Absolute versus change in pulmonary vascular resistance in relation to European Society of Cardiology/European Respiratory Society risk change in pulmonary arterial hypertension

Introduction: In pulmonary arterial hypertension (PAH), it remains unclear whether absolute haemodynamic values or treatment-induced changes are more relevant to subsequent changes in clinical status. As risk classifications are increasingly used to guide clinical management, we evaluated whether pulmonary vascular resistance (PVR) at baseline, after 4 months of therapy, or treatment-induced change better explains risk change. Methods: Among 104 screened PAH patients, 69 were included retrospectively. The primary outcome was change in clinical status, defined as a shift in ESC/ERS 4-strata risk classification from baseline to 15 months. Haemodynamics were evaluated via right heart catheterization before and after 4 months of pharmacotherapy. Linear regression examined associations of baseline PVR, 4-month PVR, and ΔPVR with risk change. ROC analyses explored the ability of PVR (baseline, 4-month, and Δ), ΔRVEDP, and ΔCI to discriminate between risk stabilization and worsening. Results: Risk classification and PVR decreased significantly following treatment (p<0.001). ΔPVR had the highest partial explained variance for risk change (R²=0.118, p=0.003), followed by baseline PVR (R²=0.098, p=0.013). Four-month PVR did not significantly predict risk classification change. In ROC analyses, only ΔPVR significantly discriminated risk stabilization (AUC=0.75, p<0.001). Bootstrapping and permutation confirmed the robustness of these findings. Conclusions: The change in PVR after 4 months of treatment outperformed baseline and 4-month PVR, but also other dynamic measures (ΔRVEDP and ΔCI), in explaining changes in 4-strata risk classification and identifying risk stabilization. These findings suggest that ΔPVR provides complementary insight when interpreting serial haemodynamic evaluations in the context of early treatment response in PAH.