Effects of the Angiotensin Converting-enzyme-inhibitor Enalapril On the Long-term Progression of Left-ventricular Dysfunction in Patients With Heart-failure

Background. In patients with heart failure, activation of the renin-angiotensin system is common an 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 Results. We 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. Conclusions. In 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

Effects of the Angiotensin-converting Enzyme-inhibitor Enalapril On the Long-term Progression of Left-ventricular Dilatation in Patients With Asymptomatic Systolic Dysfunction

Background. Patients with heart failure and reduced left ventricular (LV) ejection fraction (EF) manifest progressive LV dilatation, which is prevented by angiotensin converting enzyme (ACE) inhibitors. In patients with asymptomatic LV systolic dysfunction, in whom there is less activation of the renin-angiotensin system, ventricular remodeling might be less rapid and the benefit of ACE inhibitors less discernible. Methods and Results. One hundred eight patients enrolled in the Studies of Left Ventricular Dysfunction (SOLVD) Prevention Trial, with left ventricular ejection fraction less-than-or-equal-to 0.35 but without clinical heart failure, underwent radionuclide ventriculograms, and 49 underwent left heart catheterizations. Measurements were made before and after double-blinded randomization to enalapril (2.5 to 20 mg/d) or placebo. Repeated-measures analysis of all time points showed significant differences for change in end-diastolic volume (EDV) between enalapril and placebo groups. Significant difference between the enalapril and placebo groups (P<.05) was present for change in EDV at 1 year within the catheterization study and at a mean of 25 months within the radionuclide study. Radionuclide EDV increased in placebo patients (119+/-28 to 124+/-33 mL/m2, mean+/-SD) and decreased in enalapril patients (120+/-25 to 113+/-25 mL/m2). Differences between the two groups were significantly less than previously described in patients with symptomatic heart failure (P<.02), with less increase in LV volumes in the placebo group and less decrease in volumes in the enalapril group. Conclusions. Chronic ACE inhibitor treatment slows or reverses LV dilatation in patients with asymptomatic LV systolic dysfunction. Compared with symptomatic patients, asymptomatic patients manifest a slower rate of spontaneous LV dilatation and less reduction in LV volumes by enalapril