Impact of high-intensity exercise training (HIIT) versus moderate continuous training (MCT) on skeletal muscle alterations in HFrEF: a substudy of the SMART-EX trial

Abstract Background Skeletal muscle dysfunction contributes to exercise intolerance in chronic heart failure. The randomized multicenter Study of Myocardial Recovery After Exercise Training in Heart Failure (SMART-EX) has shown that high-intensity exercise training (HIIT) but not moderate continuous training (MCT) reduced the left ventricular end diastolic diameter. Both training modalities significantly increased exercise tolerance as determined by cardiopulmonary exercise testing (CPET). However, the underlying molecular alterations within the skeletal muscle with respect to different exercise training modalities are largely unknown. Methods In patients with chronic heart failure with reduced ejection fraction (HFrEF) who participated in the SMART-EX skeletal muscle substudy needle biopsies from the vastus lateralis muscle were performed before and after 12 weeks of supervised HIIT, MCT, or recommendation of regular exercise (RRE) to allow molecular assessment of markers for muscle catabolism, inflammation and energy supply by RT-PCR and western blotting. Echocardiography and CPET were performed in all patients. Changes over time were tested within each group. Results Skeletal muscle biopsies at baseline and follow-up were available in 31 patients (HIIT n=9; MCT n=9; RRE n=13). The majority of patients were male (87%). Median left ventricular ejection fraction was 29%. Median improvement in peak VO2 was 2.0 (IQR -0.4-2.8) in HIIT vs. 1.4 (IQR -0.9-3.4) in MCT vs. 0.0 (IQR -2.9-2.1) ml/min/kg in RRE. This was statistically not significant. HIIT reduced mRNA levels of the E3 ligases of the ubiquitine proteasome system MuRF1 by -72% (p