Levothyroxine replacement therapy enhances physical activity tolerance, heart failure severity (NYHA class), and thyroid function within 6 months in heart failure with reduced ejection fraction (HFrEF) patients with subclinical hypothyroidism, according to a multicenter trial published in the journal Cell Reports Medicine.¹

The efficacy and safety of levothyroxine (L-T4) in 117 patients with subclinical hypothyroidism and HFrEF were examined in a randomized, multicenter, open-label trial conducted by a team of researchers from China between March 2017 and December 2018. Fifty-seven participants, mean age 58.54 years were categorized into experimental group, which received L-T4 (median dose 12.50 μg) along with standard HFrEF treatment and a control group of 60 patients, mean age 57.77 years, which received standard HFrEF therapy alone.

The experimental group showed a significantly greater improvement in the 6-minute walk test distance, the primary endpoint, from baseline to 24 weeks (70.08 m) compared to the control group (27.73 m) with a mean difference of 46.90 meters. No significant differences in Minnesota Living with Heart Failure Questionnaire (MLHFQ) score, N-terminal pro-B-type natriuretic peptide (NT-proBNP), or echocardiographic measures (ejection fraction, left atrium , left ventricular, aortic diameter, interventricular septum, and left ventricular posterior wall) were observed between the two groups at both baseline and at 24 weeks.

Significant improvements were also observed in the New York Heart Association (NYHA) in the experimental group. The frequency of NYHA class I patients gradually increased over the treatment period, while the frequency of NYHA class III–IV patients gradually declined in the experimental group. The incidence of adverse events was comparable between groups (risk ratio 0.94).

The thyroid function also improved in the experimental group as evident by significant decline in TSH plus an increase in FT3 levels.

This study highlights the high prevalence of subclinical hypothyroidism in patients with HFrEF. It demonstrates the beneficial role of low-dose L-T4 as a complementary therapy in this group of patients with a favorable safety profile. However, further double-blind, placebo-controlled trials are recommended to corroborate these findings.

Reference

1.   Wenyao Wang, et al. Effects of levothyroxine in subclinical hypothyroidism and heart failure with reduced ejection fraction: An open-label randomized trial. Cell Rep Med. 2024 Apr 16;5(4):101473. doi: 10.1016/j.xcrm.2024.101473.