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Sotatercept Improves Right Heart Mechanics Despite Reduced Myocardial Contractility in Pulmonary Arterial Hypertension: A Prospective Exercise Hemodynamic Study
Key result
Sotatercept lowers resting RV contractility proportionally to afterload, preserving RV-PA coupling in PAH.
- MD -0.29 mm Hg/ml
- 95% CI -0.42 to -0.17
- P<0.0001
- n=30
Why the study?
The effects of sotatercept on right ventricular contractility, RV–PA coupling, and right heart deformation in pulmonary arterial hypertension have been inconsistent and require clarification.
Does sotatercept improve right heart mechanics and RV-PA coupling in patients with pulmonary arterial hypertension?
Population
30 participants with pulmonary arterial hypertension, mean age 49.3 years, 70% female
Comparison
Before and after 24 weeks of sotatercept treatment
Design
Prospective exercise hemodynamic study with simultaneous echocardiography and invasive pressure measurements
Follow-up
24 weeks
Authors
Discussion
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Implication
Sotatercept may favorably match RV contractility to lower afterload in PAH; extends mechanistic data but leaves open effects on hard outcomes versus prior trials.
Key Points
- To evaluate the effects of sotatercept on load-independent measures of right ventricular contractility, right ventricular–pulmonary arterial coupling, and right heart deformation at rest and exertion in pulmonary arterial hypertension.
- Prospective interventional trial (NCT06409026) in N=30 participants with pulmonary arterial hypertension recruited between July 2024 and May 2025 (mean age, 49.3 years [SD 13.5]; 70% female).
- Evaluated hemodynamic and functional changes before and after 24 weeks of sotatercept using simultaneous echocardiography and invasive catheterization during rest and exercise.
- Analyzed right ventricular contractility, afterload, coupling ratios, and chamber strain using linear mixed models.
- Sotatercept significantly reduced resting pulmonary arterial elastance (mean difference, −0.27 mm Hg/ml [95% CI, −0.43 to −0.11]; P=0.002) and right ventricular contractility (end-systolic elastance mean difference, −0.29 mm Hg/ml [95% CI, −0.42 to −0.17]; P<0.0001), while preserving ventricular–arterial coupling (mean difference, +0.08 [95% CI, −0.11 to +0.26]; P=0.42).
- Right ventricular free wall strain increased across rest and exercise (mean difference, +6.2% [95% CI, +4.5 to +7.8]; P<0.0001) alongside fractional area change (P=0.0001), despite reductions in basal annular metrics like tricuspid annular plane systolic excursion.
- Right atrial reservoir, conduit, and booster contractile performance improved significantly across rest and exercise (P<0.0001 for all), accompanied by a reduction in the maximal rate of right ventricular pressure increase (dP/dt max; P<0.001).
Structured PICO
Does sotatercept improve right heart mechanics and RV-PA coupling in patients with pulmonary arterial hypertension?
P
Population
30 symptomatic patients with pulmonary arterial hypertension on existing therapy were followed for 24 weeks after initiating sotatercept to evaluate right heart mechanics.
I
Intervention
Sotatercept added to existing PAH therapy for 24 weeks.
O
Outcome
Changes in right ventricular (RV) contractility (end-systolic elastance [Ees]), afterload (PA elastance [Ea]), RV–PA coupling (ratio of arterial Ea to Ees), and right heart deformation (RV and right atrial strain) at rest and exertion after 24 weeks.surrogate
Main Result
Mean Difference: -0.29 (95% CI -0.42–-0.17)
p-value: p=<0.0001
Sotatercept induces a physiologically appropriate reduction in right ventricular contractility that matches reduced afterload, preserving RV-PA coupling while improving global right heart deformation in pulmonary arterial hypertension.
Limitations
- Single-arm, open-label design without a placebo control group.
- Exercise Ees was estimated using an iterative model-based approach and not independently validated against exercise pressure-based methods.
- Modest sample size.
- Modest sample size
- Exercise Ees was estimated using an iterative model-based approach rather than directly measured
- Model-based estimates of exercise RV Ees were not independently validated against exercise pressure-based methods
Cite This Study
Reddy et al. (2026) studied Pulmonary Arterial Hypertension (n=30). Sotatercept vs. Baseline (pre-sotatercept) was evaluated on Change in resting right ventricular end-systolic elastance (Ees) (MD -0.29 mm Hg/ml, 95% CI -0.42 to -0.17, p=<0.0001). Sotatercept decreased resting right ventricular contractility (MD -0.29 mm Hg/ml) in proportion to reduced afterload, while preserving right ventricular-pulmonary arterial coupling.