Thyroid function and outcomes in heart failure with mildly reduced ejection fraction: insights from a large, retrospective registry

Abstract Objective This study aimed to investigate the prognostic impact of thyroid status on the outcomes of patients with heart failure with mildly reduced ejection fraction (HFmrEF). Background Thyroid function is crucial for the optimal performance of the cardiovascular system. However, the prognostic impact of subclinical thyroid dysfunction in patients with heart failure, specifically HFmrEF, remains unclear. Methods For the present study, patients hospitalized with HFmrEF and known thyroid status were included from 2016 to 2022. Patients were divided into four groups: euthyroid (reference group, n=1,186 TSH 0.45-4.5 mU/L), latent hypothyroidism (n=95 TSH 4.5 mU/L, fT4 5.5-23 pmol/L), latent hyperthyroidism (n=139 TSH 0.45 mU/L, fT4 7.5-23 pmol/L), and low T3 syndrome (n=148 fT3 ≤ 3.3 pmol/L). Patients with manifest hypo- and hypothyroidism were excluded related to the low sample size. The primary endpoint was all-cause mortality at 30 months (median follow-up). Key secondary endpoint was heart failure-related rehospitalization at 30 months. Results From 1,568 patients with HFmrEF, most patients presented with euthyroidism (75.6%), followed by low T3 syndrome (9.4%), latent hyperthyroidism (8.9%), and latent hypothyroidism (6.1%). The risk of all-cause mortality at 30 months was highest in patients with low T3 syndrome (51.4%), followed by latent hypothyroidism (38.9%) and latent hyperthyroidism (36.7%), whereas euthyroid patients (26.6%) had the lowest risk of long-term all-cause mortality (log rank p=0.001). In multivariate Cox regression analyses, latent hypothyroidism (hazard ratio HR 1.454, 95% confidence interval CI 1.001-2.113, p=0.049), latent hyperthyroidism (HR 1.458, 95% CI 1.046-2.033, p=0.026), and low T3 syndrome (HR 1.594, 95% CI 1.185-2.145, p=0.002) were identified as independent predictors of all-cause mortality at 30 months compared to euthyroid patients. Patients with low T3 syndrome were even associated with impaired prognosis as compared to patients with latent hyperthyroidism (HR 1.553, 95% CI 1.088-2.212; p=0.015). However, thyroid status was not associated with the risk of HF-related rehospitalization at 30 months. Conclusion In patients with HFmrEF, the presence of latent hypothyroidism, latent hyperthyroidism and low T3 were identified as predictors of all-cause mortality, but not of HF-related rehospitalization at 30 months.