Sotatercept improves right ventricular function but is associated with new or worsening pericardial effusions: a cardiovascular magnetic resonance study in intermediate-high risk pulmonary arterial hypertension.

Abstract

Background: Sotatercept is a novel drug therapy for pulmonary arterial hypertension (PAH) that significantly reduces clinical worsening and improves exercise capacity, functional class, and pulmonary haemodynamics. This study aims to use cardiovascular magnetic resonance (CMR) to monitor the cardiac response to sotatercept in patients with PAH.

Methods: Patients with PAH at intermediate-high or high mortality risk and already on background maximal triple PAH therapies, including parenteral prostacyclin analog for at least 3 months, were offered enrollment to a patient access program for sotatercept at the Royal Free Hospital National Pulmonary Hypertension Service. Baseline and follow-up CMR studies were performed at a median interval of 24 (interquartile range 6) weeks.

Results: Eighteen out of 23 patients enrolled in the sotatercept access program underwent baseline and follow-up CMR studies (3 patients paused or discontinued sotatercept prior to 12 weeks; 2 patients were unable to undergo CMR). All 18 patients were stratified as being of intermediate-high mortality risk. Significant improvements were observed in right ventricular (RV) size (RV end-diastolic volume -34±30 mL, p = 0.0023; RV end-systolic volume -27 ± 29 mL, p = 0.0023), RV mass (Z = -2.63, p = 0.016), RV function (RV ejection fraction 5 ± 8%, p = 0.034) and right atrial size (-6 ± 4 cm², p = 0.0023). End-systolic interventricular septal curvature also significantly improved at follow-up (Z = 2.07, p = 0.046), suggesting improvement in RV afterload. Five (28%) patients also had a new-onset (1) or larger (4) pericardial effusion without haemodynamic compromise at follow-up, despite improvements in clinical, biochemical, and CMR metrics of PAH. The median increase in pericardial effusion volume was 69% (full range 33%-203%, Z = 2.0, p = 0.043).

Conclusion: CMR tracks improvements in right heart chamber size, mass, and function along with metrics of RV afterload in patients with PAH receiving sotatercept. The improvements in RV size and function met or exceeded the clinically relevant minimally important differences for these CMR-derived metrics in patients with PAH. Routine interval surveillance with CMR in patients receiving sotatercept will also enable surveillance for the off-target finding of new-onset or worsening pericardial effusions.