PHARMACOTHERAPY

OF HEART FAILURE

BY
JASTRIA PUSMARANI, M. Sc., Apt
Heart failure (HF)  a progressive clinical
syndrome caused by inability of the heart to
pump sufficient blood to meet the body’s
metabolic needs.
HF  disorder that reduces ventricular filling
(diastolic dysfunction) and/or myocardial
contractility (systolic dysfunction).
 PATHOPHYSIOLOGY

Causes of systolic dysfunction

 (decreased contractility) are reduced muscle mass
(eg, myocardial infarction [MI]),
 dilated cardiomyopathies, and
 ventricular hypertrophycan be caused by
pressure overload (eg, systemic or pulmonary
hypertension and aortic or pulmonic valve
stenosis) or volume overload
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Causes of diastolic dysfunction

(restriction in ventricular filling) are
increased ventricular stiffness,
ventricular hypertrophy,
Myocardial ischemia and MI
The leading causes of HF  coronary artery
disease and hypertension.
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As cardiac function decreases after myocardial

injury, the heart relies on compensatory mechanisms:
 tachycardia and increased contractility through
sympathetic nervous system activation;
 vasoconstriction; and
 ventricular hypertrophy
 remodeling.
 CLINICAL PRESENTATION

Primary symptoms are dyspnea (particularly on

exertion) and fatigue, which lead to exercise
intolerance.
Other pulmonary symptoms include orthopnea,
paroxysmal nocturnal dyspnea, tachypnea, and cough.
Fluid overload can result in pulmonary congestion and
peripheral edema.
Nonspecific symptoms  fatigue, nocturia, abdominal
pain, anorexia, nausea, bloating, ascites, poor appetite,
mental status changes, and weight gain.
Physical examination findings may include pulmonary
crackles, cool extremities, cardiomegaly, symptoms of
pulmonary edema (extreme breathlessness and anxiety,
sometimes with coughing, frothy sputum), peripheral
edema
PERIPHERAL OEDEMA WITH EVIDENCE
OF PITTING
PULMONARY OEDEMA ON CHEST X-RAY
 PRELOAD

Cardiac preload, the cardiac filling pressure, is

determined by blood volume
 increased by salt and water retention – and
 capacitance vessel tone,
 increased by sympathetic nervous system activation.
Drugs can reduce blood volume (diuretics)
reduce capacitance vessel tone (venodilators).
 N E W YO R K H E A R T A S S O C I AT I O N ( N Y H A ) F U N C T I O N A L
C L A S S I F I C A T I O N A N D A M E R I CA N C O L L E G E O F C A R D I O LO GY / A M E R I C A N
H E A R T A S S O C I AT I O N ( A C C / A H A ) S T A G I N G
PATHOPHYSIOLOGY MECHANISMS OF
HEART FAILURE AND MAJOR SITES OF
DRUG ACTION
 GENERAL APPROACH
ACC/AHA stage A
angiotensin-converting enzyme (ACE) inhibitors or
angiotensin receptor blockers (ARBs)
ACC/AHA stage B
ACE inhibitors (or ARBs in patients intolerant of ACE
inhibitors) and β-blockers
ACC/AHA stage C
diuretic (if clinical evidence of fluid retention),
ACE inhibitor, and β-blocker
aldosterone receptor antagonist, ARB (in ACE
inhibitor–intolerant patients), digoxin, and/or
hydralazine/isosorbide dinitrate (ISDN) may be useful
with carefully screened patients.
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ACC/AHA stage D

They should be considered for specialized therapies,

including mechanical circulatory support, continuous IV
positive inotropic therapy, cardiac transplantation, or
hospice care
 POSITIVE INOTROPIC AGENTS

Dobutamine  β1- and β2-receptor agonist with some α1-

agonist effects.
 The net vascular effect is usually vasodilation.
 It has a potent inotropic effect without producing a
significant change in heart rate.
Milrinone inhibits phosphodiesterase III and produces
positive inotropic and arterial and venous vasodilating
effects (an inodilator).
Dopamine produces dose-dependent hemodynamic effects
because of its relative affinity for α1-, β1-, β2-, and D1-
(vascular dopaminergic) receptors.