Retransplantation of the Pediatric Heart Recipient

  • Richard Kirk
  • Ryan J. Butts
Reference work entry
Part of the Organ and Tissue Transplantation book series (OTT)


While graft survival has continued to improve after pediatric heart transplantation, graft failure still occurs at median of 15 years post-transplant. When graft failure occurs, retransplantation is an option to improve quality and length of life. It, however, has unique challenges compared to primary transplantation. Patients awaiting retransplantation have longer wait list times and double the wait list mortality. Operative mortality is higher, and immediate peritransplant morbidities (rejection, renal dysfunction, and infection) are more frequent compared to primary transplantation. Long-term outcomes are also worse, with median graft survival of 8.7 years versus 15 years, although survival after retransplantation is dependent to a large extent on the indication for retransplant and the inter-transplant interval. Patients undergoing retransplantation for coronary vasculopathy (CAV) with more than 5 years after primary transplant have good survival; however, patients undergoing retransplantation within the first year after primary transplantation have the worse outcomes. After retransplantation, the recipient is more likely to suffer from rejection, renal dysfunction, late-onset malignancy, and CAV. Despite these complexities, retransplantation remains a viable option in selected patients and can improve their length and quality of life.


Pediatric heart retransplantation Graft survival Immunosuppression Outcomes Graft failure 


  1. Ameduri RK, Zheng J, Schechtman KB, Hoffman TM, Gajarski RJ, Chinnock R, Naftel DC, Kirklin JK, Dipchand AI, Canter CE (2012) Has late rejection decreased in pediatric heart transplantation in the current era? A multi-institutional study. J Heart Lung Transplant 31:980–986CrossRefPubMedGoogle Scholar
  2. Andreassen AK, Andersson B, Gustafsson F, Eiskjaer H, Radegran G, Gude E, Jansson K, Solbu D, Karason K, Arora S, Dellgren G, Gullestad L, Schedule investigators (2016) Everolimus initiation with early Calcineurin inhibitor withdrawal in de novo heart transplant recipients: three-year results from the randomized SCHEDULE study. Am J Transplant 16:1238–1247CrossRefPubMedGoogle Scholar
  3. Asante-Korang A, Amankwah EK, Lopez-Cepero M, Ringewald J, Carapellucci J, Krasnopero D, Berg A, Quintessenza J, Jacobs JP (2015) Outcomes in highly sensitized pediatric heart transplant patients using current management strategies. J Heart Lung Transplant 34:175–181CrossRefPubMedGoogle Scholar
  4. Awad M, Czer LS, Esmailian F, Jordan S, De Robertis MA, Mirocha J, Patel J, Chang DH, Kittleson M, Ramzy D, Arabia F, Chung JS, Cohen JL, Trento A, Kobashigawa JA (2017) Combined heart and kidney transplantation: a 23-year experience. Transplant Proc 49:348–353CrossRefPubMedGoogle Scholar
  5. Azarbal B, Cheng R, Vanichsarn C, Patel JK, Czer LS, Chang DH, Kittleson MM, Kobashigawa JA (2016) Induction therapy with antithymocyte globulin in patients undergoing cardiac transplantation is associated with decreased coronary plaque progression as assessed by intravascular ultrasound. Circ Heart Fail 9:e002252PubMedGoogle Scholar
  6. Bock MJ, Nguyen K, Malerba S, Harrison K, Bagiella E, Gelb BD, Pinney SP, Lytrivi ID (2015) Pediatric cardiac retransplantation: waitlist mortality stratified by age and era. J Heart Lung Transplant 34:530–537CrossRefPubMedGoogle Scholar
  7. Boucek RJ Jr, Naftel D, Boucek MM, Chinnock R, Morrow RW, Pahl E, DiSano S (1999) Induction immunotherapy in pediatric heart transplant recipients: a multicenter study. J Heart Lung Transplant 18:460–469CrossRefPubMedGoogle Scholar
  8. Butts RJ, Savage AJ, Atz AM, Heal EM, Burnette AL, Kavarana MM, Bradley SM, Chowdhury SM (2015) Validation of a simple score to determine risk of early rejection after pediatric heart transplantation. JACC Heart Fail 3:670–676CrossRefPubMedPubMedCentralGoogle Scholar
  9. Butts R, Davis M, Savage A, Burnette A, Kavarana M, Bradley S, Atz A, Nietert PJ (2016) Effect of induction therapy on graft survival in primary pediatric heart transplantation: a propensity score analysis of the UNOS database. Transplantation 34:S325Google Scholar
  10. Chin C, Naftel D, Pahl E, Shankel T, Clark ML, Gamberg P, Kirklin J, Webber S, Study Pediatric Heart Transplant (2006) Cardiac re-transplantation in pediatrics: a multi-institutional study. J Heart Lung Transplant 25:1420–1424CrossRefPubMedGoogle Scholar
  11. Conway J, Manlhiot C, Kirk R, Edwards LB, McCrindle BW, Dipchand AI (2014) Mortality and morbidity after retransplantation after primary heart transplant in childhood: an analysis from the registry of the International Society for Heart and Lung Transplantation. J Heart Lung Transplant 33:241–251CrossRefPubMedGoogle Scholar
  12. Dearani JA, Razzouk AJ, Gundry SR, Chinnock RE, Larsen RL, del Rio MJ, Johnston JK, Bailey LL (2001) Pediatric cardiac retransplantation: intermediate-term results. Ann Thorac Surg 71:66–70CrossRefPubMedGoogle Scholar
  13. Dipchand AI, Naftel DC, Feingold B, Spicer R, Yung D, Kaufman B, Kirklin JK, Allain-Rooney T, Hsu D, Investigators Pediatric Heart Transplant Study (2009) Outcomes of children with cardiomyopathy listed for transplant: a multi-institutional study. J Heart Lung Transplant 28:1312–1321CrossRefPubMedGoogle Scholar
  14. Dipchand AI, Edwards LB, Kucheryavaya AY, Benden C, Dobbels F, Levvey BJ, Lund LH, Meiser B, Yusen RD, Stehlik J, Heart International Society of, and Transplantation Lung (2014) The registry of the International Society for Heart and Lung Transplantation: seventeenth official pediatric heart transplantation report – 2014; focus theme: retransplantation. J Heart Lung Transplant 33:985–995CrossRefPubMedGoogle Scholar
  15. Dipchand AI, Rossano JW, Edwards LB, Kucheryavaya AY, Benden C, Goldfarb S, Levvey BJ, Lund LH, Meiser B, Yusen RD, Stehlik J, Heart International Society for, and Transplantation Lung (2015) The registry of the International Society for Heart and Lung Transplantation: eighteenth official pediatric heart transplantation report – 2015; focus theme: early graft failure. J Heart Lung Transplant 34:1233–1243CrossRefPubMedGoogle Scholar
  16. Goldberg JF, Jeewa A, Dreyer WJ, Adams GJ, Cabrera AG, Price JF, Heinle JS, Denfield SW (2014) Postoperative complications associated with perioperative sirolimus prior to pediatric cardiac retransplantation. J Pediatr Pharmacol Ther 19:30–34PubMedPubMedCentralGoogle Scholar
  17. Hong KN, Merlo A, Chauhan D, Davies RR, Iribarne A, Johnson E, Jeevanandam V, Russo MJ (2016) Evidence supports severe renal insufficiency as a relative contraindication to heart transplantation. J Heart Lung Transplant 35:893–900CrossRefPubMedGoogle Scholar
  18. Huang J, Trinkaus K, Huddleston CB, Mendeloff EN, Spray TL, Canter CE (2004) Risk factors for primary graft failure after pediatric cardiac transplantation: importance of recipient and donor characteristics. J Heart Lung Transplant 23:716–722CrossRefPubMedGoogle Scholar
  19. Jeewa A, Chin C, Pahl E, Atz AM, Carboni MP, Pruitt E, Naftel DC, Rodriguez R, Dipchand AI, Investigators Pediatric Heart Transplant Study (2015) Outcomes after percutaneous coronary artery revascularization procedures for cardiac allograft vasculopathy in pediatric heart transplant recipients: a multi-institutional study. Lung Transplant 34:1163–1168CrossRefGoogle Scholar
  20. Kaczorowski DJ, Datta J, Kamoun M, Dries DL, Woo YJ (2013) Profound hyperacute cardiac allograft rejection rescue with biventricular mechanical circulatory support and plasmapheresis, intravenous immunoglobulin, and rituximab therapy. J Cardiothorac Surg 8:48CrossRefPubMedPubMedCentralGoogle Scholar
  21. Karamlou T, Welke KF, McMullan DM, Cohen GA, Gelow J, Tibayan FA, Mudd JM, Slater MS, Song HK (2014) Combined heart-kidney transplant improves post-transplant survival compared with isolated heart transplant in recipients with reduced glomerular filtration rate: analysis of 593 combined heart-kidney transplants from the united network organ sharing database. J Thorac Cardiovasc Surg 147(456–461):e1Google Scholar
  22. Kindel SJ, Law YM, Chin C, Burch M, Kirklin JK, Naftel DC, Pruitt E, Carboni MP, Arens A, Atz AM, Dreyer WJ, Mahle WT, Pahl E (2015) Improved detection of cardiac allograft vasculopathy: a multi-institutional analysis of functional parameters in pediatric heart transplant recipients. J Am Coll Cardiol 66:547–557CrossRefPubMedGoogle Scholar
  23. Kobashigawa J, Zuckermann A, Macdonald P, Leprince P, Esmailian F, Luu M, Mancini D, Patel J, Razi R, Reichenspurner H, Russell S, Segovia J, Smedira N, Stehlik J, Wagner F, Participants Consensus Conference (2014) Report from a consensus conference on primary graft dysfunction after cardiac transplantation. J Heart Lung Transplant 33:327–340CrossRefPubMedGoogle Scholar
  24. Mahle WT (2008) Cardiac retransplantation in children. Pediatr Transplant 12:274–280CrossRefPubMedGoogle Scholar
  25. Mahle WT, Vincent RN, Kanter KR (2005) Cardiac retransplantation in childhood: analysis of data from the united network for organ sharing. J Thorac Cardiovasc Surg 130:542–546CrossRefPubMedGoogle Scholar
  26. Mahle WT, Tresler MA, Edens RE, Rusconi P, George JF, Naftel DC, Shaddy RE, Group Pediatric Heart Transplant Study (2011) Allosensitization and outcomes in pediatric heart transplantation. J Heart Lung Transplant 30:1221–1227CrossRefPubMedGoogle Scholar
  27. Marasco SF, Esmore DS, Negri J, Rowland M, Newcomb A, Rosenfeldt FL, Bailey M, Richardson M (2005) Early institution of mechanical support improves outcomes in primary cardiac allograft failure. J Heart Lung Transplant 24:2037–2042CrossRefPubMedGoogle Scholar
  28. Marshall CD, Richmond ME, Singh RK, Gilmore L, Beddows K, Chen JM, Addonizio LJ (2013) A comparison of traditional versus contemporary immunosuppressive regimens in pediatric heart recipients. J Pediatr 163:132–136CrossRefPubMedGoogle Scholar
  29. May LJ, Yeh J, Maeda K, Tyan DB, Chen S, Kaufman BD, Bernstein D, Rosenthal DN, Hollander SA (2014) HLA desensitization with bortezomib in a highly sensitized pediatric patient. Pediatr Transplant 18:E280–E282CrossRefPubMedGoogle Scholar
  30. Mehra MR, Crespo-Leiro MG, Dipchand A, Ensminger SM, Hiemann NE, Kobashigawa JA, Madsen J, Parameshwar J, Starling RC, Uber PA (2010) International Society for Heart and Lung Transplantation working formulation of a standardized nomenclature for cardiac allograft vasculopathy-2010. J Heart Lung Transplant 29:717–727CrossRefPubMedGoogle Scholar
  31. Oliva M, Singh TP, Gauvreau K, Vanderpluym CJ, Bastardi HJ, Almond CS (2013) Impact of medication non-adherence on survival after pediatric heart transplantation in the USA. J Heart Lung Transplant 32:881–888CrossRefPubMedGoogle Scholar
  32. Raj S, Ruiz P, Rusconi P (2017) Early primary graft failure after a pediatric heart transplant and successful rescue with plasmapheresis, immunoglobulins, and alemtuzumab. Ann Pediatr Cardiol 10:69–71CrossRefPubMedPubMedCentralGoogle Scholar
  33. Rossano JW, Morales DL, Zafar F, Denfield SW, Kim JJ, Jefferies JL, Dreyer WJ (2010) Impact of antibodies against human leukocyte antigens on long-term outcome in pediatric heart transplant patients: an analysis of the united network for organ sharing database. J Thorac Cardiovasc Surg 140:694–699 e1–2CrossRefPubMedGoogle Scholar
  34. Rossano JW, Dipchand AI, Edwards LB, Goldfarb S, Kucheryavaya AY, Levvey Rn BJ, Lund LH, Meiser B, Yusen RD, Stehlik J, Heart International Society for, and Transplantation Lung (2016) The registry of the International Society for Heart and Lung Transplantation: nineteenth pediatric heart transplantation Report-2016; focus theme: primary diagnostic indications for transplant. J Heart Lung Transplant 35:1185–1195CrossRefPubMedGoogle Scholar
  35. Saito S, Matsumiya G, Fukushima N, Sakaguchi T, Fujita T, Ueno T, Miyagawa S, Yamauchi A, Sawa Y (2009) Successful treatment of cardiogenic shock caused by humoral cardiac allograft rejection. Circ J 73:970–973CrossRefPubMedGoogle Scholar
  36. Schumacher KR, Ramon DS, Kamoun M, Caruthers R, Gajarski RJ (2012) HLA desensitization in pediatric heart transplant candidates: efficacy of rituximab and IVIg. J Heart Lung Transplant 31:1041–1042CrossRefPubMedGoogle Scholar
  37. Segovia J, Cosio MD, Barcelo JM, Bueno MG, Pavia PG, Burgos R, Serrano-Fiz S, Garcia-Montero C, Castedo E, Ugarte J, Alonso-Pulpon L (2011) RADIAL: a novel primary graft failure risk score in heart transplantation. J Heart Lung Transplant 30:644–651CrossRefPubMedGoogle Scholar
  38. Singh TP, Faber C, Blume ED, Worley S, Almond CS, Smoot LB, Dillis S, Nasman C, Boyle GJ (2010) Safety and early outcomes using a corticosteroid-avoidance immunosuppression protocol in pediatric heart transplant recipients. J Heart Lung Transplant 29:517–522CrossRefPubMedPubMedCentralGoogle Scholar
  39. Thrush PT, Gossett JG, Costello JM, Matthews KL, Nubani R, Bhagat H, Backer CL, Pahl E (2014) Role for immune monitoring to tailor induction prophylaxis in pediatric heart recipients. Pediatr Transplant 18:79–86CrossRefPubMedGoogle Scholar
  40. Tissot C, Buckvold S, Phelps CM, Ivy DD, Campbell DN, Mitchell MB, da Cruz SO, Pietra BA, Miyamoto SD (2009) Outcome of extracorporeal membrane oxygenation for early primary graft failure after pediatric heart transplantation. J Am Coll Cardiol 54:730–737CrossRefPubMedPubMedCentralGoogle Scholar
  41. Uber WE, Uber LA, VanBakel AB, Crumbley AJ 3rd, Pereira NL, Ikonomidis JS, Feldman DS (2004) CD3 monitoring and thymoglobulin therapy in cardiac transplantation: clinical outcomes and pharmacoeconomic implications. Transplant Proc 36:3245–3249CrossRefPubMedGoogle Scholar
  42. Vincenti F, Monaco A, Grinyo J, Kinkhabwala M, Roza A (2003) Multicenter randomized prospective trial of steroid withdrawal in renal transplant recipients receiving basiliximab, cyclosporine microemulsion and mycophenolate mofetil. Am J Transplant 3:306–311CrossRefPubMedGoogle Scholar
  43. Weil R 3rd, Clarke DR, Iwaki Y, Porter KA, Koep LJ, Paton BC, Terasaki PI, Starzl TE (1981) Hyperacute rejection of a transplanted human heart. Transplantation 32:71–72PubMedPubMedCentralGoogle Scholar
  44. Zafar F, Castleberry C, Khan MS, Mehta V, Bryant R 3rd, Lorts A, Wilmot I, Jefferies JL, Chin C, Morales DL (2015) Pediatric heart transplant waiting list mortality in the era of ventricular assist devices. J Heart Lung Transplant 34:82–88CrossRefPubMedGoogle Scholar
  45. Zinn MD, Wallendorf MJ, Simpson KE, Osborne AD, Kirklin JK, Canter CE (2017) Impact of age on incidence and prevalence of moderate-to-severe cellular rejection detected by routine surveillance biopsy in pediatric heart transplantation. J Heart Lung Transplant 36:451–456CrossRefPubMedGoogle Scholar

Copyright information

© Springer International Publishing AG, part of Springer Nature 2018

Authors and Affiliations

  1. 1.University of Texas Southwestern Medical CenterDallasUSA

Section editors and affiliations

  • Ryan R. Davies
    • 1
  1. 1.University of Texas Southwestern Medical CenterDallasUSA

Personalised recommendations