title: Cardiac electrophysiological substrate underlying the ECG phenotype and electrogram abnormalities in Brugada syndrome patients.
abstract: BACKGROUND
  Brugada syndrome (BrS) is a highly arrhythmogenic cardiac disorder, associated with an increased incidence of sudden death. Its arrhythmogenic substrate in the intact human heart remains ill-defined.
  
  
  RESULTS
  Using noninvasive ECG imaging, we studied 25 BrS patients to characterize the electrophysiological substrate and 6 patients with right bundle-branch block for comparison. Seven healthy subjects provided control data. Abnormal substrate was observed exclusively in the right ventricular outflow tract with the following properties (in comparison with healthy controls; P<0.005): (1) ST-segment elevation and inverted T wave of unipolar electrograms (2.21±0.67 versus 0 mV); (2) delayed right ventricular outflow tract activation (82±18 versus 37±11 ms); (3) low-amplitude (0.47±0.16 versus 3.74±1.60 mV) and fractionated electrograms, suggesting slow discontinuous conduction; (4) prolonged recovery time (381±30 versus 311±34 ms) and activation-recovery intervals (318±32 versus 241±27 ms), indicating delayed repolarization; (5) steep repolarization gradients (Δrecovery time/Δx=96±28 versus 7±6 ms/cm, Δactivation-recovery interval/Δx=105±24 versus 7±5 ms/cm) at right ventricular outflow tract borders. With increased heart rate in 6 BrS patients, reduced ST-segment elevation and increased fractionation were observed. Unlike BrS, right bundle-branch block had delayed activation in the entire right ventricle, without ST-segment elevation, fractionation, or repolarization abnormalities on electrograms.
  
  
  CONCLUSIONS
  The results indicate that both slow discontinuous conduction and steep dispersion of repolarization are present in the right ventricular outflow tract of BrS patients. ECG imaging could differentiate between BrS and right bundle-branch block.
authors: From Cardiac Bioelectricity and Arrhythmia Center (J.Z., P.C., J.S., D.C., M.F., Y.R.) and Department of Biomedical Engineering (J.Z., Y.R.), Washington University, St. Louis, MO; Bordeaux University Hospital, LIRYC Institute, Pessac, France (F.S., M. Hocini, M. Haïssaguerre); School of Medicine, University of Wisconsin, Madison (K.H.); Institute for Computational Medicine, Johns Hopkins University, Baltimore, MD (T.O.); CardioInsight Technologies, Cleveland, OH (M. Strom); School of Medicine, Washington University, St. Louis, MO (P.C., J.S., D.C., M.F., Y.R.); and School of Medicine, University of California, San Francisco (M. Scheinman).
authors: Junjie
authors: J
authors: Zhang
authors: From Cardiac Bioelectricity and Arrhythmia Center (J.Z., P.C., J.S., D.C., M.F., Y.R.) and Department of Biomedical Engineering (J.Z., Y.R.), Washington University, St. Louis, MO; Bordeaux University Hospital, LIRYC Institute, Pessac, France (F.S., M. Hocini, M. Haïssaguerre); School of Medicine, University of Wisconsin, Madison (K.H.); Institute for Computational Medicine, Johns Hopkins University, Baltimore, MD (T.O.); CardioInsight Technologies, Cleveland, OH (M. Strom); School of Medicine, Washington University, St. Louis, MO (P.C., J.S., D.C., M.F., Y.R.); and School of Medicine, University of California, San Francisco (M. Scheinman).
authors: Frédéric
authors: F
authors: Sacher
authors: From Cardiac Bioelectricity and Arrhythmia Center (J.Z., P.C., J.S., D.C., M.F., Y.R.) and Department of Biomedical Engineering (J.Z., Y.R.), Washington University, St. Louis, MO; Bordeaux University Hospital, LIRYC Institute, Pessac, France (F.S., M. Hocini, M. Haïssaguerre); School of Medicine, University of Wisconsin, Madison (K.H.); Institute for Computational Medicine, Johns Hopkins University, Baltimore, MD (T.O.); CardioInsight Technologies, Cleveland, OH (M. Strom); School of Medicine, Washington University, St. Louis, MO (P.C., J.S., D.C., M.F., Y.R.); and School of Medicine, University of California, San Francisco (M. Scheinman).
authors: Kurt
authors: K
authors: Hoffmayer
authors: From Cardiac Bioelectricity and Arrhythmia Center (J.Z., P.C., J.S., D.C., M.F., Y.R.) and Department of Biomedical Engineering (J.Z., Y.R.), Washington University, St. Louis, MO; Bordeaux University Hospital, LIRYC Institute, Pessac, France (F.S., M. Hocini, M. Haïssaguerre); School of Medicine, University of Wisconsin, Madison (K.H.); Institute for Computational Medicine, Johns Hopkins University, Baltimore, MD (T.O.); CardioInsight Technologies, Cleveland, OH (M. Strom); School of Medicine, Washington University, St. Louis, MO (P.C., J.S., D.C., M.F., Y.R.); and School of Medicine, University of California, San Francisco (M. Scheinman).
authors: Thomas
authors: T
authors: O'Hara
authors: From Cardiac Bioelectricity and Arrhythmia Center (J.Z., P.C., J.S., D.C., M.F., Y.R.) and Department of Biomedical Engineering (J.Z., Y.R.), Washington University, St. Louis, MO; Bordeaux University Hospital, LIRYC Institute, Pessac, France (F.S., M. Hocini, M. Haïssaguerre); School of Medicine, University of Wisconsin, Madison (K.H.); Institute for Computational Medicine, Johns Hopkins University, Baltimore, MD (T.O.); CardioInsight Technologies, Cleveland, OH (M. Strom); School of Medicine, Washington University, St. Louis, MO (P.C., J.S., D.C., M.F., Y.R.); and School of Medicine, University of California, San Francisco (M. Scheinman).
authors: Maria
authors: M
authors: Strom
authors: From Cardiac Bioelectricity and Arrhythmia Center (J.Z., P.C., J.S., D.C., M.F., Y.R.) and Department of Biomedical Engineering (J.Z., Y.R.), Washington University, St. Louis, MO; Bordeaux University Hospital, LIRYC Institute, Pessac, France (F.S., M. Hocini, M. Haïssaguerre); School of Medicine, University of Wisconsin, Madison (K.H.); Institute for Computational Medicine, Johns Hopkins University, Baltimore, MD (T.O.); CardioInsight Technologies, Cleveland, OH (M. Strom); School of Medicine, Washington University, St. Louis, MO (P.C., J.S., D.C., M.F., Y.R.); and School of Medicine, University of California, San Francisco (M. Scheinman).
authors: Phillip
authors: P
authors: Cuculich
authors: From Cardiac Bioelectricity and Arrhythmia Center (J.Z., P.C., J.S., D.C., M.F., Y.R.) and Department of Biomedical Engineering (J.Z., Y.R.), Washington University, St. Louis, MO; Bordeaux University Hospital, LIRYC Institute, Pessac, France (F.S., M. Hocini, M. Haïssaguerre); School of Medicine, University of Wisconsin, Madison (K.H.); Institute for Computational Medicine, Johns Hopkins University, Baltimore, MD (T.O.); CardioInsight Technologies, Cleveland, OH (M. Strom); School of Medicine, Washington University, St. Louis, MO (P.C., J.S., D.C., M.F., Y.R.); and School of Medicine, University of California, San Francisco (M. Scheinman).
authors: Jennifer
authors: J
authors: Silva
authors: From Cardiac Bioelectricity and Arrhythmia Center (J.Z., P.C., J.S., D.C., M.F., Y.R.) and Department of Biomedical Engineering (J.Z., Y.R.), Washington University, St. Louis, MO; Bordeaux University Hospital, LIRYC Institute, Pessac, France (F.S., M. Hocini, M. Haïssaguerre); School of Medicine, University of Wisconsin, Madison (K.H.); Institute for Computational Medicine, Johns Hopkins University, Baltimore, MD (T.O.); CardioInsight Technologies, Cleveland, OH (M. Strom); School of Medicine, Washington University, St. Louis, MO (P.C., J.S., D.C., M.F., Y.R.); and School of Medicine, University of California, San Francisco (M. Scheinman).
authors: Daniel
authors: D
authors: Cooper
authors: From Cardiac Bioelectricity and Arrhythmia Center (J.Z., P.C., J.S., D.C., M.F., Y.R.) and Department of Biomedical Engineering (J.Z., Y.R.), Washington University, St. Louis, MO; Bordeaux University Hospital, LIRYC Institute, Pessac, France (F.S., M. Hocini, M. Haïssaguerre); School of Medicine, University of Wisconsin, Madison (K.H.); Institute for Computational Medicine, Johns Hopkins University, Baltimore, MD (T.O.); CardioInsight Technologies, Cleveland, OH (M. Strom); School of Medicine, Washington University, St. Louis, MO (P.C., J.S., D.C., M.F., Y.R.); and School of Medicine, University of California, San Francisco (M. Scheinman).
authors: Mitchell
authors: M
authors: Faddis
authors: From Cardiac Bioelectricity and Arrhythmia Center (J.Z., P.C., J.S., D.C., M.F., Y.R.) and Department of Biomedical Engineering (J.Z., Y.R.), Washington University, St. Louis, MO; Bordeaux University Hospital, LIRYC Institute, Pessac, France (F.S., M. Hocini, M. Haïssaguerre); School of Medicine, University of Wisconsin, Madison (K.H.); Institute for Computational Medicine, Johns Hopkins University, Baltimore, MD (T.O.); CardioInsight Technologies, Cleveland, OH (M. Strom); School of Medicine, Washington University, St. Louis, MO (P.C., J.S., D.C., M.F., Y.R.); and School of Medicine, University of California, San Francisco (M. Scheinman).
authors: Mélèze
authors: M
authors: Hocini
authors: From Cardiac Bioelectricity and Arrhythmia Center (J.Z., P.C., J.S., D.C., M.F., Y.R.) and Department of Biomedical Engineering (J.Z., Y.R.), Washington University, St. Louis, MO; Bordeaux University Hospital, LIRYC Institute, Pessac, France (F.S., M. Hocini, M. Haïssaguerre); School of Medicine, University of Wisconsin, Madison (K.H.); Institute for Computational Medicine, Johns Hopkins University, Baltimore, MD (T.O.); CardioInsight Technologies, Cleveland, OH (M. Strom); School of Medicine, Washington University, St. Louis, MO (P.C., J.S., D.C., M.F., Y.R.); and School of Medicine, University of California, San Francisco (M. Scheinman).
authors: Michel
authors: M
authors: Haïssaguerre
authors: From Cardiac Bioelectricity and Arrhythmia Center (J.Z., P.C., J.S., D.C., M.F., Y.R.) and Department of Biomedical Engineering (J.Z., Y.R.), Washington University, St. Louis, MO; Bordeaux University Hospital, LIRYC Institute, Pessac, France (F.S., M. Hocini, M. Haïssaguerre); School of Medicine, University of Wisconsin, Madison (K.H.); Institute for Computational Medicine, Johns Hopkins University, Baltimore, MD (T.O.); CardioInsight Technologies, Cleveland, OH (M. Strom); School of Medicine, Washington University, St. Louis, MO (P.C., J.S., D.C., M.F., Y.R.); and School of Medicine, University of California, San Francisco (M. Scheinman).
authors: Melvin
authors: M
authors: Scheinman
authors: From Cardiac Bioelectricity and Arrhythmia Center (J.Z., P.C., J.S., D.C., M.F., Y.R.) and Department of Biomedical Engineering (J.Z., Y.R.), Washington University, St. Louis, MO; Bordeaux University Hospital, LIRYC Institute, Pessac, France (F.S., M. Hocini, M. Haïssaguerre); School of Medicine, University of Wisconsin, Madison (K.H.); Institute for Computational Medicine, Johns Hopkins University, Baltimore, MD (T.O.); CardioInsight Technologies, Cleveland, OH (M. Strom); School of Medicine, Washington University, St. Louis, MO (P.C., J.S., D.C., M.F., Y.R.); and School of Medicine, University of California, San Francisco (M. Scheinman). rudy@wustl.edu.
authors: Yoram
authors: Y
authors: Rudy
mesh_terms: D001145:Arrhythmias, Cardiac / Q000175:diagnosis* / Q000235:genetics / Q000503:physiopathology*; D053840:Brugada Syndrome / Q000175:diagnosis* / Q000235:genetics / Q000503:physiopathology*; D000075224:Cardiac Conduction System Disease; D004562:Electrocardiography / Q000379:methods*; D005260:Female; D006329:Heart Conduction System / Q000002:abnormalities* / Q000503:physiopathology; D006801:Humans; D008297:Male; D010641:Phenotype
keywords: Brugada syndrome; electrocardiography; electrophysiology