The FT3/FT4 Ratio as a Metabolic Marker of Frailty and Prognosis in Older Adults with Heart Failure

Background/Objectives: Frailty is a key determinant of outcomes in older adults with heart failure (HF). The free triiodothyronine/free thyroxine (FT3/FT4) ratio has emerged as a promising frailty biomarker that reflects metabolic and systemic resilience. This study investigates its association with frailty, nutrition, muscle strength, inflammation, and one-year mortality in very old patients with HF. Methods: In this longitudinal, single-center study, we enrolled 193 older outpatients (mean age, 86.5 +/- 6.1 years; 56% women) recently discharged after acute HF. All patients underwent physical examination, blood testing, and comprehensive geriatric assessment, including handgrip strength (HGS). Participants were stratified by FT3/FT4 ratio (<1.7 vs. >= 1.7). Associations with the Clinical Frailty Scale (CFS) were examined using multivariable linear regression. Spearman's correlations assessed relationships with inflammatory and nutritional biomarkers. Cox regression evaluated the association with all-cause mortality. Results: Patients with a low FT3/FT4 ratio (31.1%) exhibited greater frailty (CFS: median [IQR], 6 [2] vs. 4 [3]; p = 0.020), poorer nutritional status (Mini Nutritional Assessment: 10 [4] vs. 12 [3]; p = 0.008), and lower HGS (mean +/- SD, 16.8 +/- 3.7 kg vs. 20.3 +/- 4.8 kg; p = 0.002). An inverse association was identified between the FT3/FT4 ratio and frailty (adjusted beta = -0.09; p = 0.019). Individuals with low FT3/FT4 also showed elevated inflammatory markers and had more than double the one-year mortality rate compared to those with higher ratios [HR 2.32 (95% CI, 1.24-4.34; p = 0.007)]. Conclusions: In very old adults recently hospitalized for HF, a lower FT3/FT4 ratio was associated with frailty, malnutrition, inflammation, and increased mortality, supporting its potential role as a marker of biological vulnerability.