Abstract
BACKGROUND: The triglyceride-glucose-body mass index (TYG-BMI) is a surrogate marker of insulin resistance associated with cardiovascular outcomes in stable populations. However, its physiological meaning in critically ill patients-where glucose and triglyceride levels are influenced by acute stress, inflammation, and treatment-remains uncertain, and the dynamic relationship between TYG-BMI and mortality in critically ill heart failure (HF) patients has not been investigated. OBJECTIVES: To examine the association between TYG-BMI intensity, exposure duration, and hospital mortality in critically ill HF patients, and to evaluate the robustness of these associations through comprehensive sensitivity analyses. METHODS: This multicenter retrospective study analyzed data from MIMIC-III, MIMIC-IV, and eICU databases. Adult HF patients with daily TYG-BMI measurements during the 7 day observation period (day 0 through day 7) were included. Restricted cubic spline regression characterized the baseline dose-response relationship. Generalized additive models with tensor product smooth functions examined the three-dimensional TYG-BMI-time-mortality association. Weighted linear regression quantified temporal trends. Multiple sensitivity analyses addressed selection bias, time-varying confounding, treatment effect modification, and temporal heterogeneity. RESULTS: Among 5133 patients (pooled mortality: 27.9%), restricted cubic spline analysis confirmed a non-linear U-shaped dose-response relationship in MIMIC-IV (non-linear P < 0.001), with consistent directional patterns across MIMIC-III and eICU. Generalized additive models demonstrated a reproducible U-shaped association across all three databases. The optimal TYG-BMI range was 250-275 (OR = 0.76, 95% CI 0.68-0.85, P < 0.001 in MIMIC-IV), with each additional day within this range reducing mortality risk by 0.4% (P < 0.01). TYG-BMI > 425 was associated with progressively increased mortality (OR = 1.61, 95% CI 1.35-1.93 for the 425-450 range), with time-dependent risk amplification reaching 2.5% per day at the highest stratum. Combining TYG-BMI with the SOFA score significantly improved discriminative performance beyond SOFA alone (AUC: 0.780 versus 0.720, DeLong P < 0.001). All sensitivity analyses yielded consistent findings. CONCLUSIONS: TYG-BMI demonstrates a reproducible, U-shaped association with hospital mortality in critically ill HF patients. Both intensity and exposure duration contribute to risk stratification, though prospective validation is warranted given the observational design and uncertain physiological specificity of TYG-BMI in the ICU setting.