NEUROENDOCRINE ACTIVATION IN RELATION TO LEFT-VENTRICULAR FUNCTION IN CHRONIC SEVERE CONGESTIVE-HEART-FAILURE - A SUBGROUP ANALYSIS FROM THE COOPERATIVE NORTH SCANDINAVIAN ENALAPRIL SURVIVAL STUDY (CONSENSUS)

Left ventricular (LV) function and plasma levels of cardiovascular hormones were examined in patients with severe chronic congestive heart failure (CHF), randomized to placebo or enalapril, in addition to conventional therapy. M-mode echocardiography and plasma hormone concentrations were available at baseline and after 6 weeks of treatment. There was a significant relationship between LV systolic function and levels of angiotensin-II and norepinephrine. Enalapril increased LV fractional shortening (FS%) (13.3 +/- 5.6 to 15.4 +/- 5.8, p < 0.05) and decreased the systolic time interval index (0.58 +/- 0.14 to 0.48 +/- 0.15, p < 0.05) concurrent with a significant decrease in angiotensin-converting enzyme activity and in aldosterone, angiotensin-II, and norepinephrine concentrations after 6 weeks. No changes were found in the placebo group. However, there was no direct relationship between the amount of change in neurohormones and improvement in LV function after 6 weeks. These findings indicate that in patients with severe chronic CHF, severe LV systolic dysfunction is associated with high plasma levels of angiotensin-II and norepinephrine, which can be favorably modified by enalapril. This may be of importance for prolonging life in severe heart failure. The lack of relationship between changes in individual hormones and systolic function suggests complex dynamic interaction. It is, therefore, not sufficient to predict changes in LV function by measuring changes in only one hormone.