title: Electrophysiologic substrate in congenital Long QT syndrome: noninvasive mapping with electrocardiographic imaging (ECGI).
abstract: BACKGROUND
  Congenital Long QT syndrome (LQTS) is an arrhythmogenic disorder that causes syncope and sudden death. Although its genetic basis has become well-understood, the mechanisms whereby mutations translate to arrhythmia susceptibility in the in situ human heart have not been fully defined. We used noninvasive ECG imaging to map the cardiac electrophysiological substrate and examine whether LQTS patients display regional heterogeneities in repolarization, a substrate that promotes arrhythmogenesis.
  
  
  RESULTS
  Twenty-five subjects (9 LQT1, 9 LQT2, 5 LQT3, and 2 LQT5) with genotype and phenotype positive LQTS underwent ECG imaging. Seven normal subjects provided control. Epicardial maps of activation, recovery times, activation-recovery intervals, and repolarization dispersion were constructed. Activation was normal in all patients. However, recovery times and activation-recovery intervals were prolonged relative to control, indicating delayed repolarization and abnormally long action potential duration (312±30 ms versus 235±21 ms in control). Activation-recovery interval prolongation was spatially heterogeneous, with repolarization gradients much steeper than control (119±19 ms/cm versus 2.0±2.0 ms/cm). There was variability in steepness and distribution of repolarization gradients between and within LQTS types. Repolarization gradients were steeper in symptomatic patients (130±27 ms/cm in 12 symptomatic patients versus 98±19 ms/cm in 13 asymptomatic patients; P<0.05).
  
  
  CONCLUSIONS
  LQTS patients display regions with steep repolarization dispersion caused by localized action potential duration prolongation. This defines a substrate for reentrant arrhythmias, not detectable by surface ECG. Steeper dispersion in symptomatic patients suggests a possible role for ECG imaging in risk stratification.
authors.affiliation: Cardiac Bioelectricity and Arrhythmia Center, Washington University in St. Louis, Saint Louis, MO.|Department of Biomedical Engineering, Washington University in St. Louis, Saint Louis, MO.
authors.forename: Ramya
authors.initials: R
authors.lastname: Vijayakumar
authors.affiliation: Cardiac Bioelectricity and Arrhythmia Center, Washington University in St. Louis, Saint Louis, MO.|Division of Pediatric Cardiology, Washington University School of Medicine/St. Louis Children's Hospital, St. Louis, MO.
authors.forename: Jennifer N A
authors.initials: JNA
authors.lastname: Silva
authors.affiliation: Cardiovascular diseases, Mount Sinai St. Luke's Roosevelt, Icahn School of Medicine at Mount Sinai, New York, NY.
authors.forename: Kavit A
authors.initials: KA
authors.lastname: Desouza
authors.affiliation: Department of Medicine and the Department of Pharmacology, Vanderbilt University School of Medicine, Nashville, TN.
authors.forename: Robert L
authors.initials: RL
authors.lastname: Abraham
authors.affiliation: CardioInsight Technologies, Cleveland, OH.
authors.forename: Maria
authors.initials: M
authors.lastname: Strom
authors.affiliation: Bordeaux University Hospital, LIRYC institute, Pessac, France.
authors.forename: Frederic
authors.initials: F
authors.lastname: Sacher
authors.affiliation: Cardiac Bioelectricity and Arrhythmia Center, Washington University in St. Louis, Saint Louis, MO.|Division of Pediatric Cardiology, Washington University School of Medicine/St. Louis Children's Hospital, St. Louis, MO.
authors.forename: George F
authors.initials: GF
authors.lastname: Van Hare
authors.affiliation: Bordeaux University Hospital, LIRYC institute, Pessac, France.
authors.forename: Michel
authors.initials: M
authors.lastname: Haïssaguerre
authors.affiliation: Department of Medicine and the Department of Pharmacology, Vanderbilt University School of Medicine, Nashville, TN.
authors.forename: Dan M
authors.initials: DM
authors.lastname: Roden
authors.affiliation: Cardiac Bioelectricity and Arrhythmia Center, Washington University in St. Louis, Saint Louis, MO.|Department of Biomedical Engineering, Washington University in St. Louis, Saint Louis, MO.|Division of Pediatric Cardiology, Washington University School of Medicine/St. Louis Children's Hospital, St. Louis, MO.|Department of Medicine (Cardiology), Washington University School of Medicine/Barnes-Jewish Hospital, St. Louis, MO.
authors.forename: Yoram
authors.initials: Y
authors.lastname: Rudy
mesh_terms: D000293:Adolescent; D000328:Adult; D002648:Child; D015331:Cohort Studies; D004562:Electrocardiography / Q000379:methods*; D056149:Epicardial Mapping / Q000379:methods*; D005260:Female; D006801:Humans; D008133:Long QT Syndrome / Q000175:diagnosis* / Q000503:physiopathology*; D008297:Male; D008875:Middle Aged; D055815:Young Adult
keywords: ECG imaging; arrhythmia; electrophysiology; imaging, diagnostic; long-QT syndrome