title: Gene-Specific Therapy With Mexiletine Reduces Arrhythmic Events in Patients With Long QT Syndrome Type 3.
abstract: BACKGROUND
  Long QT syndrome type 3 (LQT3) is a lethal disease caused by gain-of-function mutations in the SCN5A gene, coding for the alpha-subunit of the sodium channel NaV1.5. Mexiletine is used to block late sodium current and to shorten QT interval in LQT3 patients.
  
  
  OBJECTIVE
  The aim of this study was to determine whether mexiletine prevents arrhythmic events (arrhythmic syncope, aborted cardiac arrest, or sudden cardiac death) in LQT3 patients.
  
  
  METHODS
  The endpoint of this retrospective cohort study, which studied consecutive LQT3 patients who were referred to our center and treated with mexiletine, was to evaluate the antiarrhythmic efficacy of mexiletine by comparing the number of arrhythmic events per patient and the annual rate of arrhythmic events during observation periods of equal duration before and after the beginning of therapy with mexiletine.
  
  
  RESULTS
  The study population comprised 34 LQT3 patients, 19 (56%) of whom were male. The median age at beginning of treatment with mexiletine was 22 years, and median QTc interval before therapy 509 ms. The median duration of oral mexiletine therapy was 36 months, at an average daily dose of 8 ± 0.5 mg/kg. Mexiletine significantly shortened QTc (by 63 ± 6 ms; p < 0.0001) and reduced the percentage of patients with arrhythmic events (from 22% to 3%; p = 0.031), the mean number of arrhythmic events per patient (from 0.43 ± 0.17 to 0.03 ± 0.03; p = 0.027), and the annual rate of arrhythmic events (from 10.3% to 0.7%; p = 0.0097).
  
  
  CONCLUSIONS
  Besides shortening QTc interval, mexiletine caused a major reduction of life-threatening arrhythmic events in LQT3 patients, thus representing an efficacious therapeutic strategy.
authors.affiliation: Molecular Cardiology, IRCCS Salvatore Maugeri Foundation, Pavia, Italy.
authors.forename: Andrea
authors.initials: A
authors.lastname: Mazzanti
authors.affiliation: Molecular Cardiology, IRCCS Salvatore Maugeri Foundation, Pavia, Italy.
authors.forename: Riccardo
authors.initials: R
authors.lastname: Maragna
authors.affiliation: Molecular Cardiology, IRCCS Salvatore Maugeri Foundation, Pavia, Italy.
authors.forename: Alessandro
authors.initials: A
authors.lastname: Faragli
authors.affiliation: Molecular Cardiology, IRCCS Salvatore Maugeri Foundation, Pavia, Italy.
authors.forename: Nicola
authors.initials: N
authors.lastname: Monteforte
authors.affiliation: Molecular Cardiology, IRCCS Salvatore Maugeri Foundation, Pavia, Italy.
authors.forename: Raffaella
authors.initials: R
authors.lastname: Bloise
authors.affiliation: Molecular Cardiology, IRCCS Salvatore Maugeri Foundation, Pavia, Italy.
authors.forename: Mirella
authors.initials: M
authors.lastname: Memmi
authors.affiliation: Molecular Cardiology, IRCCS Salvatore Maugeri Foundation, Pavia, Italy.
authors.forename: Valeria
authors.initials: V
authors.lastname: Novelli
authors.affiliation: Molecular Cardiology, IRCCS Salvatore Maugeri Foundation, Pavia, Italy.
authors.forename: Paola
authors.initials: P
authors.lastname: Baiardi
authors.affiliation: Department of Statistics and Quantitative Methods, University of Milan-Bicocca, Milan, Italy.
authors.forename: Vincenzo
authors.initials: V
authors.lastname: Bagnardi
authors.affiliation: Division of Pediatric Cardiology, Primary Children's Hospital and University of Utah, Salt Lake City, Utah.
authors.forename: Susan P
authors.initials: SP
authors.lastname: Etheridge
authors.affiliation: Molecular Cardiology, IRCCS Salvatore Maugeri Foundation, Pavia, Italy.
authors.forename: Carlo
authors.initials: C
authors.lastname: Napolitano
authors.affiliation: Molecular Cardiology, IRCCS Salvatore Maugeri Foundation, Pavia, Italy; Department of Molecular Medicine, University of Pavia, Pavia, Italy. Electronic address: silvia.priori@fsm.it.
authors.forename: Silvia G
authors.initials: SG
authors.lastname: Priori
mesh_terms: D000284:Administration, Oral; D000293:Adolescent; D000328:Adult; D002648:Child; D004562:Electrocardiography; D005260:Female; D005500:Follow-Up Studies; D015316:Genetic Therapy / Q000379:methods*; D006339:Heart Rate / Q000187:drug effects*; D006801:Humans; D008133:Long QT Syndrome / Q000235:genetics / Q000503:physiopathology / Q000628:therapy*; D008297:Male; D008801:Mexiletine / Q000008:administration & dosage*; D012189:Retrospective Studies; D016896:Treatment Outcome; D061567:Voltage-Gated Sodium Channel Blockers / Q000008:administration & dosage; D055815:Young Adult
chemical_list: D061567:Voltage-Gated Sodium Channel Blockers; D008801:Mexiletine
keywords: SCN5A; beta-blocker; mutation; sodium channel; sudden cardiac death