C65-19 Novel Real World Use of Sotatercept in Group 3 Chronic Lung Disease Pulmonary Hypertension Patients

Abstract Introduction Group 3 pulmonary hypertension, characterized by PH secondary to chronic lung disease (CLD - PH), is associated with poor prognosis, progressive functional decline, and limited therapeutic options. Sotatercept, an activin signaling inhibitor, has shown significant clinical benefit in Group 1 PAH, but its role in Group 3 CLD-PH remains undefined. We conducted a single-center analysis to characterize real-world functional, hemodynamic, and echocardiographic responses to sotatercept in patients with Group 3 CLD-PH. Methods Sixteen patients with CLD-PH were treated with sotatercept at a tertiary PH referral center. Baseline and follow-up assessments included right heart catheterization, BNP, six-minute walk distance (6MWD), functional class (FC), oxygen requirement, hemoglobin, and transthoracic echocardiography (TTE) for right ventricular (RV) function and dilation. Paired pre- and post-treatment values were compared and mean relative percentage change was calculated for each metric. Results Sotatercept initiation was associated with improvement in multiple clinical and hemodynamic metrics, figure 1, with statistical significance (p 0.05) seen in RAP, O2 requirement, BNP, FC and 6MWD. RAP decreased from 7.1 to 3.8mmHg (n = 9, Δ − 46.8%), PASP from 75.4 to 50.6mmHg (n = 9, Δ − 33.0%), and mPAP from 47.9 to 30.7mmHg (n = 9, Δ − 36.0%). PVR decreased from 10.4 to 6.0WU (n = 9, Δ − 42.1%), and cardiac output increased from 3.46 to 4.81L/min (n = 9, +39.0%). BNP decreased from 378 to 92pg/mL (n = 13, Δ − 75.7%), oxygen requirement fell from 5.4 to 4.2 L/min (n = 16, Δ − 22.4%), and 6MWD improved from 211 to 252 meters (n = 12, Δ + 19.4%). There was a significant improvement in FC distribution: the proportion of patients in NYHA class IV decreased from 25% (4/16) to 12.5% (2/16), while those in class II increased from 25% (4/16) to 31.3% (5/16) and class III from 43.8% (7/16) to 50% (8/16) (p 0.05). TTE demonstrated improvement in RV remodeling, specifically improvement in RV function and RV dilation, figure 1. Additionally, 12 of 16 patients experienced a modest increase in hemoglobin, with a mean Hgb change of + 1.42 g/dL. Conclusion Sotatercept was associated with substantial improvements in hemodynamics, oxygen requirement, BNP, functional capacity, and echocardiographic RV remodeling in patients with CLD-PH. The mild hemoglobin rise observed was consistent with the known safety profile. These findings highlight sotatercept’s potential clinical utility beyond Group 1 PAH and support the need for prospective studies evaluating its role in Group 3 CLD-PH. This abstract is funded by: None