title: Vernakalant in an experimental model of pacing-induced heart failure: lack of proarrhythmia despite prolongation of repolarization.
abstract: BACKGROUND
  The present ESC guidelines on atrial fibrillation have introduced vernakalant (VER) for pharmacologic cardioversion of atrial fibrillation. The aim of the present study was to investigate possible proarrhythmic effects of vernakalant in an experimental model of heart failure (HF).
  
  
  RESULTS
  In 12 female rabbits, HF was induced with the use of 4 weeks of rapid ventricular pacing. Twelve rabbits were sham operated. Isolated hearts demonstrated a significant prolongation of myocardial repolarization after induction of HF. Vernakalant caused a concentration-dependent (10 μmol/L and 30 μmol/L) increase of action potential duration (APD90) and QT interval without affecting spatial and temporal dispersion of repolarization. The increase in APD90 was accompanied by a greater increase in refractory period resulting in a significant increase in post-repolarization refractoriness. In control conditions, programmed ventricular stimulation and burst pacing led to ventricular fibrillation (VF) in 2 of the 12 sham (4 episodes) and in 3 of the 12 HF (24 episodes) subjects. In the presence of 30 μmol/L vernakalant, VF was no longer inducible in both groups (0 episodes). In the presence of low K+ concentration, neither sham nor HF vernakalant-treated subjects developed early after-depolarizations or ventricular tachyarrhythmias.
  
  
  CONCLUSIONS
  In the present study, application of vernakalant led to a significant prolongation of myocardial repolarization and increased post-repolarization refractoriness but did not induce early after-depolarization and therefore did not cause proarrhythmia in failing hearts.
authors.affiliation: Division of Electrophysiology, Department of Cardiovascular Medicine, University of Münster, Münster, Germany. Electronic address: gerrit.frommeyer@ukmuenster.de.
authors.forename: Gerrit
authors.initials: G
authors.lastname: Frommeyer
authors.affiliation: Division of Electrophysiology, Department of Cardiovascular Medicine, University of Münster, Münster, Germany.
authors.forename: Jochen
authors.initials: J
authors.lastname: Schulze Grotthoff
authors.affiliation: Division of Electrophysiology, Department of Cardiovascular Medicine, University of Münster, Münster, Germany.
authors.forename: Christina
authors.initials: C
authors.lastname: Fischer
authors.affiliation: Märkische Kliniken, Department of Cardiology and Angiology, Klinikum Lüdenscheid, University of Witten-Herdecke, Witten-Herdecke, Germany.
authors.forename: Harilaos
authors.initials: H
authors.lastname: Bogossian
authors.affiliation: Division of Electrophysiology, Department of Cardiovascular Medicine, University of Münster, Münster, Germany.
authors.forename: Florian
authors.initials: F
authors.lastname: Reinke
authors.affiliation: Division of Electrophysiology, Department of Cardiovascular Medicine, University of Münster, Münster, Germany.
authors.forename: Simon
authors.initials: S
authors.lastname: Kochhäuser
authors.affiliation: Division of Electrophysiology, Department of Cardiovascular Medicine, University of Münster, Münster, Germany.
authors.forename: Dirk G
authors.initials: DG
authors.lastname: Dechering
authors.affiliation: Clinic of Exotic Pets, Reptiles, and Exotic and Feral Birds, University of Hanover, Hanover, Germany.
authors.forename: Michael
authors.initials: M
authors.lastname: Fehr
authors.affiliation: Division of Electrophysiology, Department of Cardiovascular Medicine, University of Münster, Münster, Germany.
authors.forename: Peter
authors.initials: P
authors.lastname: Milberg
authors.affiliation: Division of Electrophysiology, Department of Cardiovascular Medicine, University of Münster, Münster, Germany.
authors.forename: Lars
authors.initials: L
authors.lastname: Eckardt
mesh_terms: D000818:Animals; D000840:Anisoles / Q000494:pharmacology*; D000889:Anti-Arrhythmia Agents / Q000494:pharmacology; D001281:Atrial Fibrillation / Q000175:diagnosis / Q000188:drug therapy* / Q000209:etiology; D058406:Cardiac Resynchronization Therapy / Q000009:adverse effects*; D004195:Disease Models, Animal; D004562:Electrocardiography; D005260:Female; D006329:Heart Conduction System / Q000187:drug effects; D006333:Heart Failure / Q000209:etiology / Q000503:physiopathology*; D006352:Heart Ventricles / Q000473:pathology / Q000503:physiopathology; D008955:Models, Cardiovascular; D011759:Pyrrolidines / Q000494:pharmacology*; D011817:Rabbits
chemical_list: D000840:Anisoles; D000889:Anti-Arrhythmia Agents; D011759:Pyrrolidines; C524581:vernakalant
keywords: Vernakalant; dispersion of repolarization; heart failure; polymorphic ventricular tachycardia; proarrhythmia