The “Adipo-Muscular” association in heart failure with preserved ejection fraction: synergistic impact of epicardial adipose tissue and skeletal muscle endurance on functional capacity

Heart failure with preserved ejection fraction (HFpEF) is increasingly recognized as a systemic multiorgan syndrome driven by low-grade inflammation. While epicardial adipose tissue (EAT) and skeletal muscle dysfunction are known contributors to exercise intolerance, their synergistic association remains undefined. We aimed to investigate the “Adipo-Muscular” association—the synergistic interplay between local cardiac inflammatory potential and peripheral muscle fatigability—as a predictor of functional capacity in HFpEF. This cross-sectional study enrolled 192 stable HFpEF patients and 200 age- and sex-matched healthy controls. EAT thickness was quantified via echocardiography. Peripheral muscle function was assessed through maximal isometric strength and handgrip endurance (maintenance time at 50% maximal voluntary contraction), the latter serving as a surrogate for Type I fiber oxidative capacity. Functional capacity was validated using the 6-Minute Pegboard Ring Test (6PBRT), specifically chosen for its sensitivity to upper extremity “myopenia” (qualitative bioenergetic failure). A novel EAT-Endurance Index was calculated as: Index = (EAT thickness mm / Handgrip endurance sec) ×100. Despite comparable BMI between groups, HFpEF patients displayed significantly greater EAT thickness (5. 46 ± 1. 65 vs. 3. 20 ± 1. 03 mm, p < 0. 001). While maximal strength showed a moderate decline, handgrip endurance was profoundly compromised in HFpEF (48. 48 ± 14. 4 vs. 72. 24 ± 12. 1 s, p < 0. 001), representing a massive effect size (Cohen’s d = -1. 791). In multivariate analysis adjusting for age, sex, BMI, and major comorbidities (Hypertension, Diabetes, and Coronary Artery Disease), the EAT-Endurance Index emerged as the strongest independent predictor of impaired functional capacity (β = 0. 385, p < 0. 001). Sensitivity analysis confirmed this association was independent of glycemic status. We identified a distinct “Adipo-Muscular” phenotype in HFpEF, characterized by expanded epicardial fat and profound skeletal muscle fatigability. This association predicts functional decline independently of systemic obesity, maximal strength, and classic comorbidities. Targeting the interface between central adiposity and skeletal muscle mitochondrial function may offer novel therapeutic avenues for this challenging population.