Sex Differences Across the Donor Heart Offer-to-Outcome Pathway: A Linked National Cohort Study

Background

Sex differences occur across heart transplantation, but where they become apparent between donor-heart offers and post-transplant outcomes is uncertain.

Methods

We linked UNOS STAR Q2 2025 candidate, donor, transplant, and PTR match-run data across pre- and post-2018 eras. Analyses included 51,970 listing episodes, 1,388,553 actual offers, and 38,417 recipients and evaluated access, conditional final acceptance, donor profiles, severe predicted heart mass (PHM) undersizing (ratio <0.86), treated rejection, and 365-day survival.

Results

Transplant access increased in both sexes without evidence of sex-by-era modification (P=.133). Offers made to female candidates had higher adjusted conditional final-acceptance probabilities in both eras (interaction P=.172). After recipient-size standardization, severe PHM undersizing among realized offers remained less frequent for women than men pre-policy (28.9% vs 38.3%) and post-policy (25.5% vs 35.4%); acceptance of undersized offers was not lower for female candidates (three-way interaction P=.800). The threshold donor composite showed modest differences that reversed direction across eras. Adjusted treated rejection remained higher among women (male vs female OR, 0.667; 95% CI, 0.589-0.756), including after post-policy cPRA adjustment (OR, 0.678; 95% CI, 0.583-0.790). Adjusted post-policy 365-day survival was 91.0% in women and 92.3% in men; the sex difference did not change across eras (−0.64 percentage points; 95% CI, −1.97 to 0.68; P=.341).

Conclusions

Sex-associated patterns were stage-specific and multidirectional. The final-graft PHM difference was already evident among realized offers after size standardization and was not explained solely by lower acceptance of undersized offers for female candidates. Women nonetheless had more treated rejection, while short-term survival differences did not change significantly across eras. Transplantation performance should be assessed separately across offer exposure, acceptance, matching, and outcomes.

What Is Known

• Sex differences have been reported in heart-transplant access, donor-heart acceptance, sensitization, rejection, and survival, but these stages have usually been examined separately.

• Offer exposure, conditional acceptance, donor-recipient size matching, and downstream outcomes may not show the same direction of association with recipient sex.

What the Study Adds

• By linking 1.39 million actual donor-heart offers to listing and transplant records, this study found higher adjusted conditional final-acceptance probabilities for offers made to female candidates in both allocation eras.

• After recipient-size standardization, women encountered and received fewer severely PHM-undersized hearts; the difference was already apparent among realized offers and was not explained solely by lower acceptance of undersized offers for female candidates.

• Conventional donor profiles, treated rejection, and survival did not move uniformly: women had more adjusted registry-reported treated rejection, whereas short-term survival differences did not change significantly across eras.