title: Entropy of cardiac repolarization predicts ventricular arrhythmias and mortality in patients receiving an implantable cardioverter-defibrillator for primary prevention of sudden death.
abstract: OBJECTIVE
  The need for a readily available, inexpensive, non-invasive method for improved risk stratification of heart failure (HF) patients is paramount. Prior studies have proposed that distinct fluctuation patterns underlying the variability of physiological signals have unique prognostic value. We tested this hypothesis in an extensively phenotyped cohort of HF patients using EntropyXQT, a novel non-linear measure of cardiac repolarization dynamics.
  
  
  RESULTS
  In a prospective, multicentre, observational study of 852 patients in sinus rhythm undergoing clinically indicated primary prevention implantable cardioverter-defibrillator (ICD) implantation (2003-10), exposures included demographics, history, physical examination, medications, laboratory results, serum biomarkers, ejection fraction, conventional electrocardiographic (ECG) analyses of heart rate and QT variability, and EntropyXQT. The primary outcome was first 'appropriate' ICD shock for ventricular arrhythmias. The secondary outcome was composite events (appropriate ICD shock and all-cause mortality). After exclusions, the cohort (n = 816) had a mean age of 60 ± 13 years, 28% women, 36% African Americans, 56% ischaemic cardiomyopathy, and 29 ± 16% Seattle HF risk score (SHFS) 5-year predicted mortality. Over 45 ± 24 months, there were 134 appropriate shocks and 166 deaths. After adjusting for 30 exposures, the hazard ratios (comparing the 5th to 1st quintile of EntropyXQT) for primary and secondary outcomes were 3.29 (95% CI 1.74-6.21) and 2.28 (1.53-3.41), respectively. Addition of EntropyXQTto a model comprised of the exposures or SHFS significantly increased net reclassification and the ROC curve area.
  
  
  CONCLUSIONS
  EntropyXQTmeasured during ICD implantation strongly and independently predicts appropriate shock and all-cause mortality over follow-up. EntropyXQTcomplements conventional risk predictors and has the potential for broad clinical application.
authors.affiliation: Division of Cardiology, Johns Hopkins University School of Medicine, 720 North Rutland Avenue, Ross 844, Baltimore, MD 21205, USA deep@jhmi.edu gtomasel@jhmi.edu.
authors.forename: Deeptankar
authors.initials: D
authors.lastname: DeMazumder
authors.affiliation: Division of Cardiology, Johns Hopkins University School of Medicine, 720 North Rutland Avenue, Ross 844, Baltimore, MD 21205, USA.
authors.forename: Worawan B
authors.initials: WB
authors.lastname: Limpitikul
authors.affiliation: Division of Cardiology, Johns Hopkins University School of Medicine, 720 North Rutland Avenue, Ross 844, Baltimore, MD 21205, USA.
authors.forename: Miguel
authors.initials: M
authors.lastname: Dorante
authors.affiliation: Division of Cardiology, Johns Hopkins University School of Medicine, 720 North Rutland Avenue, Ross 844, Baltimore, MD 21205, USA.
authors.forename: Swati
authors.initials: S
authors.lastname: Dey
authors.affiliation: Division of Cardiology, Johns Hopkins University School of Medicine, 720 North Rutland Avenue, Ross 844, Baltimore, MD 21205, USA.
authors.forename: Bhasha
authors.initials: B
authors.lastname: Mukhopadhyay
authors.affiliation: Department of Epidemiology and Welch Center for Prevention, Epidemiology, and Clinical Research, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD, USA.
authors.forename: Yiyi
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: Division of Cardiology, University of Virginia, Charlottesville, VA, USA.
authors.forename: J Randall
authors.initials: JR
authors.lastname: Moorman
authors.affiliation: Division of Cardiology, Johns Hopkins University School of Medicine, 720 North Rutland Avenue, Ross 844, Baltimore, MD 21205, USA.
authors.forename: Alan
authors.initials: A
authors.lastname: Cheng
authors.affiliation: Division of Cardiology, Johns Hopkins University School of Medicine, 720 North Rutland Avenue, Ross 844, Baltimore, MD 21205, USA.
authors.forename: Ronald D
authors.initials: RD
authors.lastname: Berger
authors.affiliation: Department of Epidemiology and Welch Center for Prevention, Epidemiology, and Clinical Research, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD, USA.
authors.forename: Eliseo
authors.initials: E
authors.lastname: Guallar
authors.affiliation: Division of Cardiology, Johns Hopkins University School of Medicine, 720 North Rutland Avenue, Ross 844, Baltimore, MD 21205, USA.
authors.forename: Steven R
authors.initials: SR
authors.lastname: Jones
authors.affiliation: Division of Cardiology, Johns Hopkins University School of Medicine, 720 North Rutland Avenue, Ross 844, Baltimore, MD 21205, USA deep@jhmi.edu gtomasel@jhmi.edu.
authors.forename: Gordon F
authors.initials: GF
authors.lastname: Tomaselli
mesh_terms: D000368:Aged; D001145:Arrhythmias, Cardiac / Q000175:diagnosis*; D016757:Death, Sudden, Cardiac / Q000517:prevention & control*; D017147:Defibrillators, Implantable; D004562:Electrocardiography; D019277:Entropy; D005260:Female; D006333:Heart Failure / Q000453:epidemiology; D006339:Heart Rate; D006801:Humans; D008297:Male; D008875:Middle Aged; D017202:Myocardial Ischemia / Q000453:epidemiology; D011322:Primary Prevention / Q000379:methods; D016016:Proportional Hazards Models; D011446:Prospective Studies; D018570:Risk Assessment; D012307:Risk Factors; D014481:United States
keywords: Chaos theory; Heart failure; Heart rate variability; Non-linear dynamics; QT variability; Risk prediction; Sudden cardiac death