Background and Aims:
Heart transplantation (HTx) represents an established procedure in end-stage heart failure patients with good long-term results. In this study, we aimed to investigate 1) sex differences in clinical characteristics; 2) to identify independent predictors for outcomes; and 3) to analyze outcomes such as all-cause mortality, graft failure (GF), cardiac allograft vasculopathy (CAV) and malignancy in patients post HTx.

Methods:
49,200 HTx recipients (24.6% women) enrolled from April 1995 to January 2019 in the Organ Procurement and Transplantation Network (OPTN), were analyzed for sex differences in waiting list characteristics. Patients <18 years and those with re-transplantation were excluded. Analyses were based on OPTN data (June 30, 2019). We used Kaplan-Meier estimation to show sex differences in outcomes within 20 years of follow up and multivariable Cox regression models were fitted in order to investigate independent predictors for differences in outcomes between men and women.

Results:
At time of listing, men were significantly older compared to women (56 years vs. 53 years, p<0.001). Ischemic cardiomyopathy was highly prevalent in men (men 48.2% vs. women 22.2%, p<0.001), whereas dilated cardiomyopathy was more common in women (men 41.3% vs. women 51.6%, p<0.001). Regarding the classical cardiovascular risk factors, men were more likely to have diabetes [men 19.3% vs. women 15.1%, p<0.001] and had more history of smoking [men 51.1% vs. women 35.8%, p<0.001]). Notably, men had less frequently a history of malignancy compared to women (men 5.1% vs. women 10.2%, p<0.001). Men were listed more often as status 1a (men 46.3% vs. women 40.3%, p<0.001) and had longer waiting list time compared to women (men 101 vs. women 73 days, p<0.001). 

All-cause mortality (men 76.6% vs. women 71.8%, p=0.012), CAV (72% vs. 68%, p<0.001) and rates of malignancy (59.1% vs. 39.4%, p<0.001) were higher in men than in women. Women showed more often GF than men (21.8% vs. 24.6%, p<0.001). After adjustment for sociodemographic characteristics, differences in mortality and graft failure disappeared. Sex differences persisted for CAV and malignancy (hazard ratio (HR) 1.21 [1.13, 1.29], p<0.001; and HR 1.80 [1.63, 2.0], p<0.001) even after adjustment for age, sociodemographic factors, ethnicity, education, cardiovascular conditions, blood group, human lymphocyte antigen mismatch, previous malignancy, urgency status, mechanical ventilator, circulatory support, and dialysis.

Conclusion:
In this large-scale registry of patients post HTx, we observed major differences in pre-transplantation characteristics. Male patients post HTx had a higher risk for all-cause mortality, CAV and malignancy, whereas female patients showed a higher risk for GF. Sex differences in CAV and malignancy persisted even after adjustment for sociodemographic variables, classical risk factors, and measures of disease status.