Hostname: page-component-8448b6f56d-t5pn6 Total loading time: 0 Render date: 2024-04-24T05:54:34.245Z Has data issue: false hasContentIssue false

Emerging science in paediatric heart transplantation: donor allocation, biomarkers, and the quest for evidence-based medicine

Published online by Cambridge University Press:  17 September 2015

Kevin P. Daly*
Affiliation:
Department of Cardiology, Transplant Research Program, Boston Children’s Hospital, Boston, Massachusetts, United States of America Department of Pediatrics, Harvard Medical School, Boston, Massachusetts, United States of America
*
Correspondence to: Dr K. P. Daly, MD, Department of Cardiology, Boston Children’s Hospital, 300 Longwood Avenue, Boston, MA 02115, United States of America. Tel: +617 355 6329; Fax: +617 734 9930; E-mail: kevin.daly@cardio.chboston.org

Abstract

Heart transplantation offers excellent survival benefit to children with end-stage heart failure. With its success, the number of potential recipients continues to exceed the number of available donors. Developing strategies to safely increase donor utilisation is crucial to decreasing wait-list mortality. A new paediatric heart allocation policy is set to be implemented with the goal of prioritising the most urgent listed candidates. Owing to excellent outcomes of ABO-incompatible heart transplantation, the sickest infants will soon receive priority for heart offers irrespective of blood group. Allosensitisation poses unique challenges within the paediatric population; ongoing multi-centre studies are poised to refine our understanding of key risk factors and optimal treatment strategies. Biomarkers for acute cellular rejection, such as donor-specific cell-free DNA, and cardiac allograft vasculopathy, such as VEGF-A, may lead to a decreased need for invasive screening. Ultimately, well-designed and executed randomised control trials of post-transplant immunosuppression are required to improve long-term outcomes after paediatric heart transplantation.

Type
Original Articles
Copyright
© Cambridge University Press 2015 

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. Dipchand, AI, Edwards, LB, Kucheryavaya, AY, et al. 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 2014; 33: 985995.Google Scholar
2. Easterwood, R, Singh, RK, McFeely, ED, et al. Pediatric cardiac transplantation using hearts previously refused for quality: a single center experience. Am J Transplant 2013; 13: 14841490.Google Scholar
3. MacKenzie, EJ. Epidemiology of injuries: current trends and future challenges. Epidemiol Rev 2000; 22: 112119.Google Scholar
4. Khush, KK, Menza, R, Nguyen, J, Zaroff, JG, Goldstein, BA. Donor predictors of allograft use and recipient outcomes after heart transplantation. Circ Heart Fail 2013; 6: 300309.Google Scholar
5. Rossano, JW, Lin, KY, Paridon, SM, et al. Pediatric heart transplantation from donors with depressed ventricular function: an analysis of the United Network of Organ Sharing Database. Circ Heart Fail 2013; 6: 12231229.CrossRefGoogle ScholarPubMed
6. McCurry, K, Jeevanandam, V, Mihaljevic, T, et al. Prospective Multi-Center Safety and Effectiveness Evaluation of the Organ Care System Device for Cardiac Use (PROCEED). J Heart Lung Transplant 2008; 27: S166.Google Scholar
7. Esmailian, F, Kobashigawa, JA, Naka, Y, et al. The PROCEED II International Heart Transplant Trial with the Organ Care System Technology (OCS). J Heart Lung Transplant 2013; 32: S95S96.Google Scholar
8. Iyer, A, Gao, L, Doyle, A, et al. Normothermic ex vivo perfusion provides superior organ preservation and enables viability assessment of hearts from DCD donors. Am J Transplant 2015; 15: 371380.CrossRefGoogle ScholarPubMed
9. Webber, S, Rogers, J. OPTN/UNOS Thoracic Organ Transplantation Committee Report to the Board of Directors. 2014, June 23–24. Retrieved 26 January 2015 from http://optn.transplant.hrsa.gov/converge/CommitteeReports/board_main_ThoracicOrganTransplantationCommittee_7_3_2014_10_58.pdf Google Scholar
10. Almond, CS, Smoot, LB, VanderPluym, C, et al. Are smaller children waiting longer? Trends in median waiting time for smaller children listed for heart transplant in the US. J Heart Lung Transplant 2013; 32: S35.Google Scholar
11. West, LJ, Pollock-Barziv, SM, Dipchand, AI, et al. ABO-incompatible heart transplantation in infants. N Engl J Med 2001; 344: 793800.CrossRefGoogle ScholarPubMed
12. Henderson, HT, Canter, CE, Mahle, WT, et al. ABO-incompatible heart transplantation: analysis of the Pediatric Heart Transplant Study (PHTS) database. J Heart Lung Transplant 2012; 31: 173179.CrossRefGoogle ScholarPubMed
13. Almond, CS, Gauvreau, K, Thiagarajan, RR, et al. Impact of ABO-incompatible listing on wait-list outcomes among infants listed for heart transplantation in the United States: a propensity analysis. Circulation 2010; 121: 19261933.Google Scholar
14. Meyer, DM, Rogers, JG, Edwards, LB, et al. The future direction of the adult heart allocation system in the United States. Am J Transplant 2015; 15: 4454.CrossRefGoogle ScholarPubMed
15. Kobashigawa, JA, Johnson, M, Rogers, J, et al. Report from a forum on US heart allocation policy. Am J Transplant 2015; 15: 5563.Google Scholar
16. Shaddy, RE, Hunter, DD, Osborn, KA, et al. Prospective analysis of HLA immunogenicity of cryopreserved valved allografts used in pediatric heart surgery. Circulation 1996; 94: 10631067.Google Scholar
17. Lavee, J, Kormos, RL, Duquesnoy, RJ, et al. Influence of panel-reactive antibody and lymphocytotoxic crossmatch on survival after heart transplantation. J Heart Lung Transplant 1991; 10: 921929; discussion 929–930.Google ScholarPubMed
18. Smith, JD, Danskine, AJ, Laylor, RM, Rose, ML, Yacoub, MH. The effect of panel reactive antibodies and the donor specific crossmatch on graft survival after heart and heart-lung transplantation. Transpl Immunol 1993; 1: 6065.CrossRefGoogle ScholarPubMed
19. Daly, KP, Singh, TP, Piercey, G, Gauvreau, K, Almond, CS. Which T-cell crossmatch method best predicts allograft loss in pediatric heart transplant recipients? J Heart Lung Transplant 2012; 31: S210.Google Scholar
20. Daly, KP, Chandler, SF, Almond, CS, et al. Antibody depletion for the treatment of crossmatch-positive pediatric heart transplant recipients. Pediatr Transplant 2013; 17: 661669.Google Scholar
21. Holt, DB, Lublin, DM, Phelan, DL, et al. Mortality and morbidity in pre-sensitized pediatric heart transplant recipients with a positive donor crossmatch utilizing peri-operative plasmapheresis and cytolytic therapy. J Heart Lung Transplant 2007; 26: 876882.Google Scholar
22. Berry, GJ, Burke, MM, Andersen, C, et al. The 2013 International Society for Heart and Lung Transplantation Working Formulation for the standardization of nomenclature in the pathologic diagnosis of antibody-mediated rejection in heart transplantation. J Heart Lung Transplant 2013; 32: 11471162.CrossRefGoogle ScholarPubMed
23. Morrow, WR, Frazier, EA, Mahle, WT, et al. Rapid reduction in donor-specific anti-human leukocyte antigen antibodies and reversal of antibody-mediated rejection with bortezomib in pediatric heart transplant patients. Transplantation 2012; 93: 319324.Google Scholar
24. Deng, MC, Eisen, HJ, Mehra, MR, et al. Noninvasive discrimination of rejection in cardiac allograft recipients using gene expression profiling. Am J Transplant 2006; 6: 150160.Google Scholar
25. Sparks, JD, Boston, U, Eghtesady, P, Canter, CE. B-type natriuretic peptide trends after pediatric heart transplantation. Pediatr Transplant 2014; 18: 477484.CrossRefGoogle ScholarPubMed
26. Patel, PC, Hill, DA, Ayers, CR, et al. High-sensitivity cardiac troponin I assay to screen for acute rejection in patients with heart transplant. Circ Heart Fail 2014; 7: 463469.Google Scholar
27. Knecht, KR, Alexander, ML, Swearingen, CJ, Frazier, EA. NTproBNP as a marker of rejection in pediatric heart transplant recipients. Pediatr Transplant 2012; 16: 335339.Google Scholar
28. Dyer, AK, Barnes, AP, Fixler, DE, 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: 595600.Google Scholar
29. Lunze, FI, Colan, SD, Gauvreau, K, et al. Tissue Doppler imaging for rejection surveillance in pediatric heart transplant recipients. J Heart Lung Transplant 2013; 32: 10271033.CrossRefGoogle ScholarPubMed
30. De Vlaminck, I, Valantine, HA, Snyder, TM, et al. Circulating cell-free DNA enables noninvasive diagnosis of heart transplant rejection. Sci Transl Med 2014; 6: 241277.Google Scholar
31. Hidestrand, M, Tomita-Mitchell, A, Hidestrand, PM, et al. Highly sensitive noninvasive cardiac transplant rejection monitoring using targeted quantification of donor-specific cell-free deoxyribonucleic acid. J Am Coll Cardiol 2014; 63: 12241226.Google Scholar
32. Bruneau, S, Woda, CB, Daly, KP, et al. Key features of the intragraft microenvironment that determine long-term survival following transplantation. Front Immunol 2012; 3: 54.Google Scholar
33. Daly, KP, Seifert, ME, Chandraker, A, 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: 120128.CrossRefGoogle ScholarPubMed
34. Daly, K, Stack, M, Eisenga, M, et al. VEGF-A predicts the development of moderate or severe cardiac allograft vasculopathy in pediatric heart transplant recipients. Am J Transplant 2014; 14: 45.CrossRefGoogle Scholar
35. Costanzo, MR, Dipchand, A, Starling, R, et al. The International Society of Heart and Lung Transplantation Guidelines for the care of heart transplant recipients. J Heart Lung Transplant 2010; 29: 914956.CrossRefGoogle ScholarPubMed