Circulation
September 22, 2026 · via Europe PMC
Sotatercept Improves Right Heart Mechanics Despite Reduced Myocardial Contractility in Pulmonary Arterial Hypertension: A Prospective Exercise Hemodynamic Study.
Reddy YNV, Kazui S, Miranda WR, Harada T, Frantz RP, Burkhoff D, Borlaug BA.
AI summary — for doctors, generated from the abstract only
In a small prospective exercise hemodynamic study, sotatercept reduced right ventricular contractility in proportion to reduced afterload while preserving RV-pulmonary artery coupling, and was associated with improved global right heart performance measures at rest and exercise.
What was studied
A prospective trial of 30 patients (21 analyzed) with pulmonary arterial hypertension, using simultaneous echocardiography and invasive pressure measurements at rest and exercise before and after 24 weeks of sotatercept, assessing right ventricular (RV) contractility, afterload, RV-pulmonary artery coupling, and right heart strain via mixed models.
Key findings
- Sotatercept decreased pulmonary artery elastance (afterload), which was associated with reduced RV contractility, pulmonary artery pulsatility index, and maximal rate of RV pressure rise; some exact statistical values are not reported in the available truncated abstract text.
- Annular-based systolic indices (tricuspid annular plane systolic excursion, tricuspid annular systolic velocity) decreased after treatment, but RV free wall strain increased both at rest and exercise (mean difference +6.2%, 95% CI +4.5 to +7.8).
- Right atrial filling and contractile performance also improved across rest and exercise.
Clinical relevance
This suggests sotatercept produces an energetically favorable reduction in RV contractility matched to reduced afterload, without apparent detriment to overall right heart function or exercise reserve, which may help explain how this therapy benefits the right heart in pulmonary arterial hypertension over time.
Who should care
Limitations
This was a small sample size (21-30 patients); it is a mechanistic/physiologic study, not designed to assess clinical outcomes; parts of the statistical reporting are truncated in the available abstract text.
Sotatercept lowers RV contractility in proportion to reduced afterload in pulmonary arterial hypertension, but overall right heart performance, including free wall strain and atrial function, improves, suggesting a favorable physiologic adaptation.
This is an AI-generated summary of the published abstract, not a clinical recommendation. It may not reflect the full text or subsequent updates — verify against the original source before acting on it.
Abstract
Background
The right ventricular (RV) response to pressure overload is a crucial determinant of outcomes in pulmonary arterial (PA) hypertension. Sotatercept improves clinical outcomes, but its effects on the right ventricle have been inconsistent. We evaluated the effects of sotatercept on load-independent measures of RV contractility, RV-PA coupling, and right heart deformation at rest and exertion in patients with PA hypertension.
Methods
In this prospective trial among participants with PA hypertension recruited between July 2024 and May 2025, we performed simultaneous echocardiography and invasive pressure measurements during rest and exercise to evaluate changes in RV contractility (end-systolic elastance [Ees]), afterload (PA elastance [Ea]), RV-PA coupling (ratio of arterial Ea to Ees), and right heart deformation, including RV and right atrial strain, before and after 24 weeks of sotatercept using mixed models.
Results
Among 30 participants (n=21; 70% female; mean age, 49.3 years [SD 13.5]), sotatercept decreased PA Ea. These changes were associated with reduced RV contractility, PA pulsatility index, and the maximal rate of RV pressure increase over time (dP/dtmax; PPP=0.42). Although systolic indices measured at the base of the right ventricle (tricuspid annular plane systolic excursion and systolic velocity of the lateral tricuspid annulus) decreased after sotatercept use, there was an increase in RV free wall-dependent systolic indices, including resting and exercise RV free wall strain (mean difference, +6.2% [95% CI, +4.5 to +7.8]; PP=0.0001). Beyond the right ventricle, there was also improved right atrial filling and contractile performance across rest and exercise (P<0.0001 for all).
Conclusions
Sotatercept decreases RV contractility in proportion to reduced afterload, while preserving the RV-PA coupling relationship. Despite decreased RV contractility, global measures of right heart performance, such as RV free wall strain and RA strain, improve, alongside redistribution of RV deformation from annular motion to free wall shortening. These data suggest that sotatercept causes an energetically favorable reduction in resting RV contractility to match the lower afterload, which does not appear physiologically detrimental when considering the concurrent improvement in RV free wall contractile mechanics and exertional right heart reserve.
Registration
URL: https://www.clinicaltrials.gov; Unique identifier: NCT06409026.
DOI
10.1161/circulationaha.126.081334
PMID
42770225
Research metadata (titles, abstracts, authors, publication dates) is sourced from Europe PMC, which aggregates content from PubMed/MEDLINE, PubMed Central, and other providers under the U.S. National Library of Medicine (NLM/NCBI). NLM does not claim copyright on abstracts; the original journal publishers or authors may hold rights to the full articles. AI-generated summaries are derived only from the abstract, never the full text, and are always labeled as AI-generated.
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