Increased Beat-to-Beat Variability of T-Wave Heterogeneity Measured From Standard 12-Lead Electrocardiogram Is Associated With Sudden Cardiac Death: A Case–Control Study

In myocardial infarction patients, heart rate-adjusted QT interval (QTc), an electrocardiographic indicator of sympathetic balance, is prognostic for survival. In a 28-year follow-up, the association between QTc and all-cause, cardiovascular, and ischemic heart disease mortality was studied in a population of 3,091 apparently healthy Dutch civil servants and their spouses, aged 40-65 years, who participated in a medical examination during 1953-1954. Moderate (QTc, 420-440 msec) and extensive (QTc, more than 440 msec) QTc prolongations significantly predict all-cause mortality during the first 15 years among men (adjusted respective relative risks [RRs], 1.5 and 1.7) and among women (RRs, 1.7 and 1.6). In men, cardiovascular (RRs, 1.6 and 1.8) and ischemic heart disease mortality (RRs, 1.8 and 2.1) mainly account for this association. In women, the association cannot be attributed specifically to cardiovascular and ischemic heart disease mortality. RRs for a subpopulation without any sign of heart disease at baseline are similar. The same is observed for QTc prolongation after light exercise, although in this situation most associations are not statistically significant, probably because of smaller numbers in the QTc prolongation categories. Our results suggest that QTc contributes independently to cardiovascular risk. If autonomic imbalance is an important mechanism, it might be speculated that changes in life-style (e.g., with regard to physical exercise and smoking) may have a preventive impact.

Fifty-five patients with recent myocardial infarction and 55 healthy controls, matched for age, sex, race, height, weight, education and job, had an electrocardiogram taken every two months for seven years. Twenty-eight patients and one control had a sudden cardiac death. The QTc (mean of all values recorded) was found prolonged in one control (2%), five of 27 surviving patients (18%) and in 16 of 28 patients who had sudden death (57%). The difference between surviving and sudden death patients is significant (P less than 0.01). It is interesting that the only control with a long QT was the one when died suddenly of myocardial infarction. Among patients with previous myocardial infarction a prolonged QTc constitutes a 2.16 times greater risk for sudden death. We conclude that a constant prolongation of QTc in patients with myocardial infarction may help, with other risk factors, in defining a subgroup at higher risk for sudden death.

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 interval [CI] 1.34 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.