Role of neurohormonal mechanisms in determining survival in patients with severe chronic heart failure.

Support for the concept that neurohormonal mechanisms play an important role in determining the survival of patients with severe chronic heart failure is derived from two lines of evidence: circulating levels of neurohormones are markedly elevated in patients who have a poor long-term prognosis and the survival of high-risk patients may be favorably modified by treatment with specific neurohormonal antagonists. Plasma norepinephrine is a major prognostic factor in patients with severe chronic heart failure, the most markedly elevated levels being observed in patients with the most unfavorable long-term prognosis. Data from uncontrolled studies suggest that low-dose beta-blockade may improve the survival of patients with dilated cardiomyopathy. Similar trends were noted in the Beta-Blocker Heart Attack Trial, in which patients with congestive heart failure before or accompanying their acute myocardial infarction experienced a significant reduction in sudden death when treated with beta-blockers. In contrast, there appeared to be little selective benefit in patients without heart failure, who presumably had low circulating levels of catecholamines. Similarly, serum sodium concentration is a major prognostic factor in patients with severe chronic heart failure, the shortest survival being observed in patients with the most severe hyponatremia. The poor long-term outcome of hyponatremic patients appears to be related to the marked elevation of plasma renin activity in these individuals, since (in retrospective studies) hyponatremic patients appeared to fare significantly better when treated with converting-enzyme inhibitors than when treated with vasodilator drugs that did not interfere with angiotensin II formation. In contrast, there appeared to be no selective benefit of converting-enzyme inhibition on the survival of patients with a normal serum sodium concentration, in whom plasma renin activity was low. These data suggest that neurohormonal systems may exert a deleterious effect on the survival of some patients with severe chronic heart failure, which may be favorably modified by long-term treatment with specific neurohormonal antagonists.