Comparative prognostic performance of bmi-indexed and height-indexed appendicular skeletal muscle mass for risk stratification in older patients with heart failure: insights from FRAGILE-HF

Background The Asian Working Group for Sarcopenia 2025 consensus newly endorses appendicular skeletal muscle mass (ASMM) indexed to body mass index (BMI), in addition to conventional height indexing. In heart failure, BMI may fluctuate with congestion and decongestion, potentially weakening the clinical interpretability of BMI-indexed ASMM. However, direct comparative data on the prognostic utility of BMI-indexed versus height-indexed ASMM in older patients with heart failure remain limited. Purpose To compare the prognostic utility of BMI-indexed versus height-indexed ASMM in older patients hospitalized for heart failure. Methods This was a post-hoc analysis of the FRAGILE-HF study, a prospective, multicentre observational cohort of patients aged ≥65 years hospitalized for heart failure. Of 1,332 participants, 900 with bioelectrical impedance analysis data were included (median age 81 [IQR 74–86] years; 42.4% women). BMI-indexed ASMM (ASMM/BMI) and height-indexed ASMM (ASMM/height²) were calculated, and low muscle mass was defined using established sex-specific thresholds. Two logistic regression models were constructed for the primary outcome. Specifically, low versus high muscle mass, defined using BMI-indexed ASMM and height-indexed ASMM, was added to a baseline model comprising the MAGGIC risk score and log-transformed BNP. Prognostic performance across the three models was compared using the area under the receiver operating characteristic curve (ROC-AUC) and net reclassification improvement (NRI). The primary outcome was 2-year all-cause mortality. Results Low BMI-indexed ASMM and low height-indexed ASMM were present in 17.6% and 26.2% of patients, respectively. During 2-year follow-up, 160 deaths occurred (18.0%). Kaplan–Meier analysis demonstrated no difference in survival between low and high BMI-indexed ASMM (log-rank P=0.492); conversely, survival differed significantly between low and high height-indexed ASMM (log-rank P<0.001). In an adjusted Cox proportional hazards model, low BMI-indexed ASMM was not associated with 2-year mortality (HR 1.24 [95% CI 0.82–1.88], P=0.308), whereas low height-indexed ASMM was associated with a higher risk of death (HR 1.76 [95% CI 1.24–2.49], P=0.002). When comparing the model including height-indexed ASMM with the model including BMI-indexed ASMM, discrimination did not differ significantly (AUC 0.703 vs 0.686, P=0.155). Nonetheless, replacing BMI-indexed ASMM with height-indexed ASMM significantly improved risk reclassification (NRI 0.350 [95% CI 0.173–0.527], P<0.001). Conclusion In older patients hospitalised for heart failure, low height-indexed, but not BMI-indexed, ASMM was associated with higher 2-year post-discharge all-cause mortality and improved risk reclassification, supporting the use of height-indexed ASMM for prognostic risk stratification in this population.Figure_for_abstract