Abstract
Introduction: Heart failure with preserved ejection fraction (HFpEF) is characterized by marked exercise intolerance (EI) and increased mortality. HFpEF is now thought to involve multi-organ dysfunction and skeletal muscle (SkM) changes including muscle loss and muscle fatty infiltration have been reported in HFpEF patients. However, it is not known if SkM changes are associated with cardiovascular (CV) mortality. Hypothesis: Skeletal muscle fat accumulation in symptomatic HFpEF patients is associated with worse EI and decreased survival. Methods: Patients with a clinical diagnosis of HFpEF and left ventricular ejection fraction > 50% (n=64, age 65.2±11.2, BMI 38.6±8.2, mean±SD, 53% women) underwent 3T conventional magnetic resonance imaging (MRI) of the calf muscle to determine SkM mass and T2-weighted MRI for SkM fat fraction (FF) with subcutaneous fat excluded. Baseline EI was quantified by six-minute walk distance (6MW). HFpEF patients were followed prospectively for a minimum of 18 months for survival (median follow up 39.3 months). Simple linear regression was used to determine relationships with EI while Kaplan-Meier survival curves with log rank tests were created to explore CV mortality. Results: SkM FF was closely and inversely associated with 6MW (1A), but SkM mass (1B) was not, indicating that EI in HFpEF is more closely associated with SkM quality than quantity. SkM FF was not related to body mass index (BMI) (1C). When the HFpEF cohort was stratified based on median FF (median=18.79%), SkM FF predicted significantly worse survival from CV death (1D, p=0.0192). Conclusions: This is the first report to show that SkM fat content predicts cardiovascular mortality in HFpEF patients. Further, EI in HFpEF patients is closely associated with SkM fat accumulation but not sarcopenia. Thus, reducing SkM fat content may represent a new target for reducing EI and improving CV survival in HFpEF patients.
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