OUTLINE

I.​ Heart Failure ●​ Clinical trials have shown that treatment

A.​ Types of HF directed at non- cardiac targets is more
B.​ NYHA functional classification
C.​ Goal of treatment valuable in the long-term treatment, such as:
D.​ Drug used in HF ✔​ ACE inhibitors
E.​ Pathophysiology
II.​ Basic Pharmacology of Drugs Used in Heart Failure
A.​ Digitalis
✔​ Angiotensin receptor blockers
B.​ Other positive inotropic drugs used in HF
C.​ B-adrenoreceptor agonist ✔​ Beta blockers
D.​ Drugs w/out positive inotropic effects
E.​ Diuretics ✔​ Aldosterone receptor antagonists
F.​ Ace inhibitors
G.​ Vasodilators ✔​ Combined hydralazine-nitrate therapy
H.​ B-adrenoreceptor blocker
III.​ Clinical Pharmacology of Drug Used in Heart
Failure 2 MAJOR TYPES
IV.​ Management of Diastolic HF ●​ Systolic failure
V.​ Management of Acute HF →​ Heart failure with reduced ejection fraction or
HEART FAILURE “HFrEF”
●​ Occurs when cardiac output is inadequate to →​ ​Systolic failure
provide the oxygen needed by the body -​ Decreased LV contractility
●​ 5-year mortality rate is 50% -​ Reduced mechanical pumping action
●​ Most common cause: -​ Reduced ejection fraction (EF) (upon
✔​ Coronary artery disease doing 2D echo)
●​ Diastolic failure
✔​ Hypertension →​ Heart failure with preserved ejection fraction
●​ HF is a progressive disease that is or “HFpEF”
characterized by a gradual reduction in →​ Diastolic Failure
cardiac performance, punctuated in many -​ Stiffening and loss of adequate LV
cases by episodes of acute decompensation, relaxation
often requiring hospitalization. -​ A major role in reducing left ventricular
●​ The primary defect in early systolic HF filling and CO
resides in the excitation-contraction coupling -​ EF may be normal, despite stroke
mechanism of the heart. volume is significantly reduced
●​ Clinical conditions or factors that may -​ Incidence increases as the person is
influence HF: aging
✔​ Baroreceptor reflex Based on 2016 European HF Guidelines
Classification of HF according to LV EF
✔​ Sympathetic nervous system
​ Heart Failure with reduced ejection fraction
✔​ Kidneys
(HFrEF)
✔​ Angiotensin II -​ Previously known as systolic HF
-​ EF ≤ 40%
✔​ Peptides
​ Heart Failure with preserved ejection fraction
✔​ Aldosterone (HFpEF)
-​ Previously known as diastolic HF
✔​ Apoptosis of cardiac cells (worst) -​ EF ≥ 50%
​ Heart Failure with mid-range (or borderline)
Ejection Fraction (HFmrEF)

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 -​ Newer term as of April 2021, adapted by ●​ Amount of trigger calcium
HFS of America, HF Assoc of ESC, ●​ Activity of sodium-calcium exchanger
Japanese HFS and Writing Committee of ●​ Intracellular sodium concentration and
the Universal Definition of HF: activity of Na+/K+-ATPase
o​ HF with mildly reduced EF
-​ EF of 41% and 49% Pathophysiology of Heart Failure
●​ HF is a syndrome with many causes that
NYHA FUNCTIONAL CLASSIFICATION may involve one or both ventricles
Class I ●​ CO is usually below the normal range
●​ No limitation of physical activity ✔​ "low-output" failure
●​ No symptoms with ordinary exertion
●​ Systolic dysfunction
✔​ Reduced CO and reduced Ejection Fraction
(EF <45%) (Normal, EF is >60%)
Class II
●​ Slight limitation of physical activity ✔​ Is typical of acute failure, especially due to MI
●​ Ordinary activity causes symptoms
●​ Diastolic dysfunction
Class III
✔​ A result of ventricular hypertrophy and
●​ Marked limitation of physical activity
●​ Less than ordinary activity causes symptoms stiffening of the myocardium
●​ Asymptomatic at rest ✔​ Reduced CO but the EF may be normal

Class IV ✔​ Does not improved with inotropic drugs

●​ Inability to carry out any physical activity ●​ "High-output" failure is a rare form of HF
without discomfort ✔​ The demands of the body are so great that
●​ Symptoms at rest even increased CO is insufficient

Goal of Treatment ✔​ Causes:

●​ Reducing symptoms and slowing ▪​ Hyperthyroidism
progression as much as possible during
relatively stable periods ▪​ Beriberi
●​ Managing acute episodes of decompensated
failure ▪​ Anemia

Drug Group Used in HF ▪​ Arteriovenous shunts

CHRONIC HF ACUTE HF ●​ Treatment gears toward correction of the
●​ Diuretics ●​ Diuretics underlying causes
●​ Aldosterone receptor ●​ Vasodilators
antagonists ●​ Beta agonists Primary Signs and Symptoms of All Types of HF
●​ ACE inhibitors ●​ Bipyridines ●​ Tachycardia
●​ Angiotensin receptor ●​ Natriuretic peptides ✔​ Due to sympathetic reflex
blockers
✔​ 1st Manifestation
●​ Beta blockers
●​ Cardiac glycosides ●​ Shortness of breath
●​ Vasodilators ●​ Cardiomegaly
●​ Peripheral edema
Control Normal Cardiac Contractility ●​ Pulmonary edema
●​ Sensitivity of the contractile proteins to ✔​ Due to congestive heart failure
calcium and other contractile protein
●​ Decreased exercise tolerance
modifications
●​ Amount of calcium released from the ✔​ Due to rapid muscular fatigue
sarcoplasmic reticulum
●​ Amount of calcium stored in the ✔​ Major direct consequence of diminished CO
sarcoplasmic reticulum

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 Vicious Spiral Progression of Heart Failure →​ Angiotensin II Can send (+) feedback in
●​ When heart failure starts, CO will decrease
and as a compensatory mechanism there is
sympathetic response and NE, AII, ET
(vasoconstrictors) will increase. These
vasoconstrictors will increase the afterload.
●​ The increase in afterload is an added work to
the myocardium. Because of the increase in
afterload, it is expected that the ejection
fraction will decrease
●​ Decrease in ejection fraction can further
reduce the cardiac output
●​ As the vicious process progress, there is a
decline in cardiac performance.
CO – Cardiac Output
NE – norepinephrine Sympathetic nervous system further inc in
AII – Angiotensin II sympathetic discharge inc Preload, Force
ET - Endothelin and Rate
→​ Sympa Discharge can also send (+) feedback
Pathophysiology of Heart Failure: Compensatory to renin Inc Renin release
Response
●​ In a Failing Heart there shouldn’t be:
→​ ⇧ preload – because we want to unload our
heart to ease the HF
→​ ⇧ Rate
→​ ⇧ Force
→​ ⇧ Afterload
→​ Remodeling can result to dilatation of the
heart
▪​ dilation of heart can further worsen the
systolic function of the heart

Pathophysiology of Cardiac Performance

●​ Cardiac performance is a function of:
→​ Preload
→​ Afterload
→​ Contractility
In a Diastolic or Systolic type of HF, both can
→​ Heartrate
present a decrease in CO
Preload
●​ Left side:
→​ Dec CO reduction of carotid sinus firing ●​ Ventricular filling pressure
can stimulate Sympathetic activity Inc ●​ End-diastolic fiber length
●​ Normal individual where ventricular filling
sympa discharge Inc production of
pressure is <15mmHg
Catecholamines (Ex. Epi) Improvement of
CO by increasing Force, Rate and Preload ✔​ Increase in LV performance with increasing LV
→​ Compensatory response can initially help but filling pressure
as time goes by, it will not compensate well. It
will result to progressive reduction of CO ✔​ It represents the classic Frank-Starling
relationship
●​ Right Side: ●​ Ventricular filling pressure
→​ Dec CO reduction of renal BF kidney will
✔​ Beyond 15 mmHg
sense dec in renal BF Inc renin release Inc
Angiotensin II Constriction of artery Inc ▪​ There is plateau of performance
Preload, Afterload and Remodeling

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 Heart rate
▪​ Despite increase in filling pressure no
●​ Is a major determinant of cardiac output
more corresponding increase in cardiac ●​ In heart failure, the stroke volume decreases
function →​ Increases in HR due to sympathetic activation
✔​ Greater than 20-25 mmHg- results in of B adrenoreceptors
pulmonary congestion →​ The first compensatory mechanism that
●​ Increase in preload in HF is due to increase comes into play to maintain CO
in blood volume and venous tone
●​ Increased in fiber length (or filling pressure)
BASIC PHARMACOLOGY OF DRUGS USED IN
✔​ Increases in oxygen demand in the HEART FAILURE
myocardium Digitalis
●​ Goal: reduction of high filling pressure
✔​ Salt restriction

✔​ Diuretics

✔​ Nitroglycerin
●​ The genus name of the family of plants that
✔​ Venodilator provide most of the medically useful cardiac
glycosides.
▪​ Redistribution of blood away from the ●​ Prototype:
chest into the peripheral veins
✔​ Digoxin
Afterload ●​ Recovered by Withering, an English
●​ Is the resistance against which the heart physician and Botanist
must pump blood ●​ Described the clinical effects of an extract of
●​ Represented by aortic impedance and the purple fox glove plant, Digitalis purpurea
systemic vascular resistance (SVR) ●​ Asteroid nucleus linked to a lactone ring at
●​ CO decreases in chronic HF is due to: the 17 position and a series of sugars at
carbon 3 of the nucleus
✔​ Reflex increase in SVR ●​ Not good for diastolic dysfunction
✔​ Increase in sympathetic activity
Pharmacokinetics
✔​ Increase in circulating catecholamines ●​ Digoxin is the only cardiac glycoside used in
the USA
✔​ Activation of renin-angiotensin system -​ 65-80% absorbed after oral administration
-​ In the blood, it is widely distributed to the
✔​ Endothelin involvement tissues, including the CNS
●​ Goal: to reduce SVR -​ Not extensively metabolized 2/3 is excreted
⇨​ To use drugs that reduce the arteriolar unchanged by the kidneys
●​ Its renal clearance is proportional to the
tone creatinine clearance
Contractility ●​ Half-life:
●​ Reduction in the velocity of muscle -​ 36-40 hours in patient with normal renal
shortening function
✔​ Decrease in cardiac contractility ●​ Dose should be adjusted in patients with
renal impairment. Given once daily only
●​ In patient with low-out failure depending on creatinine clearance
✔​ There is reduction in intrinsic contractility ●​ Not dialyzable
●​ Goal: to increase cardiac muscle contractility -​ Don’t give to patient with End Stage Renal
⇨​ Use of inotropic drugs Disease

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Pharmacodynamics
✔​ A result of inhibition of the sodium pump and
●​ Digoxin has multiple direct and indirect
cardiovascular effects, with both therapeutic reduced intracellular potassium
and toxic consequences ●​ As toxicity progresses, oscillatory
●​ It has undesirable effects on the CNS and depolarizing after potentials appears
GIT following a normal action potential
●​ It inhibits Na+/K+ ATPase, the membrane- ●​ After potentials are associated with
bound transporter often called the sodium overloading of the intracellular calcium stores
pump and oscillations in the free intracellular
→​ Receptor of cardiac glycoside exists on the calcium ion concentration
sodium pump ●​ When after potentials reach threshold, they
elicit an action potential (premature
depolarizations, an ectopic beats)
2 CARDIAC EFFECTS ●​ In purkinje conducting system, may trigger a
●​ Mechanical Effects premature depolarization in bigeminy
●​ Electrical Effects ●​ With further increase in digitalis level into
intoxication, each after potential-evoked
Mechanical Effects action potential will itself elicit a
suprathreshold after-potential and a
●​ It increases contractility of the cardiac
self-sustaining tachycardia
sarcomere by increasing the free calcium
●​ VT may deteriorate into ventricular
concentration in the vicinity of the contractile
fibrillation, which is fatal
proteins during systole
●​ Increase in calcium concentration is the
Autonomic Actions of Cardiac Glycosides
result of 2 step processes:
Involve:
✔​ Increase of intracellular sodium concentration ●​ At lower dose, cardio selective
because of Na+/K+ ATPase inhibition parasympathetic effects
-​ These cholinomimetic effects are useful in the
✔​ Reduction of calcium expulsion from the cell treatment of certain arrhythmias
by the sodium-calcium exchanger caused by ●​ At high toxic levels, sympathetic outflow is
the increase in intercellular sodium increased
●​ The increased cytoplasmic calcium is ●​ The most common cardiac manifestation of
sequestered by SERCA in the SR for later the digitalis toxicity:
release ✔​ Atrioventricular junction rhythm
●​ The net result of the action of therapeutic
concentrations is a distinctive increase in ✔​ Premature ventricular depolarizations
cardiac contractility
●​ The rate of development of tension and of ✔​ Bigeminal rhythm
relaxation are both increased
●​ No significant change in time to peak tension ✔​ Second-degree atrioventricular block
●​ May occur in both normal and failing
myocardium Non-Cardiac Effects
●​ Cardiac glycosides may affect all excitable
Electrical Effects tissues
●​ Direct actions in the membranes of cardiac ●​ Smooth muscle
cells follow a well-defined progression ✔​ GIT is the most common site affected outside
✔​ An elderly, brief prolongation of the action the heart
potential followed by shortening in action -​ Anorexia
potential duration -​ Nausea
✔​ Results of increased potassium conductance -​ Vomiting
-​ Diarrhea
that is caused by increased intracellular ●​ CNS
calcium
●​ At higher concentration, resting membrane ✔​ Disorientation
potential is reduced (less negative)
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 Bipyridines
✔​ Hallucinations
●​ Although they have opposite inotropic
✔​ Visual disturbances effects, most of their benefits appear to
derive from vasodilation
-​ Aberration of color perception ●​ Are active orally and parenterally but are
●​ Gynecomastia is a rare adverse effect in available only in parenteral form
men ●​ Examples:
Interactions with Potassium ✔​ Inamrinone, previously called Amrinone
●​ Potassium and digitalis interact in two ways: ✔​ Milrinone
→​ They inhibit each other's binding to Na+/K+- MOA:
ATPase ●​ Inhibit phosphodiesterase isozyme 3
→​ Hyperkalemia reduces the enzyme-inhibiting (PDE-3)
actions of the cardiac glycosides ●​ Drugs that inhibit phosphodiesterase, the
→​ Hypokalemia facilitates the enzyme-inhibiting family of enzymes that inactivate cAMP and
action cGMP
→​ Abnormal cardiac automaticity is inhibited by
hyperkalemia Elimination half-life
●​ Is 3-6 hours, with 10-40% being excreted in
Interactions with Calcium and Magnesium the urine
●​ Calcium ion facilitates the toxic action of
cardiac glycosides Pharmacodynamics
●​ By accelerating the overloading of ●​ Increase myocardial contractility by
intracellular calcium stores that appears to increasing inward calcium flux in the heart
be responsible for the digitalis-induced during action potential
abnormal automaticity ●​ May also alter the intracellular movements of
✔​ Hypercalcemia & Hypomagnesemia calcium by influencing the SR
-​ Increases the risk of digitalis-induced ●​ They also have an important vasodilating
arrhythmia effect
✔​ The effects of magnesium ion are opposite to ●​ Inhibition of phosphodiesterase results in an
increase in cAMP and the increase in
those of calcium contractility and vasodilation
OTHER POSITIVE INOTROPIC DRUGS USED IN
HEART FAILURE
Istaroxime Toxicity
●​ Is an investigation steroid derivative
●​ Nausea and vomiting
●​ Less arrhythmogenic than digoxin
●​ Arrhythmias
●​ In phase 2 clinical trials
●​ Thrombocytopenia
●​ Liver enzyme changes
●​ Has been withdrawn in some countries
●​ Milrinone appears less likely to cause bone
marrow and liver toxicity than Inamrinone
●​ Used for acute HF and severe exacerbation
of CHF

Beta-Adrenoceptor Agonists
Dobutamine
MOA: ●​ Intermittent infusion may benefit patients with
✔​ Increases contractility by inhibiting Na+/K+- CHF
ATPase (like digitalis) MOA:
✔​ But in addition, facilitates sequestration of ✔​ Selective B1 agonist that has been most
Ca++ by the sarcoplasmic reticulum (SR) widely used in patients with HF

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 ✔​ Parenteral drug that produces an increase in ✔​ Diuretics
CO together with a decrease in ventricular
✔​ Vasodilators
filling pressure
Adverse effect:
●​ Tachycardia
-​ Increase in myocardial O2 consumption Diuretics
-​ Potential for producing angina or arrhythmias Furosemide
in patients with CAD

Dopamine
●​ Has been used in acute HF that needs to
increase BP
If you have hypotension already and heart failure, ●​ Drug of choice in HF
dopamine should be your choice over ●​ No direct effect on cardiac contractility
dobutamine because dobutamine only improves
the contractility of the heart but it may not Pharmacodynamics:
increase your blood pressure ●​ Major mechanism:
→​ To reduce venous pressure and ventricular
preload
●​ Reduction of salt and water retention
●​ Reduction of edema
Reduction of cardiac size, which leads to improve
pump efficiency

Spironolactone and Eplerenone

●​ Additional benefit of decreasing morbidity
and mortality in patients with severe HF, who
are also receiving ACE inhibitors and other
standard therapy
→​ Aldosterone may cause myocardial and
vascular fibrosis and baroreceptor dysfunction
●​ Study has proven these drugs are good in
the management of heart failure not just for
acute decompensated heart failure but rather
as part of the regimen in chronic
hypertension
●​ Specifically, with regards to Spironolactone,
the rales trial proves that the use of
spironolactone in patients with congestive
heart failure really improves their survival
DRUGS WITHOUT POSITIVE INOTROPIC and even the functional capacity
EFFECTS USED IN HF
●​ Not positive inotropic drugs MOA:
●​ Are the first-line therapies for CHF →​ Aldosterone antagonists
●​ These drugs are:
✔​ Diuretics

✔​ ACE inhibitors

✔​ Angiotensin receptor antagonist

✔​ Aldosterone antagonists

✔​ Beta-blockers
●​ For acute HF:
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 ACE Inhibitors Examples
Prototype: ●​ Prototype:
●​ Captopril →​ Losartan
●​ Others:
→​ Valsartan, Candesartan, Eprosartan,
Irbisartan, and Telmisartan
→​ Telmisartan has the longest half-life

Aliskiren
●​ A renin inhibitor for treatment of HPN
●​ No definitive benefit in clinical trials for HF
●​ Removed from the market because of its
side effects
Pharmacodynamics:
Vasodilators
●​ These drugs reduce peripheral vascular Pharmacodynamics:
resistance and thereby reduce afterload
●​ Are effective in acute HF because they
●​ They also reduce salt and water retention (by
provide a reduction in preload (through
reducing aldosterone secretion) reduce
venodilation), or reduction in afterload
preload
(through arteriolar dilation), or both.
●​ Reduce the long-term remodeling of the
●​ Long-term use of Hydralazine and
heart and vessels, an effect that maybe
Isosorbide Dinitrate can also reduce
responsible for the observed reduction in
cardiac remodeling
mortality and morbidity
●​ Hydralazine if used only as monotherapy is
not a good drug for heart failure, but if
Examples:
combined if with nitrates they are used in the
●​ Other ACE inhibitors: management of heart failure
→​ Enalapril, prodrug of enalaprilat
→​ Lisinopril, a lysine derivative of enalaprilat Nesiritide
→​ In the management of heart failure, we use ●​ A synthetic form of Brain natriuretic peptide
low dose compared to patients with HPN. (BNP)
●​ Other long-acting drugs: ●​ Approved for use in acute HF
→​ Benazepril, Fosinopril, Moexinopril, ●​ A recombinant product
Perindopril, Quinalapril, Ramipril, and ●​ Failed to show an improvement in mortality
Trandolapril or rehospitalization based from large trials
●​ IV bolus followed by infusion
●​ Short half-life
→​ 18 minutes
Angiotensin Receptor Blockers
MOA:
●​ Increased cGMP in smooth muscle cells and
reduces venous and arteriolar tone
●​ It also causes diuresis

Adverse Effects
●​ Have similar but more limited beneficial ●​ The most common adverse effect:
effects than ACE inhibitors →​ Excessive hypotension
●​ Should only be considered in patients ●​ Reports of significant renal damage and
intolerant of ACE inhibitors due to incessant deaths have resulted in extra warning
cough regarding this agent
●​ It should be used in great caution
MOA:
●​ Angiotensin AT1 receptor blocker

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 Beta-Adrenoceptor Blockers ●​ Thiazide- mild diuretic
●​ Most patients with CHF respond favorably to ●​ Hypokalemia- due to potassium loss
certain β-blockers in spite of the fact that this →​ Potassium supplementation
drug can precipitate acute decompensation →​ Combined with ACE inhibitor
of cardiac function →​ Potassium sparing diuretics
●​ Supported by studies, that showed a Ex. Eplerenone/ Spironolactone
reduction in mortality in patients with stable →​ adverse effect of furosemide and thiazide
severe HF
2. ACE Inhibitors
Examples: ●​ First drug to use in patient with LV
●​ Bisoprolol, Carvedilol, Metoprolol and dysfunction but no edema
Nebivolol ●​ Together with diuretics
●​ But NOT Bucindolol →​ First-line therapy for CHF
●​ Patients already on digoxin, ACE inhibitors
Suggested mechanism: cannot replace Digoxin
●​ Full understanding of the beneficial action is →​ Once digoxin is withdrawn, patient will
lacking deteriorate
●​ Attenuation of the adverse effects of high ●​ Slow down the progress of ventricular
concentrations of catecholamines (including dilation = reduces ventricular remodeling
apoptosis) ●​ Class effect– all ACE Inhibitors appear to be
→​ Remember in heart failure your compensatory effective
mechanisms, particularly sympathetic activity,
results in increased concentration in 3. Angiotensin Receptor Blockers
catecholamines but we do not want that for a ●​ Angiotensin II AT1 receptor blocker
long time because it would result in apoptosis ●​ E.g., Losartan (Prototype)
particularly the heart muscle cells. ●​ Produce beneficial hemodynamic effects
●​ Up-regulation of B-receptor similar to ACE I
●​ Decreased HR ●​ Are best reserved for patients who cannot
→​ Particularly in patients with ischemic heart tolerate ACE inhibitors (they are just
disease which is the common cause of heart alternative drugs for ACE inhibitor)
failure. To reduce the oxygen demand of the
heart. 4. Angiotensin Receptor Neprilysin Inhibitors
●​ Reduced remodeling through inhibition of the (ARNI)
mitogenic activity of catecholamines ●​ A new HF therapeutic class of agents:
→​ With prolonged exposure with catecholamines →​ Antagonizes RAAS
it will result in dilatation of the heart further →​ Inhibits the neutral endopeptidase system
reducing its systolic function. ●​ The first agent is a molecule that combines:
→​ Valsartan
CLINICAL PHARMACOLOGY OF DRUG USED IN →​ An AT1 receptor antagonist
HEART FAILURE →​ Antagonizes RAAS
Management of CHF →​ Sacubitril
1. Sodium Removal (very important thing) →​ A neprilysin inhibitor
●​ Dietary salt restriction and a diuretic →​ Inhibits the neutral endopeptidase system
→​ Is the mainstay in management of ●​ Brand name of Valsartan/Sacubitril
symptomatic HF combination is Entresto (very good drug in
→​ If you remove Na reduced intravascular the management of HF)
volume reduction in preload improving the ●​ Has additional benefit in HFrEF
function of the heart ●​ Degradation natriuretic peptides, bradykinin
→​ Mainstay in the management of symptomatic and adrenomedullin
HF →​ Thereby enhancing diuresis, natriuresis, and
→​ For ex., tell your px not to drink more than 1L myocardial relaxation
of fluid/day and restrict sodium intake to ●​ Inhibits renin and aldosterone secretion
2-4g/day →​ selectively blocking the angiotensin type 1
●​ Especially if edema is present receptor that reduces vasoconstriction,
●​ Furosemide– loop diuretic is required
​ ​ 9 / 11
 sodium, and water retention and myocardial ●​ Slow loading digitalization: 0.125-0.25mg per
hypertrophy. day is safer and just as effective as the rapid
●​ It is better than ACE-I (enalapril) in patient method
with mild to moderate HF (NYHA Class II to →​ Rapid ventricular response= digitalization
IV with LV Ejection Fraction of </=35% ●​ Rapid digitalization: 0.5–0.75mg every 8
●​ so far, we really have good feedback with hours for 3 doses, followed by (maintenance
using this drug improves the functional dose) 0.125-0.25mg per day
capacity reduction in hospitalization, only ●​ Measurement of plasma digoxin levels is
concern is it’s really expensive but one of the useful in patients who appear unusually
best drugs resistant or sensitive
●​ A level of 1ng/mL or less is appropriate
5. Vasodilators ●​ Narrow therapeutic window
●​ Selective arteriolar dilators
→​ In patients with fatigue due to low LV output Digitalis Toxicity:
hydralazine ●​ Visual changes or GI disturbances
●​ Selective venous dilators →​ Reduce the dose
→​ In patients with high filling pressures in whom ●​ Cardiac arrhythmia
the principal symptoms are dyspnea due to →​ More vigorous therapy is necessary
pulmonary congestion nitrates ●​ Serum digitalis and serum potassium level
●​ Nonselective vasodilators should be monitored
→​ In patients with severe CHF, elevated filling ●​ ECG
pressure with low CO→ ACE inhibitors plus →​ If there is PR interval prolongation of more
combination of hydralazine and nitrates, than 0.24 s, it is a sign that the patient already
especially among African Americans has digitalis toxicity
Blacks respond better in combination of ●​ Severe digitalis intoxication
hydralazine + nitrates ●​ Use of antiarrhythmic agents may lead to
cardiac arrest
6. Beta Blockers ●​ Temporary pacemaker insertion
●​ This therapy is beneficial if initiated →​ In patients with digitalis toxicity presenting with
cautiously at low doses bradycardia or atrioventricular block, you may
●​ Several months of therapy may be required need a temporary pacemaker to increase the
before improvement is noted: heart rate of the patient
→​ Start with low those that can be tolerated by ●​ Administration of digitalis antibodies (digoxin
your patient and try to increase the dose immunefab)
slowly and observe how the patient respond to →​ Not available in the Philippines
it ●​ Digitalis-induced arrhythmias are frequently
o​ Slight rise in EF made worse by cardioversion
o​ Slower HR ●​ Ventricular fibrillation
o​ Reduction in symptoms →​ Defibrillation
●​ Proven useful:
→​ Bisoprolol, Carvedilol, Metoprolol and 8. Cardiac Resynchronization
Nebivolol ●​ Non-pharmacologic intervention
●​ Not all beta blockers have proved useful ●​ Patients with normal sinus rhythm and a
wide QRS interval, e.g. greater than 0.12 sec
7. Digitalis ●​ Have impaired synchronization of the right
●​ Is indicated in patients with HF and atrial and left ventricular contraction
fibrillation ●​ Poor synchronization of the ventricular
→​ Remember usually px w/ atrial fibrillation has contraction results in diminished CO
also symptoms with HF, this is a good drug in ●​ Resynchronization, with left ventricular or
HF with atrial fib Biventricular pacing, has been shown to
●​ Is usually given only when diuretics and ACE reduce mortality in patients with CHF who
Inhibitors have failed to control symptoms were already receiving medical therapy
●​ Better results are obtained in patients with In cardiac resynchronization basically you implant a
atrial fibrillation than in sinus rhythm pacemaker inside your patient but the purpose of
this is not just to improve the heart rate but to
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 resynchronize the contraction of the right and left ADDITIONAL NOTES:
ventricle to improve the cardiac output. ●​ Heart failure is not a medical emergency per
se, unless the patient goes into acute
MANAGEMENT OF DIASTOLIC HF decompensation. The patient will present
●​ Nebivolol is effective in both systolic and with difficulty breathing, even hypoxemia if
diastolic heart failure you measure the auto-saturation. If the
●​ Control of HPN cause of acute HF is due to acute myocardial
●​ Revascularization if with coronary artery infarction then it is already a medical
disease (CAD) emergency.
→​ If the patient showed symmetrical stenosis in →​ For example, if you have hypotension that
the coronary arteries like in CAD, presents with dizziness or syncope, so that
percutaneous coronary intervention (PCI) or will make that an emergency condition. But
coronary artery bypass graft surgery (CABG) patients with HF in a stable state, meaning the
may improve the symptoms of diastolic blood pressure and vital signs are
dysfunction. okay—those who exhibit symptoms only in
●​ ACE inhibitors and ARB are useful exertion but at rest they are okay—they are
●​ Ivabradine a bradycardic drug, may also be not in an emergency. Unless they are
used classified under the New York Heart
Association Class IV where they are
MANAGEMENT OF ACUTE HF symptomatic even at rest; so they can be
●​ The most common cause of acute HF is considered to be in a medical emergency.
acute myocardial infarction ●​ Patients who have blood loss due to
→​ Best treated with emergency revascularization vehicular accidents experience hypovolemia
particularly if it is an ST elevation myocardial and are not directly considered to have heart
infarction failure. Heart failure is just a consequence of
●​ Either: the shock. When there is significant blood
→​ Coronary angioplasty with stent implantation loss, the heart will go into failure not because
or percutaneous coronary interventions (PCI) it is a failing heart but because of blood loss.
→​ Thrombolytic agent That is why the management really gears
→​ Emergency revascularization such as PCI or towards the correction of hypovolemia. So
angioplasty with stent. But if the hospital has you give IV fluids to replace the intravascular
no angioplasty or PCI, settle with giving a volume, and of course best would be to
thrombolytic agent so that we could do a replace the blood loss by giving blood
pharmacologic revascularization. transfusion.
●​ Measurements of hemodynamic parameters, ●​ If symptoms of heart failure appear and you
such as arterial pressure, CO, stroke work are in an outside-of-the-hospital setting, treat
index, pulmonary capillary wedge pressure the patient based on the symptoms he/she is
●​ IV treatment is the rule for acute HF presenting in the case of an emergency.
→​ Furosemide is the most commonly used to Most common would be difficulty breathing.
reduce intravascular volume The best thing you can do is to let the patient
→​ drug of choice especially if the patient is lie down with an elevated head or high back
presenting with pulmonary edema rest position This will improve oxygenation.
●​ Dopamine or Dobutamine are positive Give oxygen supplements if possible. Do not
inotropic drugs do CPR on a patient with heart failure unless
→​ Most useful for severe hypotension the patient is no longer breathing or
●​ Levosimendan responding. Do not do CPR on patients who
→​ Acute HF, approved in Europe are still awake, with pulses
→​ Not available in Philippines
●​ Nitroprusside, Nitroglycerin and
Nesiritide are vasodilators use in patients
with acute decompensation

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