December 8, 2025Open Access

Transthoracic echocardiography of left ventricular underfilling improves risk stratification in pulmonary arterial hypertension

Key Points

Left ventricular underfilling is linked to poorer survival outcomes in pulmonary arterial hypertension, enhancing risk stratification.
Cox regression determined that key left ventricular parameters are significant predictors of survival outcomes in PAH.
Transthoracic echocardiography assessment was utilized to evaluate prognostic accuracy compared to established models.
Integrating left ventricular parameters offers better discrimination for patient prognosis in pulmonary arterial hypertension management.

Abstract

Abstract Pulmonary arterial hypertension (PAH) is characterized by right ventricular (RV) adaptation to elevated afterload. However, the prognostic value of left ventricular (LV) underfilling in response to RV volume overload is unknown. We aimed to investigate the prognostic value of LV underfilling in PAH. Does Trans-thoracic echocardiography (TTE) assessed LV underfilling enhance prognostic accuracy in PAH beyond existing models such as REVEAL-Lite 2.0 and REVEAL-ECHO? 270 patients with PAH were prospectively enrolled. LV underfilling was defined as the LV volume-to-mass (V/M) ratio of < 0.8 ml/g. TTE and hemodynamic parameters were compared between patients with and without LV underfilling. The Cox regression model identified LV parameters significantly predictive of survival. The current LV model was developed incorporating LV parameters and was compared with established models, including REVEAL-Lite 2.0 and REVEAL-ECHO. Cox-regression and model performance metrics, including the C-index, Akaike Information Criterion (AIC), Net Reclassification Improvement (NRI), and Integrated Discrimination Improvement (IDI), were used to assess the model’s prognostic accuracy. Patients with LV underfilling exhibited more advanced disease, with higher hemodynamic indices and impaired RV function (all p < .0001). Over a median 29.8 months follow-up, LV underfilling was associated with worse survival (Log-rank p < .0001). LV underfilling (HR: 5.32, 95% CI; 3.05–9.28, p = < .0001), RV/LV-basal diameter (HR: 1.96, 95% CI; 1.066–3.624, p = 0.03), LV end-diastolic diameter (HR: 1.071, 95% CI: 1.030–1.114, p = 0.0005) served as independent predictors of adverse outcomes. The current LV model integrating LV parameters demonstrated superior discrimination (Mean C-index: 0.716 ± 0.06) vs REVEAL-Lite 2.0 (Mean C-index: 0.585 ± 0.07) and REVEAL-ECHO (Mean C-index: 0.717 ± 0.11). The model also demonstrated superior reclassification and discrimination performance compared to traditional models (NRI: 0.225, IDI: 2.28). TTE-assessed LV underfilling is a novel, valuable prognostic marker in PAH. The Current LV model, in addition to REVEAL-ECHO, offers enhanced prognostic capabilities for PAH management and may serve as a key tool in optimizing PAH patient care.

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