Gender differences and risk of ventricular tachycardia or ventricular fibrillation

Background: Healthy women have longer QT intervals and more drug-induced proarrhythmia compared to men, yet those given implantable cardioverter-difibrillators (ICDs) for ischemic cardiomyopathy have fewer episodes of ventricular tachycardia/ventricular fibrillation (VT/VF) than men. The role of repolarization duration and stability in arrhythmogenesis in men and women with structural heart disease has not been explored. Objectives: The purpose of this study was to analyze repolarization differences between men and women and their relation to the risk of VT/VF. Methods: Multicenter Automatic Defibrillator Trial II study patients underwent 10-minute, resting digitized recordings at study entry. QT and heart rate were measured for each beat with a semiautomated method. QT variance was normalized for mean QT (QTVN) or for heart rate variance (QTVI). Spectral analysis of heart rate and QT time series was performed; coherence was indexed to quantify consistency of heart rate and QT power spectra. The incidence of VT/VF was determined by ICD interrogation. Results: There were 805 usable recordings (142 females); 463 received ICDs (86 females). There was no gender difference in mean or median QT, QTc, or heart rate. QTVN and QTVI were slightly (but significantly) higher, and the mean coherence was lower in women. In a Cox multivariate analysis, increased QTVN or QTVI (top quartile) was associated with a significantly higher risk for VT/VF in men (QTVN hazard ratio (HR) 2.2; confidence interval [CI] 1.4-3.4; P = .001; QTVI HR 1.9; CI 1.2-3.0; P = .006) but not in women, while reduced coherence (bottom quartile) predicted VT/VF in women (HR 3.3; CI 1.2-9.0; P = .021) but not in men. Conclusions: In post-myocardial infarcation patients with depressed ejection fraction, both women and men manifest increased temporal variability in the QT interval. In men, QT variability by itself raised arrhythmic risk. In women, however, QT variability dissociated from HR variability (low coherence) appeared to be a uniquely significant predictor of arrhythmic events.