This study aimed to determine whether increased QT interval variability is associated with an increased risk for ventricular tachycardia(VT) or ventricular fibrillation(VF), documented by interrogation of the implantable cardioverter-defibrillator (ICD), in patients enrolled in the Multicenter Automatic Defibrillator Implantation Trial (MADIT) II. Unstable repolarization has been proposed as a risk factor for re-entrant arrhythmias, but confirmatory data from clinical trials are lacking. The QT variability was assessed in 10-min, resting high-resolution electrocardiogram recordings at study entry using a semiautomated algorithm that measured beat-to-beat QT duration in 817 MADIT II patients. The incidence of VT/VF requiring device therapy was determined by ICD interrogation. Median normalized QT variability(QTVN) was 0.179 and 0.125, respectively, in patients with VT/VF versus those without VT/VF(p=0.001); QTVI(QTVN adjusted for heart rate variance) also was significantly(p < 0.05) higher in VT/VF patients than in those without VT/VF. Either QTVN or QTVI was linked with a significantly higher probability of VT/VF: two-year risk of VT/VF from Kaplan-Meier curves was 40%in highest quartile versus 21%in lower quartiles for QTVN, and 37%versus 22%for QTVI (p< 0.05 for each). In multivariate Cox regression models adjusting for clinical covariates(race, New York Heart Association functional class, time after myocardial infarction), top-quartile QTVI and QTVN were independently associated with VT/VF(hazard ratio for QTVN 2.18, 95%confidence interval1.34 to 3.55, p=0.002; hazard ratio for QTVI 1.80, 95%CI 1.09 to 2.95, p=0.021). In postinfarction patients with severe left ventricular dysfunction, increased QT variability, a marker of repolarization lability, is associated with an increased risk for VT/VF.
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