Relative Contributions of Functional Capacity and Inflammatory Activity to Quality of Life in Heart Failure with Preserved Ejection Fraction

Background/Objectives: Impaired quality of life (QoL) represents one of the most important clinical determinants in heart failure with preserved ejection fraction (HFpEF). This study aimed to evaluate the incremental explanatory value of functional performance and inflammatory biomarkers for QoL in a clinically stable HFpEF cohort. Methods: A single-center observational study enrolled 110 consecutive patients with stable HFpEF. Functional capacity was assessed using the six-minute walk test (6MWT), expressed mainly as percentage of predicted distance. Health-related QoL was measured using the EQ-5D-5L utility index (primary outcome). Circulating IL-6, CRP, and NT-proBNP were obtained from peripheral blood. Hierarchical multivariable linear regression was applied to quantify the incremental contribution of clinical variables, functional capacity, and biomarkers. Results: The median age was 72 years, and 52.7% of the participants were women. The median 6MWT distance was 340 m (75.9% of predicted), and the median EQ-5D index was 0.76. The baseline clinical regression model (age, sex, atrial fibrillation, and glomerular filtration rate) explained 23.5% of EQ-5D variance. The addition of functional capacity increased explained variance to 45.2% (ΔR2 = +0.217). The inclusion of IL-6 and NT-proBNP provided a modest additional increase (R2 = 0.468; ΔR2 = +0.042 in addition to Model 2). In the fully adjusted model, functional capacity (β = 0.376, p < 0.001) and IL-6 (β = −0.185, p < 0.05) remained independent predictors, whereas NT-proBNP lost significance. Conclusions: In stable HFpEF, objective functional capacity represents the dominant determinant of QoL, while inflammatory activation provides an independent but smaller contribution. Functional assessment may therefore be central to patient-centered phenotyping and therapeutic targeting.