Analysis of Skeletal Muscle Torque Capacity and Circulating Ceramides in Patients with Advanced Heart Failure

• Heart failure (HF) results in reduced peak torque and power in the skeletal muscle of the lower limbs compared with healthy controls.
• Muscle function in the upper limbs of HF patients is not significantly different from healthy controls.
• Patients with HF have prolonged skeletal muscle contractility dynamics, which may be a result of neuromuscular coupling dysfunction.
• HF patients have increased adiposity and lower lean muscle than age-matched controls.
• There was an increase in circulating ceramides levels, but a decrease in circulating unsaturated fatty acids in HF patients.

BackgroundHeart failure (HF)-related exercise intolerance is thought to be perpetuated by peripheral skeletal muscle functional, structural, and metabolic abnormalities. We analyzed specific dynamics of muscle contraction in patients with HF compared with healthy, sedentary controls.MethodsIsometric and isokinetic muscle parameters were measured in the dominant upper and lower limbs of 45 HF patients and 15 healthy age-matched controls. Measurements included peak torque normalized to body weight, work normalized to body weight, power, time to peak torque, and acceleration and deceleration to maximum strength times. Body morphometry (dual energy X-ray absorptiometry scan) and circulating fatty acids and ceramides (lipodomics) were analyzed in a subset of subjects (18 HF and 9 controls).ResultsExtension and flexion time-to-peak torque was longer in the lower limbs of HF patients. Furthermore, acceleration and deceleration times in the lower limbs were also prolonged in HF subjects. HF subjects had increased adiposity and decreased lean muscle mass compared with controls. Decreased circulating unsaturated fatty acids and increased ceramides were found in subjects with HF.ConclusionsDelayed torque development suggests skeletal muscle impairments that may reflect abnormal neuromuscular functional coupling. These impairments may be further compounded by increased adiposity and inflammation associated with increased ceramides.