Heart transplantation: current practice and outlook to the future
QUESTIONS UNDER STUDY: The field of heart transplantation has seen substantial progress in the last 40 years. The breakthroughs in long-term survival were followed by a period of stagnation in the last decade. This review summarises current recommendations for the identification of candidates for heart transplantation and their immunological and non-immunological postoperative follow-up.
RESULTS: The progress made in the treatment of patients with advanced heart failure has considerably changed the profile of candidates for heart transplantation. Patients are older, and the load of co-morbidities is more important requiring careful evaluation for candidacy.
Long-standing research in the field of immunosuppression made available various drugs, which decrease the risk of acute allograft rejection and prolong survival after heart transplantation. Powerful new molecules are entering early phase clinical studies, suggesting further improvement in the near future. As a consequence, treatment of non-immunological co-morbidity after heart transplantation will gain in importance, however, the base of evidence guiding current recommendations is poor.
CONCLUSIONS: The substantial progress in heart failure treatment and immunosuppression after heart transplantation has changed the profile of heart transplant recipients. The arrival of new molecules will provide additional alternatives for immunosuppressive treatment while studies have to address non-immunological treatment in order to improve long-term survival after heart transplantation.
- Stehlik J, Edwards LB, Kucheryavaya AY, Aurora P, Christie JD, Kirk R, et al. The registry of the International Society of Heart and Lung transplantation: twenty-seventh official adult heart transplant report-2010. J Heart Lung Transplant. 2011;29:1089–103.
- Jessup M, Abraham WT, Casey DE, Feldman AM, Francis GS, Ganiats TG, et al. 2009 focused update: ACCF/AHA guidelines for the diagnosis and management of heart failure in adulta: a report from the American College of Cardiology/American Heart Association Task Force on practice guidelines: developed in collaboration with the international Society for Heart and Lung Transplantation. Circulation. 2009;119:1977–2016.
- Banner NR, Bonser RS, Clark AL, Clark S, Cowburn PJ, Gardner RS, et al. UK guidelines for referral and assessment of adults for heart transplantation. Heart. 2011;97:1520–2.
- Hillege HL, Nitsch D, Pfeffer MA, Swedberg K, McMurray JJ, Yusuf S, et al. Renal function as a predictor of outcome in a broad spectrum of patients with heart failure. Circulation. 2006;113:671–8.
- Ganesh JS, Rogers CA, Banner NR, Bonser RS, Steering Group of the UK Cardiothoracic Transplant Audit. Development and validation of a model to predict perioperative mortality following heart transplantation in the UK. J Heart Lung Transplant. 2004;23(2 suppl):S118–9.
- Mehra MR, Kobashigawa J, Starling R, Russell S, Uber PA, Parameshwar J, et al. Listing criteria for heart transplantation: International Society of Heart and Lung Transplantation guidelines for care of cardiac transplant cadidates-2006. J Heart Lung Transplant. 2006;25:1024–42.
- Allen LA, Felker GM, Pocock S, McMurray JJ, Pfeffer MA, Swedberg K, et al. Liver function abnormalities and outcome in patients chronic heart failure: data from the Candesartan in heart failure: Assessment of mortality and morbidity in the CHARM program. Eur J Heart Fail. 2009;1:170–7.
- Torre Amione G, Southard RE, Loebe MM, Youker KA, Bruckner B, Estep JP, et al. Reversal of secondary pulmonary hypertension by axial and pulsatile mechanical circulatory support. J Heart Lung Transplant. 2010;29:195–200.
- Organ Procurement and Transplantation Network (OPTN) and Scientific Registry of Transplant Recipients (SRTR). OPTN / SRTR 2010 Annual Data Report. Rockwell MD: Department of Health and Human Services, Health Resources and Services Administration. Healthcare Systems Bureau, Division of Transplantation: 2011:89–106.
- Singh TP, Almond CS, Taylor DO, Graham DA. Decline in heart transplant wait list mortality in the United States following broader sharing of donor hearts. Circ Heart Fail. 2012;5:249–58.
- Swisstransplant Jahresbericht 2005; page 30.
- Swisstransplant Jahresbericht 2012; page 12
- Costanzo MR. The International Society of Heart and Lung Transplantation Guidelines for the care of heart transplant recipients. J Heart Lung Transplant. 2010;29:114–56.
- Keogh A, Richardson RM, Rugyrok P, Spratt P, Galbraith A, O’Driscoll G, et al. Sirolimus in de novo heart transplant recipients reduces acute rejection and prevents coronary artery disease at 2 years: a randomized controlled trial. Circulation. 2004;110:2694–700.
- Eisen HJ, Tuczu EM, Dorent R, Kobashigawa J, Mancini D, Valentine-von Kaeppler HA, et al. Everolimus for the prevention of allograft rejection and vasculopathy in cardiac transplant recipients. N Engl J Med. 2003;349:847–58.
- Eisen HJ, Kobashigawa J, Startling RC, Pauly DF, Kfoury A, Ross H, et al. Everolimus vs. myocophenolate mofetil in heart transplantation: a randomized, multicenter trial. Am J Transplant. 2013;13:1206–13.
- Zuckermann A, Wang SS, Ross H, Frigerio M, Eisen HJ, Bara C, et al. Impact of de novo everolimus based immunosuppression on incisional complications after heart transplantation. Transplantation. 2011;92:594–600.
- Kushwaha SS, Kalpey Z, Frantz RP, Rodeheffer RJ, Clavell AL, Daly RC, et al. Sirolimus in cardiac transplantation: use as a primary immunosuppressant in calcineurin inhibitor-induced nephrotoxicity. J Heart Lung Transplant. 2005;24:2129–36.
- Topilsky Y, Hasin T, Raichlin E, Boilson BA, Schirger JA, Pereira NL, et al. Sirolimus as primary immunosuppression attenuates allograft vasculopathy with improved survival and decreased cardiac events after cardiac transplantation. Circulation. 2012;125:708–20.
- Kauffman HM, Cherikh WS, Cheng Y, Hanto DW, Kahan BD. Maintenance immunosuppression with target-of-rapamycin inhibitors is associated with a reduced incidence of de novo malignancies. Transplantation. 2005;80:883–9.
- Rubio-Viquera B, Hidalgo M. Targeting mTOR for cancer treatment. Adv Exp Med Biol. 2006;587:309–27.
- Shah MR, Starling RC, Schwartz Longacre L, Mehra MR, on behalf of the working groups participants. Heart transplantation research in the next decade-a goal to achieving evidence-based outcomes. J Am Coll Cardiol. 2012;59:1263–9.
- Halloran PF. Immunosuppressive drugs for kidney transplantation. N Engl J Med. 2004;351:2715–29.
- Fontenot JD, Gavin MA, Rudensky AY. FoxP3 programs the development of and function of CD41CD251 regulatory T cells. Nat Immunol. 2003;3:330–6.
- Wood KJ, Sakaguchi S. Regulatory T cells in transplantation tolerance. Nat Rev Immunol. 2003;3:199–210.
- Mauri C, Blair PA. Regulatory B cells in autoimmunity: developments and controversies. Nat Rev Rheumatol. 2010;6:636–43.
- Fehr T, Sykes M. Clinical experience with mixed chimerism to induce transplantation tolerance. Transplant Int. 2008;21:1118–35.
- National Institute of Health. Bone marrow transplant to induce tolerance in heart transplant recipients. Available at: http://clinicaltrials.gov/ct2/show/NCT00497757. Accessed 2013.
- Kokko KE, Newell KA, Pearson TC, Larsen CP. Enhanced immunosuppression enhanced by cytotoxic T lymphocyte antigen-4 immunoglobulin. Curr Opin Organ Transplant. 2005;10:265–9.
- Archdeacon P, Dixon C, Belen O, Albrecht R, Meyer J. Summary of the US FDA approval of betalacept. Am J Transplant. 2012;12:554–62.
- Kobashigawa JA. The future of heart transplantation. Am J Transplant. 2012;12:2875–91.
- 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.
- National institute of Allergy and Infectious Diseases. Prevention of cardiac allograft vasculopathy using rituximab (rituxan) therapy in cardiac transplantation. Available at: http://clinicaltrials.gov/ct2/show/NCT01278745. Accessed 12/2013.
- Patel J, Everly M, Chang D, Kittleson M, Reed E, Kobashigawa J. Reduction of alloantibodies via proteasome inhibition in cardiac transplantation. J Heart Lung Transplant. 2011;30:1320–6.
- Locke E, Magro CM, Singer AL, Segev DL, Haas M, Hillel AT, et al. The use of antibody to complement protein C5 for salvage treatment of severe antibody-mediated rejection. Am J Transplant. 2009;9:231–5.
- Pinderski LJ, Kirklin JK, McGiffin KD, Brown D, Naftel DC, Young KR, et al. Multi-organ transplantation: is there a protective effect against acute and chronic rejection? J Heart Lung Transplant. 2005;24:1828–33.
- Bloom RD, Doyle AM. Kidney disease after heart and lung transplantation. Am J Transplant. 2006;6:671–9.
- Fröhlich GM, Rufibach K, Enseleit F, Wolfrum M, von Babo M, Frank M, et al. Statins and the risk of cancer after heart transplantation. Circulation. 2012;126:440–7.
- Nakleh RE, Jones J, Goswitz JJ, Anderson EA, Titus J. Correlation of endomyocardial biopsy findings with autopsy findings in human cardiac allografts. J Heart Lung Transplant. 1992;11:479–85.
- Rossano JW, Denfield SW, Kim JJ, Price JF, Jefferies JL, Decker JA, et al. Assessment of the Cylex ImmuKnow cell function assay in pediatric heart transplant recipients. J Heart Lung Transplant. 2009;28:26–31.
- Pham MX, Teuteberg JJ, Kfoury AG, Starling RC, Deng MC, Cappola TP, et al. Gene expression profiling for rejection surveillance after cardiac transplantation. N Engl J Med. 2010;310:1890–900.
- 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.
- 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 Mag Res. 2009;11:7–18.
- van Heeswijk RB, Feliciano H, Bonanno G, Coppo S, Lauriers N, Locca D, et al. Quantitative Free-Breathing 3T T2–mapping of the heart designed for longitudinal Studies. J Cardiovasc Magn Reson. 2012,14(Suppl 1):O14.