Effects of flecainide in patients with new SCN5A mutation: Mutation- specific therapy for long-QT syndrome?

J. Benhorin*, R. Taub, M. Goldmit, B. Kerem, R. S. Kass, I. Windman, A. Medina

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

184 Scopus citations

Abstract

Background - Mutations in the cardiac sodium channel gene (SCN5A) can cause one variant of the congenital long-QT syndrome. The effects of some of these mutations on the α-subunit channel properties can be blocked by type Ib antiarrhythmic drugs. Recently, we have described a new SCN5A mutation (D1790G) that affects the channel properties in a manner suggesting that sodium blockers of the Ib type will be ineffective in carriers of this mutation. Hence, the ECG effects of flecainide-acetate, a type Ic sodium blocker, were evaluated in carriers of this mutation. Methods and Results - Eight asymptomatic mutation carriers and 5 control subjects were studied. Intravenous lidocaine was tested first in only 2 mutation carriers and had no significant effect on any ECG parameter. Flecainide significantly shortened all heart rate-corrected repolarization duration parameters only in carriers and not in control subjects: QT(c) shortened by 9.5% (from 517±45 to 468±36 ms, P=0.011), and the S-offset to T-onset interval shortened by 64.7% (from 187±88 to 66±50 ms, P=0.0092). Flecainide also normalized the marked baseline repolarization dispersion in most mutation carriers. These effects among carriers were maintained during long-term (9 to 17 months) outpatient flecainide therapy with no adverse effects. Conclusions - This report is the first to describe SCN5A mutation carriers who significantly responded to flecainide therapy yet did not respond to lidocaine. These results have important implications for long-QT allele-specific therapeutic strategies.

Original languageAmerican English
Pages (from-to)1698-1706
Number of pages9
JournalCirculation
Volume101
Issue number14
DOIs
StatePublished - 11 Apr 2000

Keywords

  • Genetics
  • Long-QT syndrome
  • Sodium (ion) channels

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