Heart failure & cardiomyopathiesResearch article

Sex Differences in Skeletal Muscle Inflammation and Dysfunction in Patients With Heart Failure and Reduced Ejection Fraction

Circ Heart FailPublished

  • Study of patients with heart failure with reduced ejection fraction (HFrEF) and age- and sex-matched healthy controls
  • vastus lateralis muscle biopsies analyzed by flow cytometry
  • linear regression with sex-by-HFrEF interaction

Authors' conclusion

Skeletal muscle immune cell alterations, particularly macrophage and lymphocyte imbalances, are associated with muscle dysfunction in HFrEF, exhibiting distinct sex-specific patterns. These findings demonstrate sex-specific skeletal muscle inflammation and dysfunction in HFrEF.

Study context

Population
Patients with heart failure with reduced ejection fraction (HFrEF) and age- and sex-matched healthy controls (mean age, 71±7 years; 32% women)86 patients with HFrEF and 41 age- and sex-matched healthy controls · patients with HFrEF 86 · age- and sex-matched healthy controls 41
Participants
86 vs 41
Comparison
HFrEF vs healthy controls
  • HFrEFn = 86
  • healthy controlsn = 41

Main finding

As reported in the abstract

Skeletal muscle immune cell composition, sex-by-HFrEF interaction

macrophage fraction, interaction

P =0.006

lymphocyte content, interaction

P =0.045

lymphocyte fraction, interaction

P =0.039

Further findings

OutcomeValuesGMR (CI)P value
Lymphocyte fraction in women with HFrEF · increased lymphocyte fraction in women in HFrEF1.27 (1.06–1.53)P = 0.014
Macrophage content in men with HFrEF · increased macrophage content in men in HFrEF1.75 (1.16–2.64)P = 0.009
Association of macrophage content with muscle mass and strengthwomen mass R 0.42, P =0.014 · strength R 0.42, P =0.013 · men mass R −0.25, P =0.017 · strength R −0.21, P =0.046
Muscle stem cells and fibro-adipogenic progenitor cells — HFrEF · muscle stem cells; reduced in HFrEF1.92 (0.99–3.74)P = 0.054
Muscle stem cells and fibro-adipogenic progenitor cells — HFrEF · fibro-adipogenic progenitor cells; reduced in HFrEF1.72 (1.03–2.85)P = 0.038
  • Association of macrophage content with muscle mass and strength: greater muscle mass and strength in women, reduced mass and strength in men

Original publication

Sex Differences in Skeletal Muscle Inflammation and Dysfunction in Patients With Heart Failure and Reduced Ejection Fraction. Circ Heart Fail. Published 27 August 2026. doi:10.1161/circheartfailure.125.014062

Summarised from the published abstract; every number is checked against it