Diagnosis and Management of Fetal Arrhythmias
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Foreword
Huge progress has been made in the diagnosis and treatment of various fetal conditions. Ultrasound has provided the
essential information regarding the nature of abnormalities of structure, growth, and function and has allowed the
understanding of how the fetus adapts to these conditions. It is now clear that the fetal heart, while centrally involved in
structural anomalies, can also play a major secondary functional role in other conditions involving the placenta and fetal
brain. On the maternal side of the placenta, diabetes, obesity, autoimmune diseases, hemoglobinopathies, and even
medications can have a major effect on the fetal heart, which is the epicenter of fetal response to these challenges.
Ultrasound has been the major diagnostic vehicle for identifying congenital heart disease. Interestingly, the technology has
undergone an exponential expansion, evolving from 2D and M-mode ultrasound, through pulsed and color Doppler real-time
advances to the new speckle tracking techniques used to assess fetal ventricular contractility. However, the current
technology has arrived before many clinicians in the field have had a chance to understand, or even exploit, its potential.
This book should fill the knowledge gap that has arisen from one set of particularly thorny problems: fetal cardiac
arrhythmias. A novel challenge for healthcare providers managing fetal arrhythmias is the care of two patients—the fetus
and the mother. This book, a compilation of topics written by multidisciplinary experts in the field and edited by Cuneo,
Drose, and Benson, is the first textbook to exclusively address fetal cardiac arrhythmias. In this book, the approach to fetal
cardiac arrhythmias is comprehensive and includes diagnosis, treatment of the fetus, maternal management, and etiology
including genetic origins.
The editors represent an ideal coalition of professionals, each representing a separate component in the collaborative
delivery of care to fetuses suspected of having cardiac arrhythmias. Julia Drose is a sonographer who has been immersed in
fetal echocardiography almost from its inception. D. Woodrow Benson is a well-known and prolific electrophysiologist and
cardiovascular geneticist, and Bettina Cuneo is a widely published fetal cardiologist who has made numerous contributions
to our understanding of fetal cardiac arrhythmias.
Each chapter is well laid out by selected contributors from pediatric cardiology and maternal-fetal medicine and embellished
with beautiful images to illustrate the accompanying text. Every aspect of the diagnosis, treatment, and surveillance of
arrythmias is addressed in the book, as well as future approaches to dealing with problem arrhythmias, that will become
standard of care in the coming years.
This book beautifully arms the clinician with the most up-to-date knowledge to deal with some of our greatest challenges.
John Hobbins, MD
Professor Emeritus of Obstetrics and Gynecology
Division of Maternal Fetal Medicine
University of Colorado School of Medicine
Aurora, Colorado
Preface
The birth of fetal arrhythmology, the diagnosis and treatment of arrhythmias, occurred in the
early 1980s. Using a 3.5-MHz nonfocused transducer with a strip chart recorder, teams of
maternal fetal medicine (MFM) specialists and pediatric cardiologists from Yale University
and the Cardiothoracic Unit in Guy's Hospital successfully diagnosed various fetal
arrhythmias. The first transplacental treatment of “fetal paroxysmal atrial tachycardia” with
digoxin was reported in the New England Journal of Medicine in 1983 by the team of Charlie
Kleinman, Greg DeVore, John Hobbins, and others at Yale University. Across the pond at
Guy's Hospital in London, Lindsey Allan was publishing her results of transplacental
treatment of fetal arrhythmias with digoxin and verapamil. The fortitude and “disruptive
thinking” of these early investigators can be summed up in the dedication to Dr. Allan’s
Manual of Fetal Echocardiography: “To all those people….who have inspired me by telling
me my proposed next step was impossible.” We think it is important to acknowledge the
bravery, determination, and vision of the “founders of fetal arrhythmology.”
Over the next 25 years, the field of fetal arrhythmology will advance to a state where the
electrophysiology mechanisms of complex arrhythmias will be incorporated into clinical
practice. Currently, the precise diagnosis and treatment of fetal tachycardia is the standard of
care, and the genetics of fetal arrhythmias are making their way to the bedside. It was time
for a book about fetal arrhythmias, written in the spirit of the multidisciplinary collaboration,
so essential for a successful fetal cardiology program.
The diagnosis and treatment of fetal arrhythmias are intended for a broad audience. There are
many illustrations and a chapter on how to obtain the Doppler and M-mode images that allow
for accurate diagnosis. Parts 1 and 2 focus on the basics of fetal rhythm analysis. Parts 3 to 5
cover arrhythmias in greater detail and include suggestions for fetal management, maternal
arrhythmia treatment, and care of the mother at risk for fetal arrhythmia. Part 6 is intended to
spark interest in newer techniques that we believe will further advance the field.
Compiling a book of this type requires a village, and we wish to acknowledge those who
made the undertaking possible. First, we are forever humbled by the mothers and families
who have entrusted the care of their children to us. Their bravery and resilience are
inspirational. Second, we are grateful for what we have learned from our mentors, students,
and colleagues. This acknowledgment includes the obstetricians, maternal fetal medicine
specialists, pediatric cardiologists, radiologists, electrophysiologists, cardiovascular
geneticists, and sonographers with whom we collaborate everyday. We are so fortunate that
they have shared our passion for excellent patient care and advancement of the field.
Lastly, we wish to thank our families for their continued support and encouragement, which
provide the inspiration for us to “dream things that never were” for other families.
Bettina F. Cuneo Julia A. Drose D. Woodrow Benson
Denver, CO Denver, CO Milwaukee, WI
Contributors
Alfred Abuhamad, MD
Mason C. Andrews Professor of Obstetrics & Gynecology, Chairman Department of Obstetrics & Gynecology, Eastern
Virginia Medical School, Norfolk, Virginia
Fayeza Alrais, MBSS, FRCSC
Consultant, Maternal-Fetal-Medicine (MFM), Department of Obstetrics and Gynecology, Tawam Hospital in Affiliation
with Johns Hopkins Medicine, SEHA Abu Dhabi Health Services, Co., Al Ain, United Arab Emirates
Yaniv Bar-Cohen, MD
Professor of Clinical Pediatrics and Medicine, Department of Pediatrics, Keck School of Medicine, University of Southern
California, Los Angeles, California
Nico A. Blom, MD, PhD
Head Pediatric Cardiology, Department of Pediatrics, AUMC, Amsterdam, The Netherlands
Ramen H. Chmait, MD
Associate Professor, Department of Obstetrics and Gynecology, University of Southern California, Los Angeles, California
Sally-Ann Barker Clur, MBBCh, MSc(Med), FCP(Paed)SA, PhD
Paediatric Cardiologist and Head of Fetal Cardiology Center for Congenital Heart Defects Amsterdam-Leiden (CAHAL),
Department of Paediatric Cardiology, Amsterdam UMC, University of Amsterdam, Heart Center, Amsterdam, The
Netherlands
Bettina F. Cuneo, MD
Professor, Pediatrics (Cardiology) and Obstetrics, Director of Perinatal Cardiology and Fetal Cardiac Telemedicine,
University of Colorado School of Medicine, Aurora, Colorado
Mary T. Donofrio, MD
Professor of Pediatrics, George Washington University, Washington, District of Columbia
Julia A. Drose, BA, RDMS, RDCS, RVT
Associate Professor, Radiology, Chief Sonographer, Divisions of Diagnostic Ultrasound and Prenatal Diagnosis & Genetics,
University of Colorado School of Medicine, Aurora, Colorado
Susan Etheridge, MD
Professor, Department of Pediatrics, University of Utah, Salt Lake City, Utah
Frank A. Fish, MD
Professor, Departments of Pediatrics and Medicine, Vanderbilt University Medical Center, Nashville, Tennessee
Gerard Frunzi, MBA
Telehealth Services Manager, Telehealth, Children’s Hospital Colorado, Aurora, Colorado
Henry L. Galan, MD
Professor, Department of Obstetrics and Gynecology, Division of Maternal-Fetal Medicine, University of Colorado School
of Medicine, Colorado Fetal Care Center, Children’s Hospital of Colorado, Aurura, Colorado
Helena M. Gardiner, MD, PhD
Professor, The Fetal Center, UT Health, Houston, Texas
John Hobbins, MD
Professor Emeritus of Obstetrics and Gynecology, Division of Maternal Fetal Medicine, University of Colorado School of
Medicine, Aurora, Colorado
Hitoshi Horigome, MD, PhD
Professor, University of Tsukuba, Department of Pediatrics, Tsukuba, Ibarkai, Japan
Lisa K. Hornberger, MD
Professor of Pediatrics/Adjunct Professor, Department of Pediatrics/Obstetrics & Gynecology, University of Alberta,
Edmonton, Alberta
Lisa Willis Howley, MD
Director, Fetal Cardiology, The Children’s Heart Clinic, Children’s Hospital Minnesota, Minneapolis, Minnesota
Stacy Ann Stratemann Killen, MD, MSCI
Assistant Professor, Department of Pediatrics, Division of Pediatric Cardiology, Vanderbilt University School of Medicine,
Nashville, Tennessee
Katherine Anne Kosiv, MD
Assistant Professor of Clinical Pediatrics, Department of Pediatrics, Yale University School of Medicine, New Haven,
Connecticut
Gerald E. Loeb, MD
Professor, Biomedical Engineering, University of Southern California, Los Angeles, California
Lindsay Meyers, MS, LCGC
Adjunct Faculty, Department of Pediatrics, University of Utah, Salt Lake City, Utah
Anita J. Moon-Grady, MD
Professor of Clinical Pediatrics, Department of Pediatrics, University of California San Francisco, San Francisco, California
Christina A. Olson, MD
Assistant Professor, Department of Pediatrics, University of Colorado, Aurora, Colorado
Jay D. Pruetz, MD
Associate Professor of Clinical Pediatrics and Obstetrics and Gynecology, Department of Pediatrics, Keck School of
Medicine, University of Southern California, Los Angeles, California
Rachel L. Rodel, MD
Clinical Assistant Professor, Department of Obstetrics and Gynecology, University of South Dakota Sanford School of
Medicine, Vermillion, South Dakota
Michael J. Silka, MD
Professor of Pediatrics, Keck School of Medicine, University of Southern California, Los Angeles, California
Danna Spears, MSc, MD, FRCP(C)
Division of Cardiology - Electrophysiology, Medical Director - UHN Cartwright Inherited Cardiomyopathy and Arrhythmia
Program, U of T Pregnancy and Heart Disease Program - Arrhythmia Clinic, University Health Network - Toronto General
Hospital, Toronto, Ontario, Canada
Janette F. Strasburger, MD
Professor of Pediatrics, Department of Pediatrics and Cardiology Medical College of Wisconsin, Milwaukee, Wisconsin
J. Fred Thomas, PhD
Associate Professor, Department of Medicine, Public Health and Nursing, School of Medicine and School of Public Health,
University of Colorado Anschutz Medical Campus, Aurora, Colorado
Arja Suzanne Vink, MD, MSc (EBP)
Department of Clinical and Experimental Cardiology, Amsterdam UMC, University of Amsterdam, Heart Center,
Amsterdam, The Netherlands
Ronald Wakai, PhD
Professor, Department of Medical Physics, University of Wisconsin, Madison, Wisconsin
Contents
Part 1 Background
1 Overview of Fetal Arrhythmias
Julia A. Drose and Bettina F. Cuneo
2 Before Diagnosis: Initial Evaluation of the Pregnancy With Fetal Arrhythmia
Julia A. Drose and Bettina F. Cuneo
3 Genetics of Fetal Arrhythmias
Susan Etheridge and Lindsay Meyers
Part 2 Techniques to Analyze Fetal Rhythm
1 Electronic Monitoring
Rachel L. Rodel and Henry L. Galan
2 Echocardiography
Lisa Willis Howley
3 Magnetocardiography
Ronald Wakai
Part 3 Presentation and Diagnosis of Fetal Arrhythmias
1 Ectopy
Katherine Anne Kosiv and Anita J. Moon-Grady
2 Supraventricular Tachyarrhythmias
Stacy Ann Stratemann Killen and Frank A. Fish
3 Ventricular Tachycardias
Sally-Ann Barker Clur, Lisa K. Hornberger, Arja Suzanne Vink, and Nico A. Blom
4 Atrioventricular Block and Structural Cardiac Defects
Fayeza Alrais and Anita J. Moon-Grady
5 Immune-Mediated Atrioventricular Block
Helena M. Gardiner and Bettina F. Cuneo
6 Channelopathies
Hitoshi Horigome
Part 4 Treatment of Fetal Arrhythmias
1 Treatment of Supraventricular Tachyarrhythmias
Stacy Ann Stratemann Killen and Frank A. Fish
2 Treatment of Ventricular Tachycardias
Sally-Ann Barker Clur, Arja Suzanne Vink, Nico A. Blom, and Hitoshi Horigome
3 Treatment of Immune-Mediated Atrioventricular Block
Helena M. Gardiner and Bettina F. Cuneo
Part 5 Care of the Pregnancy at Risk for Maternal or Fetal Arrhythmia
1 The Inherited Arrhythmia Syndromes
Danna Spears
2 The Anti-Ro/SSA Positive Pregnancy
Helena M. Gardiner and Bettina F. Cuneo
3 Delivery Planning
Mary T. Donofrio and Alfred Abuhamad
Part 6 Fetal Arrhythmias: Future Directions
1 The Elusive Fetal Electrocardiogram
Helena M. Gardiner
2 Magnetocardiography for the Fetus at Risk for Stillbirth
Janette F. Strasburger
3 The Fetal Pacemaker
Yaniv Bar-Cohen, Gerald E. Loeb, Michael J. Silka, Jay D. Pruetz, and Ramen H.
Chmait
4 Diagnosis from a Distance: Telecardiology in the Evaluation of Fetal Arrhythmias
J. Fred Thomas, Christina A. Olson, Gerard Frunzi, and Bettina F. Cuneo
Index
PA R T 1
Background
1 Overview of Fetal Arrhythmias
2 Before Diagnosis: Initial Evaluation of the Pregnancy With Fetal
Arrhythmia
3 Genetics of Fetal Arrhythmias
CHAPTER 1
Overview of Fetal Arrhythmias
Julia A. Drose • Bettina F. Cuneo
The Normal Cardiac Conduction System
An understanding of the normal cardiac conduction system is necessary to understand fetal
arrhythmia (Fig. 1.1.1). Electrical conduction begins in the sinoatrial (SA) node located in
the right atrium (RA). The SA node fires, sending electrical impulses to the left and right
atria, causing them to contract. These impulses are then conducted to the atrioventricular
(AV) node.
FIGURE 1.1.1 Normal cardiac conduction system.(Modified from Jones RM. Patient Assessment
in Pharmacy Practice. 3rd ed. Philadelphia, PA: Wolters Kluwer; 2015.)
From the AV node, electrical impulses are conducted to the right and left bundle branches,
via the bundle of His, then to the Purkinje fibers within the myocardium, resulting in
ventricular contraction. If the impulses from the AV node are delayed, 1° block occurs. If the
impulses are not conducted due to a structural or functional anomaly of the AV node, 2° or 3°
block results and the ventricles beat at an independent and slower rate than the atria. The
more distal the damage to the conduction system, the slower the ventricular rate. On the other
hand, if electrical impulses from the bundle of His to the Purkinje fibers are accelerated,
ventricular or junctional tachycardia occurs.
Atrial depolarization corresponds to the P-wave on the ECG (Fig. 1.1.2), the A-wave on the
mitral inflow/aortic outflow spectral Doppler (Fig. 1.1.3A), retrograde flow during atrial
systole on the spectral Doppler tracing of a systemic or pulmonary vein (Fig. 1.1.3B and C),
and the atrial deflections on simultaneous M-mode tracing of atria and ventricles (Fig.
1.1.3D). Atrial deflections are unusually sharp and clear when the M-mode cursor is
positioned simultaneously through the RA and LA in the longitudinal view of the aortic arch
(Fig. 1.1.4).
FIGURE 1.1.2 Diagram of a normal electrocardiogram (ECG) tracing. The P-wave represents the
onset of atrial contraction. The QRS complex represents ventricular contraction. The T-wave
represents ventricular repolarization. The distance between the P-wave and the R-wave represents
the time interval from atrial to ventricular contraction of the heart (the PR interval).
