title: Frequency of toxicity with chemical conversion of atrial fibrillation with dofetilide.
abstract: Dofetilide is a class III antiarrhythmic agent approved for the maintenance of sinus rhythm in patients with persistent atrial fibrillation (AF). The goal of this study was to determine if chemical cardioversion (CCV) suggests a greater sensitivity to dofetilide and, therefore, portends a higher risk of proarrhythmia. We analyzed 99 consecutive patients with persistent AF who were loaded on dofetilide before cardioversion. CCV occurred after 2 ± 1.5 doses of dofetilide in 46 patients whereas electrical cardioversion (ECV) was required in the remaining 53 patients after 4.7 ± 1.3 doses. During index hospitalization, there were higher rates of dofetilide discontinuation because of QT prolongation or torsades de pointes (TdP) in the CCV group compared with the ECV group (24% vs 2%, p = 0.001). All patients with CCV requiring drug discontinuation converted after a single dose of dofetilide. Additionally, all 3 patients with TdP were in the CCV group. Furthermore, 15 of the 21 patients with CCV (71%) who converted after the first dose of dofetilide developed significant QT prolongation, requiring dose adjustment or discontinuation of drug. Among patients discharged on drug, AF recurrence and drug discontinuation rates were similar between groups at 2-year follow-up. In patients hospitalized for initiation of dofetilide, CCV occurs in almost 50% and is associated with higher rates of pathologic QT prolongation and TdP compared with those who require ECV. Once discharged on dofetilide, safety and efficacy is similar in both groups. In conclusion, patients with CCV may require closer monitoring for proarrhythmia.
authors.affiliation: Center for Atrial Fibrillation, University of Pittsburgh Medical Center Heart and Vascular Institute, Pittsburgh, PA, USA.
authors.forename: Genevieve
authors.initials: G
authors.lastname: Brumberg
authors.forename: Nitin
authors.initials: N
authors.lastname: Gera
authors.forename: Chris
authors.initials: C
authors.lastname: Pray
authors.forename: Evan
authors.initials: E
authors.lastname: Adelstein
authors.forename: William
authors.initials: W
authors.lastname: Barrington
authors.forename: Raveen
authors.initials: R
authors.lastname: Bazaz
authors.forename: G Stuart
authors.initials: GS
authors.lastname: Mendenhall
authors.forename: Jan
authors.initials: J
authors.lastname: Nemec
authors.forename: Andrew
authors.initials: A
authors.lastname: Voigt
authors.forename: Norman C
authors.initials: NC
authors.lastname: Wang
authors.forename: David
authors.initials: D
authors.lastname: Schwartzman
authors.forename: Samir
authors.initials: S
authors.lastname: Saba
authors.forename: Sandeep K
authors.initials: SK
authors.lastname: Jain
mesh_terms: D000889:Anti-Arrhythmia Agents / Q000009:adverse effects*; D000925:Anticoagulants / Q000627:therapeutic use; D001281:Atrial Fibrillation / Q000188:drug therapy*; D016009:Chi-Square Distribution; D004554:Electric Countershock; D004562:Electrocardiography; D005260:Female; D006801:Humans; D008133:Long QT Syndrome / Q000139:chemically induced; D008297:Male; D008875:Middle Aged; D010627:Phenethylamines / Q000009:adverse effects*; D012008:Recurrence; D012189:Retrospective Studies; D013449:Sulfonamides / Q000009:adverse effects*; D016171:Torsades de Pointes / Q000139:chemically induced
chemical_list: D000889:Anti-Arrhythmia Agents; D000925:Anticoagulants; D010627:Phenethylamines; D013449:Sulfonamides; C063533:dofetilide