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Heart Failure pp 241-253 | Cite as

Immunosuppression, Including Drug Toxicity, Interactions, New Immunosuppressants in the Pipeline

  • Denise Wang
  • Bruno Meiser
  • Howard J. EisenEmail author
  • Sandra Eifert
Chapter
Part of the Cardiovascular Medicine book series (CVM)

Abstract

The success of organ transplantation depends on the prevention of the allograft rejection with immunosuppression. The three types of rejections are hyperacute, acute, and chronic and are categorized by when the rejection occurs, and the mechanisms of organ injury. The type of tissue, specificity and memory of the lymphocytes, and the type of organ being transplanted are factors that dictate the risk of the type of rejection that may occur.

References

  1. 1.
    Eng HS, Leffell MS. Histocompatibility testing after fifty years of transplantation. J Immunol Methods. 2011;369(1–2):1–21.PubMedGoogle Scholar
  2. 2.
    Wang D, Matsumoto R, You Y, et al. CD3/CD28 costimulation-induced NF-kappaB activation is mediated by recruitment of protein kinase C-theta, Bcl10, and IkappaB kinase beta to the immunological synapse through CARMA1. Mol Cell Biol. 2004;24:164–71.PubMedPubMedCentralGoogle Scholar
  3. 3.
    Halloran PF. Immunosuppressive drugs for kidney transplantation. N Engl J Med. 2004;351:2715–29.PubMedGoogle Scholar
  4. 4.
    Robertson H, Ali S, McDonnell BJ, Burt AD, Kirby JA. Chronic renal allograft dysfunction: the role of T cell-mediated tubular epithelial to mesenchymal cell transition. J Am Soc Nephrol. 2004;15:390–7.PubMedGoogle Scholar
  5. 5.
    Halloran PF, Melk A, Barth C. Rethinking chronic allograft nephropathy: the concept of accelerated senescence. J Am Soc Nephrol. 1999;10:167–81.PubMedGoogle Scholar
  6. 6.
    Raichlin E, Bae JH, Khalpey Z, et al. Conversion to sirolimus as primary immunosuppression attenuates the progression of allograft vasculopathy after cardiac transplantation. Circulation. 2007;116:2726–33.PubMedGoogle Scholar
  7. 7.
    Sanchez-Fructuoso AI, Sanchez-Fructuoso AI. Everolimus: an update on the mechanism of action, pharmacokinetics and recent clinical trials. Expert Opin Drug Metab Toxicol. 2008;4:807–19.PubMedGoogle Scholar
  8. 8.
    Carr SF, Papp E, Wu JC, et al. Characterization of human type I and type II IMP dehydrogenases. J Biol Chem. 1993;268:27286–90.PubMedGoogle Scholar
  9. 9.
    Coutinho AE, Chapman KE. The anti-inflammatory and immunosuppressive effects of glucocorticoids, recent developments and mechanistic insights. Mol Cell Endocrinol. 2011;335:2.PubMedPubMedCentralGoogle Scholar
  10. 10.
    Taylor D, Meiser B, Webber S. The international society of heart and lung transplantation guidelines for the care of heart transplant recipients task force 2: immunosuppression and rejection (Nov. 8, 2010).Google Scholar
  11. 11.
    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;34:1244.PubMedPubMedCentralGoogle Scholar
  12. 12.
    Bourdage JS, Hamlin DM. Comparative polyclonal antithymocyte globulin and antilymphocyte/antilymphoblast globulin anti-CD antigen analysis by flow cytometry. Transplantation. 1995;59(8):1194–200.PubMedGoogle Scholar
  13. 13.
    Rebellato LM, Gross U, Verbanac KM, Thomas JM. A comprehensive definition of the major antibody specificities in polyclonal rabbit antithymocyte globulin. Transplantation. 1994;57(5):685–94.PubMedGoogle Scholar
  14. 14.
    Genestier L, Fournel S, Flacher M, Assossou O, Revillard JP, Bonnefoy-Berard N. Induction of Fas (Apo-1, CD95) mediated apoptosis of activated lymphocytes by polyclonal antithymocyte globulins. Blood. 1998;91(7):2360–8.PubMedGoogle Scholar
  15. 15.
    Crespo-Leiro MG, Alonso-Pulpon L, Arizon JM, et al. Influence of induction therapy, immunosuppressive regimen and anti-viral prophylaxis on development of lymphomas after heart transplantation: data from the Spanish post-heart transplant tumour registry. J Heart Lung Transplant. 2007;26(11):1105–9.PubMedGoogle Scholar
  16. 16.
    Carrier M, White M, Perrault LP, et al. A 10-year experience with intravenous thymoglobuline in induction of immunosuppression following heart transplantation. J Heart Lung Transplant. 1999;18(12):1218–23.PubMedGoogle Scholar
  17. 17.
    Zuckermann AO, Grimm M, Czerny M, et al. Improved long-term results with thymoglobuline induction therapy after cardiac transplantation: a comparison of two different rabbit-antithymocyte globulines. Transplantation. 2000;69(9):1890–8.PubMedGoogle Scholar
  18. 18.
    Schnetzler B, Leger P, Volp A, Dorent R, Pavie A, Gandjbakhch I. A prospective randomized controlled study on the efficacy and tolerance of two antilymphocytic globulins in the prevention of rejection in first-heart transplant recipients. Transpl Int. 2002;15(6):317–25.PubMedGoogle Scholar
  19. 19.
    Koch A, Daniel V, Dengler TJ, Schnabel PA, Hagl S, Sack FU. Effectivity of a T-cell-adapted induction therapy with anti-thymocyte globulin (Sangstat). J Heart Lung Transplant. 2005;24(6):708–13.PubMedGoogle Scholar
  20. 20.
    Delgado DH, Rao V, Hamel J, Miriuka S, Cusimano RJ, Ross HJ. Monitoring of cyclosporine 2-hour post-dose levels in heart transplantation: improvement in clinical outcomes. J Heart Lung Transplant. 2005;24(9):1343–6.PubMedGoogle Scholar
  21. 21.
    Cantarovich M, Giannetti N, Barkun J, Cecere R. Antithymocyte globulin induction allows a prolonged delay in the initiation of cyclosporine in heart transplant patients with postoperative renal dysfunction. Transplantation. 2004;78(5):779–81.PubMedGoogle Scholar
  22. 22.
    Mattei MF, Redonnet M, Gandjbakhch I, et al. Lower risk of infectious deaths in cardiac transplant patients receiving basiliximab versus anti-thymocyte globulin as induction therapy. J Heart Lung Transplant. 2007;26(7):693–9.PubMedGoogle Scholar
  23. 23.
    Beniaminovitz A, Itescu S, Lietz K, Donovan M, Burke EM, Groff BD, et al. Prevention of rejection in cardiac transplantation by blockade of the interleukin-2 receptor with a monoclonal antibody. N Engl J Med. 2000;342(9):613–9.PubMedGoogle Scholar
  24. 24.
    Nashan B, Moore R, Amlot P, Schmidt AG, Abeywickrama K, Soulillou JP. Randomised trial of basiliximab versus placebo for control of acute cellular rejection in renal allograft recipients. CHIB 201 international study group. Lancet. 1997;350(9086):1193–8.PubMedGoogle Scholar
  25. 25.
    Hershberger RE, Starling RC, Eisen HJ, et al. Daclizumab to prevent rejection after cardiac transplantation. N Engl J Med. 2005;352(26):2705–13.PubMedGoogle Scholar
  26. 26.
    Mehra MR, Zucker MJ, Wagoner L, et al. A multicenter, prospective, randomized, double-blind trial of basiliximab in heart transplantation. J Heart Lung Transplant. 2005;24(9):1297–304.PubMedGoogle Scholar
  27. 27.
    Rosenberg PB, Vriesendorp AE, Drazner MH, et al. Induction therapy with basiliximab allows delayed initiation of cyclosporine and preserves renal function after cardiac transplantation. J Heart Lung Transplant. 2005;24(9):1327–31.PubMedGoogle Scholar
  28. 28.
    Almenar L, Garcia-Palomar C, Martinez-Dolz L, et al. Influence of induction therapy on rejection and survival in heart transplantation. Transplant Proc. 2005;37(9):4024–7.PubMedGoogle Scholar
  29. 29.
    Cuppoletti A, Perez-Villa F, Vallejos I, Roig E. Experience with single-dose daclizumab in the prevention of acute rejection in heart transplantation. Transplant Proc. 2005;37(9):4036–8.PubMedGoogle Scholar
  30. 30.
    Carlsen J, Johansen M, Boesgaard S, et al. Induction therapy after cardiac transplantation: a comparison of antithymocyte globulin and daclizumab in the prevention of acute rejection. J Heart Lung Transplant. 2005;24(3):296–302.PubMedGoogle Scholar
  31. 31.
    Chou NK, Wang SS, Chen YS, et al. Induction immunosuppression with basiliximab in heart transplantation. Transplant Proc. 2008;40(8):2623–5.PubMedGoogle Scholar
  32. 32.
    Morris PJ, Russell NK. Alemtuzumab (Campath-1H): a systematic review in organ transplantation. Transplantation. 2006;81:1361.PubMedGoogle Scholar
  33. 33.
    Teuteberg J, Shullo M, Zomak R, et al. Alemtuzumab induction facilitates corticosteroid-free maintenance immunosuppression inhuman cardiac transplantation. J Heart Lung Transplant. 2008;27(2):S201–2.Google Scholar
  34. 34.
    Adamson R, Obispo E, Dychter S, et al. Long-term outcome with the use of OKT3 induction therapy in heart transplant patients: a single-center experience. Transplant Proc. 1998;30(u):1107–9.PubMedGoogle Scholar
  35. 35.
    Carrier M, Jenicek M, Pelletier LC. Value of monoclonal antibody OKT3 in solid organ transplantation: a metaanalysis. Transplant Proc. 1992;24(6):2586–91.PubMedGoogle Scholar
  36. 36.
    Swinnen LJ, Costanzo-Nordin MR, Fisher SG, et al. Increased incidence of lymphoproliferative disorder after immunosuppression with the monoclonal antibody OKT3 in cardiac-transplant recipients. N Engl J Med. 1990;323(25):1723–8.PubMedGoogle Scholar
  37. 37.
    Opelz G, Dohler B. Lymphomas after solid organ transplantation: a collaborative transplant study report. Am J Transplant. 2004;4(2):222–30.PubMedGoogle Scholar
  38. 38.
    Yamashita M, Katsumata M, Iwashima M, Kimura M, Shimizu C, Kamata T, et al. T cell receptor-induced calcineurin activation regulates T helper type 2 cell development by modifying the interleukin 4 receptor signaling complex. J Exp Med. 2000;191(11):1869–79.PubMedPubMedCentralGoogle Scholar
  39. 39.
    Meiser BM. The best dosing for initial tacrolimus application is trough level adapted! Transplantation. 2005;79(1):10–1.PubMedGoogle Scholar
  40. 40.
    Borel JF, Feurer C, Gubler HU, Stahelin H. Biological effects of cyclosporin A: a new antilymphocytic agent. Agents Actions. 1976;6(4):468–75.PubMedGoogle Scholar
  41. 41.
    Nagao T, White DJ, Calne RY. Kinetics of unresponsiveness induced by a short course of cyclosporin a. Transplantation. 1982;33(1):31–5.PubMedGoogle Scholar
  42. 42.
    Kostakis A. Early experience with cyclosporine: a historic perspective. Transplant Proc. 2004;36(2 Suppl):22S–4S.PubMedGoogle Scholar
  43. 43.
    Merrill JP. Publications of John P. Merrill. Nephron. 1978;22(1–3):265–80.PubMedGoogle Scholar
  44. 44.
    Kahan BD. Cyclosporine: nursing and paraprofessional aspects. Transplant Proc. 1983;15(4 Suppl 1–2):3109–83.Google Scholar
  45. 45.
    Kahan BD. Cyclosporine: a revolution in transplantation. Transplant Procs. 1999;31(1-2A):14S–5S.Google Scholar
  46. 46.
    Oyer PE. Heart transplantation in the cyclosporine era. Ann Thorac Surg. 1988;46(5):489–90.PubMedGoogle Scholar
  47. 47.
    Wallwork J, McGregor CG, Wells FC, Cory-Pearce R, English TA. Cyclosporin and intravenous sulphadimidine and trimethoprim therapy. Lancet. 1983;1(8320):366–7.PubMedGoogle Scholar
  48. 48.
    Cabrol C, Gandjbakhch I, Guiraudon G, Pavie A, Villemot JP, Viars P, et al. Heart transplantation. Our experience at the Pitie Hospital in Paris. Bull Acad Natl Med. 1982;166(2):235–50.PubMedGoogle Scholar
  49. 49.
    Cooney GF, Jeevanandam V, Choudhury S, Feutren G, Mueller EA, Eisen HJ. Comparative bioavailability of Neoral and Sandimmune in cardiac transplant recipients over 1 year. Transplant Proc. 1998;30(5):1892–4.PubMedGoogle Scholar
  50. 50.
    Eisen HJ, Hobbs RE, Davis SF, et al. Safety, tolerability, and efficacy of cyclosporine microemulsion in heart transplant recipients: a randomized, multicenter, doubleblind comparison with the oil-based formulation of cyclosporine–results at 24 months after transplantation. Transplantation. 2001;71(1):70–8.PubMedGoogle Scholar
  51. 51.
    Cantarovich M, Ross H, Arizon JM, et al. Benefit of Neoral C2 monitoring in de novo cardiac transplant recipients receiving basiliximab induction. Transplantation. 2008;85(7):992–9.PubMedGoogle Scholar
  52. 52.
    Barnard JB, Thekkudan J, Richardson S, et al. Cyclosporine profiling with C2 and C0 monitoring improves outcomes after heart transplantation. J Heart Lung Transplant. 2006;25(5):564–8.PubMedGoogle Scholar
  53. 53.
    Oyer P, Stinson E, Jamieson S, et al. CYA in cardiac transplantation: a 2 1/2 year follow-up. Transplant Proc. 1983;15:2546.Google Scholar
  54. 54.
    Kino T, Hatanaka H, Miyata S, Inamura N, Nishiyama M, Yajima T, et al. FK-506, a novel immunosuppressant isolated from a streptomyces. II. Immunosuppressive effect of FK-506 in vitro. J Antibiot. 1987;40(9):1256–65.PubMedGoogle Scholar
  55. 55.
    Ochiai T, Nakajima K, Nagata M, Suzuki T, Asano T, Uematsu T, et al. Effect of a new immunosuppressive agent, FK 506, on heterotopic cardiac allotransplantation in the rat. Transplant Proc. 1987;19(1 Pt 2):1284–6.PubMedGoogle Scholar
  56. 56.
    Armitage JM, Kormos RL, Morita S, Fung J, Marrone GC, Hardesty RL, et al. Clinical trial of FK 506 immunosuppression in adult cardiac transplantation. Ann Thorac Surg. 1992;54(2):205–10. discussion 10–1PubMedPubMedCentralGoogle Scholar
  57. 57.
    Armitage JM, Kormos RL, Fung J, Starzl TE. The clinical trial of FK 506 as primary and rescue immunosuppression in adult cardiac transplantation. Transplant Proc. 1991;23(6):3054–7.PubMedPubMedCentralGoogle Scholar
  58. 58.
    Taylor DO, Barr ML, Meiser BM, Pham SM, Mentzer RM, Gass AL. Suggested guidelines for the use of tacrolimus in cardiac transplant recipients. J Heart Lung Transplant. 2001;20(7):734–8.PubMedGoogle Scholar
  59. 59.
    Park SI, Felipe CR, Pinheiro-Machado PG, Garcia R, Tedesco-Silva H Jr, Medina-Pestana JO. Circadian and time-dependent variability in tacrolimus pharmacokinetics. Fundam Clin Pharmacol. 2007;21(2):191–7.PubMedGoogle Scholar
  60. 60.
    Langers P, Press RR, den Hartigh J, et al. Flexible limited sampling model for monitoring tacrolimus in stable patients having undergone liver transplantation with samples 4 to 6 hours after dosing is superior to trough concentration. Ther Drug Monit. 2008;30(4):456–61.PubMedGoogle Scholar
  61. 61.
    Grimm M, Rinaldi M, Yonan NA, et al. Superior prevention of acute rejection by tacrolimus vs. cyclosporine in heart transplant recipients–a large European trial. Am J Transplant. 2006;6:1387.PubMedGoogle Scholar
  62. 62.
    Groetzner J, Meiser BM, Schirmer J, et al. Tacrolimus or cyclosporine for immunosuppression after cardiac transplantation: which treatment reveals more side effects during long-term follow-up? Transplant Proc. 2001;33:1461.PubMedGoogle Scholar
  63. 63.
    Meiser BM, Uberfuhr P, Fuchs A, et al. Single-center randomized trial comparing tacrolimus (FK506) and cyclosporine in the prevention of acute myocardial rejection. J Heart Lung Transplant. 1998;17:782.PubMedGoogle Scholar
  64. 64.
    Reichart B, Meiser B, Viganò M, et al. European multicenter Tacrolimus (FK506) heart pilot study: one-year results–European Tacrolimus multicenter heart study group. J Heart Lung Transplant. 1998;17:775.PubMedGoogle Scholar
  65. 65.
    Taylor DO, Barr ML, Radovancevic B, et al. A randomized, multicenter comparison of tacrolimus and cyclosporine immunosuppressive regimens in cardiac transplantation: decreased hyperlipidemia and hypertension with tacrolimus. J Heart Lung Transplant. 1999;18:336.PubMedGoogle Scholar
  66. 66.
    Kobashigawa JA, Stevenson LW, Brownfield ED, Gleeson MP, Moriguchi JD, Kawata N, et al. Corticosteroid weaning late after heart transplantation: relation to HLA-DR mismatching and long-term metabolic benefits. J Heart Lung Transplant. 1995;14(5):963–7.PubMedGoogle Scholar
  67. 67.
    Dipchand AI, Rossano JW, Edwards LB, et al. 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. 2015;34:1233–43.PubMedGoogle Scholar
  68. 68.
    Cross SA, Perry CM. Tacrolimus once-daily formulation: in the prophylaxis of transplant rejection in renal or liver allograft recipients. Drugs. 2007;67(13):1931–43.PubMedGoogle Scholar
  69. 69.
    Alloway R, Steinberg S, Khalil K, et al. Two years postconversion from a prograf-based regimen to a oncedaily tacrolimus extended-release formulation in stable kidney transplant recipients. Transplantation. 2007;83(12):1648–51.PubMedGoogle Scholar
  70. 70.
    Florman S, Alloway R, Kalayoglu M, et al. Once-daily tacrolimus extended release formulation: experience at 2 years postconversion from a Prograf-based regimen in stable liver transplant recipients. Transplantation. 2007;83(12):1639–42.PubMedGoogle Scholar
  71. 71.
    Allison AC, Eugui EM. Purine metabolism and immunosuppressive effects of mycophenolate mofetil (MMF). Clin Transpl. 1996;10:77–84.Google Scholar
  72. 72.
    Giblett ER, Anderson JE, Cohen F, Pollara B, Meuwissen HJ. Adenosine-deaminase deficiency in two patients with severely impaired cellular immunity. Lancet. 1972;2:1067–9.PubMedGoogle Scholar
  73. 73.
    Allison AC, Hovi T, Watts RWE, Webster ADB. Immunological observations on patients with the Lesch-Nyhan syndrome, and on the role of de-novo purine synthesis in lymphocyte transformation. Lancet. 1975;2:1179–83.PubMedGoogle Scholar
  74. 74.
    Blaheta RA, Leckel K, Wittig B, et al. Mycophenolate mofetil impairs transendothelial migration of allogeneic CD4 and CD8 T-cells. Transplant Proc. 1999;31:1250–2.PubMedGoogle Scholar
  75. 75.
    Morath C, Schwenger V, Beimler J, et al. Antifibrotic actions of mycophenolic acid. Clin Transpl. 2006;20:25–9.Google Scholar
  76. 76.
    Meier-Kriesche HU, Steffen BJ, Hochberg AM, et al. Long-term use of mycophenolate mofetil is associated with a reduction in the incidence and risk of late rejection. Am J Transplant. 2003;3:68–73.PubMedGoogle Scholar
  77. 77.
    Gourishankar S, Hunsicker LG, Jhangri GS, Cockfield SM, Halloran PF. The stability of the glomerular filtration rate after renal transplantation is improving. J Am Soc Nephrol. 2003;14:2387–94.PubMedGoogle Scholar
  78. 78.
    CellCept [package insert]. South San Francisco: Genentech USA, Inc.; 2015.Google Scholar
  79. 79.
    Myfortic [package insert]. East Hanover: Novartis Pharmaceutical Corporation; 2016.Google Scholar
  80. 80.
    Prednisone [package insert]. Columbus: Roxane Laboratories; 2012.Google Scholar
  81. 81.
    Lindenfeld J, Miller GG, Shakar SF, et al. Drug therapy in the heart transplant recipient: part I: cardiac rejection and immunosuppressive drugs. Circulation. 2004;110:3734–40.PubMedGoogle Scholar
  82. 82.
    Lindenfeld J, Miller GG, Shakar SF, et al. Drug therapy in the heart transplant recipient: part II: immunosuppressive drugs. Circulation. 2004;110:3858–65.PubMedGoogle Scholar
  83. 83.
    Grad I, Picard D. The glucocorticoid responses are shaped by molecular chaperones. Mol Cell Endocrinol. 2007;275(1–2):2–12.PubMedGoogle Scholar
  84. 84.
    Lamming DW, Ye L, Katajisto P, Katajisto P, Goncalves MD, Saitoh M, Stevens DM, Davis JG, Salmon AB, Richardson A, Ahima RS, Guertin DA, Sabatini DM, Baur JA, et al. Rapamycin-induced insulin resistance is mediated by mTORC2 loss and uncoupled from longevity. Science. 2012;335(6076):1638–43.PubMedPubMedCentralGoogle Scholar
  85. 85.
    Rapamune [package insert]. Philadelphia: Wyeth Pharmaceuticals Inc.; 2015.Google Scholar
  86. 86.
    MacDonald AS. A worldwide, phase III, randomized, controlled, safety and efficacy study of a sirolimus/cyclosporine regimen for prevention of acute rejection in recipients of primary mismatched renal allografts. Transplantation. 2001;71:271–80.PubMedGoogle Scholar
  87. 87.
    Afinitor [package insert]. East Hanover: Novartis Pharmaceuticals Corp.; 2016.Google Scholar
  88. 88.
    Rosing K, Fobker M, Kannenberg F, Gunia S, Dell’aquila AM, Kwiecien R, Nofer J. Everolimus therapy is associated with reduced lipoprotein-associated phospholipase A2 (Lp-Pla2) activity and oxidative stress in heart transplant recipients. Atherosclerosis. 2013;230(1):164–70.PubMedGoogle Scholar
  89. 89.
    Hiemann NE, Wellnhofer E, Lehmkuhl HB, Knosalla C, Hetzer R, Meyer R. Everolimus prevents endomyocardial remodeling after heart transplantation. Transplantation. 2011;92:1165e72.Google Scholar
  90. 90.
    Jensen L, Thayssen P, Christiansen E, et al. Safety and efficacy of Everolimus- versus Sirolimus-eluting stents: 5-year results from SORT OUT IV. J Am Coll Cardiol. 2016;67(7):751–62.PubMedGoogle Scholar
  91. 91.
    Eisen HJ, Tuzcu EM, Dorent R, Kobashigawa J, Mancini D, Valantine-Von Kaeppler HA, Starling RC, Sorensen K, Hummel M, Lind JM, Abeywickrama KH, Bernhardt P. Everolimus for the prevention of allograft rejection and vasculopathy in cardiac transplant recipients. N Engl J Med. 2003;349:847–58.PubMedPubMedCentralGoogle Scholar
  92. 92.
    Eisen HJ, Kobashigawa J, Starling RC, Pauly DF, Kfoury A, Ross H, Wang SS, Cantin B, Van Bakel A, Ewald G, Hirt S, Lehmkuhl H, Keogh A, Rinaldi M, Potena L, Zuckermann A, Dong G, Cornu-Artis C, Lopez P. Everolimus versus mycophenolate mofetil in heart transplantation: a randomized, multicenter trial. Am J Transplant. 2013;13:1203–16.PubMedPubMedCentralGoogle Scholar
  93. 93.
    Kobashigawa JA, Pauly DF, Starling RC, Eisen H, Ross H, Wang SS, Cantin B, Hill JA, Lopez P, Dong G, Nicholls SJ. A2310 IVUS substudy investigators. Cardiac allograft vasculopathy by intravascular ultrasound in heart transplant patients: substudy from the everolimus versus mycophenolate mofetil randomized, multicenter trial. JACC Heart Fail. 2013;5:389–99.Google Scholar
  94. 94.
    Andreassen AK, Andersson B, Gustafsson F, Eiskjaer H, Rådegran G, Gude E, Jansson K, Solbu D, Karason K, Arora S, Dellgren G, Gullestad L, SCHEDULE investigators. Everolimus initiation with early Calcineurin inhibitor withdrawal in De novo heart transplant recipients: three-year results from the randomized SCHEDULE study. Am J Transplant. 2016;4:1238–47.Google Scholar
  95. 95.
    Chandraker A, Kobashigawa J, Stehlik J, Givertz M, Pierson R, Pinney S, Joren M, Nissen S, Guleria I, Morrison Y, Armstrong B, Bridges N, Sayegh M, Starling R. Rituximab induction in cardiac transplantation is associated with accelerated coronary artery vasculopathy: CTOT11. [abstract]. Am J Transplant. 2016; 16 (suppl 3).Google Scholar

Copyright information

© Springer Nature Switzerland AG 2019

Authors and Affiliations

  • Denise Wang
    • 1
  • Bruno Meiser
    • 2
  • Howard J. Eisen
    • 1
    Email author
  • Sandra Eifert
    • 2
  1. 1.Drexel University College of MedicinePhiladelphiaUSA
  2. 2.Ludwig Maximillians University of Munich Medical CenterMunichGermany

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