Purkinje system hyperexcitability and ventricular arrhythmia risk in type 3 long QT syndrome.

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  • Additional Information
    • Source:
      Publisher: Elsevier Country of Publication: United States NLM ID: 101200317 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1556-3871 (Electronic) Linking ISSN: 15475271 NLM ISO Abbreviation: Heart Rhythm Subsets: MEDLINE
    • Publication Information:
      Original Publication: New York, NY : Elsevier, c2004-
    • Subject Terms:
      Cardiac Conduction System Disease/*physiopathology ; Long QT Syndrome/*physiopathology ; Purkinje Cells/*physiology ; Tachycardia, Ventricular/*physiopathology; Adolescent ; Adult ; Cardiac Conduction System Disease/complications ; Cardiac Conduction System Disease/diagnosis ; Child ; Female ; Humans ; Long QT Syndrome/complications ; Long QT Syndrome/diagnosis ; Male ; Myocytes, Cardiac/physiology ; Patch-Clamp Techniques ; Retrospective Studies ; Tachycardia, Ventricular/complications ; Young Adult
    • Abstract:
      Background: Gain-of-function variants in the SCN5A-encoded Na v 1.5 sodium channel cause type 3 long QT syndrome (LQT3) and multifocal ectopic Purkinje-related premature contractions. Although the Purkinje system is uniquely sensitive to the action potential-prolonging effects of LQT3-causative variants, the existence of additional Purkinje phenotype(s) in LQT3 is unknown.
      Objective: The purpose of this study was to determine the prevalence and clinical implications of frequent fascicular/Purkinje-related premature ventricular contractions (PVCs) and short-coupled ventricular arrhythmias (VAs), suggestive of Purkinje system hyperexcitability (PSH), in a single-center LQT3 cohort.
      Methods: A retrospective analysis of 177 SCN5A-positive patients was performed to identify individuals with a LQT3 phenotype. Available electrocardiographic, electrophysiology study, device, and genetic data from 91 individuals with LQT3 were reviewed for evidence of presumed fascicular PVCs and short-coupled VAs. The relationship between PSH and ventricular fibrillation events was assessed by Kaplan-Meier and Cox regression analyses.
      Results: Overall, 30 of 91 patients with LQT3 (33%) exhibited evidence of presumed PSH (fascicular PVCs 30 of 30 [100%]; short-coupled VAs 17 of 30 [56%]). Kaplan-Meier and Cox regression analyses demonstrated an increased risk of ventricular fibrillation events in individuals with LQT3 and PSH (log-rank, P < .03; hazard ratio 3.95; 95% confidence interval 1.15-15.7; P = .03). Interestingly, variants in the voltage-sensing domain regions of Na v 1.5 were more frequently observed in patients with LQT3 and PSH than those without (19 of 30 [63%] vs 9 of 61 [15%]; P < .0001).
      Conclusion: This study demonstrates that a discernible Purkinje phenotype is present in one-third of LQT3 cases and increases the risk of potentially lethal VAs. Further study is needed to determine whether a distinct cellular electrophysiology phenotype underlies this phenomenon.
      (Copyright © 2020. Published by Elsevier Inc.)
    • Comments:
      Comment in: Heart Rhythm. 2020 Oct;17(10):1777-1778. (PMID: 32497765)
    • Contributed Indexing:
      Keywords: Cardiac events; Premature ventricular contractions; Purkinje system; Type 3 long QT syndrome; Ventricular arrhythmias
    • Subject Terms:
      Long QT syndrome type 3
    • Publication Date:
      Date Created: 20200527 Date Completed: 20210914 Latest Revision: 20210914
    • Publication Date:
      20240829
    • Accession Number:
      10.1016/j.hrthm.2020.05.019
    • Accession Number:
      32454217