Abstract 13472: Physical Incapacity in Heart Failure Patients is Associated With Skeletal Muscle Mitochondrial Dysfunction

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Introduction: The role of skeletal muscle mitochondrial dysfunction in exercise intolerance in heart failure patients is unknown. Therefore, this study aimed to identify the relationship between physical capacity and skeletal muscle mitochondrial function in patients with heart failure and reduced ejection fraction (HFrEF). Methods A total of 53 HFrEF patients and 20 age- and sex-matched controls underwent dual-energy X-ray absorptiometry to assess muscle mass by the appendicular lean mass index (ALMI), cardiopulmonary exercise testing (peakVO2), 6-minute walking test (6MWD) and maximal isometric knee-extensor strength test. In skeletal muscle biopsies from vastus lateralis, mitochondrial respiratory capacity was measured by high resolution respirometry. We performed Pearson correlations to examine the relationships between physical capacity tests and mitochondrial function. Results Mean age of the study cohort was 71.7 ±7.0 years. Compared with healthy controls, HFrEF patients had a lower peakVO2 (14.6 ±4.1 vs. 26.2 ±8.0 mL/kg/min, p <0.001) and a shorter 6MWD (429 ±106 vs. 581 ±93 m, p <0.001). HFrEF patients had a lower ALMI (0.74 ±0.15 vs. 0.86 ±0.16 kg/(kg/m 2 ), p = 0.005). Maximal coupled mitochondrial respiration was decreased in HFrEF patients compared with healthy controls (59.1 ±19.0 vs. 92.6 ±38.8 ρmol O 2 *s -1 mg -1 , p <0.001) as well as the respiratory control ratio (7.2 ±2.5 vs. 9.7 ±3.1). Maximal coupled mitochondrial respiration was correlated to peakVO2 (r = 0.58, p <0.001) and 6MWD (r = 0.44, p <0.001), but not to muscle mass or maximal knee-extensor strength. Conclusions HFrEF patients had a lower peakVO2, shorter 6MWD and impaired skeletal muscle mitochondrial function as compared with controls. Maximal coupled mitochondrial respiration was correlated with physical capacity across the population of HFrEF patients and healthy controls establishing an association between skeletal muscle mitochondrial dysfunction and physical incapacity.