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