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

OBJECTIVE: This study aimed to investigate the prognostic impact of thyroid function 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 (HF), specifically HFmrEF, remains unclear. METHODS: For the present study, patients hospitalized with HFmrEF and known thyroid function were included from 2016 to 2022. Patients were divided into four groups: euthyroid (reference group, n = 1186 [TSH 0.45-4.5 mU/L]), subclinical hypothyroidism (n = 95 [TSH > 4.5 mU/L, fT4 7.5-23 pmol/L]), subclinical 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 hyper- 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 HF-related rehospitalization at 30 months. RESULTS: From 1568 patients with HFmrEF, most patients presented with euthyroidism (75.6%), followed by low T3 syndrome (9.4%), subclinical hyperthyroidism (8.9%), and subclinical hypothyroidism (6.1%). The risk of all-cause mortality at 30 months was highest in patients with low T3 syndrome (51.4%), followed by subclinical hypothyroidism (38.9%) and subclinical hyperthyroidism (36.7%), whereas euthyroid patients (26.6%) had the lowest risk of long-term all-cause mortality (p = 0.001). In multivariable Cox regression analyses, subclinical hypothyroidism (hazard ratio [HR] 1.454, 95% confidence interval [CI] 1.001-2.113, p = 0.049), subclinical 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 subclinical 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 subclinical hypothyroidism, subclinical hyperthyroidism, and low T3 syndrome were identified as predictors of all-cause mortality, but not of HF-related rehospitalization at 30 months.