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, J., Crotti, L., Rohatgi, R., Castelletti, S., Dagradi, F., Schwartz, P., et al. (2019). Mexiletine Shortens the QT Interval in Patients With Potassium Channel-Mediated Type 2 Long QT Syndrome. CIRCULATION. ARRHYTHMIA AND ELECTROPHYSIOLOGY, 12(5) [10.1161/CIRCEP.118.007280].
|Citazione:||Bos, J., Crotti, L., Rohatgi, R., Castelletti, S., Dagradi, F., Schwartz, P., et al. (2019). Mexiletine Shortens the QT Interval in Patients With Potassium Channel-Mediated Type 2 Long QT Syndrome. CIRCULATION. ARRHYTHMIA AND ELECTROPHYSIOLOGY, 12(5) [10.1161/CIRCEP.118.007280].|
|Tipo:||Articolo in rivista - Articolo scientifico|
|Carattere della pubblicazione:||Scientifica|
|Presenza di un coautore afferente ad Istituzioni straniere:||Si|
|Titolo:||Mexiletine Shortens the QT Interval in Patients With Potassium Channel-Mediated Type 2 Long QT Syndrome.|
|Autori:||Bos, J; Crotti, L; Rohatgi, R; Castelletti, S; Dagradi, F; Schwartz, P; Ackerman, M|
|Data di pubblicazione:||2019|
|Rivista:||CIRCULATION. ARRHYTHMIA AND ELECTROPHYSIOLOGY|
|Digital Object Identifier (DOI):||http://dx.doi.org/10.1161/CIRCEP.118.007280|
|Appare nelle tipologie:||01 - Articolo su rivista|