Circadian Distribution of Ventricular Tachyarrhythmias and Association with Mortality in the MADIT‐CRT Trial

BACKGROUND: It is unknown whether circadian variation of ventricular tachyarrhythmias (VTA) affects clinical outcome in heart failure patients. METHODS: A total of 1,790 patients (males 75%) with heart failure, NYHA class I and II and implantable cardioverter defibrillators (ICD) or cardiac resynchronization (CRT-D) enrolled in the MADIT-CRT study were included. Time of first and all VTAs as detected and treated by the device with appropriate ICD therapy (antitachycardia pacing or shock) was evaluated by hours of the day and weekdays and related to all-cause mortality using Cox regression analyses. RESULTS: During a mean follow-up period of 40 months, a total of 3,300 VTA episodes were registered. Of all VTAs recorded, most of them (n = 2977, 90%) occurred in males. Recurrent as well as first VTA episodes were more common in the morning and evening with bimodal peaks from 7:00 to 10:59 (21%) and 18:00-21:59 (23%). VTAs that occurred during morning hours were associated with higher mortality when compared to VTA episodes occurring at other hours (hazard ratios [HR] = 2.07; confidence interval [CI]: 1.135-3.77; P = 0.018) with a significant gender interaction placing females at significantly higher risk of death (HR 6.78; CI 1.55-29.860; P = 0.011) than males (HR 1.79; CI 0.92-3.46; P = 0.086) (interaction P = 0.041) despite an overall lower probability for morning VTA among females (HR 0.32; CI 0.16-0.68; P = 0.003). CONCLUSIONS: The occurrence of VTAs in heart failure patients shows a circadian variation with highest incidence during morning hours that translates into a significant higher risk of all-cause mortality, with significantly higher risk among females than males.