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Publication stageIn Press Journal Pre-Proof
Funding Sources: This work was supported by the Mayo Clinic Windland Smith Rice Comprehensive Sudden Cardiac Death Program.
Disclosures: Dr Ackerman is a consultant for Abbott, Boston Scientific, Bristol Myers Squibb, Daiichi Sankyo, Invitae, Medtronic, Tenaya Therapeutics, and UpToDate. Dr Ackerman and Mayo Clinic are involved in an equity/royalty relationship with AliveCor, Anumana, ARMGO Pharma, Pfizer, and Thryv Therapeutics; however, none of these entities have contributed to this study in any manner. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose.
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- Variant-specific therapy for long QT syndrome type 3Heart Rhythm
- PreviewCongenital long QT syndrome (LQTS) is an inherited cardiac arrhythmia syndrome characterized by a prolonged QT interval on the electrocardiogram.1 Long QT syndrome type 3 (LQT3) is caused by gain-of-function variants in the SCN5A-encoded α-subunit of the voltage-gated cardiac sodium (Na+) channel Nav1.5. LQT3-linked SCN5A variants typically interfere with fast inactivation of the channel, which causes increased sustained inward Na+ current (INa) and prolongation of the cardiac action potential.2 In addition, some variants such as p.D1790G can prolong the ventricular action potential in the absence of an LQT3 variant-induced sustained Na+ current.