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CLINICAL STUDY: HEART FAILURE

Antiremodeling effects on the left ventricle during beta-blockade with metoprolol in the treatment of chronic heart failure

Bjoern A. Groenning, MD^* , Jens C. Nilsson, MD^*, Lars Sondergaard, MD^* , Thomas Fritz-Hansen, MD^*, Henrik B. W. Larsson, MD, DMSc^* and Per R. Hildebrandt, MD, DMSc

^* Danish Research Center of Magnetic Resonance, Department of Magnetic Resonance, H:S Hvidovre Hospital, University of Copenhagen, Copenhagen, Denmark
Department of Cardiology and Endocrinology, H:S Frederiksberg Hospital, University of Copenhagen, Copenhagen, Denmark

Manuscript received January 14, 2000; revised manuscript received June 23, 2000, accepted August 11, 2000.

Reprint requests and correspondence: Dr. Bjoern A. Groenning, Danish Research Center of Magnetic Resonance, Department of Magnetic Resonance, Section 340, H:S Hvidovre Hospital, Kettegaard Allé 30, DK-2650 Hvidovre, Denmark
bjoerng{at}dadlnet.dk

OBJECTIVES

The purpose of the study was to investigate the effects of beta₁-blockade on left ventricular (LV) size and function for patients with chronic heart failure.

BACKGROUND

Large-scale trials have shown that a marked decrease in mortality can be obtained by treatment of chronic heart failure with beta-adrenergic blocking agents. Possible mechanisms behind this effect remain yet to be fully elucidated, and previous studies have presented insignificant results regarding suspected LV antiremodeling effects.

METHODS

In this randomized, placebo-controlled and double-blind substudy to the Metoprolol CR/XL Randomized Intervention Trial in Heart Failure (MERIT-HF), 41 patients were examined with magnetic resonance imaging three times in a six-month period, assessing LV dimensions and function.

RESULTS

Decreases in both LV end-diastolic volume index (150 ml/m² at baseline to 126 ml/m² after six months, p = 0.007) and LV end-systolic volume index (107 ml/m² to 81 ml/m², p = 0.001) were found, whereas LV ejection fraction increased in the metoprolol CR/XL group (29% to 37%, p = 0.005). No significant changes were seen in the placebo group regarding these variables. Left ventricular stroke volume index remained unchanged, whereas LV mass index decreased in both groups (175 g/m² to 160 g/m² in the placebo group [p = 0.005] and 179 g/m² to 164 g/m² in the metoprolol CR/XL group [p = 0.01]).

CONCLUSIONS

This study is the first randomized study to demonstrate that the beta₁-blocker metoprolol CR/XL has antiremodeling effects on the LV in patients with chronic heart failure and consequently provides an explanation for the highly significant decrease in mortality from worsening heart failure found in the MERIT-HF trial.

Abbreviations and Acronyms   CI = cardiac index   HR = heart rate   LV = left ventricle or ventricular   LVEDV = left ventricular end-diastolic volume   LVEDVI = left ventricular end-diastolic volume index   LVEF = left ventricular ejection fraction   LVESV = left ventricular end-systolic volume   LVESVI = left ventricular end-systolic volume index   LVmassI = left ventricular mass index   LVSI = left ventricular stroke volume index   LVSV = left ventricular stroke volume   MERIT-HF = metoprolol CR/XL randomized intervention trial in heart failure   MRI = magnetic resonance imaging   NYHA = New York Heart Association

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