Effects of short- and long-term carvedilol administration on rest and exercise hemodynamic variables, exercise capacity and clinical conditions in patients with idiopathic dilated cardiomyopathy

Cattedra di Cardiologia, Universita di Brescia, Italy.

OBJECTIVES. The study evaluated the effects of short- and long-term administration of carvedilol in patients with idiopathic dilated cardiomyopathy. BACKGROUND. Carvedilol is a beta-adrenergic blocking agent with vasodilator activity that might be well tolerated in patients with heart failure. METHODS. Forty patients with idiopathic dilated cardiomyopathy treated with digoxin, furosemide and angiotensin-converting enzyme inhibitors were randomized in a double-blind manner to receive either placebo or carvedilol. Right heart hemodynamic variables were evaluated up to 8 h after short-term drug administration and, on the next day, during cardiopulmonary exercise testing before and 3 h after drug ingestion. Placebo or carvedilol was added to standard therapy, starting with a dose of 6.25 mg twice a day with weekly increments up to the maximum of 25 mg twice a day. Patients were reevaluated after 4 months by cardiopulmonary exercise testing and measurement of right heart hemodynamic variables 12 h after last drug ingestion and 3 h after drug readministration. Left ventricular ejection fraction and volume, measured by equilibrium radionuclide ventriculography, quality of life and submaximal exercise duration were assessed before and after long-term therapy. RESULTS. Compared with placebo, carvedilol produced a short-term reduction in heart rate and pulmonary artery and pulmonary wedge pressures and, after long-term administration, increased both rest and peak exercise cardiac, stroke volume and stroke work indexes, with a further reduction in right atrial, pulmonary artery and pulmonary wedge pressures. Long-term carvedilol administration also improved rest left ventricular ejection fraction (from 20 +/- 7% to 30 +/- 12%, p < 0.001), submaximal exercise capacity, quality of life and New York Heart Association functional class. No baseline variable was predictive of the response to therapy. CONCLUSIONS. Short-term carvedilol administration reduces heart rate and mean pulmonary artery and pulmonary wedge pressures, whereas it improves both long-term rest and exercise left ventricular systolic function, reduces heart failure symptoms and improves submaximal exercise tolerance in patients with idiopathic cardiomyopathy.

This article has been cited by other articles:

				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]

				D. Merkus, B. Houweling, V. J. de Beer, Z. Everon, and D. J. Duncker Alterations in endothelial control of the pulmonary circulation in exercising swine with secondary pulmonary hypertension after myocardial infarction J. Physiol., May 1, 2007; 580(3): 907 - 923. [Abstract] [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]

				J. Kim, A. Ogai, S. Nakatani, K. Hashimura, H. Kanzaki, K. Komamura, M. Asakura, H. Asanuma, S. Kitamura, H. Tomoike, et al. Impact of Blockade of Histamine H2 Receptors on Chronic Heart Failure Revealed by Retrospective and Prospective Randomized Studies J. Am. Coll. Cardiol., October 3, 2006; 48(7): 1378 - 1384. [Abstract] [Full Text] [PDF]

				V. L. Wittmer, G. M. S. Simoes, L. C. M. Sogame, and E. C. Vasquez Effects of continuous positive airway pressure on pulmonary function and exercise tolerance in patients with congestive heart failure. Chest, July 1, 2006; 130(1): 157 - 163. [Abstract] [Full Text] [PDF]

				Developed in Collaboration With the American Colle, Endorsed by the Heart Rhythm Society, S. A. Hunt, W. T. Abraham, M. H. Chin, A. M. Feldman, G. S. Francis, T. G. Ganiats, M. Jessup, M. A. Konstam, et al. ACC/AHA 2005 Guideline Update for the Diagnosis and Management of Chronic Heart Failure in the Adult--Summary Article: A Report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines (Writing Committee to Update the 2001 Guidelines for the Evaluation and Management of Heart Failure) J. Am. Coll. Cardiol., September 20, 2005; 46(6): 1116 - 1143. [Full Text] [PDF]

				S. A. Hunt, W. T. Abraham, M. H. Chin, A. M. Feldman, G. S. Francis, T. G. Ganiats, M. Jessup, M. A. Konstam, D. M. Mancini, K. Michl, et al. ACC/AHA 2005 Guideline Update for the Diagnosis and Management of Chronic Heart Failure in the Adult--Summary Article: A Report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines (Writing Committee to Update the 2001 Guidelines for the Evaluation and Management of Heart Failure): Developed in Collaboration With the American College of Chest Physicians and the International Society for Heart and Lung Transplantation: Endorsed by the Heart Rhythm Society Circulation, September 20, 2005; 112(12): 1825 - 1852. [Full Text] [PDF]

				T. E. Sirak, S. Jelic, and T. H. Le Jemtel Therapeutic update: Non-selective beta- and alpha-adrenergic blockade in patients with coexistent chronic obstructive pulmonary disease and chronic heart failure J. Am. Coll. Cardiol., August 4, 2004; 44(3): 497 - 502. [Abstract] [Full Text] [PDF]

				H. Asanuma, T. Minamino, S. Sanada, S. Takashima, H. Ogita, A. Ogai, M. Asakura, Y. Liao, Y. Asano, Y. Shintani, et al. {beta}-Adrenoceptor Blocker Carvedilol Provides Cardioprotection via an Adenosine-Dependent Mechanism in Ischemic Canine Hearts Circulation, June 8, 2004; 109(22): 2773 - 2779. [Abstract] [Full Text] [PDF]

				M. Penicka, J. Bartunek, B. De Bruyne, M. Vanderheyden, M. Goethals, M. De Zutter, P. Brugada, and P. Geelen Improvement of Left Ventricular Function After Cardiac Resynchronization Therapy Is Predicted by Tissue Doppler Imaging Echocardiography Circulation, March 2, 2004; 109(8): 978 - 983. [Abstract] [Full Text] [PDF]

				T. J. Vittorio, C. C. Lang, S. D. Katz, M. Packer, D. M. Mancini, and U. P. Jorde Vasopressor Response to Angiotensin II Infusion in Patients With Chronic Heart Failure Receiving {beta}-Blockers Circulation, January 21, 2003; 107(2): 290 - 293. [Abstract] [Full Text] [PDF]

				M. Metra, S. Nodari, A. D'Aloia, C. Muneretto, A. D. Robertson, M. R. Bristow, and L. Dei Cas Beta-blocker therapy influences the hemodynamic response to inotropic agents in patients with heart failure: A randomized comparison of dobutamine and enoximone before and after chronic treatment with metoprolol or carvedilol J. Am. Coll. Cardiol., October 2, 2002; 40(7): 1248 - 1258. [Abstract] [Full Text] [PDF]

				K. Stoschitzky Beta-blockers in chronic heart failure Eur. Heart J., March 1, 2002; 23(5): 426 - 426. [Full Text] [PDF]

				J. M. Foody, M. H. Farrell, and H. M. Krumholz {beta}-Blocker Therapy in Heart Failure: Scientific Review JAMA, February 20, 2002; 287(7): 883 - 889. [Abstract] [Full Text] [PDF]

				A. Nohria, E. Lewis, and L. W. Stevenson Medical Management of Advanced Heart Failure JAMA, February 6, 2002; 287(5): 628 - 640. [Abstract] [Full Text] [PDF]

				T. Kubo, E. R. Azevedo, G. E. Newton, J. D. Parker, and J. S. Floras Lack of evidence for peripheral alpha1- adrenoceptor blockade during long-term treatment of heart failure with carvedilol J. Am. Coll. Cardiol., November 1, 2001; 38(5): 1463 - 1469. [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]

				C Opasich, G.D Pinna, A Mazza, O Febo, R Riccardi, P.G Riccardi, S Capomolla, G Forni, F Cobelli, and L Tavazzi Six-minute walking performance in patients with moderate-to-severe heart failure; is it a useful indicator in clinical practice? Eur. Heart J., March 2, 2001; 22(6): 488 - 496. [Abstract] [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]

				A. Mortara, M. T. La Rovere, G. D. Pinna, R. Maestri, S. Capomolla, and F. Cobelli Nonselective beta-adrenergic blocking agent, carvedilol, improves arterial baroflex gain and heart rate variability in patients with stable chronic heart failure J. Am. Coll. Cardiol., November 1, 2000; 36(5): 1612 - 1618. [Abstract] [Full Text] [PDF]

				G. Cice, E. Tagliamonte, L. Ferrara, and A. Iacono Efficacy of carvedilol on complex ventricular arrhythmias in dilated cardiomyopathy: double-blind, randomized, placebo-controlled study Eur. Heart J., August 1, 2000; 21(15): 1259 - 1264. [Abstract] [PDF]

				M. L. Kukin, M. M. Mannino, R. S. Freudenberger, J. Kalman, C. Buchholz-Varley, and O. Ocampo Hemodynamic comparison of twice daily metoprolol tartrate with once daily metoprolol succinate in congestive heart failure J. Am. Coll. Cardiol., January 1, 2000; 35(1): 45 - 50. [Abstract] [Full Text] [PDF]

				A. Di Lenarda, G. Sabbadini, L. Salvatore, G. Sinagra, L. Mestroni, B. Pinamonti, D. Gregori, F. Ciani, A. Muzzi, S. Klugmann, et al. Long-term effects of carvedilol in idiopathic dilated cardiomyopathy with persistent left ventricular dysfunction despite chronic metoprolol J. Am. Coll. Cardiol., June 1, 1999; 33(7): 1926 - 1934. [Abstract] [Full Text] [PDF]

				P. S. Macdonald, A. M. Keogh, C. L. Aboyoun, M. Lund, R. Amor, and D. J. McCaffrey Tolerability and efficacy of carvedilol in patients with New York Heart Association class IV heart failure J. Am. Coll. Cardiol., March 15, 1999; 33(4): 924 - 931. [Abstract] [Full Text] [PDF]

				W. Carlson and K. Oberg Clinical Pharmacology of Carvedilol Journal of Cardiovascular Pharmacology and Therapeutics, January 1, 1999; 4(4): 205 - 218. [Abstract] [PDF]

				W. T. Abraham Pharmacologic Management of Chronic Heart Failure: A Review Seminars in Cardiothoracic and Vascular Anesthesia, September 1, 1998; 2(3): 168 - 190. [Abstract] [PDF]