RESUMEN
OBJECTIVE: Myotonic dystrophy type 1 (DM1) is the most frequent muscular dystrophy in adults. DM1 is a multisystem disorder also affecting the heart with an increased incidence of sudden death, which has been explained with the common impairment of the conduction system often requiring pacemaker implantation; however, the occurrence of sudden death despite pacemaker implantation and the observation of major ventricular arrhythmias generated the hypothesis that ventricular arrhythmias may play a causal role as well. The aim of the study was to assess the 2-year cumulative incidence and the value of noninvasive and invasive findings as predictive factors for sudden death, resuscitated cardiac arrest, ventricular fibrillation, sustained ventricular tachycardia and severe sinus dysfunction or high-degree atrioventricular block. METHODS/DESIGN: More than 500 DM1 patients will be evaluated at baseline with a clinical interview, 12-lead ECG, 24-h ECG and echocardiogram. Conventional and nonconventional indications to electrophysiological study, pacemaker, implantable cardioverter defibrillator or loop recorder implantation have been developed. In the case of an indication to electrophysiological study, pacemaker, implantable cardioverter defibrillator or loop recorder implant at baseline or at follow-up, the patient will be referred for the procedure. At the end of 2-year follow-up, all candidate prognostic factors will be tested for their association with the endpoints. TRIAL REGISTRATION: ClinicalTrials.gov ID NCT00127582. CONCLUSION: The available evidence supports the hypothesis that both bradyarrhythmias and tachyarrhythmias may cause sudden death in DM1, but the course of cardiac disease in DM1 is still unclear. We expect that this large, prospective, multicenter study will provide evidence to improve diagnostic and therapeutic strategies in DM1.
Asunto(s)
Arritmias Cardíacas/etiología , Distrofia Miotónica/complicaciones , Proyectos de Investigación , Arritmias Cardíacas/diagnóstico , Arritmias Cardíacas/prevención & control , Bloqueo Atrioventricular/etiología , Estimulación Cardíaca Artificial , Reanimación Cardiopulmonar , Muerte Súbita Cardíaca/etiología , Desfibriladores Implantables , Progresión de la Enfermedad , Supervivencia sin Enfermedad , Ecocardiografía , Electrocardiografía , Técnicas Electrofisiológicas Cardíacas , Femenino , Paro Cardíaco/etiología , Paro Cardíaco/terapia , Humanos , Italia , Estimación de Kaplan-Meier , Masculino , Distrofia Miotónica/diagnóstico , Distrofia Miotónica/terapia , Marcapaso Artificial , Valor Predictivo de las Pruebas , Estudios Prospectivos , Medición de Riesgo , Taquicardia Ventricular/etiología , Factores de Tiempo , Fibrilación Ventricular/etiologíaRESUMEN
Ursodeoxycholic acid (UDCA) is used both as the treatment of choice in many cholestatic syndromes and as complementary therapy in many liver diseases. However, few dose-finding studies exist, and none has evaluated the efficacy and long-term safety of UDCA therapy in primary biliary cirrhosis (PBC). There is an open debate about UDCA's impact on the natural history of PBC, and no universal evidence of benefits on the major endpoint exists. This is perhaps due to a UDCA dosage deficit. Most clinical trials on PBC therapy have used conservative dosages of UDCA similar to those of chenodeoxycholic acid (CDCA) used for dissolution of gallstones. It may be necessary to re-evaluate the dosage of UDCA that provides the most effective treatment.