Presentation is loading. Please wait.

Presentation is loading. Please wait.

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

Similar presentations


Presentation on theme: "Compassionate Allowances Outreach Hearing on Cardiovascular Disease and Multiple Organ Transplants Clive O. Callender, M.D., FACS November 9, 2010 Clive."— Presentation transcript:

1 Compassionate Allowances Outreach Hearing on Cardiovascular Disease and Multiple Organ Transplants Clive O. Callender, M.D., FACS November 9, 2010 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 ObjectiveObjective Current Status of Heart Transplantation

6 Growth in Number of Transplanted Organs Source: 2005 OPTN/SRTR Organs End of Year Percent Change Total 25,083 26, % Kidney 14,856 15, % –Deceased donor 8,388 9, % –Living donor 6,468 6, % PTA % PAK % Kidney-pancreas % Liver 5,364 5, % –Deceased donor 5,043 5, % –Living donor % Intestine % Heart 2,026 1, % Lung 1,080 1, % Heart-lung % Organs End of Year Percent Change Total 25,083 26, % Kidney 14,856 15, % –Deceased donor 8,388 9, % –Living donor 6,468 6, % PTA % PAK % Kidney-pancreas % Liver 5,364 5, % –Deceased donor 5,043 5, % –Living donor % Intestine % Heart 2,026 1, % Lung 1,080 1, % Heart-lung %

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, PAK K-P879 2,410 Liver 6,4055,780 (5,457)17,133 Intestine Heart 2,096 1,9613,237 Lung 1,973 1,168 3,852 Heart-lung Source: 2005 OPTN/SRTR Annual Report, Recovered Transplanted Waiting List Total 25,237 26,539 86,378 Kidney 12,575 15,671 (9,025) 57,910 PTA 2, PAK K-P879 2,410 Liver 6,4055,780 (5,457)17,133 Intestine Heart 2,096 1,9613,237 Lung 1,973 1,168 3,852 Heart-lung Source: 2005 OPTN/SRTR Annual Report,

8 Graft Survival Follow-up Period 1 Year 10 Years Tx Tx 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% Follow-up Period 1 Year 10 Years Tx Tx 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 3 rd December 1967 Nearly 40 years and 70,000 transplants

10

11 Orthotopic Implantation Positioning of donor heart Creation of left atrial anastomosis Positioning of donor heart Creation of left atrial anastomosis

12 Orthotopic Implantation Completion of right atrial anastomosis (standard technique)

13 Aortic anastomosis Pulmonary artery anastomosis Aortic anastomosis Pulmonary artery anastomosis Orthotopic Implantation

14 Completed transplant Pacing wires on donor portion of right atrium and ventricle Pericardium left open Completed transplant Pacing wires on donor portion of right atrium and ventricle Pericardium left open

15 15

16 ISHLT/UNOS Registry Database Number of Transplants Performed ISHLT 2003 J Heart Lung Transplant 2003; 22: Organ Transplants reported through 2001 Heart61,533 Heart- Lung 2,935 Lung14,588

17 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 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.

18 18

19 19

20 20

21 21

22 22

23 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) 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)

24 Immunosuppression Management During Maintenance Phase LowBreakthrough rejection HighInfectionsMalignancies Therapeutic Nephrotoxicit y Hypertension Diabetes Neurotoxicity % % % %

25 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) 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)

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

27 Major Post Transplant Complications Rejection Infection Cardiac allograft vasculopathy (CAV) Hypertension Nephrotoxicity Malignancy Rejection Infection Cardiac allograft vasculopathy (CAV) Hypertension Nephrotoxicity Malignancy

28 RejectionRejection Invasive surveillance biopsies are the best established method for following patients Typically 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

29

30 R = Revised Stewart S, et al. JHLT 2005 in press Treatment required Acute Cellular Rejection 2004 proposed grade1990 ISHLT 0No rejection 1 RMildCombines former 1A, 1B, and 2 2 RModerateFormer 3A 3 RSevereFormer 3B and 4

31 Incidence of BPR in Randomized Heart Transplant Immunosuppression Trials Trial 1st year published 1st year % patients with BPR Tac vs CSA (European) (n = 54; n = 28) % vs 81.5% p = (1yr) MMF vs Aza (n = 289; n = 289) % vs 52.9% p = (1yr) Tac vs CSA (US) (n = 39; n = 46) % vs 44% p = (6 mo) Neoral vs Sandimune (n = 188; n = 192) % vs 41.7% p = ns (6 mo)

32 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 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

33 RejectionRejection 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 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

34 Specific Causes of Death One Year After Cardiac Transplantation Kirklin JK, et al. J Thorac Cardiovasc Surg 2003; 125: Time after transplant (years) CRTD: , n = Deaths / year Rejection Infection Non-specific graft failure Neurologic Sudden Malignancy Allograft CAD

35 Long Term Challenges Renal failure and metabolic adverse effects Cardiac allograft vasculopathy Malignancy Renal failure and metabolic adverse effects Cardiac allograft vasculopathy Malignancy

36 Post-Heart Transplant Morbidity For Adults Cumulative Incidence for Survivors (Apr,94 - Dec00) OutcomeBy 1 yearBy 5 years Hypertension72,4% (N = 12,496)95.1% (N = 3,465) Renal functionN = 12,511N = 3,776 Normal74.8%69.1% Renal dysfunction14.9%17.6% Creatinine > 2.5 mg/dL9.0%10.4% Chronic dialysis1.2%2.5% Renal transplant0.2%0.4% Hyperlipidemia48.7% (N = 13,183)81.3% (N = 3,899) Diabetes24.1% (N = 12,487)32.0% (N = 3,444) CAV8.2% (N = 11,260)33.2% (N = 2,376) ISHLT

37 37

38 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 = –p < Ojo AO et al. N Engl J Med 2003; 349: Time since transplantation (months) Cumulative incidence of CRF Intestine Live r Lung Heart Heart - lung

39 39

40 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 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

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

42 Maximal Intimal Thickening Predicts 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: Early Mid Late Normal Severe Abnormal Low High Moderate Risk of cardiac event Post- transplant time “Prognostically relevant” - High plaque burden - Link with cardiac events

43 43

44 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 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):

45 Effects on Human Tumor Cell Growth Growth inhibition (%) Hepatic cancerColorectal cancerMyelodysplasia Casadio F. Transplant Proc 2005; 37:2144.

46 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 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


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

Similar presentations


Ads by Google