What is the clinical evidence from this study?

Study design: Cross-Sectional. Population: Congenital Long QT Syndrome (n=31). Intervention: Mexiletine infusion vs. LQT1/LQT2 patients. Primary outcome: Change in QTc interval (ΔQTc) (p=0.0004).

December 2, 2015Open Access

Pronounced Shortening of QT Interval With Mexiletine Infusion Test in Patients With Type 3 Congenital Long QT Syndrome

MFMoritoshi FunasakoElectrophysiology TATakeshi AibaElectrophysiology KIKohei IshibashiNational Cerebral and Cardiovascular Center

Key Result

Mexiletine infusion significantly shortened the QTc interval to a greater extent in LQT3 patients compared to LQT1 and LQT2 patients (99 ms vs 48 ms, P=0.0004).

Study Design

Type

Cross-Sectional (n=31)

Multicenter

Structured PICO

Does an intravenous mexiletine infusion test improve the differentiation of LQT3 from LQT1 and LQT2 in patients with congenital long QT syndrome?

Population

31 genotype-positive congenital long QT syndrome (LQTS) patients (15 LQT3, 4 LQT1, 12 LQT2), mean age 29 ± 18 years, 12 male. All patients were off oral β-blockers and anti-arrhythmic agents at the time of the test.

Intervention

Intravenous mexiletine infusion (2 mg/kg) over 10 minutes during sinus rhythm.

Comparator

LQT1 and LQT2 patients (to compare the degree of QTc shortening against LQT3 patients).

Outcome

Change in QTc interval (∆QTc) after mexiletine infusion.surrogate

A mexiletine infusion test demonstrating pronounced QTc shortening (≥69 ms) is a safe and useful clinical tool to differentiate LQT3 from LQT1 and LQT2, facilitating targeted genetic testing.

Main Result

Absolute Event Rate: 99% vs 48%

p-value: p=0.0004

Limitations

Small number of patients with genotype-positive LQTS, which may introduce selection bias
Cross-sectional study conducted at a single center
Reproducibility of the response of ECG parameters to mexiletine infusion was not evaluated
Chronic effect of oral mexiletine therapy on QT interval remains unknown

Abstract

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 (∆QTc) 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 ∆QTc 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.

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