Evaluation of mexiletine effect on conduction delay and bradyarrhythmic complications in patients with myotonic dystrophy type 1 over long-term follow-up.
Antiarrhythmic drugs
Atrioventricular block
Bundle branch block
Myotonic dystrophy
Neuromuscular disorder
Pacemaker
Sudden cardiac death
Journal
Heart rhythm
ISSN: 1556-3871
Titre abrégé: Heart Rhythm
Pays: United States
ID NLM: 101200317
Informations de publication
Date de publication:
11 2020
11 2020
Historique:
received:
10
04
2020
revised:
19
05
2020
accepted:
20
05
2020
pubmed:
12
6
2020
medline:
15
9
2021
entrez:
12
6
2020
Statut:
ppublish
Résumé
Myotonic dystrophy type 1 (DM1) is a multisystemic disorder characterized by progressive cardiac conduction impairment, arrhythmias, and sudden death. Mexiletine is a sodium channel blocker drug used by patients with DM1 for treatment of myotonia, even though definitive proof of its safety over long-term follow-up is lacking. The purpose of this study was to assess the impact of mexiletine for treatment of neurological symptoms on the composite endpoint of significant electrocardiogram modification (new onset or worsening of atrioventricular [AV] or intraventricular conduction delay) and bradyarrhythmic complications requiring pacemaker (PM) implantation (advanced AV block, symptomatic sinus pause >3 seconds). This retrospective longitudinal study included a series of consecutive patients with genetically confirmed DM1 evaluated at our neurology and cardiology clinics from January 1, 2011, to January 1, 2020, who received mexiletine 200 mg twice daily. Patients with a PM, implantable cardioverter-defibrillator, or severe conduction abnormality (PQ interval ≥230 ms, complete bundle branch block, or atrial fibrillation) at enrollment were excluded. The study comprised 18 mexiletine-treated patients and 68 mexiletine-free controls. Over median follow-up of 53 months, the endpoint was reached by 4 (22%) mexiletine-treated patients and 23 (33%) non-mexiletine-treated patients (log-rank P = .45). In 3 non-mexiletine-treated patients, bradyarrhythmic complications requiring PM implantation were observed. At univariable analysis, only the presence of mild conduction delay (first-degree AV block with PQ interval <230 ms or left anterior fascicular block) at baseline predicted the endpoint (hazard ratio 2.22; 95% confidence interval 1.04-4.76). Mexiletine 200 mg twice daily is safe in patients with DM1 and no severe conduction abnormality.
Sections du résumé
BACKGROUND
Myotonic dystrophy type 1 (DM1) is a multisystemic disorder characterized by progressive cardiac conduction impairment, arrhythmias, and sudden death. Mexiletine is a sodium channel blocker drug used by patients with DM1 for treatment of myotonia, even though definitive proof of its safety over long-term follow-up is lacking.
OBJECTIVE
The purpose of this study was to assess the impact of mexiletine for treatment of neurological symptoms on the composite endpoint of significant electrocardiogram modification (new onset or worsening of atrioventricular [AV] or intraventricular conduction delay) and bradyarrhythmic complications requiring pacemaker (PM) implantation (advanced AV block, symptomatic sinus pause >3 seconds).
METHODS
This retrospective longitudinal study included a series of consecutive patients with genetically confirmed DM1 evaluated at our neurology and cardiology clinics from January 1, 2011, to January 1, 2020, who received mexiletine 200 mg twice daily. Patients with a PM, implantable cardioverter-defibrillator, or severe conduction abnormality (PQ interval ≥230 ms, complete bundle branch block, or atrial fibrillation) at enrollment were excluded.
RESULTS
The study comprised 18 mexiletine-treated patients and 68 mexiletine-free controls. Over median follow-up of 53 months, the endpoint was reached by 4 (22%) mexiletine-treated patients and 23 (33%) non-mexiletine-treated patients (log-rank P = .45). In 3 non-mexiletine-treated patients, bradyarrhythmic complications requiring PM implantation were observed. At univariable analysis, only the presence of mild conduction delay (first-degree AV block with PQ interval <230 ms or left anterior fascicular block) at baseline predicted the endpoint (hazard ratio 2.22; 95% confidence interval 1.04-4.76).
CONCLUSION
Mexiletine 200 mg twice daily is safe in patients with DM1 and no severe conduction abnormality.
Identifiants
pubmed: 32525073
pii: S1547-5271(20)30546-4
doi: 10.1016/j.hrthm.2020.05.043
pii:
doi:
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
1944-1950Commentaires et corrections
Type : CommentIn
Type : CommentIn
Type : CommentIn
Informations de copyright
Copyright © 2020 Heart Rhythm Society. Published by Elsevier Inc. All rights reserved.