Right ventricular remodelling in pulmonary arterial hypertension after sotatercept therapy

Abstract

The expanding therapeutic armamentarium for pulmonary arterial hypertension (PAH), including the recent approval of sotatercept, is shifting treatment goals beyond achieving low-risk status towards haemodynamic improvement and right ventricular (RV) recovery. In this context, there is growing interest in echocardiography as a pragmatic, non-invasive tool to track RV adaptation during follow-up. A recently published echocardiographic model combining the RV end-diastolic area to left ventricular end-diastolic area ratio (RVEDA/LVEDA) and tricuspid annular plane systolic excursion to pulmonary artery systolic pressure ratio (TAPSE/PASP) enables RV phenotyping in 4 types beyond the traditional 4-strata risk assessment1. To evaluate longitudinal changes in RV phenotypes and associated clinical outcomes following sotatercept therapy. We included 46 consecutive PAH patients treated with sotatercept at a referral centre (2018–2025). All underwent echocardiography and right heart catheterization (RHC) at baseline and ≥3 months. Within-patient changes were analysed with Wilcoxon signed-rank or McNemar tests, and between-phenotype comparisons with Kruskal–Wallis or Fisher’s exact tests. Reclassification was shown using a Sankey diagram. The study was ethics-approved, and all patients provided informed consent. Median time since diagnosis was 8.7 years (4.6–12.8); median age 49.0 years (40.9–58.0), 71.3% women. Baseline haemodynamic severity was substantial (mean pulmonary arterial pressure (mPAP) 55 [42–64] mmHg; pulmonary vascular resistance (PVR) 9.9 [7.5–12.4] WU), with predominantly adverse echocardiographic phenotypes. During follow-up, 6 patients died or underwent lung transplantation. Events segregated by echocardiographic phenotype, occurring exclusively in baseline phenotypes 3–4, with no events in phenotypes 1–2 (Table 1). By contrast, according to ESC/ERS 4-strata events were distributed across intermediate risk strata (2/19 intermediate-low and 4/11 intermediate-high), with none in low or high risk (0/2). Among survivors (n=40), NT-proBNP decreased (573 vs 125 pg/mL; p<0.001) and 6-minute walk distance improved (422 vs 450 m; p=0.005); RHC confirmed reductions in mPAP and PVR (both p<0.001). Echocardiography showed RV reverse remodelling, with reduced right-sided chamber size, lower estimated PASP and improved RV function/coupling, accompanied by a marked shift towards favourable phenotypes (phenotype 1: 8.7% to 47.5%; p<0.001) (Figure 1). In PAH, sotatercept was associated with RV reverse remodelling, translating into a shift towards lower-risk echocardiographic phenotypes that may complement risk assessment and support follow-up monitoring.Table 1For image description, please refer to the figure legend and surrounding text.Figure 1For image description, please refer to the figure legend and surrounding text.