title: Time-dependent responses to provocative testing with flecainide in the diagnosis of Brugada syndrome.
abstract: BACKGROUND
  Time-dependent variability of electrocardiogram (ECG) in patients with Brugada syndrome could affect the interpretation of provocative testing.
  
  
  OBJECTIVE
  The aim of this study was to characterize ECG changes during and after flecainide infusion.
  
  
  METHODS
  We studied 59 consecutive patients. The ECG was continuously analyzed during the first 30 minutes of provocative testing, and a single ECG was recorded 60 minutes later. We analyzed CYP2D6 and CYP3A5 variants affecting flecainide metabolism and performed blinded measurements at lead II.
  
  
  RESULTS
  At baseline, ECG patterns were classified as follows: type II in 31 patients (53%), type III in 15 (25%), and normal ECG in 13 (22%). Because of induction of type I ECG, the percentage of responders progressively increased with longer recording time periods (6.8% in 10 minutes vs 11.9% in 20-30 minutes vs 18.6% in 90 minutes; P < .01). Four patients displayed a late response, which was evidenced 90 minutes after the initiation of provocative testing. QRS width differentially increased between responders and nonresponders (P < .01), with a maximum QRS width of 110 ms during the first 30 minutes being effective for identifying possible late responders (sensitivity 100%; specificity 85.6%; positive predictive value 88%; negative predictive value 100%). The incidence of CYP2D6 variants was lower in late responders than in early or delayed responders (0% vs 75% vs 100%; P = .04), while a homogeneous distribution of CYP3A5*3/*3 was observed in our population.
  
  
  CONCLUSIONS
  Response to flecainide exhibits time-dependent variability of ECG patterns and intervals. Longer periods of ECG recording increase the recognition probability of type I ECG.
authors.affiliation: Arrhythmia Unit, Cardiology Department. Electronic address: dcalvo307@secardiologia.es.
authors.forename: David
authors.initials: D
authors.lastname: Calvo
authors.affiliation: Arrhythmia Unit, Cardiology Department.
authors.forename: José M
authors.initials: JM
authors.lastname: Rubín
authors.affiliation: Arrhythmia Unit, Cardiology Department.
authors.forename: Diego
authors.initials: D
authors.lastname: Pérez
authors.affiliation: Department of Molecular Genetics, Hospital Universitario Central de Asturias, Oviedo, Spain; Red de Investigación Renal (REDINREN), Hospital Universitario Central de Asturias, Oviedo, Spain.
authors.forename: Juan
authors.initials: J
authors.lastname: Gómez
authors.affiliation: Arrhythmia Unit, Cardiology Department.
authors.forename: Juan Pablo
authors.initials: JP
authors.lastname: Flórez
authors.affiliation: Cardiology Department, Hospital Universitario Central de Asturias, Oviedo, Spain.
authors.forename: Pablo
authors.initials: P
authors.lastname: Avanzas
authors.affiliation: Cardiology Department, Hospital Universitario Central de Asturias, Oviedo, Spain.
authors.forename: José Manuel
authors.initials: JM
authors.lastname: García-Ruíz
authors.affiliation: Red de Investigación Renal (REDINREN), Hospital Universitario Central de Asturias, Oviedo, Spain.
authors.forename: Jesús María
authors.initials: JM
authors.lastname: de la Hera
authors.affiliation: Cardiology Department, Hospital Universitario Central de Asturias, Oviedo, Spain.
authors.forename: Julián
authors.initials: J
authors.lastname: Reguero
authors.affiliation: Department of Molecular Genetics, Hospital Universitario Central de Asturias, Oviedo, Spain; Red de Investigación Renal (REDINREN), Hospital Universitario Central de Asturias, Oviedo, Spain.
authors.forename: Eliecer
authors.initials: E
authors.lastname: Coto
authors.affiliation: Cardiology Department, Hospital Universitario Central de Asturias, Oviedo, Spain.
authors.forename: César
authors.initials: C
authors.lastname: Morís
mesh_terms: D000328:Adult; D000889:Anti-Arrhythmia Agents / Q000008:administration & dosage; D053840:Brugada Syndrome / Q000175:diagnosis* / Q000503:physiopathology; D004562:Electrocardiography / Q000187:drug effects*; D005260:Female; D005424:Flecainide / Q000008:administration & dosage; D005500:Follow-Up Studies; D006339:Heart Rate / Q000187:drug effects*; D006801:Humans; D007275:Injections, Intravenous; D008297:Male; D012189:Retrospective Studies
chemical_list: D000889:Anti-Arrhythmia Agents; D005424:Flecainide
keywords: Brugada syndrome; Cytochrome P450; Electrocardiogram; Flecainide; Provocative testing