Inadvertent treatment with a pure IKr blocker in LQT2 syndrome

Long QT syndrome (LQTS) results from
structural abnormalities in the potassium
channels of the heart, which predispose
affected persons to an accelerated
heart rhythm (arrhythmia). Nifekalant,
a new class III antiarrhythmic agent
developed in US, blocks selectively a
rapidly-activating component of the
delayed rectifier potassium channel
(IKr) in cardiac myocytes, and causes
dose-dependent increase in artrial
and ventricular refractory periods and
repolarization. We report a case of
congenital long QT syndrome (LQTS)
with recurrent ventricular fibrillation
inadvertently treated with intravenous
nifekalant. Treatment neither modified
the rate-corrected QT interval nor
induced torsades de points. Subsequent
genotyping of the patient revealed a
missense mutation in the extracellular
loop between S5 and the pore region of
HERG (K595E). Since HERG encodes
the IKr channel, LQT2 patient may be
more tolerant of pure IKr blockers than
other LQTS genotypes.