Alterations of skeletal muscle in chronic heart failure.

TLDR

The study aimed to determine the prevalence and characteristics of skeletal muscle alterations in chronic heart failure and their association with exercise capacity. Ultrastructural morphometry of skeletal muscle from 57 CHF patients and 18 controls quantified mitochondrial volume and cristae surface densities as proxies for oxidative capacity. Patients with severe CHF exhibited ~20% reductions in mitochondrial volume and cristae surface densities, decreased cytochrome oxidase activity, reduced capillary density, a shift toward type II fibers, and strong correlations between these structural deficits and impaired peak VO₂ and anaerobic threshold, indicating that skeletal muscle abnormalities underlie exercise limitation but may be reversible with treatment.

Abstract

The present study was designed to define the prevalence and characteristics of skeletal muscle alterations in patients with chronic heart failure (CHF) and their relation to exercise capacity.The ultrastructure of skeletal muscle was analyzed by ultrastructural morphometry in 57 patients with CHF and 18 healthy controls. The volume density of mitochondria (Vvm) and the surface density (Svmc) of mitochondrial cristae were evaluated as a structural correlate of oxidative capacity of skeletal muscle. Vvm and Svmc were reduced by approximately 20% in patients with severe CHF irrespective of age and etiology. The cytochrome oxidase activity in mitochondria as determined by cytochemistry and subsequent morphometry in a subset of patients (n = 10) was significantly decreased in heart failure (p less than 0.01). The capillary length density of skeletal muscle was reduced in CHF (n = 12, p less than 0.05), and the fiber type distribution was shifted to type II fibers (n = 15, p less than 0.05). Vvm and Svmc were significantly related to peak exercise VO2 (r = 0.56, p less than 0.001, n = 60) and to VO2 at anaerobic threshold (r = 0.535, p less than 0.0001, n = 60). In 16 patients with severe heart failure, Vvm was inversely related to the duration of heart failure (r = 0.545, p less than 0.03). In 11 patients who underwent repeat biopsies after 4 months, a correlation was observed between the change in Vvm and the change in peak exercise VO2 (r = 0.89, p less than 0.001).These findings indicate that patients with CHF develop significant ultrastructural abnormalities of skeletal muscle reflecting a depressed oxidative capacity of working muscle. It appears that these alterations of skeletal muscle contribute to the decreased exercise capacity of these patients but are, in principle, reversible by an effective treatment regimen.