Risk factors and predictors of Torsade de pointes ventricular tachycardia in patients with left ventricular systolic dysfunction receiving Dofetilide.
Level 3 - non-randomized controlled study
Secondary observational cohort analysis of treated participants from two randomized controlled trials
PubMed 17719337 · doi:10.1016/j.amjcard.2007.04.020
What was done
Analyzed pooled data from 1,511 patients with left ventricular systolic dysfunction treated exclusively with the class III antiarrhythmic dofetilide across two trials: DIAMOND-HF (heart failure) and DIAMOND-MI (recent myocardial infarction). Baseline clinical characteristics and electrocardiographic parameters were evaluated to determine predictors and risk factors for Torsade de pointes (TdP) ventricular tachycardia.
What was found
Torsade de pointes occurred in 2.1% of patients (32 of 1,511). TdP was significantly more frequent in the DIAMOND-HF study than DIAMOND-MI (25 cases vs 7 cases, p = 0.0015) and more frequent in women than men (47% vs 28%, p = 0.02). Significant risk factors for developing TdP included female gender (odds ratio 2.2, 95% CI 1.0 to 5.0), NYHA class III or IV heart failure (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 increase). Recent MI within 8 weeks had lower odds of TdP (odds ratio 0.3, 95% CI 0.1 to 0.7). In women with chronic HF, baseline QTc >400 ms, and NYHA class III/IV, the risk of TdP reached 10%, whereas no TdP episodes occurred in patients with a baseline QTc <400 ms.
Why it matters
This study defines key clinical predictors—female sex, severe chronic heart failure, and prolonged baseline QTc—that identify patients at high risk of drug-induced proarrhythmia before starting dofetilide.
Limits
This was a post-hoc observational analysis restricted to dofetilide-treated patients from trials. The total number of TdP events was small (32 cases), leading to imprecise estimates with wide confidence intervals. The abstract reports no data on electrolyte levels, renal function, dosing adjustments, or concomitant QT-prolonging drugs.
Cited by
- supports Tikosyn (dofetilide) carries an approximate 1-in-100 risk of inducing torsades de pointes.