Early experience with sotatercept in adult patients with repaired and unrepaired congenital heart disease and pulmonary hypertension

Background Pulmonary arterial hypertension associated with congenital heart disease (ACHD-PAH) is a condition underrepresented in initial clinical trials investigating sotatercept, a first-in-class activin signaling inhibitor. Patients with unrepaired defects or complex congenital heart disease were excluded from these trials. Here, we describe real-world outcomes in a cohort of ACHD-PAH patients treated with sotatercept. Methods A single-center retrospective review was performed of 14 adults with ACHD-PAH initiated on sotatercept between May 2024 and January 2026. Patients had heterogeneous congenital anatomy; with half having unrepaired defects. Paired pre- and post-treatment measures were compared, and each patient served as their own control, over a median follow-up of 542 days. Results Eleven of 14 patients (79%) continued therapy. Three patients discontinued: one for epistaxis and two for clinical deterioration leading to heart-lung transplant listing. Adverse effects occurred in 50% of patients, most commonly epistaxis (43%). Hemoglobin increased by a median of 1.5 g/dL (p=0.002). Symptomatic improvement was reported by 79%, and 29% improved by at least one WHO functional class. Exertional oxygen-saturation nadir improved in 71%. Echocardiography showed favorable subpulmonary ventricular remodeling, with increased fractional area change (+5.0%, p=0.020) and reductions in right ventricular basal, mid-chamber, and longitudinal dimensions (all p≤0.03). Lack of response was associated with advanced disease, pulmonary veno-occlusive physiology, and systemic ventricular dysfunction. Conclusions In this cohort of ACHD-PAH patients, sotatercept was generally well-tolerated and was associated with symptomatic improvement and echocardiographic signs of favorable ventricular remodeling.