Redefining risk in HFrEF: a novel 3D-echocardiographic index of RV PA coupling as a predictor of early mortality

Abstract Background Right ventriculo-pulmonary arterial (RV-PA) coupling, an essential measure of adaptation of right ventricle to increased afterload, is a relevant prognostic parameter in heart failure with reduced ejection fraction (HFrEF). Although several echocardiographic indices are proposed for its assessment, their comparative value in predicting mortality and rehospitalization remains uncertain. Objective To compare prognostic value of multiple echocardiographic parameters reflecting RV–PA coupling, measured by 2D, tissue Doppler imaging (TDI), and 3D echocardiography, in patients hospitalized with decompensated HFrEF, at 5 years follow up. Methods We prospectively enrolled 340 patients (59±13 years, 80% male, LVEF 30±10%), hospitalized with acute decompensated HFrEF. Right ventricular systolic function was assessed using the following echocardiographic parameters: TAPSE, FAC, S’, RV free wall longitudinal strain (FWLS), and 3D-derived RV volumes and ejection fraction (RVEF). RV–PA coupling was assessed using the following indices: TAPSE/sPAP, RV S' (TDI)/sPAP, RV Fractional Area Change (FAC)/sPAP, 3D RVEF/sPAP, and RV Stroke Volume/RV End-Systolic Volume (RVSV/RVESV), derived from 3D echocardiography. Primary endpoint was all-cause mortality at 5 years. Binary univariate and multivariable logistic regression, ROC analysis, and survival analyses (Kaplan-Meyer curves) were performed. Results By binary univariate analysis, all 2D parameters and 3D RV-PA coupling indices were significantly associated with mortality (p < 0.001). By multivariate logistic regression, only 3D RVSV/RVESV remained an independent predictor of death (OR = 0.57, 95%CI 0.38–0.86, p = 0.007). ROC analysis to predict mortality showed that RVSV/RVESV < 0.60 had the highest area under the curve (AUC = 0.82), significantly outperforming TAPSE/sPAP < 0.55 (AUC = 0.70), FAC/sPAP ??? (AUC = 0.73), and RVEF/sPAP ??? (AUC = 0.78) (Figure 1A). A cut-off < 0.60 for RVSV/RVESV had a sensitivity of 88% and a specificity of 60% for predicting death, outperforming TAPSE/PAPs < 0.55 (sensitivity of 84%, and specificity of 65%), and other conventional metrics. Kaplan-Meier survival analysis showed that patients with an RVSV/RVESV < 0.6 had a median survival of 5.5 months (95%CI: 1.2–9.8), with a steep decline in early survival (Figure 1B). This logarithmic curve identifies an high-risk population, with markedly reduced early survival. Conclusion Among echocardiographic indices of RV–PA coupling, the 3D-derived RVSV/RVESV provides the strongest independent prognostic information regarding early mortality in patients hospitalized for decompensated HFrEF. This novel parameter may offer improved risk stratification and should be considered in routine assessment.