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Primary Graft Failure: The Major Cause of Death Following Cardiac Transplantation in 2013

Primary Graft Failure: The Major Cause of Death Following Cardiac Transplantation in 2013. Jack Copeland, MD University of California San Diego. HEART TRANSPLANTS Kaplan-Meier Survival (Transplants: January 1982 - June 2010). N = 96,273. N at risk at 25 years = 112. ISHLT. 2012.

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Primary Graft Failure: The Major Cause of Death Following Cardiac Transplantation in 2013

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  1. Primary Graft Failure: The Major Cause of Death Following Cardiac Transplantation in 2013 Jack Copeland, MD University of California San Diego

  2. HEART TRANSPLANTSKaplan-Meier Survival(Transplants: January 1982 - June 2010) N = 96,273 N at risk at 25 years = 112 ISHLT 2012 Survival is based on adult and pediatric transplant recipients J Heart Lung Transplant.  2012 Oct; 31(10): 1045-1095

  3. My Impression • Recipients are sicker • Longer courses of medical therapy • Often have renal and hepatic disease • Diabetics are more commonly transplanted • A higher percentage of LVAD patients

  4. ADULT HEART TRANSPLANTS% of Patients Bridged with Mechanical Circulatory Support* (Transplants: January 2000 – December 2010) ISHLT * LVAD, RVAD, TAH 2012 J Heart Lung Transplant.  2012 Oct; 31(10): 1045-1095

  5. Graft Failure is the Problem • In the first 30 days • Primarily from poor hemodynamic function • For the next 15 years • Some of this mortality may be directly be related to the quality of the donor heart or to donor heart damage • Years later on electron microscopy intracellular tangles observed in greater numbers in hearts subjected to longer ischemic times

  6. ADULT HEART RECIPIENTS Cause of Death from Leading Causes by Time since Transplant and Era (Deaths: January 1994 - June 2011) Deaths 1994 – 2001 Deaths 2002 – 6/2011 ISHLT 2012 J Heart Lung Transplant.  2012 Oct; 31(10): 1045-1095

  7. ADULT HEART TRANSPLANT RECIPIENTS Relative Incidence of Leading Causes of Death(Deaths: January 1994 - June 2011) ISHLT 2012 J Heart Lung Transplant.  2012 Oct; 31(10): 1045-1095

  8. ADULT HEART TRANSPLANT RECIPIENTS Cumulative Incidence of Leading Causes of Death(Transplants: January 1994 - June 2010) ISHLT 2012 J Heart Lung Transplant.  2012 Oct; 31(10): 1045-1095

  9. Causes of Death 0- >15 yearsn=26,061 • Graft failure 21% (5509) • Malignancy 16% (4186) • Infection 14% (3732) • Coronary vasculopathy 11% (2792) • Acute rejection 5% (1221) • Combined GF+CV+AR=37% (9522)

  10. Causes of Death 1-5 years post transplantation • Graft failure 23% • Coronary vasculopathy 13.8% • Acute rejection 7.8% • Combined 44.4%

  11. HEART TRANSPLANTSMedian Donor Age by Location ISHLT 2012 J Heart Lung Transplant.  2012 Oct; 31(10): 1045-1095

  12. HEART TRANSPLANTSDonor Age by Year of Transplant ISHLT 2012 J Heart Lung Transplant.  2012 Oct; 31(10): 1045-1095

  13. ADULT HEART TRANSPLANTS (2005-6/2010)Risk Factors For 1 Year Mortality with 95% Confidence Limits Donor Age p < 0.0001 ISHLT 2012 (N = 10,288) J Heart Lung Transplant.  2012 Oct; 31(10): 1045-1095

  14. ADULT HEART TRANSPLANTS (2005-6/2010)Risk Factors For 1 Year Mortality with 95% Confidence Limits Ischemia Time p < 0.0001 ISHLT 2012 (N = 10,288) J Heart Lung Transplant.  2012 Oct; 31(10): 1045-1095

  15. Donor Risk Factors for 1 year mortality from ISHLT Registry • Significant • Age risk increased by X1.5 at 47, by X2 at 55 • Ischemic time risk up X1.25 at 240 min, X1.5 at 330 • Not Significant • Infection, history of diabetes, gender, hypertension, cause of death, history of malignancy

  16. Recipient 1 year Mortality ISHLT Registry • Creatinine mortality increased X2 with creat≥ 2.5 X1.5 at creat = 2 • PVR ≥ 8 Woods units increased X1.2 • PRA > 80% increased X1.5 • Age ≥ 70 increased X1.75 • Ht <155 cm X1.75, Wt ≥ 130 kg X 1.75 • Total Bilirubin X 1.3 at ≥ 3.5 mg/dl • Pulmonary artery wedge mean > 30 increase X 1.2

  17. Other Factors from Other Sources • Sydney St Vincent’s • Age • Echo poor LVEF • High dose inotropes • Ischemic time > 240 min • Donor recipient weight mismatch, D/R<0.8 • Female donor male recipient

  18. Others • La Pitie, Paris, Primary graft failure • Trauma as cause of death X2.5 • LVEF < 55% X2.75 • Norepinephrine dose > 0.1 mcg/kg/min X2

  19. Others • Columbia Presbyterian • Donor age > 30 X2, age 40 X1.4 • Ischemic time < 1 hour X6, > 6h X3.8 • Female to male recip X1.6 • Multi-organ donor X1.6

  20. Others • Palermo/Pittsburgh • Dopamine >10 mcg/kg/min • Alpha agents at > 0.6 mcg/kg/min either increased primary graft failure X7.5

  21. Others • Hannah Copeland • 37,000 donors were used no difference in graft survival among: dopamine, dobutamine, 3 inotrope/pressors, 1 pressor • Valencia • Mortality not increased, but morbidity increased ie severe infections, prolonged ventilation in “high inotrope/pressor” donors

  22. Proposed Donor Checklist Modified from checklist currently in use at Johns Hopkins

  23. Proposed Donor Checklist Donor Offer Date:______ Location of Donor:___________________ Potential recipient:__________ Cause of brain death:__________________________________________________________________

  24. A Few Recent Donor Related Problems • 16 yo F hanging unknown down time, elevated troponin, but LVEF 55%, transplanted to similar size M recipient • Heart failed, had transmural infarcts, eventual mortality • 30 yo F cerebral bleed with excellent cardiac function, but LV end diastolic dimension of 3.7 cm. to slightly larger M recipient • LV failure, PHT, severe TR, required prolonged inotropes, persistent CHF • 42 yo M trauma 75% LVEF with LVDD of 4.2 and septal and posterior wall thicknesses of 1.2 cm • AMR caused more wall thickening, patient developed severe diastolic failure, resolved with plasmapheresis

  25. Conclusions • High mortality from graft failure and sicker recipients are the pressures faced by cardiac transplant physicians and surgeons • The checklist based on evidence may help the team consider important contraindications

  26. Thank You

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