Skeletal muscle fiber characteristics in patients with chronic heart failure: Impact of disease severity and relation with muscle oxygenation during exercise

Abstract

Skeletal muscle function in patients with heart failure and reduced ejection fraction (HFrEF) greatly determines exercise capacity. However, reports on skeletal muscle fiber dimensions, fiber capillarization, and their physiological importance are inconsistent. Twenty-five moderately impaired patients with HFrEF and 25 healthy control (HC) subjects underwent muscle biopsy sampling. Type I and type II muscle fiber characteristics were determined by immunohistochemistry. In patients with HFrEF, enzymatic oxidative capacity was assessed, and pulmonary oxygen uptake (VO2) and skeletal muscle oxygenation during maximal and moderateintensity exercise were measured using near-infrared spectroscopy. While muscle fiber cross-sectional area (CSA) was not different between patients with HFrEF and HC, the percentage of type I fibers was higher in HC (46 ± 15 vs. 37 ± 12%, respectively, P = 0.041). Fiber type distribution and CSA were not different between patients in New York Heart Association (NYHA) class II and III. Type I muscle fiber capillarization was higher in HFrE.compared with HC[capillary- to-fiber perimeter exchange (CFPE) index: 5.70 ± 0.92 vs. 5.05 ± 0.82, respectively, P = 0.027]. Patients in NYHA class III had slower VO2 and muscle deoxygenation kinetics during onset of exercise and lower muscle oxidative capacity than those in class II (P < 0.05). Also, fiber capillarization was lower but no.compared with HC. Higher CFPE index was related to faster deoxygenation (rspearman±±0.682, P±0.001), however, not to muscle oxidative capacity (r±±0.282, P± 0.216). Type I muscle fiber capillarization is higher in HFrE.compared with HC but not in patients with greater exercise impairment. Greater capillarization may positively affect VO2 kinetics by enhancing muscle oxygen diffusion. NEW & NOTEWORTHY The skeletal myopathy of chronic heart failure (HF) includes a greater percentage of fatigable type II fibers and, for less impaired patients, greater skeletal muscle fiber capillarization. Near-infrared spectroscopy measurements of skeletal muscle oxygenation indicate that greater capillarization ma.compensate for reduced blood flow in mild HF by enhancing the diffusive capacity of skeletal muscle. This thereby augments and speeds oxygen extraction during contractions, which is translated into faster pulmonary oxygen uptake kinetics.