Normalization of ventricular repolarization with flecainide in long QT syndrome patients with SCN5A:ΔKPQ mutation

被引:75
作者
Windle, JR [1 ]
Geletka, RC
Moss, AJ
Zareba, W
Atkins, DL
机构
[1] Univ Nebraska, Med Ctr, Omaha, NE 68198 USA
[2] Univ Rochester, Med Ctr, Cardiol Unit, Rochester, NY 14642 USA
[3] Univ Iowa, Coll Med, Iowa City, IA USA
关键词
long QT syndrome; ion channels; antiarrhythmia agents; genetics;
D O I
10.1111/j.1542-474X.2001.tb00100.x
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
Background: The Long QT Syndrome (LQTS) is a genetic channelopathy with life-threatening implications. The LQT3 form of this disease is caused by mutations of the SCN5A sodium-channel gene. A specific mutation, SCN5A:Delta KPQ, is associated with repetitive reopenings of the sodium channel and prolonged inward current. This dominant inward current is manifest on the electrocardiogram as QT prolongation. Flecainide is a potent blacker of the open sodium channel. Methods and Results: The effect of flecainide on the duration of the QT-interval and the T-wave morphology was systematically evaluated in five male patients age 2-64 years having the SCN5A:Delta KPQ mutation. After baseline electrocardiograms were obtained, low-dose oral flecainide was administered for 48 hours. Serial electrocardiograms and blood flecainide levels were obtained during flecainide therapy. The QTc interval decreased on average by 104 ms, from a baseline value of 565 +/- 60 ms to 461 +/- 23 ms (P < 0.04) at a mean flecainide level of 0.28 +/- 0.08 mg/L, with shortening of the QTonset interval (P < 0.003) and normalization of T-wave morphology. The effects of flecainide were compared with oral mexiletine in two patients, with flecainide showing greater QTc shortening and more complete normalization of repolarization, No adverse side effects or proarrhythmia were observed with flecainide in this study. Conclusion: Low-dose, oral flecainide consistently shortened the QTc interval and normalized the repolarization T-wave pattern in five LQT3 patients with SCN5A:Delta KPQ mutation. This preliminary study indicates that low-dose flecainide is a promising therapeutic agent for LQTS patients with the SCN5A:Delta KPQ sodium channel mutation.
引用
收藏
页码:153 / 158
页数:6
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