title: Risk factors and predictors of Torsade de pointes ventricular tachycardia in patients with left ventricular systolic dysfunction receiving Dofetilide.
abstract: The purpose of this study was to identify risk factors of Torsade de pointes (TdP) ventricular tachycardia in patients medicated with a class III antiarrhythmic drug (dofetilide) and left ventricular systolic dysfunction with heart failure (HF) or recent myocardial infarction (MI). The 2 Danish Investigations of Arrhythmia and Mortality on Dofetilide (DIAMOND) studies enrolled patients with HF (DIAMOND-HF) or MI (DIAMOND-MI) and left ventricular systolic dysfunction. The present analysis includes only patients treated solely with dofetilide. The incidence of TdP was 2.1% (32 of 1,511). Twenty-five of the incidences occurred in the DIAMOND-HF study and 7 cases in the DIAMOND-MI study (p = 0.0015). TdP was more frequent in women than in men (47% vs 28%, p = 0.02). Risk factors for developing TdP were female gender (odds ratio 2.2, 95% confidence interval [CI] 1.0 to 5.0), MI within 8 weeks (odds ratio 0.3, 95% CI 0.1 to 0.7), being in New York Heart Association class III or IV (odds ratio 3.2, 95% CI 1.2 to 8.6), and baseline QTc duration (odds ratio 1.14, 95% CI 1.00 to 1.30) per 10 ms. Women with chronic HF, QTc duration >400 ms. and New York Heart Association class III or IV had a risk of TdP of 10%, whereas no TdP episodes were observed in patients with QTc duration <400 ms. In conclusion, severity of HF, female gender, and QTc duration make it possible to identify patients with a high risk of early TdP when treated with dofetilide. Patients with recent MI less often had TdP compared with patients with chronic HF.
authors: Department of Cardiology and Endocrinology, University Hospital of Copenhagen, Frederiksberg Hospital, Frederiksberg, Denmark. henrysloth@dbmail.dk
authors: Henriette Sloth
authors: HS
authors: Pedersen
authors: Hanne
authors: H
authors: Elming
authors: Marie
authors: M
authors: Seibaek
authors: Hans
authors: H
authors: Burchardt
authors: Bente
authors: B
authors: Brendorp
authors: Christian
authors: C
authors: Torp-Pedersen
authors: Lars
authors: L
authors: Køber
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000889:Anti-Arrhythmia Agents / Q000627:therapeutic use*; D001281:Atrial Fibrillation / Q000150:complications; D002303:Cardiac Output, Low / Q000150:complications; D002423:Cause of Death; D004311:Double-Blind Method; D004562:Electrocardiography; D005260:Female; D005544:Forecasting; D006323:Heart Arrest / Q000209:etiology; D006801:Humans; D008297:Male; D008875:Middle Aged; D009203:Myocardial Infarction / Q000150:complications; D010627:Phenethylamines / Q000627:therapeutic use*; D010919:Placebos; D026902:Potassium Channel Blockers / Q000627:therapeutic use*; D012307:Risk Factors; D012737:Sex Factors; D013449:Sulfonamides / Q000627:therapeutic use*; D013997:Time Factors; D016171:Torsades de Pointes / Q000209:etiology*; D018487:Ventricular Dysfunction, Left / Q000188:drug therapy*
chemical_list: D000889:Anti-Arrhythmia Agents; D010627:Phenethylamines; D010919:Placebos; D026902:Potassium Channel Blockers; D013449:Sulfonamides; C063533:dofetilide