Pro-Arrhythmic Signaling of Thyroid Hormones and Its Relevance in Subclinical Hyperthyroidism

Abstract

A perennial task is to prevent the occurrence and/or recurrence of most frequent or life-threatening cardiac arrhythmias such as atrial fibrillation (AF) and ventricular fibrillation (VF). VF may be lethal in cases without an implantable cardioverter defibrillator or with failure of this device. Incidences of AF, even the asymptomatic ones, jeopardize the patient’s life due to its complication, notably the high risk of embolic stroke. Therefore, there has been a growing interest in subclinical AF screening and searching for novel electrophysiological and molecular markers. Considering the worldwide increase in cases of thyroid dysfunction and diseases, including thyroid carcinoma, we aimed to explore the implication of thyroid hormones in pro-arrhythmic signaling in the pathophysiological setting. The present review provides updated information about the impact of altered thyroid status on both the occurrence and recurrence of cardiac arrhythmias, predominantly AF. Moreover, it emphasizes the importance of both thyroid status monitoring and AF screening in the general population, as well as in patients with thyroid dysfunction and malignancies. Real-world data on early AF identification in relation to thyroid function are scarce. Even though symptomatic AF is rare in patients with thyroid malignancies, who are under thyroid suppressive therapy, clinicians should be aware of potential interaction with asymptomatic AF. It may prevent adverse consequences and improve the quality of life. This issue may be challenging for an updated registry of AF in clinical practice. Thyroid hormones should be considered a biomarker for cardiac arrhythmias screening and their tailored management because of their multifaceted cellular actions.

Molecular noise filtering in the β-adrenergic signaling network by phospholamban pentamers

“…A similar mechanism may contribute to the pro-arrhythmic effect of thyroid hormones, which increase SERCA and decrease PLN expression (thus decreasing pentamerization) (Tribulova et al, 2020). Apart from PLN, both PP1 and inhibitor-1 have been shown to be involved in the emergence of arrhythmias (Chiang et al, 2016).…”

Levothyroxine Treatment and the Risk of Cardiac Arrhythmias – Focus on the Patient Submitted to Thyroid Surgery

“…On the other hand, abnormal intercellular impulse propagation refers to a block of conduction and re-entry. Re-entry occurs when the propagating impulse persists due to continuous activity, after normal activation of the heart, instead of dying out, that re-excites the heart after the refractory period has ended ( 138 ).…”

The Assessment of Ventricular Arrhythmia Indicators Based on Electrocardiography in Patients With Differentiated Thyroid Cancer Followed Up With Levothyroxine Suppression

“…Although the underlying mechanism has not been fully understood yet, it has been shown that myocardial electrical instability as a consequence of overt or subclinical hyperthyroidism may facilitate the increased excitability and shorten the duration of cardiac repolarization. 26 A membrane hyperpolarization subsequent to increased levels of intracellular potassium due to an increase in cardiac sodium/potassium adenosine triphosphates activity is the most likely hypothesis about how increased thyroid hormone levels lead to QTc prolongation. 27 Higher levels of thyroid hormones have also shortened the duration of ventricular repolarization by increasing the release of calcium from myocardial sarcoplasmic reticulum.…”