With greater understanding of the impact of neuroendocrine stimulation on the adverse outcomes of
heart failure, especially lethal arrhythmias and
sudden cardiac death, focus has returned to the potential benefits of beta-
adrenergic blockade. In patients with
myocardial infarction and left ventricular (
LV) dysfunction, particularly those prone to life-threatening arrhythmias, beta-blocker
therapy has been associated with a lower incidence of arrhythmias and improved survival. Even in the absence of
angiotensin-converting enzyme (ACE) inhibition, beta blockade has improved cardiac function and LV contractility in nonischemic
heart failure, leading to a decrease in LV end-diastolic pressure and improved clinical status. Both the
Metoprolol in
Dilated Cardiomyopathy (MDC) trial and the Cardiac Insufficiency
Bisoprolol Study (CIBIS) found beta blockade to be associated with decreased mortality rates in patients with nonischemic
heart failure. Of the 3 large randomized mortality trials now under way, the
Metoprolol CR/XL Randomized Intervention Trial in
Heart Failure (MERIT-HF) is specifically designed to investigate the effects of beta blockade on total mortality when used as an adjunct to ACE inhibition in patients with ischemic or nonischemic
heart failure. Unresolved issues to be addressed include whether: (1) beta-blocker
therapy in
heart failure can improve survival and/or reduce the incidence of
sudden cardiac death; (2) beta blockade is equally effective in ischemic and nonischemic
heart failure; (3) any specific beta blocker may be better tolerated initially and cause fewer adverse effects; and (4) all beta blockers result in improved exercise tolerance and quality of life.