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Research Article: Association between peripheral thyroid sensitivity defined by the FT3/FT4 ratio and composite adverse outcome among inpatients with heart failure

Date Published: 2025-09-16

Abstract:
The free triiodothyronine to free thyroxine (FT3/FT4) ratio is an indicator of peripheral thyroid hormone sensitivity. However, its prognostic value in heart failure (HF) remains unclear. This single center prospective cohort study included a total of 402 HF patients. The primary composite outcome was established as either mortality from any cause or HF-related hospitalization within one year. Multivariate Cox regression and Kaplan-Meier analysis assessed associations between the FT3/FT4 ratio and composite endpoint risks, with restricted cubic splines (RCS) exploring potential non-linear relationships. Among 402 heart failure patients, 188 (46.8%) experienced the primary composite endpoint. The highest FT3/FT4 tertile (T3) had 38% lower risk than the lowest tertile (T1) (adjusted HR 0.62, 95% CI 0.41-0.94). In the subgroup of patients with subclinical hypothyroidism (SCH), T3 individuals showed an 84% lower risk compared to T1 (adjusted HR 0.16, 95% CI 0.03–0.81). Both the overall cohort and SCH subgroup exhibited an inverse association between FT3/FT4 ratios and adverse outcomes, whereas euthyroid patients demonstrated a U-shaped relationship with composite endpoint hazards (P for nonlinear = 0.004). Our findings suggest that maintaining or restoring higher FT3/FT4 levels may improve clinical outcomes in HF patients. Regular monitoring of this ratio, coupled with tailored interventions based on thyroid functional status, could enhance risk stratification and therapeutic decision-making.

Introduction:
Thyroid hormones directly modulate cardiovascular function by enhancing myocardial contractility while also exerting significant indirect effects through sympathetic nervous system activation ( 1 ). Even subtle disturbances in thyroid homeostasis are linked to adverse cardiovascular outcomes ( 2 ). Heart failure (HF) patients frequently exhibit alterations in thyroid hormone metabolism, including low T3 syndrome and subclinical hypothyroidism (SCH), both established predictors of poor prognosis ( 3 – 5 ).…

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