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J Am Coll Cardiol, 2000; 36:2072-2080
© 2000 by the American College of Cardiology Foundation
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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* {dagger}, Jens C. Nilsson, MD*, Lars Sondergaard, MD* {dagger}, Thomas Fritz-Hansen, MD*, Henrik B. W. Larsson, MD, DMSc* and Per R. Hildebrandt, MD, DMSc{dagger}

* Danish Research Center of Magnetic Resonance, Department of Magnetic Resonance, H:S Hvidovre Hospital, University of Copenhagen, Copenhagen, Denmark
{dagger} 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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