(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
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
(M
O2). 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
This article has been cited by other articles:
 |
|
 |
|
  L. H. Opie and J. Knuuti The adrenergic-Fatty Acid load in heart failure. J. Am. Coll. Cardiol., October 27, 2009; 54(18): 1637 - 1646. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. Saraste, S. G. Nekolla, and M. Schwaiger Cardiovascular molecular imaging: an overview Cardiovasc Res, September 1, 2009; 83(4): 643 - 652. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
F. M. Bengel, T. Higuchi, M. S. Javadi, and R. Lautamaki Cardiac positron emission tomography. J. Am. Coll. Cardiol., June 30, 2009; 54(1): 1 - 15. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 H. Tuunanen, E. Engblom, A. Naum, K. Nagren, M. Scheinin, B. Hesse, K.E. Juhani Airaksinen, P. Nuutila, P. Iozzo, H. Ukkonen, et al. Trimetazidine, a Metabolic Modulator, Has Cardiac and Extracardiac Benefits in Idiopathic Dilated Cardiomyopathy Circulation, September 16, 2008; 118(12): 1250 - 1258. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
R. A.H. Stewart, O. C. Raffel, A. J. Kerr, R. Gabriel, I. Zeng, A. A. Young, and B. R. Cowan Pilot Study to Assess the Influence of {beta}-Blockade on Mitral Regurgitant Volume and Left Ventricular Work in Degenerative Mitral Valve Disease Circulation, September 2, 2008; 118(10): 1041 - 1046. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 T. H. Marwick and M. Schwaiger The Future of Cardiovascular Imaging in the Diagnosis and Management of Heart Failure, Part 1: Tasks and Tools Circ Cardiovasc Imaging, July 1, 2008; 1(1): 58 - 69. [Full Text] [PDF]
|
|
|
|
 |
|
 J Knuuti and F M Bengel Positron emission tomography and molecular imaging Heart, March 1, 2008; 94(3): 360 - 367. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. G. Haworth The cell and molecular biology of right ventricular dysfunction in pulmonary hypertension Eur. Heart J. Suppl., December 1, 2007; 9(suppl_H): H10 - H16. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
D. Neglia, R. De Maria, S. Masi, M. Gallopin, P. Pisani, S. Pardini, A. Gavazzi, A. L'Abbate, and O. Parodi Effects of long-term treatment with carvedilol on myocardial blood flow in idiopathic dilated cardiomyopathy Heart, July 1, 2007; 93(7): 808 - 813. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. Oh, J.-H. Chung, S.-M. Kang, S. W. Smith, D. Niederseer, C. Thaler, J. Niebauer, P. Korantzopoulos, J. A. Goudevenos, P. Knaapen, et al. The Failing Heart N. Engl. J. Med., June 14, 2007; 356(24): 2544 - 2546. [Full Text] [PDF]
|
|
|
|
|
|
P. Knaapen, T. Germans, J. Knuuti, W. J. Paulus, P. A. Dijkmans, C. P. Allaart, A. A. Lammertsma, and F. C. Visser Myocardial Energetics and Efficiency: Current Status of the Noninvasive Approach Circulation, February 20, 2007; 115(7): 918 - 927. [Full Text] [PDF]
|
|
|
|
 |
|
 L. Groban and J. Butterworth Perioperative management of chronic heart failure. Anesth. Analg., September 1, 2006; 103(3): 557 - 575. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. Pilz, H. Scharnagl, B. Tiran, U. Seelhorst, B. Wellnitz, B. O. Boehm, J. R. Schaefer, and W. Marz Free Fatty Acids Are Independently Associated with All-Cause and Cardiovascular Mortality in Subjects with Coronary Artery Disease J. Clin. Endocrinol. Metab., July 1, 2006; 91(7): 2542 - 2547. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. Al-Hesayen, E. R. Azevedo, J. S. Floras, S. Hollingshead, G. D. Lopaschuk, and J. D. Parker Selective versus nonselective {beta}-adrenergic receptor blockade in chronic heart failure: differential effects on myocardial energy substrate utilization Eur J Heart Fail, June 1, 2005; 7(4): 618 - 623. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 L. G. Olsson, K. Swedberg, A. L. Clark, K. K. Witte, and J. G.F. Cleland Six minute corridor walk test as an outcome measure for the assessment of treatment in randomized, blinded intervention trials of chronic heart failure: a systematic review Eur. Heart J., April 2, 2005; 26(8): 778 - 793. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 K. Yoshinaga, C. Katoh, R. S.B. Beanlands, K. Noriyasu, K. Komuro, S. Yamada, Y. Kuge, K. Morita, A. Kitabatake, and N. Tamaki Reduced Oxidative Metabolic Response in Dysfunctional Myocardium with Preserved Glucose Metabolism but with Impaired Contractile Reserve J. Nucl. Med., November 1, 2004; 45(11): 1885 - 1891. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
L. H. Opie Cellular Basis for Therapeutic Choices in Heart Failure Circulation, October 26, 2004; 110(17): 2559 - 2561. [Full Text] [PDF]
|
|
|
|
|
|
M. Faadiel Essop and L. H. Opie Metabolic therapy for heart failure Eur. Heart J., October 2, 2004; 25(20): 1765 - 1768. [Full Text] [PDF]
|
|
|
|
|
|
D Baller, J Vogt, O Lindner, B Lamp, J Holzinger, A Kammeier, P Wielepp, W Burchert, and D Horstkotte Myocardial oxygen consumption and perfusion before and after cardiac resynchronization therapy: experimental observations and clinical implications Eur. Heart J. Suppl., August 1, 2004; 6(suppl_D): D91 - D97. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. Sorensen, E. Stahle, B. Langstrom, G. Frostfeldt, G. Wikstrom, and G. Hedenstierna Simple and Accurate Assessment of Forward Cardiac Output by Use of 1-11C-Acetate PET Verified in a Pig Model J. Nucl. Med., July 1, 2003; 44(7): 1176 - 1183. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. P. Chandler, P. N. Chavez, T. A. McElfresh, H. Huang, C. S. Harmon, and W. C. Stanley Partial inhibition of fatty acid oxidation increases regional contractile power and efficiency during demand-induced ischemia Cardiovasc Res, July 1, 2003; 59(1): 143 - 151. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. Scorsin, A. Mebazaa, N. A. Attar, B. Medini, J. Callebert, R. Raffoul, R. Ramadan, J. M. Maillet, A. Ruffenach, F. Simoneau, et al. Efficacy of esmolol as a myocardial protective agent during continuous retrograde blood cardioplegia J. Thorac. Cardiovasc. Surg., May 1, 2003; 125(5): 1022 - 1029. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
K. Q. Stolen, J. Kemppainen, H. Ukkonen, K. K. Kalliokoski, M. Luotolahti, P. Lehikoinen, H. Hamalainen, T. Salo, K. E. Juhani Airaksinen, P. Nuutila, et al. Exercise training improves biventricular oxidative metabolism and left ventricular efficiency in patients with dilated cardiomyopathy J. Am. Coll. Cardiol., February 5, 2003; 41(3): 460 - 467. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 D. T. Lucas, P. Aryal, L. I. Szweda, W. J. Koch, and L. A. Leinwand Alterations in mitochondrial function in a mouse model of hypertrophic cardiomyopathy Am J Physiol Heart Circ Physiol, February 1, 2003; 284(2): H575 - H583. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. P. Chandler, W. C. Stanley, H. Morita, G. Suzuki, B. A. Roth, B. Blackburn, A. Wolff, and H. N. Sabbah Short-Term Treatment With Ranolazine Improves Mechanical Efficiency in Dogs With Chronic Heart Failure Circ. Res., August 23, 2002; 91(4): 278 - 280. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. Zaugg, M. C. Schaub, T. Pasch, and D. R. Spahn Modulation of {beta}-adrenergic receptor subtype activities in perioperative medicine: mechanisms and sites of action Br. J. Anaesth., January 1, 2002; 88(1): 101 - 123. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
T. R. Wallhaus, M. Taylor, T. R. DeGrado, D. C. Russell, P. Stanko, R. J. Nickles, and C. K. Stone Myocardial Free Fatty Acid and Glucose Use After Carvedilol Treatment in Patients With Congestive Heart Failure Circulation, May 22, 2001; 103(20): 2441 - 2446. [Abstract] [Full Text] [PDF]
|
|