Sex-Mismatching in Isolated Heart Transplant Confers No Postoperative Risk

Background: For heart transplantation, optimal donor-recipient matching is an important factor in the ongoing development of the United Network for Organ Sharing (UNOS) continuous distribution framework. Donor-recipient sex-mismatch has decreased since the 1990s, but this may be related to the risk posed by size mismatching, particularly when donor hearts are undersized. Thus, the impact of sex-mismatching, controlling for other factors including size mismatch, is uncertain. Methods: Adult first-time, isolated heart transplant patients from the UNOS database between October 1, 1987 and December 31, 2022 were analyzed. Cohorts were separated into male and female recipients. Propensity score matching on known preoperative risk factors was performed. Equivalence testing via Two One-Sided Testing (TOST) was performed to assess between-arm equivalence in postoperative outcomes. Survival differences were measured by the between-arm ratio of Restricted Mean Survival Time and binary outcome differences by the Odds Ratio (OR). Results: In the propensity matched cohort, we found significant equivalence between arms in both male (TOST P<0.001) and female (TOST P<0.001) recipients for overall survival at all temporal endpoints, postoperative treatment for rejection within one year, and pre-discharge dialysis. Conclusions: Sex-mismatch in isolated heart transplantation confers no additional risk to postoperative outcomes when controlling for other factors, including size mismatch. Consequently, sex-mismatch should not factor into individual assessments of organ acceptance or be incorporated into any national organ allocation policy. Increasing the acceptance of sex-mismatched donors has the potential to expand the donor pool and increase female donor utilization. ### Competing Interest Statement The authors have declared no competing interest. ### Funding Statement The authors have no funding sources to disclose. ### Author Declarations I confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained. Yes The details of the IRB/oversight body that provided approval or exemption for the research described are given below: This study is a retrospective review of deidentified data supplied by UNOS in the form of a deidentified Standard Research Analysis File. Our project was determined to be Institutional Review Board exempt following a human subjects research determination (protocol #71189). I confirm that all necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived, and that any patient/participant/sample identifiers included were not known to anyone (e.g., hospital staff, patients or participants themselves) outside the research group so cannot be used to identify individuals. Yes I understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance). Yes I have followed all appropriate research reporting guidelines, such as any relevant EQUATOR Network research reporting checklist(s) and other pertinent material, if applicable. Yes Dr. Reid Dale had full access to all the data in the study and takes responsibility for its integrity and the data analysis.