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Review| Volume 28, ISSUE 1, P22-30, January 2019

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Channelopathies That Lead to Sudden Cardiac Death: Clinical and Genetic Aspects

  • Jonathan R. Skinner
    Correspondence
    Corresponding author at: Green Lane Paediatric and Congenital Cardiac Services, Starship Children’s Hospital, Private Bag 92024, Auckland 1142, New Zealand. Tel.: +64 9 3074949 Fax: +64 9 6310785.
    Affiliations
    The Cardiac Inherited Disease Group, Auckland, New Zealand

    Greenlane Paediatric and Congenital Cardiac Services, Starship Children’s Hospital, Auckland, New Zealand

    Department of Paediatrics, Child and Youth Health, University of Auckland, New Zealand
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  • Annika Winbo
    Affiliations
    The Cardiac Inherited Disease Group, Auckland, New Zealand

    Greenlane Paediatric and Congenital Cardiac Services, Starship Children’s Hospital, Auckland, New Zealand

    Department of Neurophysiology, University of Auckland, New Zealand
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  • Dominic Abrams
    Affiliations
    Inherited Cardiac Arrhythmia Program, Department of Cardiology, Boston Children’s Hospital, Boston, MA, USA

    Harvard Medical School, Boston, MA, USA
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  • Jitendra Vohra
    Affiliations
    Cardiology Department and Department Of Genomics, The Royal Melbourne Hospital, Melbourne, Vic, Australia

    University Of Melbourne, Melbourne, Vic, Australia
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  • Arthur A. Wilde
    Affiliations
    Heart Centre AMC, Department of Clinical and Experimental Cardiology, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands

    Department of Medicine, Columbia University Irving Medical Center, New York, NY, USA
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Published:October 03, 2018DOI:https://doi.org/10.1016/j.hlc.2018.09.007
      Forty per cent (40%) of sudden unexpected natural deaths in people under 35 years of age are associated with a negative autopsy, and the cardiac ion channelopathies are the prime suspects in such cases. Long QT syndrome (LQTS), Brugada syndrome (BrS) and catecholaminergic polymorphic ventricular tachycardia (CPVT) are the most commonly identified with genetic testing. The cellular action potential driving the heart cycle is shaped by a specific series of depolarising and repolarising ion currents mediated by ion channels. Alterations in any of these currents, and in the availability of intracellular free calcium, leaves the myocardium vulnerable to polymorphic ventricular tachycardia or ventricular fibrillation. Each channelopathy has its own electrocardiogram (ECG) signature, typical mode of presentation, and most commonly related gene. Long QT type 1 (gene, KCNQ1) and CPVT (gene, RyR2) typically present with cardiac events (ie syncope or cardiac arrest) during or immediately after exercise in young males; long QT type 2 (gene, KCNH2) after startle or during the night in adult females-particularly early post-partum, and long QT type 3 and Brugada syndrome (gene, SCN5A) during the night in young adult males. They are commonly misdiagnosed as seizure disorders. Fever-triggered cardiac events should also raise the suspicion of BrS. This review summarises genetics, cellular mechanisms, risk stratification and treatments. Beta blockers are the mainstay of treatment for long QT syndrome and CPVT, and flecainide is remarkably effective in CPVT. Brugada syndrome is genetically a more complex disease than the others, and risk stratification and management is more difficult.

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