Hostname: page-component-7c8c6479df-hgkh8 Total loading time: 0 Render date: 2024-03-28T17:35:41.437Z Has data issue: false hasContentIssue false

Pulmonary vasodilator therapy in the failing Fontan circulation: rationale and efficacy*

Published online by Cambridge University Press:  16 December 2015

Brian S. Snarr
Affiliation:
The Cardiac Center, The Children’s Hospital of PhiladelphiaPhiladelphia, Pennsylvania, United States of America
Stephen M. Paridon
Affiliation:
The Cardiac Center, The Children’s Hospital of PhiladelphiaPhiladelphia, Pennsylvania, United States of America Division of Cardiology, Department of Pediatrics, The Perelman School of Medicine at the University of Pennsylvania, Philadelphia, Pennsylvania, United States of America
Jack Rychik
Affiliation:
The Cardiac Center, The Children’s Hospital of PhiladelphiaPhiladelphia, Pennsylvania, United States of America Division of Cardiology, Department of Pediatrics, The Perelman School of Medicine at the University of Pennsylvania, Philadelphia, Pennsylvania, United States of America
David J. Goldberg*
Affiliation:
The Cardiac Center, The Children’s Hospital of PhiladelphiaPhiladelphia, Pennsylvania, United States of America Division of Cardiology, Department of Pediatrics, The Perelman School of Medicine at the University of Pennsylvania, Philadelphia, Pennsylvania, United States of America
*
Correspondence to: Dr D. J. Goldberg, MD, Assistant Professor of Pediatrics, Division of Cardiology, The Children’s Hospital of Philadelphia, 34th Street and Civic Center Boulevard, Philadelphia, Pennsylvania 19010-4399, United States of America. Tel: +267-426-8143; Fax: +267-425-6108; E-mail: goldbergda@email.chop.edu

Abstract

The Fontan operation is the final step of palliation for patients with a functionally single ventricle. Since its introduction in the 1970s, the Fontan surgery has become part of a successful surgical strategy that has improved single ventricle mortality. In recent years, we have become more aware of the limitations and long-term consequences of the Fontan physiology. Pulmonary vascular resistance plays an important role in total cavopulmonary circulation, and has been identified as a potential therapeutic target to mitigate Fontan sequelae. In this review, we will discuss the results of different pulmonary vasodilator trials and the use of pulmonary vasodilators as a treatment strategy for Fontan patients.

Type
Original Articles
Copyright
© Cambridge University Press 2015 

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

*

Presented at the Children’s Hospital of Philadelphia Cardiology 2015: 18th Annual Update on Pediatric and Congenital Cardiovascular Disease: “Challenges and Dilemmas”, Scottsdale, Arizona, United States of America, Wednesday February 11, 2015 – Sunday, February 15, 2015.

References

1.Fontan, F, Baudet, E. Surgical repair of tricuspid atresia. Thorax 1971; 26: 240248.CrossRefGoogle ScholarPubMed
2.Bridges, ND, Mayer, JE Jr., Lock, JE, et al. Effect of baffle fenestration on outcome of the modified Fontan operation. Circulation 1992; 86: 17621769.CrossRefGoogle ScholarPubMed
3.Giannico, S, Hammad, F, Amodeo, A, et al. Clinical outcome of 193 extracardiac Fontan patients: the first 15 years. J Am Coll Cardiol 2006; 47: 20652073.CrossRefGoogle Scholar
4.Rogers, LS, Glatz, AC, Ravishankar, C, et al. 18 years of the Fontan operation at a single institution: results from 771 consecutive patients. J Am Coll Cardiol 2012; 60: 10181025.CrossRefGoogle Scholar
5.Rychik, J, Goldberg, D, Rand, E, et al. End-organ consequences of the Fontan operation: liver fibrosis, protein-losing enteropathy and plastic bronchitis. Cardiol Young 2013; 23: 831840.CrossRefGoogle ScholarPubMed
6.Rychik, J, Goldberg, DJ. Late consequences of the Fontan operation. Circulation 2014; 130: 15251528.CrossRefGoogle ScholarPubMed
7.Avitabile, CM, Goldberg, DJ, Dodds, K, Dori, Y, Ravishankar, C, Rychik, J. A multifaceted approach to the management of plastic bronchitis after cavopulmonary palliation. Ann Thorac Surg 2014; 98: 634640.CrossRefGoogle Scholar
8.Avitabile, CM, Goldberg, DJ, Zemel, BS, et al. Deficits in bone density and structure in children and young adults following Fontan palliation. Bone 2015; 77: 1216.CrossRefGoogle Scholar
9.Goldberg, DJ, French, B, McBride, MG, et al. Impact of oral sildenafil on exercise performance in children and young adults after the Fontan operation: a randomized, double-blind, placebo-controlled, crossover trial. Circulation 2011; 123: 11851193.CrossRefGoogle Scholar
10.Hebert, A, Mikkelsen, UR, Thilen, U, et al. Bosentan improves exercise capacity in adolescents and adults after Fontan operation: the tempo (treatment with endothelin receptor antagonist in Fontan patients, a randomized, placebo-controlled, double-blind study measuring peak oxygen consumption) study. Circulation 2014; 130: 20212030.CrossRefGoogle ScholarPubMed
11.Rhodes, J, Ubeda-Tikkanen, A, Clair, M, et al. Effect of inhaled iloprost on the exercise function of Fontan patients: a demonstration of concept. Int J Cardiol 2013; 168: 24352440.CrossRefGoogle ScholarPubMed
12.Gewillig, M, Goldberg, DJ. Failure of the Fontan circulation. Heart Fail Clin 2014; 10: 105116.CrossRefGoogle ScholarPubMed
13.Cohen, MS, Zak, V, Atz, AM, et al. Anthropometric measures after Fontan procedure: implications for suboptimal functional outcome. Am Heart J 2010; 160: 10921098; 1098 e1091.CrossRefGoogle ScholarPubMed
14.Avitabile, CM, Leonard, MB, Zemel, BS, et al. Lean mass deficits, vitamin d status and exercise capacity in children and young adults after Fontan palliation. Heart 2014; 100: 17021707.CrossRefGoogle Scholar
15.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: 693702.CrossRefGoogle ScholarPubMed
16.Henaine, R, Vergnat, M, Bacha, EA, et al. Effects of lack of pulsatility on pulmonary endothelial function in the Fontan circulation. J Thorac Cardiovasc Surg 2013; 146: 522529.CrossRefGoogle ScholarPubMed
17.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: 32043208.CrossRefGoogle ScholarPubMed
18.Ishida, H, Kogaki, S, Ichimori, H, et al. Overexpression of endothelin-1 and endothelin receptors in the pulmonary arteries of failed Fontan patients. Int J Cardiol 2012; 159: 3439.CrossRefGoogle ScholarPubMed
19.Ishida, H, Kogaki, S, Takahashi, K, Ozono, K. Attenuation of bone morphogenetic protein receptor type 2 expression in the pulmonary arteries of patients with failed Fontan circulation. J Thorac Cardiovasc Surg 2012; 143: e24e26.CrossRefGoogle ScholarPubMed
20.Levy, M, Danel, C, Laval, AM, Leca, F, Vouhe, PR, Israel-Biet, D. Nitric oxide synthase expression by pulmonary arteries: a predictive marker of Fontan procedure outcome? J Thorac Cardiovasc Surg 2003; 125: 10831090.CrossRefGoogle ScholarPubMed
21.Ridderbos, FJ, Wolff, D, Timmer, A, et al. Adverse pulmonary vascular remodeling in the Fontan circulation. J Heart Lung Transplant 2015; 34: 404413.CrossRefGoogle ScholarPubMed
22.Giardini, A, Balducci, A, Specchia, S, Gargiulo, G, Bonvicini, M, Picchio, FM. Effect of sildenafil on haemodynamic response to exercise and exercise capacity in Fontan patients. Eur Heart J 2008; 29: 16811687.CrossRefGoogle ScholarPubMed
23.Archer, SL, Weir, EK, Wilkins, MR. Basic science of pulmonary arterial hypertension for clinicians: new concepts and experimental therapies. Circulation 2010; 121: 20452066.CrossRefGoogle ScholarPubMed
24.Goldberg, DJ, French, B, Szwast, AL, et al. Impact of sildenafil on echocardiographic indices of myocardial performance after the Fontan operation. Pediatr Cardiol 2012; 33: 689696.CrossRefGoogle ScholarPubMed
25.Van De Bruaene, A, La Gerche, A, Claessen, G, et al. Sildenafil improves exercise hemodynamics in Fontan patients. Circ Cardiovasc Imaging 2014; 7: 265273.CrossRefGoogle ScholarPubMed
26.Hiramatsu, T, Imai, Y, Takanashi, Y, et al. Time course of endothelin-1 and adrenomedullin after the Fontan procedure. Ann Thorac Surg 1999; 68: 169172.CrossRefGoogle ScholarPubMed
27.Schuuring, MJ, Vis, JC, van Dijk, AP, et al. Impact of bosentan on exercise capacity in adults after the Fontan procedure: a randomized controlled trial. Eur J Heart Fail 2013; 15: 690698.CrossRefGoogle ScholarPubMed
28.Hirsch, JC, Goldberg, C, Bove, EL, et al. Fontan operation in the current era: a 15-year single institution experience. Ann Surg 2008; 248: 402410.CrossRefGoogle Scholar
29.Thacker, D, Patel, A, Dodds, K, Goldberg, DJ, Semeao, E, Rychik, J. Use of oral budesonide in the management of protein-losing enteropathy after the Fontan operation. Ann Thorac Surg 2010; 89: 837842.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: 12321233.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: e39e40.CrossRefGoogle ScholarPubMed