Risk factors and predictors of Torsade de pointes ventricular tachycardia in patients with left ventricular systolic dysfunction receiving Dofetilide.
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.
Pedersen
Henriette Sloth
HS
Department of Cardiology and Endocrinology, University Hospital of Copenhagen, Frederiksberg Hospital, Frederiksberg, Denmark. henrysloth@dbmail.dk
Elming
Hanne
H
Seibaek
Marie
M
Burchardt
Hans
H
Brendorp
Bente
B
Torp-Pedersen
Christian
C
Køber
Lars
L
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*
D000889:Anti-Arrhythmia Agents; D010627:Phenethylamines; D010919:Placebos; D026902:Potassium Channel Blockers; D013449:Sulfonamides; C063533:dofetilide