Current concepts in the management of long QT syndrome

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Abstract
Congenital and acquired long QT syndromes (LQTS) are diseases characterised by QT prolongation on the surface electrocardiogram (ECG) and a specific form of polymorphic ventricular tachycardia termed Torsade de Pointes (TdP). LQTS is caused by a net decrease in repolarising current, due to either gene mutation or drug action on late inward sodium current (INa), slowly activating delayed rectifier potassium current (IKs) and rapidly activating delayed rectifier potassium current (IKr). LQTS is associated with increased transmural dispersion of repolarisation (TDR) and phase 2 early afterdepolarisation (EAD), which are well-known risk factors for the development of TdP under conditions of QT prolongation. β-Adrenergic stimulation triggers the onset of TdP by inducing EAD and enhancing TDR. β-Adrenergic receptor blockade is the classic treatment for congenital forms of LQTS caused by gene mutation of ionic channels for IKs and IKr. Agents that shorten the QT interval, including a potassium supplement, INa blockers and IKs agonists, have been proposed to be useful in the treatment of LQTS. The strategies for the development of noncardiac, as well as cardiac, drugs with little risk of QT prolongation and TdP are also discussed.