Quick and sustained right ventricular reverse remodeling at early, mid and late follow-Up under sotatercept

Background Sotatercept, an activin signaling inhibitor, is a novel therapy for patients with pulmonary arterial hypertension (PAH). While clinical trials have demonstrated hemodynamic and functional benefits, the time course of right ventricular (RV) reverse remodeling under treatment remains incompletely characterized. Aim We aimed to determine whether the effects of sotatercept on RV remodeling occur early after initiation or progress gradually over time. Methods Eighty-nine patients with PAH were enrolled in the French early access program for sotatercept. Echocardiographic follow-up was performed within 6 months (n=26), between 6–12 months (n=51), and beyond 12 months (n=10). RV reverse remodeling was assessed comprehensively, including chamber size, systolic function, loading conditions, right atrial parameters, and indices of RV–LV interaction. Results Mean age was 51±15 y, and 77% were female. Baseline and follow-up mean pulmonary arterial pressure and pulmonary vascular resistance were 50±11 mmHg vs. 37±9 mmHg (p=0.0002) and 7.8±2.4 vs. 7.0±2.7 WU (p=0.47), respectively. Significant improvements were observed in 6-MWT (p<0.001), NT-proBNP (p=0.009). Echocardiography demonstrated marked RV reverse remodeling, including reductions in RV end-diastolic area (p=0.003), RA volume (p<0.0003) along with improvement in TAPSE/sPAP (from 0.27±0,10 vs. 0.38±0,13, p=0.0002). Parameters reflecting RV–LV interaction (septal flattening p=0.009; LV end-diastolic diameter p=0.025) showed significant favorable changes. Importantly, the majority of remodeling occurred within the first 6 months of therapy. These improvements were sustained at 6–12 months and beyond 12 months, without evidence of further incremental remodeling over time. Conclusion in PAH patients, structural, functional, and loading condition improvements occur early after Sotatercept initiation and are maintained at mid- and long-term follow-up, suggesting an early therapeutic impact that stabilizes over time.