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Gene-Specific Therapy With Mexiletine Reduces Arrhythmic Events in Patients With Long QT Syndrome Type 3

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. OBJECTIVES: The aim of this s...

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Autores principales: Mazzanti, Andrea, Maragna, Riccardo, Faragli, Alessandro, Monteforte, Nicola, Bloise, Raffaella, Memmi, Mirella, Novelli, Valeria, Baiardi, Paola, Bagnardi, Vincenzo, Etheridge, Susan P., Napolitano, Carlo, Priori, Silvia G.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Elsevier Biomedical 2016
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4773513/
https://www.ncbi.nlm.nih.gov/pubmed/26940925
http://dx.doi.org/10.1016/j.jacc.2015.12.033
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author Mazzanti, Andrea
Maragna, Riccardo
Faragli, Alessandro
Monteforte, Nicola
Bloise, Raffaella
Memmi, Mirella
Novelli, Valeria
Baiardi, Paola
Bagnardi, Vincenzo
Etheridge, Susan P.
Napolitano, Carlo
Priori, Silvia G.
author_facet Mazzanti, Andrea
Maragna, Riccardo
Faragli, Alessandro
Monteforte, Nicola
Bloise, Raffaella
Memmi, Mirella
Novelli, Valeria
Baiardi, Paola
Bagnardi, Vincenzo
Etheridge, Susan P.
Napolitano, Carlo
Priori, Silvia G.
author_sort Mazzanti, Andrea
collection PubMed
description 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. OBJECTIVES: 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.
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spelling pubmed-47735132016-03-14 Gene-Specific Therapy With Mexiletine Reduces Arrhythmic Events in Patients With Long QT Syndrome Type 3 Mazzanti, Andrea Maragna, Riccardo Faragli, Alessandro Monteforte, Nicola Bloise, Raffaella Memmi, Mirella Novelli, Valeria Baiardi, Paola Bagnardi, Vincenzo Etheridge, Susan P. Napolitano, Carlo Priori, Silvia G. J Am Coll Cardiol Original Investigation 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. OBJECTIVES: 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. Elsevier Biomedical 2016-03-08 /pmc/articles/PMC4773513/ /pubmed/26940925 http://dx.doi.org/10.1016/j.jacc.2015.12.033 Text en © 2016 Elsevier Inc. All rights reserved.
spellingShingle Original Investigation
Mazzanti, Andrea
Maragna, Riccardo
Faragli, Alessandro
Monteforte, Nicola
Bloise, Raffaella
Memmi, Mirella
Novelli, Valeria
Baiardi, Paola
Bagnardi, Vincenzo
Etheridge, Susan P.
Napolitano, Carlo
Priori, Silvia G.
Gene-Specific Therapy With Mexiletine Reduces Arrhythmic Events in Patients With Long QT Syndrome Type 3
title Gene-Specific Therapy With Mexiletine Reduces Arrhythmic Events in Patients With Long QT Syndrome Type 3
title_full Gene-Specific Therapy With Mexiletine Reduces Arrhythmic Events in Patients With Long QT Syndrome Type 3
title_fullStr Gene-Specific Therapy With Mexiletine Reduces Arrhythmic Events in Patients With Long QT Syndrome Type 3
title_full_unstemmed Gene-Specific Therapy With Mexiletine Reduces Arrhythmic Events in Patients With Long QT Syndrome Type 3
title_short Gene-Specific Therapy With Mexiletine Reduces Arrhythmic Events in Patients With Long QT Syndrome Type 3
title_sort gene-specific therapy with mexiletine reduces arrhythmic events in patients with long qt syndrome type 3
topic Original Investigation
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4773513/
https://www.ncbi.nlm.nih.gov/pubmed/26940925
http://dx.doi.org/10.1016/j.jacc.2015.12.033
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