title: Effects of almokalant, a class III antiarrhythmic agent, on supraventricular, reentrant tachycardias. Almokalant Paroxysmal Supraventricular Tachycardia Study Group.
abstract: The aim of the present study was to investigate the effects of almokalant on sustained reentrant supraventricular tachycardias. Reentrant tachycardias were induced, using transesophageal atrial stimulation, in 82 patients with atrioventricular reentrant tachycardia (n = 54) or AV nodal reentrant tachycardia (n = 28). After a baseline procedure during which the tachycardia was induced and overdrive terminated, the tachycardia was reinduced and studied during 12 minutes of infusion of either placebo or almokalant, aiming at plasma concentrations of 20, 50, 100, and 150 nmol/l. Each patient was studied at two dose levels during the same procedure. There was an increase in the RR interval during tachycardia of 6% at 100 nmol/l (p = 0.001 vs. baseline tachycardia). The QT interval during tachycardia increased by 5% (p = 0.001) at 50 nmol/l and by 10% (p = 0.001) at 100 nmol/l. Bundle branch block during tachycardia developed in 13% during almokalant infusion, aiming at 20 nmol/l, in 25% at 50 nmol/l, in 50% at 100 nmol/l, and in 33% at 150 nmol/l. Rapid baseline tachycardia, increasing almokalant dose, and an increasing number of induced tachycardias correlated with the appearance of bundle branch block. In six patients with AV nodal reentrant tachycardia, 2:1 AV block occurred, in all cases preceded by bundle branch block. The QT prolongation during sustained tachycardia was larger in patients who were noninducible at the same plasma concentration level than in the inducible patients. Almokalant caused bundle branch block and 2:1 AV block during sustained supraventricular tachycardia. These findings emphasize the importance of studying drug effects at rates in the range of clinical tachycardias that expose the conduction system to the limits of its refractoriness.
authors.affiliation: Department of Cardiology, Karolinska Hospital, Stockholm, Sweden.
authors.forename: B
authors.initials: B
authors.lastname: Darpö
authors.forename: N
authors.initials: N
authors.lastname: Edvardsson
mesh_terms: D000328:Adult; D000368:Aged; D000889:Anti-Arrhythmia Agents / Q000009:adverse effects / Q000627:therapeutic use*; D002037:Bundle-Branch Block / Q000139:chemically induced; D004558:Electric Stimulation; D004562:Electrocardiography; D004594:Electrophysiology; D005260:Female; D006801:Humans; D007262:Infusions, Intravenous; D008297:Male; D008875:Middle Aged; D011412:Propanolamines / Q000009:adverse effects / Q000494:pharmacology / Q000627:therapeutic use*; D013611:Tachycardia, Atrioventricular Nodal Reentry / Q000188:drug therapy*; D013617:Tachycardia, Supraventricular / Q000188:drug therapy*
chemical_list: D000889:Anti-Arrhythmia Agents; D011412:Propanolamines; C074334:almokalant