Sex mismatch following heart transplantation in the United States: Characteristics and impact on outcomes

Background: Available literature indicates the possible detrimental effect of sex mismatching on mortality in patients undergoing heart transplantation. Our objective was to examine the role of sex and heart mass (predicted heart mass [PHM]) mismatch on mortality and graft rejection in patients undergoing heart transplantation in the US. Methods: Data on adult patients who underwent heart transplantation between January 2015 and October 2021 were queried from the United Network of Organ Sharing (UNOS) registry. The main outcomes were all-cause mortality, 1-year all-cause mortality and treated acute rejection. Results: A total of 19 805 adult patients underwent heart transplant during the study period. 92.2% of the patients in the female graft to male group had a PHM mismatch <25%, while only 38.5% had such a mismatch in the male graft to female group. In male to male and female to female groups, 79% and 76% of the patients had a PHM mismatch <25% (p =.122). Proportion of PHM mismatch was similar throughout the study period. Unadjusted analysis showed that male recipients of female grafts had increased risk for all-cause mortality (hazard ratio [HR]: 1.13; 95% confidence intervals [CI]: 1.02, 1.27; p =.026) and 1-year mortality (HR: 1.26; 95% CI: 1.09, 1.45; p =.002) compared to male recipients of male grafts. Graft failure incidence was also higher (HR: 1.12; 95% CI: 1.01, 1.25; p =.041). However, all these associations were non- significant after risk factor adjustment. Conclusions: Sex mismatching is associated with post-transplant mortality with transplantation of female donor grafts to male recipients demonstrating worse outcomes, although this association disappears after risk factor adjustment. Further research is required to elucidate the need for potential changes in clinical practice.