Echocardiographic Parameters and Risk Prediction in Pulmonary Arterial Hypertension: Insights From the Redefining Pulmonary Hypertension Through Pulmonary Vascular Disease Phenomics Network.

backgroundEchocardiographic 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? STUDY DESIGN AND

methodsIn the Redefining Pulmonary Hypertension Through Pulmonary Vascular Disease Phenomics (PVDOMICS) program, 405 (prevalent, n = 336; incident, n = 69) participants were investigated. Multivariable linear regression examined associations with 6-minute walk distance and the Comparative Prospective Registry for Newly Initiated Therapies (COMPERA) and the Registry to Evaluate Early and Long-Term PAH Disease Management (REVEAL) Lite 2.0 PAH risk scores. Penalized Cox regression was used to develop new models combining prior risk score variables with echo parameters. Cluster analysis combined with survival analysis adjusting for potential confounders was used to demonstrate prognostic significance.

resultsIn both incident and prevalent PAH, reduced RV function was associated with increased N-terminal pro-B-type natriuretic peptide levels, reduced 6-minute walk distance, and increased COMPERA and REVEAL Lite 2.0 risk scores after adjusting for duration of PAH and relevant confounders. The addition of echocardiographic variables to models incorporating the COMPERA and REVEAL 2.0 scores yielded a 10% increase in the C-statistic. The severe RV dysfunction group was associated with increased all-cause mortality, with up to a threefold increase in mortality in multivariable models adjusted for relevant confounders, PAH duration, and invasive pulmonary vascular resistance.

interpretationOur results show that reduced RV function on echocardiography in PAH is associated with worsened outcomes in incident and prevalent PAH. Echocardiographic assessment of RV function provided 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.