Modern Day Care of Patients With Single Ventricle Heart Disease: Late Complications of Fontan Palliation

  • M. Abigail Simmons
  • Robert W. ElderEmail author
Cardiology (W Zuckerman and E Silver, Section Editors)
Part of the following topical collections:
  1. Cardiology


Purpose of Review

The majority of individuals who have undergone Fontan palliation are surviving into adulthood, yet complications are common. This review will focus on late complications—cardiac and extra-cardiac—which may present insidiously.

Recent Findings

Recent meta-analysis of patients after Fontan operation suggests that over 80% will survive 20 years beyond surgery. This group is at risk for structural complications, arrhythmias, vascular complications, and heart failure. Not all forms of Fontan failure are the same, and categorization into separate entities such as failure with preserved versus reduced function may help guide therapies. Pulmonary vasodilators in particular may be useful to improve hemodynamics. Novel therapies aimed at lymphatic complications are emerging and promising. Late hepatic complications including ascites and liver cancer may be seen, and scoring systems may identify patients at higher risk.


Individuals who have undergone a Fontan surgery face challenges as they age which include both cardiac and non-cardiac systems.


Fontan procedure Single ventricle Survival Cirrhosis Congenital heart disease Hepatocellular carcinoma Pulmonary vasodilators Lymphatic complications 


Compliance with Ethical Standards

Conflict of Interest

The authors declare that they have no conflict of interest.

Human and Animal Rights and Informed Consent

This article does not contain any studies with human or animal subjects performed by any of the authors.


Papers of particular interest, published recently, have been highlighted as: • Of importance •• Of major importance

  1. 1.
    •• Gewillig M, Brown SC. The Fontan circulation after 45 years: update in physiology. Heart. 2016;102:1081–6 This paper details the current understanding of Fontan physiology including optimal and suboptimal hemodynamic conditions. Google Scholar
  2. 2.
    •• Poh CL, d’Udekem Y. Life after surviving fontan surgery: a meta-analysis of the incidence and predictors of late death. Heart Lung Circ. 2018;27(5):552–9 One of the largest series detailing the long-term outcomes in Fontan patients. Google Scholar
  3. 3.
    •• Stout KK, Daniels CJ, Aboulhosn JA, Bozkurt B, Broberg CS, Colman JM, et al. 2018 AHA/ACC guideline for the management of adults with congenital heart disease: executive summary: a report of the American College of Cardiology/American Heart Association Task Force on Clinical Practice Guidelines. J Am Coll Cardiol. 2018;S0735-1097(18):36845–1 The guidelines detail the anatomic and physiologic classification of congenital heart disease, general guidelines for the care of adult congenital heart disease, and lesion-specific guidance. Google Scholar
  4. 4.
    Deal BJ, Jacobs ML. Management of the failing Fontan circulation. Heart. 2012;98(14):1098–104.Google Scholar
  5. 5.
    McElhinney D, Reddy V, Hanley F, Moore P. Systemic venous collateral channels causing desaturation after bidirectional cavopulmonary anastomosis: evaluation and management. J Am Coll Cardiol. 1997;30(3):817–24.Google Scholar
  6. 6.
    Lluri G, Levi DS, Aboulhosn J. Systemic to pulmonary venous collaterals in adults with single ventricle physiology after cavopulmonary palliation. Int J Cardiol. 2015;189:159–63.Google Scholar
  7. 7.
    Hoffman J. Normal and abnormal pulmonary arteriovenous shunting: occurrence and mechanisms. Cardiol Young. 2013;23(5):629–41.Google Scholar
  8. 8.
    Sundareswaran KS, de Zelicourt D, Sharma S, Kanter KR, Spray TL, Sotiropoulos F, et al. Correction of pulmonary artery malformation using image-based surgical planning. JACC Cardiovasc Imaging. 2009;2(8):1024–30.Google Scholar
  9. 9.
    Triedman JK, Bridges ND, Mayer JE, Lock JE. Prevalence and risk factors for aortopulmonary collateral vessels after Fontan and bidirectional Glenn procedures. JACC. 1993;22(1):207–15.Google Scholar
  10. 10.
    Grosse-Wortmann L, Al-Otay A, Yoo S-J. Aortopulmonary collaterals after bidirectional cavopulmonary connection or Fontan completion quantification with MRI. Circulation. 2(3):219–25.Google Scholar
  11. 11.
    Wang R-P, Liang C-H, Huang M-P, Liu H, Deng Q-P, Yang M-F. Assessment of aortopulmonary collateral flow and pulmonary vascular growth using a 3.0 T magnetic resonance imaging system in patients who underwent bidirectional Glenn shunting. Eur J Cardiothorac Surg. 2012;41(6):e146–53.Google Scholar
  12. 12.
    Pundi KN, Johnson JN, Dearani JA, Pundi KN, Li Z, Hinck CA, et al. 40-year follow-up after the Fontan operation long-term outcomes of 1,052 patients. JACC. 2015;66(15):1700–10.Google Scholar
  13. 13.
    Lasa J, Glatz AC, Daga A, Shah M. Prevalence of arrhythmias late after the Fontan operation. Am J Cardiol. 2014;113(7):1184–8.Google Scholar
  14. 14.
    Pundi KN, Johnson JN, Dearani JA, Li Z, Driscoll DJ, et al. Sudden cardiac death and late arrhythmias after the Fontan operation. Congenit Heart Dis. 2017;12(1):17–23.Google Scholar
  15. 15.
    Fontan F, Kirkin JW, Fernandez G, Costa F, Naftel DC, Tritto F, et al. Outcome after a perfect Fontan. Circulation. 1990;81(5):1520–36.Google Scholar
  16. 16.
    d’Udekem Y, Iyengar AJ, Galati JC, Forsdick V, Weintraub RG, Wheaton GR, et al. Redefining expectations of long-term survival after the Fontan procedure. Circulation. 2014;130(11 suppl 1):S32–8.Google Scholar
  17. 17.
    •• Hebson C, Book W, Elder RW, Ford R, Jokhadar M, Kanter K, et al. Frontiers in Fontan failure: a summary of conference proceedings. Congenit Heart Dis. 2017;12(1):6–16 This document introduced the use of a standardized classification system for Fontan failure including the clinical findings associated with different phenotypes of Fontan failure. Google Scholar
  18. 18.
    •• Book WM, Geradin J, Saraf A, Valente AM, Rodriguez F. Clinical phenotypes of Fontan failure: implications for management. Congenit Heart Dis. 2016;11:296–308 A document summarizing phenotype-specific management strategies for Fontan failure. Google Scholar
  19. 19.
    Wilson TG, Iyengar AJ, d’Udekem Y. The use and misuse of ACE inhibitors in patients with single ventricle physiology. Heart Lung Circ. 2016;25(3):229–36.Google Scholar
  20. 20.
    Kouatli A, Garcia J, Zellers TM, Weinstein E, Mahony LM. Enalapril does not enhance exercise capacity in patients after Fontan procedure. Circulation. 1997;96(5):1507–12.Google Scholar
  21. 21.
    Hebert A, Mikkelsen U, Thilen U, Idorn L, Jensen A, Nagy E, 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(23):2021–30.Google Scholar
  22. 22.
    Wang W, Hu X, Liao W, Rutahoile WH, Malenka DJ, Zeng X, et al. The efficacy and safety of pulmonary vasodilators in patients with Fontan circulation: a meta-analysis of randomized controlled trials. Pulmonary Circulation. 2019;9(1).Google Scholar
  23. 23.
    Van der Ven J, Van den Bosch E, Bogers AJCC, Helbing WA. State of the art of the Fontan strategy for treatment of univentricular heart disease. F1000Research. 2018;935:1–14.Google Scholar
  24. 24.
    Feldt R, Driscoll D, Offord K, Cha RH, Perrault J, Schaff HV, et al. Protein-losing enteropathy after the Fontan operation. J Thorac Cardiovasc Surg. 1996;112(3):672–80.Google Scholar
  25. 25.
    Mertens L, Hagler DJ, Sauer U, Somerville J, Gewillig M. Protein-losing enteropathy after the Fontan operation: an international multicenter study. J Thorac Cardiovasc Surg. 1998;115(5):1063–73.Google Scholar
  26. 26.
    Schumacher KR, Stringer KA, Donohue JE, Yu S, Shaver A, Caruthers RL, et al. Fontan-associated protein-losing enteropathy and plastic bronchitis. J Pediatr. 2015;166(4):970–7.Google Scholar
  27. 27.
    Dori Y, Keller MS, Fogel MA, Rome JJ, Whitehead KK, Harris MA, et al. MRI of lymphatic abnormalities after functional single-ventricle palliation surgery. Am J Roentgenol. 2014;203(2):426–31.Google Scholar
  28. 28.
    • Dori Y, Keller MS, Rome JJ, Gillespie MJ, Glatz AC, Dodds K, et al. Percutaneous lymphatic embolization of abnormal pulmonary lymphatic flow as treatment of plastic bronchitis in patients with congenital heart disease. Circulation. 2016;133(12):1160–70 The authors report on the success of a novel percutaneous intervention for plastic bronchitis. Google Scholar
  29. 29.
    John AS, Johnson JA, Khan M, Driscoll DJ, Warnes CA, Cetta F. Clinical outcomes and improved survival in patients with protein-losing enteropathy after the Fontan operation. J Am Coll Cardiol. 2014;64(1):54–62.Google Scholar
  30. 30.
    • Egbe AC, Connolly HM, Niaz T, Yogeswaran V, Taggart NW, Qureshi MY, et al. Prevalence and outcome of thrombotic and embolic complications in adults after Fontan operation. Am Heart J. 2017;183:10–7 Extensive retrospective review of thromboembolic complications in 387 adults with a Fontan procedure. Google Scholar
  31. 31.
    Coon PD, Rychik J, Novello RT, Ro PS, Gaynor JW, Spray TL. Thrombus formation after the Fontan operation. Ann Thorac Surg. 2001;71(6):1990–4.Google Scholar
  32. 32.
    Dennis M, Zannino D, du Plessis K, Bullock A, Disney P, Radford DJ, et al. Clinical outcomes in adolescents and adults after the Fontan procedure. J Am Coll Cardiol. 2018;71(9):1009–17.Google Scholar
  33. 33.
    Alsaied T, Alsidawi S, Allen CC, Faircloth J, Palumbo JS, Veldtman GR. Strategies for thromboprophylaxis in Fontan circulation: a meta-analysis. Heart. 2015;101(21):1731–7.Google Scholar
  34. 34.
    • Georgekutty J, Kazerouninia A, Want Y, Ermis P, Parekh D, Franklin W, et al. Novel oral anticoagulant use in adult Fontan patients: a single center experience. Congenital Heart Dis. 2018;1–7. This study reports the outcomes of novel anticoagulant use in Fontan patients for the prevention of thromboembolic complications. Google Scholar
  35. 35.
    Yang H, Bouma BJ, Mulder BJ. Vitamin antagonist anticoagulants for prevention in adult congenital heart disease investigators NK. Is initiating NOACs for atrial arrhythmias safe in adults with congenital heart disease? Cardiovasc Drugs Ther. 2017;31(4):413–7.Google Scholar
  36. 36.
    • Goldberg DJ, Surrey LF, Glatz AC, Dodds K, O’Byrne ML, Lin HC, et al. Hepatic fibrosis is universal following Fontan operation, and severity is associated with time from surgery: a liver biopsy and hemodynamic study. J Am Heart Assoc. 2017;6(5):e004809-9 This study details the universal presence of hepatic fibrosis following Fontan palliation and correlates this fibrosis with clinical and hemodynamic outcomes. Google Scholar
  37. 37.
    •• Daniels CJ, Bradley EA, Landzberg MJ, Aboulhosn J, Beekman RH, Book W, et al. Fontan-associated liver disease proceedings from the American College of Cardiology Stakeholders Meeting, October 1 to 2, 2015, Washington DC. J Am Coll Cardiol. 2017;70(25):3173–94 This document provides the first set of suggested guidelines for the screening and management of Fontan-associated liver disease. Google Scholar
  38. 38.
    Lemmer A, VanWagner LB, Ganger D. Assessment of advanced liver fibrosis and the risk for hepatic decompensation in patients with congestive hepatopathy. Hepatology. 2018;68(4):1633–41.Google Scholar
  39. 39.
    Wu FM, Earing MG, Aboulhosn JA, Johncilla ME, Singh MN, Odze RD, et al. Predictive value of biomarkers of hepatic fibrosis in adult Fontan patients. J Heart Lung Transplant. 2017;36(2):211–9.Google Scholar
  40. 40.
    Elder RW, McCabe NM, Hebson C, Veledar E, Romero R, Ford RM, et al. Features of portal hypertension are associated with major adverse events in Fontan patients: the VAST study. Int J Cardiol. 2013;168(4):3764–9.Google Scholar
  41. 41.
    Assenza GE, Graham DA, Landzberg MJ, Valente AM, Singh MN, Bashir A, et al. MELD-XI score and cardiac mortality or transplantation in patients after Fontan surgery. Heart. 2013;99:491–6.Google Scholar
  42. 42.
    Egbe AC, Poterucha JT, Warnes CA, Connolly HM, Baskar S, Ginde S, et al. Hepatocellular carcinoma after Fontan operation. Circulation. 2018;138(7):746–8.Google Scholar
  43. 43.
    Liptzin DR, Maria MV, Younoszai A, Narkewicz MR, Kelly SL, Wolfe KR, et al. Pulmonary screening in subjects after the Fontan procedure. J Pediatr. 2018;199:140–3.Google Scholar
  44. 44.
    Opotowsky AR, Landzberg MJ, Earing MG, Wu FM, Triedman JK, Casey A, et al. Abnormal spirometry after the Fontan procedure is common and associated with impaired aerobic capacity. Am J Physiol Heart Circ Physiol. 2014;307(1):H110–7.Google Scholar
  45. 45.
    Fredriksen P, Therrien J, Veldtman G, Warsi M, Liu P, Siu S, et al. Lung function and aerobic capacity in adult patients following modified Fontan procedure. Heart. 2001;85(3):295–9.Google Scholar
  46. 46.
    Matthews I, Fredriksen P, Bjørnstad PG, Thaulow E, Gronn M. Reduced pulmonary function in children with the Fontan circulation affects their exercise capacity. Cardiol Young. 2006;16(3):261–7.Google Scholar
  47. 47.
    Nakhleh N, Francis R, Giese RA, Tian X, Li Y, Zariwala MA, et al. High prevalence of respiratory ciliary dysfunction in congenital heart disease patients with heterotaxy. Circulation. 2012;125(18):2232–42.Google Scholar
  48. 48.
    Ali L, Pingitore A, Piaggi P, Brucini F, Passera M, Marotta M, et al. Respiratory training late after Fontan intervention: impact on cardiorespiratory performance. Pediatr Cardiol. 2018;39(4):695–704.Google Scholar
  49. 49.
    Hedlund ER, Ljungberg H, Söderström L, Lundell B, Sjöberg G. Impaired lung function in children and adolescents with Fontan circulation may improve after endurance training. Cardiol Young. 2018;28(9):1115–22.Google Scholar
  50. 50.
    Marino B, Lipkin P, Newburger J, Peacock G, Gerdes M, Gaynor J, et al. Neurodevelopmental outcomes in children with congenital heart disease: evaluation and management: a scientific statement from the American Heart Association. Circulation. 2012;126(9):1143–72.Google Scholar
  51. 51.
    Bellinger DC, Watson CG, Rivkin MJ, Robertson RL, Roberts AE, Stopp C, et al. Neuropsychological status and structural brain imaging in adolescents with single ventricle who underwent the Fontan procedure. J Am Heart Assoc. 2015;4(12):e002302.Google Scholar
  52. 52.
    Luyckx K, Rassart J, Goossens E, Apers S, Oris L, Moons P. Development and persistence of depressive symptoms in adolescents with CHD. Cardiol Young. 2015;26(6):1115–22.Google Scholar
  53. 53.
    Kovacs AH, Saidi AS, Kuhl EA, Sears SF, Silversides C, Harrison JL, et al. Depression and anxiety in adult congenital heart disease: predictors and prevalence. Int J Cardiol. 2009;137(2):158–64.Google Scholar
  54. 54.
    DeMaso DR, Calderon J, Taylor GA, Holland JE, Stopp C, White MT, et al. Psychiatric disorders in adolescents with single ventricle congenital heart disease. Pediatrics. 2017;139(3):e20162241.Google Scholar
  55. 55.
    McCrindle BW, Williams RV, Mitchell PD, Hsu DT, Paridon SM, Atz AM, et al. Relationship of patient and medical characteristics to health status in children and adolescents after the Fontan procedure. Circulation. 2006;113(8):1123–9.Google Scholar
  56. 56.
    Gurvitz M, Valente A, Broberg C, Cook S, Stout K, Kay J, et al. Prevalence and predictors of gaps in care among adult congenital heart disease patients HEART-ACHD (The Health, Education, and Access Research Trial). J Am Coll Cardiol. 2013;61(21):2180–4.Google Scholar
  57. 57.
    Yeung E, Kay J, Roosevelt GE, Brandon M, Yetman AT. Lapse of care as a predictor for morbidity in adults with congenital heart disease. Int J Cardiol. 2008;125(1):62–5.Google Scholar
  58. 58.
    Sable C, Foster E, Uzark K, Bjornsen K, Canobbio MM, Connolly HM, et al. Best practices in managing transition to adulthood for adolescents with congenital heart disease: the transition process and medical and psychosocial issues. Circulation. 2011;123(13):1454–85.Google Scholar

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© Springer Science+Business Media, LLC, part of Springer Nature 2019

Authors and Affiliations

  1. 1.Section of Pediatric Cardiology, Department of Pediatrics and Internal MedicineYale University School of MedicineNew HavenUSA

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