A63-03 Sotatercept-Associated Pericardial Effusion and Tamponade in Pulmonary Arterial Hypertension: A Paradox of Pressure and Permeability

Abstract Background Sotatercept was approved in 2024 for the treatment of pulmonary arterial hypertension (PAH). This protein modulates transforming growth factor-β (TGF-β) superfamily signaling by binding activins and growth differentiation factors, reducing vascular remodeling 1. Recent literature reveals new or worsening pericardial effusions in patients receiving sotatercept, particularly among those with connective tissue disease-associated PAH (CTD-PAH) or prior prostacyclin exposure. Proposed mechanisms include inhibition of the BMP9/BMP10-ActRIIA axis, altering TGF-β/BMPR2 signaling, and increasing endothelial permeability or impairing lymphatic clearance 1,2. Case A 65-year-old female with COPD, chronic hypoxemic respiratory failure, and severe Group 1 PAH (diagnosed in 2022) presented with recurrent pericardial effusions. She received tadalafil, selexipag, and macitentan, the latter discontinued for fluid retention. She declined IV prostacyclin therapy but continued tadalafil and selexipag. Two and a half years later, echocardiography showed a large pericardial effusion with RVSP 99 mmHg. Given disease progression, sotatercept was initiated. After three months, RSVP fell to 72 mmHg, yet the effusion persisted. Five months into therapy, after a mild COVID-19 infection, she developed cardiac tamponade. RVSP was 55 mmHg with a 6 cm effusion; pericardiocentesis revealed a low-cellularity, non-inflammatory effusion. Cardiac MRI demonstrated mild pericardial enhancement without pericarditis symptoms. Three months later, tamponade reoccurred. Autoimmune workup was negative, despite Raynaud’s phenomenon and telangiectasias. Given the recent literature, sotatercept was discontinued. Repeat catheterization showed improved hemodynamics (mPAP 42 mmHg previously 70; PVR 5.6 WU, previously 8). Six months after the first tamponade, repeat serology revealed ANA 1:2560, anti-HA positive, and mildly positive anti-RNP III, while anti-Scl-70, anti-Scl-100, and anti-centromere antibodies remained negative—suggesting an evolving CTD. Discussion This case illustrates paradoxical worsening of a pericardial effusion during sotatercept therapy despite hemodynamic improvement. In PAH, tamponade is uncommon because chronically high pericardial pressures equalize slowly. Our patient developed rapid-onset tamponade as pulmonary pressures decreased. The temporal association of worsening effusions, autoimmune seroconversion, and similar findings in CTD-PAH patients suggests a link between sotatercept and effusions in predisposed patients. In a multicenter cohort, among 391 PAH patients treated with sotatercept, 5.1% developed new or worsening pericardial effusions; 65% had CTD-PAH, and 95% were concurrently on prostacyclin agents. The highest incidence (9.8%) occurred in CTD-PAH, often during hemodynamic improvement 2. These findings support the hypothesis of sotatercept-associated pericardial reactions in predisposed phenotypes. Echocardiographic surveillance is recommended until further data clarifies the risk. References: 1.Larson, J., et al. Chest, DOI:10.1016/j.chest.2025.07.4083. 2.Sahay, S., et al. The European Respiratory Journal, DOI: 10.1183/13993003.01040-2025. This abstract is funded by: none