Mexiletine significantly shortened the median QTc interval by 65±45 ms (from 547 ms to 470 ms; P=0.0005) in patients with potassium channel-mediated LQT2.
Observational (n=12)
Does mexiletine reduce the QTc interval in patients with potassium channel-mediated type 2 long QT syndrome?
Mexiletine significantly shortens the QTc interval in patients with potassium channel-mediated LQT2, suggesting it may provide added therapeutic efficacy to standard beta-blocker therapy.
Effect estimate: Median decrease of 65 ms
Absolute Event Rate: 470% vs 547%
p-value: p=0.0005
BACKGROUND: Long QT syndrome is a potentially lethal yet highly treatable cardiac channelopathy. Although β-blocker therapy is standard for most patients, concomitant therapy with sodium channel blockers, like mexiletine, is often utilized for patients with sodium channel-mediated type 3 long QT syndrome (LQT3). The potential role of sodium channel blockers in patients with potassium channel-mediated long QT syndrome (ie, LQT1 and LQT2) has not been investigated in detail. METHODS: We performed a retrospective chart review on 12 patients (5 females; median age at diagnosis 14.1 years (interquartile range IQR, 7.7-23; range, 0-59, median heart rate-corrected QT interval QTc at diagnosis 557 ms (IQR, 529-605) with genetically established LQT2 (10) or a combination of LQT1/LQT2 (1) or LQT2/LQT3 (1), who received mexiletine. Data were collected on symptomatic status, treatments, and breakthrough cardiac events after diagnosis and initiation of treatment. Additionally, 12-lead ECGs were collected at diagnosis, before initiation of mexiletine and following mexiletine to evaluate the drug's effect on QTc. RESULTS: Before diagnosis, 6 patients were symptomatic and, before initiation of mexiletine, 4 patients experienced ≥1 breakthrough cardiac event on β-blocker. Median age at first mexiletine dose was 24.3 years (IQR, 14-32.4). After mexiletine, the median QTc decreased by 65±45 ms from 547 ms (IQR, 488-558) premexiletine to 470 ms (IQR, 409-529) postmexiletine ( P=0.0005) for all patients. In 8 patients (67%), the QTc decreased by ≥ 40 ms with a mean decrease in QTc of 91 ms ( P < 0.008). For the 11 patients maintained on mexiletine therapy, there have been no breakthrough cardiac events during follow-up. CONCLUSIONS: Although commonly prescribed in patients with LQT3, mexiletine also shortens the QTc significantly in two-thirds of a small subset of patients with potassium channel-mediated LQT2. In patients with LQT2, pharmacological targeting of the physiological late sodium current may provide added therapeutic efficacy to β-blocker therapy.
Bos et al. (Mon,) conducted a observational in Potassium Channel-Mediated Type 2 Long QT Syndrome (n=12). Mexiletine vs. Baseline (premexiletine) was evaluated on Heart rate-corrected QT interval (QTc) (Median decrease of 65 ms, p=0.0005). Mexiletine significantly shortened the median QTc interval by 65±45 ms (from 547 ms to 470 ms; P=0.0005) in patients with potassium channel-mediated LQT2.