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Cardiac Allograft Rejection, Surveillance and Treatment

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Clinical Guide to Heart Transplantation

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Abstract

Since the early days of cardiac transplantation, allograft rejection has remained the main barrier to favorable long term outcomes until the introduction of effective immunosuppression, as detailed in. With the introduction of calcineurin inhibitors rejection rates have sharply declined and improvement in survival rates has permitted cardiac transplantation to become an increasingly practical therapeutic option for end-stage heart disease. While rejection rates continue to decline, the risk of rejection remains significant particularly in the early period following transplantation, necessitating routine surveillance for both acute cellular and antibody-mediated rejection. Left unchecked, acute rejection is known to lead to cardiac allograft vasculopathy (CAV), one of largest barriers to long-term survival, making surveillance and prompt treatment of acute rejection episodes even more crucial. This chapter intends to discuss the major forms of cardiac allograft rejection, methods of diagnosis, surveillance and its treatment.

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References

  1. 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(8):914–56.

    Article  PubMed  Google Scholar 

  2. Caves PK, Stinson EB, Billingham M, Shumway NE. Percutaneous transvenous endomyocardial biopsy in human heart recipients. Experience with a new technique. Ann Thorac Surg. 1973;16(4):325–36.

    Article  CAS  PubMed  Google Scholar 

  3. Kirklin JK, Naftel DC, Bourge RC, et al. Rejection after cardiac transplantation. A time-related risk factor analysis. Circulation. 1992;86(II):236e41.

    Google Scholar 

  4. Kobashigawa JA, Kirklin JK, Naftel DC, et al. Pretransplantation risk factors for acute rejection after heart transplantation: a multiinstitutional study. The transplant cardiologists research database group. J Heart Lung Transplant. 1993;12:355e66.

    Google Scholar 

  5. From AM, Maleszewski JJ, Rihal CS. Current Status of Endomyocardial Biopsy. Mayo Clin Proc. 2011;86(11):1095–102.

    Article  PubMed  PubMed Central  Google Scholar 

  6. Mehra MR, Parameshwar J. Gene expression profiling and cardiac allograft rejection monitoring: is IMAGE just a mirage? J Heart Lung Transplant. 2010;29:599e602.

    Google Scholar 

  7. Berry GJ, Burke MM, Andersen C, et al. The 2013 international sciety 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(12):1147–62.

    Article  PubMed  Google Scholar 

  8. Pikul FJ, Bolman RM, Saffitz JE, Chaplin H. Anti-B-mediated rejection of an ABO-incompatible cardiac allograft despite aggressive plasma exchange transfusion. Transplant Proc. 1987;19:4601e4.

    Google Scholar 

  9. Ratkovec RM, Hammond EH, O’Connell JB, et al. Outcome of cardiac transplant recipients with a positive donor-specific crossmatch: preliminary results with plasmapheresis. Transplantation. 1992;54:651e5.

    Article  Google Scholar 

  10. Patel R, Terasaki PI. Significance of the positive crossmatch test in kidney transplantation. N Engl J Med. 1969;280:735e9.

    Article  Google Scholar 

  11. Winters GL, Marboe CC, Billingham ME. The international society for heart and lung transplantation grading system for heart transplant biopsy specimens: clarification and commentary. J Heart Lung Transplant. 1998;17:754e60.

    Google Scholar 

  12. Stewart S, Winters GL, Fishbein MC, et al. Revision of the 1990 working formulation for the standardization of nomenclature in the diagnosis of heart rejection. J Heart Lung Transplant. 2005;24:1710–20.

    Article  PubMed  Google Scholar 

  13. Deng MC, Eisen HJ, Mehra MR, et al. Noninvasive discrimination of rejection in cardiac allograft recipients using gene expression profiling. Am J Transplant. 2006;6:150e60.

    Google Scholar 

  14. Jarcho J, Naftel DC, Shroyer TW, et al. Influence of HLA mismatch on rejection after heart transplantation: a multiinstitutional study. The cardiac transplant research database group. J Heart Lung Transplant. 1994;13:583e95. discussion 95e6.

    Google Scholar 

  15. Lund LH, Edwards LB, Kucheryavaya AY, et al. The registry of the international society for heart and lung transplantation: thirty-second official adult heart transplantation report--2015; focus theme: early graft failure. J Heart Lung Transplant. 2015;34(10):1244–54.

    Article  PubMed  Google Scholar 

  16. Michaels PJ, Espejo ML, Kobashigawa J, et al. Humoral rejection in cardiac transplantation: risk factors, hemodynamic consequences and relationship to transplant coronary artery disease. J Heart Lung Transplant. 2003;22:58e69.

    Article  Google Scholar 

  17. Colvin MM, Cook JL, Chang P, et al. Antibody-mediated rejection in cardiac transplantation: emerging knowledge in diagnosis and management: a scientific statement from the American Heart Association. Circulation. 2015;131:1608–39.

    Article  PubMed  Google Scholar 

  18. Reed EF, Demetris AJ, Hammond E, et al. Acute antibody-mediated rejection of cardiac transplants. J Heart Lung Transplant. 2006;25:153e9.

    Article  Google Scholar 

  19. Kfoury AG, Hammond ME, Snow GL, et al. Cardiovascular mortality among heart transplant recipients with asymptomatic antibody-mediated or stable mixed cellular and antibody-mediated rejection. J Heart Lung Transplant. 2009;28:781–4.

    Article  PubMed  Google Scholar 

  20. Wu GW, Kobashigawa JA, Fishbein MC, et al. Asymptomatic antibody-mediated rejection after heart transplantation predicts poor outcomes. J Heart Lung Transplant. 2009;28:417–22.

    Article  PubMed  Google Scholar 

  21. Kfoury AG, Hammond ME, Snow GL, et al. Early screening for antibody-mediated rejection in heart transplant recipients. J Heart Lung Transplant. 2007;26:1264–9.

    Article  PubMed  Google Scholar 

  22. Hammond ME, Stehlik J, Snow G, et al. Utility of histologic parameters in screening for antibody-mediated rejection of the cardiac allograft: a study of 3,170 biopsies. J Heart Lung Transplant. 2005;24:2015–21.

    Article  PubMed  Google Scholar 

  23. Angelini A, Andersen CB, Bartoloni G, et al. A web-based pilot study of inter-pathologist reproducibility using the ISHLT 2004 classification system for biopsy diagnosis of acute cardiac allograft rejection: the European experience on behalf of the transplant Working Group of the Association for European Cardiovascular Pathology. J Heart Lung Transplant. 2010;29:S76.

    Article  Google Scholar 

  24. Gupta S, Mitchell JD, Lavingia B, et al. Utility of routine immunofluorescence staining for C4d in cardiac transplant recipients. J Heart Lung Transplant. 2009;28:776–80.

    Article  PubMed  Google Scholar 

  25. Smith RN, Brousaides N, Grazette L, et al. C4d deposition in cardiac allografts correlates with alloantibody. J Heart Lung Transplant. 2005;24:1202–10.

    Article  PubMed  Google Scholar 

  26. Rodriguez ER, Skojec DV, Tan CD, et al. Antibody-mediated rejection in human cardiac allografts: evaluation of immunoglobulins and complement activation products C4d and C3d as markers. Am J Transplant. 2005;5:2778–85.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  27. Tan CD, Sokos GG, Pidwell DJ, et al. Correlation of donor-specific antibodies, complement and its regulators with graft dysfunction in cardiac antibody-mediated rejection. Am J Transplant. 2009;9:2075–84.

    Article  CAS  PubMed  Google Scholar 

  28. Kfoury AG, Hammond ME. Controversies in defining cardiac antibody-mediated rejection: need for updated criteria. J Heart Lung Transplant. 2010;29:389–94.

    Article  PubMed  Google Scholar 

  29. Tan CD, Rodriguez ER. Diagnosis of antibody-mediated rejection in cardiac transplantation: a call for standardization. Curr Opin Organ Transplant. 2010;15:769–73.

    Article  PubMed  Google Scholar 

  30. Burke M, Andersen CB, Ashworth M, et al. C4d methodolody and interpretation in diagnosis of cardiac antibody-mediated rejection: a European survey from the Association for European Cardiovascular Pathology (AECVP). J Heart Lung Transplant. 2010;29:S37–8.

    Article  Google Scholar 

  31. Kobashigawa J, Crespo-Leiro MG, Ensminger SM, et al. Report from a consensus conference on antibody-mediated rejection in heart transplantation. J Heart Lung Transplant. 2011;30(3):252–69.

    Article  PubMed  Google Scholar 

  32. Tambur AR, Pamboukian SV, Costanzo MR, et al. The presence of HLA-directed antibodies after heart transplantation is associated with poor allograft outcome. Transplantation. 2005;80:1019e25.

    Article  Google Scholar 

  33. Kfoury AG, Stehlik J, Renlund DG, et al. Impact of repetitive episodes of antibody mediated or cellular rejection on cardiovascular mortality in cardiac transplant recipients: defining rejection patterns. J Heart Lung Transplant. 2006;25:1277e82.

    Article  Google Scholar 

  34. Taylor DO, Yowell RL, Kfoury AG, Hammond EH, Renlund DG. Allograft coronary artery disease: clinical correlations with circulating anti-HLA antibodies and the immunohistopathologic pattern of vascular rejection. J Heart Lung Transplant. 2000;19:518e21.

    Article  Google Scholar 

  35. Coutance G, Ouldamar S, Rouvier P, et al. Late antibody-mediated rejection after heart transplantation: mortality, graft function, and fulminant cardiac allograft vasculopathy. J Heart Lung Transplant. 2015;34(8):1050–7.

    Article  PubMed  Google Scholar 

  36. Hammond EH, Wittwer CT, Greenwood J, et al. Relationship of OKT3 sensitization and vascular rejection in cardiac transplant patients receiving OKT3 rejection prophylaxis. Transplantation. 1990;50:776e82.

    Article  Google Scholar 

  37. Leech SH, Rubin S, Eisen HJ, Mather PJ, Goldman BI, McClurken JB, et al. Cardiac transplantation across a positive prospective lymphocyte cross-match in sensitized recipients. Clin Transpl. 2003;17(Suppl. 9):17e26.

    Google Scholar 

  38. Toyoda M, Petrosian A, Jordan SC. Immunological characterization of anti-endothelial cell antibodies induced by cytomegalovirus infection. Transplantation. 1999;68:1311e8.

    Article  Google Scholar 

  39. Hodges AM, Lyster H, McDermott A. et al.Late antibody-mediated rejection after heart transplantation following the development of de novo donor-specific human leukocyte antigen antibody. Transplantation. 2012;93(6):650–6.

    CAS  PubMed  Google Scholar 

  40. Tang Z, Kobashigawa J, Rafiei M, Stern LK, Hamilton M. The natural history of biopsy-negative rejection after heart transplantation. J Transplant. 2013;2013:236720.

    PubMed  PubMed Central  Google Scholar 

  41. Pham MX, Teuteberg JJ, Kfoury AG, et al. Gene-expression profiling for rejection surveillance after cardiac transplantation. N Engl J Med. 2010;362(20):1890–900.

    Article  CAS  PubMed  Google Scholar 

  42. Kobashigawa J, Patel J, Azarbal B, et al. Randomized pilot trial of gene expression profiling versus heart biopsy in the first year after heart transplant: early invasive monitoring attenuation through gene expression trial. Circ Heart Fail. 2015;8(3):557–64.

    Article  PubMed  Google Scholar 

  43. Auer T, Schreier G, Hutten H, et al. Intramyocardialelectrograms for monitoring of allograft rejection after heart transplantation. Transplant Proc. 1995;27:1983e5.

    Google Scholar 

  44. Auer T, Schreier G, Hutten H, et al. Intramyocardialelectrograms for the monitoring of allograft rejection after heart transplantation using spontaneous and paced beats. Transplant Proc. 1995;27:2621e4.

    Google Scholar 

  45. Bourge R, Eisen H, Hershberger R, et al. Noninvasive rejection monitoring of cardiac transplants using high resolution intramyocardialelectrograms: initial US multicenter experience. Pacing Clin Electrophysiol. 1998;21:2338e44.

    Article  Google Scholar 

  46. Grasser B, Iberer F, Schaffellner S, et al. Non-invasive graft monitoring after heart transplantation: rationale to reduce the number of endomyocardial biopsies. TransplInt. 2000;13(Suppl. 1):S225e7.

    Google Scholar 

  47. Grasser B, Iberer F, Schreier G, et al. Computerized heart allograft-recipient monitoring: a multicenter study. TransplInt. 2003;16:225e30.

    Google Scholar 

  48. Behera SK, Trang J, Feeley BT, Levi DS, Alejos JC, Drant S. The use of Doppler tissue imaging to predict cellular and antibody-mediated rejection in pediatric heart transplant recipients. Pediatr Transplant. 2008;12:207e14.

    Article  Google Scholar 

  49. Dandel M, Hummel M, Muller J, et al. Reliability of tissue Doppler wall motion monitoring after heart transplantation for replacement of invasive routine screenings by optimally timed cardiac biopsies and catheterizations. Circulation. 2001;104:I184e91.

    Article  Google Scholar 

  50. Butler CR, Thompson R, Haykowsky M, Toma M, Paterson I. Cardiovascular magnetic resonance in the diagnosis of acute heart transplant rejection: a review. J Cardiovasc Magn Reson. 2009;11:7.

    Article  PubMed  PubMed Central  Google Scholar 

  51. Taylor AJ, Vaddadi G, Pfluger H, et al. Diagnostic performance of multisequential cardiac magnetic resonance imaging in acute cardiac allograft rejection. Eur J Heart Fail. 2010;12:45e51.

    Article  Google Scholar 

  52. Butler CR, Savu A, Bakal JA, et al. Correlation of cardiovascular magnetic resonance imaging findings and endomyocardial biopsy results in patients undergoing screening for heart transplant rejection. J Heart Lung Transplant. 2015;34(5):643–50.

    Article  PubMed  Google Scholar 

  53. Gleissner CA, Klingenberg R, Nottmeyer W, et al. Diagnostic efficiency of rejection monitoring after heart transplantation with cardiac troponin T is improved in specific patient subgroups. Clin Transpl. 2003;17:284e91.

    Article  Google Scholar 

  54. Avello N, Molina BD, Llorente E, Bernardo MJ, Prieto B, Alvarez FV. N-terminal pro-brain natriuretic peptide as a potential non-invasive marker of cardiac transplantation rejection. Ann Clin Biochem. 2007;44:182e8.

    Article  Google Scholar 

  55. Hammerer-Lercher A, Mair J, Antretter H, et al. B-type natriuretic peptide as a marker of allograft rejection after heart transplantation. J Heart Lung Transplant. 2005;24:1444.

    Article  PubMed  Google Scholar 

  56. Kittleson MM, Skojec DV, Wittstein IS, et al. The change in B-type natriuretic peptide levels over time predicts significant rejection in cardiac transplant recipients. J Heart Lung Transplant. 2009;28:704e9.

    Article  Google Scholar 

  57. Kobashigawa JA, Miller LW, Russell SD, et al. Tacrolimus with mycophenolatemofetil (MMF) or sirolimus vs. Cyclosporine with mmf in cardiac transplant patients: 1-year report. Am J Transplant. 2006;6:1377.

    Article  CAS  PubMed  Google Scholar 

  58. Kobashigawa JA, Patel J, Furukawa H, et al. Five-year results of a randomized, single-center study of tacrolimusvsmicroemulsion cyclosporine in heart transplant patients. J Heart Lung Transplant. 2006;25:434.

    Article  PubMed  Google Scholar 

  59. Arbustini E, Roberts WC. Morphological observations in the epicardial coronary arteries and their surroundings late after cardiac transplantation (allograft vascular disease). Am J Cardiol. 1996;78:814.

    Article  CAS  PubMed  Google Scholar 

  60. Fishbein MC, Kobashigawa J. Biopsy-negative cardiac transplant rejection: etiology, diagnosis, and therapy. Curr Opin Cardiol. 2004;19:166.

    Article  PubMed  Google Scholar 

  61. Kittleson MM, Patel JK, Moriguchi JD, et al. Heart transplant recipients supported with extracorporeal membrane oxygenation: outcomes from a single-center experience. J Heart Lung Transplant. 2011;30:1250.

    Article  PubMed  Google Scholar 

  62. Ghadjar P, Joos D, Martinelli M, et al. Tailored total lymphoid irradiation in heart transplant patients: 10-years experience of one center. Radiat Oncol. 2010;5:3.

    Article  PubMed  PubMed Central  Google Scholar 

  63. Patel JK, Kittleson M, Kobashigawa JA. Cardiac allograft rejection. Surgeon. 2011;9:160.

    Article  PubMed  Google Scholar 

  64. Patel J, Everly M, Chang D, et al. Reduction of alloantibodies via proteosome inhibition in cardiac transplantation. J Heart Lung Transplant. 2011;30:1320.

    Article  PubMed  Google Scholar 

  65. Kirklin JK, Brown RN, Huang ST, et al. Rejection with hemodynamic compromise: objective evidence for efficacy of photopheresis. J Heart Lung Transplant. 2006;25:283.

    Article  CAS  PubMed  Google Scholar 

  66. Chang DH, Kittleson MM, Kobashigawa JA. Immunosuppression following heart transplantation: prospects and challenges. Immunotherapy. 2014;6:181–94.

    Article  CAS  PubMed  Google Scholar 

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Authors and Affiliations

  1. Heart Failure/Transplant Cardiologist, Cedars-Sinai Heart Institute, Los Angeles, CA, USA

    David Chang MD

  2. Director, Advanced Heart Disease Section, Cedars-Sinai Heart Institute, Los Angeles, CA, USA

    Jon Kobashigawa MD

  3. Director, Heart Transplant Program, Cedars-Sinai Heart Institute, Los Angeles, CA, USA

    Jon Kobashigawa MD

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  1. David Chang MD
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  2. Jon Kobashigawa MD
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Correspondence to David Chang MD .

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Editors and Affiliations

  1. Director, Advanced Heart Disease Section, Cedars-Sinai Heart Institute, Los Angeles, California, USA

    Jon Kobashigawa

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Chang, D., Kobashigawa, J. (2017). Cardiac Allograft Rejection, Surveillance and Treatment. In: Kobashigawa, J. (eds) Clinical Guide to Heart Transplantation. Springer, Cham. https://doi.org/10.1007/978-3-319-43773-6_12

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  • DOI: https://doi.org/10.1007/978-3-319-43773-6_12

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