Hormones regulating cardiovascular function in patients with severe congestive heart failure and their relation to mortality. CONSENSUS Trial Study Group.

Abstract

There is a varying hormonal activation in heart failure. To be able to evaluate this activation and relate it to prognosis, we took blood samples at baseline and after 6 weeks from 239 patients with severe heart failure (all in New York Heart Association class IV) randomized to additional treatment with enalapril or placebo. In this study (CONSENSUS), which has previously been reported, there was a significant reduction in mortality among patients treated with enalapril. The present data show in the placebo group a significant positive relation between mortality and levels of angiotensin II (p<0.05), aldosterone (p=0.003), noradrenaline (p<0.001), adrenaline (p=0.001), and atrial natriuretic factor (p=0.003). A similar relation was not observed among the patients treated with enalapril. Significant reductions in mortality in the groups of patients treated with enalapril were consistently found among patients with baseline hormone levels above median values. There were significant reductions in hormone levels from baseline to 6 weeks in the group of patients treated with enalapril for all hormones except adrenaline. There were no correlations between these changes in hormone levels. Summarily, there is a pronounced but variable neurohormonal activation in heart failure even in patients with similar clinical findings. This activation is reduced by enalapril therapy. The results suggest that the effect of enalapril on mortality is related to hormonal activation in general and the renin-angiotensin system in particular. (Circulation 1990;82:1730-1736 T he long-term prognosis for patients with severe congestive heart failure has been very poor.1 In severe congestive heart failure, compensatory activation of neurohormonal mechanisms,2 the importance of which is unclear, takes place. The increased sympathetic activity may even induce myocardial deterioration in certain types of congestive heart failure.3 The neurohormonal activation may increase myocardial oxygen consumption by elevating heart rate and afterload and may also induce coronary vasoconstriction. A direct cardiotoxic effect of angiotensin II has also been recently

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