Beta-blockade in heart failure. Basic concepts and clinical results.

Both experimental and clinical observation suggest that activation of the sympathetic nervous system exerts an important deleterious effect in patients with chronic heart failure. The precise mechanisms responsible for this effect have not been defined, but prolonged exposure to norepinephrine is associated with a variety of adverse physiologic and biochemical/molecular actions. Identification of these deleterious pathways has helped to explain why drugs that block the cardiac effects of norepinephrine (i.e., beta-blockers) retard remodeling and prolong life in experimental models of heart failure. beta-Blockers have been shown to reduce the mortality of patients after an acute myocardial infarction; this effect appears to be particularly marked in patients with postinfarction heart failure. Results of several trials suggest that long-term treatment with beta-blockers can improve symptoms and reduce the frequency of hospitalizations for heart failure. Most recently, carvedilol has been shown to reduce the risk of all-cause mortality by 65% in patients with either an ischemic or nonischemic cardiomyopathy. These findings, taken together, suggest that pharmacologic interference with the sympathetic nervous system can produce important clinical benefits in patients with left ventricular systolic dysfunction.