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Heart Lung Circ. 2019 Jan;28(1):22-30. doi: 10.1016/j.hlc.2018.09.007. Epub 2018 Oct 4.

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

Author information

1
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. Electronic address: jskinner@adhb.govt.nz.
2
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.
3
Inherited Cardiac Arrhythmia Program, Department of Cardiology, Boston Children's Hospital, Boston, MA, USA; Harvard Medical School, Boston, MA, USA.
4
Cardiology Department and Department Of Genomics, The Royal Melbourne Hospital, Melbourne, Vic, Australia; University Of Melbourne, Melbourne, Vic, Australia.
5
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.

Abstract

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.

KEYWORDS:

Brugada syndrome; CPVT; Channelopathy; Genetics; Long QT syndrome; Sudden death

PMID:
30389366
DOI:
10.1016/j.hlc.2018.09.007
[Indexed for MEDLINE]

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