Sex Differences in Simultaneous Heart-Kidney Transplantation: A 25-Year United Network for Organ Sharing Analysis.

BACKGROUND

Sex differences after cardiac transplantation are well described; whether similar sex differences exist after simultaneous heart-kidney transplantation (SHKT) remains unknown.

METHODS AND

RESULTS

Adults (≥18 years) undergoing first-time SHKT between January 1, 1999, and September 30, 2024, were identified in the United Network for Organ Sharing registry. Rates of SHKT by sex were examined across allocation-policy eras. Post-transplant survival was compared by sex using multivariable Cox regression. Among 3068 recipients (19.7% women), women were more likely to have nonischemic cardiomyopathy and a higher pulmonary vascular resistance and less likely to have durable left ventricular assist device support at the time of transplant. Unadjusted survival did not differ by sex at 1 or 5 years (log-rank P = .236 and P = .593, respectively). After multivariable adjustment, as sex violated proportional hazards, a piecewise constant Cox model showed a numerically higher perioperative than postperioperative sex hazard, neither significant in the full cohort (adjusted hazard ratio [aHR] 1.38 [P = .061] and aHR 1.19 [P = .473]). The perioperative disparity was significant in the prespecified 90-day landmark analysis (days 0-90, aHR 1.58, 95% confidence interval 1.12-2.22 [P = .009]; days 91-365, aHR 0.91 [P = .729]) and in the contemporary allocation era (aHR 1.78, 95% confidence interval 1.19-2.65, P = .005). No sex differences were observed at 5 years and no significant sex interactions were identified across 10 prespecified effect modifiers (all P > .005).

CONCLUSIONS

Women demonstrated an early post-transplant mortality signal concentrated within the first 90 days after SHKT, without excess long-term risk. These findings underscore the need for earlier referral and perioperative optimization of high-risk women to improve equity in SHKT outcomes.