Opinion statement
Heart transplantation is the preferred therapy for patients with end-stage heart failure with refractory symptoms despite optimal medical and device therapy. The major impediment to survival is rejection and infection in the short term and cardiac allograft vasculopathy and malignancy in the long term. Current therapies are focused on the prevention and treatment of rejection and limiting the long-term problems of cardiac allograft vasculopathy and malignancy. Advances in monitoring assays now allow better assessment of rejection and the level of immune response. This will allow clinicians, in the future, to tailor current therapies to the needs of individual heart transplant recipients to maximize benefit and minimize toxicity.
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McMurray JJ. Clinical practice. Systolic heart failure. N Engl J Med. 2010;362:228–38.
Costanzo MR, Costanzo MR, Dipchand A, et al. The International Society of Heart and Lung Transplantation Guidelines for the care of heart transplant recipients. J Heart Lung Transplant. 2010;29:914–56. These guidelines are a comprehensive reference and resource on the management of heart transplant recipients.
Stehlik J, Edwards LB, Kucheryavaya AY, et al. The Registry of the International Society for Heart and Lung Transplantation: twenty-seventh official adult heart transplant report–2010. J Heart Lung Transplant. 2010;29:1089–103.
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.
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;30:252–69. This is a summary of the current state of the art on the diagnosis and treatment of antibody-mediated rejection based on the consensus of experts in the field.
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.
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;25:1277–82.
Deng MC, Eisen HJ, Mehra MR, et al. Noninvasive discrimination of rejection in cardiac allograft recipients using gene expression profiling. Am J Transplant. 2006;6:150–60.
Pham MX, Teuteberg JJ, Kfoury AG, et al. Gene-expression profiling for rejection surveillance after cardiac transplantation. N Engl J Med. 2010;362:1890–900. This was the first trial of the use of the AlloMap gene expression profile to detect rejection in heart transplant recipients.
Kowalski R, Post D, Schneider MC, et al. Immune cell function testing: an adjunct to therapeutic drug monitoring in transplant patient management. Clin Transplant. 2003;17:77–88.
Kowalski RJ, Post DR, Mannon RB, et al. Assessing relative risks of infection and rejection: a meta-analysis using an immune function assay. Transplantation. 2006;82:663–8.
Kobashigawa JA, Kiyosaki KK, Patel JK, et al. Benefit of immune monitoring in heart transplant patients using ATP production in activated lymphocytes. J Heart Lung Transplant. 2011;29:504–8. This is one of the largest studies to date in heart transplant recipients examining the utility of the Cylex blood test in the detection of subsequent infection and rejection.
Saraiva F, Matos V, Goncalves L, et al. Complications of endomyocardial biopsy in heart transplant patients: a retrospective study of 2117 consecutive procedures. Transplant Proc. 2011;43:1908–12.
Baraldi-Junkins C, Levin HR, Kasper EK, et al. Complications of endomyocardial biopsy in heart transplant patients. J Heart Lung Transplant. 1993;12:63–7.
Evans RW, Williams GE, Baron HM, et al. The economic implications of noninvasive molecular testing for cardiac allograft rejection. Am J Transplant. 2005;5:1553–8.
Kobashigawa JA, Miller LW, Russell SD, et al. 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.
Mathew T, Kreis H, Friend P. Two-year incidence of malignancy in sirolimus-treated renal transplant recipients: results from five multicenter studies*. Clin Transplant. 2004;18:446–9.
Campistol JM, Eris J, Oberbauer R, et al. Sirolimus therapy after early cyclosporine withdrawal reduces the risk for cancer in adult renal transplantation. 2006. p. 581–589.
Salgo R, Gossmann J, Schöfer H, et al. Switch to a sirolimus-based immunosuppression in long-term renal transplant recipients: reduced rate of (pre-)malignancies and nonmelanoma skin cancer in a prospective, randomized, assessor-blinded, controlled clinical trial. Am J Transplant. 2010;10:1385–93.
Jensen P, Hansen S, Moller B, et al. Skin cancer in kidney and heart transplant recipients and different long-term immunosuppressive therapy regimens. J Am Acad Dermatol. 1999;40:177–86.
Dantal J, Soulillou JP. Immunosuppressive drugs and the risk of cancer after organ transplantation. N Engl J Med. 2005;352:1371–3.
Caforio ALP, Fortina AB, Piaserico S, et al. Skin cancer in heart transplant recipients : risk factor analysis and relevance of immunosuppressive therapy. 2000. p. III–222–III–227.
Eisen HJ, Tuzcu EM, Dorent R, et al. Everolimus for the prevention of allograft rejection and vasculopathy in cardiac-transplant recipients. N Engl J Med. 2003;349:847–58.
Keogh A, Richardson M, Ruygrok P, et al. Sirolimus in de novo heart transplant recipients reduces acute rejection and prevents coronary artery disease at 2 years: a randomized clinical trial. Circulation. 2004;110:2694–700.
Kobashigawa JA, Patel J, Furukawa H, et al. Five-year results of a randomized, single-center study of tacrolimus vs microemulsion cyclosporine in heart transplant patients. J Heart Lung Transplant. 2006;25:434–9.
Eisen HJ, Kobashigawa J, Keogh A, et al. Three-year results of a randomized, double-blind, controlled trial of mycophenolate mofetil versus azathioprine in cardiac transplant recipients. J Heart Lung Transplant. 2005;24:517–25.
Hershberger RE, Starling RC, Eisen HJ, et al. Daclizumab to prevent rejection after cardiac transplantation. 2005. p. 2705–2713.
Gaber AO, First MR, Tesi RJ, et al. Results of the double-blind, randomized, multicenter, phase III clinical trial of Thymoglobulin versus Atgam in the treatment of acute graft rejection episodes after renal transplantation. Transplantation. 1998;66:29–37.
Kobashigawa JA, Stevenson LW, Moriguchi JD, et al. Is intravenous glucocorticoid therapy better than an oral regimen for asymptomatic cardiac rejection? A randomized trial. J Am Coll Cardiol. 1993;21:1142–4.
Mancini D, Pinney S, Burkhoff D, et al. Use of rapamycin slows progression of cardiac transplantation vasculopathy. Circulation. 2003;108:48–53.
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;78:814–20.
Fishbein MC, Kobashigawa J. Biopsy-negative cardiac transplant rejection: etiology, diagnosis, and therapy. Curr Opin Cardiol. 2004;19:166–9.
Vo AA, Lukovsky M, Toyoda M, et al. Rituximab and intravenous immune globulin for desensitization during renal transplantation. N Engl J Med. 2008;359:242–51.
Patel JK, Kittleson M, Kobashigawa JA. Cardiac allograft rejection. Surgeon. 2011;9:160–7.
Barr ML, Meiser BM, Eisen HJ, et al. Photopheresis for the prevention of rejection in cardiac transplantation. Photopheresis Transplantation Study Group. N Engl J Med. 1998;339:1744–51.
Kirklin JK, Brown RN, Huang ST, et al. Rejection with hemodynamic compromise: objective evidence for efficacy of photopheresis. J Heart Lung Transplant. 2006;25:283–8.
Kobashigawa J, Mehra M, West L, et al. Report from a consensus conference on the sensitized patient awaiting heart transplantation. J Heart Lung Transplant. 2009;28:213–25. This is a summary of the current state of the-art on the diagnosis and management of sensitized heart transplant candidates based on the consensus of experts in the field.
Patel J, Everly M, Chang D, et al. Reduction of alloantibodies via proteosome inhibition in cardiac transplantation. J Heart Lung Transplant. 2011;30:1320–6.
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Kittleson, M.M. New Issues in Heart Transplantation for Heart Failure. Curr Treat Options Cardio Med 14, 356–369 (2012). https://doi.org/10.1007/s11936-012-0184-7
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DOI: https://doi.org/10.1007/s11936-012-0184-7