Abstract
BACKGROUND: Defining qualitative grades of echocardiographic metrics of right heart chamber size and function is critical for screening, clinical assessment, and measurement of therapeutic response in individuals with pulmonary vascular disease (PVD). In a population enriched for PVD, we sought to establish qualitative grades and prognostic value of right heart chamber size and function. METHODS: We investigated 1053 study participants in the Redefining Pulmonary Hypertension through PVD Phenomics program (PVDOMICS) to determine clinical and echocardiographic differences associated with increasing pulmonary vascular resistance (PVR) severity. Right heart chamber size and function were qualitatively assessed using a percentile-based approach above the median values to create a clinical grading system for right heart adaptation. The relationship between echocardiographic categories and all-cause mortality was examined using survival analyses adjusted for potential confounders. RESULTS: A stepwise increase in adverse right heart remodeling was observed with a concomitant decrease in functional parameters by PVR strata (p<0.001 for all). Mild, moderate, and severe categories of right heart chamber size and dysfunction were defined using a percentile-based approach across the spectrum of PVD. During a median follow up of 2.07 years (interquartile range 1.23 - 3.01 years), 130 participants died (11.4%). Progressive PVR increase and 2DE evidence of right heart dysfunction inclusive of fractional area change, and right ventricular (RV) global longitudinal strain were independently associated with increased all-cause mortality risk in multivariate analysis adjusted for age, disease duration and male sex. CONCLUSIONS: In this well-characterized sample of adults with diverse etiologies and varying PVD severity, we define categories of abnormal right heart chamber size and function. Further, we demonstrate a stepwise relationship between these categories of abnormal morphology and function and all-cause mortality. Defining grades of RV dysfunction in individuals with known PVD has important clinical implications for monitoring disease progression and response to therapies.