title: Prediction of sudden cardiac death with automated high-throughput analysis of heterogeneity in standard resting 12-lead electrocardiograms.
abstract: BACKGROUND
  Heterogeneity of depolarization and repolarization underlies the development of lethal arrhythmias.
  
  
  OBJECTIVE
  We investigated whether quantification of spatial depolarization and repolarization heterogeneity identifies individuals at risk for sudden cardiac death (SCD).
  
  
  METHODS
  Spatial R-, J-, and T-wave heterogeneity (RWH, JWH, and TWH, respectively) was analyzed using automated second central moment analysis of standard digital 12-lead electrocardiograms in 5618 adults (2588, 46% men; mean ± SEM age 50.9 ± 0.2 years), who took part in the epidemiological Health 2000 Survey as representative of the entire Finnish adult population.
  
  
  RESULTS
  During the follow-up period of 7.7 ± 0.2 years, a total of 72 SCDs occurred (1.3%), with an average yearly incidence rate of 0.17% per year. Increased RWH, JWH, and TWH in left precordial leads (V4-V6) were univariately associated with SCD (P < .001 for each). When adjusted with standard clinical risk markers, JWH and TWH remained independent predictors of SCD. Increased TWH (≥102 µV) was associated with a 1.7-fold adjusted relative risk for SCD (95% confidence interval [CI] 1.0-2.9; P = .048) and increased JWH (≥123 µV) with a 2.0-fold adjusted relative risk for SCD (95% CI 1.2-3.3; P = .006). When both TWH and JWH were above the threshold, the adjusted relative risk for SCD was 2.9-fold (95% CI 1.5-5.7; P = .002). When RWH (≥470 µV), JWH, and TWH were all above the threshold, the adjusted relative risk for SCD was 3.2-fold (95% CI 1.4-7.1; P = .009).
  
  
  CONCLUSIONS
  Second central moment analysis of standard resting 12-lead electrocardiographic morphology provides an ultrarapid means for the automated measurement of spatial RWH, JWH, and TWH, enabling analysis of high subject volumes and screening for SCD risk in the general population.
authors.affiliation: Medical Research Center Oulu, University of Oulu and University Hospital of Oulu, Oulu, Finland; Beth Israel Deaconess Medical Center, Boston, Massachusetts.
authors.forename: Tuomas V
authors.initials: TV
authors.lastname: Kenttä
authors.affiliation: Beth Israel Deaconess Medical Center, Boston, Massachusetts; Harvard Medical School, Boston, Massachusetts.
authors.forename: Bruce D
authors.initials: BD
authors.lastname: Nearing
authors.affiliation: Division of Cardiology, Heart and Lung Center, Helsinki University Central Hospital, Helsinki, Finland.
authors.forename: Kimmo
authors.initials: K
authors.lastname: Porthan
authors.affiliation: Medical Research Center Oulu, University of Oulu and University Hospital of Oulu, Oulu, Finland; Emergency Department, Haartman Hospital, Helsinki, Finland.
authors.forename: Jani T
authors.initials: JT
authors.lastname: Tikkanen
authors.affiliation: Division of Cardiology, Heart and Lung Center, Helsinki University Central Hospital, Helsinki, Finland.
authors.forename: Matti
authors.initials: M
authors.lastname: Viitasalo
authors.affiliation: Division of Cardiology, Heart and Lung Center, Helsinki University Central Hospital, Helsinki, Finland.
authors.forename: Markku S
authors.initials: MS
authors.lastname: Nieminen
authors.affiliation: National Institute for Health and Welfare, Helsinki, Finland.
authors.forename: Veikko
authors.initials: V
authors.lastname: Salomaa
authors.affiliation: Division of Cardiology, Heart and Lung Center, Helsinki University Central Hospital, Helsinki, Finland.
authors.forename: Lasse
authors.initials: L
authors.lastname: Oikarinen
authors.affiliation: National Institute for Health and Welfare, Helsinki, Finland.
authors.forename: Antti
authors.initials: A
authors.lastname: Jula
authors.affiliation: Department of Medicine, University of Helsinki, Helsinki, Finland.
authors.forename: Kimmo
authors.initials: K
authors.lastname: Kontula
authors.affiliation: Cardiovascular Research Center and Center for Human Genetic Research, Massachusetts General Hospital, Boston, Massachusetts; Program in Medical and Population Genetics, Broad Institute, Cambridge, Massachusetts.
authors.forename: Chris
authors.initials: C
authors.lastname: Newton-Cheh
authors.affiliation: Medical Research Center Oulu, University of Oulu and University Hospital of Oulu, Oulu, Finland.
authors.forename: Heikki V
authors.initials: HV
authors.lastname: Huikuri
authors.affiliation: Beth Israel Deaconess Medical Center, Boston, Massachusetts; Harvard Medical School, Boston, Massachusetts. Electronic address: rverrier@bidmc.harvard.edu.
authors.forename: Richard L
authors.initials: RL
authors.lastname: Verrier
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001145:Arrhythmias, Cardiac / Q000175:diagnosis / Q000401:mortality* / Q000503:physiopathology; D016757:Death, Sudden, Cardiac / Q000453:epidemiology*; D004562:Electrocardiography; D005260:Female; D005387:Finland / Q000453:epidemiology; D006801:Humans; D008297:Male; D008875:Middle Aged; D011159:Population Surveillance; D011237:Predictive Value of Tests; D011379:Prognosis; D012146:Rest / Q000502:physiology*; D018570:Risk Assessment / Q000379:methods*; D012307:Risk Factors; D015996:Survival Rate / Q000639:trends
keywords: Depolarization; Electrocardiogram; Heterogeneity; Repolarization; Sudden cardiac death; Ventricular arrhythmias