Tachycardia-bradycardia syndrome: Electrophysiological mechanisms and future therapeutic approaches (Review)

Abstract

Sick sinus syndrome (SSS) encompasses a group of disorders whereby the heart is unable to perform its pacemaker function, due to genetic and acquired causes. Tachycardia-bradycardia syndrome (TBS) is a complication of SSS characterized by alternating tachycardia and bradycardia. Techniques such as genetic screening and molecular diagnostics together with the use of pre-clinical models have elucidated the electrophysiological mechanisms of this condition. Dysfunction of ion channels responsible for initiation or conduction of cardiac action potentials may underlie both bradycardia and tachycardia; bradycardia can also increase the risk of tachycardia, and vice versa. The mainstay treatment option for SSS is pacemaker implantation, an effective approach, but has disadvantages such as infection, limited battery life, dislodgement of leads and catheters to be permanently implanted in situ. Alternatives to electronic pacemakers are gene-based bio-artificial sinoatrial node and cell-based bio-artificial pacemakers, which are promising techniques whose long-term safety and efficacy need to be established. The aim of this article is to review the different ion channels involved in TBS, examine the three-way relationship between ion channel dysfunction, tachycardia and bradycardia in TBS and to consider its current and future therapies.

TRPM7 regulates angiotensin II-induced sinoatrial node fibrosis in sick sinus syndrome rats by mediating Smad signaling

“…In addition, the atrium in sinus node disease due to extensive atrial fibrosis can lead to an atrial standstill [ 8 ]. Mechanistically, abnormal ion channels responsible for the initiation and/or conduction of cardiac action potentials are considered the main electrophysiological mechanism underlying the occurrence of SSS [ 9 , 10 ]. For instance, increased Ca 2+ flux promoted the pathogenesis of SSS [ 11 ] and the suppression of muscarinic-gated K + channel by chemicals or genetic deletion reduced SSS in a mouse SSS model [ 12 ].…”

"Preventive" pacing in patients with tachy‐brady syndrome (TBS): Confirming a common practice

“…Tachycardia-bradycardia syndrome (TBS) is a subgroup of SSS, accounting for up to 40% of SSS patients, characterised by alternating sinus bradycardia and rapid atrial tachyarrhythmia, usually paroxysmal atrial fibrillation (AF). 3,[5][6][7] Important interplay exists between bradyarrhythmias and tachyarrhythmias in TBS, including "conversion pauses" upon termination of AF and resumption of sinus rhythm, because of prolonged sinus recovery time. 3,6 On the contrary, sinus bradycardia and prolonged pauses may trigger AF episodes.…”

Association between routine biomarkers and atrial fibrillation in patients undergoing implantation of a dual‐chamber pacemaker

“…[9][10][11][12][13][14] SND is associated with atrial fibrosis, atrial myopathy, and structural remodeling, creating a substrate that facilitates AF development and perpetuation. 3,4 Furthermore, bradycardia per se, ion-channel remodeling, abnormal calcium handling, electrophysiological alterations, and autonomic abnormalities contribute to the atrial arrhythmogenesis. 3,4 Indeed, up to 70% of patients implanted a dual chamber for SND may suffer AF, while in 40%-70% of SND patients atrial arrhythmias are evident at the time of diagnosis.…”