title: High-density substrate mapping in Brugada syndrome: combined role of conduction and repolarization heterogeneities in arrhythmogenesis.
abstract: BACKGROUND
  Two principal mechanisms are thought to be responsible for Brugada syndrome (BS): (1) right ventricular (RV) conduction delay and (2) RV subepicardial action potential shortening. This in vivo high-density mapping study evaluated the conduction and repolarization properties of the RV in BS subjects.
  
  
  RESULTS
  A noncontact mapping array was positioned in the RV of 18 BS patients and 20 controls. Using a standard S(1)-S(2) protocol, restitution curves of local activation time and activation recovery interval were constructed to determine local maximal restitution slopes. Significant regional conduction delays in the anterolateral free wall of the RV outflow tract of BS patients were identified. The mean increase in delay was 3-fold greater in this region than in control (P=0<0.001). Local activation gradient was also maximally reduced in this area: 0.33+/-0.1 (mean+/-SD) mm/ms in BS patients versus 0.51+/-0.15 mm/ms in controls (P<0.0005). The uniformity of wavefront propagation as measured by the square of the correlation coefficient, r(2), was greater in BS patients versus controls (0.94+/-0.04 versus 0.89+/-0.09 [mean+/-SD]; P<0.05). The odds ratio of BS hearts having any RV segment with maximal restitution slope >1 was 3.86 versus controls. Five episodes of provoked ventricular tachycardia arose from wave breaks originating from RV outflow tract slow-conduction zones in 5 BS patients.
  
  
  CONCLUSIONS
  Marked regional endocardial conduction delay and heterogeneities in repolarization exist in BS. Wave break in areas of maximal conduction delay appears to be critical in the initiation and maintenance of ventricular tachycardia. These data indicate that further studies of mapping BS to identify slow-conduction zones should be considered to determine their role in spontaneous ventricular arrhythmias.
authors: Heart Hospital, University College Hospital, University College London, London, UK. pier.lambiase@uclh.nhs.uk
authors: P D
authors: PD
authors: Lambiase
authors: A K
authors: AK
authors: Ahmed
authors: E J
authors: EJ
authors: Ciaccio
authors: R
authors: R
authors: Brugada
authors: E
authors: E
authors: Lizotte
authors: S
authors: S
authors: Chaubey
authors: Ron
authors: R
authors: Ben-Simon
authors: A W
authors: AW
authors: Chow
authors: M D
authors: MD
authors: Lowe
authors: W J
authors: WJ
authors: McKenna
mesh_terms: D000200:Action Potentials / Q000502:physiology; D000328:Adult; D000368:Aged; D001145:Arrhythmias, Cardiac / Q000503:physiopathology*; D053840:Brugada Syndrome / Q000235:genetics / Q000503:physiopathology*; D016022:Case-Control Studies; D004562:Electrocardiography; D022062:Electrophysiologic Techniques, Cardiac; D004699:Endocardium / Q000503:physiopathology; D005260:Female; D005820:Genetic Testing; D006329:Heart Conduction System / Q000503:physiopathology*; D006801:Humans; D008297:Male; D008875:Middle Aged; D009124:Muscle Proteins / Q000235:genetics; D009154:Mutation / Q000235:genetics; D062554:NAV1.5 Voltage-Gated Sodium Channel; D015222:Sodium Channels / Q000235:genetics; D017180:Tachycardia, Ventricular / Q000503:physiopathology
chemical_list: D009124:Muscle Proteins; D062554:NAV1.5 Voltage-Gated Sodium Channel; C568320:SCN5A protein, human; D015222:Sodium Channels