Male Sex is Associated with Worse Right Ventricular Function and Survival in Pulmonary Hypertension in the PVDOMICS Cohort

Background Sex-based differences are important in the development and progression of pulmonary arterial hypertension (PAH). However, it is not established whether these differences are generalizable to all forms of pulmonary hypertension (PH). Research Question To assess sex-based differences in right ventricular (RV) function and transplant-free survival in subjects with PH from the PVDOMICS cohort. Study Design and Methods Subjects with PH enrolled in PVDOMICS cohort study underwent right heart catheterization, cardiac MRI, and echocardiogram. A multivariable linear regression model was used to investigate the interactive effect between sex and pulmonary vascular resistance (PVR) on RV ejection fraction (EF). Effects of sex, RVEF, and PVR on transplant-free survival were assessed using a Cox proportional hazards model. Results 750 subjects with PH (62.8% female) were enrolled, including 397 subjects with Groups 2-5 PH. Group 1 was most predominantly female (73.4%). Men had multiple markers of worse RV function with significantly lower RVEF (Adjusted difference 5.5%, 95% CI: 3.2-7.8%, P<0.001) on cardiac MRI and lower RV fractional shortening (Adjusted difference 4.0%, 95% CI: 2.3 to 5.8%, P<0.001) and worse RV free wall longitudinal strain (Adjusted difference 2.4%, 95% CI: 1.2 to 3.6%, P<0.001) on echocardiogram. There was significant interaction between PVR and sex on RVEF with largest sex-based differences in RVEF noted at mild to moderate PVR elevation. Male sex was associated with decreased transplant-free survival (adjusted HR 1.46, 95% CI: 1.07 to 1.98, P=0.02), partially mediated by differences in RVEF (P=0.003). Interpretation In subjects with PH in PVDOMICS, female sex is more common, while male sex is associated with worse RV function and decreased transplant-free survival, most notably at mild to moderate elevation of PVR.