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http://dx.doi.org/10.3345/cep.2019.01417

Pediatric heart transplantation: how to manage problems affecting long-term outcomes?  

Kim, Young Hwue (Department of Pediatric Cardiology, Asan Medical Center Children's Hospital, University of Ulsan College of Medicine)
Publication Information
Clinical and Experimental Pediatrics / v.64, no.2, 2021 , pp. 49-59 More about this Journal
Abstract
Since the initial International Society of Heart Lung Transplantation registry was published in 1982, the number of pediatric heart transplantations has increased markedly, reaching a steady state of 500-550 transplantation annually and occupying up to 10% of total heart transplantations. Heart transplantation is considered an established therapeutic option for patients with end-stage heart disease. The long-term outcomes of pediatric heart transplantations were comparable to those of adults. Issues affecting long-term outcomes include acute cellular rejection, antibody-mediated rejection, cardiac allograft vasculopathy, infection, prolonged renal dysfunction, and malignancies such as posttransplant lymphoproliferative disorder. This article focuses on medical issues before pediatric heart transplantation, according to the Korean Network of Organ Sharing registry and as well as major problems such as graft rejection and cardiac allograft vasculopathy. To reduce graft failure rate and improve long-term outcomes, meticulous monitoring for rejection and medication compliance are also important, especially in adolescents.
Keywords
Pediatric heart transplantation; Graft failure; Long-term issue; Rejection; Cardiac allograft vasculopathy;
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1 Agbor-Enoh S, Tunc I, Vlaminck ID, Fideli U, Davis A, Cuttin K, et al. Applying rigor and reproducibility standards to assay donor-drived cell-free DNA as a non-invasive method for detection of acute rejection and graft injury after heart transplantation. J Heart Lung Transplant 2017;36:1004-12.   DOI
2 Pahl E, Naftel DC, Canter CE, Fraiser EA, Kirklin JK, Morrow WR, et al. Death after rejection with severe hemodynamic compromise in pediatric heart transplant recipients: a multi-institutional study. J Heart Lung Transplant 2001;20:279-87.   DOI
3 Stoica S, MMath FC, Pauriah M, Taylor CJ, Sharples LD, Wallwork J, et al. The cumulative effect of acute rejection on development of cardiac allograft vasculopathy. J Heart Lung Transplant 2006;25:420-5.   DOI
4 From AM, Maleszewski JJ, Rihal CS. Current status of endomyocardial biopsy. Mayo Clin Proc 2011;86:1095-102.   DOI
5 Aggarwal S, Blake J, Sehgal S. Right ventricular dysfunction as an echocardiographic measure of acute rejection following heart transplantation in children. Pediatr Cardiol 2017;38:442-7.   DOI
6 Bhat G, Burwig S, Walsh R. Morbidity of endomayocardial biopsy in cardiac transplant recipients. Am Heart J 1993;125:1180-1.   DOI
7 Phelps CM, Tissort C, Buckvold S, Gralla J, Ivy DD, Pietra BA, et al. Outcome of acute graft rejection associated with hemodynamic compromise in pediatric heart transplant recipients. Pediatr Cardiol 2011;32:1-7.   DOI
8 Rossano JW, Dipchand AI, Edward LB, Goldfarb S, Kucheryavaya AY, Levvey BJ, et al. The registry of the international society for heart and lung transplantation: Nineteenth pediatric heart transplantation report-2016: Focus theme: Primary diagnostic indications for transplantation. J Heart Lung Transplant 2016;35;1185-95.   DOI
9 Herskowitz A, Soule LM, Ueda K, Tamura F, Baumgartner WA, Borkon AM, et al. Arteriolar vasculitis on endomyocardial biopsy: a histologic predictor of poor outcome in cyclosporine treated heart transplant recipients. J Heart Transplant 1987;6:127-36.
10 VanBuskirk AM, Pidwell DJ, Adams PW, Orosz CG. Transplantation immunology. JAMA 1997;278:1993-9.   DOI
11 Kindel SJ, Law YM, Chin C, Burch M, Kirklin JK, Naftel DC, et al. Improved detection of cardiac allograft vasculopathy. A multi-institutional anaylsis of functional parmeters in pediatric heart transplant recipients. J Am Coll Cardiol 2015;66:547-57.   DOI
12 Mahle WT, Vincent RN, Berg AM, Kanter KR. Pravastatin therapy is associated with reduction in coronary allograft vasculopathy in pediatric heart transplantation. J Heart Lung Transplant 2005;24:63-6.   DOI
13 Chin C. Cardiac antibody-mediated rejection. Pediatr Transplant 2012;16:404-12.   DOI
14 Zakliczynski M, Nozynski J, Konecka-Mrowka D, Babinska A, Flak B, Hrakowitcz T, et al. Coincidence of cellular and antibody mediated rejection in heart transplant recipients-preliminary report. Kardiochir Torakochirurgia Pol 2014;11:52-5.
15 Thrush PT, Pahl E, Naftel DC, Rruitt E, Everitt MD, Missler H, et al. A multi-institutional evaluation of antibody-mediated rejection utilizing the Pediatric Heart Transplant Study database: incidence, therapies and outcomes. J Heart Lung Transplant 2016;35:1497-504.   DOI
16 Kfoury AG, Snow GL, Budge D, Alharethi RA, Stehlik J, Everitt MD, et al. A longitudinal study of the course of asymptomatic antibody-mediated rejection in heart transplantation. J Heart Lung Transplant 2012;31:46-51.   DOI
17 Roman-Oritz E, Oteiza SM, Pinto S, Lopez-Trascasa M, Sanchez-Corral P, Rodriguez de Cordoba S. Eculizumab long-term therapy for pediatric renal transplant in aHUS with CFH/CFHR1 hybrid gene. Pediatr Nephrol 2014;29:149-53.   DOI
18 Kittleson MM. Changing role of heart transplantation. Heart Failure Clin 2016;12:411-21.   DOI
19 Dyer AK, Barnes AP, Fixler DE, Shah TK, Sutcliffe DL, Hashim I, et al. Use of a highly sensitive assay for cardiac troponin T and N-terminal pro-brain natriuretic peptide to diagnose acute rejection in pediatric cardiac transplant recipients. Am Heart J 2012;163:595-600.   DOI
20 Pham MX, Deng MC, Kfoury AG, Teuteberg JJ, Starling RC, Valentine H. Molecular testing for long-term rejection surveillance in heart transplant recipients: design of the invasive monitoring attenuation through gene expression (IMAGE) trial. J Heart Lung Transplant 2007;26:808-14.   DOI
21 Daly KP, Seifert ME, Chandraker A, Zurakowski D, Nohria A, Givertz MM, et al. VEGF-C, VEGF-A and related angiogenesis factors as biomarkers of allograft vasculopathy in cardiac transplant recipients. J Heart Lung Transplant 2013;32:120-8.   DOI
22 Martinez-Dolz L, Almenar L, Reganon E, Vila V, Sanchez-Soriano R, Martinez-Sales V, et al. What is the best biomarker for diagnosis of rejection in the heart transplantation? Clin Tranplant 2009;23:672-80.   DOI
23 Mathews LR, Lott JM, Isse K, Lesniak A, Landsittel D, Demetris AJ, et al. Elevated ST2 distinguishes incidences of pediatric heart and small bowel transplant rejection. Am J Transplant 2016;16:938-50.   DOI
24 Kobayashi D, Du W, L'Ecuyer TJ. Predictors of cardiac allograft vasculopathy in pediatric heart transplant recipients. Pediatr Transplant 2013;17:436-440.   DOI
25 Kantrowitz A, Haller JD, Joos H, Cerruti MM, Carstensen HE. Transplantation of the heart an infant and an adult. Am J Cardiol 1968;22:782-90.   DOI
26 Jeewa A, Dreyer WJ, Kearney DL, Denfield SW. The presentation and diagnosis of coronary allograft vasculopathy in pediatric heart transplant recipients. Congenit Heart Dis 2012;7:302-11.   DOI
27 Pahl E, Naftel DC, Kuhn MA, Shaddy RE, Morrow WR, Canter CE, et al. The impact and outcome of transplant coronary artery disease in a pediatric population: 9-year multi-institutional study. J Heart Lung Transplant 2005;24:645-51.   DOI
28 Schumacher KR, Gajarski R, Urschel S. Pediatric coronary allograft vasculopathy - a review of pathogenesis and risk factors. Congenit Heart Dis 2012;7:312-23.   DOI
29 Mehra MR, Crespo-Leiro MG, Dipchand A, Ensminger SM, Hiemanm NE, Kobashigawa JA, et al. International Society for Heart and Lung Transplantation working formulation of a standardized nomencleature for cardiac allograft vasculopathy-2010. J Heart Lung Transplant 2010;29:717-27.   DOI
30 Kowashigawa JA, Patel JK, Kittleson MM, Kawano MA, Kiyosaki KK, Davis SN, et al. The long-term outcome of treated sensitized patients who undergo heart transplantation. Clin Transplant 2011;25:E61-67.   DOI
31 Daly KP. Emerging science in paediatric heart transplantation: donor allocation, biomarkers, and the quest for evidence-based medicine. Cardiol Young 2015;25 Suppl 2(Suppl 2):117-23.   DOI
32 Deng MC, Eisen HJ, Mehra MR, Billingham M, Marboe CC, Berry G, et al. Noninvasive discrimination of rejection in cardiac allograft recipients using gene expression profiling. Am J Transplant 2006;6:150-60.   DOI
33 Bae JH. Rihal CS, Edwards BS, Kuchwaha SS, Mathew V, Prasad A, et al. Association of angiotensin-converting enzyme inhibitors and serum lipids with plague regression in cardiac allograft vasculopathy. Transplantation 2006;82:1108-11.   DOI
34 Khush KK, Patel J, Pinney S, Kao A, Alharethi R, DePasquale E, et al. Noninvasive detection of graft injury after heart transplant using donor-drived cell-free DNA: a prospective multicenter study. Am J Transplant 2019;19:2889-99.   DOI
35 Reed EF, Demetris AJ, Hammond E, Itescu S, Kobashigawa JA, Rainsmoen NL, et al. Acute antibody mediated rejection of cardiac transplants. J Heart Lung Transplant 2006;25:153-9.   DOI
36 Kobashigawa J, Crespo-Leiro MG, Ensminger SM, Reichenspurner H, Angelini A, Berry G, et al. Report from a concensus conference on antibody-mediated rejection in heart transplantation. J Heart Lung Transplant 2011;30:252-69.   DOI
37 Kirk R, Edward LB, Kucheryavaya AY, Aurora P, Christie JD, Dobbels F, et al. The registry of the International Society for Heart and Lung Transplantation: Thirteenth official pediatric heart transplantation report-2010. J Heart Lung Transplant 2010;29:1119-28.   DOI
38 Wu GW, Kowashigawa JA, Fishbein MC, Patel JK, Kittleson MM, Reed EF, et al. Asymptomatic antibody-mediated rejection after heart transplantation predict poor outcomes. J Heart Lung Transplant 2009;28:417-22.   DOI
39 Castleberry C, Ryan TD, Chin C. Transplantation in the highly sensitized pediatric patient. Circulation 2014;129:2313-9.   DOI
40 Price JF, Towbin JA, Dreyer WJ, Radovancevic B, Rosenblatt HM, Clunie SK, et al. Symptom complex is associated with transplant coronary artery disease and sudden death/resuscitated sudden death in pediatric heart transplant recipients. J Heart Lung Transplant 2005;24:1798-803.   DOI
41 Baraldo M, Gregoraci G, Livi U. Steroid-free and steroid withdrawal protocols in heart transplantation: the review of literature. Transpl Int 2014;27:515-29.   DOI
42 Asante-Korang A, Amankwah EK. Lopez-Cepero M, Ringewald J, Carapellucci J, Krasnopero D, et al. Outcomes in highly sensitized pediatric heart transplant patients using current management strategies. J Heart Lung Transplant 2015;34:175-81.   DOI
43 Kirk R, Edward LB, Aurora P, Taylor DO, Christie JD, Dobbels F, et al. Registry of the international society heart and lung transplantation: Twelfth official pediatric heart transplantation report-2009. J Heart Lung Transplant 2009;28:993-1006.   DOI
44 Gazit AZ, Fehr J. Perioperative management of the pediatric cardiac transplantation patient. Curr Treat Option in Cardiovasc Med 2011;13:425-43.   DOI
45 Mills RM, Naftel DC. Heart transplant rejection with hemodynamic compromise: a multiintstitutional study of the role of endomyocardial cellular infiltrate. Cardiac Transplant Research Database. J Heart Lung Transplant 1997;16:813-21.
46 Everitt MD, Hammon MEH, Snow GL, Stehlik J, Revelo MP, Miller DV, et al. Biopsy-diagnosed antibody-mediated rejection based on the proposed International Society for Heart and Lung Transplantation working formulation is associated with adverse cardiovascular outcomes after pediatric heart transplant. J Heart Lung Transplant 2012;31:686-93.   DOI
47 Kanani M, Hoskote A, Carter C, Burch M, Tsang V, Kostolny M. Increasing donor-recipient weight mismatch in pediatric orthotopic heart transplantation does not adversely affect outcome. Eur J Cardiothorac Surg 2012;41:427-34.   DOI
48 Hayes D Jr, Cherikh WS, Chambers DC, Harhay MO, Khush KK, Lehman RR, et al. The International Thoracic Organ Transplant Registry of the International Society for Heart and Lung Transplantation: twenty-second pediatric lung and heart-lung transplantation report-2019; Focus theme: Donor and recipient size match. J Heart Lung Transplant 2019;38:1015-27.   DOI
49 Boyle GJ, Michaels MG. Evaluation of the candidate for heart transplantation. In: Tejani AH, Harmon WE, Fine RN, editors. Pediatric solid organ transplantation. Copenhagen (Denmark): Munksgaard, 2000:328-33.
50 Webber SA. Evaluaton and management of the cardiac donor. In: Tejani AH, Harmon WE, Fine RN, editors. Pediatric solid organ transplantation. Copenhagen (Denmark): Munksgaard, 2000:342-7.
51 Mahle WT, Tresler MA, Edens RE, Rusconi P, George JF, Naftel DC, et al. Allosensitization and outcomes in pediatric heart transplantation. J Heart Lung Transplant 2011;30:1221-7.   DOI
52 Zuppan CW, Wells LM, Kerstetter JC, Johnston JK, Baily LL, Chinnock RE. Cause of death in pediatric and infant heart transplant recipients: review of a 20-year, single institution cohort. J Heart Lung Transplant 2009;28:579-84.   DOI
53 Jeewa A, Chin C, Pahl E, Atz AM, Carboni MP, Pruitt E, et al. Outcome after percutaneous coronary artery revascularization procedures for cardiac allograft vasculoplathy in pediatric heart transplant recipients: a multi-institutional study. J Heart Lung Transplant 2015;34:1163-8.   DOI
54 Patel JK, Kobashigawa JA. Should we be doing routine biopsy after heart transplantation in a new era of anti-rejection? Curr Opin Cardiol 2006;21:127-31.   DOI
55 Pascual-Figal DA, Garrido IP, Blanco R, Minguela A, Lax A, Ordonez-Llanos J, et al. Soluble ST2 is a marker for acute cardiac allograft rejection. Ann Thorac Surg 2011;92:2118-24.   DOI
56 Eisen HJ, Tuzcu EM, Dorent R, Kobashigawa J, Mancini D, Valantinevon Kaeppler HA, et al. Everolimus for the prevention of allograft rejection and vasculopathy in cardiac transplant recipients. N Engl J Med 2003;349:847-58.   DOI
57 Holt DB, Lublin DM, Phelan DL, Boslaugh SE, Gandhi SK, Huddleston CB, et al. Mortality and morbidity in pre-sensitized pediatric heart transplant recipients with a positive donor crossmatch utilizing perioperative plasmapheresis and cytolytic therapy. J Heart Lung Transplant 2007;26:876-82.   DOI
58 Profita EL, Gauvreau K, Rycus P, Thiagarajan R, Singh TP. Incidence, predictors, and outcomes after severe primary graft dysfunction in pediatric heart transplant recipients. J Heart Lung Transplant 2019;38:601-8.   DOI
59 Hertz MI. The registry of the international society for heart and lung transplantation- Introduction to the 2012 annual reports; New leadership, same version. J Heart and lung Transplant 2012;31;1045-95.   DOI
60 Mehra MR, Uber PA, Potluri S, Ventura HO, Scott RL, Park MH. Usefulness of an elevated B-type natriuretic peptide to predict allograft failure, cardiac allograft vasculopathy, and survival after heart transplantation. Am J cardiol 2004;94:454-8.   DOI
61 Asante-Korang A, Fickey M, Boucek MM, Boucek RJ Jr. Diastolic performance assessed by tissue doppler after pediatric heart transplantation. J Heart Lung Transplant 2004;23:865-72.   DOI
62 Buddhe S, Richimond ME, Gilbreath J, Lai WW. Longitudianl strain by speckle tracking echocardiography in pediatric heart transplant recipients. Congenit Heart Dis 2015;10:362-70.   DOI
63 Claudius I, Lan YT, Chang RK, Wetzel GT, Alejos J. Usefulness of B-type natriuretic peptide as a non-invasive screening tools for cardiac allograft pathology in pediatric heart transplant recipeints. Am J Cardiol 2003;92:1368-70.   DOI
64 Flanagan R, Cain N, Tatum GH, DeBrunner MG, Drant S, Feingold B. Left ventricular myocardial performance index change for the detection of acute cellular rejection in pediatric heart transplantation. Pediatr Transplant 2013;17:782-6.   DOI
65 Rossano JW, Denfield SW, Kim JJ, Price JF, Jefferies JL, Decker JA, et al. B-type natriuretic peptide level late after transplant predict graft survival in pediatric heart transplant patients. J Heart Lung Transplant 2010;29:385-6.   DOI
66 Sarvari SI, Gjesdal O, Gude E, Arora S, Andereassen AK, Gullestad L, et al. Early postoperative left ventricular function by echocardiographic strain is a predict of 1 year mortality in heart transplant reipients. J Am Soc Echocardiogr 2012;25:1007-14.   DOI
67 Clemmensen TS, Logstrup BB, Eiskjaer H, Poulsen SH. Evaluation of longitudinal myocardial deformation by 2-dimensional speckle-tracking echocardiography in heart transplant recipients: relation to cardiac allograft vasculopathy. J Heart Lung Transplant 2015;34:195-203.   DOI
68 Ware AL, Malmberg E, Delgado JC, Hammond ME, Miller DV, Stehlik J, et al. The use of circulating donor specific antibody to predict biopsy diagnosis of antibody-mediated rejection and to provide prognostic value after heart transplantation in children. J Heart Lung Transplant 2016;35:179-85.   DOI
69 Costanza MR. Special feature: The international society of heart and lung transplantation: guidelines for the care of heart transplant recipients. J Heart Lung Transplant 2010;29:914-56.   DOI