Heart failure results when cardiac output is inadequate for the needs of the body. A defect in cardiac contractility is complicated by multiple compensatory processes that further weaken the failing heart. The drugs used in heart failure fall into 3 major groups with varying targets and actions.
Heart failure is an extremely serious cardiac condition associated with high mortality. The fundamental physiologic defect in heart failure is a decrease in cardiac output relative to the needs of the body, and the major manifestations are dyspnea and fatigue. The causes of heart failure are still not completely understood. In some cases, it can be ascribed to simple loss of functional myocardium, as in myocardial infarction. It is frequently associated with chronic hypertension, valvular disease, coronary artery disease, and a variety of cardiomyopathies. About one third of cases are due to a reduction of cardiac contractile force and ejection fraction (systolic failure). Another third is caused by stiffening or other changes of the ventricles that prevent adequate filling during diastole; ejection fraction may be normal (diastolic failure). The remainder of cases can be attributed to a combination of systolic and diastolic dysfunction. The natural history of heart failure is characterized by a slow deterioration of cardiac function, punctuated by episodes of acute cardiac decompensation that are often associated with pulmonary or peripheral edema or both (congestive heart failure).
The reduction in cardiac output is best shown by the ventricular function curve (Frank-Starling curve; Figure 13–1). The changes in the ventricular function curve reflect some compensatory responses of the body and demonstrate some of the responses to drugs. As ventricular ejection decreases, the end-diastolic fiber length increases, as shown by the shift from point A to point B in Figure 13–1. Operation at point B is intrinsically less efficient than operation at shorter fiber lengths because of the increase in myocardial oxygen requirement associated with increased fiber tension and length (see Figure 12–1).
Ventricular function (Frank-Starling) curves. The abscissa can be any measure of preload: fiber length, filling pressure, pulmonary capillary wedge pressure, etc. The ordinate is a measure of useful external cardiac work: stroke volume, cardiac output, etc. In heart failure, output is reduced at all fiber lengths, and the heart expands because ejection fraction is decreased or filling pressure is increased (or both). As a result, the heart moves from point A to point B. Compensatory sympathetic discharge or effective treatment allows the heart to eject more blood, and the heart moves to point C on the middle curve.
The homeostatic responses to depressed cardiac output are extremely important and are mediated mainly by the sympathetic nervous system and the renin-angiotensin-aldosterone system. They are summarized in Figure 13–2. Increased blood volume results in edema and pulmonary congestion ...