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Introduction: HF definition
 HF is a complex, progressive disorder in which the heart
is unable to pump sufficient blood (oxygen) to meet the
needs of the body
 cxized by dyspnea & fatigue, at rest or with exertion,

 Occurs due to structural &/or functional abnormalities of the

heart

 It is a highly lethal condition

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 Causes

• Include
 arteriosclerotic heart disease
 myocardial infarction,
 hypertensive heart disease
 valvular heart disease
 dilated cardiomyopathy, and
 congenital heart disease

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 Two major types of heart failure may be distinguished.
 Systolic failure
 Diastolic failure

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Systolic failure

 Reduced mechanical pumping

action (contractility) &
 With reduced CO and
ejection fraction (EF).
 is typical of acute failure,
especially that resulting from
MI

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Echocardiography
– ejection fraction
(EF) < 45%

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Diastolic failure

 Due to stiffening & loss of adequate relaxation

 reduced cardiac filling & , thus, CO
 Ejection fraction can be normal as the heart may contract
normally.
 often is result of cardiac hypertrophy
 stroke volume is significantly reduced.
 does not usually respond optimally to positive inotropic
drugs.

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Cardiac hypertrophy can reduce cardiac filling, and
thus result in significant reduction in stroke volume
The left ventricle is markedly thickened and
undergone hypertrophy. Result in sever heart
failure
Pathophysiology HF

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 Signs & symptoms of HF

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Management of Heart Failure
 The treatment of CHF aims to
 reduce preload and afterload

 increase myocardial contractility.

 Drugs used to treat heart failure can be broadly

divided into:
 Drugs with positive inotropic effect.

 Drugs without positive inotropic effect.

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Drugs with positive inotropic effect
 increase the force of contraction of the heart
muscle.
 Includes:
 Cardiac glycosides,
 PDE Inhibitors,
 Methylxanthines, and
 Sympathomimetics
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Cardiac glycosides.

 Commonly used cardiac glycosides are digoxin and digitoxin.

 MOA:
 Cardiac glycosides inhibit the membrane-bound Na+/K+
ATPase often called the “Sodium Pump”.
 This leads to an increase in accumulation of sodium in the cells.
 As a consequence of the higher intracellular sodium,
transmembrane exchange of sodium and calcium is decreased.
 Ultimately, leading to an increase in the intracellular
calcium that acts on contractile proteins.

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 Therapeutic uses of cardiac glycosides include:
 Heart failure (left, right or both sided heart failure)
 Cardiac arrhythmias (Atrial flutter, atrial fibrillation
with or without CHF)
 Toxicity of cardiac glycosides include:
 Gastrointestinal effects such as anorexia, nausea,
vomiting, diarrhea
 Cardiac effects such as heart block and arrhythmias
 CNS effects such as headache, malaise, hallucinations,
delirium, visual disturbances

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Phosphoiesterase Enzyme (PDE) Inhibitors :
Pharmacodynamics
 Inamrinone (amrinone) & milrinone inhibit PDE
isozyme 3 (PDE-3)
 Inhibition of PDE results in an ↑ in cAMP
 ↑ed cAMP in cardiac muscle cells increases inward
Ca2+ flux – contraction
 ↑ Myocardial contractility
 ↑ in cAMP in smooth muscle cell inhibits binding of
myosin to actin – relaxation
 vasodilation.
 Thus, PDE Inhibitors result in increase in
myocardial contractility & vasodilation.
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Toxicity of Inamrinone Includes:

 Nausea & vomiting

 Arrhythmias
 Thrombocytopenia & hepatotoxicity.

 Milrinone appears less likely to cause bone

marrow and liver toxicity than inamrinone but it
does cause arrhythmias.

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Methylxanthines

 Methylxanthines, e.g. theophylline in the form of

aminophylline
 Aminophylline has a positive inotropic effect,
bronchodilating effect and a modest effect on renal
blood flow.
 MOA: block phosphodiesterase enzyme – incr. [cAMP]
 It is used for management of acute left ventricular
failure or pulmonary edema.
 Not suitable for diabetics as it increases blood glucose
level
 Via stimulation of glycogenolysis, gluconeogenesis, and lipolysis.

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β-adrenoceptor stimulants
(Sympathomimetics): Dobutamine
 Selective β1 agonist

 Increases heart rate and force of contraction (1°)

 increases CO
 widely used in pts with acute HF

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Sympathomimetics…

Dopamine
 β1 agonist, and increase heart rate and force of
contraction
 Has also been used in acute HF

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 Drugs without positive
Inotropic effects used in HF

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 Drugs without positive Inotropic effects

 Paradoxically, these agents (non positive

inotropic drugs) are the first-line therapies for
chronic HF.
 The drugs most commonly used are
 Diuretics
 ACE inhibitors
 Angiotensin receptor antagonists (ARBs)
 Aldosterone antagonists &
 β-blockers.
 In acute HF, diuretics & vasodilators play
important roles 28
β-Blockers

 Most chronic pts respond favorably to certain β blockers

 Start from small dose, and titrate up slowly – otherwise, it can
aggravate the symptoms
 MOA: not clearly known,
 improve left ventricular structure and function (↓ in chamber
size & ↑ in ejection fraction)
 reduce excessive stimulation from excess circulating
catecholamines in CHF
 May induce overexpression of the β1 receptor in the
myocardium 29
Diuretics
 Diuretics are effective alone in mild cases of CHF and in
combination with digitalis in severe cases
 The following diuretics may be used:
• Thiazdes in combination with spironolactone and triameterene
(potassium sparing diuretic) in mild cases
• Loop diuretics (furosemide or ethacrynic acid) may be used in severe
cases with potassium sparing diuretics.
• Major MOA in HF is to reduce venous return & ventricular
preload.
• The reduction of cardiac size, which leads to improved pump
efficiency, is of major importance in systolic failure.

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Vasodilators
 Vasodilator drugs can be divided as:
 Selective arteriolar dilators Eg. Hydralazine
 Reduce peripheral resistance and thereby reduce afterload

 Venous dilators E.g. Isosorbide dinitrate

 Reduce preload

 Calcium channel blockers E.g. Nifedipine (vasodialator)

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 Spironolactone & Eplerenone
 Aldosterone antagonist diuretics
 Aldosterone is believed to cause myocardial &
vascular fibrosis & baroreceptor dysfunction in
addition to its renal effects.
 Thus, aldosterone antagonists may decrease
 myocardial & vascular fibrosis
 baroreceptor dysfunction
 Salt and water retention
 Thereby, improve cardiac and vascular function

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ACE Inhibitors

Example: Captopril, Lisinopril, Enalapril

 Reduce peripheral resistance and thereby reduce afterload.

 Reduce salt and water retention (by reducing aldosterone

secretion) and in that way reduce preload.

 Reduce the long-term remodeling of the heart and blood

vessels

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ARBs

 AT1 RBs such as losartan

 Appear to have similar but more limited

beneficial effects over ACEIs

 should be considered in pts intolerant of ACEIs

 Especially in the case of incessant (unceasing) cough.

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Drug treatment
Generally acute heart failure should be treated with:
Loop diuretics
Prompt acting positive inotrpic agent such as a β agonists
or PDEI and
Vasodilators as required to optimize filling pressure and BP
Chronic failure is best treated with
diuretics (loop agent + spiranolactone) plus ACEI or if
tolerated β-blockers
Digitalis is used if systolic dysfunction is prominent

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