CTG repeat length underlying cardiac events and sudden death in myotonic dystrophy type 1.

Aims: Myotonic dystrophy Type 1 (DM1) is caused by the expansion of CTG repeats (CTGn) in the DM1 protein kinase (DMPK) gene, while it remains unclear whether CTGn may be associated with the incidence of cardiac events or sudden death in Japan as well as Europe. The aim of this study was to investigate the association between CTGn and cardiac involvements.

Methods And Results: This cohort study included patients with DM1 who were retrospectively recruited from nine Japanese hospitals specializing in neuromuscular diseases. A total of 496 patients with DM1 who underwent a genetic test in the DMPK gene were analysed. Patients with congenital form or under 15 years old were excluded and patients were assigned into the quartiles. When we compared the incidence of cardiac events including advanced/complete atrioventricular block, pacemaker implantation, and ventricular tachycardias or mortality among four groups, patients with 1300 or longer CTGn experienced composite cardiac events [hazard ratio (HR): 3.19, 95% confidence interval (CI): 1.02-9.99, = 0.014] more frequently and had significantly higher mortality rate (HR: 6.79, 95% CI: 2.05-22.49, < 0.001) than those under 400 CTGn while the rate of sudden death was not significantly different.

Conclusion: Regarding the cardiac events and mortality in patients with DM1, patients with 1300 or longer CTGn are at especially high risk.