BackgroundCardiac arrhythmias are common causes of death in patients with myotonic dystrophy (dystrophia myotonica [DM]). Evidence shows that atrial tachyarrhythmia is an independent risk factor for sudden death; however, the relationship is unclear.Methods and ResultsControl wild‐type (Mbnl1+/+; Mbnl2+/+) and DM mutant (Mbnl1−/−; Mbnl2+/−) mice were generated by crossing double heterozygous knockout (Mbnl1+/−; Mbnl2+/−) mice. In vivo electrophysiological study and optical mapping technique were performed to investigate mechanisms of ventricular tachyarrhythmias. Transmission electron microscopy scanning was performed for myocardium ultrastructural analysis. DM mutant mice were more vulnerable to anesthesia medications and program electrical pacing: 2 of 12 mice had sudden apnea and cardiac arrest during premedication of general anesthesia; 9 of the remaining 10 had atrial tachycardia and/or atrioventricular block, but none of the wild‐type mice had spontaneous arrhythmias; and 9 of 10 mice had pacing‐induced ventricular tachyarrhythmias, but only 1 of 14 of the wild‐type mice. Optical mapping studies revealed prolonged action potential duration, slower conduction velocity, and steeper conduction velocity restitution curves in the DM mutant mice than in the wild‐type group. Spatially discordant alternans was more easily inducible in DM mutant than wild‐type mice. Transmission electron microscopy showed disarranged myofibrils with enlarged vacuole‐occupying mitochondria in the DM mutant group.ConclusionsThis DM mutant mouse model presented with clinical myofibril ultrastructural abnormality and cardiac arrhythmias, including atrial tachyarrhythmias, atrioventricular block, and ventricular tachyarrhythmias. Optical mapping studies revealed prolonged action potential duration and slow conduction velocity in the DM mice, leading to vulnerability of spatially discordant alternans and ventricular arrhythmia induction to pacing.