A randomized invasive cardiac electrophysiology study of the combined ion channel blocker AZD1305 in patients after catheter ablation of atrial flutter.
BACKGROUND
This study assessed the cardiac electrophysiological and hemodynamic effects of an intravenous infusion of the combined ion channel blocker AZD1305.


METHODS
After successful ablation of atrial flutter, patients were randomized to receive placebo (n = 12) or AZD1305 (n = 38) in 4 ascending dose groups. Electrophysiological and hemodynamic measurements were performed before and commencing 20 minutes after start of infusion.


RESULTS
Left atrial effective refractory period increased dose and the primary outcome measure increased dose and plasma concentration dependently, with a mean increase of 55 milliseconds in dose group 3. There was a corresponding increase in right atrial effective refractory period of 84 milliseconds. The right ventricular effective refractory period and the paced QT interval also increased dose and concentration dependently, by 59 and 70 milliseconds, respectively, in dose group 3. There were indications of moderate increases of atrial, atrioventricular nodal, and ventricular conduction times. No consistent changes in intracardiac pressures were observed, but there was a small transient decrease in systolic blood pressure. Adverse events were consistent with the study population and procedure, and there were no signs of proarrhythmia despite marked delay in ventricular repolarization in some individuals.


CONCLUSIONS
AZD1305 shows electrophysiological characteristics indicative of potential antiarrhythmic efficacy in atrial fibrillation.
Toivonen
Lauri
L
Department of Cardiology, University Central Hospital, Helsinki, Finland.
Raatikainen
Pekka
P
Walfridsson
Håkan
H
Englund
Anders
A
Hegbom
Finn
F
Anfinsen
Ole-Gunnar
OG
Gjesdal
Knut
K
Pehrson
Steen
S
Johansson
Susanne
S
Frison
Lars
L
Berggren
Anders R
AR
Edvardsson
Nils
N
D000328:Adult; D000368:Aged; D001282:Atrial Flutter / Q000601:surgery*; D053961:Azabicyclo Compounds / Q000008:administration & dosage / Q000009:adverse effects / Q000494:pharmacology*; D002121:Calcium Channel Blockers / Q000008:administration & dosage / Q000009:adverse effects / Q000494:pharmacology*; D002219:Carbamates / Q000008:administration & dosage / Q000009:adverse effects / Q000494:pharmacology*; D017115:Catheter Ablation; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D004562:Electrocardiography; D022062:Electrophysiologic Techniques, Cardiac; D005260:Female; D006329:Heart Conduction System / Q000187:drug effects; D006439:Hemodynamics / Q000187:drug effects; D006801:Humans; D007262:Infusions, Intravenous; D008297:Male; D008875:Middle Aged; D012032:Refractory Period, Electrophysiological / Q000187:drug effects; D026941:Sodium Channel Blockers / Q000008:administration & dosage / Q000009:adverse effects / Q000494:pharmacology*
D053961:Azabicyclo Compounds; D002121:Calcium Channel Blockers; D002219:Carbamates; D026941:Sodium Channel Blockers; C550721:tert-butyl (2-(7-(2-(4-cyano-2-fluorophenoxy)ethyl)-9-oxa-3,7-diazabicyclo(3.3.1)non3-yl)ethyl)carbamate