Trial reportJournal of the American College of Cardiology2026
Sotatercept in Pulmonary Arterial Hypertension: Central, Hematologic, and Peripheral Mechanisms of Benefit.
Trial report in Journal of the American College of Cardiology, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 5 papers.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
5 citing papers in PubMed.
- Sotatercept Improves Right Heart Mechanics Despite Reduced Myocardial Contractility in Pulmonary Arterial Hypertension: A Prospective Exercise Hemodynamic Study.Circulation · 2026Article
- Disentangling Pulmonary Vascular Phenotypes in Group 2 Pulmonary Hypertension Using Bioactive Lipid Profiling.Circulation. Heart failure · 2026Article
- Activin Signaling Inhibitors in Pulmonary Hypertension: A State-of-the-Art Review.Pulmonary circulation · 2026Review
- Observed Weight Gain in Patients With Pulmonary Arterial Hypertension Treated With Sotatercept.Pulmonary circulation · 2026Article
- Picking Up the Tempo on Treatment of Combined Post- and Pre-capillary Pulmonary Hypertension: Viewpoint on the CADENCE Trial.US cardiology · 2026Review
Corrections and comments
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Authors and funding
6 authors.
Funding
Abstract
backgroundSotatercept is an activin ligand trap that markedly improves exercise tolerance in patients with pulmonary arterial hypertension (PAH).
objectivesThe aim of this study was to determine the mechanisms of these functional benefits.
methodsThe effects of 24-week sotatercept treatment on central and peripheral determinants of aerobic capacity, hemodynamic status, cardiovascular function, and oxygen transport in patients with PAH were comprehensively evaluated. Participants underwent blood volume quantification, supine invasive cardiopulmonary exercise testing with simultaneous echocardiography, single-leg exercise catheterization, and exercise femoral venous blood sampling. Participants underwent 7 paired hemodynamic assessments before and after sotatercept (rest, nitric oxide, passive leg raise, 20-W exercise, peak exercise, repeat baseline, and single-leg exercise).
resultsAmong 30 participants (mean age 49.3 ± 13.5 years, 70% women), sotatercept improved the primary endpoint of peak exercise mean pulmonary artery (PA)/cardiac output (CO) (-2.1 mm Hg/L/min; 95% CI: -3.1 to -1.1 mm Hg/L/min; P = 0.0003). Sotatercept reduced pulmonary vascular resistance (-2.6 WU; 95% CI: -3.0 to -2.2 WU; P < 0.0001), mean PA pressure (-12.5 mm Hg; 95% CI: -13.8 to -11.2 mm Hg; P < 0.0001), and right ventricular (RV) work (-1.1 kg-m/min; 95% CI: -1.4 to -0.9 kg-m/min; P < 0.0001) and improved RV-PA coupling across rest and exercise. Sotatercept reduced systemic congestion, evidenced 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 in resting hemoglobin were observed (1.7 g/dL; 95% CI: +1.1 to +2.2 g/dL; P < 0.0001) that were related to reduction in plasma volume (P < 0.0001), as there was no effect on red cell mass (P = 0.12). A decrease in resting CO was observed with sotatercept (-0.58 L/min; 95% CI: -0.85 to -0.32 L/min; P < 0.0001), which appeared to be related to the increase in hemoglobin. Despite lower resting CO, CO reserve with exercise was enhanced (+0.74 L/min; 95% CI: +0.15 to +1.32 L/min; P = 0.015), which was associated with improved aerobic capacity (peak oxygen consumption; r = +0.69; 95% CI: +0.43 to +0.84; P < 0.0001). Single-leg exercise performance also improved after sotatercept. Sotatercept increased both convective oxygen delivery with exertion (P = 0.002; interaction P = 0.018) and peripheral oxygen uptake in skeletal muscle, as evidenced by an increase in arterial-femoral venous O
conclusionsSotatercept improves exercise tolerance in patients with PAH through multiple, previously unappreciated mechanisms beyond the pulmonary vasculature, including increased hemoglobin (driven in part by systemic decongestion with hemoconcentration), which along with enhanced RV-PA coupling and CO reserve increases skeletal muscle O
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