Risk stratification with echocardiographic biomarkers in heart failure with preserved ejection fraction: the media echo score

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.

Keywords: Cardiac oedema; Cardiovascular diseases; Diastolic function; Echocardiography; Heart failure, diastolic; Preserved ejection fraction; Risk prediction.

Figure 1

Associations between echocardiographic measurements and high levels of N‐terminal pro‐brain natriuretic peptide (> 450 pg/mL in patients below 50 years, >900 in patients aged 50–75 years, and >1800 in patients over 75 years). *Adjusted on age, estimated glomerular filtration rate, body mass index, atrial fibrillation, and clinical presentation.

Figure 2

Associations between echocardiographic parameters and time to cardiovascular/heart failure hospitalization or all‐cause death. *Adjusted for dichotomous N‐terminal pro‐brain natriuretic peptide, age, estimated glomerular filtration rate, gender, left ventricular ejection fraction, atrial fibrillation, and clinical presentation.

Figure 3

Multivariable integrated echocardiographic models in the MEDIA project (Panel A) and its added prognostic value in the MEDIA project (Panel B) and the KaRen cohort (Panel C). Panel A: Cox regression model using subset of variables retained after backward selection (using missing‐indicator method) with N‐terminal pro‐brain natriuretic peptide (NT‐proBNP) as a dichotomous or linear variable; Panels B and C: Improvement in prognostic value for the primary endpoint on top of clinical model (including age, estimated glomerular filtration rate, atrial fibrillation, and heart failure status), assessed by net reclassification improvement (NRI) and C‐index.