Echocardiographic Parameters Enhance Risk Prediction Scores in Pulmonary Arterial Hypertension: Insights from the PVDOMICS Network.

Abstract

BACKGROUND Echocardiographic metrics of right ventricular (RV) chamber size and function enhance prognostication, risk stratification, and measurement of therapeutic response in patients with pulmonary arterial hypertension (PAH), though the most effective metrics remain unclear. RESEARCH QUESTION In a well phenotyped cohort of patients with incident and prevalent PAH, can qualitative grades of RV echocardiographic function be established based on their association with functional outcomes, and do they demonstrate prognostic value beyond traditional risk scores? METHODS In the Redefining Pulmonary Hypertension through Pulmonary Vascular Disease Phenomics program (PVDOMICS), 405 (336 prevalent, 69 incident) participants were investigated. Multivariable linear regression examined associations with six-minute walk distance and COMPERA and REVEAL Lite 2.0 PAH risk scores. Penalized Cox Regression was used to develop new models combining prior risk score variables with echo parameters, and cluster analysis combined with survival analysis adjusting for potential confounders to demonstrate prognostic significance. RESULTS In both incident and prevalent PAH, reduced RV function was associated with increased NT-proBNP, reduced six-minute walk distance, and increased COMPERA and REVEAL Lite 2.0 risk scores after adjusting for duration of PAH and relevant confounders. Addition of echocardiographic variables to models incorporating the COMPERA and REVEAL 2.0 scores yielded a 10% increase in the C-statistic compared to either score alone. Mild, moderate, and severe categories of RV dysfunction associated with increased all-cause mortality, with up to a 3.0-fold increase in mortality in multivariable models adjusted for relevant confounders, PAH duration, and invasive pulmonary vascular resistance. INTERPRETATION Reduced RV function on echocardiography in PAH associates with worsened outcomes in incident and prevalent PAH. Echocardiographic assessment of RV function provides additional value to existing PH risk prediction scores and invasive hemodynamics. Furthermore, defining severity of RV function through cluster analysis has important implications for risk prognostication with potential application to monitor response to therapy.