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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...
Autores principales: | , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Elsevier Biomedical
2016
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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. |
format | Online Article Text |
id | pubmed-4773513 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2016 |
publisher | Elsevier Biomedical |
record_format | MEDLINE/PubMed |
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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