Use of extended criteria donor cardiac allografts after multiple offers is associated with inferior post-transplant outcomes.

Purpose: Extended criteria donor (ECD) cardiac allografts have increased the donor pool for heart transplant (HT). The effect of donor sequence number (DSN), number of times a recipient's donor organ has been offered prior to acceptance, on post-ECD HT outcomes is unknown. Methods: Adults undergoing first-time isolated HT using ECD from 2012 to 2022 were identified in the United Network for Organ Sharing database. ECD was defined as donor age ≥55 years, ejection fraction (EF) <50%, left ventricular or septal wall thickness >11 mm, valve or wall motion abnormality, abnormal catheterization, or size mismatch >20%. Patients were stratified by DSN, forming 3 groups: 1-5, 6-10, and >10. Results: 12,438 patients underwent ECD HT. 8374 (67%) donors were accepted after 1-5 offers, 1537 (12%) after 6-10 offers, and 2527 (20%) after >10 offers. Compared to those with DSN >10, recipients with DSN 1-5 were more likely to be of high listing status (status 1A or 1-2) (72% vs. 37%, p<0.001) and require waitlist life support (88% vs. 76%, p<0.001). Compared to DSN ≤10, DSN >10 was associated with lower 3-year graft survival estimates (82% vs. 85%, log-rank p=0.011), largely driven by the subgroup of donors with EF <50%. Single-unit increases in DSN were not associated with significantly increased predicted hazard of 3-year graft failure (average marginal effect 0.0003 [-0.0007 - 0.0012], p=0.550). Conclusions: Although there is an association between high DSN and inferior post-transplant outcomes in ECD HT, large differences in DSN are needed to observe meaningful increase in graft failure.