Acute and chronic exercise in patients with HFrEF: Evidence of structural and functional plasticity and intact angiogenic signaling in skeletal muscle

This study examined the response to acute submaximal exercise and the effect of training in patients with heart failure with reduced ejection fraction (HFrEF). The acute angiogenic response to submaximal exercise in HFrEF after small muscle mass training is debated. The direct Fick method, with vascular pressures, was performed across the leg during knee-extensor exercise (KE) at 50% of maximum work rate (WRmax) in patients (n = 6) and controls (n = 6) and then after KE training in patients. Muscle biopsies facilitated the assessment of skeletal muscle structure and vascular endothelial growth factor (VEGF) mRNA levels. Prior to training, HFrEF exhibited significantly higher leg vascular resistance (LVR) (approximate to 15%) and significantly greater noradrenaline spillover (approximate to 385%). Apart from mitochondrial volume density, which was significantly lower (approximate to 22%) in HFrEF, initial skeletal muscle structure, including capillarity, was not different between groups. Resting VEGF mRNA levels, and the increase with exercise, was not different between patients and controls. Following training, LVR was no longer elevated and noradrenaline spillover was curtailed. Skeletal muscle capillarity increased with training, as assessed by capillary-to-fibre ratio (approximate to 13%) and number of capillaries around a fibre (N-CAF) (approximate to 19%). VEGF mRNA was now not significantly increased by acute exercise. Muscle fibre cross-sectional area and percentage area of type I fibres both increased significantly with training (approximate to 18% and approximate to 21%, respectively), while the percentage area of type II fibres fell significantly (approximate to 11%), and mitochondrial volume density now exceeded that of controls. These data reveal structural and functional plasticity and appropriate angiogenic signalling in skeletal muscle of HFrEF patients.