title: A New Electrocardiographic Marker of Sudden Death in Brugada Syndrome: The S-Wave in Lead I.
abstract: BACKGROUND
  Risk stratification in asymptomatic patients remains by far the most important yet unresolved clinical problem in the Brugada syndrome (BrS).
  
  
  OBJECTIVE
  This study sought to analyze the usefulness of electrocardiographic parameters as markers of sudden cardiac death (SCD) in BrS.
  
  
  METHODS
  This study analyzed data from 347 consecutive patients (78.4% male; mean age 45 ± 13.1 years) with spontaneous type 1 BrS by ECG parameters but with no history of cardiac arrest (including 91.1% asymptomatic at presentation, 5.2% with a history of atrial fibrillation [AF], and 4% with a history of arrhythmic syncope). Electrocardiographic characteristics at the first clinic visit were analyzed to predict ventricular fibrillation (VF)/SCD during follow-up.
  
  
  RESULTS
  During the follow-up (48 ± 38 months), 276 (79.5%) patients remained asymptomatic, 39 (11.2%) developed syncope, and 32 (9.2%) developed VF/SCD. Patients who developed VF/SCD had a lower prevalence of SCN5A gene mutations (p = 0.009) and a higher prevalence of positive electrophysiological study results (p < 0.0001), a family history of SCD (p = 0.03), and AF (p < 0.0001). The most powerful marker for VF/SCD was a significant S-wave (≥0.1 mV and/or ≥40 ms) in lead I. In the multivariate analysis, the duration of S-wave in lead I ≥40 ms (hazard ratio: 39.1) and AF (hazard ratio: 3.7) were independent predictors of VF/SCD during follow-up. Electroanatomic mapping in 12 patients showed an endocardial activation time significantly longer in patients with an S-wave in lead I, mostly because of a significant delay in the anterolateral right ventricular outflow tract.
  
  
  CONCLUSIONS
  The presence of a wide and/or large S-wave in lead I was a powerful predictor of life-threatening ventricular arrhythmias in patients with BrS and no history of cardiac arrest at presentation. However, the prognostic value of a significant S-wave in lead I should be confirmed by larger studies and by an independent confirmation cohort of healthy subjects.
authors.affiliation: Division of Cardiology, Policlinico Casilino, ASL Rome B, Rome, Italy. Electronic address: leonardo.calo@tin.it.
authors.forename: Leonardo
authors.initials: L
authors.lastname: Calò
authors.affiliation: Division of Cardiology, University of Torino, Department of Medical Sciences, Città della Salute e della Scienza Hospital, Torino, Italy.
authors.forename: Carla
authors.initials: C
authors.lastname: Giustetto
authors.affiliation: Division of Cardiology, Policlinico Casilino, ASL Rome B, Rome, Italy.
authors.forename: Annamaria
authors.initials: A
authors.lastname: Martino
authors.affiliation: Division of Cardiology, Policlinico Casilino, ASL Rome B, Rome, Italy.
authors.forename: Luigi
authors.initials: L
authors.lastname: Sciarra
authors.affiliation: Division of Cardiology, University of Torino, Department of Medical Sciences, Città della Salute e della Scienza Hospital, Torino, Italy.
authors.forename: Natascia
authors.initials: N
authors.lastname: Cerrato
authors.affiliation: Division of Cardiology, Policlinico Casilino, ASL Rome B, Rome, Italy.
authors.forename: Marta
authors.initials: M
authors.lastname: Marziali
authors.affiliation: Department of Clinical and Molecular Medicine, School of Medicine and Psychology, Sapienza University of Rome, Ospedale S. Andrea and IRCCS Neuromed, Pozzilli (Isernia), Italy.
authors.forename: Jessica
authors.initials: J
authors.lastname: Rauzino
authors.affiliation: Department of Cardiology, University of L'Aquila, L'Aquila, Italy.
authors.forename: Giulia
authors.initials: G
authors.lastname: Carlino
authors.affiliation: Division of Cardiology, Policlinico Casilino, ASL Rome B, Rome, Italy.
authors.forename: Ermenegildo
authors.initials: E
authors.lastname: de Ruvo
authors.affiliation: Cardiology Clinic, Ospedali Riuniti Umberto I-Lancisi-Salesi, Ancona, Italy.
authors.forename: Federico
authors.initials: F
authors.lastname: Guerra
authors.affiliation: Division of Cardiology, Policlinico Casilino, ASL Rome B, Rome, Italy.
authors.forename: Marco
authors.initials: M
authors.lastname: Rebecchi
authors.affiliation: Division of Cardiology, Policlinico Casilino, ASL Rome B, Rome, Italy.
authors.forename: Chiara
authors.initials: C
authors.lastname: Lanzillo
authors.affiliation: Division of Cardiology, University of Torino, Department of Medical Sciences, Città della Salute e della Scienza Hospital, Torino, Italy.
authors.forename: Matteo
authors.initials: M
authors.lastname: Anselmino
authors.affiliation: Division of Cardiology, Policlinic Sandro Pertini, ASL Rome B, Rome, Italy.
authors.forename: Antonio
authors.initials: A
authors.lastname: Castro
authors.affiliation: Division of Cardiology, Policlinic Sandro Pertini, ASL Rome B, Rome, Italy.
authors.forename: Federico
authors.initials: F
authors.lastname: Turreni
authors.affiliation: Department of Cardiology, University of L'Aquila, L'Aquila, Italy.
authors.forename: Maria
authors.initials: M
authors.lastname: Penco
authors.affiliation: Department of Clinical and Molecular Medicine, School of Medicine and Psychology, Sapienza University of Rome, Ospedale S. Andrea and IRCCS Neuromed, Pozzilli (Isernia), Italy.
authors.forename: Massimo
authors.initials: M
authors.lastname: Volpe
authors.affiliation: Cardiology Clinic, Ospedali Riuniti Umberto I-Lancisi-Salesi, Ancona, Italy.
authors.forename: Alessandro
authors.initials: A
authors.lastname: Capucci
authors.affiliation: Division of Cardiology, University of Torino, Department of Medical Sciences, Città della Salute e della Scienza Hospital, Torino, Italy.
authors.forename: Fiorenzo
authors.initials: F
authors.lastname: Gaita
mesh_terms: D053840:Brugada Syndrome / Q000150:complications / Q000175:diagnosis* / Q000503:physiopathology; D016757:Death, Sudden, Cardiac / Q000453:epidemiology / Q000209:etiology*; D004562:Electrocardiography; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D007558:Italy / Q000453:epidemiology; D008297:Male; D008875:Middle Aged; D015995:Prevalence; D011379:Prognosis; D011446:Prospective Studies; D018570:Risk Assessment / Q000379:methods*; D015996:Survival Rate / Q000639:trends; D013997:Time Factors
keywords: arrhythmia; electrocardiography; prognosis