Non-invasive right ventricular pressure-volume analysis using three-dimensional echocardiography to assess cardiac performance in health and disease

Pressure-volume (PV) analysis is the reference standard for assessing right ventricular (RV) contractility and ventriculoarterial coupling (VAC), yet its invasive nature limits clinical use. Recent advances enable reconstruction of RV pressure waveforms from Doppler-derived peak systolic pressure, facilitating non-invasive PV loop assessment. Our aim was to develop and evaluate a three-dimensional echocardiography (3DE)-based method for non-invasive RV PV analysis by establishing normative reference values and determining prognostic relevance across diverse disease states. A total of 933 individuals (644 healthy subjects from the WASE study and 289 patients with heart failure, valvular heart disease, post-heart transplantation, or pulmonary hypertension) with available 3DE data and Doppler-derived RV peak systolic pressure were included. Non-invasive RV pressure waveforms were reconstructed and combined with 3DE-derived volume traces to generate PV loops (Figure, Panel A) and calculate end-systolic elastance (Ees), using the Pmax single-beat method, arterial elastance (Ea), and VAC (Ees/Ea). The primary outcome was all-cause mortality. Associations between non-invasive RV PV metrics and outcomes were assessed and visualized using restricted cubic spline (RCS) analyses. In a separate validation cohort (n=23), pressure-conductance catheter-derived PV-loop measurements were available to validate corresponding non-invasive PV-derived metrics. Non-invasively derived Ees and Ea correlated strongly with invasive Ees (r=0.798, p<0.001) and Ea (r=0.887, p<0.001), respectively (Figure, Panel B). In healthy individuals, females and those aged >65 years exhibited higher Ees and Ea, whereas VAC remained similar. Across all disease cohorts, Ees and Ea were higher, and VAC was lower compared with matched controls (all p<0.05). During a median follow-up of 34 months, 69 patients died. RCS analyses demonstrated a significant, non-linear, U-shaped association between Ees and mortality, and a linear association between Ea and mortality, in the disease cohort (Figure, Panel C). In multivariable models, VAC was independently associated with mortality in left-sided cardiac diseases (HR 0.41 [95% CI 0.19–0.90]; p<0.05), whereas Ees (HR 2.39 [95% CI 1.28–4.49]; p<0.05) and Ea (HR 2.11 [95% CI 1.11–4.04]; p<0.05) were independently associated with outcome in pulmonary hypertension. Non-invasive 3DE-derived PV-loop analysis enables comprehensive quantification of RV performance and VAC, demonstrates strong correlation with invasive gold-standard measurements, and identifies disease-specific alterations with independent prognostic value.