Intact skeletal muscle mitochondrial enzyme activity but diminished exercise capacity in advanced heart failure patients on optimal medical and device therapy

Abstract

Background: A skeletal myopathy, perhaps attributable to neuro-endocrine excitation or disuse, has been described in heart failure (HF) patients, and is thought to contribute to their exercise limitation. Our purpose was to assess biochemical and morphometric characteristics of skeletal muscles of HF patients on optimal HF therapy. A secondary purpose was to explore the effects of clonidine, which interrupts the neuro-endocrine excitation, on these same muscle characteristics.

Methods and results: Eleven HF patients (50.8 ± 3.4 years, peak VO2 11.6 ± 2.5 ml/kg/min) underwent two vastus lateralis biopsies (pre/post clonidine). Baseline values were compared to biopsies in 11 age-matched, healthy controls. Scatter plots of individual values for each mitochondrial enzyme revealed almost complete overlap between HF and control groups; mean values, although tending to be greater in controls versus HF patients, were not significantly different. The proportion of type 1 fibers was diminished in 10 of 11 patients. There was no difference in any of the variables after 3 months clonidine versus placebo.

Conclusion: In HF patients treated with optimal medical and device therapy, characteristic abnormalities of mitochondrial enzyme activity are not found, but muscle fiber type shifts are present. The remaining severe impairment in exercise capacity cannot be attributed to mitochondrial abnormalities.

Conflict of interest statement

On behalf of all authors, the corresponding author states that there is no conflict of interest.

Figures

Figure 1

Scatter plots of individual values (filled circles) of mitochondrial enzymes from 11 HF patients and 11 age-matched controls. Mean values (open circles) of each enzyme is lower in the HF versus control group, but not significantly so. There is almost complete overlap of individual values between the groups. NCP=non-collagen protein

Figure 2

Scatter plots of individual measures (filled circles) and mean values (open circles) of morphometry in 11 HF patients. Panel A. Vascular index was within or above the normal range in all HF patients. Panel B. The proportion of type 1 fibers was diminished in 10 of 11 HF patients, consistent with a fiber shift from oxidative type 1 fibers to glycolytic type 2 fibers. Panel C. The overall mean fiber diameter is within the normal range in HF patients on optimal medical and device therapy. Panel D. Total number of fibers per mm2 is within the normal range in HF patients on optimal medical and device therapy. Shaded area represents the normal range established in prior published studies from the UCLA Neuropathology Lab [26] and in the literature [25,31,32].