Marked Clinical and Haemodynamic Improvement with Sotatercept in Severe Refractory Pulmonary Arterial Hypertension Associated with Corrected Complex Congenital Heart Disease

ABSTRACT : Pulmonary arterial hypertension (PAH) is a progressive disease associated with high morbidity despite combination therapy. Sotatercept, a recombinant fusion protein that acts as an activin signaling inhibitor, has shown significant clinical and haemodynamic benefit in phase 3 trials. However, evidence in PAH associated with congenital heart disease (PAH-CHD) is very limited. 37-year-old woman with repaired pulmonary atresia with ventricular septal defect and major aortopulmonary collateral arteries, who developed severe PAH years later. Despite treatment with tadalafil, ambrisentan, and high dose subcutaneous treprostinil, she remained at intermediate-high risk, with WHO-FC III, NT-proBNP 3773 pg/mL and a 6-minute walk distance (6MWD) of 480 m. Sotatercept was initiated through an expanded access program. Over the following months, she markedly improved to WHO-FC II, NT-proBNP 230 pg/mL and 6MWD 540 m. Right heart catheterization showed a reduction in mean pulmonary artery pressure from 48 to 26 mmHg, PVR from 14 to 5.4 Wood units, and an increase in cardiac index from 1.17 to 2.91 L/min/m 2 . A significant and rapid improvement in haemodynamics and functional capacity was observed after starting sotatercept, in a patient with severe PAH-CHD refractory to maximal therapy. Sotatercept may represent an effective rescue therapy and a potential therapeutic option for complex and severe PAH patients.