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

Background-Mutations in the cardiac sodium channel gene (SCN5A) can cause o ne variant of the congenital long-QT syndrome, The effects of some of these mutations on the alpha-subunit channel properties can be blocked by type I b antiarrhythmic drugs. Recently, we have described a new SCN5A mutation (D 1790G) that affects the channel properties in a manner suggesting that sodi um 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, w ere evaluated in carriers of this mutation. Methods and Results-Eight asymptomatic mutation carriers and 5 control subj ects were studied. Intravenous lidocaine was tested first in only 2 mutatio n carriers and had no significant effect on any ECG parameter. Flecainide s ignificantly shortened all heart rate-corrected repolarization duration par ameters only in carriers and not in control subjects: QT, shortened by 9.5% (from 517+/-45 to 468+/-36 ms, P=0.011), and the S-offset to T-onset inter val shortened by 63.7% (ft om 187+/-88 to 66+/-50 ms, P=0.0092), Flecainide also normalized the marked baseline repolarization dispersion in most muta tion carriers. These effects among carriers were maintained during long-ter m (9 to 17 months) outpatient flecainide therapy with no adverse effects. Conclusions-This report is the first to describe SCN5A mutation carriers wh o significantly responded to flecainide therapy yet did not respond to lido caine, These results have important implications for long-QT allele-specifi c therapeutic strategies.