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Effects of therapeutic beta blockade on myocardial function and cardiac remodelling in congenital cardiac disease

Published online by Cambridge University Press:  18 April 2005

Reiner Buchhorn ,
Martin Hulpke-Wette ,
Wolfgang Ruschewski ,
Robert D Ross ,
Jens Fielitz ,
Reinhard Pregla ,
Roland Hetzer  and
Vera Regitz-Zagrosek
Reiner Buchhorn
Affiliation:
Department of Pediatric Cardiology, Georg-August-University, Göttingen, Germany
Martin Hulpke-Wette
Affiliation:
Department of Pediatric Cardiology, Georg-August-University, Göttingen, Germany
Wolfgang Ruschewski
Affiliation:
Department of Cardiothoracic and Vascular Surgery, Georg-August-University, Göttingen, Germany
Robert D Ross
Affiliation:
Children's Hospital of Michigan, Wayne State University School of Medicine, Detroit, MI, USA
Jens Fielitz
Affiliation:
Cardiothoracic and Vascular Surgery, Deutsches Herzzentrum Berlin, Berlin, Germany
Reinhard Pregla
Affiliation:
Cardiothoracic and Vascular Surgery, Deutsches Herzzentrum Berlin, Berlin, Germany
Roland Hetzer
Affiliation:
Cardiothoracic and Vascular Surgery, Deutsches Herzzentrum Berlin, Berlin, Germany
Vera Regitz-Zagrosek
Affiliation:
Cardiothoracic and Vascular Surgery, Deutsches Herzzentrum Berlin, Berlin, Germany
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Abstract

Background: Cardiac remodelling is now recognised as an important aspect of cardiovascular disease progression and is, therefore, emerging as a therapeutic target in cardiac failure due to different etiologies. Little is known about the influence of different therapies for cardiac failure on the remodelling seen in infants with congenital cardiac disease. Methods: During follow-up of a prospective and randomized trial, we investigated therapeutic effects on neurohormonal activation, ventricular function, and myocardial gene expression. We compared the data from 8 infants with severe congestive heart failure due to left-to-right shunts, who received digoxin and diuretics alone, to 9 infants who received additional treatment with propranolol. Results: In these infants, β-adrenergic blockade significantly reduced highly elevated levels of renin, from 284 ± 319 μU/ml compared to 1061 ± 769 μU/ml. Systolic ventricular function was normal in both groups, but diastolic ventricular function was improved in those receiving propranolol, indicated by significantly lower left atrial pressures, lower end-diastolic pressures, and less pronounced ventricular hypertrophy, the latter estimated by lower ratios of myocardial wall to ventricular cavity areas on average of 42%. Further hemodynamic parameters showed no significant differences between the groups, except for the lower heart rate in infants treated with propranolol. In those treated with digoxin and diuretics, there was a significant downregulation of β2-receptor and angiotensin-2 receptor genes, and up-regulation of endothelin A receptor and connective tissue growth factor genes, that were partially prevented by additional treatment with propranolol. Conclusions: β-blockade is a new therapeutic approach for congestive heart failure in infants with congenital cardiac disease, producing with significant benefits on neurohormonal activation, diastolic ventricular function, and cardiac remodelling.

Keywords

Cardiac remodellingcongenital heart defectscongestive heart failuretrialsbeta blockade treatment
Type
Original Article
Information
Cardiology in the Young , Volume 13 , Issue 1 , February 2003 , pp. 36 - 43
Copyright
© 2003 Cambridge University Press

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Footnotes

This study was supported by grant DFG Re 662/2-3

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