Total Body Muscle Mass in Heart Failure: A Marker of Muscle Loss or Systemic Vulnerability?

Dear Editor,

We read with great interest the study by Ikeda et al. investigating the prognostic value of total body muscle mass (TBMM) in patients with acute heart failure [1]. The authors assessed TBMM in patients with acute heart failure and demonstrated that TBMM was strongly correlated with estimated appendicular skeletal muscle mass index (ASMI) and independently associated with postdischarge all‐cause mortality [1]. These findings suggest that muscle‐related indices derived from routinely available laboratory parameters may provide clinical value for risk stratification. However, the biological interpretation of TBMM warrants further consideration, as its prognostic value may not be entirely explained by skeletal muscle mass alone.

TBMM was originally proposed as a blood‐based surrogate marker of skeletal muscle mass and was derived from serum creatinine, cystatin C, and body weight [2]. However, in the complex clinical context of acute heart failure, the biological information reflected by TBMM may extend beyond muscle quantity alone. Reduced muscle reserve frequently coexists with malnutrition, inflammation, renal dysfunction, and disease‐related catabolic states [3]. Therefore, low TBMM may represent a broader state of systemic vulnerability rather than simply indicating reduced skeletal muscle mass. In the study by Ikeda et al., patients with lower TBMM were older and had lower body mass index, lower hemoglobin levels, and higher B‐type natriuretic peptide concentrations [1]. These characteristics reflect not only reduced muscle reserve but also clinical features associated with frailty, cardiac cachexia, and greater disease burden. Thus, the association between TBMM and mortality may represent a composite physiological vulnerability phenotype, and whether its predictive value primarily reflects muscle alterations or the integration of multisystem health information remains to be determined.

Furthermore, the interpretation of the correlation between TBMM and estimated ASMI deserves further consideration. Ikeda et al. reported strong correlations between TBMM and ASMI estimated using different approaches, suggesting that TBMM may capture muscle‐related status. However, the biomarker‐based ASMI estimation model incorporates creatinine and cystatin C, which are also key components of the TBMM equation. Therefore, the observed correlation may partly result from shared variables and mathematical coupling rather than representing independent biological agreement between different measurements. In addition, the anthropometric ASMI model includes body weight, which is also incorporated into TBMM estimation. Consequently, the correlation between TBMM and estimated ASMI should be interpreted as consistency between related prediction models rather than definitive evidence that TBMM directly reflects skeletal muscle mass.

In conclusion, Ikeda et al. provide important evidence supporting the prognostic value of TBMM in patients with acute heart failure. Nevertheless, TBMM should not necessarily be interpreted solely as a surrogate marker of skeletal muscle mass. Clarifying whether TBMM functions primarily as a marker of muscle loss or as an integrated biomarker of systemic vulnerability will be essential for understanding its biological meaning and guiding personalized risk assessment in patients with heart failure.

Funding

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Ethics Statement

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Conflicts of Interest

The authors declare no conflicts of interest.

Data Availability Statement

Data sharing not applicable to this article as no datasets were generated or analysed during the current study.