title: Circadian distribution of ventricular tachyarrhythmias and association with mortality in the MADIT-CRT trial.
abstract: 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.
authors.affiliation: Heart Research Follow-up Program, University of Rochester Medical Center, Rochester, New York, USA; Department of Cardiology, Gentofte Hospital, Hellerup, Denmark.
authors.forename: Martin H
authors.initials: MH
authors.lastname: Ruwald
authors.forename: Arthur J
authors.initials: AJ
authors.lastname: Moss
authors.forename: Wojciech
authors.initials: W
authors.lastname: Zareba
authors.forename: Christian
authors.initials: C
authors.lastname: Jons
authors.forename: Anne-Christine
authors.initials: AC
authors.lastname: Ruwald
authors.forename: Scott
authors.initials: S
authors.lastname: McNitt
authors.forename: Bronislava
authors.initials: B
authors.lastname: Polonsky
authors.forename: Valentina
authors.initials: V
authors.lastname: Kutyifa
mesh_terms: D058406:Cardiac Resynchronization Therapy / Q000401:mortality*; D002940:Circadian Rhythm; D017147:Defibrillators, Implantable; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D008297:Male; D009026:Mortality / Q000639:trends; D017180:Tachycardia, Ventricular / Q000175:diagnosis / Q000401:mortality* / Q000628:therapy*
keywords: MADIT-CRT; biventricular pacing; circadian rhythms; death; gender; implantable cardioverter defibrillator; ventricular arrhythmias