Improvement of size, shape but not RV function with sotatercept in pulmonary arterial hypertension: insights from a french nationwide real-world echocardiographic study
M El Blidi, T Duval, E Artaud-Macari, S Valentin, H Bouvaist, M Riou, N Lamblin, O Sitbon, L Savale, A Boucly, D Montani, M Humbert, F BauerAbstract
Background
In pulmonary arterial hypertension (PAH), prognosis is mainly driven by the ability of the right ventricle (RV) to adapt to increased afterload. Sotatercept, an activin signaling inhibitor, has demonstrated significant clinical and hemodynamic benefits in randomized trials. However, data regarding its effects on RV loading conditions, structural remodeling, systolic function, and RV–pulmonary arterial coupling in routine clinical practice remain limited.
Methods
We conducted a prospective, real-world, multi-center study including adult patients with World Health Organization functional class II or III pulmonary arterial hypertension, insufficiently stabilized with a double or triple therapy and receiving add-on subcutaneous sotatercept. Comprehensive transthoracic echocardiography was performed before treatment initiation and during follow-up. Several parameters assessing RV preload and afterload, RV structural remodeling, RV–pulmonary arterial coupling and RV function were analyzed according to the 2022 ESC/ERS guidelines for the diagnosis and treatment of pulmonary hypertension 1. Pre–post comparisons were performed using paired Student’s t-tests. Results are expressed as mean ± standard deviation. A two-sided p value <0.05 was considered statistically significant.
Results
A total of 100 patients were included. The mean age was 52 yo, 75 patients were female. The median delay between sotatercept initiation and follow-up echocardiography was 6 [1–30] months. Systolic pulmonary artery pressure decreased from 71 mmHg to 48 mmHg (p < 0,001). Sotatercept therapy was associated with a significant improvement in RV afterload parameters including pulmonary artery acceleration time (p 0.003) and mid-systolic notch (p<0.001) as well as RV preload parameters including right atrial area (p<0.001) and IVC diameters (p < 0.001). RV–pulmonary arterial coupling assessed by the TAPSE/sPAP ratio significantly improved (p<0.001), while structural parameters showed evidence of reverse remodeling, with significant reductions in RV end-diastolic surface area (p<0.001), RV/LV ratio (p<0.001) and eccentricity index (p <0.001). No improvement in RV systolic function parameters was observed including cardiac output (CO), TAPSE, S’ velocity, RV fractional shortening and RV free wall strain.
Conclusion
In a real-life PAH population, sotatercept treatment was associated with significant improvements in right ventricular loading parameters, ventriculo-arterial coupling, and right heart structural remodeling while no improvement was observed in conventional RV systolic function parameters, including cardiac output.For image description, please refer to the figure legend and surrounding text.For image description, please refer to the figure legend and surrounding text.