Skip to main content Accessibility help
×
×
Home

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

  • Brian S. Snarr (a1), Stephen M. Paridon (a1) (a2), Jack Rychik (a1) (a2) and David J. Goldberg (a1) (a2)
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.

Copyright
Corresponding author
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
Footnotes
Hide All
*

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.

Footnotes
References
Hide All
1.Fontan, F, Baudet, E. Surgical repair of tricuspid atresia. Thorax 1971; 26: 240248.
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.
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.
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.
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.
6.Rychik, J, Goldberg, DJ. Late consequences of the Fontan operation. Circulation 2014; 130: 15251528.
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.
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.
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.
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.
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.
12.Gewillig, M, Goldberg, DJ. Failure of the Fontan circulation. Heart Fail Clin 2014; 10: 105116.
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.
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.
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.
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.
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.
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.
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.
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.
21.Ridderbos, FJ, Wolff, D, Timmer, A, et al. Adverse pulmonary vascular remodeling in the Fontan circulation. J Heart Lung Transplant 2015; 34: 404413.
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.
23.Archer, SL, Weir, EK, Wilkins, MR. Basic science of pulmonary arterial hypertension for clinicians: new concepts and experimental therapies. Circulation 2010; 121: 20452066.
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.
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.
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.
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.
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.
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.
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.
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.
Recommend this journal

Email your librarian or administrator to recommend adding this journal to your organisation's collection.

Cardiology in the Young
  • ISSN: 1047-9511
  • EISSN: 1467-1107
  • URL: /core/journals/cardiology-in-the-young
Please enter your name
Please enter a valid email address
Who would you like to send this to? *
×

Keywords

Metrics

Full text views

Total number of HTML views: 0
Total number of PDF views: 0 *
Loading metrics...

Abstract views

Total abstract views: 0 *
Loading metrics...

* Views captured on Cambridge Core between <date>. This data will be updated every 24 hours.

Usage data cannot currently be displayed