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 Mocker drug used by patients with DM1 for treatment of myotonia, even though definitive proof of its safety over longterm 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 longitudinalstudy 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.
Vio, R., Zorzi, A., Bello, L., Bozzoni, V., Botta, A., Rivezzi, F., et al. (2020). Evaluation of mexiletine effect on conduction delay and bradyarrhythmic complications in patients with myotonic dystrophy type 1 over long-term follow-up. HEART RHYTHM, 17(11), 1944-1950 [10.1016/j.hrthm.2020.05.043].
Evaluation of mexiletine effect on conduction delay and bradyarrhythmic complications in patients with myotonic dystrophy type 1 over long-term follow-up
Botta A.;
2020-01-01
Abstract
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 Mocker drug used by patients with DM1 for treatment of myotonia, even though definitive proof of its safety over longterm 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 longitudinalstudy 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.I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.
