Right ventricular remodelling in pulmonary arterial hypertension after sotatercept therapy
E Gutierrez Ortiz, I Martin de Miguel, A Cruz-Utrilla, C Jimenez Lopez-Guarch, B Brown Arreola, M L Coronel, F Pastor Perez, M J Cristo Ropero, N Ochoa Parra, M Velazquez Martin, F Arribas Ynsurriaga, P Escribano SubiasAbstract
Background
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.
Purpose
To evaluate longitudinal changes in RV phenotypes and associated clinical outcomes following sotatercept therapy.
Methods
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.
Results
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).
Conclusion
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.