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(Circulation. 2007;116:49-56.)
© 2007 American Heart Association, Inc.

Heart Failure

Metoprolol Reverses Left Ventricular Remodeling in Patients With Asymptomatic Systolic Dysfunction

The REversal of VEntricular Remodeling with Toprol-XL (REVERT) Trial

Wilson S. Colucci, MD; Theodore J. Kolias, MD; Kirkwood F. Adams, MD; William F. Armstrong, MD; Jalal K. Ghali, MD; Stephen S. Gottlieb, MD; Barry Greenberg, MD; Michael I. Klibaner, MD, PhD; Marrick L. Kukin, MD; Jennifer E. Sugg, MS, on behalf of the REVERT Study Group^*

From Boston University Medical Center, Boston, Mass (W.S.C.); University of Michigan Medical Center, Ann Arbor (T.J.K., W.F.A.); University of North Carolina School of Medicine, Chapel Hill (K.F.A.); Wayne State University, Detroit, Mich (J.K.G.); University of Maryland Hospital, Baltimore (S.S.G.); University of California at San Diego (B.G.); AstraZeneca LP, Wilmington, Del (M.I.K., J.E.S.); and St Luke’s–Roosevelt Hospitals, Columbia University College of Physicians and Surgeons, New York, NY (M.L.K.).

Correspondence to Wilson S. Colucci, MD, Cardiovascular Medicine, Boston University Medical Center, 88 E Newton St, Boston, MA 02118. E-mail wilson.colucci{at}bmc.org

Received October 5, 2006; accepted April 20, 2007.

Background— There are no randomized, controlled trial data to support the benefit of ß-blockers in patients with asymptomatic left ventricular systolic dysfunction. We investigated whether ß-blocker therapy ameliorates left ventricular remodeling in asymptomatic patients with left ventricular systolic dysfunction.

Method and Results— Patients with left ventricular ejection fraction <40%, mild left ventricular dilation, and no symptoms of heart failure (New York Heart Association class I) were randomly assigned to receive extended-release metoprolol succinate (Toprol-XL, AstraZeneca) 200 mg or 50 mg or placebo for 12 months. Echocardiographic assessments of left ventricular end-systolic volume, end-diastolic volume, mass, and ejection fraction were performed at baseline and at 6 and 12 months. The 149 patients randomized to the 3 treatment groups (200 mg, n=48; 50 mg, n=48; and placebo, n=53) were similar with regard to all baseline characteristics including age (mean, 66 years), gender (74% male), plasma brain natriuretic peptide (79 pg/mL), left ventricular end-diastolic volume index (110 mL/m²), and left ventricular ejection fraction (27%). At 12 months in the 200-mg group, there was a 14±3 mL/m² decrease (least square mean±SE) in end-systolic volume index and a 6±1% increase in left ventricular ejection fraction (P<0.05 versus baseline and placebo for both). The decrease in end-diastolic volume index (14±3) was different from that seen at baseline (P<0.05) but not with placebo. In the 50-mg group, end-systolic and end-diastolic volume indexes decreased relative to baseline but were not different from what was seen with placebo, whereas ejection fraction increased by 4±1% (P<0.05 versus baseline and placebo).

Conclusion— ß-Blocker therapy can ameliorate left ventricular remodeling in asymptomatic patients with left ventricular systolic dysfunction.

Key Words: heart failure • receptors, adrenergic, beta • remodeling • ventricles

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