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(Circulation. 2000;102:2070.)
© 2000 American Heart Association, Inc.

Clinical Investigation and Reports

The Effects of ß₁-Blockade on Oxidative Metabolism and the Metabolic Cost of Ventricular Work in Patients With Left Ventricular Dysfunction

A Double-Blind, Placebo-Controlled, Positron-Emission Tomography Study

R. S. B. Beanlands, MD; C. Nahmias, PhD; E. Gordon, MD; G. Coates, MD; R. deKemp, PhD; G. Firnau, PhD; E. Fallen, MD

From the Department of Nuclear Medicine, ES Garnett Memorial PET Centre, the Division of Cardiology, McMaster University Medical Centre (C.N., E.G., G.C., E.F., G.F.), Hamilton, Canada, and the Cardiac PET Centre in the Division of Cardiology at the University of Ottawa Heart Institute (R.B., R.d.K., G.F.), Ottawa, Canada.

Correspondence to Rob Beanlands, MD, FRCP(C), Director of Cardiac Imaging, University of Ottawa Heart Institute, H149-40 Ruskin Street, Ottawa, Ontario, K1Y 4W7, Canada. E-mail rbeanlands{at}ottawaheart.ca

Background—The mechanism for the beneficial effect of ß-blocker therapy in patients with left ventricular (LV) dysfunction is unclear, but it may relate to an energy-sparing effect that results in improved cardiac efficiency. C-11 acetate kinetics, measured using positron-emission tomography (PET), are a proven noninvasive marker of oxidative metabolism and myocardial oxygen consumption (MO₂). This approach can be used to measure the work-metabolic index, which is a noninvasive estimate of cardiac efficiency.

Methods and Results—The aim of this study was to determine the effect of metoprolol on oxidative metabolism and the work-metabolic index in patients with LV dysfunction. Forty patients (29 with ischemic and 11 with nonischemic heart disease; LV ejection fraction <40%) were randomized to receive metoprolol or placebo in a treatment protocol of titration plus 3 months of stable therapy. Seven patients were not included in analysis because of withdrawal from the study, incomplete follow-up, or nonanalyzable PET data. The rate of oxidative metabolism (k) was measured using C-11-acetate PET, and stoke volume index (SVI) was measured using echocardiography. The work-metabolic index was calculated as follows: (systolic blood pressurexSVIxheart rate)/k. No significant change in oxidative metabolism occurred with placebo (k=0.061±0.022 to 0.054±0.012 per minute). Metoprolol reduced oxidative metabolism (k=0.062±0.024 to 0.045±0.015 per minute; P=0.002). The work-metabolic index did not change with placebo (from 5.29±2.46x10⁶ to 5.14±2.06x10⁶ mm Hg · mL/m²), but it increased with metoprolol (from 5.31±2.15x10⁶ to 7.08±2.36x10⁶ mm Hg · mL/m²; P<0.001).

Conclusions—Selective ß-blocker therapy with metoprolol leads to a reduction in oxidative metabolism and an improvement in cardiac efficiency in patients with LV dysfunction. It is likely that this energy-sparing effect contributes to the clinical benefits observed with ß-blocker therapy in this patient population.

Key Words: heart failure • acetates • metabolism