Pericardial Effusion and Prostacyclin Analog Toxicity After Initiation of Sotatercept

Pulmonary arterial hypertension (PAH) is a disorder characterized by progressive remodeling of small pulmonary arteries, leading to increased pulmonary vascular resistance, right ventricular failure and premature death (1-2). Over the past 30 years, significant advancements have been made in the treatment of PAH, including the recent approval of sotatercept, a first-in-class fusion protein that acts as a ligand trap for activins and growth differentiation factors, which are key players in the transforming growth factor β (TGF-β) superfamily (3-4). Sotatercept improves exercise capacity, as assessed by 6-min walk distance and World Health Organization (WHO) functional class, reduces pulmonary vascular resistance and NT-pro brain natriuretic peptide, and improves the simplified French risk score while extending the time to death or nonfatal clinical worsening (3). The 7th World Symposium in pulmonary hypertension recommends the addition of sotatercept as an option in PAH patients who have not achieved low risk despite combination therapy with at least an endothelin receptor antagonist and phosphodiesterase type-5 inhibitor, in intermediate or high-risk patients. The STELLAR study of sotatercept in PAH patients demonstrated the efficacy of this medication in patients receiving background therapy (3). In fact, 34% of the patients were on double and 60% of the patients on triple therapy. Interestingly 40% were on prostacyclin infusion therapy (3). Post-hoc analysis of the stellar study showed a beneficial effect for those on double or triple background PAH therapy as well as those receiving prostacyclin infusion at baseline (1,5). It remains unclear if the addition of sotatercept to other PAH treatments may have unexpected complications. It is possible that by rebalancing the proliferative/antiproliferative effects in the pulmonary circulation, the effect of other treatments for PAH may become excessive, particularly when parenteral prostacyclin is used at high doses. This phenomenon may manifest with the typical characteristics of prostacyclin overdose, including enhanced side effects and high cardiac output heart failure. Hereby we describe a patient with PAH on triple PAH-specific therapy, who after the initiation of sotatercept developed a large pericardial effusion and high cardiac output heart failure.