Sotatercept in Congenital Heart Disease–Associated Pulmonary Arterial Hypertension and Eisenmenger Syndrome

BACKGROUND: Eisenmenger syndrome (ES) is a form of World Health Organization Group 1 pulmonary arterial hypertension (PAH). Initial therapy typically involves monotherapy with an endothelin-receptor antagonist or a phosphodiesterase-5 inhibitor, whereas evidence for advanced therapies remains limited. Sotatercept, a first-in-class therapy, modulates vascular cell proliferation. Phase 3 results were promising; however, they excluded patients with ES. Concerns exist that sotatercept could exacerbate pre-existing erythrocytosis and bleeding risk. This case series describes the authors' experience with the use of sotatercept in patients with ES and illustrates its feasibility. CASE SUMMARY: A retrospective chart review was performed for all adult patients with PAH and ES seen at the PAH clinic from June 1, 2024, to May 30, 2025. This is a consecutive case series of patients treated with sotatercept. Six patients with ES initiated sotatercept. Five continued therapy, whereas one discontinued because of family preference. Adverse effects included diarrhea and headaches, which were manageable. No major safety signals were observed in the cohort. No patient experienced treatment-limiting erythrocytosis or bleeding. DISCUSSION: This case series describes a single-center experience with sotatercept in PAH and ES. All patients who continued therapy have sustained improvement in their functional capacity. No major safety signals were observed. Patients with ES are heterogeneous, the results are hypothesis-generating. Clinicians should carefully assess patient-specific physiology when selecting treatments. TAKE-HOME MESSAGE: This case series suggests the feasibility of sotatercept in patients with ES.