The Effects of β ₁ -Blockade on Oxidative Metabolism and the Metabolic Cost of Ventricular Work in Patients With Left Ventricular Dysfunction

Abstract

Background-The mechanism for the beneficial effect of ␤-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 (MV O 2 ). 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 Ͻ40%) 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 pressureϫSVIϫheart rate)/k. No significant change in oxidative metabolism occurred with placebo (kϭ0.061Ϯ0.022 to 0.054Ϯ0.012 per minute). Metoprolol reduced oxidative metabolism (kϭ0.062Ϯ0.024 to 0.045Ϯ0.015 per minute; Pϭ0.002). The work-metabolic index did not change with placebo (from 5.29Ϯ2.46ϫ10 6 to 5.14Ϯ2.06ϫ10 6 mm Hg ⅐ mL/m 2 ), but it increased with metoprolol (from 5.31Ϯ2.15ϫ10 6 to 7.08Ϯ2.36ϫ10 6 mm Hg ⅐ mL/m 2 ; PϽ0.001). Conclusions-Selective ␤-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 ␤-blocker therapy in this patient population.

Abnormal Myocardial Energy-Production State in Mitochondrial Cardiomyopathy and Acute Response to L-Arginine Infusion - C-11 Acetate Kinetics Revealed by Positron Emission Tomography -

“…One proposed mechanism for these potentially deleterious effects of inotropic agents is that improved cardiac performance occurs at the expense of increased oxygen consumption. 32, 33 On the other hand, treatment such as β-blocker therapy 34 or cardiac resynchronization therapy 35 leads to an improvement of myocardial efficiency in patients with LV dysfunction. In this context, we evaluated the myocardial efficiency of L-Arg administration using DP/kmono, but no significant alteration was observed.…”

Heterogeneous Reduction of Myocardial Oxidative Metabolism in Patients With Ischemic and Dilated Cardiomyopathy Using C-11 Acetate PET

“…The start of the curve was visually defined corresponding to when the blood-pool activity had cleared (usually 3-5 min) and the curve fitting as automated. [4][5][6][13][14][15]18 The modeling procedure resulted in 16-segment parametric polar maps of acetate clearance (rate constant, Kmono; given in min -1 ). Kmono values of all 16 segments of each measurement were averaged, and then the coefficient of variation (CV) of regional Kmono was derived as a measure of heterogeneity.…”

Tight software, methodological/physiological variation, less so

“…The ability to measure MBFrst and MVO2 with a single tracer injection makes the PET 11 C-acetate a very attractive one. 1,[3][4][5][6] List mode data acquisition also makes possible measurement of LV end diastolic and systolic volumes as well as LV mass and hence MEE. 7 Thus, parenthetically, any variation in test-retest repeatability related to non-simultaneous acquisition of PET and echo data alluded to by the authors potentially could have been mitigated had list mode acquisition of the PET data been obtained.…”