Background: Sotatercept has been shown to reduce the pulmonary vascular resistance (PVR), usually without changing cardiac index (CI) or stroke volume index (SVI). In contrast, with prostacyclins and other oral pulmonary arterial hypertension (PAH) therapies, PVR reduction is commonly accompanied by increases in both CI and SVI.

Methods: We retrospectively evaluated the haemodynamic trajectory of patients with PAH who sequentially received parenteral prostacyclins and sotatercept as part of the French early access program.

Results: Sixty-two patients were included. Before treatment with prostacyclins associated or not with oral therapies, the median CI was 2.00 [1.70; 2.20] L·min^-1 ·m^-2 . After treatment, the PVR and the mean pulmonary artery pressure (mPAP) decreased by -54.6% (95% confidence intervals -60.4%; -47.9%) and -21.3% (-25.4%; -16.9%) respectively. The CI and the right ventricular (RV) power increased by 63.1% (52.0%; 75.1%) and 26.3% (18.3%; 34.8%) respectively. Before sotatercept, the median CI was 3.00 [2.60; 3.50] L·min^-1 ·m^-2 . After sotatercept, the PVR and the mPAP decreased by -25.8% (-31.5%; -19.7%) and -23.8% ( -27.7%; -19.7%) respectively, possibly associated with a small decrease of CI (-4.7% (-9.2%; -0.1%)). By contrast with prostacyclins, RV power decreased by -26.9% after sotatercept (-31.7%; -21.7%). Baseline CI and change in hemoglobin were independently associated with change in CI after sotatercept in multivariable analyses. The model was statistically significant and explained 44% of the variation in CI (p<0.001).

Conclusions: Unlike parenteral prostacyclins, sotatercept initiation reduces PVR without increasing CI, resulting in a concomitant decrease in RV power. Different effects on CI may reflect distinct physiological mechanisms or differences in baseline patient characteristics.