Left Atrial Stiffness, Exercise Intolerance and Injury Biomarkers Predict Adverse Outcomes in Patients with Heart Failure with Preserved Ejection Fraction

Heart failure with preserved ejection fraction (HFpEF) is a complex condition associated with high morbidity and mortality. This exploratory study aimed to assess the prognostic value of left atrial (LA) stiffness, exercise tolerance, and selected biomarkers in patients with HFpEF. We evaluated LA mechanics using 2D speckle tracking in 43 patients (mean age: 77.2 years) from the OPTIMISE HFpEF study (NCT03617848). Biomarkers such as N-terminal pro-brain-type natriuretic peptide, growth differentiation factor 15, and galectin-3 were measured. Patients also completed a six-minute walk test. Over a mean follow-up of 24.5 months, there were five deaths (11.4%) and 21 all-cause hospitalisations (48.8%). LA stiffness (HR: 1.81; p = 0.028) and N-terminal pro-brain-type natriuretic peptide (HR: 1.01; p = 0.013) were independent mortality predictors. For hospitalisations, six-minute walk distance (HR: 0.99; p = 0.011) and growth differentiation factor 15 (HR: 1.01; p = 0.007) were significant independent predictors. This exploratory analysis indicates that LA stiffness, N-terminal pro-brain-type natriuretic peptide, exercise intolerance, and growth differentiation factor 15 independently predict adverse events in HFpEF. Implementing a comprehensive therapeutic approach, including lifestyle modifications, medical therapy, and, if necessary, more advanced interventions to improve LA mechanics, functional capacity, and clinical biomarkers, may improve outcomes for HFpEF patients.