Drugs Used in Heart Failure

Drugs Used in Heart Failure

Heart failure occurs when cardiac output is inadequate to provide the oxygen needed by the body. It is a highly lethal condition, with a 5-year mortality rate conventionally said to be about 50%. The most common cause of heart failure in the USA is coronary artery disease, with hypertension also an important factor. Two major types of failure may be distinguished. Approximately 50% of younger patients have systolic failure, with reduced mechanical pumping action (contractility) and reduced ejection fraction. The remaining group has diastolic failure, with stiffening and loss of adequate relaxation playing a major role in reducing filling and cardiac output; ejection fraction may be normal even though stroke volume is significantly reduced. The proportion of patients with diastolic failure increases with age. Because other cardiovas-cular conditions (especially myocardial infarction) are now being treated more effectively, more patients are surviving long enough for heart failure to develop, making heart failure one of the cardio-vascular conditions that is actually increasing in prevalence.Heart failure is a progressive disease that is characterized by a gradual reduction in cardiac performance, punctuated in many cases by episodes of acute decompensation, often requiring hospitalization.

Treatment is therefore directed at two somewhat different goals: (1) reducing symptoms and slowing progression as much as possible during relatively stable periods and (2) managing acute episodes of decompensated failure. These factors are discussed in Clinical Pharmacology of Drugs Used in Heart Failure.

Although it is believed that the primary defect in early systolic heart failure resides in the excitation-contraction coupling machin-ery of the heart, the clinical condition also involves many other processes and organs, including the baroreceptor reflex, the sym-pathetic nervous system, the kidneys, angiotensin II and other peptides, aldosterone, and apoptosis of cardiac cells. Recognition of these factors has resulted in evolution of a variety of drug treat-ment strategies (Table 13–1).

Large clinical trials have shown that therapy directed at non-cardiac targets is more valuable in the long-term treatment of heart failure than traditional positive inotropic agents (cardiac glycosides [digitalis]). Extensive trials have shown that ACE inhibitors, angiotensin receptor blockers, certain β blockers, aldosterone receptor antagonists, and combined hydralazine-nitrate therapy are the only agents in current use that actually prolong life in patients with chronic heart failure. These strategies are useful in both systolic and diastolic failure. Positive inotropic drugs, on the other hand, are helpful mainly in acute systolic fail-ure. Cardiac glycosides also reduce symptoms in chronic systolic heart failure. Other positive inotropic drugs have consistently reduced survival in chronic failure, and their use is discouraged.

CASE STUDY

65-year-old man has developed shortness of breath with exertion several weeks after experiencing a viral illness. This is accompanied by swelling of the feet and ankles and increasing fatigue. On physical examination he is found to be mildly short of breath lying down, but feels better sitting upright. Pulse is 105 and regular, and blood pressure is 90/60 mm Hg. His lungs show crackles at both bases, and his jugular venous pressure is elevated. The liver is enlarged, and there is 3+ edema of the ankles and feet. An echocardiogram shows a dilated, poorly contracting heart with a left ventricu-lar ejection fraction of about 20% (normal: 60%). The pre-sumptive diagnosis is dilated cardiomyopathy secondary to a viral infection with stage C, class III heart failure. What treat-ment is indicated?