Hostname: page-component-8448b6f56d-cfpbc Total loading time: 0 Render date: 2024-04-18T00:21:32.282Z Has data issue: false hasContentIssue false
  • English
  • Français

End-organ consequences of the Fontan operation: liver fibrosis, protein-losing enteropathy and plastic bronchitis

Published online by Cambridge University Press:  09 January 2014

Jack Rychik ,
David Goldberg ,
Elizabeth Rand ,
Edisio Semeao ,
Pierre Russo ,
Yoav Dori  and
Kathryn Dodds
Jack Rychik*
Affiliation:
Division of Cardiology, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, Pennsylvania, United States of America Department of Pediatrics, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, Pennsylvania, United States of America
David Goldberg
Affiliation:
Division of Cardiology, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, Pennsylvania, United States of America Department of Pediatrics, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, Pennsylvania, United States of America
Elizabeth Rand
Affiliation:
Division of Gastroenterology, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, Pennsylvania, United States of America Department of Pediatrics, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, Pennsylvania, United States of America
Edisio Semeao
Affiliation:
Division of Gastroenterology, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, Pennsylvania, United States of America Department of Pediatrics, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, Pennsylvania, United States of America
Pierre Russo
Affiliation:
Department of Pediatrics, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, Pennsylvania, United States of America Department of Pathology, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, Pennsylvania, United States of America
Yoav Dori
Affiliation:
Division of Cardiology, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, Pennsylvania, United States of America Department of Pathology and Laboratory Medicine at The Children's Hospital of Philadelphia, Philadelphia, Pennsylvania, United States of America
Kathryn Dodds
Affiliation:
Division of Cardiology, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, Pennsylvania, United States of America
*
Correspondence to: J. Rychik, MD, The Children's Hospital of Philadelphia, 34th Street and Civic Center Boulevard, Philadelphia, PA 19104, United States of America. Tel: 215.590.2192; Fax: 267.426.5082; E-mail: Rychik@email.chop.edu
Get access Rights & Permissions [Opens in a new window]

Abstract

The Fontan operation, although part of a life-saving surgical strategy, manifests a variety of end-organ complications and unique morbidities that are being recognised with increasing frequency as patients survive into their second and third decades of life and beyond. Liver fibrosis, protein-losing enteropathy and plastic bronchitis are consequences of a complex physiology involving circulatory insufficiency, inflammation and lymphatic derangement. These conditions are manifest in a chronic, indolent state. Management strategies are emerging, which shed some light on the origins of these complications. A better characterisation of the end-organ consequences of the Fontan circulation is necessary, which can then allow for development of specific methods for treatment. Ideally, the goal is to establish systematic strategies that might reduce or eliminate the development of these potentially life-threatening challenges.

Keywords

Fontan operationliver fibrosisprotein-losing enteropathyplastic bronchitis
Type
Original Article
Information
Cardiology in the Young , Volume 23 , Issue 6: HeartWeek 2013 , December 2013 , pp. 831 - 840
Copyright
Copyright © Cambridge University Press 2013 

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.)

References

1.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: 1018–1025.CrossRefGoogle Scholar
2.Fontan, F, Baudet, E. Surgical repair of tricuspid atresia. Thorax 1971; 26: 240–248.CrossRefGoogle ScholarPubMed
3.de Leval, MR, Deanfield, JE. Four decades of Fontan palliation. Nat Rev Cardiol 2010; 7: 520–527.CrossRefGoogle ScholarPubMed
4.Gewillig, M, Brown, SC, Eyskens, B, et al. The Fontan circulation: who controls cardiac output? Interact Cardiovasc Thorac Surg 2010; 10: 428–433.CrossRefGoogle ScholarPubMed
5.de Leval, MR, Dubini, G, Migliavacca, F, et al. Use of computational fluid dynamics in the design of surgical procedures: application to the study of competitive flows in cavo-pulmonary connections. J Thorac Cardiovasc Surg 1996; 111: 502–513.CrossRefGoogle Scholar
6.Penny, DJ, Redington, AN. Diastolic ventricular function after the Fontan operation. Am J Cardiol 1992; 69: 974–975.Google Scholar
7.Ho, PK, Lai, CT, Wong, SJ, Cheung, YF. Three-dimensional mechanical dyssynchrony and myocardial deformation of the left ventricle in patients with tricuspid atresia after Fontan procedure. J Am Soc Echocardiogr 2012; 25: 393–400.CrossRefGoogle ScholarPubMed
8.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: 522–529.CrossRefGoogle ScholarPubMed
9.Rychik, J, Fogel, MA, Donofrio, MT, et al. Comparison of patterns of pulmonary venous blood flow in the functional single ventricle heart after operative aortopulmonary shunt versus superior cavopulmonary shunt. Am J Cardiol 1997; 80: 922–926.Google Scholar
10.Steding-Ehrenborg, K, Carlsson, M, Stephensen, S, Arheden, H. Atrial aspiration from pulmonary and caval veins is caused by ventricular contraction and secures 70% of the total stroke volume independent of resting heart rate and heart size. Clin Physiol Funct Imaging 2013; 33: 233–240.CrossRefGoogle ScholarPubMed
11.Gewillig, M, Brown, SC, Heying, R, et al. Volume load paradox while preparing for the Fontan: not too much for the ventricle, not too little for the lungs. Interact Cardiovasc Thorac Surg 2010; 10: 262–265.Google Scholar
12.Rychik, J. Forty years of the Fontan operation: a failed strategy. Seminars in thoracic and cardiovascular surgery Pediatr Cardiac Surg Ann 2010; 13: 96–100.Google Scholar
13.Lemmer, JH, Coran, AG, Behrendt, DM, Heidelberger, KP, Stern, AM. Liver fibrosis (cardiac cirrhosis) five years after modified Fontan operation for tricuspid atresia. J Thorac Cardiovasc Surg 1983; 86: 757–760.Google Scholar
14.Schwartz, MC, Sullivan, L, Cohen, MS, et al. Hepatic pathology may develop before the Fontan operation in children with functional single ventricle: an autopsy study. J Thorac Cardiovasc Surg 2012; 143: 904–909.Google Scholar
15.Ghaferi, AA, Hutchins, GM. Progression of liver pathology in patients undergoing the Fontan procedure: chronic passive congestion, cardiac cirrhosis, hepatic adenoma, and hepatocellular carcinoma. J Thorac Cardiovasc Surg 2005; 129: 1348–1352.Google Scholar
16.Schwartz, MC, Sullivan, LM, Glatz, AC, et al. Portal and sinusoidal fibrosis are common on liver biopsy after Fontan surgery. Pediatr Cardiol 2013; 34: 135–142.Google Scholar
17.Kendall, TJ, Stedman, B, Hacking, N, et al. Hepatic fibrosis and cirrhosis in the Fontan circulation: a detailed morphological study. J Clin Pathol 2008; 61: 504–508.Google Scholar
18.Kiesewetter, CH, Sheron, N, Vettukattill, JJ, et al. Hepatic changes in the failing Fontan circulation. Heart 2007; 93: 579–584.Google Scholar
19.Bryant, T, Ahmad, Z, Millward-Sadler, H, et al. Arterialised hepatic nodules in the Fontan circulation: hepatico-cardiac interactions. Int J Cardiol 2011; 151: 268–272.Google Scholar
20.Friedrich-Rust, M, Koch, C, Rentzsch, A, et al. Noninvasive assessment of liver fibrosis in patients with Fontan circulation using transient elastography and biochemical fibrosis markers. J Thorac Cardiovasc Surg 2008; 135: 560–567.CrossRefGoogle ScholarPubMed
21.Baek, JS, Bae, EJ, Ko, JS, et al. Late hepatic complications after Fontan operation; non-invasive markers of hepatic fibrosis and risk factors. Heart 2010; 96: 1750–1755.Google Scholar
22.Ferraioli, G, Tinelli, C, Dal Bello, B, et al. Accuracy of real-time shear wave elastography for assessing liver fibrosis in chronic hepatitis C: a pilot study. Hepatology 2012; 56: 2125–2133.Google Scholar
23.Rychik, J, Veldtman, G, Rand, E, et al. The precarious state of the liver after a Fontan operation: summary of a multidisciplinary symposium. Pediatr Cardiol 2012; 33: 1001–1012.Google Scholar
24.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.Google Scholar
25.Meadows, J, Jenkins, K. Protein-losing enteropathy: integrating a new disease paradigm into recommendations for prevention and treatment. Cardiol Young 2011; 21: 363–377.Google Scholar
26.Thorne, SA, Hooper, J, Kemp, M, Somerville, J. Gastro-intestinal protein loss in late survivors of Fontan surgery and other congenital heart disease. Eur Heart J 1998; 19: 514–520.Google Scholar
27.Rychik, J. Protein-losing enteropathy after Fontan operation. Congenit Heart Dis 2007; 2: 288–300.Google Scholar
28.Rychik, J, Gui-Yang, S. Relation of mesenteric vascular resistance after Fontan operation and protein-losing enteropathy. Am J Cardiol 2002; 90: 672–674.Google Scholar
29.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.Google Scholar
30.Cohen, MI, Rhodes, LA, Wernovsky, G, Gaynor, JW, Spray, TL, Rychik, J. Atrial pacing: an alternative treatment for protein-losing enteropathy after the Fontan operation. J Thorac Cardiovasc Surg 2001; 121: 582–583.Google Scholar
31.Jacobs, ML, Rychik, J, Byrum, CJ, Norwood, WI Jr. Protein-losing enteropathy after Fontan operation: resolution after baffle fenestration. Ann Thorac Surg 1996; 61: 206–208.CrossRefGoogle ScholarPubMed
32.Rychik, J, Rome, JJ, Jacobs, ML. Late surgical fenestration for complications after the Fontan operation. Circulation 1997; 96: 33–36.Google Scholar
33.Bernstein, D, Naftel, D, Chin, C, et al. Outcome of listing for cardiac transplantation for failed Fontan: a multi-institutional study. Circulation 2006; 114: 273–280.Google Scholar
34.Ostrow, AM, Freeze, H, Rychik, J. Protein-losing enteropathy after Fontan operation: investigations into possible pathophysiologic mechanisms. Ann Thorac Surg 2006; 82: 695–700.Google Scholar
35.Rychik, J, Piccoli, DA, Barber, G. Usefulness of corticosteroid therapy for protein-losing enteropathy after the Fontan procedure. Am J Cardiol 1991; 68: 819–821.CrossRefGoogle ScholarPubMed
36.Zellers, TM, Brown, K. Protein-losing enteropathy after the modified Fontan operation: oral prednisone treatment with biopsy and laboratory proved improvement. Pediatr Cardiol 1996; 17: 115–117.Google Scholar
37.Bode, L, Eklund, EA, Murch, S, Freeze, HH. Heparan sulfate depletion amplifies TNF-alpha-induced protein leakage in an in vitro model of protein-losing enteropathy. Am J Physiol Gastrointest Liver Physiol 2005; 288: G1015–G1023.CrossRefGoogle Scholar
38.Bode, L, Murch, S, Freeze, HH. Heparan sulfate plays a central role in a dynamic in vitro model of protein-losing enteropathy. J Biol Chem 2006; 281: 7809–7815.Google Scholar
39.Amadi, B, Fagbemi, AO, Kelly, P, et al. Reduced production of sulfated glycosaminoglycans occurs in Zambian children with kwashiorkor but not marasmus. Am J Clin Nutr 2009; 89: 592–600.Google Scholar
40.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: 837–842.Google Scholar
41.Turner, Z, Lanford, L, Webber, S. Oral budesonide as a therapy for protein-losing enteropathy in patients having undergone Fontan palliation. Congenit Heart Dis 2012; 7: 24–30.CrossRefGoogle ScholarPubMed
42.Rychik, J. Invited commentary. Ann Thorac Surg 2011; 92: 1456.Google Scholar
43.John, AS, Driscoll, DJ, Warnes, CA, Phillips, SD, Cetta, F. The use of oral budesonide in adolescents and adults with protein-losing enteropathy after the Fontan operation. Ann Thorac Surg 2011; 92: 1451–1456.Google Scholar
44.Schumacher, KR, Cools, M, Goldstein, BH, et al. Oral budesonide treatment for protein-losing enteropathy in Fontan-palliated patients. Pediatr Cardiol 2011; 32: 966–971.Google Scholar
45.Mertens, L, Dumoulin, M, Gewillig, M. Effect of percutaneous fenestration of the atrial septum on protein-losing enteropathy after the Fontan operation. Br Heart J 1994; 72: 591–592.Google Scholar
46.Kanter, KR, Mahle, WT, Vincent, RN, Berg, AM, Kogon, BE, Kirshbom, PM. Heart transplantation in children with a Fontan procedure. Ann Thorac Surg 2011; 91: 823–829; discussion 9–30.CrossRefGoogle ScholarPubMed
47.Larue, M, Gossett, JG, Stewart, RD, Backer, CL, Mavroudis, C, Jacobs, ML. Plastic bronchitis in patients with Fontan physiology: review of the literature and preliminary experience with Fontan conversion and cardiac transplantation. World J Pediatr Congenit Heart Surg 2012; 3: 364–372.CrossRefGoogle ScholarPubMed
48.Stiller, B, Riedel, F, Paul, K, van Landeghem, FK. Plastic bronchitis in children with Fontan palliation: analogue to protein-losing enteropathy? Pediatr Cardiol 2002; 23: 90–94.Google Scholar
49.Racz, J, Mane, G, Ford, M, et al. Immunophenotyping and protein profiling of Fontan-associated plastic bronchitis airway casts. Ann Am Thorac Soc 2013; 10: 98–107.CrossRefGoogle ScholarPubMed
50.Caruthers, RL, Kempa, M, Loo, A, et al. Demographic characteristics and estimated prevalence of Fontan-associated plastic bronchitis. Pediatr Cardiol 2013; 34: 256–261.Google Scholar
51.Wilson, J, Russell, J, Williams, W, Benson, L. Fenestration of the Fontan circuit as treatment for plastic bronchitis. Pediatr Cardiol 2005; 26: 717–719.Google Scholar
52.Chaudhari, M, Stumper, O. Plastic bronchitis after Fontan operation: treatment with stent fenestration of the Fontan circuit. Heart 2004; 90: 801.Google Scholar
53.Barber, BJ, Burch, GH, Tripple, D, Balaji, S. Resolution of plastic bronchitis with atrial pacing in a patient with Fontan physiology. Pediatr Cardiol 2004; 25: 73–76.CrossRefGoogle Scholar
54.Laubisch, JE, Green, DM, Mogayzel, PJ, Reid Thompson, W. Treatment of plastic bronchitis by orthotopic heart transplantation. Pediatr Cardiol 2011; 32: 1193–1195.Google Scholar
55.ElMallah, MK, Prabhakaran, S, Chesrown, SE. Plastic bronchitis: resolution after heart transplantation. Pediatr Pulmonol 2011; 46: 824–825.CrossRefGoogle ScholarPubMed
56.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
57.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.Google Scholar
58.Costello, JM, Steinhorn, D, McColley, S, Gerber, ME, Kumar, SP. Treatment of plastic bronchitis in a Fontan patient with tissue plasminogen activator: a case report and review of the literature. Pediatrics 2002; 109: e67.Google Scholar
59.Wakeham, MK, Van Bergen, AH, Torero, LE, Akhter, J. Long-term treatment of plastic bronchitis with aerosolized tissue plasminogen activator in a Fontan patient. Pediatr Crit Care Med 2005; 6: 76–78.Google Scholar
60.Do, TB, Chu, JM, Berdjis, F, Anas, NG. Fontan patient with plastic bronchitis treated successfully using aerosolized tissue plasminogen activator: a case report and review of the literature. Pediatr Cardiol 2009; 30: 352–355.Google Scholar
61.Lubcke, NL, Nussbaum, VM, Schroth, M. Use of aerosolized tissue plasminogen activator in the treatment of plastic bronchitis. Ann Pharmacother 2013; 47: e13.Google Scholar
62.Parikh, K, Witte, MH, Samson, R, et al. Successful treatment of plastic bronchitis with low fat diet and subsequent thoracic duct ligation in child with fontan physiology. Lymphology 2012; 45: 47–52.Google Scholar
63.Shah, SS, Drinkwater, DC, Christian, KG. Plastic bronchitis: is thoracic duct ligation a real surgical option? Ann Thorac Surg 2006; 81: 2281–2283.CrossRefGoogle ScholarPubMed
64.Ezmigna, DR, Morgan, WJ, Witte, MH, Brown, MA. Lymphoscintigraphy in plastic bronchitis, a pediatric case report. Pediatr Pulmonol 2013; 48: 515–518.CrossRefGoogle ScholarPubMed