Abstract Body (Do not enter title and authors here): Introduction: Sotatercept, an activin/GDF ligand-trapping fusion protein approved for pulmonary arterial hypertension (PAH), primarily targets vascular remodeling pathways with demonstrated hemodynamic improvements at 24 weeks. However, data from clinical trials and anecdotal patient reports suggest earlier symptomatic relief, raising the question of possible acute hemodynamic effects. We investigated whether sotatercept exerts immediate hemodynamic benefits by directly comparing it with rapid intravenous uptitration of treprostinil, a potent pulmonary vasodilator.
Methods: Ten patients with WHO Group 1 PAH (NYHA class III) were enrolled in the RV-Monitoring study (NCT05935865). The CorLog system was installed during routine right-heart catheterization for continuous RV pressure monitoring. Five patients received a single subcutaneous sotatercept dose (0.3 mg/kg), while five underwent rapid intravenous treprostinil titration (target dose: 20 ng/kg/min). RV end-systolic pressure (ESP), RV pulse pressure (RVPP), theoretical isovolumetric pressure (Piso), heart rate (HR), and RV–PA coupling (Ees/Ea) were calculated per heartbeat, aggregated hourly, and compared between groups.
Results: Baseline characteristics were comparable, except for lower PAWP in the sotatercept group. Both therapies produced distinct acute hemodynamic profiles. Sotatercept induced a rapid decline in RV afterload (ESP, RVPP), accompanied by a parallel decrease in contractility (Piso), leaving RV–PA coupling relatively unchanged. HR notably decreased, indicating selective pulmonary vascular unloading without systemic vasodilation, as suggested by a reduced RVPP × HR product. Conversely, treprostinil initially showed minimal effects on ESP and RVPP until infusion rates exceeded 10 ng/kg/min. At higher rates, pulmonary vasodilation became predominant, leading to improved Ees/Ea and elevated HR most likely due to systemic vasodilation-induced baroreflex activation.
Conclusion: Our findings provide the first indication of an acute pulmonary vasodilatory effect of sotatercept. Sotatercept may rapidly unload the RV but does not influence RV–PA coupling acutely. Clinically, sotatercept could be beneficial for immediate RV unloading in acute settings. Treprostinil, in contrast, improves RV–PA coupling but is accompanied by systemic vasodilation, baroreflex activation, most likely caused by alterations in systemic vascular resistance.