Until recently, beta-blockers were recommended only for the treatment of mild to moderate heart failure in adults. However, the recent Carvedilol Prospective Randomized Cumulative Survival Trial (COPERNICUS) found a 35% reduction in all-cause mortality in adults with severe heart failure symptoms who had received carvedilol. [Packer: 2001] Although the mechanism of action of beta-blockers in heart failure is still being defined, a large body of basic and clinical investigation indicates that their major benefit is prevention or reversal of the myocardial dysfunction that occurs because of sympathetic activation, primarily from norepinephrine.[Bristow: 1997]
The effects of beta-blockers in children with heart failure is entirely anecdotal. There are reports of the efficacy of metoprolol in small groups of children with cardiomyopathy. [Shaddy: 1995] [Shaddy: 1998] [Shaddy: 1999] A multicenter retrospective report of carvedilol in children has also suggested a potential benefit in improved ventricular performance and symptoms. [Bruns: 2001] However, as of yet no prospective randomized trials of beta-blockers in children have been completed that could clearly define safety and efficacy. A meta-analysis found mixed results in studies investigating the effects of beta-blockers on CHF in children, although the studies were notably heterogeneous in terms of beta-blocking agent and doses used, patient age, and nature of cardiac condition. [Frobel: 2009] The authors concluded insufficient evidence exists to recommend or discourage the use of these medications in the pediatric population.
Buchhorn et al., has reported the beneficial effects of propranolol in infants with congestive heart failure from left-to-right intracardiac shunts. [Buchhorn: 2001] [Buchhorn: 1998] In these studies, treatment with propranolol resulted in lower respiratory rates and heart rates, and improved weight gain. There were also significant changes in circulating neurohormonal parameters. These effects of propranolol seem to be better than those seen with low-dose captopril. [Buchhorn: 2000] Thus, there may be some benefit of beta-blockers in this clinical setting, although further study is indicated.
Beta-blockers are currently recommended for adults with stable NYHA class II or III heart failure caused by left ventricular systolic dysfunction, unless they are unable to tolerate treatment or have a contraindication to use of these drugs. [Packer: 1999] The dosing of beta-blockers differs for each agent, but all beta-blockers are initiated at a very low dose and increased slowly over several weeks while the patient is carefully monitored for adverse effects. Children who receive carvedilol for the treatment of heart failure have a high incidence of adverse effects. [Bruns: 2001] These medications need to be used with caution and patients monitored closely. Dosing in children has been extrapolated from adult data, and thus the ideal dosing schedules for beta-blockers in children with heart failure are unknown.
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|Content Last Updated:||10/2014|
Mechanism of action of beta-blocking agents in heart failure.
Am J Cardiol. 1997;80(11A):26L-40L. PubMed abstract
Bristow MR, Gilbert EM, Abraham WT, Adams KF, Fowler MB, Hershberger RE, Kubo SH, Narahara KA, Ingersoll H, Krueger S, Young
S, Shusterman N.
Carvedilol produces dose-related improvements in left ventricular function and survival in subjects with chronic heart failure. MOCHA Investigators.
Circulation. 1996;94(11):2807-16. PubMed abstract
Bruns LA, Chrisant MK, Lamour JM, Shaddy RE, Pahl E, Blume ED, Hallowell S, Addonizio LJ, Canter CE.
Carvedilol as therapy in pediatric heart failure: an initial multicenter experience.
J Pediatr. 2001;138(4):505-11. PubMed abstract
Buchhorn R, Bartmus D, Siekmeyer W, Hulpke-Wette M, Schulz R, Bürsch J.
Beta-blocker therapy of severe congestive heart failure in infants with left to right shunts.
Am J Cardiol. 1998;81(11):1366-8. PubMed abstract
Buchhorn R, Hulpke-Wette M, Hilgers R, Bartmus D, Wessel A, Bürsch J.
Propranolol treatment of congestive heart failure in infants with congenital heart disease: The CHF-PRO-INFANT Trial. Congestive heart failure in infants treated with propanol.
Int J Cardiol. 2001;79(2-3):167-73. PubMed abstract
Buchhorn R, Ross RD, Hulpke-Wette M, Bartmus D, Wessel A, Schulz R, Bürsch J.
Effectiveness of low dose captopril versus propranolol therapy in infants with severe congestive failure due to left-to-right shunts.
Int J Cardiol. 2000;76(2-3):227-33. PubMed abstract
CIBIS-II Study Group.
The Cardiac Insufficiency Bisoprolol Study II (CIBIS-II): a randomised trial.
Lancet. 1999;353(9146):9-13. PubMed abstract
Frobel AK, Hulpke-Wette M, Schmidt KG, Läer S.
Beta-blockers for congestive heart failure in children.
Cochrane Database Syst Rev. 2009;(1):CD007037. PubMed abstract
MERIT-HF Study Group.
Effect of metoprolol CR/XL in chronic heart failure: Metoprolol CR/XL Randomised Intervention Trial in Congestive Heart Failure (MERIT-HF).
Lancet. 1999;353(9169):2001-7. PubMed abstract
Packer M, Bristow MR, Cohn JN, Colucci WS, Fowler MB, Gilbert EM, Shusterman NH.
The effect of carvedilol on morbidity and mortality in patients with chronic heart failure. U.S. Carvedilol Heart Failure Study Group.
N Engl J Med. 1996;334(21):1349-55. PubMed abstract
Packer M, Coats AJ, Fowler MB, Katus HA, Krum H, Mohacsi P, Rouleau JL, Tendera M, Castaigne A, Roecker EB, Schultz MK, DeMets
Effect of carvedilol on survival in severe chronic heart failure.
N Engl J Med. 2001;344(22):1651-8. PubMed abstract
Packer M, Cohn J.
Consensus recommendations for the management of chronic heart failure. On behalf of the membership of the advisory council to improve outcomes nationwide in heart failure.
Am J Cardiol. 1999;83(2A):1A-38A. PubMed abstract
Beta-blocker therapy in young children with congestive heart failure under consideration for heart transplantation.
Am Heart J. 1998;136(1):19-21. PubMed abstract
Shaddy RE, Olsen SL, Bristow MR, Taylor DO, Bullock EA, Tani LY, Renlund DG.
Efficacy and safety of metoprolol in the treatment of doxorubicin-induced cardiomyopathy in pediatric patients.
Am Heart J. 1995;129(1):197-9. PubMed abstract
Shaddy RE, Tani LY, Gidding SS, Pahl E, Orsmond GS, Gilbert EM, Lemes V.
Beta-blocker treatment of dilated cardiomyopathy with congestive heart failure in children: a multi-institutional experience.
J Heart Lung Transplant. 1999;18(3):269-74. PubMed abstract