Reduced right ventricular ejection fraction predicts incident heart failure and mortality in individuals without prevalent heart failure: a propensity score-matched UK Biobank analysis
M Tokodi, L Szabo, A Szijarto, E Surkova, A Kalapos, B K Lakatos, A Fabian, S E Petersen, B Merkely, A KovacsAbstract
Background
Right ventricular (RV) dysfunction is increasingly recognized as a determinant of adverse outcomes in established cardiovascular disease. However, the prognostic relevance of reduced RV ejection fraction (RVEF) in individuals without heart failure and with preserved left ventricular ejection fraction (LVEF) remains insufficiently characterized in large population-based cohorts.
Objective
We aimed to investigate the prognostic value of reduced RVEF in a large cohort of UK Biobank participants without a history of heart failure and with preserved LVEF.
Methods
From the UK Biobank, participants who had undergone cardiovascular magnetic resonance (CMR) imaging with quantified LVEF and RVEF were included in the present analysis. Participants with a history of heart failure or reduced LVEF (<50%), CMR performed after the hospital inpatient data censoring date, missing key demographic or clinical variables, or outliers (>5 standard deviations from the population mean) in principal CMR parameters were excluded. The primary endpoint was the composite of heart failure hospitalization or all-cause death. Reduced RVEF was defined as <45%. To assess the independent prognostic value of reduced RVEF, propensity score matching was performed in a 1:4 ratio (reduced vs. preserved RVEF) based on age at imaging, sex, body mass index, hypertension, diabetes, chronic kidney disease, atrial fibrillation, ischemic heart disease, valvular heart disease, non-ischemic cardiomyopathy, and CMR-derived LVEF. In the matched cohort, the association between reduced RVEF and outcomes was evaluated using Kaplan-Meier analysis with log-rank testing and univariable Cox regression analysis.
Results
After applying the inclusion and exclusion criteria, the study cohort comprised 56,915 UK Biobank participants (65±8 years old, 46% male), of whom 1,570 (3%) reached the primary endpoint, and 965 (2%) had reduced RVEF on CMR. After successful propensity score matching, as indicated by standardized mean differences <0.1 across covariates in the matched cohort, the event-free survival curves for the reduced and preserved RVEF subgroups were significantly separated (log-rank test: p=0.007, Figure 1), and reduced RVEF was also associated with a higher risk of reaching the composite endpoint of heart failure hospitalization or all-cause death in a univariable Cox regression model (univariable HR: 1.577 [95% confidence interval: 1.123–2.216], p=0.009).
Conclusions
In a large population-based cohort free of prevalent heart failure and with preserved LVEF, reduced RVEF was independently associated with a higher risk of incident heart failure or death. These findings support the concept that RV dysfunction may represent an early phenotypic marker within the heart failure continuum, warranting mechanistic and genetic investigations into its role in disease initiation and progression.Event-free survival of the subgroups