Circulation, Vol 86, 431-438, Copyright © 1992 by American Heart Association
MA Konstam, MF Rousseau, MW Kronenberg, JE Udelson, J Melin, D Stewart, N Dolan, TR Edens, S Ahn and D Kinan
BACKGROUND. In 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 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
less than 0.01), end- systolic volume (ESV; p less than 0.005), and EF (p
less than 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 less
than 0.01). There was a significant treatment difference in LV end-
diastolic pressure at 1 year (p less than 0.05), with changes paralleling
those of EDV. The time constant of LV relaxation changed only in the
placebo group (p less than 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.
ARTICLES
Effects of the angiotensin converting enzyme inhibitor enalapril on the long-term progression of left ventricular dysfunction in patients with heart failure. SOLVD Investigators
Department of Medicine, Tufts University, New England Medical Center, Boston, MA 02111.
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