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What makes an allograft marginal & Methods of evaluation: Hearts

Papworth Hospital NHS Foundation Trust. NHS. British Transplant Society Congress 2010 Pre-congress Clinical Symposium Tuesday 16 th March 2010. What makes an allograft marginal & Methods of evaluation: Hearts. Steven SL Tsui Director of Transplantation, Papworth Hospital, Cambridge, U.K.

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What makes an allograft marginal & Methods of evaluation: Hearts

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  1. Papworth Hospital NHS Foundation Trust NHS British Transplant Society Congress 2010 Pre-congress Clinical Symposium Tuesday 16th March 2010 What makes an allograft marginal & Methods of evaluation:Hearts Steven SL Tsui Director of Transplantation, Papworth Hospital, Cambridge, U.K.

  2. Papworth Hospital NHS Foundation Trust NHS Heart Transplant 1967 1st successful HTx Standard Donor Criteria 1970 1980 2000 2010 1990 1979 1st successful UK HTx

  3. NUMBER OF HEART TRANSPLANTSREPORTED BY YEAR ISHLT NOTE: This figure includes only the heart transplants that are reported to the ISHLT Transplant Registry. As such, this should not be construed as evidence that the number of hearts transplanted worldwide has declined in recent years. 2008 J Heart Lung Transplant 2008;27: 937-983

  4. Papworth Hospital NHS Foundation Trust NHS Heart Transplant 1967 1st successful HTx Standard Donor Criteria 1970 1980 2000 2010 1990 1979 1st successful UK HTx

  5. Papworth Hospital NHS Foundation Trust NHS Heart Transplant Poison Brain Malignancy 1967 1st successful HTx Standard Donor Criteria Longer Ischaemic Times LV Hypertrophy Coronary Disease 1970 1980 2000 2010 1990 1979 1st successful UK HTx Older Donors Valve Repair Hep C +VE NHBD Drug Abuse Cardiac Arrest

  6. Papworth Hospital NHS Foundation Trust NHS Heart Transplant Rates 2006 2009 UK Heart Transplant Rate

  7. Papworth Hospital NHS Foundation Trust NHS Variations in Heart Transplant Rates • Heart donation rate • Yield rate: • 19% to 62% (mean 39%)1 • Donor cause of death • Donor age • Threshold for using marginal organs • Even in the most aggressive program, a significant % of donated hearts are not transplanted 1 1999 survey by Assoc. of Organ Procurement Organizations (AOPO)

  8. Papworth Hospital NHS Foundation Trust NHS ADULT HEART TRANSPLANT RECIPIENTS: Cause of Death (Deaths: January 1992 - June 2006) ISHLT 2008 J Heart Lung Transplant 2008;27: 937-983

  9. Papworth Hospital NHS Foundation Trust NHS A 1994 Definition of Marginal Donor Heart • Definition of High Risk Donor (HRD): • Donor age > 40 yr • High dose inotropes (dopamine > 12 μg.kg-1.min-1 ) • CPR > 5 minutes • Elevated CK-MB • D/R weight ratio < 80% • Wall motion abnormality • Rhythm disturbances • Total ischemic time > 5 hrs • HRD accounted for 38.3% of 188 heart transplants between 1985-92 in Oregon Ott et al. Ann Thorac Surg1994;57:76-82

  10. Papworth Hospital NHS Foundation Trust NHS A 2009 Definition of Marginal Donor Heart • Definition of Marginal Donor: • Donor age > 55 years • cocaine or intravenous drug use • diabetes mellitus • hepatitis C +ve • EF < 45% • D:R weight ratio < 0.7 • UNOS Jan 1999 – Dec 2005: 13,024 heart transplants • Marginal donors, 10.2% of all Heart Tx in USA Russo et al. Ann Thorac Surg 2009;87:1066–71

  11. ADULT HEART TRANSPLANTS (1/2002-6/2006)Relative Risk of 1 Year Mortality with 95% Confidence LimitsDonor Age ISHLT 2008 (N=8,823) J Heart Lung Transplant 2008;27: 937-983

  12. ADULT HEART TRANSPLANTS (1/2002-6/2006)Relative Risk of 1 Year Mortality with 95% Confidence LimitsDonor BMI ISHLT 2008 (N=8,823) J Heart Lung Transplant 2008;27: 937-983

  13. ADULT HEART TRANSPLANTS (1/2002-6/2006)Relative Risk of 1 Year Mortality with 95% Confidence LimitsIschemia Time ISHLT 2008 (N=8,823) J Heart Lung Transplant 2008;27: 937-983

  14. ADULT HEART TRANSPLANTS(1/2002-6/2006) Factors Not Significant for 1 Year Mortality ISHLT 2008 Recipient Factors: Prior malignancy, gender, hospitalized, prior pregnancy, balloon pump, diabetes, PRA Donor Factors: Clinical infection, history of diabetes, gender, history of hypertension, cause of death, history of malignancy Transplant Factors: HLA mismatch, CMV mismatch, prior transplant J Heart Lung Transplant 2008;27: 937-983

  15. Papworth Hospital NHS Foundation Trust NHS Consensus Conference Definition of Marginal Donor Heart • Organs that fail to meet 1 or more of the traditional criteria for an optimal cardiac donor 1 Zaroff et al. Circulation. 2002;106:836-841

  16. Papworth Hospital NHS Foundation Trust NHS Extra Cardiac Factors • Donor age < 55 y.o. • Donor medical history • Recent cardiac arrest • Hep C +ve • Risk of coronary disease: smoking, hypertension, diabetes, lipids • Donor lifestyle • Cocaine use • IV drug abuse • Unprotected sex/multiple partners • Donor/recipient size mismatch

  17. Papworth Hospital NHS Foundation Trust NHS Structural Abnormalities • Coronary artery disease • LV hypertrophy • Valvular abnormality • Congenital lesions • Bicuspid AV • Secundum ASD

  18. Papworth Hospital NHS Foundation Trust NHS Functional Abnormalities • Echocardiogram • EF > 45% • Hemodynamic targets • CVP < 12 mmHg • PCWP < 12 mmHg • MAP > 60 mmHg • C.I. > 2.4 L.min-1.m-2 • SVR 800 – 1200 dyne.sec-1.cm-5 • Dopamine/dobutamine > 10 μg.kg-1.min-1

  19. Papworth Hospital NHS Foundation Trust NHS Donor Heart Assessment • Biochemical • Structural • ECG • Echocardiogram • Coronary angiogram • Functional • Echocardiogram • Invasive monitoring

  20. Papworth Hospital NHS Foundation Trust NHS Biochemical Markers • CK-MB • Troponin • Anderson et al. Transplantation. 1994;58:1056-57 • Vijay et al. Ann Thorac Surg. 1998;66:1934-39 • Pro-calcitonin • Venkateswaran et al. Transplantation. 2009;88:582-8 • TNF-alpha • SMARCAL-1 • Aharinejadet al. Circulation. 2009;120:S198-205

  21. Papworth Hospital NHS Foundation Trust NHS Structural Assessment • ECG criteria • S in V1 + R in V5/V6 > 35 mm • Echocardiogram • Posterior wall or septum > 12 mm • Associated risk factors: • History of hypertension • Ischaemic time > 180 min. 1 Marelli et al. J Heart Lung Transplant. 2000;19:496-503

  22. Papworth Hospital NHS Foundation Trust NHS Coronary Angiography • 1 Recommended: • Male > 45 yr • Female > 50 yr • Consider in > 35 y.o. if • cocaine use • >2 risk factors • 2 Bench coronary cine-angiography • Hypertension • Diabetes • Smoking • Dyslipidemia • Family history of CAD 1 Zaroff et al. Circulation. 2002;106:836-841 2Robiscek et al. JTCVS 1992;102:490-5

  23. Papworth Hospital NHS Foundation Trust NHS Functional Assessment • Serial echocardiogram • Stress echocardiogram 1 • Dipyridamol • Dobutamine • Invasive hemodynamic assessment 1 Leone et al. J Heart Lung Transplant. 2009;28:1141-9

  24. Papworth Hospital NHS Foundation Trust NHS Hemodynamic Monitoring Swan-Ganz provides: • Preload - CVP / PCWP • Afterload - SVR • Cardiac output trends Wheeldon et al. J Heart Lung Transplant 1995;14:734-8 Venkateswaran et al. Eur Heart J 2009;30:1771-80

  25. Papworth Hospital NHS Foundation Trust NHS Principles of Donor Resuscitation:Papworth Protocol • Achieve isovolaemia • Acid-base balance • Powner et al. Prog Transplant 2000;10:25 • Minimise catecholamine • Hormone replacement • Novitzky et al. Transplantation. 1987;43:852-9 • Vasopressin for: Pennefather et al. Transplantation 1990;49:311 • diabetes insipidus • vascular tone Wheeldon et al. J Heart Lung Transplant 1995;14:734-8 Zaroff et al. Circulation. 2002;106:836-41

  26. Papworth Hospital NHS Foundation Trust NHS “…….. it makes little sense to replace one diseased heart with another.” N. DePasquale Editorial: how normal is the donor heart? Am Heart J 1969;77:719 ………….unless it can confer significant prognostic benefit to the recipient.

  27. Papworth Hospital NHS Foundation Trust NHS The Alternate Recipient List for Heart Transplant Marginal Donor Heart Standard Donor Heart Status 1 Patient Status 1 Patient Status 2 Patient Alternate Recipient since 1992 1 Laks et al. J Heart Lung Transplant. 1997;16:735-42

  28. ADULT HEART TRANSPLANT RECIPIENTS: Cause of Death (Deaths: January 1992 - June 2006) ISHLT J Heart Lung Transplant 2008;27: 937-983 Last updated based on data as of December 2006

  29. ADULT HEART TRANSPLANT RECIPIENTS: Cause of Death (Deaths: January 1992 - June 2006) ISHLT J Heart Lung Transplant 2008;27: 937-983 Last updated based on data as of December 2006

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