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
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Article info
Publication history
Published online: October 03, 2018
Identification
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Crown Copyright © 2018 Published by Elsevier B.V. on behalf of Australian and New Zealand Society of Cardiac and Thoracic Surgeons (ANZSCTS) and the Cardiac Society of Australia and New Zealand (CSANZ). All rights reserved.
