Pronounced shortening of QT interval with mexiletine infusion test in patients with type 3 congenital long QT syndrome

Background: Mexiletine is often used for medical therapy in LQT3 patients, however, the usefulness of mexiletine infusion test for LQT3 patients has not been reported. The aim of this study was to evaluate the usefulness of mexiletine infusion test for detecting LQT3 patients. Methods and Results: We analyzed response in 12-lead electrocardiogram parameters measured in II or V5 to i.v. mexiletine infusion (2 mg/kg) during sinus rhythm among 31 genotype-positive LQT patients (29±18 years, 12 male). Change in QTc interval after mexiletine was compared between LQT3 (n=15, 24±21 years, 9 male) and other LQT patients (4 LQT1 and 12 LQT2; 34±14 years, 3 male). Baseline RR, QT, and QTc interval were not different between the 2 groups (981±182 vs. 1,023±192 ms; 550±94 vs. 524±75 ms; 556±66 vs. 520±62 ms, respectively). While QTc interval was shortened with mexiletine in both groups (P<0.0001 vs. baseline), degree of QTc shortening (ΔQTc) was significantly larger in LQT3 than in LQT1/LQT2 patients (99±39 vs. 48±32 ms; P=0.0004). The sensitivity, specificity and predictive accuracy of mexiletine infusion test for differentiating LQT3 from LQT1/LQT2 were 86.7%, 81.3% and 81.3%, respectively, and the optimal cut-off for ΔQTc was 69 ms on receiver operating characteristic analysis. No pro-arrhythmic event was observed. Conclusions: Pronounced shortening of QT interval with mexiletine may facilitate genetic testing in patients with LQT3 syndrome.