Heart failure

Results from any structural or functional cardiac disorder that impairs the ability of the ventricle to fill with or eject blood to meet the body,s needs at rest or during exercise.

Low out put failure

Factors affecting cardiac output

Intrinsic factors which regulate myocardial contractility .

Extrinsic factors including contractile state of arterioles & veins.

Pathophysiology of cardiac performance in heart failure

- Intrinsic changes .- Extrinsic changes.

Intrinsic changes:Myocardial hypertrophy to maintain cardiac

performance in the face of adverse effects as decrease in myocardial contractility.

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Extrinsic changes:Decrease in cardiac outputrenal blood

flow renin release , angiotensin 11 in after load, preload ,sympathetic

dischargecardiac output Remodeling: Proliferation of connective tissue

cells, abnormal myocardial cells.

Clinical manifestations of heart failure

Tachycardia, decreased exercise tolerance with rapid muscular fatigue, dyspnea ( pulmonary congestion) peripheral edema, cardiomegaly.

Classification of Low out put Failure

Left Heart Failure :Most common due to L.V.S . Dysfunction

Right Heart Failure : In Pulmonary hypertension

Classification of Heart Failure

According to NYHA

Class 1: No limitations on ordinary activities and symptoms occur only with greater than ordinary exercise.

Class11: Slight limitation of ordinary activities , that result in fatigue & palpitation

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Class 111: No symptoms at rest, fatigue occur with less than ordinary physical activity

Class 1V : Is associated with symptoms even at rest

High output failure

Even though there is an increase in cardiac output; still not enough to meet all the body needs as in hyperthyroidism, anemia.

Drugs used in treatment of heart failure

Drugs with positive inotropic effect as : Cardiac glycosidesPhosphodiesterase inhibitors β- adrenoceptor agonist

Drugs without positive inotropic effect

Diuretics

Aldosterone antagonist

ACEI & Angiotensin receptor blockers

Vasodilators

β- adrenoceptor blockers

Vasodilators

The chose of vasodilators according to signs and symptoms and hemodynamic changes : Selective venodilators as nitrate group is used

when the main symptoms is dyspnea due to pulmonary congestion.

Selective arteriodilators as hydralazine is used when the main complain is rapid fatigue due to low cardiac output.

Non-selective vasodilators as ACEI

Clinical uses of vasodilators

1. Acute heart failure 2. Chronic heart failure

Long-term use of hydralazine & isosorbide dinitrate can reduce remodeling of heart

ACEI & Angiotensin11 receptor blockers

afterload

preload

sympathetic activity

remodelingmortality rate

β-adrenoceptor blockers

Antagonism the enhancing action of sympathetic overactivity .Reduce mortality ( reduce the remodeling changes through inhibition the mitogenic activity of catecholamines.Inhibit renin releaseSome of them have antioxident activityE.g. carvedilol & metoprolol

Diuretics

Reduce salt and water retentionventricular preload .Reduction of edema and its symptomsReduction of cardiac size improve cardiac performanceSpironolactone has two benefits:potassium sparing effect & inhibit the action of aldosterone .

β-agonist

Dopamine :acts on α ,β1 and dopamine receptors.

Dobutamine :selective β1- agonist.

Both of them are given intravenously & used in acute cardiac emergencies.

Dopamine is effective in patients with impaired renal function.

Adverse effects

TachycardiaAngina Tachyphylaxis

Phosphodiesterase inhibitors

Bipyridines : (Amrinone ,Milrinone )

They are given only intravenously.

Half-life 3-6hrs.

10-40% excreted in urine.

Mechanism of action

Inhibit phosphodiesterase enzyme (isozyme 3) in both cardiac & smooth muscles resulting an ↑ in cAMP leading to:

- Positive inotropism .

- Dilation in both resistance & capacitance vessels (reduction in after load & preload.)

Therapeutic uses

Used only for acute heart failure

( Short term use )

Adverse effects

Nausea ,vomiting

Arrhythmias (less than digitalis )

Thrombocytopenia

Liver toxicity

Milrinone less hepatotoxic and less bone marrow depression than amrinone.

Digitalis (cardiac glycosides )

Origin

Chemistry

Preparations

Structure o of cardiac glycoside

Pharmacokinetics

Oral availabilityOuabain Digoxin Digitoxin 0 75 > 90 Half- life 21 40 168 Plasma protein binding 0 20-40 > 90Percentage metabolized 0 < 40 > 80

Pharmacodynamics

At the molecular level cardiac glycosides inhibit Na+ / K+ ATP ase (sodium pump ).

Cardiac effects :

A) Mechanical

B) Electrical

Mechanism of action Mechanism of action

(A) MECHANICAL EFFECT(A) MECHANICAL EFFECT

Increase in myocardial contractility

(B) ELECTRICAL EFFECTS(B) ELECTRICAL EFFECTS

At Therapeutic DosesAt Therapeutic Doses

A) Slow conduction through S.A.N. & A.V.N.

prolong conduction time between atrium and ventricles ( prolong P-R interval in ECG.) .

B) Short duration of action potential & refractory periods

of both atrium & ventricles (Short in QT interval ).

At Toxic DosesAt Toxic Doses

in automaticity of ectopic focus All forms of arrhythmias can be detected : -

- Second-degree of A-V block.

- In Purkinje conducting system leading bigeminy rhythm.

Extra cardiac effectsExtra cardiac effects

GIT :Anorexia, nausea,vomiting, diarrhea.

C.N.S. :Disorientation,hallucination,visual disturbances, agitation, convulsions.

Gynecomastia

Kidney : Diuretic effect

I. Improve renal function .

II. Inhibit Na+ reabsorption from P.C.T.

Adverse effects

Heart

All forms of cardiac arrhythmias

GIT

C.N.S.

Skin : rash

Gynecomastia

Contraindications

Toxic myocarditis

Constrictive pericarditis

Cardioversion

Digitalis are effective in H.F. due to hypertension, atherosclerosis or ischemic heart diseases.

Factors increase digitalis toxicity

Small Lean body massRenal diseaseHypothyroidismHypokalemia Hypomagnesemia Hypercalemia

Treatment of digitalis toxicity

Stop drug

Potassium therapy

Cholestyramine

Atropine

Lidocaine

Fab antibodies in life-threating or severe cases.

Clinical uses

Heart failure ( LVSD)

2-Atrial flutter or fibrillation

Drug interactions

Diuretics hypokalemia (arrhythmia)Quinidine : plasma level of digitalis through (1) displaces from protein binding sites (2) renal clearance.Antibiotics that alter intestinal flora digoxin bioavailability Agents that release catecholamines sensitize myocardium to digitalis to induce arrhythmias.

Management of chronic heart failure

Reduce work load of the heart

Limit activity

Reduce weight

Control hypertension

Restrict sodium

Diuretics

ACEI or receptor blockers

Cont.

Digitalis

β- blockers ( class II-IV stable HF)

Vasodilators

Management of acute heart failure

Volume replacement

Diuretics

Positive inotropic drugs

Vasodilators