title: Effect of flecainide on atrial and ventricular refractoriness and conduction in patients with normal left ventricle. Implications for possible antiarrhythmic and proarrhythmic mechanisms.
abstract: We studied the effects of intravenous flecainide (2 mg.kg-1) on atrial and ventricular refractoriness and conduction during sinus rhythm, induced atrial fibrillation and atrial pacing at rates of 100, 120 and 150 ppm, in 14 patients with normal left ventricle. Flecainide caused a significant increase in QRS duration during sinus rhythm (mean +/- SD: 87.2 +/- 8.4 ms vs 102.8 +/- 9.1 ms, P < 0.001), atrial fibrillation (87.8 +/- 10.0 ms vs 108.8 +/- 13.7 ms, P < 0.001) and at all paced rates. The duration of the atrial electrogram was significantly increased during sinus rhythm (54.9 +/- 13.2 ms vs 64.8 +/- 16.6 ms, P = 0.003) and at all pacing rates. The PA interval was also significantly prolonged, as was the pacing stimulus-to-atrial-electrogram interval at all pacing rates. There was increased QRS duration and atrial electrogram prolongation at higher pacing rates. Atrial refractoriness was prolonged during sinus rhythm (216.4 +/- 28.2 vs 228.6 +/- 36.1, P = 0.02), but not during atrial pacing at any rate. The QT interval, but not the JT interval or ventricular refractoriness, was significantly prolonged during sinus rhythm and at all pacing rates. Flecainide slows atrial conduction in a use dependent manner and increases atrial refractoriness during sinus rhythm but not during faster atrial pacing, thus not displaying a use-dependent effect. QRS duration is prolonged in a use-dependent manner without a commensurate increase in ventricular refractoriness. In the presence of rapidly conducted atrial fibrillation, which was not found to be slowed by flecainide, this effect may constitute a proarrhythmic mechanism even in patients with no apparent myocardial abnormality.
authors.affiliation: Department of Cardiological Sciences, St George's Hospital Medical School, London, U.K.
authors.forename: D
authors.initials: D
authors.lastname: Katritsis
authors.forename: E
authors.initials: E
authors.lastname: Rowland
authors.forename: S
authors.initials: S
authors.lastname: O'Nunain
authors.forename: C F
authors.initials: CF
authors.lastname: Shakespeare
authors.forename: J
authors.initials: J
authors.lastname: Poloniecki
authors.forename: A J
authors.initials: AJ
authors.lastname: Camm
mesh_terms: D000328:Adult; D000889:Anti-Arrhythmia Agents / Q000009:adverse effects / Q000627:therapeutic use*; D001281:Atrial Fibrillation / Q000139:chemically induced / Q000188:drug therapy; D001282:Atrial Flutter / Q000139:chemically induced / Q000188:drug therapy; D002304:Cardiac Pacing, Artificial; D004305:Dose-Response Relationship, Drug; D004562:Electrocardiography / Q000187:drug effects*; D005260:Female; D005424:Flecainide / Q000009:adverse effects / Q000627:therapeutic use*; D006325:Heart Atria / Q000187:drug effects* / Q000503:physiopathology; D006352:Heart Ventricles / Q000187:drug effects* / Q000503:physiopathology; D006801:Humans; D007262:Infusions, Intravenous; D008297:Male; D008875:Middle Aged; D012307:Risk Factors; D013617:Tachycardia, Supraventricular / Q000139:chemically induced / Q000188:drug therapy*
chemical_list: D000889:Anti-Arrhythmia Agents; D005424:Flecainide