Abstract
AIMS: Echocardiographic predictors of outcomes in heart failure with preserved ejection fraction (HFpEF) have not been systematically or independently validated. We aimed at identifying echocardiographic predictors of cardiovascular events in a large cohort of patients with HFpEF and to validate these in an independent large cohort. METHODS AND RESULTS: We assessed the association between echocardiographic parameters and cardiovascular outcomes in 515 patients with heart failure with preserved left ventricular (LV) ejection fraction (>50%) in the MEtabolic Road to DIAstolic Heart Failure (MEDIA) multicentre study. We validated out findings in 286 patients from the Karolinska-Rennes Prospective Study of HFpEF (KaRen). After multiple adjustments including N-terminal pro-brain natriuretic peptide (NT-proBNP), the significant predictors of death or cardiovascular hospitalization were pulmonary arterial systolic pressure > 40 mmHg, respiratory variation in inferior vena cava diameter > 0.5, E/e' > 9, and lateral mitral annular s' < 7 cm/s. The combination of these four variables differentiated patients with <10% vs. >35% 1 year risk. Adding these four echocardiographic variables on top of clinical variables and NT-proBNP yielded significant net reclassification improvement (33.8%, P < 0.0001) and increase in C-index (5.3%, a change from 72.2% to 77.5%, P = 0.015) of similar magnitude as the addition of NT-proBNP on top of clinical variables alone. In the KaRen cohort, these four variables yielded a similar improvement in net reclassification improvement (22.3%, P = 0.014) and C-index (4.0%, P = 0.029). CONCLUSIONS: Use of four simple echocardiographic parameters (within the MEDIA echo score), indicative of pulmonary hypertension, elevated central venous pressure, LV diastolic dysfunction, and LV long-axis systolic dysfunction, independently predicted prognosis and improved risk stratification additionally to clinical variables and NT-proBNP in HFpEF. This finding was validated in an independent cohort.