Heart Transplant: State of the Art. Dr Nick Banner

Transcription

1 Heart Transplant: State of the Art Dr Nick Banner

2 Heart Transplantation What is achieved Current challenges Donor scarcity More complex recipients Long-term limitations Non-specific Pharmacological Immunosuppression The versatile immune system

3 Heart Transplantation What is achieved Current challenges Donor scarcity More complex recipients Long-term limitations Non-specific Pharmacological Immunosuppression The versatile immune system

4 Survival (%) Adult Heart Transplants Kaplan-Meier Survival by Era (Transplants: January 1982 June 2013) All pair-wise comparisons were significant at p < Median survival (years): =8.4; =10.4; =NA; /2013=NA Years (N=21,215) (N=39,368) (N=24,023) /2013 (N=16,200) JHLT Oct; 34(10): 33(10):

5 Adult Heart Transplants Kaplan-Meier Survival by Era Conditional on Survival to 1 Year (Transplants: January 1982 June 2013) (N=15,876) (N=30,861) (N=19,309) /2013 (N=11,994) Survival (%) All pair-wise comparisons were significant at p < 0.05 except vs /2013. Median survival (years): =11.7; =13.2; =NA; /2013=NA JHLT Oct; 34(10): 33(10): Years

6 Benefit of transplantation Relative risk of death following transplantation Relative risk By HFSS risk at listing Low HFSS risk Moderate HFSS risk High HFSS risk Urgent (non-ambulatory) Transplantation 2008; 86: Time since transplant (months) Risk less than on the waiting list after (days (95% CI)) Net benefit after (days) Urgent (non-ambulatory) 7 (0 to 46). 15. High risk 31 (16 to 46) Moderate risk 64 (41 to 82) Low risk 95 (54 to 136). 729.

7 Quality of life of patients in UK heart transplant pathway: EQ-5D dimensions. Median score and interquartile range Symptom Stability Self Efficacy Medical assessment Medical list LVAD Heart Transplant Median score and interquartile range Symptom Frequency Symptom Burden Total Symptom Score Eur J Cardiothorac Surg 2016; doi: /ejcts/ezw054 Physical Limitation Clinical Summary Score QoL Overall Summary Score Social Limitation EQ-5D Index (x100)

8 Heart Transplantation What is achieved Current challenges Donor scarcity More complex recipients Long-term limitations Non-specific Pharmacological Immunosuppression The versatile immune system

9 5000 Adult and Pediatric Heart Transplants Number of Transplants by Year 4500 Number of transplants JHLT Oct; 34(10): 33(10): NOTE: This figure includes only the heart transplants that are reported to the ISHLT Transplant Registry. As such, the presented data may not mirror the changes in the number of heart transplants performed worldwide.

10 Adult and Pediatric Heart Transplants Median Donor Age by Location 50 Europe North America Other Median donor age (years) JHLT Oct; 34(10): 33(10):

11 Methods of heart donation Donation after circulatory death (DCD) The method used for the first heart transplants Death certified on the basis of standard somatic criteria Family discussion must be anticipatory Donation procedure reactive Potential for hypoxic cardiac injury during the apnoeic period Injury may be potentiated by subsequent ischaemia Heart assessment limited Donation after brain-stem death (DBD) The standard method once BSD criteria were established Family discussion based on a firm diagnosis Potential cardiac injury during BSD Subsequent loss of donor homeostatic functions Donation procedure fully controlled Heart Function assessed fully before donation

12 DCD heart donation with distant procurement Lancet 2015; 385(9987):

13 Source of adult heart transplant donors in UK Source NHSBT, courtesy of Dr Mehew

14 Adult Heart Transplants % of Patients Bridged with Mechanical Circulatory Support* by Year and Device Type 50 ECMO VAD+ECMO 40 TAH RVAD LVAD+RVAD LVAD % of Patients Year of Transplant 2015 * LVAD, RVAD, TAH, ECMO JHLT Oct; 34(10): 33(10):

15 Adult Heart Transplants Kaplan-Meier Survival by VAD usage (Transplants: January 1999 June 2013) All pair-wise comparisons with ECMO were significant at p < Continuous flow vs. Pulsatile flow and No LVAD / Inotropes vs. Pulsatile flow were significant at p < No other pair-wise comparisons were significant at p < Survival (%) Pulsatile flow (N=3,602) Continuous flow (N=3,703) ECMO (N=157) No LVAD / No Inotropes (N=11,042) No LVAD / Inotropes (N=11,446) Years JHLT Oct; 34(10): 33(10):

16 Adult Heart Transplants Kaplan-Meier Survival Within 1 Year by Diagnosis (Transplants: January 1982 June 2013) Survival (%) All pair-wise comparisons were significant at p < 0.01 except congenital vs. valvular Cardiomyopathy (N=46,886) CAD (N=41,505) Congenital (N=2,101) Retransplant (N=2,070) Valvular (N=3,575) JHLT Oct; 34(10): 33(10): Months For some retransplants, a diagnosis other than retransplant is reported, so the total number of retransplants may be greater.

17 Adult Heart Transplants Kaplan-Meier Survival by Diagnosis Conditional on Survival to 1 Year (Transplants: January 1982 June 2013) Median survival (years): Cardiomyopathy=14.1; CAD=11.7; Congenital=20.2; Retransplant=11.0; Valvular=14.3 Survival (%) All pair-wise comparisons were significant at p < except cardiomyopathy vs. valvular and CAD vs. retransplant. Cardiomyopathy (N=36,912) CAD (N=32,373) Congenital (N=1,529) Retransplant (N=1,395) Valvular (N=2,632) JHLT Oct; 34(10): 33(10): Years For some retransplants, a diagnosis other than retransplant is reported, so the total number of retransplants may be greater.

18 30-day patient survival by IT 100 % survival estimate IT (mins) Number at risk at day 0 % survival estimate 95% CI < >= Log-Rank p= Days after transplant Transplantation 2008; 86:542-7

19 Potential advantages of OCS for DCD donation Active heart resuscitation during normothermic perfusion Ischemia time minimised Functional assessment of the donor heart during ex-vivo perfusion Removal of time-pressure in the complex recipient

20 Heart Transplantation What is achieved Current challenges Donor scarcity More complex recipients Long-term limitations Non-specific Pharmacological Immunosuppression The versatile immune system

21 Mechanisms of acute allograft rejection Central role of the CD4+ T-cell

22 Clinical Immunosuppression: History and Mechanisms of Action azathioprine corticosteroids antilymphocyte globulin 1980 ciclosporin [muromonab-cd3] Effects on the T-cell activation cascade tacrolimus mycophenolate basiliximab/ [daclizumab] sirolimus everolimus

23 Kobashigawa J et al. J Heart Lung Transplant 2011;30:252

24 Conceptual framework and diagnostic criteria for AMR Applied to Heart Transplantation Stage 4 Allograft dysfunction Clinical Acute AMR Histological evidence of AMR Antibody binding to capillaries C4d C3d Donor Specific Antibody Subclinical AMR Silent? Pre-rejection? accommodation Latent Takemoto SK et al. Am J Transplant 2004:4; 1033 Stewart S et al. J Heart Lung Transplant 2005;24:

25 Influence of de-novo donor specific HLA antibody formation on survival following heart transplantation Predicted survival curve for the time dependent variable de novo DSA from fitted Cox model for patients producing DSA at the outset (-----) and patients with no detectable DSA at any time point ( ) following cardiac transplantation. Smith JD et al. Am J Transplant 2011; 11: 312

26 50 40 Adult Heart Transplants Relative Incidence of Leading Causes of Death (Deaths: January 1994 June 2014) CAV Acute Rejection Malignancy (non-lymph/ptld) Infection (non-cmv) Graft Failure Multiple Organ Failure Renal Failure % of Deaths Days (N=5,888) 31 Days 1 Yr (N=5,053) >1 3 Years (N=3,686) 2015 JHLT Oct; 34(10): 33(10): >3 5 Years (N=3,215) >5 10 Years (N=8,114) >10 15 Years (N=5,576) >15 Years (N=3,504) Since only leading causes of death are shown, the sum of percentages for each time period is less than 100%.

27 Heart Transplantation What is achieved Current challenges Donor scarcity More complex recipients Long-term limitations Non-specific Pharmacological Immunosuppression The versatile immune system