Low triiodothyronine syndrome as a factor of an unfavorable course of heart failure in patients with ischemic heart disease and COVID-19 history

Objective — to establish the association of low triiodothyronine syndrome (LT3S) with the risk of an unfavorable course of heart failure (HF) in patients with ischemic heart disease who have had COVID‑19, taking into account some clinical, pharmacogenetic, and biomarker indicators. Materials and methods. The study included 352 patients with ischemic origin of HF arising in individuals with ischemic heart disease. Of these, 128 (36.4%) patients had a history of COVID‑19 with lung involvement, and 224 (63.6%) without lung involvement. The patients were followed up for 24 months to study the impact of the presence of LT3S, levels of tumor necrosis factor α (TNF‑α), interleukin‑6 (IL‑6), and polymorphisms of the β‑adrenergic receptor system genes on the course of HF, taking into account the frequency of hospitalizations due to HF decompensation. Results. The frequency of recurrent hospitalizations of HF patients without lung involvement in COVID‑19 was 20.6%, while in patients with lung involvement — 45.3% (χ2=24.505; p=0.0001). There is a tendency to the increase in the frequency of recurrent hospitalizations in HF patients with established LT3S compared to those without this syndrome (31.7% vs. 22.9%, χ2=3.326; p=0.068). It was found that the risk of LT3S increased in homozygous carriers of CC polymorphism at the Ser275 site of the G‑protein β3 subunit gene: the odds ratio (OR) was 1.75 (95% confidence interval (CI) 0.99—3.07; p=0.054). The risk of increasing concentration of TNF‑α and IL‑6 in HF patients was higher in homozygous carriers of CC polymorphism at the Ser275 site of the G‑protein β3 subunit gene: OR=4.55 (95% CI 1.27—16.34); p=0.028) and OR=5.86 (95% CI 1.81—19.00; p=0.003). The risk of recurrent hospitalizations in HF patients with lung involvement in COVID‑19 was associated with the heterozygous C/T polymorphism at the Ser275 site of the G‑protein β3 subunit gene (OR=4.36 (95% CI 1.85—10.27; p=0.022). Conclusions. In patients with ischemic HF low T3 blood serum level can be a predictor of unfavorable prognosis. LT3S in such patients is associated with more severe course of COVID­­19. The inducer of LT3S development may be proinflammatory cytokines that affect the conversion of T4 to T3. The risk of LT3S development in patients with IHD and COVID­­19 history is associated with b­­adrenoreceptor system gene polymorphism. Measuring T3 level in blood serum is a simple instrument for the risk stratification in patients with severe form of COVID­­19 on the background of HF syndrome.