title: Inverse Correlation between the Atrial Fibrillatory Rate and the Ventricular Repolarization Time: Observations at Baseline and after an Intravenous Infusion of a Combined Potassium and Sodium Current Blocker.
abstract: BACKGROUND
  The atrial fibrillatory rate (AFR) and the ventricular rate and repolarization (QTcF) were studied at baseline and under the influence of the combined potassium and sodium current blocker AZD7009.
  
  
  METHODS
  Ninety-two patients with atrial fibrillation (AF) were randomized to an intravenous infusion of AZD7009 or placebo. The atrial fibrillatory activity in lead V1 was extracted using spatiotemporal QRST cancellation. The exponential decay (ED) characterized the degree of atrial signal organization.
  
  
  RESULTS
  The mean (SD) AFR at baseline was 396  ±  57 (range 253-584) and 410 ± 33 (range 363-469) bpm in patients randomized to AZD7009 and placebo, respectively. The AFR decreased within the first minutes of the AZD7009 infusion and reached its minimum of 235 ± 34 bpm after 18 minutes. On placebo, the AFR was unchanged. On AZD7009, the ED decreased from 1.2 ± 0.3 to reach its lowest level at 0.7 ± 0.2 after 14 minutes. The ventricular rate did not change significantly over time. The AFR was statistically significantly related to the ventricular repolarization at baseline, the QTcF being longer at lower AFR values, and this relationship remained during and after AZD7009. In the full multivariate linear regression model, including age, sex, left ventricular ejection fraction, QRS duration, heart rate, QTcF, AF episode duration, AF history duration, and right atrial or left atrial size, only QTcF and age were statistically significantly correlated with the AFR. The correlation remained when the uncorrected QT interval was used.
  
  
  CONCLUSIONS
  The QTcF was inversely correlated with AFR, both at baseline and during administration of AZD7009. The AFR was not correlated with the ventricular rate.
authors.affiliation: AstraZeneca R&D, Mölndal, Sweden.|Sahlgrenska Academy at the Sahlgrenska University Hospital, Göteborg, Sweden.
authors.forename: Nils
authors.initials: N
authors.lastname: Edvardsson
authors.affiliation: AstraZeneca R&D, Mölndal, Sweden.
authors.forename: Maria
authors.initials: M
authors.lastname: Aunes
authors.affiliation: AstraZeneca R&D, Mölndal, Sweden.
authors.forename: Lars
authors.initials: L
authors.lastname: Frison
authors.affiliation: AstraZeneca R&D, Mölndal, Sweden.
authors.forename: Anders R
authors.initials: AR
authors.lastname: Berggren
mesh_terms: D000328:Adult; D000368:Aged; D001281:Atrial Fibrillation / Q000188:drug therapy* / Q000503:physiopathology*; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D004562:Electrocardiography; D005260:Female; D000070276:Heart Rate Determination; D006352:Heart Ventricles / Q000187:drug effects* / Q000503:physiopathology*; D006801:Humans; D007262:Infusions, Intravenous; D008297:Male; D008875:Middle Aged; D009930:Organic Chemicals / Q000008:administration & dosage / Q000627:therapeutic use*; D016896:Treatment Outcome
chemical_list: C514242:AZD 7009; D009930:Organic Chemicals
keywords: atrial fibrillation; atrial fibrillatory rate; potassium channel blockade; repolarization; sodium channel blockade