Background: Heart failure (HF) is characterised by altered skeletal muscle morphology. The aim of this systematic review and meta-analysis was to explore cross-sectional differences in muscle morphology and metabolism between patients with HF and healthy controls.

Methods: A literature search of studies was conducted from inception to February 2025 across PubMed, Scopus, Web of Science, and the Cochrane Library. Eligible studies compared skeletal muscle morphological differences via the vastus lateralis from patients with HF vs.

healthy controls. A meta-analysis was conducted using the random effects inverse-variance model.

Results: Thirty-five studies were included in this study. Patients with HF displayed similar absolute muscle fiber areas (type I, II, IIa, IIx), lower relative type I fiber area (MD: -8.3%, 95% confidence interval (95% CI): -12.3 to -4.4), and higher type II (MD: 11.3%, 95% CI: 7.3 to 15.4) and IIx areas (MD: 7.4%, 95% CI: 4.3 to 10.4) vs.

healthy controls. Capillaries per fiber were reduced in HF (MD = -0.28, 95% CI: -0.52 to -0.03), particularly for type IIa (MD = -0.30, 95% CI: -0.54 to -0.06) and IIx fibers (MD = -0.35, 95% CI: -0.55 to -0.15).

IGF-1 was lower (-19.4 mRNA AU, 95% CI: -36.3 to -2.5), and myostatin was elevated (16.1 mRNA AU, 95% CI: 2.9 to 29.2) in HF. Citrate synthase, 3-hydroxyacyl-CoA-dehydrogenase, and succinate dehydrogenase were significantly lower in HF (p < 0.05).

Conclusions: In HF, reduced relative type I fiber area, increased type II/IIx, reduced capillarization, altered anabolic/catabolic markers, and impaired energy metabolism enzymes, were observed compared to controls.