Sotatercept improves echocardiographic risk stratification in pulmonary arterial hypertension: real-world data from the french early access program

Background Management of pulmonary arterial hypertension (PAH) is guided by multiparametric risk assessment, integrating clinical, biological, imaging, and hemodynamic parameters. Echocardiographic low-risk features include right atrial (RA) area <18 cm², TAPSE/PASP ratio >0.32 mm/mmHg, and absence of pericardial effusion. Aim To evaluate the impact of sotatercept on echocardiographic risk parameters and composite echocardiographic risk stratification in patients with PAH receiving optimized background therapy. Methods In this multicenter real-world study, 106 patients with PAH on dual or triple combination therapy received sotatercept through the French national early access program across six expert centers. Echocardiography was performed at baseline and after ≥3 months of treatment. RA area, TAPSE/PASP ratio, and pericardial effusion were assessed. Hemodynamic, clinical, and biomarker data were also collected. Results Mean pulmonary artery pressure significantly decreased (47.4 ± 12.1 to 36.9 ± 9.0 mmHg; p=0.0005), while cardiac output remained unchanged (5.2 ± 1.0 to 5.3 ± 1.4 L/min; p=0.48). Improvements were paralleled by NYHA functional class improvement (p=0.01) and NT-proBNP reduction (p=0.01). RA area decreased from 21.0 ± 7.7 to 16.7 ± 6.0 cm² (p=0.0005), and TAPSE/PASP increased from 0.28 ± 0.10 to 0.38 ± 0.14 (p=0.0001). The proportion of patients reaching low-risk echocardiographic thresholds increased accordingly. Pericardial effusion prevalence rose numerically from 10% to 17%, without statistical significance (p=0.07). A composite echocardiographic risk score from RA area <18 cm², TAPSE/PASP ratio >0.32 mm/mmHg, and absence of pericardial effusion, each contributing from 0 to 1 were summed given a score of 0=low risk and 3=high risk. The score decreased from 1.2 ± 0.7 to 1.0 ± 0.7 (p=0.04). Overall, 27 patients improved by ≥1 grade and 4 improved by ≥2 grades (see figure). Conclusion In this real-world cohort, sotatercept was associated with significant improvement in echocardiographic risk parameters and overall risk stratification. Although pericardial effusion was numerically more frequent, its clinical significance as a marker of disease progression remains uncertain.Echocardiographic risk (Sankey)