Strategies aimed at easing patients' adjustment to ICDs should be developed and tested for efficacy in the setting of ICD prophylaxis.

Chronic low-dose flecainide significantly shortens the QTc interval in LQT-3 subjects with the DeltaKPQ mutation. No major adverse drug effects were observed with flecainide during this trial, but the sample size is not large enough to evaluate the safety of flecainide therapy in patients with this mutation.

This study suggests that elevated markers of diastolic dysfunction during pre-LTx echocardiographic evaluation are associated with an excess risk of HF and may predict post-LTx survival.

Background:The Long QT Syndrome (LQTS) i s 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:AKPQ, 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 blocker 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: AKPQ 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 2 23 ms (P < 0.04) at a mean flecainide level of 0.28 5 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:AKPQ mutation. This preliminary study indicates that low-dose flecainide is a promising therapeutic agent for LQTS patients with the long QT syndrome; ion channels; antiarrhythmia agents; genetics SCN5A:AKPQ sodium channel mutation.