Dottorato in FISIOPATOLOGIA ED IMAGING CARDIO-TORACO-VASCOLARE

Titolo della tesi: Echocardiography of the right heart in pulmonary arterial hypertension. Insights from the ULTRA RIGHT VALUE study

Aims: In pulmonary arterial hypertension (PAH), outcomes are determined by right ventricular (RV) functional adaption to increased afterload. Echocardiography is readily available for bedside RV evaluation; however, it remains poorly implemented in guideline-directed clinical decision-making due to evidence quality concerns not meeting regulatory standards. Methods and Results: This multicenter study gathered echocardiographic data with centralized reading from 401 patients with prevalent PAH. Clinical data—including World Health Organization (WHO) functional class (FC), 6- minute walk distance (6MWD), brain natriuretic peptide (BNP)/NT-pro-BNP, invasive hemodynamics, the European Society of Cardiology (ESC)/European Respiratory Society (ERS) guidelines-derived 4-strata score, and the United States REVEAL 2.0 score—were also collected. The primary outcome was a composite of all-cause mortality and heart failure hospitalizations. The secondary outcome was the maintenance or achievement of low-risk status according to ESC/ERS and REVEAL 2.0 at the latest follow-up. Echocardiographic measurements revealed varying degrees of right heart dilation, assessed through right atrial and RV areas, along with altered indices of systolic function, including tricuspid annular plane systolic excursion (TAPSE), fractional area change, 2D strain, and estimates of RV to pulmonary artery (PA) coupling, obtained by relating RV systolic function metrics to systolic PA pressure (sPAP). All measurements were feasible. Right heart dimensions and function metrics, particularly the TAPSE/sPAP ratio, correlated with WHO functional class, 6-minute walk distance, BNP/NT-proBNP levels, invasive hemodynamics, and both ESC/ERS and REVEAL 2.0 scores. Echocardiographic assessments were significantly associated with the composite endpoint of mortality and heart failure hospitalization and were predictive of maintaining or achieving low-risk status at follow-up. Echocardiography provided additional discriminative power, enhancing both ESC/ERS and REVEAL 2.0 scores, especially when a key risk score variable was missing. Conclusions: This quality-controlled data from a network of PAH referral centers validates the associations between echocardiographic and pulmonary hemodynamic parameters and offers strong evidence for the prognostic value of morphological and functional echocardiographic variables in PAH. Our findings support the integration of echocardiographic assessments into existing risk stratification models for PAH patients.