Hostname: page-component-586b7cd67f-2plfb Total loading time: 0 Render date: 2024-11-20T17:23:38.187Z Has data issue: false hasContentIssue false
  • English
  • Français

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
Get access Rights & Permissions [Opens in a new window]

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

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.)

Footnotes

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

References

Packer M. The neurohormonal hypothesis: A theory to explain the mechanism of disease progression in heart failure. J Am Coll Cardiol 1992; 20: 248–254.Google Scholar
Dibbs Z, Kurrelmeyer K, Kalra D, et al. Cytokines in heart failure: Pathogenetic mechanisms and potential treatment. Proc Assoc Am Physicians 1999; 111: 423–428.Google Scholar
Cohn JN, Ferrari R, Sharpe N. Cardiac remodelling – Concepts and clinical implication: A consensus paper from an international forum on cardiac remodelling. J Am Coll Cardiol 2000; 35: 569–582.Google Scholar
Mann DL. Mechanisms and models of heart failure. Circulation 1999; 100: 999–1008.Google Scholar
Kimball TR, Daniels SR, Hannon DW, Khoury P, Schwartz DC. Relation of symptoms to contractility and defect size in infants with ventricular septal defect. Am J Cardiol 1991; 67: 1097–1102.Google Scholar
Buchhorn R, Ross RD, Wessel A, Hulpke-Wette M, Bürsch 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; 78: 225–230.Google Scholar
Buchhorn R, Hammersen A, Bartmus D, Bürsch J. The pathogenesis of heart failure in infants with congenital heart disease. Cardiol Young 2001; 11: 498–504.Google Scholar
Buchhorn R, Wessel A, Hulpke-Wette M, Bürsch J, Werdan K, Loppnow H. Endogenous nitric oxide production and soluble tumor necrosis factor-receptor levels are enhanced in infants with congenital heart disease. Crit Care Med 2001; 29: 2208–2210.Google Scholar
Ross RD, Danniels SR, Schwartz DC, Hannnon DW, Kaplan S. Return of plasma norepinephrine to normal after resolution of congestive heart failure in congenital heart disease. Am J Cardiol 1987; 60: 1411–1413.Google Scholar
Franklin RCG, Spiegelhalter DJ, Sullivan ID, et al. Tricuspid atresia presenting in infancy. Survival and suitability for Fontan operation. Circulation 1993; 87: 427–439.Google Scholar
Jenkins KJ, Gauvreau K, Newburger JW, Spray TL, Moller JH, Iezzoni LI. Consensus-based method for risk adjustment for surgery for congenital heart disease. J Thorac Cardiovasc Surg 2002; 101: 110–118.Google Scholar
Seliem M, Muster AJ, Paul MH, Benson DW. Relation between preoperative left ventricular muscle mass and outcome of the Fontan procedure in patients with tricuspid atresia. J Am Coll Cardiol 1989; 14: 750–755.Google Scholar
Kirklin JK, Blackstone EH, Kirklin JW, Pacifico AD, Bargeron LM. The Fontan operation. Ventricular hypertrophy, age, and date of operation as risk factors. J Thorac Cardiovasc Surg 1986; 92: 1049–1064.Google Scholar
Hunter JJ, Chien KR. Signaling pathways for cardiac hypertrophy and failure. N Engl J Med 1999; 341: 1276–1283.Google Scholar
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. Int J Cardiol 2001; 79: 167–173.Google Scholar
Ross RD, Bollinger RO, Pinsky WW. Grading the severity of congestive heart failure in infants. Ped Cardiol 1992; 13: 72–75.Google Scholar
Colan SD, Borrow KM, Neumann A. Left ventricular end-systolic wall stress-velocity of fiber shortening relation: a load-independent index of myocardial contractility. J Am Coll Cardiol 1984; 4: 715–724.Google Scholar
Wessel A, Buchhorn R, Löber M, Eigster G, Hulpke-Wette M, Bürsch J. Nichtinvasive Bestimmung des Kontratilitätsindex “wandspannungsbezogene zirkumferentielle Verkürzungsgeschwindigkeit des linken Ventrikels” bei Kindern. Z Kardiol 1999; 88: 802–811.Google Scholar
Kim MH, Devlin WH, Das SK, Petrusha J, Montgomery D, Starling MR. Effects of beta-adrenergic blocking therapy on left ventricular diastolic relaxation properties in patients with dilated cardiomyopathy. Circulation 1999; 100: 729–735.Google Scholar
Senzaki H, Paolocci N, Gluzband YA, et al. Beta-blockade prevents sustained metalloproteinase activation and diastolic stiffening induced by angiotensin II combined with evolving cardiac dysfunction. Circ Res 2000; 86: 807–815.Google Scholar
Katz AM. The cardiomyopathy of overload: An unnatural growth response in the hypertrophied heart. Ann Intern Med 1994; 121: 363–371.Google Scholar
Black SM, Bekker JM, Johengen MJ, Parry AJ, Soiffer SJ, Fineman JR. Altered regulation of the ET-1 cascade in lambs with increased pulmonary blood flow and pulmonary hypertension. Pediatr Res 2000; 47: 97–106.Google Scholar
Yamamoto K, Masuyama T, Sakata Y, et al. Local neurohumoral regulation in the transition to isolated diastolic heart failure in hypertensive heart disease: absence of AT 1 receptor downregulation and overdrive of the endothelin system. Cardiovasc Res 2000; 46: 421–432.Google Scholar
Buchhorn R, Hulpke-Wette M, Ruschewski W, et al. β-adrenoceptor downregulation in children with congenital heart disease: a risk factor for complications after surgical repair? Ann Thorac Surg 2002; 73: 610–613.Google Scholar
Brodde OE, Zerkowski HR, Doetsch N, Motomura S, Khamssi M, Michel MC. Myocardial beta-adrenoceptor changes in heart failure: concomitant reduction in beta 1- and beta 2-adrenoceptor function related to the degree of heart failure in patients with mitral valve disease. J Am Coll Cardiol 1989; 14: 323–331.Google Scholar
Wu JR, Chang HR, Huang TY, Chiang CH, Chen SS. Reduction in lymphocyte β-adrenergic receptor density in infants and children with heart failure secondary to congenital heart disease. Am J Cardiol 1996; 77: 170–174.Google Scholar
Steinberg SF. The molecular basis for distinct beta-adrenergic receptor subtype actions in cardiomyocytes. Circ Res 1999; 85: 1101–1111.Google Scholar
Kuznetsov V, Pak E, Robinson RB, Steinberg SF. Beta2-adrenergic receptor actions in neonatal and adult rat ventricular myocytes. Circ Res 1995; 76: 40–52.Google Scholar
Shaddy RE. Optimizing treatment for chronic congestive heart failure in children. Crit Care Med 2001; 29 [Suppl.]: S237–240.Google Scholar
Ross RD. Medical management of chronic heart failure in children. Am J Cardiovasc Drugs 2001; 1: 37–44.Google Scholar