Effect of metoprolol on myocardial function and energetics in patients with nonischemic dilated cardiomyopathy: a randomized, double-blind, placebo-controlled study

Cardiac Catheterization Laboratory, Dallas Veterans Administration Hospital, Texas.

OBJECTIVES. This study examined the effects of metoprolol on left ventricular performance, efficiency, neurohormonal activation and myocardial respiratory quotient in patients with dilated cardiomyopathy. BACKGROUND. The mechanism by which beta-adrenergic blockade improves ejection fraction in patients with dilated cardiomyopathy remains an enigma. Thus, we undertook an extensive hemodynamic evaluation of this mechanism. In addition, because animal models have shown that catecholamine exposure may increase relative fatty acid utilization, we hypothesized that antagonism of sympathetic stimulation may result in increased carbohydrate utilization. METHODS. This was a randomized, double-blind, prospective trial in which 24 men with nonischemic dilated cardiomyopathy underwent cardiac catheterization before and after 3 months of therapy with metoprolol (n = 15) or placebo (n = 9) in addition to standard therapy. Pressure-volume relations were examined using a micromanometer catheter and digital ventriculography. RESULTS. At baseline, the placebo-treated patients had somewhat more advanced left ventricular dysfunction. Ejection fraction and left ventricular performance improved only in the metoprolol-treated patients. Stroke and minute work increased without an increase in myocardial oxygen consumption, suggesting increased myocardial efficiency. Further increases in ejection fraction were seen between 3 and 6 months in the metoprolol group. The placebo group had a significant increase in ejection fraction only after crossover to metoprolol. A significant relation between the change in coronary sinus norepinephrine and myocardial respiratory quotient was seen, suggesting a possible effect of adrenergic deactivation on substrate utilization. CONCLUSIONS. These data demonstrate that in patients with cardiomyopathy, metoprolol treatment improves myocardial performance and energetics, and favorably alters substrate utilization. Beta-adrenergic blocking agents, such as metoprolol, are hemodynamically and energetically beneficial in the treatment of myocardial failure.

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]

				M. S. Maurer, J. D. Sackner-Bernstein, L. El-Khoury Rumbarger, M. Yushak, D. L. King, and D. Burkhoff Mechanisms Underlying Improvements in Ejection Fraction With Carvedilol in Heart Failure Circ Heart Fail, May 1, 2009; 2(3): 189 - 196. [Abstract] [Full Text] [PDF]

				L. Frankenstein, C. Zugck, D. Schellberg, M. Nelles, H. Froehlich, H. Katus, and A. Remppis Prevalence and prognostic significance of adrenergic escape during chronic {beta}-blocker therapy in chronic heart failure Eur J Heart Fail, February 1, 2009; 11(2): 178 - 184. [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]

				V. Sharma, P. Dhillon, R. Wambolt, H. Parsons, R. Brownsey, M. F. Allard, and J. H. McNeill Metoprolol improves cardiac function and modulates cardiac metabolism in the streptozotocin-diabetic rat Am J Physiol Heart Circ Physiol, April 1, 2008; 294(4): H1609 - H1620. [Abstract] [Full Text] [PDF]

				S. Kasama, T. Toyama, T. Hatori, H. Sumino, H. Kumakura, Y. Takayama, S. Ichikawa, T. Suzuki, and M. Kurabayashi Evaluation of cardiac sympathetic nerve activity and left ventricular remodelling in patients with dilated cardiomyopathy on the treatment containing carvedilol Eur. Heart J., April 4, 2007; (2007) ehm048v1. [Abstract] [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]

				I. A. Nasr, A. Bouzamondo, J.-S. Hulot, O. Dubourg, J.-Y. Le Heuzey, and P. Lechat Prevention of atrial fibrillation onset by beta-blocker treatment in heart failure: a meta-analysis Eur. Heart J., February 8, 2007; (2007) ehl484v1. [Abstract] [Full Text] [PDF]

				P. Chareonthaitawee and V. Somers Continuous Positive Airway Pressure and Increased Ejection Fraction in Heart Failure and Obstructive Sleep Apnea: Is There a Metabolic Cost or Benefit? J. Am. Coll. Cardiol., January 30, 2007; 49(4): 459 - 460. [Full Text] [PDF]

				G. D. Lopaschuk Optimizing cardiac Fatty Acid and glucose metabolism as an approach to treating heart failure. Seminars in Cardiothoracic and Vascular Anesthesia, September 1, 2006; 10(3): 228 - 230. [Abstract] [PDF]

				J. Abdulla, L. Kober, E. Christensen, and C. Torp-Pedersen Effect of beta-blocker therapy on functional status in patients with heart failure -- A meta-analysis Eur J Heart Fail, August 1, 2006; 8(5): 522 - 531. [Abstract] [Full Text] [PDF]

				Q. Zhang, J. W.-H. Fung, A. Auricchio, J. Y.-S. Chan, L. C.C. Kum, L. W. Wu, and C.-M. Yu Differential change in left ventricular mass and regional wall thickness after cardiac resynchronization therapy for heart failure Eur. Heart J., June 2, 2006; 27(12): 1423 - 1430. [Abstract] [Full Text] [PDF]

				L. A. Nikolaidis, I. Poornima, P. Parikh, M. Magovern, Y.-T. Shen, and R. P. Shannon The Effects of Combined Versus Selective Adrenergic Blockade on Left Ventricular and Systemic Hemodynamics, Myocardial Substrate Preference, and Regional Perfusion in Conscious Dogs With Dilated Cardiomyopathy J. Am. Coll. Cardiol., May 2, 2006; 47(9): 1871 - 1881. [Abstract] [Full Text] [PDF]

				W. C. Stanley, F. A. Recchia, and G. D. Lopaschuk Myocardial Substrate Metabolism in the Normal and Failing Heart Physiol Rev, July 1, 2005; 85(3): 1093 - 1129. [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]

				B. F. McBride and C. M. White Critical Differences Among Beta-Adrenoreceptor Antagonists in Myocardial Failure: Debating the MERIT of COMET J. Clin. Pharmacol., January 1, 2005; 45(1): 6 - 24. [Abstract] [Full Text] [PDF]

				S. Kasama, T. Toyama, H. Kumakura, Y. Takayama, S. Ichikawa, S. Tange, T. Suzuki, and M. Kurabayashi Dobutamine Stress 99mTc-Tetrofosmin Quantitative Gated SPECT Predicts Improvement of Cardiac Function After Carvedilol Treatment in Patients with Dilated Cardiomyopathy J. Nucl. Med., November 1, 2004; 45(11): 1878 - 1884. [Abstract] [Full Text] [PDF]

				J. S. Ingwall and R. G. Weiss Is the Failing Heart Energy Starved?: On Using Chemical Energy to Support Cardiac Function Circ. Res., July 23, 2004; 95(2): 135 - 145. [Abstract] [Full Text] [PDF]

				L. A. Nikolaidis, D. Trumble, T. Hentosz, A. Doverspike, R. Huerbin, M. A. Mathier, Y.-T. Shen, and R. P. Shannon Catecholamines restore myocardial contractility in dilated cardiomyopathy at the expense of increased coronary blood flow and myocardial oxygen consumption (MvO2 cost of catecholamines in heart failure) Eur J Heart Fail, June 1, 2004; 6(4): 409 - 419. [Abstract] [Full Text] [PDF]

				E. J. Eichhorn, P. A. Grayburn, S. A. Mayer, M. St John Sutton, C. Appleton, J. Plehn, J. Oh, B. Greenberg, A. DeMaria, R. Frantz, et al. Myocardial Contractile Reserve by Dobutamine Stress Echocardiography Predicts Improvement in Ejection Fraction With {beta}-Blockade in Patients With Heart Failure: The {beta}-Blocker Evaluation of Survival Trial (BEST) Circulation, November 11, 2003; 108(19): 2336 - 2341. [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]

				D. H. Au, E. M. Udris, V. S. Fan, J. R. Curtis, M. B. McDonell, and S. D. Fihn Risk of Mortality and Heart Failure Exacerbations Associated With Inhaled {beta}-Adrenoceptor Agonists Among Patients With Known Left Ventricular Systolic Dysfunction Chest, June 1, 2003; 123(6): 1964 - 1969. [Abstract] [Full Text] [PDF]

				P. G. Shekelle, M. W. Rich, S. C. Morton, Col. S. W. Atkinson, W. Tu, M. Maglione, S. Rhodes, M. Barrett, G. C. Fonarow, B. Greenberg, et al. Efficacy of angiotensin-converting enzyme inhibitors and beta-blockers in the management of left ventricular systolic dysfunction according to race, gender, and diabetic status: A meta-analysis of major clinical trials J. Am. Coll. Cardiol., May 7, 2003; 41(9): 1529 - 1538. [Abstract] [Full Text] [PDF]

				R. Liao, M. Jain, L. Cui, J. D'Agostino, F. Aiello, I. Luptak, S. Ngoy, R. M. Mortensen, and R. Tian Cardiac-Specific Overexpression of GLUT1 Prevents the Development of Heart Failure Attributable to Pressure Overload in Mice Circulation, October 15, 2002; 106(16): 2125 - 2131. [Abstract] [Full Text] [PDF]

				H. N. Sabbaha and W. C. Stanley Partial fatty acid oxidation inhibitors: a potentially new class of drugs for heart failure Eur J Heart Fail, January 1, 2002; 4(1): 3 - 6. [Full Text] [PDF]

				B. Stanek, B. Frey, M. Hulsmann, R. Berger, B. Sturm, J. Strametz-Juranek, J. Bergler-Klein, P. Moser, A. Bojic, E. Hartter, et al. Prognostic evaluation of neurohumoral plasma levels before and during beta-blocker therapy in advanced left ventricular dysfunction J. Am. Coll. Cardiol., August 1, 2001; 38(2): 436 - 442. [Abstract] [Full Text] [PDF]

				M. C. Shibata, M. D. Flather, and D. Wang Systematic review of the impact of beta blockers on mortality and hospital admissions in heart failure Eur J Heart Fail, June 1, 2001; 3(3): 351 - 357. [Abstract] [Full Text] [PDF]

				J. M. Brophy, L. Joseph, and J. L. Rouleau {beta}-Blockers in Congestive Heart Failure: A Bayesian Meta-Analysis Ann Intern Med, April 3, 2001; 134(7): 550 - 560. [Abstract] [Full Text] [PDF]

				T. M. Ramahi, M. D. Longo, A. R. Cadariu, K. Rohlfs, S. A. Carolan, K. M. Engle, H. Samady, and F. J. T. Wackers Left ventricular inotropic reserve and right ventricular function predict increase of left ventricular ejection fraction after beta-blocker therapy in nonischemic cardiomyopathy J. Am. Coll. Cardiol., March 1, 2001; 37(3): 818 - 824. [Abstract] [Full Text] [PDF]

				B. A. Groenning, J. C. Nilsson, L. Sondergaard, T. Fritz-Hansen, H. B. W. Larsson, and P. R. Hildebrandt Antiremodeling effects on the left ventricle during beta-blockade with metoprolol in the treatment of chronic heart failure J. Am. Coll. Cardiol., December 1, 2000; 36(7): 2072 - 2080. [Abstract] [Full Text] [PDF]

				W. C Stanley and C. L Hoppel Mitochondrial dysfunction in heart failure: potential for therapeutic interventions? Cardiovasc Res, March 1, 2000; 45(4): 805 - 806. [Full Text] [PDF]

				J. E. Sanderson, S. K. W. Chan, G. Yip, L. Y. C. Yeung, K. W. Chan, K. Raymond, and K. S. Woo Beta-blockade in heart failure: A comparison of carvedilol with metoprolol J. Am. Coll. Cardiol., November 1, 1999; 34(5): 1522 - 1528. [Abstract] [Full Text] [PDF]

				B. Andersson, S.-O. Stromblad, M. Lomsky, and F. Waagstein Heart rate dependency of cardiac performance in heart failure patients treated with metoprolol Eur. Heart J., April 2, 1999; 20(8): 575 - 583. [Abstract] [PDF]

				A. Luchner, J. C. Burnett Jr., M. Jougasaki, H.-W. Hense, G.u. A. J. Riegger, and H. Schunkert Augmentation of the cardiac natriuretic peptides by beta-receptor antagonism: evidence from a population-based study J. Am. Coll. Cardiol., December 1, 1998; 32(7): 1839 - 1844. [Abstract] [Full Text] [PDF]

				J. D. Sackner-Bernstein and D. M. Mancini Rationale for Treatment of Patients With Chronic Heart Failure With Adrenergic Blockade JAMA, November 8, 1995; 274(18): 1462 - 1467. [Abstract] [PDF]