Ex-vivo heart perfusion attenuates early post-transplant risk after prolonged agonal period in DCD heart transplantation.

BACKGROUND

Warm ischemic injury during the agonal period (AP) threatens graft viability in donation-after-circulatory-death (DCD) heart transplantation. Whether ex vivo heart perfusion (EVHP) mitigates these risks remains unclear.

METHODS

Adult (≥18 years) isolated heart transplants reported to the United Network for Organ Sharing (UNOS) thoracic registry (January 2019-April 2025) were reviewed. Recipients lacking AP or perfusion data were excluded. The primary exposure was EVHP, defined as use of an ex vivo perfusion device following donor cardiectomy; static cold storage served as the reference. Multivariable Cox and logistic models adjusted for donor, recipient, procedural, and center-level factors. Propensity score matching was performed in the prolonged AP subgroup.

RESULTS

Among 1,682 donation after circulatory death (DCD) recipients, 1,175 (69.9%) received ex vivo heart perfusion (EVHP). Prolonged AP (≥30 min) occurred in 359 cases. One-year survival was 90.7% overall. In the fully adjusted Cox model, no-EVHP grafts with AP ≥30 min had higher 1-year mortality versus the reference (no-EVHP + <30 min) (HR 2.17; 95% CI 1.05-4.47; p = 0.037). EVHP grafts showed no excess risk regardless of AP (EVHP + <30 min: HR 0.93; 95% CI 0.54-1.62; p = 0.809; EVHP + ≥30 min: HR 0.98; 95% CI 0.49-1.96; p = 0.953). Age, creatinine, out-of-body time, and adult congenital heart disease (ACHD) increased mortality; ventricular assist device (VAD) at listing and high-volume centers were protective; sex was not significant. In the AP ≥30-min propensity score matching (PSM) subgroup (n = 240; 120 EVHP, 120 no EVHP), EVHP improved 1-year survival (log-rank p = 0.03). Spline modeling showed rising mortality beginning ∼20 min of AP for static-preserved grafts, with a flat risk curve under EVHP. Static-preserved prolonged-AP grafts had higher odds of acute rejection before discharge (aOR 2.56; 95% CI 1.07-6.14; p = 0.04); stroke, dialysis, and pacemaker use did not differ.

CONCLUSIONS

EVHP may mitigate survival and rejection penalties of prolonged AP in the U.S. DCD heart transplantation. Broader EVHP adoption for donors with AP ≥30 min may safely expand the DCD heart pool without compromising outcomes.