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The effect of bosentan in patients with a failing Fontan circulation

Published online by Cambridge University Press:  01 August 2009

Caroline Ovaert ,
Daisy Thijs ,
Daniel Dewolf ,
Jaap Ottenkamp ,
Hugues Dessy ,
Philip Moons ,
Marc Gewillig  and
Luc Mertens
Caroline Ovaert
Affiliation:
Department of Pediatric Cardiology, Cliniques Universitaires Saint-Luc, Université Catholique de Louvain, Brussels, Belgium
Daisy Thijs
Affiliation:
Department of Pediatric Cardiology, University Hospitals Leuven, Leuven, Belgium
Daniel Dewolf
Affiliation:
Department of Pediatric Cardiology, Universitair Ziekenhuis Gent, Gent, Belgium
Jaap Ottenkamp
Affiliation:
Department of Pediatric Cardiology, University Medical Centre, Leiden, Netherlands
Hugues Dessy
Affiliation:
Hôpital Universitaire des Enfants Reine Fabiola, Université Libre de Bruxelles, Brussels, Belgium
Philip Moons
Affiliation:
Center for Health Services and Nursing Research, University Hospitals Leuven, Leuven, Belgium
Marc Gewillig
Affiliation:
Department of Pediatric Cardiology, University Hospitals Leuven, Leuven, Belgium
Luc Mertens*
Affiliation:
Department of Pediatric Cardiology, University Hospitals Leuven, Leuven, Belgium
*
Correspondence to: Luc Mertens, MD, PhD, The Hospital for Sick Children, The Labatt Family Heart Centre, 555 University Avenue, Toronto, ON, M5G 1X8, Canada. Tel: +1-416-813-7291; Fax: +1-416-813-5857; E-mail: [email protected]
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Abstract

Objectives

To investigate the effect of bosentan in patients with a failing Fontan circulation.

Design

A multicentric open label, non-controlled study.

Setting

5 tertiary care centres for congenital cardiology.

Patients

We included 10 patients with a failing Fontan circulation. Their median age at inclusion was 12.12 years, with a range from 4.41 to 33,41 years. The median interval between the Fontan operation and inclusion was 7.84 years, with a range from 1.96 to 12,18 years. Participants received half the usual dose of bosentan for 4 weeks, and then the full dose for a further 12 weeks.

Main measures of outcomes

We assessed saturations of oxygen at rest and during exercise, using a 6 minutes walk test, at baseline, and during and after 16 weeks of treatment. At each visit, we assessed blood chemistry and hepatic function, and asked the patients to complete a questionnaire concerning quality of life. All medical events and possible side effects were recorded.

Results

Of the cohort, 1 patient withdrew. The changes in saturations of oxygen, exercise performance, and scores for the questionnaire did not reach statistical significance for the whole group. We noted, nonetheless, that saturations of oxygen and/or exercise capacity improved in 5 of the patients. This was further confirmed when those patients deteriorated again when the drug was discontinued.

Conclusions

Our study failed to show significant improvement after 3 months of treatment with bosentan in a small group of patients with failing Fontan circulations. Some individuals, nonetheless, did improve. When planning larger trials, it would be better to identify those patients who might potentially benefit from the treatment prior to commencing the trial.

Keywords

Congenital heart defectfunctionally single ventricleendothelin receptor antagonistpulmonary vascular resistance
Type
Original Articles
Information
Cardiology in the Young , Volume 19 , Issue 4 , August 2009 , pp. 331 - 339
Copyright
Copyright © Cambridge University Press 2009

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References

1.Gewillig, M. The Fontan circulation. Heart 2005; 91: 839–846.CrossRefGoogle ScholarPubMed
2.d’Udekem, Y, Iyengar, AJ, Cochrane, AD, et al. The Fontan procedure: contemporary techniques have improved long-term outcomes. Circulation 2007; 116: I157–I164.CrossRefGoogle ScholarPubMed
3.Gentles, TL, Mayer, JE Jr., Gauvreau, K, et al. Fontan operation in five hundred consecutive patients: factors influencing early and late outcome. J Thorac Cardiovasc Surg 1997; 114: 376–391.CrossRefGoogle ScholarPubMed
4.Gentles, TL, Gauvreau, K, Mayer, JE Jr., et al. Functional outcome after the Fontan operation: factors influencing late morbidity. J Thorac Cardiovasc Surg 1997; 114: 392–403; discussion 404–405.CrossRefGoogle ScholarPubMed
5.Cetta, F, Feldt, RH, O’Leary, PW, et al. Improved early morbidity and mortality after Fontan operation: the Mayo Clinic experience, 1987 to 1992. J Am Coll Cardiol 1996; 28: 480–486.CrossRefGoogle Scholar
6.Earing, MG, Cetta, F, Driscoll, DJ, et al. Long-term results of the Fontan operation for double-inlet left ventricle. Am J Cardiol 2005; 96: 291–298.CrossRefGoogle ScholarPubMed
7.Burkhart, HM, Dearani, JA, Mair, DD, et al. The modified Fontan procedure: early and late results in 132 adult patients. J Thorac Cardiovasc Surg 2003; 125: 1252–1259.CrossRefGoogle ScholarPubMed
8.Mertens, L, Hagler, DJ, Sauer, U, Somerville, J, Gewillig, M. Protein-losing enteropathy after the Fontan operation: an international multicenter study. PLE study group. J Thorac Cardiovasc Surg 1998; 115: 1063–1073.CrossRefGoogle ScholarPubMed
9.Khairy, P, Fernandes, SM, Mayer, JE Jr., et al. Long-Term Survival, Modes of Death, and Predictors of Mortality in Patients With Fontan Surgery. Circulation 2008; 117: 85–92.CrossRefGoogle ScholarPubMed
10.Mitchell, MB, Campbell, DN, Ivy, D, et al. Evidence of pulmonary vascular disease after heart transplantation for Fontan circulation failure. J Thorac Cardiovasc Surg 2004; 128: 693–702.CrossRefGoogle ScholarPubMed
11.Khambadkone, S, Li, J, de Leval, MR, Cullen, S, Deanfield, JE, Redington, AN. Basal pulmonary vascular resistance and nitric oxide responsiveness late after Fontan-type operation. Circulation 2003; 107: 3204–3208.CrossRefGoogle ScholarPubMed
12.Schulze-Neick, I, Li, J, Reader, JA, Shekerdemian, L, Redington, AN, Penny, DJ. The endothelin antagonist BQ123 reduces pulmonary vascular resistance after surgical intervention for congenital heart disease. J Thorac Cardiovasc Surg 2002; 124: 435–441.CrossRefGoogle ScholarPubMed
13.Yamagishi, M, Kurosawa, H, Hashimoto, K, Nomura, K, Kitamura, N. The role of plasma endothelin in the Fontan circulation. J Cardiovasc Surg 2002; 43: 793–797.Google ScholarPubMed
14.Clozel, M. Endothelin receptor antagonists: current status and perspectives. J Cardiovasc Pharmacol 2000; 35: S65–S68.CrossRefGoogle Scholar
15.Barst, RJ, Ivy, D, Dingemanse, J, et al. Pharmacokinetics, safety, and efficacy of bosentan in pediatric patients with pulmonary arterial hypertension. Clin Pharmacol Ther 2003; 73: 372–382.CrossRefGoogle ScholarPubMed
16.Rubin, LJ, Badesch, DB, Barst, RJ, et al. Bosentan therapy for pulmonary arterial hypertension. N Engl J Med 2002; 346: 896–903.CrossRefGoogle ScholarPubMed
17.Varni, JW, Seid, M, Kurtin, PS. PedsQL 4.0: reliability and validity of the Pediatric Quality of Life Inventory version 4.0 generic core scales in healthy and patient populations. Med Care 2001; 39: 800–812.CrossRefGoogle ScholarPubMed
18.Lammers, AE, Hislop, AA, Flynn, Y, Haworth, SG. The six-minute walk test: Normal values for children of 4–11 years of age. Arch Dis Child 2008; 93: 464–468.CrossRefGoogle ScholarPubMed
19.Sitbon, O, McLaughlin, VV, Badesch, DB, et al. Survival in patients with class III idiopathic pulmonary arterial hypertension treated with first line oral bosentan compared with an historical cohort of patients started on intravenous epoprostenol. Thorax 2005; 60: 1025–1030.CrossRefGoogle ScholarPubMed
20.Denton, CP, Humbert, M, Rubin, L, Black, CM. Bosentan treatment for pulmonary arterial hypertension related to connective tissue disease: a subgroup analysis of the pivotal clinical trials and their open-label extensions. Ann Rheumatic Dis 2006; 65: 1336–1340.CrossRefGoogle ScholarPubMed
21.Denton, CP, Pope, JE, Peter, HH, et al. Long-term effects of bosentan on quality of life, survival, safety and tolerability in pulmonary arterial hypertension related to connective tissue diseases. Ann Rheumatic Dis 2008; 67: 1222–1228.CrossRefGoogle ScholarPubMed
22.Rosenzweig, EB, Ivy, DD, Widlitz, A, et al. Effects of long-term bosentan in children with pulmonary arterial hypertension. J Am Coll Cardiol 2005; 46: 697–704.CrossRefGoogle ScholarPubMed
23.Galie, N, Beghetti, M, Gatzoulis, MA, et al. Bosentan therapy in patients with Eisenmenger syndrome: a multicenter, double-blind, randomized, placebo-controlled study. Circulation 2006; 114: 48–54.CrossRefGoogle ScholarPubMed
24.Barst, RJ, Langleben, D, Badesch, D, et al. Treatment of pulmonary arterial hypertension with the selective endothelin-A receptor antagonist sitaxsentan. J Am Coll Cardiol 2006; 47: 2049–2056.CrossRefGoogle ScholarPubMed
25.Barst, RJ. A review of pulmonary arterial hypertension: role of ambrisentan. Vasc Health Risk Manag 2007; 3: 11–22.Google ScholarPubMed
26.Benza, RL, Mehta, S, Keogh, A, Lawrence, EC, Oudiz, RJ, Barst, RJ. Sitaxsentan treatment for patients with pulmonary arterial hypertension discontinuing bosentan. J Heart Lung Transplant 2007; 26: 63–69.CrossRefGoogle ScholarPubMed
27.Humpl, T, Reyes, JT, Holtby, H, Stephens, D, Adatia, I. Beneficial effect of oral sildenafil therapy on childhood pulmonary arterial hypertension: twelve-month clinical trial of a single-drug, open-label, pilot study. Circulation 2005; 111: 3274–3280.CrossRefGoogle Scholar
28.Apostolopoulou, SC, Papagiannis, J, Rammos, S. Bosentan induces clinical, exercise and hemodynamic improvement in a pre-transplant patient with plastic bronchitis after Fontan operation. J Heart Lung Transplant 2005; 24: 1174–1176.CrossRefGoogle Scholar
29.Miyaji, K, Nagata, N, Miyamoto, T, Kitahori, K. Combined therapy with inhaled nitric oxide and intravenous epoprostenol (prostacyclin) for critical pulmonary perfusion after the Fontan procedure. J Thorac Cardiovasc Surg 2003; 125: 437–439.CrossRefGoogle ScholarPubMed
30.Haseyama, K, Satomi, G, Yasukochi, S, Matsui, H, Harada, Y, Uchita, S. Pulmonary vasodilation therapy with sildenafil citrate in a patient with plastic bronchitis after the Fontan procedure for hypoplastic left heart syndrome. J Thorac Cardiovasc Surg 2006; 132: 1232–1233.CrossRefGoogle Scholar
31.Uzun, O, Wong, JK, Bhole, V, Stumper, O. Resolution of protein-losing enteropathy and normalization of mesenteric Doppler flow with sildenafil after Fontan. Ann Thorac Surg 2006; 82: e39–e40.CrossRefGoogle ScholarPubMed
32.Giardini, A, Balducci, A, Specchia, S, Gargiulo, G, Bonviccini, M, Picchio, FM. Effect of sildenafil on haemodynamic response to exercise and exercise capacity in Fontan patients. Eur Heart J 2008; 29: 1681–1687.CrossRefGoogle ScholarPubMed