Abstract
Landmark trials of sotatercept in pulmonary arterial hypertension (PAH) excluded patients with significant cardiopulmonary comorbidities. To evaluate the real-world effectiveness and safety of sotatercept in patients with Group I PAH and cardiopulmonary comorbidities. We conducted a single-center prospective observational study of adults with PAH on stable background therapy who initiated sotatercept between August 2024 and April 2025. Clinical, echocardiographic, and adverse event data were collected at baseline, 3 months, and 6 months. Forty-five patients (mean age 59.1 years old; 88.8% female) were included. Common comorbidities include CAD (44.7%), HTN (40.4%), ILD (23.4%), and COPD (12.7%). Most patients were on triple background pulmonary vasodilator therapy (63.8%). At 6-month follow-up, oxygen requirement at rest improved from 4.64 to 3.20 L/min (p = 0.001), 6MWD increased by 20 meters (310.5 ± 142.4 m to 330.4 ± 132.3 m, p = 0.01). REVEAL Lite 2 scores improved, with over half the cohort achieving or maintaining low risk status. Adverse effects were mild, including epistaxis and increased hematocrit. Sotatercept appears safe and clinically beneficial in PAH patients with cardiopulmonary comorbidities.