Hostname: page-component-669899f699-g7b4s Total loading time: 0 Render date: 2025-04-27T19:04:26.688Z Has data issue: false hasContentIssue false
  • English
  • Français

Modulation of neurohormonal activity after treatment of children in heart failure with carvedilol

Published online by Cambridge University Press:  24 May 2005

Alessandro Giardini ,
Roberto Formigari ,
Gabriele Bronzetti ,
Daniela Prandstraller ,
Andrea Donti ,
Marco Bonvicini  and
Fernando M. Picchio
Alessandro Giardini
Affiliation:
Pediatric Cardiology, Policlinico “S. Orsola”, University of Bologna, Italy
Roberto Formigari
Affiliation:
Pediatric Cardiology, Policlinico “S. Orsola”, University of Bologna, Italy
Gabriele Bronzetti
Affiliation:
Pediatric Cardiology, Policlinico “S. Orsola”, University of Bologna, Italy
Daniela Prandstraller
Affiliation:
Pediatric Cardiology, Policlinico “S. Orsola”, University of Bologna, Italy
Andrea Donti
Affiliation:
Pediatric Cardiology, Policlinico “S. Orsola”, University of Bologna, Italy
Marco Bonvicini
Affiliation:
Pediatric Cardiology, Policlinico “S. Orsola”, University of Bologna, Italy
Fernando M. Picchio
Affiliation:
Pediatric Cardiology, Policlinico “S. Orsola”, University of Bologna, Italy
Get access Rights & Permissions [Opens in a new window]

Abstract

Background: In adults with heart failure, neurohormonal overstimulation is related to the progression of the disease, and influences prognosis. β-blockers, which modulate neurohormonal activation, now play an essential role in the pharmacological management of heart failure in adults, but their use in children is very limited. Patients and Methods: To investigate the effects of carvedilol administration on neurohormonal activation and left ventricular function, carvedilol was added to standard treatment for heart failure in 9 patients with dilated cardiomyopathy due to heart muscle disease. Standard treatment has been in place for at least 1 month. The protocol consisted in a baseline evaluation to assess neurohormonal activation, and echocardiographic evaluation of left ventricular function. This was followed by a final evaluation at 12 months from carvedilol loading. Carvedilol was started at 0.05 mg/kg/day, and increased every two weeks until the target dose of 0.8 mg/kg/day was reached. Results: Carvedilol administration was associated with a significant reduction in plasma norepinephrine (p = 0.00001), dopamine (p = 0.0001), aldosterone (p = 0.00001) and activation of the renin-angiotensin system (p = 0.0006). Similar reductions in vanilmandelic and homovanillic acid were noted. After 12 months, a positive remodeling took place, with significant reductions in end-diastolic (p = 0.004) and end-systolic diameters (p = 0.009), and an increase in left ventricular ejection fraction (p = 0.001). No adverse effects needing reduction or interruption in the dosage were noted in the run-in phase, nor in the period of maintenance. Conclusion: Carvedilol is a safe complement to standard therapy for heart failure in children, allowing a significant reduction of neurohormonal activation with evident benefits on both ventricular function and the clinical condition.

Keywords

β-blockadecardiomyopathycardiac failure
Type
Original Article
Information
Cardiology in the Young , Volume 13 , Issue 4 , August 2003 , pp. 333 - 336
Copyright
© 2003 Cambridge University Press

Access options

Get access to the full version of this content by using one of the access options below. (Log in options will check for institutional or personal access. Content may require purchase if you do not have access.)

Article purchase

Temporarily unavailable

References

Packer M. Current role of beta-adrenergic blockers in the management of chronic heart failure. Am J Med 2001; 110: 81–94.Google Scholar
Campbell DJ, Aggarwal A, Esler M, Kaye D. β-blockers, angiotensin II, and ACE inhibitors in patients with heart failure. Lancet 2001; 358: 1609–1610.Google Scholar
Packer M, Coats AJS, Fowler MB, et al. Effect of carvedilol on survival in severe chronic heart failure. N Engl J Med 2001; 344: 1651–1658.Google Scholar
Packer M, Antonopulos GV, Berlin JA, Chittams J, Konstam MA, Udelson JE. Comparative effects of carvedilol and metoprolol on left ventricular ejection fraction in heart failure: results of a meta-analysis. Am Heart J 2001; 141: 899–907.Google Scholar
Laer S, Mir TS, Behn F, et al. Carvedilol therapy in pediatric patients with congestive heart failure: a study investigating clinical and pharmacokinetic parameters. Am Heart J 2002; 143: 916–922.Google Scholar
Williams RV, Tani LY, Shaddy RE. Intermediate effects of treatment with metoprolol or carvedilol in children with left ventricular systolic dysfunction. J Heart Lung Transplant 2002; 21: 906–909.Google Scholar
Bruns LA, Chrisant MK, Lamour JM, et al. Carvedilol as therapy in pediatric heart failure: an initial multicenter experience. J Pediatr 2001; 138: 505–511.Google Scholar
Azeka E, Franchini Ramirez JA, Valler C, Bochi EA. Delisting of infants and children from heart transplantation waiting list after carvedilol treatment. J Am Coll Cardiol 2002; 40: 2034–2038.Google Scholar
Eichhorn EJ, Bristow MR. Medical therapy can improve the biological properties of the chronically failing heart. A new era in the treatment of heart failure. Circulation 1996; 94: 2285–2296.Google Scholar
Ruffolo RR, Feuerstein GZ. Neurohormonal activation, oxygen free radicals and apoptosis in the pathogenesis of congestive heart failure. J Cardiovasc Pharmacol 1998; 32 (Suppl 1): S22–S30.Google Scholar
Conraads V, Paelinck B, Vorlat A, Goethals M, Jacobs W, Vrints C. Isolated non-compaction of the left ventricle: a rare indication for heart transplantation. J Heart Lung Transplant 2001; 20: 904–907.Google Scholar
Packer M, Cohn JN. Consensus recommendations for the management of chronic heart failure. Am J Cardiol 1999; 83: 39A–42A.Google Scholar
Francis GS, Benedict C, Johnstone DE, et al. Comparison of neurohendocrine activation in patients with left ventricular dysfunction with and without congestive heart failure. Circulation 1990; 82: 1724–1729.Google Scholar
Cohn JN, Levine TB, Olivari MT, et al. Plasma norepinephrine as a guide to prognosis in patients with chronic congestive heart failure. N Engl J Med 1984; 311: 819–823.Google Scholar
Yates JC, Beamish RE, Dhalla NS. Ventricular dysfunction and necrosis produced by adrenochrome metabolite of epinephrine: relation to pathogenesis of chatecholamine cardiomyopathy. Am Heart J 1981; 102: 210–221.Google Scholar
Mann DL, Kent RL, Parsons B, Cooper G IV. Adrenergic effects on the biology of the adult mammalian cardiocyte. Circulation 1992; 85: 790–804.Google Scholar
Levine TB, Francis GS, Goldsmith SR, Simon AB, Cohn JN. Activity of the sympathetic nervous system and renin–angiotensin system assessed by plasma hormone levels and their relation to hemodynamic abnormalities in congestive heart failure. Am J Cardiol 1982; 49: 1659–1666.Google Scholar
Sabbah HN. Apoptotic cell death in heart failure. Cardiovasc Res 2000; 45: 704–712.Google Scholar
Khattar RS, Senior R, Soman P, Van der Does R, Lahiri A. Regression of left ventricular remodeling in chronic heart failure: comparative and combined effects of captopril and carvedilol. Am Heart J 2001; 142: 704–713.Google Scholar
Shaddy RE, Curtin EL, Sower B, et al. The pediatric randomized carvedilol trial in children with heart failure: rationale and design. Am Heart J 2002; 144: 383–389.Google Scholar
Buchhorn R, Bartmus D, Siekmeyer W, Hulpke-Wette M, Schulz R, Buersch J. Beta-blocker therapy of severe congestive heart failure in infants with left to right shunts. Am J Cardiol 1998; 11: 1366–1368.Google Scholar
Buchhorn R, Ross RD, Bartmus D, Wessel A, Hulpke-Wette M, Buersch J. Activity of the renin–angiotensin–aldosterone and sympathetic nervous system and their relation to hemodynamic and clinical abnormalities in infants with left-to-right shunts. Int J Cardiol 2001; 70: 225–230.Google Scholar