Problems and limitations of cardiac transplantation A. Rukosujew, S. Klotz, H.H. Scheld Westfälische Willhelms -Universität Münster Klinik und Poliklinik für Thorax-, Herz- und Gefäßchirurgie

Cancer End-stage Heart Failure Prognosis* Problems and limitations of cardiac transplantation Survival *Harrison‘s Principles of Internal Medicine (14th Edition) 1998

Problems and limitations of cardiac transplantation Progressive improvement in survival* *Hunt SA, Haddad F JACC 2008;52: In terms of days or weeks over 3 decades 10 In excess of 10 years

Eurotransplant Problems and limitations of cardiac transplantation Tolerance of ischemia 4 h Transport time< 2,5 h Explant radius > 1000 km

Problems and limitations of cardiac transplantation Organ donation in Europa/Germany

International organ donation Problems and limitations of cardiac transplantation

Top 10 Problems and limitations of cardiac transplantation : 377 transplantations in Germany

Donor shortage I Problems and limitations of cardiac transplantation 29%

Donor shortage II Problems and limitations of cardiac transplantation Eurotransplant waiting list

Biatrial technique Biatrial technique* Problems and limitations of cardiac transplantation * Lower RR, Shumway NE Surg Forum 1960;11:18-19

Bicaval technique* Problems and limitations of cardiac transplantation * Sievers HH et al Thorac Cardiovasc Surg 1991;39:70-72

Total orthotopic technique* Problems and limitations of cardiac transplantation Total orthotopic HTX by W.P. Demichow in 1951 * Dreyfus G et al Ann Thorac Surg 1991;52:1181-4

Survival after HTX* Problems and limitations of cardiac transplantation HTX (UKM) 396 *1990 – oHTX in Muenster

After HTX I Problems and limitations of cardiac transplantation Rejection Infection Corticosteriods Cyclosporine Tacrolimus Azathioprine Mycophenolic acid Sirolimus Hypertension Hyperlipidemia Renal failure Osteoporosis Diabetes mellitus Malignant tumours Graft vasculopathy Graft vasculopathy host-graft adaptation

After HTX II Problems and limitations of cardiac transplantation

Day-to-day problems Problems and limitations of cardiac transplantation Crowded gathering Plants Domestic animals Transport facilities

Immunosuppression I Problems and limitations of cardiac transplantation Goal: to prevent or treat rejection minimizing the risk of infection or cancer 6-Mercaptopurin Azathioprine Ciclosporine OKT3 Tacrolimus Mycophenolate mofetil (MMF) Basiliximab/daclizumab Sirolimus Na-Mycophenolate (EC-MPS) Everolimus

Immunosuppressive agents Problems and limitations of cardiac transplantation Calcineurin inhibitorsCyclosporine Tacrolimus Purine synthesis inhibitorsMycophenolate mofetil Azathioprine Proliferation signal inhibitorsSirolimus Everolimus CorticosteroidsPrednisone / Prednisolone Polyclonal antibodiesAntithymocyte globulin Antilymphocyte globulin Monoclonal antibodiesRituximab Daclizumab / Basiliximab

Immunosuppression II Problems and limitations of cardiac transplantation Dual therapy  CsA + Steroids  Tac + Steroids  CsA + polyklonal antibodies Triple therapy  CsA + Aza + Steroids  CsA + EC-MPS + Steroids  CsA/Tac + MMF + Steroids  Basiliximab + CsA + Steroids  CsA + Everolimus + Steroids Quadruple therapy  CsA + Aza + Ster. + OKT3  CsA + Sirolimus + MMF + Ster.  CsA + Everolimus + MMF + Ster. 200 There are more then 200 maintenance regimens & methods for rejection managing

Immunosuppression III Problems and limitations of cardiac transplantation

Quality of life I Problems and limitations of cardiac transplantation

Quality of life Problems and limitations of cardiac transplantation

Summary Heart transplantation not be planned (waiting time) donor shortage hypothermic organ preservation (reperfusion injury) side effects of immunsuppression (infection, tumour) better quality and length of life improved monitoring of rejection development of better immunosuppresive regimens