Cardiac Failure

•	Pathophysiology.
•	Principles of therapy.
•	Individual drugs.

Pathophysiology

1.	Cardiac failure is present when the heart cannot provide all organs with the blood supply appropriate to demand, i.e. the cardiac output is inadequate.

2.	Cardiac output = Heart rate x Stroke volume.

3.	Factors regulating stroke volume:

a.	Preload: the load on the heart created by the volume of blood injected into the left ventricle by the left atrium.

b.	Afterload: the load on the contracting ventricle created by the resistance to the blood injected by the ventricle into the arterial system.

c.	Contractility: the capacity of the myocardium to generate the force necessary to response to preload and to overcome afterload.

Principles of Drug therapy

1.	Objectives:

a.	To reduce morbidity.

b.	To reduce mortality.

2.	Target of therapy:

a.	Treatment of failing pump: to increase contractility.

b.	Treatment of underlying causes of cardiac failure, e.g. hypertension.

c.	Treatment of associated problems, e.g. atrial fibrillation, pulmonary edema.

3.	Drug therapy serves to:

a.	increase cardiac output.

b.	reduces myocardial workload and oxygen demand.

4.	Cardiac output can be increased by strengthening the heart or by reducing the resistance against which it has to work.

5.	Afterload reduction by vasodilators includes more options, and the ACE inhibitors are the most widely used.

6.	The nitrates also act by partly reducing afterload, but also improve coronary blood flow.

7.	Classification of drugs:

a.	Reduction of preload: diuretics, nitrates.

b.	Reduction of preload and afterload: ACE inhibitors.

c.	Stimulation of myocardium: digoxin.

8.	Management:

a.	Mild cardiac failure should be treated with a thiazide diuretic, if renal function is normal.

b.	If not, or if edema persists, the next step is a loop diuretic in lowly daily dose, e.g. frusemide, to which amiloride can be added to conserve potassium.

c.	The addition of a thiazide, usually metolazone, to a loop diuretic is usually effective in stimulating a diuresis.

d.	All patients requiring chronic diuretic treatment for heart failure should also now receive an ACE inhibitor which improve survival even in mild failure.

e.	ACE inhibitors have a diuretic-sparing effect, which improves the patients’ symptoms by maintaining peripheral perfusion, and reducing the neurohumoral response to excessive diuresis.

f.	An alternative to ACE inhibitors as a vasodilator is isosorbide mononitrate to which hydralazine may later be combined. 

Drugs used in cardiac failure

1.	Diuretics:

a.	Increase salt and water loss, reduce blood volume and lower excessive venous filling pressure.

b.	The congestive features of edema, in the lungs and periphery, are alleviated.

c.	When the heart is grossly enlarged, cardiac output will also increase.

2.	Nitrates:

a.	Dilate the smooth muscle in venous capacitance vessels, increase the volume of the venous vascular bed, reduce ventricular filling pressure, thus decreasing heart wall stretch, and reduce myocardial oxygen.

b.	Glyceryl trinitrate may be given sublingually for acute left ventricular failure.

c.	For chronic left ventricular failure isosorbide dinitrate or isosorbide mononitrate may be given by mouth in divided doses

d.	Exercise capacity is improved but tolerance to nitrates may develop with chronic use.

3.	Reduction of afterload:

a.	Hydralazine relaxes arterial smooth muscle and reduces peripheral vascular resistance.

b.	Reflex tachycardia, however, limits its usefulness and lupus erythematosus may be induced.

4.	ACE inhibitors:

a.	Reduce afterload by preventing the conversion of angiotensin I to angiotensin II, a powerful vasoconstrictor.

b.	Reduce preload, because the formation of aldosterone, and thus retention of salt and water, is prevented by reduction of angiotensin II.

c.	ACE inhibitors are the only drugs which reduce peripheral resistance without causing a reflex activation of the sympathetic system. 

5.	Digoxin:

a.	Improves myocardial contractility most effectively in the dilated, failing heart.

b.	Ventricular filling is improved.