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Heart Transplantation: Current Status and Growth in Number of Transplanted Organs

This article discusses the current status of heart transplantation and the growth in the number of transplanted organs. It covers topics such as the history of heart transplantation, immunosuppression management, major post-transplant complications, and treatment of rejection.

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Heart Transplantation: Current Status and Growth in Number of Transplanted Organs

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  1. Compassionate Allowances Outreach Hearing on Cardiovascular Disease and Multiple Organ Transplants Clive O. Callender, M.D., FACS November 9, 2010

  2. Howard University Hospital Transplantation Services“Heart Transplantation”

  3. El Centro de Transplantes de Howard University Hospital In 1973, Dr. Callender developed the first minority oriented transplant center in this country. National Minority Organ Tissue Transplant Education Program Founder (MOTTEP®)

  4. Waiting list candidates 109,100 as of today 4:24pm

  5. Objective • Current Status of Heart Transplantation

  6. Growth in Number of Transplanted OrgansSource: 2005 OPTN/SRTR • Organs End of Year Percent Change • 2003 2004 • Total 25,083 26,539 5.8% • Kidney 14,856 15,671 5.5% • Deceased donor 8,388 9,025 7.6% • Living donor 6,468 6,646 2.8% • PTA 117 132 12.8% • PAK 343 418 21.9% • Kidney-pancreas 868 879 1.3% • Liver 5,364 5,780 7.8% • Deceased donor 5,043 5,457 8.2% • Living donor 321 323 0.6% • Intestine 52 52 0.0% • Heart 2,026 1,961 -3.2% • Lung 1,080 1,168 8.1% • Heart-lung 28 37 32.1%

  7. No of Transplanted Organs vs Waiting List 2004 Recovered Transplanted Waiting List • Total 25,237 26,539 86,378 • Kidney 12,575 15,671 (9,025) 57,910 • PTA 2,021 132 504 • PAK 418 973 • K-P 879 2,410 • Liver 6,405 5,780 (5,457) 17,133 • Intestine 167 52 196 • Heart 2,096 1,961 3,237 • Lung 1,973 1,168 3,852 • Heart-lung 37 171 • Source: 2005 OPTN/SRTR Annual Report,

  8. Graft Survival Follow-up Period 1 Year 10 Years Tx 2002-2003 Tx 1993-2003 Kidney Deceased Donor • Graft Survival 89.0% 40.5% • Patient Survival 94.6% 60.7% Kidney: Living Donor • Graft Survival 95.1% 56.4% • Patient Survival 97.9% 76.4% Kidney-Pancreas Kidney Graft Survival 91.7% 52.5% Pancreas Graft Survival 85.8% 53.6% Liver Deceased Donor • Graft Survival 82.2% 52.5% • Patient Survival 81.7% 67.0% Intestine Graft Survival 73.8% 22.0% Heart Graft Survival 86.8% 51.1% Lung Graft Survival 81.4% 22.1% Heart-Lung Graft Survival 55.8% 24.6% UNOS/SRTR, 2003

  9. The History Of Heart Transplantation 3rd December 1967 Nearly 40 years and 70,000 transplants

  10. Orthotopic Implantation • Positioning of donor heart • Creation of left atrial anastomosis

  11. Orthotopic Implantation • Completion of right atrial anastomosis (standard technique)

  12. Orthotopic Implantation • Aortic anastomosis • Pulmonary artery anastomosis

  13. Orthotopic Implantation • Completed transplant • Pacing wires on donor portion of right atrium and ventricle • Pericardium left open

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  15. ISHLT/UNOS Registry DatabaseNumber of Transplants Performed ISHLT 2003 J Heart Lung Transplant 2003; 22: 610-72.

  16. Current Trends In Transplant Candidacy • Older patients, > 65 years of age • Generally sicker at time of transplant (Emergent (status 1A) or urgent transplants (status 1B) more common) • More women (typically older at time of listing) • More patients on mechanical circulatory devices 2004 OPTN/SRTR annual report.

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  22. Heart Transplantation • Although NEVER subjected to a randomized control trial, heart transplantation is the ONLY therapy for advanced heart failure observationally associated with an excellent survival • Advances in close follow-up and newer immunosuppression have led to improvement in 1 year survival close to 90% • The problem is in survival beyond 1 year which is still limited (70% at 3 to 5 years, 50% at 10 years)

  23. Immunosuppression Management During Maintenance Phase

  24. Common Immunosuppressive Regimen in 2005 • Primary: cyclosporine / tacrolimus(utilized in conjuction with therapeutic drug monitoring) • Adjunctive: mycophenolate mofetil • Supportive: prednisone (only 20 to 30% centers wean prednisone off if possible) • Additive: statins (shown to be immunomodulatory and associated with improved long term survival)

  25. Trends in Maintenance Immunosuppression Prior to Discharge for Heart Transplantation, 1995-2004 Source: 2005OPTN/SRTR Annual Report.

  26. Major Post Transplant Complications • Rejection • Infection • Cardiac allograft vasculopathy (CAV) • Hypertension • Nephrotoxicity • Malignancy

  27. Rejection • Invasive surveillance biopsies are the best established method for following patients • Typically 13-15 biopsies are done in the first year • Each biopsy requires a minimum of 3 samples from 3 different sites to be meaningful • A new biopsy grading has been developed for widespread adoption

  28. Acute Cellular Rejection Treatment required R = Revised Stewart S, et al. JHLT 2005 in press

  29. Incidence of BPR in Randomized Heart Transplant Immunosuppression Trials

  30. Treatment of Rejection • Rejection without hemodynamic compromise • Oral prednisone (100 mg daily for 3 days) • IV steroids • Decision dependent on grading severity and time post transplantation • Steroid resistant rejection with or without hemodynamic compromise • Cytolytic antibodies; IVIG; plasmapheresis; photopheresis; anti-B cell antibodies; rapamycin; methotrexate; cyclophosphamide; total lymphoid irradiation

  31. Rejection • Cellular rejection remains an important issue despite the incidence having declined over the past two decades • Antibody mediated rejection is now recognized as an important entity but has not been previously standardized therefore not uniformly incorporated in trials of immunosuppressive therapy or investigations pertaining to transplantation

  32. Specific Causes of Death One Year After Cardiac Transplantation CRTD: 1990-1999, n = 7290 Rejection Infection Non-specific graft failure Neurologic Sudden 0.025 Malignancy 0.020 0.015 Allograft CAD Deaths / year 0.010 0.005 0.000 7 3 8 1 4 10 6 9 2 5 Time after transplant (years) Kirklin JK, et al. J Thorac Cardiovasc Surg 2003; 125:881-90.

  33. Long Term Challenges • Renal failure and metabolic adverse effects • Cardiac allograft vasculopathy • Malignancy

  34. Post-Heart Transplant Morbidity For AdultsCumulative Incidence for Survivors (Apr,94 - Dec00) ISHLT

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  36. 0.35 0.30 0.25 0.20 0.15 0.10 0.05 0.00 Renal Function in Transplantation • CRF developed in 16.5% • Of these, 28.9% required maintenance dialysis or renal transplantation • CRF significantly associated with increased risk of death • Relative risk = 4.55 • 95% CI = 4.38 - 4.74 • p < 0.001 Liver Intestine Lung Cumulative incidence of CRF Heart Heart- lung 0 12 24 36 48 60 72 84 96 108 120 Time since transplantation (months) Ojo AO et al. N Engl J Med 2003; 349:931-40.

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  38. The Problem Of Cardiac Allograft Vasculopathy • Cardiac allograft vasculopathy (CAV) is the leading cause of death in cardiac transplant recipients at 5 years post-transplant, accounting for up to 30% of deaths • CAV is characterized by a proliferation of the allograft vascular intima, resulting in narrowing of the vascular lumen • Due to the lack of premonitory signs, CAV often presents as sudden death, silent myocardial infarction or severe arrhythmia

  39. Platelets Immune Factors Cellular Rejection score Antibody –mediated rejection Balance of Immunosuppression PDGF, FGF, IGF TGF-ß, TNF, IL-1 T-lymphocyte Macrophage SMC EC Denuding injury INFLAMMATION Nondenuding injury MHC-II NonImmune factors Mode of Brain Death Ischemia Reperfusion injury Hyperlipidemia Hypertension CMV infection Donor age ICAM,VCAM selectins IL-1, IL-2, IL-6, TNF PDGF, FGF, IGF, TGF-ß Mehra MR. AJT 2006 (in press)

  40. Risk of cardiac event Low Moderate High Late Post-transplant time Mid Early 0 0.35 0.50 1.00 Normal Abnormal Severe Maximal Intimal Thickening Predicts Cardiac Events “Prognostically relevant” - High plaque burden - Link with cardiac events Intimal thickening (mm) Mehra M et al. J Heart Lung Transplant 1995; 14:S207-11; Kobashigawa JA et al. J Am Coll Cardiol 2005; 45:1532-7; Tuzcu EM et al. J Am Coll Cardiol 2005; 45:1538-42.

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  42. Areas of Current Uncertainty and Future Research Regarding Malignancies in Heart Transplantation • Relationship between different immunosuppressants and cancer risk • Relationship between duration and intensity of immunosuppression and cancer risk • Efficacy of low or minimal immunosuppression regimens • Frequency of cancer screening • Components of cancer screening Hauptman PJ and Mehra MR. J Heart Lung Transplant. 2005;24(8):1111-3.

  43. Effects on Human Tumor Cell Growth Growth inhibition (%) Hepatic cancer Colorectal cancer Myelodysplasia Casadio F. Transplant Proc 2005; 37:2144.

  44. Heart Transplantation:2005 and Beyond • Need for improved immunosuppression with less rejection, cardiac allograft vasculopathy and side effects • Need for better non-invasive methods to detect acute and chronic rejection • Need to focus on improved survival and quality of life • Challenges in performing long-term adequately powered multi-centered trials

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