Abnormal Cardiac Repolarization in Thyroid Diseases: Results of an Observational Study

Abstract

Background: The relationship between thyroid function and cardiac disease is complex. Both hypothyroidism and thyrotoxicosis can predispose to ventricular arrhythmia and other major adverse cardiovascular events (MACE), so that a U-shaped relationship between thyroid signaling and the incidence of MACE has been postulated. Moreover, recently published data suggest an association between thyroid hormone concentration and the risk of sudden cardiac death (SCD) even in euthyroid populations with high-normal FT4 levels. In this study, we investigated markers of repolarization in ECGs, as predictors of cardiovascular events, in patients with a spectrum of subclinical and overt thyroid dysfunction.Methods: Resting ECGs of 100 subjects, 90 patients (LV-EF > 45%) with thyroid disease (60 overt hyperthyroid, 11 overt hypothyroid and 19 L-T4-treated and biochemically euthyroid patients after thyroidectomy or with autoimmune thyroiditis) and 10 healthy volunteers were analyzed for Tp-e interval. The Tp-e interval was measured manually and was correlated to serum concentrations of thyroid stimulating hormone (TSH), free triiodothyronine (FT3) and thyroxine (FT4).Results: The Tp-e interval significantly correlated to log-transformed concentrations of TSH (Spearman's rho = 0.30, p < 0.01), FT4 (rho = −0.26, p < 0.05), and FT3 (rho = −0.23, p < 0.05) as well as log-transformed thyroid's secretory capacity (SPINA-GT, rho = −0.33, p < 0.01). Spearman's rho of correlations of JT interval to log-transformed TSH, FT4, FT3, and SPINA-GT were 0.51 (p < 1e−7), −0.45 (p < 1e−5), −0.55 (p < 1e−8), and −0.43 (p < 1e−4), respectively. In minimal multivariable regression models, markers of thyroid homeostasis correlated to heart rate, QT, Tp-e, and JT intervals. Group-wise evaluation in hypothyroid, euthyroid and hyperthyroid subjects revealed similar correlations in all three groups.Conclusion: We observed significant inverse correlations of Tp-e and JT intervals with FT4 and FT3 over the whole spectrum of thyroid function. Our data suggest a possible mechanism of SCD in hypothyroid state by prolongation of repolarization. We do not observe a U-shaped relationship, so that the mechanism of SCD in patients with high FT4 or hyperthyroidism seems not to be driven by abnormalities in repolarization.

Critically ill severe hypothyroidism: a retrospective multicenter cohort study

“…The hemodynamic effects of a deficit in thyroid hormone combine with an increase in systemic vascular resistance and a decrease in cardiac contractility leading to a decrease in the cardiac output [25][26][27]. Severe bradycardia and arrhythmias related to abnormal cardiac repolarization and prolonged QT interval may also occur [28,29], as well as cardiac tamponade due to the accumulation of fluid rich in mucopolysaccharides in the pericardium [2]. Moreover, hemodynamic instability could be worsened by thyroid hormone introduction in several reports [8].…”

Deciphering the roles of triiodothyronine (T3) and thyroid-stimulating hormone (TSH) on cardiac electrical remodeling in clinical and experimental hypothyroidism

“…Therefore, based on correlation analyses performed in healthy individuals and in hypothyroid patients, with or without treatment, several groups proposed that QTc and QTd alterations are caused by elevated TSH levels [ 21 , 38 , 60 ]. In the same line of research, a correlation between TSH concentration and the duration of the T peak –T end has recently been described [ 4 ].…”

“…Either QTc prolongation, QTd increase, or T peak –T end lengthening is independently associated with an elevated incidence of polymorphic ventricular tachyarrhythmias, such as torsades de pointes (TdP). Although TdP usually extinguish spontaneously, if they persist, they can ultimately lead to ventricular fibrillation and sudden cardiac death [ 3 , 4 , 10 , 20 , 60 ]. Animal models of HT consistently reproduce the electrocardiographic alterations observed in patients [ 15 , 16 , 69 ].…”

Impaired autonomic function and somatosensory disturbance in patients with treated autoimmune thyroiditis

“…To assess the relative contributions of the pituitary gland, the thyroid and peripheral tissues to the variations in hormone concentrations, Jostel's TSH index (JTI), the thyroid's secretory capacity (SPINA-GT) and the sum activity of peripheral deiodinases (SPINA-GD) were calculated from steady-state concentrations of TSH, thyroid hormones and constants for plasma protein binding and kinetics, as recently described and recommended for thyroid trial design [24][25][26] . SPINA-GT was only calculated in subjects not on levothyroxine substitution therapy.…”