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Congestive Heart Failure and Cardiac Transplantation pp 505–515Cite as

Late Complications Following Heart Transplant

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Abstract

Late complications following heart transplantation (HT) have been a significant barrier to improvement in longevity of HT recipients. While improvement in surgical techniques has reduced perioperative morbidity and mortality and adoption of virtual donor-recipient cross-matching and new strategies for identifying and treating the hypersensitized recipients have reduced the incidence of hyperacute rejection, late complications of HT, including allograft rejection and vasculopathy, infection, and malignancy, have remained the major cause of morbidity and mortality among HT recipients (Fig. 31.1). Most late complications following HT are somehow linked to the lack of ideal immunosuppressive balance. Treatment remains rudimentary with little guidance from the literature regarding tailoring therapy except in the case of an adverse event. From this perspective, late complications following HT can be divided into three major categories: In this chapter, we will review common late complications after transplant and their management.

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Abbreviations

HT:

Heart transplantation

CAV:

Cardiac allograft vasculopathy

IST:

Immunosuppressive therapy

ECMO:

Extra corporal membrane oxygenation

TAH:

Total artificial heart

DSA:

Donor-specific antibodies

IVUS:

Intravascular ultrasound

References

  1. Guethoff S, Meiser BM, Groetzner J, Eifert S, Grinninger C, Ueberfuhr P, Reichart B, Hagl C, Kaczmarek I. Ten-year results of a randomized trial comparing tacrolimus versus cyclosporine a in combination with mycophenolate mofetil after heart transplantation. Transplantation. 2013;95:629–34.

    Article  CAS  PubMed  Google Scholar 

  2. Webber SA, Naftel DC, Parker J, Mulla N, Balfour I, Kirklin JK, Morrow R, Pediatric Heart Transplant Study G. Late rejection episodes more than 1 year after pediatric heart transplantation: risk factors and outcomes. J Heart Lung Transplant. 2003;22:869–75.

    Article  PubMed  Google Scholar 

  3. Kubo SH, Naftel DC, Mills Jr RM, O’Donnell J, Rodeheffer RJ, Cintron GB, Kenzora JL, Bourge RC, Kirklin JK. Risk factors for late recurrent rejection after heart transplantation: a multiinstitutional, multivariable analysis. Cardiac transplant research database group. J Heart Lung Transplant. 1995;14:409–18.

    CAS  PubMed  Google Scholar 

  4. Gradek WQ, D’Amico C, Smith AL, Vega D, Book WM. Routine surveillance endomyocardial biopsy continues to detect significant rejection late after heart transplantation. J Heart Lung Transplant. 2001;20:497–502.

    Article  CAS  PubMed  Google Scholar 

  5. Loupy A, Cazes A, Guillemain R, Amrein C, Hedjoudje A, Tible M, Pezzella V, Fabiani JN, Suberbielle C, Nochy D, Hill GS, Empana JP, Jouven X, Bruneval P, Duong Van Huyen JP. Very late heart transplant rejection is associated with microvascular injury, complement deposition and progression to cardiac allograft vasculopathy. Am J Transplant. 2011;11:1478–87.

    Article  CAS  PubMed  Google Scholar 

  6. White JA, Guiraudon C, Pflugfelder PW, Kostuk WJ. Routine surveillance myocardial biopsies are unnecessary beyond one year after heart transplantation. J Heart Lung Transplant. 1995;14:1052–6.

    CAS  PubMed  Google Scholar 

  7. Crespo-Leiro MG, Stypmann J, Schulz U, Zuckermann A, Mohacsi P, Bara C, Ross H, Parameshwar J, Zakliczynski M, Fiocchi R, Hoefer D, Colvin M, Deng MC, Leprince P, Elashoff B, Yee JP, Vanhaecke J. Clinical usefulness of gene-expression profile to rule out acute rejection after heart transplantation: Cargo II. Eur Heart J. 2016; pii: ehv682.

    Google Scholar 

  8. Wu GW, Kobashigawa JA, Fishbein MC, Patel JK, Kittleson MM, Reed EF, Kiyosaki KK, Ardehali A. Asymptomatic antibody-mediated rejection after heart transplantation predicts poor outcomes. J Heart Lung Transplant. 2009;28:417–22.

    Article  PubMed  Google Scholar 

  9. Kfoury AG, Hammond ME, Snow GL, Drakos SG, Stehlik J, Fisher PW, Reid BB, Everitt MD, Bader FM, Renlund DG. 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 

  10. Kittleson MM, Kobashigawa JA. Antibody-mediated rejection. Curr Opin Organ Transplant. 2012;17:551–7.

    Article  CAS  PubMed  Google Scholar 

  11. Billingham ME. Histopathology of graft coronary disease. J Heart Lung Transplant. 1992;11:S38–44.

    CAS  PubMed  Google Scholar 

  12. Tuzcu EM, De Franco AC, Goormastic M, Hobbs RE, Rincon G, Bott-Silverman C, McCarthy P, Stewart R, Mayer E, Nissen SE. Dichotomous pattern of coronary atherosclerosis 1 to 9 years after transplantation: insights from systematic intravascular ultrasound imaging. J Am Coll Cardiol. 1996;27:839–46.

    Article  CAS  PubMed  Google Scholar 

  13. Taylor DO, Stehlik J, Edwards LB, Aurora P, Christie JD, Dobbels F, Kirk R, Kucheryavaya AY, Rahmel AO, Hertz MI. Registry of the international society for heart and lung transplantation: Twenty-sixth official adult heart transplant report-2009. J Heart Lung Transplant. 2009;28:1007–22.

    Article  PubMed  Google Scholar 

  14. Colvin-Adams M, Harcourt N, Duprez D. Endothelial dysfunction and cardiac allograft vasculopathy. J Cardiovasc Transl Res. 2013;6:263–77.

    Article  PubMed  Google Scholar 

  15. Colvin-Adams M, Agnihotri A. Cardiac allograft vasculopathy: current knowledge and future direction. Clin Transplant. 2011;25:175–84.

    Article  PubMed  Google Scholar 

  16. Gao SZ, Alderman EL, Schroeder JS, Hunt SA, Wiederhold V, Stinson EB. Progressive coronary luminal narrowing after cardiac transplantation. Circulation. 1990;82:IV269–75.

    CAS  PubMed  Google Scholar 

  17. St Goar FG, Pinto FJ, Alderman EL, Valantine HA, Schroeder JS, Gao SZ, Stinson EB, Popp RL. Intracoronary ultrasound in cardiac transplant recipients. In vivo evidence of “angiographically silent” intimal thickening. Circulation. 1992;85:979–87.

    Article  CAS  PubMed  Google Scholar 

  18. Barbir M, Lazem F, Banner N, Mitchell A, Yacoub M. The prognostic significance of non-invasive cardiac tests in heart transplant recipients. Eur Heart J. 1997;18:692–6.

    Article  CAS  PubMed  Google Scholar 

  19. Mehra MR, Ventura HO, Stapleton DD, Smart FW, Collins TC, Ramee SR. Presence of severe intimal thickening by intravascular ultrasonography predicts cardiac events in cardiac allograft vasculopathy. J Heart Lung Transplant. 1995;14:632–9.

    CAS  PubMed  Google Scholar 

  20. Kobashigawa JA, Tobis JM, Starling RC, Tuzcu EM, Smith AL, Valantine HA, Yeung AC, Mehra MR, Anzai H, Oeser BT, Abeywickrama KH, Murphy J, Cretin N. Multicenter intravascular ultrasound validation study among heart transplant recipients: outcomes after five years. J Am Coll Cardiol. 2005;45:1532–7.

    Article  PubMed  Google Scholar 

  21. Tuzcu EM, Kapadia SR, Sachar R, Ziada KM, Crowe TD, Feng J, Magyar WA, Hobbs RE, Starling RC, Young JB, McCarthy P, Nissen SE. Intravascular ultrasound evidence of angiographically silent progression in coronary atherosclerosis predicts long-term morbidity and mortality after cardiac transplantation. J Am Coll Cardiol. 2005;45:1538–42.

    Article  PubMed  Google Scholar 

  22. Haddad F, Khazanie P, Deuse T, Weisshaar D, Zhou J, Nam CW, Vu TA, Gomari FA, Skhiri M, Simos A, Schnittger I, Vrotvec B, Hunt SA, Fearon WF. Clinical and functional correlates of early microvascular dysfunction after heart transplantation. Circ Heart Fail. 2012;5:759–68.

    Article  PubMed  Google Scholar 

  23. Spes CH, Klauss V, Mudra H, Schnaack SD, Tammen AR, Rieber J, Siebert U, Henneke KH, Uberfuhr P, Reichart B, Theisen K, Angermann CE. Diagnostic and prognostic value of serial dobutamine stress echocardiography for noninvasive assessment of cardiac allograft vasculopathy: a comparison with coronary angiography and intravascular ultrasound. Circulation. 1999;100:509–15.

    Article  CAS  PubMed  Google Scholar 

  24. Elhendy A, van Domburg RT, Vantrimpont P, Poldermans D, Bax JJ, van Gelder T, Baan CC, Schinkel A, Roelandt JR, Balk AH. Prediction of mortality in heart transplant recipients by stress technetium-99m tetrofosmin myocardial perfusion imaging. Am J Cardiol. 2002;89:964–8.

    Article  PubMed  Google Scholar 

  25. Braggion-Santos MF, Lossnitzer D, Buss S, Lehrke S, Doesch A, Giannitsis E, Korosoglou G, Katus HA, Steen H. Late gadolinium enhancement assessed by cardiac magnetic resonance imaging in heart transplant recipients with different stages of cardiac allograft vasculopathy. Eur Heart J Cardiovasc Imaging. 2014;15:1125–32.

    Article  PubMed  Google Scholar 

  26. Barthelemy O, Toledano D, Varnous S, Fernandez F, Boutekadjirt R, Ricci F, Helft G, Le Feuvre C, Gandjbakhch I, Metzger JP, Pavie A, Cluzel P. Multislice computed tomography to rule out coronary allograft vasculopathy in heart transplant patients. J Heart Lung Transplant. 2012;31:1262–8.

    Article  PubMed  Google Scholar 

  27. Seki A, Fishbein MC. Predicting the development of cardiac allograft vasculopathy. Cardiovasc Pathol. 2014;23:253–60.

    Article  PubMed  Google Scholar 

  28. Costanzo MR, Dipchand A, Starling R, Anderson A, Chan M, Desai S, Fedson S, Fisher P, Gonzales-Stawinski G, Martinelli L, McGiffin D, Smith J, Taylor D, Meiser B, Webber S, Baran D, Carboni M, Dengler T, Feldman D, Frigerio M, Kfoury A, Kim D, Kobashigawa J, Shullo M, Stehlik J, Teuteberg J, Uber P, Zuckermann A, Hunt S, Burch M, Bhat G, Canter C, Chinnock R, Crespo-Leiro M, Delgado R, Dobbels F, Grady K, Kao W, Lamour J, Parry G, Patel J, Pini D, Towbin J, Wolfel G, Delgado D, Eisen H, Goldberg L, Hosenpud J, Johnson M, Keogh A, Lewis C, O’Connell J, Rogers J, Ross H, Russell S, Vanhaecke J, International Society of H, Lung Transplantation G. The international society of heart and lung transplantation guidelines for the care of heart transplant recipients. J Heart Lung Transplant. 2010;29:914–56.

    Article  PubMed  Google Scholar 

  29. Potena L, Frascaroli G, Grigioni F, Lazzarotto T, Magnani G, Tomasi L, Coccolo F, Gabrielli L, Magelli C, Landini MP, Branzi A. Hydroxymethyl-glutaryl coenzyme a reductase inhibition limits cytomegalovirus infection in human endothelial cells. Circulation. 2004;109:532–6.

    Article  CAS  PubMed  Google Scholar 

  30. Kobashigawa JA, Moriguchi JD, Laks H, Wener L, Hage A, Hamilton MA, Cogert G, Marquez A, Vassilakis ME, Patel J, Yeatman L. Ten-year follow-up of a randomized trial of pravastatin in heart transplant patients. J Heart Lung Transplant. 2005;24:1736–40.

    Article  PubMed  Google Scholar 

  31. Mehra MR, Raval NY. Metaanalysis of statins and survival in de novo cardiac transplantation. Transplant Proc. 2004;36:1539–41.

    Article  CAS  PubMed  Google Scholar 

  32. Potena L, Grigioni F, Ortolani P, Magnani G, Marrozzini C, Falchetti E, Barbieri A, Bacchi-Reggiani L, Lazzarotto T, Marzocchi A, Magelli C, Landini MP, Branzi A. Relevance of cytomegalovirus infection and coronary-artery remodeling in the first year after heart transplantation: a prospective three-dimensional intravascular ultrasound study. Transplantation. 2003;75:839–43.

    Article  PubMed  Google Scholar 

  33. Potena L, Grigioni F, Magnani G, Lazzarotto T, Musuraca AC, Ortolani P, Coccolo F, Fallani F, Russo A, Branzi A. Prophylaxis versus preemptive anti-cytomegalovirus approach for prevention of allograft vasculopathy in heart transplant recipients. J Heart Lung Transplant. 2009;28:461–7.

    Article  PubMed  Google Scholar 

  34. 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, Group RBS. Everolimus for the prevention of allograft rejection and vasculopathy in cardiac-transplant recipients. N Engl J Med. 2003;349:847–58.

    Article  CAS  PubMed  Google Scholar 

  35. Topilsky Y, Hasin T, Raichlin E, Boilson BA, Schirger JA, Pereira NL, Edwards BS, Clavell AL, Rodeheffer RJ, Frantz RP, Maltais S, Park SJ, Daly RC, Lerman A, Kushwaha SS. Sirolimus as primary immunosuppression attenuates allograft vasculopathy with improved late survival and decreased cardiac events after cardiac transplantation. Circulation. 2012;125:708–20.

    Article  CAS  PubMed  Google Scholar 

  36. Luciani GB, Faggian G, Montalbano G, Casali G, Forni A, Chiominto B, Mazzucco A. Blood versus crystalloid cardioplegia for myocardial protection of donor hearts during transplantation: a prospective, randomized clinical trial. J Thorac Cardiovasc Surg. 1999;118:787–95.

    Article  CAS  PubMed  Google Scholar 

  37. Benza RL, Zoghbi GJ, Tallaj J, Brown R, Kirklin JK, Hubbard M, Rayburn B, Foley B, McGiffin DC, Pinderski LJ, Misra V, Bourge RC. Palliation of allograft vasculopathy with transluminal angioplasty: a decade of experience. J Am Coll Cardiol. 2004;43:1973–81.

    Article  PubMed  Google Scholar 

  38. Bader FM, Kfoury AG, Gilbert EM, Barry WH, Humayun N, Hagan ME, Thomas H, Renlund D. Percutaneous coronary interventions with stents in cardiac transplant recipients. J Heart Lung Transplant. 2006;25:298–301.

    Article  PubMed  Google Scholar 

  39. Park KE, Huo T, Muller KE, Aranda JM, Hill JA, Anderson RD. Drug-eluting stents may not reduce target lesion revascularization in cardiac allograft vasculopathy. J Interv Cardiol. 2014;27:80–5.

    Article  PubMed  Google Scholar 

  40. Musci M, Loebe M, Wellnhofer E, Meyer R, Pasic M, Hummel M, Bocksch W, Grauhan O, Weng Y, Hetzer R. Coronary angioplasty, bypass surgery, and retransplantation in cardiac transplant patients with graft coronary disease. Thorac Cardiovasc Surg. 1998;46:268–74.

    Article  CAS  PubMed  Google Scholar 

  41. Christie JD, Edwards LB, Kucheryavaya AY, Benden C, Dobbels F, Kirk R, Rahmel AO, Stehlik J, Hertz MI. The registry of the international society for heart and lung transplantation: Twenty-eighth adult lung and heart-lung transplant report--2011. J Heart Lung Transplant. 2011;30:1104–22.

    Article  PubMed  Google Scholar 

  42. Engels EA, Pfeiffer RM, Fraumeni Jr JF, Kasiske BL, Israni AK, Snyder JJ, Wolfe RA, Goodrich NP, Bayakly AR, Clarke CA, Copeland G, Finch JL, Fleissner ML, Goodman MT, Kahn A, Koch L, Lynch CF, Madeleine MM, Pawlish K, Rao C, Williams MA, Castenson D, Curry M, Parsons R, Fant G, Lin M. Spectrum of cancer risk among us solid organ transplant recipients. JAMA. 2011;306:1891–901.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  43. Sampaio MS, Cho YW, Qazi Y, Bunnapradist S, Hutchinson IV, Shah T. Posttransplant malignancies in solid organ adult recipients: an analysis of the U.S. National transplant database. Transplantation. 2012;94:990–8.

    Article  PubMed  Google Scholar 

  44. Hojo M, Morimoto T, Maluccio M, Asano T, Morimoto K, Lagman M, Shimbo T, Suthanthiran M. Cyclosporine induces cancer progression by a cell-autonomous mechanism. Nature. 1999;397:530–4.

    Article  CAS  PubMed  Google Scholar 

  45. Frohlich GM, Rufibach K, Enseleit F, Wolfrum M, von Babo M, Frank M, Berli R, Hermann M, Holzmeister J, Wilhelm M, Falk V, Noll G, Luscher TF, Ruschitzka F. Statins and the risk of cancer after heart transplantation. Circulation. 2012;126:440–7.

    Article  PubMed  Google Scholar 

  46. Opelz G, Dohler B. Lymphomas after solid organ transplantation: a collaborative transplant study report. Am J Transplant. 2004;4:222–30.

    Article  PubMed  Google Scholar 

  47. Gutierrez-Dalmau A, Campistol JM. Immunosuppressive therapy and malignancy in organ transplant recipients: a systematic review. Drugs. 2007;67:1167–98.

    Article  CAS  PubMed  Google Scholar 

  48. Sigurdardottir V, Bjortuft O, Eiskjaer H, Ekmehag B, Gude E, Gustafsson F, Hagerman I, Halme M, Lommi J, Mared L, Riise GC, Simonsen S. Long-term follow-up of lung and heart transplant recipients with pre-transplant malignancies. J Heart Lung Transplant. 2012;31:1276–80.

    Article  PubMed  Google Scholar 

  49. Jensen P, Hansen S, Moller B, Leivestad T, Pfeffer P, Geiran O, Fauchald P, Simonsen S. Skin cancer in kidney and heart transplant recipients and different long-term immunosuppressive therapy regimens. J Am Acad Dermatol. 1999;40:177–86.

    Article  CAS  PubMed  Google Scholar 

  50. Euvrard S, Kanitakis J, Claudy A. Skin cancers after organ transplantation. N Engl J Med. 2003;348:1681–91.

    Article  PubMed  Google Scholar 

  51. Guba M, Graeb C, Jauch KW, Geissler EK. Pro- and anti-cancer effects of immunosuppressive agents used in organ transplantation. Transplantation. 2004;77:1777–82.

    Article  CAS  PubMed  Google Scholar 

  52. Duncan FJ, Wulff BC, Tober KL, Ferketich AK, Martin J, Thomas-Ahner JM, Allen SD, Kusewitt DF, Oberyszyn TM, Vanbuskirk AM. Clinically relevant immunosuppressants influence uvb-induced tumor size through effects on inflammation and angiogenesis. Am J Transplant. 2007;7:2693–703.

    Article  CAS  PubMed  Google Scholar 

  53. O’Donovan P, Perrett CM, Zhang X, Montaner B, Xu YZ, Harwood CA, McGregor JM, Walker SL, Hanaoka F, Karran P. Azathioprine and uva light generate mutagenic oxidative DNA damage. Science. 2005;309:1871–4.

    Article  PubMed  PubMed Central  Google Scholar 

  54. de Graaf YG, Rebel H, Elghalbzouri A, Cramers P, Nellen RG, Willemze R, Bouwes Bavinck JN, de Gruijl FR. More epidermal p53 patches adjacent to skin carcinomas in renal transplant recipients than in immunocompetent patients: the role of azathioprine. Exp Dermatol. 2008;17:349–55.

    Article  PubMed  Google Scholar 

  55. Tsao L, Hsi ED. The clinicopathologic spectrum of posttransplantation lymphoproliferative disorders. Arch Pathol Lab Med. 2007;131:1209–18.

    PubMed  Google Scholar 

  56. Al-Mansour Z, Nelson BP, Evens AM. Post-transplant lymphoproliferative disease (ptld): risk factors, diagnosis, and current treatment strategies. Curr Hematol Malig Rep. 2013;8:173–83.

    Article  PubMed  PubMed Central  Google Scholar 

  57. Nourse JP, Jones K, Gandhi MK. Epstein-barr virus-related post-transplant lymphoproliferative disorders: pathogenetic insights for targeted therapy. Am J Transplant. 2011;11:888–95.

    Article  CAS  PubMed  Google Scholar 

  58. Buda A, Caforio A, Calabrese F, Fagiuoli S, Pevere S, Livi U, Naccarato R, Burra P. Lymphoproliferative disorders in heart transplant recipients: role of hepatitis c virus (hcv) and epstein-barr virus (ebv) infection. Transplant Int. 2000;13 Suppl 1:S402–5.

    Article  Google Scholar 

  59. Cockfield SM. Identifying the patient at risk for post-transplant lymphoproliferative disorder. Transplant Infect Dis. 2001;3:70–8.

    Article  CAS  Google Scholar 

  60. Reshef R, Luskin MR, Kamoun M, Vardhanabhuti S, Tomaszewski JE, Stadtmauer EA, Porter DL, Heitjan DF, de Tsai E. Association of hla polymorphisms with post-transplant lymphoproliferative disorder in solid-organ transplant recipients. Am J Transplant. 2011;11:817–25.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  61. Jagadeesh D, Woda BA, Draper J, Evens AM. Post transplant lymphoproliferative disorders: risk, classification, and therapeutic recommendations. Curr Treat Options Oncol. 2012;13:122–36.

    Article  PubMed  Google Scholar 

  62. Penn I, Hammond W, Brettschneider L, Starzl TE. Malignant lymphomas in transplantation patients. Transplant Proc. 1969;1:106–12.

    CAS  PubMed  PubMed Central  Google Scholar 

  63. Swinnen LJ, Mullen GM, Carr TJ, Costanzo MR, Fisher RI. Aggressive treatment for postcardiac transplant lymphoproliferation. Blood. 1995;86:3333–40.

    CAS  PubMed  Google Scholar 

  64. Knight JS, Tsodikov A, Cibrik DM, Ross CW, Kaminski MS, Blayney DW. Lymphoma after solid organ transplantation: risk, response to therapy, and survival at a transplantation center. Journal Clin Oncol. 2009;27:3354–62.

    Article  Google Scholar 

  65. Haddad E, Paczesny S, Leblond V, Seigneurin JM, Stern M, Achkar A, Bauwens M, Delwail V, Debray D, Duvoux C, Hubert P, Hurault de Ligny B, Wijdenes J, Durandy A, Fischer A. Treatment of b-lymphoproliferative disorder with a monoclonal anti-interleukin-6 antibody in 12 patients: a multicenter phase 1-2 clinical trial. Blood. 2001;97:1590–7.

    Article  CAS  PubMed  Google Scholar 

  66. Komrokji RS, Oliva JL, Zand M, Felgar R, Abboud CN. Mini-beam and autologous hematopoietic stem-cell transplant for treatment of post-transplant lymphoproliferative disorders. Am J Hematol. 2005;79:211–5.

    Article  PubMed  Google Scholar 

  67. Lund LH, Edwards LB, Kucheryavaya AY, Benden C, Christie JD, Dipchand AI, Dobbels F, Goldfarb SB, Levvey BJ, Meiser B, Yusen RD, Stehlik J, International Society of H, Lung T. The registry of the international society for heart and lung transplantation: Thirty-first official adult heart transplant report--2014; focus theme: retransplantation. J Heart Lung Transplant. 2014;33:996–1008.

    Article  PubMed  Google Scholar 

  68. Montoya JG, Giraldo LF, Efron B, Stinson EB, Gamberg P, Hunt S, Giannetti N, Miller J, Remington JS. Infectious complications among 620 consecutive heart transplant patients at Stanford University Medical Center. Clin Infect Dis. 2001;33:629–40.

    Article  CAS  PubMed  Google Scholar 

  69. Ljungman P, Griffiths P, Paya C. Definitions of cytomegalovirus infection and disease in transplant recipients. Clin Infect Dis. 2002;34:1094–7.

    Article  PubMed  Google Scholar 

  70. Grattan MT, Moreno-Cabral CE, Starnes VA, Oyer PE, Stinson EB, Shumway NE. Cytomegalovirus infection is associated with cardiac allograft rejection and atherosclerosis. JAMA. 1989;261:3561–6.

    Article  CAS  PubMed  Google Scholar 

  71. Paya C, Humar A, Dominguez E, Washburn K, Blumberg E, Alexander B, Freeman R, Heaton N, Pescovitz MD, Valganciclovir Solid Organ Transplant Study G. Efficacy and safety of valganciclovir vs. Oral ganciclovir for prevention of cytomegalovirus disease in solid organ transplant recipients. Am J Transplant. 2004;4:611–20.

    Article  CAS  PubMed  Google Scholar 

  72. Potena L, Holweg CT, Chin C, Luikart H, Weisshaar D, Narasimhan B, Fearon WF, Lewis DB, Cooke JP, Mocarski ES, Valantine HA. Acute rejection and cardiac allograft vascular disease is reduced by suppression of subclinical cytomegalovirus infection. Transplantation. 2006;82:398–405.

    Article  CAS  PubMed  Google Scholar 

  73. Kobashigawa JA, Miller LW, Russell SD, Ewald GA, Zucker MJ, Goldberg LR, Eisen HJ, Salm K, Tolzman D, Gao J, Fitzsimmons W, First R, Study I. Tacrolimus with mycophenolate mofetil (mmf) or sirolimus vs. Cyclosporine with mmf in cardiac transplant patients: 1-year report. Am J Transplant. 2006;6:1377–86.

    Article  CAS  PubMed  Google Scholar 

  74. Grimm M, Rinaldi M, Yonan NA, Arpesella G, Arizon Del Prado JM, Pulpon LA, Villemot JP, Frigerio M, Rodriguez Lambert JL, Crespo-Leiro MG, Almenar L, Duveau D, Ordonez-Fernandez A, Gandjbakhch J, Maccherini M, Laufer G. Superior prevention of acute rejection by tacrolimus vs. Cyclosporine in heart transplant recipients--a large european trial. Am J Transplant. 2006;6:1387–97.

    Article  CAS  PubMed  Google Scholar 

  75. Hamour IM, Lyster HS, Burke MM, Rose ML, Banner NR. Mycophenolate mofetil may allow cyclosporine and steroid sparing in de novo heart transplant patients. Transplantation. 2007;83:570–6.

    Article  CAS  PubMed  Google Scholar 

  76. Lehmkuhl HB, Arizon J, Vigano M, Almenar L, Gerosa G, Maccherini M, Varnous S, Musumeci F, Hexham JM, Mange KC, Livi U, Study I. Everolimus with reduced cyclosporine versus mmf with standard cyclosporine in de novo heart transplant recipients. Transplantation. 2009;88:115–22.

    Article  CAS  PubMed  Google Scholar 

  77. Thomas HL, Banner NR, Murphy CL, Steenkamp R, Birch R, Fogarty DG, Bonser AR, Steering Group of the UKCTA. Incidence, determinants, and outcome of chronic kidney disease after adult heart transplantation in the united kingdom. Transplantation. 2012;93:1151–7.

    Article  CAS  PubMed  Google Scholar 

  78. Hertz MI. The registry of the international society for heart and lung transplantation--introduction to the 2012 annual reports: new leadership, same vision. J Heart Lung Transplant. 2012;31:1045–51.

    Article  PubMed  Google Scholar 

  79. Issa N, Kukla A, Ibrahim HN. Calcineurin inhibitor nephrotoxicity: a review and perspective of the evidence. Am J Nephrol. 2013;37:602–12.

    Article  CAS  PubMed  Google Scholar 

  80. Pinney SP, Balakrishnan R, Dikman S, Nair A, Hammond K, Domanski M, Anyanwu AC, Deboccardo G. Histopathology of renal failure after heart transplantation: a diverse spectrum. J Heart Lung Transplant. 2012;31:233–7.

    Article  PubMed  Google Scholar 

  81. Naesens M, Kuypers DR, Sarwal M. Calcineurin inhibitor nephrotoxicity. Clin J Am Soc Nephrol. 2009;4:481–508.

    CAS  PubMed  Google Scholar 

  82. Watarai Y, Morita K, Shimoda N, Miura M, Yoshioka M, Togashi H, Nonomura K, Koyanagi T. Effect of tacrolimus and cyclosporine on renal microcirculation and nitric oxide production. Transplant Proc. 2004;36:2130–2.

    Article  CAS  PubMed  Google Scholar 

  83. Heering P, Ivens K, Aker S, Grabensee B. Distal tubular acidosis induced by fk506. Clin Transplant. 1998;12:465–71.

    CAS  PubMed  Google Scholar 

  84. Lin HY, Rocher LL, McQuillan MA, Schmaltz S, Palella TD, Fox IH. Cyclosporine-induced hyperuricemia and gout. N Engl J Med. 1989;321:287–92.

    Article  CAS  PubMed  Google Scholar 

  85. Bobadilla NA, Gamba G. New insights into the pathophysiology of cyclosporine nephrotoxicity: a role of aldosterone. Am J Physiol Renal Physiol. 2007;293:F2–9.

    Article  CAS  PubMed  Google Scholar 

  86. Michel S, Bigdeli AK, Hagl C, Meiser B, Kaczmarek I. Renal recovery after conversion to an everolimus-based immunosuppression in early and late heart transplant recipients: a 12-month analysis. Exp Clin Transplant. 2013;11:429–34.

    Article  PubMed  Google Scholar 

  87. Zuckermann A, Keogh A, Crespo-Leiro MG, Mancini D, Vilchez FG, Almenar L, Brozena S, Eisen H, Tai SS, Kushwaha S. Randomized controlled trial of sirolimus conversion in cardiac transplant recipients with renal insufficiency. Am J Transplant. 2012;12:2487–97.

    Article  CAS  PubMed  Google Scholar 

  88. Boissonnat P, Gaillard S, Mercier C, Redonnet M, Lelong B, Mattei MF, Mouly-Bandini A, Pattier S, Sirinelli A, Epailly E, Varnous S, Billes MA, Sebbag L, Ecochard R, Cornu C, Gueyffier F. Impact of the early reduction of cyclosporine on renal function in heart transplant patients: a French randomised controlled trial. Trials. 2012;13:231.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  89. van de Beek D, Kremers W, Daly RC, Edwards BS, Clavell AL, McGregor CG, Wijdicks EF. Effect of neurologic complications on outcome after heart transplant. Arch Neurol. 2008;65:226–31.

    PubMed  Google Scholar 

  90. Bechstein WO. Neurotoxicity of calcineurin inhibitors: impact and clinical management. Transplant Int. 2000;13:313–26.

    Article  CAS  Google Scholar 

  91. Neff RT, Hurst FP, Falta EM, Bohen EM, Lentine KL, Dharnidharka VR, Agodoa LY, Jindal RM, Yuan CM, Abbott KC. Progressive multifocal leukoencephalopathy and use of mycophenolate mofetil after kidney transplantation. Transplantation. 2008;86:1474–8.

    Article  PubMed  Google Scholar 

  92. Pittock SJ, Rabinstein AA, Edwards BS, Wijdicks EF. Okt3 neurotoxicity presenting as akinetic mutism. Transplantation. 2003;75:1058–60.

    Article  CAS  PubMed  Google Scholar 

  93. Adair JC, Woodley SL, O’Connell JB, Call GK, Baringer JR. Aseptic meningitis following cardiac transplantation: clinical characteristics and relationship to immunosuppressive regimen. Neurology. 1991;41:249–52.

    Article  CAS  PubMed  Google Scholar 

  94. Taylor DO, Barr ML, Radovancevic B, Renlund DG, Mentzer Jr RM, Smart FW, Tolman DE, Frazier OH, Young JB, VanVeldhuisen P. A randomized, multicenter comparison of tacrolimus and cyclosporine immunosuppressive regimens in cardiac transplantation: decreased hyperlipidemia and hypertension with tacrolimus. J Heart Lung Transplant. 1999;18:336–45.

    Article  CAS  PubMed  Google Scholar 

  95. Artz MA, Boots JM, Ligtenberg G, Roodnat JI, Christiaans MH, Vos PF, Moons P, Borm G, Hilbrands LB. Conversion from cyclosporine to tacrolimus improves quality-of-life indices, renal graft function and cardiovascular risk profile. Am J Transplant. 2004;4:937–45.

    Article  CAS  PubMed  Google Scholar 

  96. Shane E, Rivas M, McMahon DJ, Staron RB, Silverberg SJ, Seibel MJ, Mancini D, Michler RE, Aaronson K, Addesso V, Lo SH. Bone loss and turnover after cardiac transplantation. J Clin Endocrinol Metab. 1997;82:1497–506.

    CAS  PubMed  Google Scholar 

  97. Guo CY, Johnson A, Locke TJ, Eastell R. Mechanisms of bone loss after cardiac transplantation. Bone. 1998;22:267–71.

    Article  CAS  PubMed  Google Scholar 

  98. Maalouf NM, Shane E. Osteoporosis after solid organ transplantation. J Clin Endocrinol Metab. 2005;90:2456–65.

    Article  CAS  PubMed  Google Scholar 

  99. Leidig-Bruckner G, Hosch S, Dodidou P, Ritschel D, Conradt C, Klose C, Otto G, Lange R, Theilmann L, Zimmerman R, Pritsch M, Ziegler R. Frequency and predictors of osteoporotic fractures after cardiac or liver transplantation: a follow-up study. Lancet. 2001;357:342–7.

    Article  CAS  PubMed  Google Scholar 

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Authors and Affiliations

  1. Section of Cardiology, Department of Medicine, University of Minnesota, 420 Delaware St S.E., MMC 508, Minneapolis, MN, 55455, USA

    Khalil Murad MD, MS

  2. Cardiovascular Division, University of Michigan, 1500 East Medical Drive, Ann Arbor, MI, 48109, USA

    Monica M. Colvin MD, MS

Authors
  1. Khalil Murad MD, MS
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  2. Monica M. Colvin MD, MS
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Correspondence to Khalil Murad MD, MS .

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Editors and Affiliations

  1. Lillehei Heart Institute, Department of Medicine, University of Minnesota Medical Center, University of Minnesota, Minneapolis, Minnesota, USA

    Daniel J. Garry

  2. Division of Cardiovascular Medicine, University of Minnesota, Minneapolis, Minnesota, USA

    Robert F. Wilson

  3. Division of Cardiovascular Medicine, University of Minnesota, Minneapolis, Minnesota, USA

    Zeev Vlodaver

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Murad, K., Colvin, M.M. (2017). Late Complications Following Heart Transplant. In: Garry, D., Wilson, R., Vlodaver, Z. (eds) Congestive Heart Failure and Cardiac Transplantation. Springer, Cham. https://doi.org/10.1007/978-3-319-44577-9_31

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  • DOI: https://doi.org/10.1007/978-3-319-44577-9_31

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