Pulmonary vascular disease & thromboembolism

Sotatercept in Pulmonary Arterial Hypertension: Central, Hematologic, and Peripheral Mechanisms of Benefit

J Am Coll CardiolPublished Mechanistic study

Main finding · Peak exercise mean PA pressure/COResult — go to the resultChange −2.1 mm Hg/L/min 95% CI −3.1 to −1.1

Authors' conclusion

Sotatercept 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 O2 delivery.

Study context

Population
Patients with PAH
Participants
30 patients
Comparison
After vs before 24-week sotatercept
Outcome
Peak exercise mean PA pressure/CO
Follow-up
24 weeks
Methodological detailssingle-arm, before-and-after (24-week sotatercept)
  • Single-arm
  • Before-and-after (24-week sotatercept)

Main finding

As reported in the abstract

Change

−2.1 mm Hg/L/min

95% CI −3.1 to −1.1

P = 0.0003

Aftervs before 24-week sotatercept
change −2.1 mm Hg/L/min (95% CI −3.1 to −1.1); P = 0.0003

Further findings

Pulmonary vascular resistance, mean pulmonary artery (PA) pressure, right ventricular (RV) work

Change (WU) (95% CI)P value
SotaterceptPulmonary vascular resistance−2.6 (−3.0 to −2.2)P < 0.0001
Change (mm Hg) (95% CI)P value
SotaterceptMean PA pressure−12.5 (−13.8 to −11.2)P < 0.0001
Change (kg-m/min) (95% CI)P value
SotaterceptRV work−1.1 (−1.4 to −0.9)P < 0.0001

Resting cardiac output (CO)

Change (L/min) (95% CI)P value
Sotatercept−0.58 (−0.85 to −0.32)P < 0.0001
OutcomeChange (mL/dL) (95% CI)P value
Oxygen delivery and uptakeArterial-femoral venous O2 content difference across phases+1.1 (+0.7 to +1.4)P < 0.0001
Oxygen delivery and uptake — Increased convective oxygen delivery with exertion
P = 0.002; interaction P = 0.018

Pulmonary vascular resistance, mean PA pressure, RV work

Improved RV-PA coupling across rest and exercise

Systemic congestion

Decrease in NT-proBNP
P < 0.0001
Decrease in right atrial pressure
P = 0.04
Decrease in blood volume
P < 0.0001

Oxygen delivery and uptake

Single-leg exercise performance improved

Parts of this Brief are withheld: the automatic checks could not confirm them against the abstract.

Original publication

Sotatercept in Pulmonary Arterial Hypertension: Central, Hematologic, and Peripheral Mechanisms of Benefit. J Am Coll Cardiol. Published 2 March 2026. doi:10.1016/j.jacc.2026.02.5103

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