title: 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.
authors.affiliation: Department of Medicine and Therapeutics, Chinese University of Hong Kong, Hong Kong, SAR.
authors.forename: Gary
authors.initials: G
authors.lastname: Tse
authors.affiliation: Tianjin Key Laboratory of Ionic‑Molecular Function of Cardiovascular Disease, Department of Cardiology, Tianjin Institute of Cardiology, Second Hospital of Tianjin Medical University, Tianjin 300211, P.R. China.
authors.forename: Tong
authors.initials: T
authors.lastname: Liu
authors.affiliation: Faculty of Medicine, Newcastle University, Newcastle upon Tyne NE2 4HH, UK.
authors.forename: Ka Hou Christien
authors.initials: KH
authors.lastname: Li
authors.affiliation: Intensive Care Department, Royal Brompton and Harefield NHS Foundation Trust, London SW3 6NP, UK.
authors.forename: Victoria
authors.initials: V
authors.lastname: Laxton
authors.affiliation: Stem Cell and Regenerative Medicine Consortium, Li Ka Shing Faculty of Medicine, The University of Hong Kong, SAR, P.R. China.
authors.forename: Andy On-Tik
authors.initials: AO
authors.lastname: Wong
authors.affiliation: School of Biological Sciences, University of Cambridge, Cambridge CB2 1AG, UK.
authors.forename: Yin Wah Fiona
authors.initials: YW
authors.lastname: Chan
authors.affiliation: Stem Cell and Regenerative Medicine Consortium, Li Ka Shing Faculty of Medicine, The University of Hong Kong, SAR, P.R. China.
authors.forename: Wendy
authors.initials: W
authors.lastname: Keung
authors.affiliation: Stem Cell and Regenerative Medicine Consortium, Li Ka Shing Faculty of Medicine, The University of Hong Kong, SAR, P.R. China.
authors.forename: Camie W Y
authors.initials: CW
authors.lastname: Chan
authors.affiliation: Li Dak‑Sum Research Centre‑HKU‑Karolinska Institutet Collaboration on Regenerative Medicine, University of Hong Kong, Hong Kong, SAR, P.R. China.
authors.forename: Ronald A
authors.initials: RA
authors.lastname: Li
mesh_terms: D000818:Animals; D001919:Bradycardia / Q000209:etiology* / Q000378:metabolism* / Q000503:physiopathology / Q000628:therapy; D002118:Calcium / Q000378:metabolism; D055724:Electrophysiological Phenomena; D017629:Gap Junctions / Q000378:metabolism; D006801:Humans; D007473:Ion Channels / Q000378:metabolism; D012804:Sick Sinus Syndrome / Q000150:complications; D012849:Sinoatrial Node / Q000378:metabolism / Q000503:physiopathology; D013577:Syndrome; D013610:Tachycardia / Q000209:etiology* / Q000378:metabolism* / Q000503:physiopathology / Q000628:therapy
chemical_list: D007473:Ion Channels; D002118:Calcium