PATHOPHYSIOLOGIC AND PHARMACOLOGICAL RATIONALES FOR CLINICAL MANAGEMENT OF CHRONIC HEART-FAILURE WITH BETA-BLOCKING-AGENTS

An understanding of the important role of neurohormonal compensatory mechanisms in heart failure has been translated into therapeutic options that can improve cardiac function, alter disease progression, and improve survival. Angiotensin-converting enzyme inhibitors are of proven benefit in this regard, and beta-adrenergic receptor antagonists are potentially another such class of agents. By inhibiting the myocardial effects of chronic adrenergic activation, beta blocking agents may improve left ventricular function or delay its deterioration in patients with heart failure. Aside from blocking beta-adrenergic receptors, other ancillary properties inherent in third-generation beta-blocking agents (such as vasodilation) may exert additional favorable effects. Clinical data generated in subjects with heart failure indicate that beta-antagonist therapy exerts its physiologic and clinical effects through neurohormonal antagonism, generally analogous to angiotensin-converting enzyme inhibitors. Virtually all controlled long-term studies show that beta-blocking agents improve cardiac function and hemodynamics in patients with chronic heart failure, but large-scale trials are needed to ascertain a favorable effect on the natural history of heart failure.