Hancox, JC, Whittaker, DG orcid.org/0000-0002-2757-5491, Du, C et al. (2 more authors) (2018) Emerging therapeutic targets in the short QT syndrome. Expert opinion on therapeutic targets, 22 (5). pp. 439-451. ISSN 1472-8222
Abstract
Introduction: Short QT Syndrome (SQTS) is a rare but dangerous condition characterised by abbreviated repolarisation, atrial and ventricular arrhythmias and risk of sudden death. Implantable cardioverter defibrillators (ICDs) are a first line protection against sudden death, but adjunct pharmacology is beneficial and desirable.
Areas covered: The genetic basis for genotyped SQTS variants (SQT1-SQT8) and evidence for arrhythmia substrates from experimental and simulation studies are discussed. The main ion channel/transporter targets for antiarrhythmic pharmacology are considered in respect of potential genotype-specific and non-specific treatments for the syndrome.
Expert opinion: Potassium channel blockade is valuable for restoring repolarisation and QT interval, though genotype-specific limitations exist in the use of some K+ channel inhibitors. A combination of K+ current inhibition during the action potential plateau, with sodium channel inhibition that collectively result in delaying repolarisation and post-repolarisation refractoriness is likely to be valuable in prolonging effective refractory period and wavelength for re-entry. Genotype-specific K+ channel inhibition is limited by a lack of targeted inhibitors in clinical use, though experimentally available selective inhibitors now exist. The relatively low proportion of successfully genotyped cases justifies an exome or genome sequencing approach, to reveal new mediators and targets, as demonstrated recently for SLC4A3 in SQT8.
Metadata
Item Type: | Article |
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Authors/Creators: |
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Copyright, Publisher and Additional Information: | © 2018 Informa UK Limited, trading as Taylor & Francis Group. This is an Accepted Manuscript of an article published by Taylor & Francis in Expert Opinion on Therapeutic Targets on 26 April 2018, available online: http://www.tandfonline.com/10.1080/14728222.2018.1470621. Uploaded in accordance with the publisher's self-archiving policy. |
Keywords: | Atrial fibrillation, atrial-selective, CACNA1C, CACNA2D1 CACNB2b hERG, KCNH2, KCNJ2, KCNQ1, Kir2.1, short QT syndrome, SLC4A3, sudden death, ventricular fibrillation |
Dates: |
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Institution: | The University of Leeds |
Academic Units: | The University of Leeds > Faculty of Biological Sciences (Leeds) > School of Biomedical Sciences (Leeds) |
Depositing User: | Symplectic Publications |
Date Deposited: | 09 May 2018 13:32 |
Last Modified: | 26 Apr 2019 00:39 |
Status: | Published |
Publisher: | Taylor & Francis |
Identification Number: | 10.1080/14728222.2018.1470621 |
Open Archives Initiative ID (OAI ID): | oai:eprints.whiterose.ac.uk:130519 |