Circulation, Vol 89, 2852-2859, Copyright © 1994 by American Heart Association
HN Sabbah, H Shimoyama, T Kono, RC Gupta, VG Sharov, G Scicli, TB Levine and S Goldstein
BACKGROUND: Recent clinical trials have suggested that therapy with
angiotensin-converting enzyme inhibitors in asymptomatic patients with
reduced left ventricular (LV) function can significantly reduce the
incidence of congestive heart failure compared with patients receiving
placebo. In the present study, we examined the effects of long-term
monotherapy with enalapril, metoprolol, and digoxin on the progression of
LV systolic dysfunction and LV chamber enlargement in dogs with reduced LV
ejection fraction (EF). METHODS AND RESULTS: LV dysfunction was produced in
28 dogs by multiple sequential intracoronary microembolizations.
Embolizations were discontinued when LVEF was 30% to 40%. Three weeks after
the last embolization, dogs were randomized to 3 months of oral therapy
with enalapril (10 mg twice daily, n = 7), metoprolol (25 mg twice daily, n
= 7), digoxin (0.25 mg once daily, n = 7), or no treatment (control, n =
7). As expected, in untreated dogs, LVEF decreased (36 +/- 1% versus 26 +/-
1%, P < .001) and LV end- systolic volume (ESV) and end-diastolic volume
(EDV) increased during the 3-month follow-up period (39 +/- 4 versus 57 +/-
6 mL, P < .001, and 61 +/- 6 versus 78 +/- 8 mL, P < .002,
respectively). In dogs treated with enalapril or metoprolol, LVEF remained
unchanged or increased after therapy compared with before therapy (35 +/-
1% versus 38 +/- 3% and 35 +/- 1% versus 40 +/- 3%, respectively, P <
.05), whereas ESV and EDV remained essentially unchanged. In dogs treated
with digoxin, EF remained unchanged but ESV and EDV increased
significantly. CONCLUSIONS: In dogs with reduced LVEF, long-term therapy
with enalapril or metoprolol prevents the progression of LV systolic
dysfunction and LV chamber dilation. Therapy with digoxin maintains LV
systolic function but does not prevent progressive LV enlargement.
ARTICLES
Effects of long-term monotherapy with enalapril, metoprolol, and digoxin on the progression of left ventricular dysfunction and dilation in dogs with reduced ejection fraction
Division of Cardiovascular Medicine, Henry Ford Heart and Vascular Institute, Detroit, Mich. 48202.
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