Skeletal Muscle Dysfunction in Heart Failure: Mechanistic Insights and Therapeutic Implications.

What was studied

A narrative review discussing the mechanisms by which skeletal muscle structural and metabolic alterations (reduced muscle mass, increased intermuscular fat, capillary loss, altered fiber composition, reduced mitochondrial content, impaired oxidative metabolism, and increased oxidative stress) contribute to exercise intolerance in heart failure patients, and discussing emerging pharmacotherapies targeting skeletal muscle dysfunction; this is not a primary research study with original patient data.

Key findings

• This is a narrative/mechanistic review; no original patient outcome data are reported.
• The review describes multiple structural and metabolic skeletal muscle alterations in heart failure patients, including reduced muscle mass, increased intermuscular adipose tissue, capillary rarefaction, altered fiber-type composition, reduced mitochondrial content, and impaired oxidative phosphorylation.
• Increased oxidative stress combined with decreased antioxidant defenses and impaired clearance of toxic lipid peroxidation products are described as perpetuating a cycle of progressive muscle dysfunction, while exercise training remains the most effective current strategy, with novel pharmacotherapies targeting skeletal muscle emerging as potential future approaches.

Clinical relevance

This review suggests that targeting skeletal muscle dysfunction directly, in addition to standard heart failure treatments, could represent an important future avenue for improving exercise capacity and quality of life in heart failure patients, which could eventually broaden treatment options beyond exercise training alone, though the authors explicitly call for future studies to clarify the clinical utility of novel muscle-targeted therapies.

Who should care