)
352 D. Stives and R. Musialowski

a PE than patients who do not. Right bundle the American College of Emergency Physicians
branch block, inverted T waves in V1-V4, and ST and American Society of Echocardiography, the
elevation in aVR are concerning features for use of focused cardiac ultrasound (FOCUS) pro-
patients with PE [18]. The ECG may clue a clini- vides great utility for the assessment of global car-
cian toward a diagnosis of acute pericarditis if diac systolic function, marked ventricular chamber
diffuse ST elevations and PR depression are seen. enlargement, or the assessment for the presence of
Nonspecific ST and T wave changes may be seen a pericardial effusion. In cases of uncertain volume
in as many as 42% of patients with acute aortic status, FOCUS may be used to aid in the assess-
dissection, and up to 5% of patients with an acute ment of intravascular volume assessment. FOCUS
aortic dissection may also have an acute inferior should also be used for guidance during pericardio-
MI due to extension into the RCA. centesis and confirmation of a transvenous pacing
wire placement [19].
In the case of an AMI, segmental wall motion
Chest Radiography abnormalities should only be evaluated under
comprehensive echocardiography and interpreted
Chest radiograph is a quick, noninvasive test that by experienced readers. FOCUS may be used to
should be performed with patient’s complaining establish the presence of a pericardial effusion in
of chest pain. Chest radiographs often do not acute pericarditis but does not replace compre-
change management in acute coronary syndrome hensive echocardiography for monitoring of effu-
but are beneficial for evaluating other potential sion size. In the case of an acute aortic dissection,
etiologies of chest pain. A pneumothorax can be comprehensive echocardiography should be used
readily identified on chest X-ray by a visible vis- to evaluate aortic valve function and measure
ceral pleura edge seen as a thin, sharp white line aortic root dilation. Pericardial effusion may also
without lung markings peripheral to this line. be seen in as many as 18% of patients with a type
Mediastinal deviation from midline suggests ten- A aortic dissection.
sion physiology and warrants urgent interven- Echocardiography should be obtained in
tion. Subcutaneous emphysema may also be patients with suspected or confirmed pulmonary
seen. A widened mediastinum may be seen in embolus. This can be useful to assess for RV size,
acute aortic dissection, although this lacks sensi- function, or the presence of a right-sided throm-
tivity and does not exclude the possibility of aor- bus. A classic finding is “McConnel’s sign”
tic dissection. Bacterial pneumonia may be seen which refers to preserved apical RV function
as a focal opacity which may produce symptoms with hypokinesis to akinesis of RV free wall.
of chest pain. Other parenchymal lung diseases This finding is highly specific for pulmonary
like malignancy may be identified. embolism. The echocardiographic findings for
pulmonary embolism lack sensitivity and should
not be used to exclude the diagnosis.
Ultrasonography

Point-of-care ultrasound (POCUS) has grown in Cardiac Biomarkers

popularity in the emergency department setting due
to the rapid high-yield information that may be Troponin
obtained. Cardiac ultrasound has developed into a
vital instrument used by emergency department cli- Troponin is a protein highly specific for myo-
nicians with proper training in bedside image cardium. Under normal physiologic states, tro-
acquisition and interpretation to guide rapid diag- ponin should be undetectable in the serum.
nosis and clinical decision-making in symptomatic Elevated troponin levels often indicate myocar-
patients with cardiovascular disease. According to dial injury or inflammation. While acute myo-
31 Acute Evaluation of Chest Pain 353

cardial infarction is one of the most considered intermediate risk of PE and a low serum D-dimer
conditions for troponin elevation, several other effectively excludes PE as a diagnosis.
conditions include chronic kidney disease, con-
gestive heart failure, pulmonary hypertension,
skeletal myopathies, chemotherapeutic agents, BNP
hypertrophic cardiomyopathy, and infiltrative
processes such as cardiac amyloid, hemochro- Cardiac brain natriuretic peptide (BNP) is a pep-
matosis, or cardiac sarcoidosis which have been tide originally isolated from porcine brain tissue,
linked to elevated troponin levels [20]. Troponin giving it its name. BNP is also found in human
assay is recommended in all patients who pres- blood with the primary source being cardiac
ent to the emergency department for chest pain myocytes. Myocyte injury and/or stretch causes
unless an obvious noncardiac etiology is present the biomarker to be released and detectable in the
[7]. Newer high-sensitivity assays have replaced blood. Cardiac BNP is not used in the diagnosis
traditional troponin assays which have mark- of acute myocardial infarction in the emergency
edly improved the early diagnosis of acute myo- department. The most common cause of elevated
cardial infarction [21]. Troponins have cardiac BNP is due to decompensated heart fail-
tremendous negative predictive value to rule out ure and volume overload. Cardiac BNP should be
AMI. The negative predictive value for myocar- obtained in the setting of a diagnosed PE for risk
dial infarction within 30 days in patients with stratification and to guide urgency for anticoagu-
undetectable high- sensitivity troponin and no lation/thrombolytics.
ischemic ECG changes with 99.8% and the neg-
ative predictive value for death was 100% [22].
Two consecutive high-sensitivity troponins Clinical Decision Pathways
below detection on high-sensitivity assays
effectively exclude acute coronary syndrome. Once STEMI has been ruled out, patients with
Patients who presented with chest pain with an acute chest pain and suspected ACS require further
initial high-sensitivity troponin that was unde- risk stratification [25]. The ACC/AHA guidelines
tectable had a less than 1% risk of MI at 30-day recommend the use of clinical decision-making
follow-up. High-sensitivity troponin has utility pathways summarized in Table 31.3. Each of these
in noncoronary pathologies as well. Troponin pathways stratifies patients into low, intermediate,
can be elevated and acute pericarditis in up to and high risk to guide further workup in manage-
40% of cases. Elevated troponin may also be ment. No decision-making pathway is known to be
seen in the cases of acute aortic dissection and superior. Patients identified as low risk have a
pulmonary embolism. In the case of a pulmo- 30-day risk of death or major adverse cardiac
nary embolism, troponin elevation is a sign of events of <1% and are often safe to discharge from
RV strain, myocardial injury, and increased dis- the emergency department. Patients identified as
ease severity. Significantly elevated troponin intermediate risk may be managed in an observa-
with a nondiagnostic EKG also warrants consid- tion unit for cardiac monitoring, serial troponins,
eration for myocarditis. and additional diagnostic evaluation such as echo-
cardiography or stress testing (see Chap. 5).
Invasive coronary angiography is recommended
D-Dimer for patients who are recommended as high risk for
short-term major adverse cardiac events. This may
D-dimer is produced by the body by natural be identified by an elevated risk score in clinical
breakdown of clot. Therefore, this biomarker will decision-making pathway but also includes new
be elevated during the acute phase of thrombus. ischemic ECG changes, acute myocardial injury
D-dimer is recommended for use in low and identified by elevated troponin levels, new-onset
intermediate risk of PE. A patient with low or left ventricular dysfunction <40%, newly diag-
354 D. Stives and R. Musialowski

Table 31.3 Summary of current clinical decision pathways

HEART 2020 ESC/
pathway EDACS ADAPT NOTR hs-cTn 2015 ESC/GRACE
Variables History Age TIMI score Age History Age
used ECG Sex 0–1 Risk ECG HR, SBP
Age Risk factors No ischemicfactors hs-cTn Serum Cr
Risk factors History ECG Previous Cardiac arrest
Troponins Troponin changes AMI or ECG
Troponins CAD Cardiac biomarker
Troponin Killip class
Low risk HEART EDACS score TIMI score 0 Age <50 Initial Chest pain free and
score <3 <16 Troponin <3 risk troponin is GRACE <140
Negative Negative negative at 0 factors “very low” Sx <6 h and troponin
troponin at 0 troponin at 0 and 2 h Negative and symptom <ULN at 0 and 3 h
and 2–3 h and 2 h No ischemic troponin at onset >3 h Sx >6 h and troponin
No ischemic ECG 0 and 2 h prior <ULN on arrival
ECG changes changes OR
Initial
troponin is
“low” and 2 h
troponin
change is
“low”
Intermediate HEART NA TIMI score NA Initial 0 h high sensitivity
risk score 4–5 2–4 troponin is troponin = 12–52 ng/L or
between 1 h change = 3–5 ng/L
“low” and
“high”
High risk HEART NA TIMI 5–7 NA Initial high Initial high-sensitivity
score 7–10 sensitivity troponin >52 ng/L or 1 h
troponin is change >5 ng/L
“high”
Or
1 or 2 h high
sensitivity
troponin
change is
“high”
Performance AMI AMI AMI AMI AMI AMI sensitivity >99%
sensitivity sensitivity sensitivity sensitivity sensitivity
100% 100% 100% 100% >99%
Increased More patients More 28%
ED identified as patients eligible for
discharged low risk vs discharged ED
by 21% ADAPT (42% <6 h (19% vs discharge
Decreased vs 31%) 11%)
length of
stay by 12 h
Decreased
30-day
objective
testing by
12%
Adapted from 2021 AHA/ACC/ASE/CHEST/SAEM/SCCT/SCMR Guideline for the Evaluation and Diagnosis of
Chest Pain: A Report of the American College of Cardiology/American Heart Association Joint Committee on Clinical
Practice Guidelines
31 Acute Evaluation of Chest Pain 355

nosed moderate-severe ischemia on stress testing, testing or evaluation. Due to the broad etiologies
or hemodynamic instability. of chest pain with varying degrees of acuity,
patients with acute chest pain should be trans-
ported to the nearest ED by emergency medical
Management services. All patients should be evaluated
promptly, and an EKG should be obtained within
Even benign etiologies of chest pain may have minutes of patient presentation. After assessment
potentially life-threatening complications, i.e., of vital signs, it is reasonable to administer sub-
pericardial tamponade in pericarditis. As such, lingual nitroglycerin (0.4 mg every 3–5 min) and
assessment and stabilization of hemodynamics, 325 mg aspirin if there is initial concern for myo-
mentation, and airway should precede additional cardial infarction.

Initial Evaluation

Cardiac monitor
Intravenous access
Oxygen therapy

Differential diagnosis based on

history, physical, and EKG. Specific
testing based on findings

Aortic Pulmonary Tension Esophageal

Pericarditis
dissection embolism Pneumothorax rupture

-beta blockade -IV heparin or SQ -needle -IV fluid -US for

LMWH decompression effusion/tampo
-IV -analgesia nade
antihypertensive -thrombolysis if -tube
therapy severe thoracostomy -IV antibiotics -NSAIDS
cardiovascular -early surgical
-decrease -colchicine
instability consultation
contractility
-cardiology
-immediate
surgical
356 D. Stives and R. Musialowski

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of Cardiology/American Heart Association joint briefs/sb277-Top-R easons-H ospital-S tays-2 018.
committee on clinical practice guidelines. https:// pdf#:~:text=%E2%96%A0%20The%20most%20
www.jacc.org/doi/10.1016/j.jacc.2021.07.053?_ frequent%20principal%20diagnoses%20for%20
gl=1*1lf07hk*_ga*MTk3OTk1NDA3Ny4xNjM hospitalizations,stays%29%20and%20the%20
yODcwMzkx*_ga_2V8VW4Y237*MTY2MzQ1 costliest%20%28%2441.5%20billion%20in%20
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1979954077.1632870391 article-abstract/2468896
Part XI
Cardiovascular Disease in Pregnancy
Cardiovascular Disease
in Pregnancy
32
Cindy Sing and Malissa J. Wood

Introduction obstetricians, anesthetists, maternal-fetal medi-

cine experts, cardiologists, and nursing. The
In the USA, the leading cause of mortality in cardio-obstetrics team’s primary goal is to focus
pregnancy is cardiovascular disease, and the on the progress of the pregnancy and create a safe
numbers continue to rise despite global improve- delivery plan. Prompt referrals of pregnant
ments in healthcare. This is due to the increase in women with any type of cardiovascular disease
women surviving congenital heart disease to can improve outcomes [3].
childbearing age, the upsurge of pregnancies at
an advanced maternal age, chronic medical con-
ditions (obesity, hypertension, and diabetes mel- hysiological Changes During
P
litus), as well as disparities related to race and Pregnancy
ethnicity. To improve cardiovascular outcomes
and reduce maternal mortality, an early and spe- Expected hemodynamic and structural changes
cialized multidisciplinary cardio-obstetrics team during pregnancy include vascular adaptations,
is vital to render a comprehensive patient review hormonal changes, increases in heart rate (HR),
and counsel regarding maternal cardiovascular volume, and cardiac output (CO), increased
risks [1]. Counseling should ideally start prior to hypercoagulability and decreased systemic vas-
pregnancy, and preferably in specialized centers cular resistance (SVR) [3]. In pregnancy, the
managed by the cardio-obstetrics interdisciplin- renin-angiotensin-aldosterone system is acti-
ary team [2]. This team is usually comprised of vated, along with hormonal fluctuations, leading
to an increase in plasma volume, rise in CO, and
decrease in SVR [1]. An increase in blood vol-
ume compared to red cell mass results in normal
physiologic anemia. In early pregnancy, ejection
fraction (EF) increases, CO increases by 30–50%
C. Sing due to increased stroke volume, and SVR
Atrium Health Pulmonary and Critical Care
Consultants, Charlotte, NC, USA decreases via prostacyclin and nitric oxide (NO).
e-mail: [email protected] In the second trimester, CO is 50% above base-
M. J. Wood (*) line, increasing HR, minute ventilation, and pulse
Corrigan Minehan Heart Center, Massachusetts pressure. Blood pressure also starts to rise in the
General Hospital, Boston, MA, USA second trimester. Lastly, by the third trimester,
e-mail: [email protected] HR peaks about 15 bpm above baseline, EF

© The Author(s), under exclusive license to Springer Nature Switzerland AG 2023 359
R. Musialowski, K. Allshouse (eds.), Cardiovascular Manual for the Advanced Practice Provider,
https://doi.org/10.1007/978-3-031-35819-7_32
360 C. Sing and M. J. Wood

Fig. 32.1
Hemodynamic changes
in Pregnancy. (Yucel, E.,
DeFaria Yeh,
D. Pregnancy in Women
with Congenital Heart
Disease. Curr Treat
Options Cardio Med 19,
73 (2017). https://doi.
org/10.1007/
s11936-017-0572-0)

decreases, CO and SVR both increase thereby SCAD and most cases of ACS is that SCAD is
increasing BP above pre-pregnancy levels [4]. due to rupture of the vasa vasorum and intramural
See Fig. 32.1. hematoma formation with coronary dissection.
This is different from rupture of atherosclerotic
plaque and thrombosis. Hormonal changes are
Chest Pain in Pregnancy suspected to increase the risk for SCAD, as pro-
gesterone reduces collagen and elastin strength
The anatomic and physiologic changes described of the coronary arteries. Therefore, pregnancy,
above are often the main cause of chest pain and multiparity, breastfeeding, and fertility treat-
shortness of breath (SOB) in pregnancy. However, ments are also considered risk factors. While
these complaints require further investigation to P-SCAD only comprises a small amount of the
rule out pathologic conditions that can affect total number of SCAD cases, its worse prognosis
maternal and/or fetal health. Differential diagno- is due to having more proximal involvement
sis for chest pain during pregnancy include isch- along with involvement of multiple vessels,
emic heart disease such as spontaneous coronary resulting in larger myocardial injury. Most cases
artery dissection (SCAD), pulmonary embolism, of P-SCAD have been reported in the third tri-
musculoskeletal issues, gastrointestinal reflux mester or post-partum [6]. In P-SCAD, percuta-
disease (GERD), and acute coronary syndrome neous coronary intervention has been linked to
(ACS) [5]. An often-missed diagnosis in preg- iatrogenic dissections, propagation of existing
nant patients with chest pain is aortic dissection dissections, and low success rate. Therefore, con-
and therefore should also be considered in the servative management needs to be considered in
differential [1]. P-SCAD when patients are stable [7].
The most common symptoms of P-SCAD
include chest pain and SOB. One study revealed
pontaneous Coronary Artery
S that 75% of these patients presented with
Dissection (SCAD) ST-segment elevation MI (STEMI) and about
25% with non-STEMI. The most common loca-
Less than 1% of total hospitalizations for ACS tion of the STEMI was anterior and anterolateral.
are due to SCAD. However, pregnancy related Some of the patients with STEMI also developed
SCAD (P-SCAD) accounts for 2–8% of all ventricular fibrillation. The average left ventricu-
SCAD cases and a little over 40% of ACS cases lar ejection fraction (LV EF) was 40% to 49%,
in this population. The main difference between and cardiogenic shock was seen in approximately
32 Cardiovascular Disease in Pregnancy 361

25% of patients. These led to higher rates of fetal related morbidity and mortality. In the USA, the
and maternal mortality [7]. sixth leading cause of maternal mortality is PE
Catheter-based reperfusion therapy in SCAD [8].
is controversial, as one study shows over 50% of Having risk factors such as previous VTE,
patients with low success rate with percutaneous family history of VTE, obesity, smoker, pre-
coronary intervention (PCI) requiring emergency eclampsia, known thrombophilia, cesarean sec-
coronary artery bypass graft (CABG) surgery. tion, or immobility can heighten the risk of VTE
The reason behind this was higher incidence of during and after pregnancy [2].
complex coronary anatomy and hemodynamic
instability. Approximately a third of the patients Clinical Presentation
were managed conservatively and developed PE has a non-specific presentation during preg-
recurrent symptoms, eventually requiring revas- nancy as clinical signs and symptoms are similar
cularization procedures. Half of the patients in to normal physiologic changes (i.e., dyspnea,
this study were treated with aspirin, a third with a chest pain, tachycardia, and sweating). These
second antiplatelet agent (prasugrel or clopido- similarities make it challenging to identify PE
grel), and some with anticoagulation. Concerns and requires a high index of suspicion for a timely
for fetal and maternal safety must be weighed diagnosis [8].
against the potential benefits of these medica-
tions. Thrombolytic therapy is also controversial Diagnosis
due to the risk of dissection extension with Echocardiograms, arterial blood gases, and
approximately 60% of patients with SCAD- D-dimer levels are usually performed, however,
associated MI developing clinical deterioration they are neither sensitive nor specific diagnosti-
after thrombolytic therapy. These findings sug- cally during pregnancy. For example, respiratory
gest that a diagnosis without invasive procedures alkalosis is common in both PE and pregnancy.
and conservative management in stable low risk Additionally, d-dimer levels slowly rise with
pregnant women should be considered. Moreover, each trimester. An echocardiogram is sometimes
close, and long-term follow-up is recommended used in this population to evaluate the size of the
in women with P-SCAD, as many show persis- right ventricle after a PE is confirmed but this has
tence of SCAD or involvement of new vessels not been officially evaluated in pregnancy.
even at their 1-year follow-up visit. Lastly, future Echocardiograms are also used to rule out cardio-
pregnancies are not recommended in women myopathy related to pregnancy [8]. Therefore,
with P-SCAD due to the high incidence of recur- when the diagnosis cannot be confirmed or ruled
rence and coronary artery vulnerability [7]. out, a computed tomographic pulmonary angiog-
raphy (CTPA) or a lung scintigraphy (ventilation/
perfusion scan [V/Q]) should be performed. Both
Pulmonary Embolism in Pregnancy modalities provide radiation exposure to the fetus
(V/Q scan>CTPA) but below the limit considered
Venous thromboembolism (VTE) has a higher dangerous [2]. Thyroid function is the major con-
incidence both during pregnancy and in the post- cern of administering iodinated contrast, but
partum period. The highest risk of VTE occurs studies have shown an exceptionally low risk of
specifically after a cesarean section [2]. VTE can neonatal hypothyroidism secondary to fetal expo-
manifest as a lower extremity deep venous throm- sure to iodine [8].
bosis (DVT) or a pulmonary embolism (PE). Due to insufficient data on diagnostic modali-
VTE represents a significant cause of pregnancy ties, the following approach is suggested:
362 C. Sing and M. J. Wood

• All patients with respiratory symptoms con- anticoagulation is not possible, an IVC filter can
cerning for PE should undergo chest be used. IVC filter can also be used if significant
radiograph. bleeding has occurred, and anticoagulation needs
• In the context of a normal chest radiograph, to be stopped. Otherwise, if labor is unforeseen,
V/Q scan is both sensitive and specific for PE proceed with delivery [9].
diagnosis. Heparin is recommended for a minimum of
• If chest radiograph is abnormal or V/Q scan is 6 weeks after delivery and a total duration of
indeterminate, CTPA is suggested. 3–6 months. Long-term therapy can consist of
subcutaneous UFH, subcutaneous LMWH or
In certain circumstances, more than one coumadin. If the latter is selected, both warfarin
modality will be required, and it is often case spe- and heparin should be administered for a mini-
cific, depending on availability of tests, renal mum of 5 days until a therapeutic INR is reached.
insufficiency, allergies to contrast, and weight Warfarin is safe during breastfeeding but DOACs
limitations [8]. should be avoided. Side effects of heparin should
be closely monitored. These include osteoporo-
Treatment sis, heparin-induced thrombocytopenia, skin
Treatment for PE in pregnancy is unique. necrosis and bleeding. These can manifest with
Thrombolytics have a high risk of maternal hem- long-term use but also with prophylactic doses
orrhage and should only be used when acute PE [9].
is life-threatening. Initial considerations include
the following:
Musculoskeletal Chest Pain
• If there is low or moderate clinical suspicion
for PE, potential empiric anticoagulation A myriad of physiologic and anatomic changes
should be considered. occur during pregnancy. Some examples include
• -If there is a high clinical suspicion for PE, increase in chest wall diameters (anterior–poste-
anticoagulation is indicated even before diag- rior and transverse), subcostal angle, as well as
nostic evaluation. overall increase of the circumference of the chest
• If anticoagulation is contraindicated but PE is wall. These changes can impact the musculoskel-
suspected, prompt diagnostic evaluation is of etal system and can cause chest wall pain due to
utmost importance and if VTE is confirmed, hormonal changes, the new body habitus, and the
inferior vena cava filter is indicated. pressure from the uterus in the lower rib area.
• If only DVT is suspected, and diagnostics can One of the rare causes of pregnancy-specific
be done in a timely manner, hold anticoagula- musculoskeletal chest pain is rib fractures, often
tion therapy, particularly if diagnostic tests in those pregnant women with pregnancy-
confirm VTE. associated osteoporosis. If chest wall discomfort
occurs with other cardiac associated symptoms,
If anticoagulation (AC) is clinically indicated, prompt evaluation is paramount [10].
heparin should be started. The options available
include unfractionated heparin (UFH) either sub-
cutaneous or intravenous, as well as low molecu- GERD
lar weight heparin (LMWH). Avoid direct oral
anticoagulants (DOACs) as there is not enough GERD is common in pregnancy, reported in
information on their safety profile in pregnancy 40–85% of pregnant women in all three trimes-
and in some cases, miscarriage has been reported ters. It is unclear if the secretion of gastric acid is
[9]. See Table 32.1. shifted during pregnancy, but mechanical and
If a patient has decreased cardiopulmonary intrinsic factors affect the tone of the lower
reserve because of an acute PE, and stopping esophageal sphincter causing GERD. During all
32 Cardiovascular Disease in Pregnancy 363

Table 32.1 Anticoagulants for PE

Subcutaneous LMWH IV UFH Subcutaneous UFH
When to use • Preferred for initial AC in • Preferred in severe renal failure Preferred in severe renal
pregnancy • Preferred in patients with increased failure
• Higher efficacy risk of bleeding or persistent
• Better safety profile hypotension 2/2 PE because short
half-life
Weight • Enoxaparin 1 mg/kg q12h • Bolus of 80 units /kg • Initiate at 17,500 units
adjusted • Dalteparin 200 μ/kg daily • Then continuous infusion 18 units/ q12h
dosing • Tinzaparin 175 units/kg daily kg/hr. • Then titrate to reach
• Titrate every 6 h until therapeutic therapeutic aPTT level
aPTT level is reached
AC monitoring • Anti Xa level monitoring • Monitor AC activity • Monitor AC activity
controversial • Once therapeutic level is reached • aPTT first measured 6 h
• If given BID check levels 4 h monitor once or twice daily after second dose
after third and fourth • Once a stable dose is
• If given daily check levels reached, measure after
after second or third dose 3–4 days of treatment
• Recheck every 1–3 months • Then measure every few
after reaching adequate anti-Xa weeks
levels • Closer monitoring in last
10 weeks of pregnancy
Discontinue • Discontinue 24 h before • Discontinue 4–6 h before delivery
delivery, particularly if
epidural anesthesia will be
used
Restart after If no significant bleeding If no significant bleeding restart: If no significant bleeding
delivery restart: • 6 h after vaginal birth restart:
• 6 h after vaginal birth • 12 h after cesarean delivery • 6 h after vaginal birth
• 12 h after cesarean delivery • 12 h after cesarean
delivery

trimesters, the pressure of the lower esophageal tion in breastmilk. Preferred PPIs are
sphincter is lower than normal, and may be pantoprazole, omeprazole, lansoprazole if symp-
explained by hormonal changes, particularly in toms persist with H2RAs. Upper endoscopy
progesterone [11]. This relaxation allows the should be reserved for severe cases such as severe
food to “reflux” back up the esophagus from the gastrointestinal bleeding and postponed until the
stomach (with stomach acid) causing the burning second trimester if possible [13].
sensation. Indigestion can occur concurrently
with GERD and cause chest pain, that initially
starts in the epigastric region and moves upward Aortic Diseases
[12].
Initial management includes dietary and life- Aortic disease can present prior to or during
style modifications including avoiding dietary pregnancy and the hemodynamic and hormonal
triggers (mint, chocolate, tomatoes, oranges), as changes of pregnancy can result in further aortic
well as elevating the head of the bed. If symp- enlargement. Most of the pregnancy-related aor-
toms persist, treatment should begin with antac- tic dissections involve the ascending aorta and
ids, alginates, or sucralfate. These are safe both in occur in the third trimester (50%) or the post-
pregnancy and while breastfeeding. If symptoms partum period (33%). Heritable thoracic aortic
are still not well controlled, histamine 2 receptor disorders that predispose patients to aortic dis-
antagonist (H2RA) and proton pump inhibitors section or aneurysm formation include Marfan
(PPI) can be used. PPIs are safe during preg- syndrome, Ehlers-Danlos syndrome, bicuspid
nancy, but not enough data exist on their secre- aortic valve, and other familial forms of aortic
364 C. Sing and M. J. Wood

Table 32.2 Heritable disorders that affect the thoracic aorta

Disorder Risks/Risks factors Considerations/management
Bicuspid 50% of patients have dilatation of ascending • Distal part of ascending aorta, not visualized by
aortic valve aorta. Dissection less often than Marfan’s echo, MRI or CT before pregnancy. If diameter
>50 mm, consider pre-pregnancy surgery
Ehlers- Exclusive to autosomal dominant trait type • Increased bruising
Danlos IV-so pregnancy is contraindicated. Rupture of • Prophylactic surgery not well established because
syndrome large vessels or uterus may occur it can lead to poor wound healing, tissue fragility
and increase hemorrhage
• Early cesarian delivery advised
Turner Prevalence of cv malformations 25–50% • If the diameter is >27 mm, consider pre-
syndrome Dissection risk is higher if other risk factors pregnancy surgery
such aortic dilatation, HTN etc.

dissection. Advanced maternal age and hyperten- blockers should also be taken in the peripartum
sion are common risk factors for aortic pathol- period. When the mother is on beta blockers, the
ogy. Pregnant patients at elevated risk for aortic growth of the fetus should be closely monitored.
complications include those with previous aortic If dilatation progresses during pregnancy before
dissection. Patients with known familiar aortic a viable fetus, an aortic repair with fetus in utero
pathology or diagnosed with Marfan syndrome, should be considered. Once the fetus is viable,
should have counseling, a thorough evaluation, the recommendation is cesarean section followed
and imaging of the aorta prior to pregnancy as by aortic surgery in a hospital with a specialized
they are at higher risk for dissection [1]. cardio-obstetrics team available. Ascending aor-
tic dissection is considered a surgical emergency.
Marfan Syndrome For patients with ascending aorta enlargement,
The diameter of the aortic root of those patients with an aorta diameter > 40–45 mm, it is recom-
with Marfan syndrome determines risk and man- mended that they undergo vaginal delivery with
agement. For example, those with a normal diam- regional anesthesia to prevent increases in blood
eter have a 1% risk of severe complications or pressure. If necessary, cesarean section is also
dissection. However, when the diameter is advised, particularly in those with a diameter
>40 mm, the risk for dissection increases. >45 mm [1]. See Table 32.2.
Moreover, pregnancy is not recommended when
the diameter is >45 mm, particularly for those
with a family history of dissection, as life- Hypertension in Pregnancy
threatening aortic dissection may occur. Other
potential complications include worsening of In the USA, hypertensive disorders of pregnancy
mitral regurgitation that can further lead to heart are common, and the number of cases has
failure or supraventricular arrythmias [1]. increased over the last five decades. Factors con-
tributing to this increased rate include older
Management maternal ages (>35 years), diabetes, and obesity
Typically, pregnant patients with aortic disease [14]. Maternal risks of pregnant women with
undergo echocardiogram at 4–12-week intervals chronic hypertension include pulmonary edema,
depending on the diameter of the aorta as well as renal failure, cerebrovascular accidents (CVA),
at 6 months after delivery. These patients require gestational diabetes, and disseminated intravas-
specialized supervision by a team aware of the cular coagulation. These risks were 5–6 times
potential complications. Beta blockers have been more likely to occur in this population than in
used in Marfan’s disease to reduce the rate of aor- those pregnant women without hypertension.
tic dilatation and prevent dissection, although Chronic hypertension in pregnancy also has been
recent studies do not confirm this benefit. Beta correlated with worse perinatal outcomes [15].
32 Cardiovascular Disease in Pregnancy 365

The fetus is at risk of growth restriction, con- Pre-eclampsia

genital abnormalities, preterm labor, placental
abruption, and fetal demise. These risks were This occurs when the systolic blood pressure is
2–4 times higher than in non-hypertensive ≥140 mmHg or diastolic blood pressure is
women [14]. ≥90 mmHg in previously normotensive women,
Two confirmed elevated blood pressure read- after 20 weeks of gestation, with evidence of pro-
ings (SBP ≥140 or DBP ≥90) on two separate teinuria (≥30 mg/mmol urinary creatinine in a
occasions are necessary for the diagnosis of random urine sample or ≥0.3 g/day in a 24 h
hypertension in pregnancy. It is recommended to urine collection) as well as poor organ perfusion.
monitor these women with basic laboratory stud- This typically resolves within 42 days post-
ies including liver enzymes, urinalysis, blood partum [2]. Compared to normal cohorts, women
count, hematocrit, serum uric acid, and serum with pre-eclampsia have a >70% increased risk
creatinine. If there is suspicion of pheochromo- of mortality due to CVD, fourfold increased risk
cytoma, ultrasound of the adrenals as well as of heart failure, and a little over twofold increased
urine catecholamine assays (urine metaneph- risk of coronary disease. Pre-eclampsia also
rines) should be considered, as this can be fatal if occurs more frequently during the first preg-
not diagnosed before labor. Also, a doppler ultra- nancy, in women with diabetes or in pregnancies
sound of the uterine arteries after 16 weeks gesta- with multiple fetuses. It is the most common
tion can be used to detect uteroplacental cause of prematurity [2].
hypoperfusion associated with a higher risk of Signs and symptoms of severe pre-eclampsia
pre-eclampsia [2]. include right upper quadrant pain secondary to
Classifications by the American College of liver fullness, occipital lobe blindness, visual dis-
Obstetricians and Gynecologists (ACOG) of turbances accompanied by headaches (cerebral
hypertensive disorders include chronic hyperten- edema), clonus/hyperreflexia, pulmonary edema,
sion, pre-eclampsia/eclampsia, gestational hyper- elevated creatinine without other etiology, and
tension, and chronic hypertension with HELLP syndrome (hemolysis, elevated liver
superimposed pre-eclampsia [1]. Please see enzymes, and low platelet count). Management
Table 32.3. focuses on recognizing the condition and deliv-
ery of the placenta [2].

Table 32.3 Definitions of hypertensive disorders Eclampsia

Type of HTN Diagnostic criteria
Chronic HTN BP ≥ 140/90 mmHg Defined as new onset of a clonic-tonic seizure in
Present before 20 weeks of women with pre-eclampsia, typically lasting
gestation 60–90 s. Seizures can happen antepartum,
Gestational HTN BP ≥ 140/90 mmHg
20 weeks after gestation, during delivery and up
Onset after 20 weeks
gestation to 6-weeks post-partum. This is a serious compli-
Preeclampsia BP ≥ 140/90 mmHg cation of pre-eclampsia related to increased mor-
Onset after 20 weeks with bidity and mortality of both mother and fetus
proteinuria when it is not recognized or diagnosed promptly
Severe preeclampsia BP > 160/110 mmHg [16].
Excessive proteinuria
Chronic HTN with BP ≥ 140/90 mmHg
superimposed Present before 20 weeks of
preeclampsia gestation Pre-existing Hypertension
New onset proteinuria
Adapted from the American College of Obstetricians and Defined as BP 140/90 mmHg present before
Gynecologists (ACOG) pregnancy or develops before 20 weeks of gesta-
366 C. Sing and M. J. Wood

tion and persist >42 days after delivery. This may not recommended in pre-eclampsia. In the multi-
go unrecognized in women not previously center Chronic Hypertension and Pregnancy
diagnosed with hypertension because the physi- (CHAP) trial, 2408 pregnant women enrolled at
ological decrease in BP in the first trimester. <23 weeks of gestation with non-severe chronic
hypertension were randomly assigned to receive
antihypertensive therapy at a threshold of
Pre-existing Hypertension 140/90 mmHg (active treatment) or no treatment
with Overlapping Gestational until development of severe hypertension (sys-
Hypertension tolic BP ≥ 160 or diastolic BP≥ 105 mmHg). The
rate of the primary composite outcome (pre-
This occurs when pre-existing hypertension is eclampsia with severe features, medically indi-
concomitant with BP worsening and protein cated preterm birth at <35 weeks of gestation,
excretion ≥3 g/day in 24-hour period after abruption, or fetal or neonatal death) was reduced
20 weeks’ gestation. About a quarter of these in the active treatment group and was not associ-
cases proceed to pre-eclampsia and it is vital to ated with a significant difference in rates of fetal
recognize for long-term prognosis. growth restriction or serious neonatal or maternal
morbidity [17].
Treatment When severe hypertension is confirmed (blood
A strategy with a multidisciplinary team to pressure ≥160/110 mmHg that persists for
include lifestyle changes such as diet, exercise, 15 min) prompt treatment should be started to
smoking cessation, and algorithms targeting car- decrease the risk of maternal heart failure, renal
diovascular risk factors was recently highlighted disease, MI, or stroke. A rapid IV infusion is rec-
by both ACOG and AHA. Many studies have ommended with reduction of BP within 60 min,
suggested regular exercise can improve vascular avoiding DBP below 80 mmHg, to prevent inter-
function and prevent pre-eclampsia, but more ruption of placental blood flow. In these cases,
studies are needed to analyze the possible rever- treatment with intravenous hydralazine or labet-
sal of endothelial dysfunction [1]. alol is recommended. Hydralazine is slower in
Other non-pharmacologic strategies include onset and longer in duration. Immediate-release
low impact exercise, a normal diet without dose nifedipine is the drug of choice if no imme-
sodium restriction, especially when close to diate IV access is available. When there is pulmo-
delivery as it may reduce intravascular volume. nary edema associated with pre-eclampsia, the
In pre-eclampsia, delivery of the fetus at 37 weeks drug of choice is IV nitroglycerin. Intravenous
should be considered with the hope of preventing magnesium sulfate is recommended to prevent
peripartum pre-eclampsia. Lastly, for obese eclampsia as well as treating seizures. First-line
women, aggressive weight loss is not recom- antihypertensive medications include methyl-
mended [4]. dopa, labetalol and nifedipine for less severe
For those with pre-existing hypertension, con- hypertension. Second line antihypertensive agent
sider continuing their current therapy except for include hydrochlorothiazide [1].
direct renin inhibitors, angiotensin receptor Assume all antihypertensive agents are pres-
blockers (ARBs) or angiotensin-converting- ent in breast milk [4]. It is also important to mon-
enzyme inhibitors (ACE-Is) due to severe toxic- itor BP in the first 1–2 weeks post-partum and
ity to the fetus, particularly in the second and continue antihypertensive therapy for those with
third trimesters [2]. Monitor for pre-eclampsia if persistent hypertension (≥150/110 mmHg).
medications are discontinued. Avoid diuretics as Lastly, adjust to maintain a BP not higher than
it reduces the blood flow to the placenta and are 150/110 mmHg [1].
32 Cardiovascular Disease in Pregnancy 367

Arrhythmias maneuvers [19]. Stable supraventricular tachy-

cardias should be treated the same way as that in
Studies have shown that there has been an the nonpregnant patient (see Chap. 9). If vagal
increase in the number of pregnancy related hos- maneuvers do not work, proceed to use intrave-
pitalizations due to arrhythmias because of the nous adenosine (first choice). If adenosine fails,
increase advanced maternal age, particularly in then IV metoprolol is recommended to terminate
women between 41 and 50 years old [1]. the tachycardia. For intolerable symptoms or if
Sustained tachyarrhythmias and premature extra tachycardia leads to hemodynamic compromise,
beats become more frequent and sometimes man- use prophylactic antiarrhythmic drugs [1]. Wolf-
ifest for the first time during pregnancy. While Parkinson-White (WPW) syndrome can also fur-
most palpitations are benign, new onset ventricu- ther deteriorate during pregnancy and IV
lar tachycardia (VT) is worrisome and should be procainamide is typically used for wide-complex
further investigated for possible structural heart tachyarrhythmias. If medical therapy fails, con-
disease [2]. Palpitations secondary to atrial and sider catheter ablation for atrial arrythmias, ide-
ventricular ectopy as well as sinus tachycardia ally with minimal exposure to radiation and only
(ST) are usually benign, self-terminating and if medical therapy does not work, during preg-
resolve without pharmacological treatment. nancy [2].
However, a cardio-obstetrics team should be used When hyperthyroidism or structural heart dis-
to manage more complex arrythmias as this may ease are present during pregnancy, atrial flutter
require not only antiarrhythmic therapy but also and atrial fibrillation may also be present. During
radiofrequency ablation or other electrophysio- pregnancy, life-threatening ventricular arryth-
logical studies [2]. mias are uncommon [1].
Arrhythmias during pregnancy are often
attributed to hormonal, hemodynamic, and auto-
nomic changes. For example, the rise in intravas- Fetal Arrhythmias
cular volume increases preload on the ventricles
and in turn increases the size of the atria and ven- While fetal arrhythmias have been reported to
tricles. Moreover, increase in myocardial stretch occur in up to 1% of pregnancies, sustained
can initiate arrythmias [18]. arrhythmias are much less common and occur in
Antiarrhythmic drugs should be assumed to approximately 0.1% of pregnancies. The most
be potentially toxic to the fetus, which is a major encountered fetal arrhythmias include supraven-
concern. The greatest teratogenic risk is during tricular tachycardia (SVT), atrial flutter, and
the first trimester, however, other adverse effects atrial tachycardia. Propranolol is the usual first-
on fetal growth and development later in preg- line agent for fetal tachycardia. Flecainide may
nancy can also occur including the increased risk also be used in fetal SVT, particularly in refrac-
of pro-arrhythmia. Patients with congenital heart tory or complicated cases. Other drugs that have
disease during pregnancy are more likely to been successfully used in the management of
develop supraventricular and ventricular arrhyth- fetal arrhythmias include digoxin and sotalol.
mias requiring treatment. For example, atrial flut- Procainamide is also safe to use in pregnancy but
ter is not well tolerated and can lead to is less commonly used to treat fetal arrhythmias
hypoperfusion of the fetus [1]. [20, 21].
Supraventricular tachycardia (SVT) is the
most prevalent arrhythmia during pregnancy. For
those women with no pre-existing structural heart Syncope
disease the most common cause behind paroxys-
mal SVT is atrioventricular nodal reentrant Also known as transient loss of consciousness,
tachycardia (AVNRT). AVNRT during pregnancy syncope may be due to many clinical conditions
should be initially treated with the use of vagal ranging from benign vasovagal episodes to more
368 C. Sing and M. J. Wood

serious and potentially deadly conditions such as pression. Infrequently, leg edema can be due to a
arrythmias. The incidence of syncope during DVT, which can be life-threatening if it dislodges
pregnancy is approximately 1%. Prognostic causing a PE [24].
information tends to correlate with timing of the When DVT occurs, it typically affects the left
syncopal episodes during pregnancy. For exam- leg because the growing uterus compresses the
ple, higher preterm births were found when the left iliac vein at the point where it crosses the
first syncopal episode occurred during the first right iliac artery [2]. DVT is manifested by leg
trimester. Moreover, syncope during pregnancy pain, erythema, or heaviness, particularly felt
seemed to correlate with higher rates of syncope when standing up [24]. When DVT is suspected,
and cardiac arrythmias 1-year post-partum, when the diagnostic imaging of choice is compression
compared to those women without syncope dur- ultrasound. This test has a high specificity and
ing pregnancy [22]. sensitivity for proximal DVT but less for distal
During pregnancy, the expectant mother DVT. If a proximal DVT is detected, treatment
undergoes many hemodynamic changes that pre- should be initiated (see Chap. 27) [2].
disposing her to the development of syncope. Moreover, excessive swelling can be a sign of
These changes include decreased systemic vas- pre-eclampsia when it occurs along with facial
cular resistance secondary to a vasodilatory state, edema, elevated blood pressure, protein in the
eccentric hypertrophy of the left ventricle, as urine and rapid weight gain [25].
well as increased heart rate and blood volume. To help prevent edema during pregnancy,
These changes can lead to an exaggerated vaso- women can elevate their legs, stay active by
vagal response. Other potential causes include walking or swimming, avoid prolonged periods
inferior vena cava compression by the enlarged of sitting or standing, avoid stockings that are too
uterus causing reduced venous return to the heart restrictive, sleep on the left side preferably and
or stimulation of the nerve plexus (behind the wear comfortable shoes [24].
uterus) [22].
Some arrythmias that may result in syncope
during pregnancy include Mobitz type II block Peripartum Cardiomyopathy
below the AV node and congenital complete heart
block. There is no clear association between Pregnancy-associated cardiomyopathy, also
pregnancy and complete heart block. Moreover, known as peripartum cardiomyopathy (PPCM),
syncope in pregnancy is rarely caused by severe is a rare cause of heart failure typically toward
arrythmia. For those women with a high degree the end of pregnancy or 5 months post-partum,
AV block and symptoms (such as syncope), inpa- without another identifiable cause of heart failure
tient monitoring and implantation of a pacemaker and with a left ventricular ejection fraction (EF)
is recommended. The most frequent concern in of <45% [26]. Predisposing factors include fam-
these cases is the exposure to radiation due to the ily history, smoking, ethnicity, pre-eclampsia,
use of fluoroscopy during implantation. However, diabetes, hypertension, multiparty, advanced
the average radiation dose to the fetus is <1 mGy maternal age, malnutrition, multiple childbirths
which has not shown to increase the risk [23]. as well as prolonged use of beta agonists. Heart
failure in PCCM can develop briskly and though
it is rare, it can result in severe complications [2].
Edema Signs and symptoms of PPCM can be vary
and may be like other forms of heart failure.
More than half of pregnant women are affected These may include dyspnea, orthopnea, cough,
by edema, starting around weeks 22 and 27 of paroxysmal nocturnal dyspnea, pedal edema,
gestation. This is due to the increase in body flu- hemoptysis, displaced apical impulse, elevated
ids because of increase in total blood flow, and jugular venous pressure, a third heart sound as
venous congestion from superior vena cava com- well as a mitral regurgitation murmur [26].
32 Cardiovascular Disease in Pregnancy 369

Treatment after diagnosis. For women with persistent symp-

Women with PCCM during pregnancy require a toms and severe LV dysfunction 6 months after
specialized team of obstetric and cardiac care, initial presentation, despite optimal medical
considering possible adverse effects on the fetus. treatment, consider implantable cardioverter
For those women with advanced heart failure defibrillator (ICD) or cardiac resynchronization
with hemodynamic instability, and urgent deliv- therapy. Also, for women who do not recover
ery should be considered. Once the baby is deliv- after 6–12 months of mechanical circulatory sup-
ered, and hemodynamic stability is reached, port, heart transplant should be considered [2].
standard therapy for heart failure can be applied.
For example, anticoagulation should be started Delivery
immediately following delivery of the baby (and If the patient is hemodynamically stable, vaginal
after bleeding has stopped) as those with a low delivery is preferred over cesarean delivery with
EF tend to have peripheral embolism including close hemodynamic monitoring. The preferred
ventricular thrombi and cerebral embolism. This method of analgesia is an epidural. With advanced
is secondary to the increase in procoagulant heart failure and hemodynamic instability despite
activity in the peripartum stage [2]. medical treatment, consider urgent delivery
Echocardiogram and EKG should be completed regardless of gestation duration. In this case,
[26]. See Table 32.4 for medical treatment. cesarean section with both spinal and epidural
Consider transferring to a facility with a spe- anesthesia is recommended [2].
cialized cardio-obstetrics team for those that are
inotrope dependent as interventions such as ven- ounseling for Future Pregnancy
C
tricular assist device (VAD), balloon pump coun- Contraception choices and risk for future preg-
ter pulsation or transplant consults may be needed nancies should be part of the education for those
[2]. with PCCM as successive pregnancies have a
The prognosis of PCCM is different from 30–50% risk of recurrence of PCCM. Subsequent
other cardiomyopathies such as dilated cardio- pregnancies should be discouraged when the EF
myopathy (DCM) as most patients with PCCM has normalized [2].
have a normalization of their EF within 6 months

Table 32.4 Treatment for PCCM in pregnancy

ulmonary Edema Post-Delivery
P
with Normal LV Function
Medical • To reduce afterload, use
Treatment hydralazine and nitrates instead of
ACE-I Approximately 0.5% of women experience acute
• If inotropes needed use dopamine pulmonary edema during pregnancy as well as
and levosimendan post-partum and can be due to pre-eclampsia or
• Beta-1 selective drugs
(metoprolol) are preferred iatrogenic volume overload. In the post-partum
• Diuretics only if pulmonary period, pulmonary edema involves a complex
congestion (furosemide and HCTZ) chain of events including increased vascular per-
Avoid • ACE-I, ARBS and renin inhibitors meability, increased intravascular hydrostatic
during pregnancy because of
fetotoxicity
pressures, decreased intravascular colloid
• Atenolol osmotic pressures that can lead to fluid extravasa-
• Aldosterone antagonist tion into the pulmonary interstitium [27].
During • If ACE-I needed, enalapril, In one study, half of the cases of pulmonary
breastfeeding captopril, and benazepril are
edema were due to cardiac disease or tocolytic
preferred
Anticoagulation • For those with low EF LMWH or medications (terbutaline) used to inhibit preterm
oral anticoagulation labor [27]. Beta 2 adrenergic receptors are stimu-
• For those with intracardiac lated with the use of tocolytics. This increases
thrombus and/or atrial fibrillation cardiac output and pulse rate leading to hemodi-
370 C. Sing and M. J. Wood

lution. Uterine contractions during delivery cause Potential risk factors include pre-eclampsia/
autotransfusion, increasing venous tone and eclampsia, abnormalities of the placenta, cesar-
blood pressure resulting in pulmonary edema ean delivery, or instrumented vaginal delivery.
post-partum [27]. The use of tocolytics is more Signs and symptoms develop abruptly and prog-
frequent in multiparity or maternal infections. ress rapidly including sudden hypotension,
Tocolytic pulmonary edema is usually caused by hypoxia, and cardiorespiratory compromise.
fluid overload from large IV fluid amounts Many times, this may be followed by non-
administered when peripheral vasodilatation cardiogenic pulmonary edema and bleeding
causes hypotension. However, increased perme- related to disseminated intravascular coagulopa-
ability of the capillaries and cardiac dysfunction thy [29].
can also contribute to the overall pulmonary For unstable patients, a specialized multi-
edema [28]. disciplinary approach should be used, focusing
Signs and symptoms of tocolytic-related pul- on controlling hemorrhage, performing high-
monary edema include basilar crackles, tachycar- quality CPR, excluding other etiologies and
dia, hypoxemia, dyspnea, tachypnea and delivery of the fetus. Initial testing to exclude
occasionally chest pain, fever, and cough. Chest other etiologies include EKG, bedside ultra-
X-ray shows airspace disease bilaterally [28]. sounds, portable chest-X-ray, CBC with plate-
Women receiving tocolytic medications who lets, CMP, BNP, ABG, blood type and screen,
develop the signs above, without an alternative troponin. After delivery and once patients are
explanation, are diagnosed with tocolytic-related stable, it is recommended to monitor closely in
pulmonary edema. Most women respond well to the intensive care unit as many patients may
supplemental oxygen, discontinuation of toco- require intubation, fluid resuscitation, vaso-
lytic therapy, diuresis, and fluid restriction. Most pressors, as well as venous or arterial access
cases resolve within 24 hours, but mechanical [29].
ventilation may be needed. Tocolytic use of cal- AFE is a leading cause of maternal mortality
cium channel blockers like nifedipine and nicar- and those who survive have a poor prognosis.
dipine can also result in pulmonary edema [28]. Hypoxemia causes about half of the deaths, and
others die from cardiac arrest or cardiogenic
shock [29].
Amniotic Fluid Embolism (AFE)
Clinical Pearls
An unusual and potentially fatal condition in the • Coronary artery dissection in pregnancy is
peripartum period is amniotic fluid embolism. often treated conservatively but some women
This occurs after the woman’s exposure to an need CABG. PCI is high risk.
unknown stimulating antigen with symptoms of • Future pregnancies are not recommended with
sudden hypoxia, seizures, and cardiovascular P-SCAD due to high recurrence risk.
collapse, in the absence of other explanations • Risk of VTE is highest after c-section.
[29]. • In PE, heparin is used, rather than DOACs.
The pathogenesis of this rare condition is not • In HTN in pregnancy, ACE-I and ARBs should
clear, but AFE occurs after the amniotic fluid be avoided as they cause severe toxicity to the
enters the maternal systemic circulation when the fetus.
breach of maternal/fetal interface results in a sys- • Arrhythmias, most frequently SVT, are com-
temic inflammatory response. This in turn, causes mon in pregnancy.
an acute increase in pulmonary pressure, increas- • Pregnancy-related cardiomyopathy can cause
ing RV pressure and RV failure from cellular com- heart failure from the end of pregnancy up to
ponents and debris from the amniotic fluid [29]. 5-months post-partum.
32 Cardiovascular Disease in Pregnancy 371

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Index

A American College of Cardiology and American Heart

Abdominal aortic aneurysms (AAAs), 289, 291, 292 Association and (ACC-AHA), 214, 244, 333,
Ablation procedures, 126 351
Abnormal automaticity, 110 Amniotic fluid embolism (AFE), 368
ACHD Care Center, 325 Amyloidosis, 203, 204
Acute aortic dissection, 297, 346 Aneurysmal degeneration of the aorta, 289
Acute aortic insufficiency, 158 Aneurysm surveillance AAA, 293
Acute coronary syndrome (ACS), 21, 23, 29, 255 Aneurysms, 289
NSTEMI (see Non-ST-elevation myocardial indication for surgical intervention, 293
infarction (NSTEMI)) size, 290, 293
Acute heart failure, 219 Angina, 43, 44, 46
Acute mitral insufficiency, 163–164 Angiotensin-converting enzyme inhibitors (ACEIs), 211
Acute myocardial infarction, 115 Angiotensin receptor blockers (ARBs), 211
Acute pulmonary embolism, 231, 348 Angiotensin receptor-neprilysin inhibitor (ARNIs), 211,
anticoagulation, 233 212
catheter-based Intervention, 233 Ankle-and toe-brachial index pressures, 282
classification, 232 Ankle-brachial index (ABI), 280
EKG, 233 Antianginal therapies, 45–46
intermediate-risk PE patients, 232 Antiarrhythmic agents, 60–73
management, 233, 234 Antiarrhythmic drugs (AAD), 365
mechanical circulatory support, 234 therapy, 114
multidisciplinary PE response teams Anticoagulation (AC), 101, 105, 360
(PERT), 233 for PE, 361
pharmacologic hemodynamic support, 233 therapy, 59–76
physical exam findings, 232–233 Anti-impulse therapy, 297
physiology, 231–232 Antiplatelet agent (prasugrel or clopidogrel), 359
presentation, 232 Antithrombotic therapy, TEER, 167
risk factors, 232 Aortic aneurysms, 289, 290, 292
risk stratification, 232 morphology and location, 291
scoring systems, 232 Aortic bioprosthetic/mechanical valve dysfunction, 157,
signs and symptoms, 232 158
surgical pulmonary embolectomy, 233–234 Aortic disease, 361, 362
systemic fibrinolysis, 233 Aortic dissection, 295–298, 348
treatment, 233 Aortic stenosis (AS), 148–150
Acute type A aortic dissections, 298 murmur, 150
Adenosine A1 receptor activators, 67 Aortic valve diseases
Adrenergic nervous system, 195 aortic cusps and origin of coronary arteries, 147
Adults with congenital heart disease, 302 cardiac catheterization, 150
Advanced heart failure therapies, 213–214 cardiac CTA, 153
for PE, 233 CT, 150
Advanced/high-grade AV heart block, 80, 81 evaluation/management, 150
Afferent pain fibers, 345 preoperative work up, 154

© The Editor(s) (if applicable) and The Author(s), under exclusive license to Springer Nature 373
Switzerland AG 2023
R. Musialowski, K. Allshouse (eds.), Cardiovascular Manual for the Advanced Practice Provider,
https://doi.org/10.1007/978-3-031-35819-7
374 Index

Aortic valve endocarditis, 188 Atrioventricular valves (AV), 4–8, 10

Aortic valve pre-intervention testing, 153–154 Atrium health vascular laboratory standardization values,
Aortic valve replacement (AVR), 156 273
Aortobifemoral bypass, 282 Autogenous-vein conduit bypass, 282
Aorto-enteric fistulas, 126 Autonomic inhibitors and activators, 65
Arrhythmias, 109, 365 AV node reentry tachycardia (AVNRT)
during pregnancy, 365, 367 anatomy and physiology, 92, 94, 95
Arrhythmogenic right ventricular cardiomyopathy atypical, 92
(ARVC), 110, 208, 209 imaging, 93
Arterial duplex ultrasound, 281 management, 93–96
Arterial walls, 289 pathology/description, 95
Aspirin, 340 physical examination, 93
Asymmetric pulses, 347 typical, 92
Asymptomatic effusions, 250
Atherosclerosis, 279
Atherosclerotic cardiovascular disease (ASCVD), 329 B
Atherosclerotic plaques, 21, 270 Balloon pulmonary angioplasty (BPA) and medical
Atrial fibrillation, 91, 96–99, 101–107 therapy, 228
anatomy and physiology, 102 Beta blockade, 114
definition, 102 Beta blockers, 45, 211
imaging, 103, 104 therapy, 293
management, 221 Bicuspid aortic valve (BAV), 147, 148, 161, 309, 310
anticoagulation, 105 Bioprosthetic aortic stenosis, 157
rate control, 103 Bioprosthetic aortic valves, 157
rhythm control, 104, 105 Bioprosthetic insufficiency, 158
stroke, 106 Bioprosthetic thrombosis, 157
physical exam correlation, 102 Biphasic pattern of BNP elevation, 200
Atrial flutter Biventricular ICD, 133
anatomy and physiology, 99 Blood pressure, 110
imaging, 99, 100 definitions, 338
management, 101 monitoring, 125
acute, 101 Blood tracking outside aorta, 243
anticoagulation, 101 Brachiocephalic artery, 269
ongoing, 101, 102 Bradycardia
Atrial functional MR (AF MR), 167 atrioventricular (AV) block, 78
Atrial septal defect (ASD) advanced/high-grade AV block, 80, 81
ACC/AHA guidelines, 307 first-degree heart block, 78, 79
anatomy, 305 second-degree heart block, 79, 80
long term surveillance, 307 third degree/complete heart block, 80, 81
management, 307 causes, 78
pathology, 306–307 clinical pearls, 85
physical exam, 306 conduction abnormalities, 82
physiology, 305 evaluation and management, 84
types, 305–306 left anterior fascicular block, 83
Atrial septostomy, 231 left bundle branch block, 83
Atrial tachycardia right bundle branch block, 82
anatomy and physiology, 89 sinus node dysfunction
imaging, 89–91 chronotropic incompetence, 78
management sinus bradycardia, 77
focal atrial tachycardia, 91–92 sinus pause, 77
multifocal atrial tachycardia, 92 Brain natriuretic peptide (BNP), 256
pathology, 89 Broken heart syndrome, 209
Atrio-esophageal fistula (AE), 126 Brugada syndrome (BrS), 117, 120, 121
Atrioventricular (AV) block Bruit, 11
advanced/high-grade AV heart block, 80, 81
first-degree heart block, 78, 79
second-degree heart block, 79, 80 C
third degree/complete heart block, 80, 81 Calcium channel blockers, 46
Atrioventricular node (AVN), 6, 7 Carcinoid heart disease, 175
Index 375

Cardiac amyloidosis, 149, 204 tobacco use, 340

Cardiac anatomy, 7, 8 risk of, 329
Cardiac brain natriuretic peptide (BNP), 351 risk-enhancing factors, 330–332
Cardiac channelopathies Cardiomyocyte loss, 195
Brugada syndrome (BrS), 120, 121 Cardiomyopathies, 200
catecholaminergic polymorphic ventricular related to pregnancy, 359
tachycardia (CPVT), 121, 123 Cardio-obstetrics interdisciplinary team, 357
long QT Syndrome (LQTS), 117–119 Cardiovascular disease
short QT Syndrome (SQTS), 119 outcomes and maternal mortality reduction, 357
Cardiac cirrhosis, 179 in pregnancy
Cardiac cycle, 4, 6, 10, 13–16 at advanced maternal age, 357, 362
Cardiac index (CI), 13, 14, 260 anatomic and physiologic changes, 358
Cardiac ischemia, 112 antepartum, 363
Cardiac MRI (CMR), 205 counselling, 357
Cardiac output (CO), 13, 14 hemodynamic changes, 357, 358
Cardiac resynchronization therapy (CRT), 213 hormonal changes, 358
Cardiac sarcoidosis, 110 mortality in, 357
Cardiac tamponade, 250 postpartum, 363
Cardiogenic shock (CS) structural changes, 357
B-lines, 259 Cardiovascular syncope
cellular and tissue hypoxia, 255 diagnostics, 140
chest X-ray, 259 management, 141
classification, 255, 256 pathophysiology, 139
clinical presentation, 257 physical exam, 140
continuous blood pressure management, 259 symptoms, 139, 140
continuous hemodynamic monitoring, 259 Cardiovascular system, 9–11
decreased myocardial contractility, 256 Cardioversion
differentiating SVO2 and ScVO2, 260 electrical cardioversion, 137
electrocardiogram, 258 pharmacologic cardioversion, 137, 138
end-organ damage, 258 Carotid anatomy, 270
etiology, 255 Carotid artery duplex, 52
identification and management, 258 ultrasound (US), 273
long term care, 261–262 Carotid artery stenosis
management, 260 carotid bruit, 272
mechanical ventilation, 259 causes of, 270
medical history, 257 development of atherosclerosis, 270
pathophysiology, 256–257 diagnostic tests, 272
physical exam findings, 257 hemodynamics of arterial flow, 270
point-of-care ultrasound (POCUS) exam, 258 historical features, 271
tissue perfusion, 259 management, 274–275
volume overloaded, 259 turbulent flow, 271
Cardiometabolic disease with/without neurological symptoms, 271
prevention of Carotid duplex ultrasound (DUS), 272, 273
ACC/AHA guidelines, 334 Carotid sinus, 269
antihypertensive medications, 338 Carotid stenosis severity, 272
blood pressure at home, 338 Carpentier classification, 166
cholesterol markers, 335 Catecholaminergic polymorphic ventricular tachycardia
confusion/memory impairment, 336 (CPVT), 110, 117, 121, 123
diets, 333 Catecholamines, 256
hypertension, 337 Catheter ablation, 120
lipid-lowering drugs, 335 Catheter based procedures, 301
moderate-or lower-intensity activity, 334 Catheter-based reperfusion therapy in SCAD, 359
myalgias, 337 Catheter-directed therapy (CDT), 285
nutrition, 333–334 Cavotricuspid isthmus (CTI), 99, 107
physical activity and exercise, 334 CEA (carotid endarterectomy), 274
single “normal” cholesterol threshold, 335 Centers for Medicare and Medicaid Services criteria, 238
T2DM, 335 Central venous pressure (CVP), 13, 14
tobacco avoidance, 341 Cerebral angiography, 272
376 Index

CHEST guidelines, 285 Continuous hemodynamic monitoring with

Chest pain, 225 PAC, 260
anatomic approach, 345 Contraception choices and risk for future pregnancies,
anginal symptoms, 348 367
assessment, 353 Conventional cerebral angiography, 272
cardiac causes, 345 Cor pulmonale, 235, 236
chest radiograph, 350 Coronary anatomy and hemodynamic instability, 359
differential diagnosis, 346 Coronary artery bypass grafting (CABG) surgery, 22,
echocardiography, 350 359
electrocardiogram, 349 conduit selection, 53
in emergency department, 346 gastroepiploic artery, 55
gastrointestinal causes, 347 greater and lesser saphenous vein, 54, 55
history, 347 indications, 49–52
non-cardiac etiologies, 345 internal mammary artery, 53, 54
onset of pain, 347 preoperative assessment and risk calculation, 52
palliating factors, 348 radial artery, 54
physical examination, 347, 348 Coronary artery calcium (CAC) score, 332
point-of-care ultrasound, 350 Coronary sinus septal defect, 306
precipitating factors, 348 Corrected QT interval (QTc), 118
during pregnancy, 358 Corticosteroids, 246
presyncope, 347 Counter-clockwise atrial flutter, 99
risk factors, 348 Critical limb ischemia (CLI), 282
sublingual nitroglycerin, 353 Cryptogenic Stroke, 106
Chordae Tendinae, 169 Cyanosis, 324
Chronic aortic insufficiency, 158–161 Cytokine system, 195
Chronic hypertension and pregnancy (CHAP) trial, 364
Chronic mitral insufficiency, 164–166
Chronic primary MR, 168 D
Chronic secondary MR, 168 D-dimer, 284, 351
Chronic ventricular scar, 109 Deep vein thrombosis (DVT), 282–285
Chronotropic incompetence, 78 anticoagulation therapy, 286
Clinical decision pathways, 351–353 contraindications, 286
Closure devices, 126 management, 285
Coarctation of the aorta, 314, 315 Degenerative, nonrheumatic calcific MS, 172–173
Common carotid artery (CCAs) Detrimental ventricular remodeling, 195
bifurcation, 269 Diagnostic pacing maneuvers, 125
carotid bifurcation, 270 Diaphragm, 9
Common carotid (CC) method, 272 Diastole, 13
Computed tomography angiography (CTA), 273, 274, Diastolic filling curve, 221
281 Diastolic murmurs, 10
Computed tomography venography (CTV), IVC stented Dilated cardiomyopathy, 205, 206
segment, 285 Direct-acting oral anticoagulants (DOACs), 285, 360
Conduction system, 6 Dissection classification, Stanford and Debakey, 296
Conduction system abnormalities, 82 Distal arteries, 279
evaluation and management, 84 Diuretics, 212
left anterior fascicular block, 83 dose ranges, 212
left bundle branch block, 83 Dobutamine, 260
right bundle branch block, 82 Dobutamine stress echo (DSE), 150
Congenital heart disease, 301 Doppler ultrasound imaging, 275
evolution of treatment, 301 Dry oral mucosa, 196
surgical, interventional and diagnostic tools, 301 D-TGA (dextro-transposition of the great arteries),
Congenitally corrected transposition of the great arteries 317–319
(CCTGA), 315, 316 Dual antiplatelet therapy (DAPT), 155
Constriction, 247 Dual chamber pacemakers, 131
and restrictive cardiomyopathy, 247 Ductus arteriosus, 3, 10
Constrictive effusive pericarditis, 248 Duke criteria for endocarditis, 184
Constrictive pericardial disease, 248 Duke major and minor criteria for IE, 184
Constrictive pericarditis, 247, 248 Duplex ultrasound (DUS), 292
evaluation for carotid severity, 273
Index 377

surveillance, 293 Gastroepiploic artery, 53, 55

DVT, see Deep vein thrombosis (DVT) Gastrointestinal causes of chest pain, 347
Gastrointestinal reflux disease (GERD), 360
Genetic testing, 114, 117
E Gastrointestinal reflux disease (GERD), 360
Ebstein’s anomaly of the tricuspid valve, 320, 321 Giant cell myocarditis, 207
Echocardiography, 114 Greater saphenous vein (GSV), 54
Eclampsia, 363 Groin bleeding/hematoma formation, 126
Edema, 366 Guideline directed medical therapies (GDMT), 196, 200,
during pregnancy, 366 209–211, 261
Ehlers-Danlos syndrome (EDS), 290 drug therapy for LV function, 152
Ejection fraction (EF), 13 Guidelines for Sudden Cardiac Death and Arrhythmia
Ekg and chest pain decision tool, 349 Evaluation, 117
Electrical cardioversion, 137
Electrical depolarization, 4
Electrical measurements, 125 H
Electricity flow, 130 HACEK organisms, 183
Electrocardiogram (ECG), 4, 6, 10, 11 Heart block. See Atrioventricular (AV) block
Electrolyte imbalance, 110 Heart failure (HF), 195, 219
Electrophysiology study (EPS), 125 classification, 197
Embrology, 3 imaging modality, 197, 198
Endoleaks (EL), 293, 294 neurohormonal process, 195
Endomyocardial biopsy (EMB), 204, 206 treatment, 204
End-organ dysfunction, 257 by valvular regurgitation or obstruction, 188
Endothelial -1, 230 Heart failure guideline directed medical therapies, 210,
Endothelin receptor antagonists, 230 211
Endovascular aortic repair, 293 Heart failure with preserved ejection fraction (HFpEF),
Enterococcal IE, 186 219–221
Epicardial ablation, 127 Heart failure with reduced ejection fraction (HFrEF)
Epinephrine, 261 ACCF/AHA stages, 197
European Carotid Surgery Trial (ECST), 272 beta blockers, 202
Euvolemic CS, 257 cardiac chamber enlargement, 199
EVAR (endovascular aortic repair), 293 cardiac devices, 199
AAA treatment with exclusion of residual thrombus, cardiac MRI, 199
294 clinical examination of patients, 196
Excitation contraction coupling (ECC), 4–5 corticosteroids, 205
External carotid arteries (ECAs), 269 dynamic LVOT obstruction, 202
Extracorporeal membrane oxygenation (ECMO), 234, dynamic outflow tract gradient induced MR, 202
263 hemodynamic profile, 196
neurohormonal influences, 196
perfusion status, 196
F positive review of system findings, 197
False aneurysm (pseudoaneurysm), 289 transthoracic echocardiography, 199
Fetal arrhythmias, 365 two-dimensional echocardiography, 197
FEVAR (fenestrated endovascular aortic repair), 293 waveform or pulsation, 196
First-degree heart block, 78, 79 Heart sounds, 10, 11
Fluoroscopy, 125 Heart team, 51
Focal atrial tachycardia, 91, 92 Heparin, 360
Fontan circuit, 324 Hepatic dysfunction, 324
Fontan palliation, 322, 323 Heritable disorders, 362
Fontan physiology, 322 HMGCoA reductase inhibitors, 45
Fontan procedure, 301 Holosystolic, 9
Frank-Starling Law, 15 Hyperpolarization-activated cyclic nucleotide-gated
Frank-Starling mechanism, 195 (HCN) channel blockers, 60
Fusiform aneurysm, 289 Hypertension, 214
Hypertensive disorders of pregnancy, 362
classification, 363
G Hypertrophic cardiomyopathy (HCM), 201–203
Gastric outlet obstruction (GOO), 291
378 Index

I Iron deficiency, 214

Immune check point inhibitor inflammation, 207 Ischemic digit from emboli, 182
Implantable cardiac defibrillators (ICDs), 212–213 Ischemic heart failure, 199–201
Implantable cardioverter defibrillators (ICDs), 119 Ischemic rest pain, 280
common problems and troubleshooting pacemakers, Isolated TR intervention, 177
134–136
device interrogations, 134
indications for, 134 J
permanent defibrillators, 133, 134 Jervell-Lange Nielson syndrome, 118
placement, 203 Jugular vein distention, 196
principles of, 132, 133 Jugular vein pressure (JVP), 196, 197
temporary defibrillators, 133
Implanted ventricular assist devices (VAD), 263
Infective endocarditis (IE), 324 K
antibiotic prophylaxis, 190 Killip classification assessment, 257
antibiotic treatment, 185, 186 Kv11.1 (HERG) channel-mediated rapid K+ current (IK)
antimicrobial therapy, 187 blockers, 70
diagnosis, 181, 182
cardiac CT, 184
aortic valve destruction, 184 L
diagnostic findings, 182, 190 Large VSD, 308
echocardiography, 183 Left anterior descending artery (LAD), 50, 53–55
empirical antibiotic therapy, 190 Left anterior fascicular block(LAFB), 83–84
homograft/freestyle aortic valves, 188 Left atrial appendage occlusion, 106
incidence, 182 Left bundle branch block (LBBB), 81, 83
indications for surgery, 188, 189 Left cervicothoracic stellectomy/gangliectomy, 119
management, 185 Left common carotid artery (LCCA), 269
medical compliance, 188 Left internal mammary artery (LIMA), 53, 54
microbiology, 183 Left ventricular ejection fraction (LV EF), 358
mitral regurgitation, 188 Left ventricular filling, 247
mitral valve, 187 Lesser saphenous vein, 53–55
organism and antibiotic regimens, 185 Lipid-lowering therapy, 336
outpatient management and follow-up evaluation, Long QT syndrome (LQTS), 117–119
190–191 Loop diuretics, 212
pathology/description, 183 Low-flow-low-gradient (LFLG) AS, 151
patient care, 190 L-transposition of the great arteries, 315, 316
physical examination findings, 182 L-type Ca2+ current blockers, 72
positive blood cultures, 183
prosthetic valve endocarditis, 187
randomized controlled trials, 185 M
risk factors, 183 Magnetic resonance angiography, 273
S. aureus, 186 Mallampati score, 236, 237
septic pulmonary emboli, 187 Manual compression, 126
surgery, 187 Marfan syndrome, 290, 362
surgical risk stratification, 189 Mean pulmonary artery pressure (mPAP), 223
symptoms, 181 Mechanical circulatory support (MCS) devices, 263, 264
therapeutic strategies, 190 Medical therapy, 293
transthoracic echocardiogram, 190 Microvascular dysfunction (MVD), 45–47
12-lead EKG, 184 Milrinone, 260
uncontrolled/complex infection, 189 Mineralocorticoid receptor antagonists, 211–212
valvular/nonvalvular structural abnormality, 183 Mitral regurgitation, 168, 214
Infrarenal AAA pre-EVAR with heavy thrombus Mitral repair, 170
(DARK) and atherosclerotic burden, 292 Mitral stenosis, 170, 171
Inotropes, 261 management, 172
Internal cardioverter defibrillator (ICD), 111 Mitral valve (MV), 3, 7, 8
Internal carotid arteries (ICAs), 269 anterior and posterior leaflets and cusps, 164
Internal mammary artery (IMA), 53, 54 cord rupture with flail segment, 164
Intra-aortic balloon pump (IABP), 263 Mitral valve prolapse, 168
Intracardiac electrical signals, 125 Mitral valve regurgitation, 9
Intramural hematoma (IMH), 295 Mitral valve repair/replacement, 168–170, 173
Ion channel dysfunction, 110 with bioprosthetic valve, 174
Index 379

Mitral valve selection, 174 Oral antihypertensives, classes, 339

Mitral valve with flail posterior leaflet, 169 Outpatient management
Mobitz Type I (Wenckebach), 80 angina, 43
Multifocal atrial tachycardia (MAT), 89, 91, 92, 103 antianginal therapy, 45
Multiple gene mutations, 117 antiplatelet therapy, 45
Murmurs, 9–11 assessment and diagnosis, 43
Muscarinic M2 receptor activators, 67 behavior modification, 46
Muscarinic M2 receptor inhibitors, 66 beta-blockers, 45
Musculoskeletal chest pain, 360 calcium channel blockers, 46
Myocardial infarction, 31 cholesterol lowering agents, 45
Myocardial ischemia, 345–346 diagnostics, 44
Myocardial scar, 110 nitrates, 46
Myocarditis, 206, 207, 247 ranolazine, 46
etiologies, 208 Oversensing, 136

N P
Natriuretic peptide elevation, 200 Pacemakers
Nitrates, 46 basics of, 129–131
Nocturnal seizures, 238 device interrogation, 132
Noncardiac chest pain, 345 indications, 131–132
Non-invasive positive pressure ventilation (NIPPV), 259 temporary pacemakers, 131
Non-ischemic Cardiomyopathy (NICM), 200–201 Pain due to ischemic heart disease, 348
Non-restrictive VSD, 308 Parietal pericardium, 243
Non-selective β- and selective β1-adrenergic receptor Patient engagement in guideline-directed changes in
inhibitors, 65 lifestyle and medication strategies, 330
Non-selective β-adrenergic receptor activators, 66 PCSK-9 inhibitors, 45
Nonselective K+ channel blockers, 68 PDE-5 inhibitors, 230–231
Non-ST-elevation myocardial infarction (NSTEMI) Pedal gangrene, 280
assessment and diagnosis Penetrating aortic ulcer (PAU), 295
history, 32 Percutaneous coronary intervention (PCI), 359
physical exam, 33 Percutaneous mechanical thrombectomy, 234
clinical pearls, 40 Percutaneous revascularization (PCI), 22–25, 27–29
diagnostics, 33, 34 Percutaneous ventricular assist device (pVAD), 263
management Pericardial disease, anatomy, 244
antiplatelet agents, 39 Pericardial effusion, 249–250
cardiac catheterization, 37 Pericardial friction rub, 349
cardiac rehabilitation, 40 Pericarditis, 243, 346
clopidogrel, 36 cardiac MRI, 245
enoxaparin verses unfractionated heparin, 35 cardiogenic shock, 245
glycoprotein 2B3A inhibitors (eptifibatide or causes of, 244
tirofiban), 36 classification, 243, 244
initial medical therapy and stabilization, 35 diagnostic criteria, 244
invasive verses non-invasive evaluation, 36 and effusion, 246
patient education, 40 EKG, 245
percutaneous coronary intervention, 37, 38 hemodynamic collapse, 245
ticagrelor, 36 inflammatory markers, 245
myocardial infarction, 31 physical exam, 243
troponin value, 35 transthoracic echocardiogram, 245
Normal hemodynamic values, 13, 14 treatment, 246
North American Symptomatic Carotid Endarterectomy Peripartum cardiomyopathy (PPCM), 208, 366
Trial (NASCET), 272 Peripheral arterial disease (PAD)
lifelong management and surveillance, 282
lifestyle modification, 281
O medical management, 281
Obstructive sleep apnea (OSA), 236–239 physical exam, 279
Occasionally assistive devices, 293 physiologic testing, 280
Open aortic repair, 293 progression of arterial disease, 279
Open revascularization options, 282 risk factor modification, 281
Oral anticoagulants, 74–75 tissue perfusion over time, 279
380 Index

Peripheral edema, 11 physical exam findings, 225

Permanent atrial fibrillation, 129 prevalence, 224
Permanent defibrillators, 133, 134 prognosis, 229
Pharmacologic cardioversion, 137 pulmonary artery (PA) angiogram, 228
Phosphodiesterase-5 inhibitors, 230–231 6 minute walk, 227
Pneumothorax, 349 supportive treatment, 228
Polymorphic VT, 109, 114 transthoracic echo, 226
Pooled cohort equation (PCE), 330 vaso reactive agent, 227
Post-ablation testing, 126 Pulmonary pathologies, 347
Post excitation epsilon waves in right precordial leads, Pulmonary stenosis (PS), 311–312
208 Pulmonary valve stenosis, 311, 312
Post-operative surveillance of EVAR of infrarenal Pulmonary vascular resistance (PVR), 3, 223
segment, 294 Pulse assessment, 11
Post TAVR valve implant management, 155 PVOD (pulmonary venous occlusive disease), 227
Post-thrombotic syndrome (PTS), 283
Power stroke, 5
P-R interval, 6 Q
Precapillary PH, 224 QT segment, 6
Precapillary pulmonary hypertension, 223 Quinidine, 120
Precision medicine, 340
PREDIMED Mediterranean diet study, 333
Preeclampsia, 363 R
Pre-existing hypertension, 363–364 Radial artery, 53–55
with overlapping gestational hypertension, 364 Randomized clinical trials, 336
Pregnancy-associated cardiomyopathy, 366 Ranolazine, 46
Pregnancy related spontaneous coronary artery dissection Re-entrant circuits, 109
(P-SCAD), 358, 359 Renin angiotensin aldosterone system (RAAS), 195, 219,
post-partum, 358 256
Premature battery depletion, 135 inhibition, 211
Premature ventricular contractions (PVCs), 121 Respiration, 10
Primary MR, 166 Restenosis, 275
Primum ASD, 305, 307 Restrictive cardiomyopathy (RCM), 203–205
Programmed electrical stimulation (PES), 111 Retroperitoneal approach, 293
Prostacyclin, 229 Retroperitoneal bleeding, 126
Prosthetic conduit bypass, 282 Revascularization procedures, 359
Protein losing enteropathy (PLE), 324 management and procedures of lower extremities,
Pseudoaneurysm, 126 281
Pulmonary arterial hypertension (PAH), see also REVEAL (Registry to Evaluate Early and Long-Term
Pulmonary hypertension (PH) PAH Disease Management) data review, 225,
without intervention, right heart failure and death, 228
223 Rheumatic mitral stenosis, 171
Pulmonary artery catheters (PAC), 259 Right bundle branch block (RBBB), 82, 84
Pulmonary capillary wedge pressure (PCWP), 13–15, Right common carotid artery (RCCA), 269
196 Right heart catheterization, 227
Pulmonary edema post-delivery with normal LV Right phrenic nerve injury, 126
function, 367, 368 Riociguat (Adempas®), 230
Pulmonary embolism (PE), 227, 347 Risk assessment, 153
in pregnancy, 359–361 R-R intervals, 109
Pulmonary embolus (PE), 10 Ruptured atherosclerotic plaque, 279
Pulmonary hypertension (PH) Rutherford classification system, 279
CMRI, 227 of acute limb ischemia, 280
CTA, 226 of claudication, 280
definition, 223
diagnostic criteria, 223
diagnostic testing, 225 S
D-shaped interventricular septum of PH and RV Sarcoidosis, 204
enlargement, 226 SBE prophylaxis, 191
EKG findings, 227 SCAD-associated MI, 359
management, 228 SCAI cardiogenic shock, 258
pharmacological therapy, 229 Secondary MR, 167
Index 381

Second-degree heart block, 79, 80 Symptomatic AS, 152

Secundum ASD, 305 Symptomatic bradycardia, 77
Sensing, 129 Synchronization, 114
Septation, 3 Syncope, 365
SGLT2 inhibitor empagliflozin, 221 Systemic arteries
Sick sinus syndrome (SSS), 77 oxygenated blood flow, 277
Single ventricle physiology, 322 single-celled layer, 277
Sinoatrial node (SAN), 4, 6, 77 Systemic heparin, 125
Sinus arrest. See Sinus pause Systemic vascular resistance (SVR), 3, 13, 14
Sinus bradycardia, 77 Systole, 13
Sinus node dysfunction Systolic murmurs, 10, 308
chronotropic incompetence, 78
sinus bradycardia, 77
sinus pause, 77 T
Sinus pause, 77 Tachycardia-bradycardia syndrome, 77, 129
Sinus tachycardia, 87–89, 107 Takotsubo cardiomyopathy, 209
anatomy and physiology, 87 Temporary defibrillators, 133
diagnosis/imaging, 88 Temporary pacemakers, 131
management, 88 Temporary skin sutures, 126
pathology/description, 88 Tetralogy of Fallot (TOF), 312, 313
Sinus venosus ASD, 305 TEVAR (thoracic endovascular repair), 293
6th World Symposium on Pulmonary Hypertension, 223 TEVAR within true lumen excluding thrombus in false
Sleep apnea, 227, 237 lumen, 298
Sleep disordered breathing (SDB), 214 Thermodilution method, 260
Small, isolated ASD, 307 Third degree/complete heart block, 80, 81
Social determinants of health, 333 Thromboembolic complications, 324
Society for vascular surgery (SVS), 295 Thrombolysis
Sodium-glucose co-transporter 2 inhibition (SGLT2i), contraindications, 286
209, 212 Thrombolytic therapy, 359
Soluble guanylate cyclase stimulator, 230–231 Tocolytic-related pulmonary edema, 368
Spontaneous coronary artery dissection (SCAD), Toe-brachial index pressures, 282
358–359 Toe pressure utilization for non-diagnostic ABI, 281
Spontaneous depolarization, 4 Total arterial anatomy, 277
Statins, 45 Tracheostomy, 239
STOP-Bang questionnaire, 237 Transcarotid artery revascularization (TCAR)
screening tool, 237 qualifying characteristics, 275
Streptococcal IE, 186 Transcatheter aortic valve replacement (TAVR), 153–155
Stress cardiomyopathy, 209 vs SAVR, 153
Stroke volume (SV), 13, 15 Transcatheter edge to edge mitral valve repair (TEER),
ST segment elevation myocardial infarction (STEMI), 167
351 Transcatheter tricuspid valve interventions, 177
anatomy and physiology, 21–22 Transcutaneous pacing, 131
clinical pearls, 29 Transposition of the great arteries, 302
complications, 28, 29 Transpulmonary gradient. (TPG), 223
diagnostics, 23–27 Transvenous pacing, 131
evaluation, 22 Tricuspid insufficiency/regurgitation (TI/TR), 175–178
follow-up, 29 Tricuspid regurgitation, 9
imaging/management, 27, 28 Tricuspid regurgitation velocity (TRV), 226
physical examination, 23 Tricuspid stenosis, 178, 179
symptoms, 22 Tricuspid valve (TV), 3, 7
STS risk calculator, 154 Troponins, 5, 258, 350
Sub-cutaneous ICD generator, 133, 134 Type 2 diabetes mellitus (T2DM), 335
Superficial femoral arteries, 277 Type B dissection (TBAD), 298
Superficial veins, 282 Typical atrial flutter, 99
Supraventricular tachycardia (SVT), 87, 89, 92–94, 99,
107, 111, 365
Surface membrane Ca2+ channel blockers, 72 U
Surgical aortic valve replacement (SAVR), 153 Uncomplicated pericarditis, 245
Surgical pulmonary embolectomy, 234 Unroofed coronary sinus, 306
Sympathomimetic drugs, 110, 125
382 Index

V physical exam, 110

Valvar pulmonary stenosis, 311, 312 QRS morphology, 109
Valve Center for replacement, 158 symptoms, 110
Valve selection in SAVR, 156, 157 Video assisted thoracoscopic technique, 119
Valve selection in TAVR, 154 Vitamin K antagonists (VKA), 23, 156
Valvular atrial fibrillation, 171 Voltage dependent K+ channel blockers, 68
Valvular heart disease (VHD), 153 Voltage-gated channels, 4, 5
Vascular wall biology, 289 Na+ channel blockers, 61–64
Vasopressors, 261
support, 261
Vasoreactivity testing, 229 W
Venous thromboembolism (VTE), 359 Warfarin, 360
Ventricular arrhythmia (VA), 109, 121 WHO Group Classifications of Pulmonary Hypertension,
Ventricular gallop, 10 224
Ventricular septal defect (VSD), 307–309 WHO Group III pulmonary hypertension, 227
Ventricular tachycardia (VT) Wide complex tachycardia (WCT), 111, 112
acute management, 114 Wilkins score, 173
diagnostics, 111, 112, 114 Wolff-Parkinson-White (WPW) syndrome, 96–98, 107
long term treatment, 114 World Health Organization’s Commission on Social
pathophysiology, 109, 110 Determinants of Health, 333

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Cardiovascular Manual For The Advanced Musialowski 2023

Uploaded by

Cardiovascular Manual For The Advanced Musialowski 2023

Uploaded by

Cardiovascular

Mastering the Basics

ISBN 978-3-031-35818-0 ISBN 978-3-031-35819-7 (eBook)

Sanger Heart & Vascular Institute/Atrium Health B. Hadley Wilson

Tom Johnson, M.D. F.A.C.C., F.A.S.E.

Part II Coronary Artery Disease

Part III Cardiac Electrophysiology

7 Antiarrhythmic and Anticoagulant Agents ���������������������������������� 63

12 Introduction to Cardiac Ablation �������������������������������������������������� 127

Part IV Structural/Valvular Heart Disease

16 Aortic Valve Disease������������������������������������������������������������������������ 149

Part V Cardiomyopathies/Congestive Heart Failure

24 Cardiogenic Shock �������������������������������������������������������������������������� 257

Part VII Peripheral Vascular Disease

26 Carotid Artery Stenosis (CAS)������������������������������������������������������� 271

Part VIII Adult Congenital Heart Disease (ACHD)

Part IX Ambulatory/Preventative Cardiology

Part X Emergency Department Evaluation of Chest Pain

Part XI Cardiovascular Disease in Pregnancy

Embryologic Development The great vessels (aorta and pulmonary

© The Author(s), under exclusive license to Springer Nature Switzerland AG 2023 3

 xcitation Contraction Coupling

A I. Troponin I can restrict the actin and myosin

Conduction System diac cycle. The P wave originates in the SA

Fig. 1.2 Normal EKG with intervals

Cardiac Anatomy MV are further described by their individual

Anterior semilunar cusp of pulmonary valve

RCC Right semilunar cusp of aortic valve

Septal cusp of tricuspid valve

Fig. 1.3 Nomenclature of the cardiac valves

Fig. 1.4 Work of the heart valves

The LAD branches into diagonal vessels. This

Physical Examination holosystolic as they begin immediately after S1.

Fig. 1.7 Heart location within thorax

Table 1.1 Murmur descriptions

Bruit: chronic arterial insufficiency and specific arterial

Cardiac Cycle the cardiac output divided by body surface area

© The Author(s), under exclusive license to Springer Nature Switzerland AG 2023 13

Fig. 2.1 Wiggers

Fig. 2.2 Atrial pressure a v

Fig. 2.4 Pressure-­ 140

Left Ventricular Pressure (mmHg)

Amy Winiger George P. Rodgers

Atherosclerosis is the development of plaques made up of fatty and pro-­

Fig. 1 Development of atherosclerotic plaque

The development of coronary atherosclerosis begins early in life. Fatty

Fig. 2 Progression of atherosclerosis over time

Amy Winiger and George P. Rodgers

A. Winiger (*) The definition of acute coronary syndrome (ACS)

© The Author(s), under exclusive license to Springer Nature Switzerland AG 2023 21

Image by Matthew Allshouse

EKG Location Coronary Distribution

Septal-V1-V2 Prox. LAD

Lateral-I, aVL, V5-V6 LCx

Inferior-II, III, aVF RCA (85%) or LCx (15%)

Posteriolateral-V7, V8, V9 RCA or LCx

Right Ventricle-V1, V4R RCA

adapted from Localization of the occluded vessel in acute myocardial infarction.

Fig. 3.2 STEMI in anterior leads V1-V5 with reciprocal changes

Fig. 3.3 Type I MI in LAD Fig. 3.4 LAD after PCI

Fig. 3.5 Inferior and posterolateral STEMI

Fig. 3.6 Left circumflex occlusion

Fig. 3.8 STEMI inferior leads

Fig. 3.9 RCA occlusion

Fig. 3.10 RCA post intervention

LV septum, there can be ventricular septal wall Clinical Pearls

Introduction vated troponin occurring secondary to plaque rup-

© The Author(s), under exclusive license to Springer Nature Switzerland AG 2023 31

Assessment and Diagnosis Table 4.2 Key historical questions summarized

Physical Exam (Fig. 4.2). These changes are present within

Fig. 4.1 Isolated T wave inversion in a vascular distribution

Troponin Trending ering but has a pleiotropic effect of decreasing

Cardiac Catheterization (Fig. 4.4) Table 4.5 Risks of cardiac catheterization

 ercutaneous Coronary Intervention

There are multiple forms of percutaneous cor-

bleeding complication. Suture-based devices

Sanger Heart & Vascular Institute/Atrium Health B. Hadley Wilson

Part II Coronary Artery Disease

Part III Cardiac Electrophysiology

7 Antiarrhythmic and Anticoagulant Agents �� 63

12 Introduction to Cardiac Ablation �� 127

Part IV Structural/Valvular Heart Disease

16 Aortic Valve Disease�� 149

Part V Cardiomyopathies/Congestive Heart Failure

24 Cardiogenic Shock �� 257

Part VII Peripheral Vascular Disease

26 Carotid Artery Stenosis (CAS)�� 271

Part VIII Adult Congenital Heart Disease (ACHD)

Part IX Ambulatory/Preventative Cardiology

Part X Emergency Department Evaluation of Chest Pain

Part XI Cardiovascular Disease in Pregnancy

Embryologic Development The great vessels (aorta and pulmonary

xcitation Contraction Coupling

Conduction System diac cycle. The P wave originates in the SA

Cardiac Anatomy MV are further described by their individual

Physical Examination holosystolic as they begin immediately after S1.

Cardiac Cycle the cardiac output divided by body surface area

Fig. 2.4 Pressure- 140

Atherosclerosis is the development of plaques made up of fatty and pro-

Introduction vated troponin occurring secondary to plaque rup-

Assessment and Diagnosis Table 4.2 Key historical questions summarized

Physical Exam (Fig. 4.2). These changes are present within

Troponin Trending ering but has a pleiotropic effect of decreasing

Cardiac Catheterization (Fig. 4.4) Table 4.5 Risks of cardiac catheterization

ercutaneous Coronary Intervention

Cardiac Rehabilitation contiguous leads can be indicative of ischemia.

Introduction Assessment and Diagnosis

Preoperative Assessment ing should be considered to investigate various

Conduit Selection Table 6.4 Bypass conduit recommendations. Adapted

CIED therapy includes pacemakers and implantable cardioverter-

Anticoagulation Therapy the antiarrhythmic agents, it is important to select

Sinus Node Dysfunction Sinus Bradycardia

hird Degree/Complete Heart Block

Conduction System Abnormalities to a block in conduction within the right bundle,

Introduction with different electrophysiologic properties

There is usually no need for pharmacologic ther- Pathology

Focal Atrial Tachycardia Ongoing management [1]

• Oral verapamil or diltiazem for patients who Anatomy and Physiology

cute management [1]

Management of coronary artery disease, renal function, and

Imaging • Cardiac CT:

Introduction acutely in the presence of ischemia. Arrhythmias

Introduction channelopathy suspected. Genetic testing is not