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Arrhythmias and sudden cardiac death have a circadian pattern of occurrence in humans. We hypothesized that a circadian pattern of arrhythmias is also present in transgenic mice with cardiac-specific overexpression of tumor necrosis factor alpha, which develop a dilated cardiomyopathy, arrhythmias and heart failure. To test this hypothesis, telemetry monitors were implanted and 24 hr, ambulatory ECG was recorded Â¿ 5 days later. Animals were maintained on a 12 hr light/dark cycle. The incidence of ventricular arrhythmias increased between 3 pm and 12 am, whereas atrial arrhythmias surged between 4 am and 12 pm. This circadian pattern of arrhythmias is in excellent agreement with human data (taking into account a 12-hour shift between activity periods in diurnal humans and nocturnal rodents). The molecular mechanisms underlying such circadian patterns of arrhythmias were examined using gene expression analysis and mathematical modeling.