Sotatercept increases exercise tolerance in patients with pulmonary arterial hypertension

Patients with pulmonary arterial hypertension treated with sotatercept demonstrate improved exercise tolerance, driven in part by increased haemoglobin, according to a study.

Thirty participants (mean age 49.3 percent, 70 percent women) received sotatercept and showed improvements in the primary endpoint of peak exercise mean pulmonary artery (PA)/cardiac output (CO; ‒2.1 mm Hg/L/min, 95 percent confidence interval [CI], ‒3.1 to ‒1.1; p=0.0003).

Moreover, sotatercept use resulted in reductions in pulmonary vascular resistance (‒2.6 WU, 95 percent CI, ‒3.0 to ‒2.2; p<0.0001), mean PA pressure (‒12.5 mm Hg, 95 percent CI, ‒13.8 to ‒11.2; p<0.0001), and right ventricular (RV) work (‒1.1 kg-m/min, 95 percent CI, ‒1.4 to ‒0.9; p<0.0001) and improved RV-PA coupling across rest and exercise.

Sotatercept also mitigated systemic congestion, as shown by decreases in N-terminal pro‒B-type natriuretic peptide (p<0.0001), right atrial pressure (p=0.04), and blood volume (p<0.0001).

Increases were likewise noted in resting haemoglobin (1.7 g/dL, 95 percent CI, 1.1‒2.2; p<0.0001) that were associated with reductions in plasma volume (p<0.0001), with no effect on red cell mass (p=0.12). Furthermore, sotatercept reduced resting CO (‒0.58 L/min, 95 percent CI, ‒0.85 to ‒0.32; p<0.0001), which may be associated with the increase in haemoglobin.

“Despite lower resting CO, CO reserve with exercise was enhanced (0.74 L/min, 95 percent CI, 0.15‒1.32; p=0.015), which was associated with improved aerobic capacity (peak oxygen consumption; r, 0.69, 95 percent CI, 0.43‒0.84; p<0.0001),” the investigators said. “Single-leg exercise performance also improved after sotatercept.”

Additionally, sotatercept use led to increases in convective oxygen delivery with exertion (p=0.002) and peripheral oxygen uptake in skeletal muscle, driven by an increase in arterial-femoral venous O₂ content difference across phases (1.1 mL/dL, 95 percent CI, 0.7‒1.4; p<0.0001).

In this study, participants underwent blood volume quantification, supine invasive cardiopulmonary exercise testing with simultaneous echocardiography, single-leg exercise catheterization, and exercise femoral venous blood sampling. They also underwent seven paired haemodynamic assessments before and after treatment with sotatercept, namely rest, nitric oxide, passive leg raise, 20-W exercise, peak exercise, repeat baseline, and single-leg exercise.