Normalization of ventricular repolarization with flecainide in Long QT Syndrome patients with SCN5A:ΔKPQ mutation

John Robert Windle, Robin C. Geletka, Arthur J. Moss, Wojciech Zareba, Dianne L. Atkins

Research output: Contribution to journalArticle

98 Citations (Scopus)

Abstract

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:ΔKPQ, 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: ΔKPQ 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:ΔKPQ mutation. This preliminary study indicates that low-dose flecainide is a promising therapeutic agent for LQTS patients with the SCN5A:ΔKPQ sodium channel mutation.

Original languageEnglish (US)
Pages (from-to)153-158
Number of pages6
JournalAnnals of Noninvasive Electrocardiology
Volume6
Issue number2
DOIs
StatePublished - Jan 1 2001

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Flecainide
Long QT Syndrome
Mutation
Sodium Channels
Electrocardiography
Channelopathies
Sodium Channel Blockers
Mexiletine

Keywords

  • Antiarrhythmia agents
  • Genetics
  • Ion channels
  • Long QT syndrome

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine
  • Physiology (medical)

Cite this

Normalization of ventricular repolarization with flecainide in Long QT Syndrome patients with SCN5A:ΔKPQ mutation. / Windle, John Robert; Geletka, Robin C.; Moss, Arthur J.; Zareba, Wojciech; Atkins, Dianne L.

In: Annals of Noninvasive Electrocardiology, Vol. 6, No. 2, 01.01.2001, p. 153-158.

Research output: Contribution to journalArticle

Windle, John Robert ; Geletka, Robin C. ; Moss, Arthur J. ; Zareba, Wojciech ; Atkins, Dianne L. / Normalization of ventricular repolarization with flecainide in Long QT Syndrome patients with SCN5A:ΔKPQ mutation. In: Annals of Noninvasive Electrocardiology. 2001 ; Vol. 6, No. 2. pp. 153-158.
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