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

Abstract

Background: Heart 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.

Methods: Isometric 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).

Results: Extension 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.

Conclusions: Delayed 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.

Keywords: Heart failure; skeletal muscle function; time to peak torque.

Fig. 1

Representative leg extension curves. Average values taken every 10 msec from 45 HF (black) and 15 control (gray) subjects during the third leg extension (of 5 repetitions) at 60°/s. Vertical line shows time to peak torque. Values expressed as means ± standard error of the mean (dashed lines). HF, heart failure.

Fig. 2

Time-to-peak torque during extension and flexion. Extension (A) and flexion (B) moving at 60°/s, and extension (C) and flexion (D) moving at 180°/s in the dominant leg of control (circles) and HF (squares) subjects. Values are means ± standard deviation. HF, heart failure.

Fig. 3

Correlation between dual energy X-ray absorptiometry and muscle function parameters. Peak torque/BW for extension (A) and flexion (B) moving at 60°/s correlated with dominant leg lean mass, and peak torque/BW for extension (C) and flexion (D) moving at 60°/s with trunk/limb mass ratio in control (dashed) and heart failure (solid) subjects. Significant correlation for HF subjects in figure B (P = .039, R² = 0.227) and C (P = .007, R² = 0.354). BW, body weight.

Fig. 4

Heat map of ceramide levels. A graphical representation of the ceramide raw data compared with the average control values for each ceramide. Green represents values >1, whereas red represents values <1. The darker the color, the close the value is to 1. There appears to be a greater amount of ceramide levels in the heart failure group compared with controls.