Sex Differences in Clinical Presentation and Outcomes in Chronic Thromboembolic Pulmonary Hypertension

Sex-related differences in chronic thromboembolic pulmonary hypertension (CTEPH) remain incompletely defined. The authors aimed to evaluate sex differences in clinical presentation, treatment response, and outcomes in a nationwide Japanese CTEPH registry. We analyzed 1,527 participants in the prospective, multicenter Chronic Thromboembolic Pulmonary Hypertension Anticoagulant Registry (UMIN000033784). Baseline and follow-up clinical status, hemodynamics, treatments, morbidity and mortality, and bleeding were compared by sex in the overall and treatment-naïve cohorts using time-to-event and adjusted regression analyses. Median follow-up was 27.4 months (Q1-Q3: 10.6-49.7) in the overall cohort and 18.6 months (Q1-Q3: 6.4-36.7) in the treatment-naïve cohort. Female patients comprised 1,080 of 1,527 (70.7%) participants and were older, with lower body mass index and shorter 6-minute walk distance than male patients (all P < 0.001). In the overall cohort, pulmonary vascular resistance index was similar between sexes, whereas cardiac index was modestly higher in female patients. Treatment-naïve female patients had worse World Health Organization functional class (P = 0.03) and higher pulmonary vascular resistance index (989.2 ± 480.3 vs 870.6 ± 501.4 dyn s cm-5 m-2; P = 0.04). Crude improvements in exercise capacity and hemodynamics were comparable or greater in female patients but were attenuated after baseline adjustment. Morbidity, mortality, and bleeding did not differ by sex in either cohort. Female patients with CTEPH, particularly when treatment-naïve, presented with more advanced disease but had comparable long-term outcomes under contemporary multimodal management. These observational associations do not establish treatment efficacy but support sex-specific awareness at diagnosis.