Abstract 12798: Mutation Site-Specific Differences in Arrhythmic Risk in the LQT3 Form of Congenital Long QT Syndrome: Multicenter Study in Japan
Risk stratification in the patients with long QT syndrome type 3 (LQT3) is lacking. We hypothesized that mutations in the pore-forming segment between S5 through S6 (S5-S6) of the cardiac sodium channel (SCN5a) are associated with malignant arrhythmic events in the LQT3 patients.
Methods: 112 LQT3 patients (54 female) from 61 proband-based families with genetically confirmed SCN5a mutations including 7 different S5-S6 mutations (11 probands and 10 family members) and 25 other mutations (50 probands and 41 family members) were enrolled from seven Japanese institutions. Endpoints were cardiac events such as syncope, aborted cardiac arrest or ventricular fibrillation (VF), and sudden cardiac death.
Results: 34 patients experienced syncope, and 15 of these events were lethal (aborted cardiac arrest, VF or sudden death). Cardiac events occurred during rest or sleep (55%), emotional stress (21%) or exercise (10%). 93% of the lethal cardiac events occurred during sleep/rest (p<0.01 by χ2 analysis) and 73% of the lethal events were the first cardiac events. Probands, increased QTc interval and mutations in the S5-S6 segment of the Na channel were related to the risk of the lethal cardiac events. Furthermore, multivariate Cox regression analysis revealed that patients with the S5-S6 mutations had a greater risk of syncope and lethal events with a hazard ratio of 7.3 and 18.4, respectively (p<0.0001) with a 15% increase in risk per 10-ms increase in QTc interval (p<0.05). On the other hand, no difference was observed in the QRS, QTc, QT peak-end interval between patients with S5-S6 and non-S5-S6 mutations. Mexiletine and beta-blockers were administrated in a larger number of patients with the S5-S6 mutations compared with other mutations. (78% vs. 13% and 44% vs.6%, respectively)
Conclusion: In this multicenter Japanese study, LQT3 patients with mutations in the S5-S6 segment of SCN5a are at higher risk of LQTS-related cardiac events including potentially lethal arrhythmias.
- © 2011 by American Heart Association, Inc.