Effects of the Angiotensin Converting Enzyme Inhibitor Enalapril on the Long‐term: Progression of Left Ventricular Dysfunction in Patients With Heart Failure

BackgroundIn patients with heart failure, activation of the renin-angiotensin system is common and has been postulated to provide a stimulus for further left ventricular (LV) structural and functional derangement. We tested the hypothesis that chronic administration of the angiotensin converting enzyme (ACE) inhibitor enalapril prevents or reverses LV dilatation and systolic dysfunction among patients with depressed ejection fraction (EF) and symptomatic heart failure. Methods and ResultsWe examined subsets of patients enrolled in the Treatment Trial of Studies of Left Ventricular Dysfunction (SOLVD). Fifty-six patients with mild to moderate heart failure underwent serial radionuclide ventriculograms, and 16 underwent serial left heart catheterizations, before and after randomization to enalapril (2.5–20 mg/day) or placebo. At 1 year, there were significant treatment differences in LV end-diastolic volume (EDV; p < 0.01), end-systolic volume (ESV; p < 0.005), and EF (p < 0.05). These effects resulted from increases in EDV (mean±SD, 136±27 to 151±38 ml/m2) and ESV (103±24 to 116±24 ml/m2) in the placebo group and decreases in EDV (140±44 to 127±37 ml/m2) and ESV (106±42 to 93±37 ml/m2) in the enalapril group. Mean LVEF increased in enalapril patients from 0.25±0.07 to 0.29±0.08 (p < 0.01). There was a significant treatment difference in LV end-diastolic pressure at 1 year (p < 0.05), with changes paralleling those of EDV. The time constant of LV relaxation changed only in the placebo group (p < 0.01 versus enalapril), increasing from 59.2±8.0 to 67.8±7.2 msec. Serial radionuclide studies over a period of 33 months showed increases in LV volumes only in the placebo group. Two weeks after withdrawal of enalapril, EDV and ESV increased to baseline levels but not to the higher levels observed with placebo. ConclusionsIn patients with heart failure and reduced LVEF, chronic ACE inhibition with enalapril prevents progressive LV dilatation and systolic dysfunction (increased ESV). These effects probably result from a combination of altered remodeling and sustained reduction in preload and afterload.