Association of Male Sex With Worse Right Ventricular Function and Survival in Pulmonary Hypertension in the Redefining Pulmonary Hypertension Through Pulmonary Vascular Disease Phenomics Cohort

Background: Sex-based differences are important in the development and progression of pulmonary arterial hypertension. However, it is not established whether these differences are generalizable to all forms of pulmonary hypertension (PH). Research Question: What are the sex-based differences in right ventricle (RV) function and transplant-free survival in patients with PH from the Redefining Pulmonary Hypertension Through Pulmonary Vascular Disease Phenomics (PVDOMICS) cohort? Study Design and Methods: Patients with PH enrolled in the PVDOMICS cohort study underwent right heart catheterization, cardiac MRI, and echocardiography. A multivariable linear regression model was used to investigate the interactive effect between sex and pulmonary vascular resistance (PVR) on RV ejection fraction (RVEF). Effects of sex, RVEF, and PVR on transplant-free survival were assessed using a Cox proportional hazards model. Results: Seven hundred fifty patients with PH (62.8% female) were enrolled, including 397 patients with groups 2 through 5 PH. Patients with group 1 PH were predominantly female (73.4%). Male patients showed multiple markers of worse RV function with significantly lower RVEF (adjusted difference, 5.5%; 95% CI, 3.2%-7.8%; P < .001) on cardiac MRI and lower RV fractional shortening (adjusted difference, 4.0%; 95% CI, 2.3%-5.8%; P < .001) and worse RV free-wall longitudinal strain (adjusted difference, 2.4%; 95% CI, 1.2%-3.6%; P < .001) on echocardiography. Significant interaction was noted between PVR and sex on RVEF, with the largest sex-based differences in RVEF noted at mild to moderate PVR elevation. Male sex was associated with decreased transplant-free survival (adjusted hazard ratio, 1.46; 95% CI, 1.07-1.98; P = .02), partially mediated by differences in RVEF (P = .003). Interpretation: In patients with PH in the PVDOMICS study, female sex was more common, whereas male sex was associated with worse RV function and decreased transplant-free survival, most notably at mild to moderate elevation of PVR. Trial Registry: ClinicalTrials.gov; No.: NCT02980887; URL: www.clinicaltrials.gov