Diurnal pattern of QTc interval: How long is prolonged?: Possible relation to circadian triggers of cardiovascular events

Objectives. This study sought to evaluate the range and variability of the QT and corrected QT (QTc) intervals over 24 h and to assess their pattern and relation to heart rate variability. Background. Recent Holter monitoring dat have revealed high degree of daily variability in the QTc interval. The pattern of this variability and its relation to heart rate variability remain poorly characterized. Methods. We developed and validated new method for continuous measurement of QT intervals from three-channel, 24-h Holter recordings. Average RR, QT, QTc and heart rate variability were measured from 5-min segments of dat from 21 healthy subjects. Results. Measurement of 6,048 segments showed mean (±SD) RR, QT and QTc intervals of 830 ± 100, 407 ± 23 and 445 ± 16 ms, respectively (mean QTc interval for men 434 ± 12 ms, 457 ± 10 ms for women, p < 0.0001). The average maximal QTc interval was 495 ± 21 ms and the average QTc range 95 ± 20 ms. The maximal QTc interval was ≥500 ms in 6 subjects and ≥490 ms in 13. The 95% upper confidence limit for the mean 24-h QTc interval was 452 ms (men 439 ms, women 461 ms). The RR, QT and QTc intervals and the high frequency component of heart rate variability were greater during sleep. Both the QTc interval and the variability between hourly minimal and maximal QTc intervals reached their circadian peak shortly after awakening, before declining to daytime levels. Conclusions. The maximal QTc interval over 24 h in normal subjects is longer than heretofore thought. Both QT and QTc intervals are longer during sleep. The QTc interval and QTc variability reach peak shortly after awakening, which may reflect increased autonomic instability during early waking hours, and the time of the peak value corresponds in time to the period of reported increased vulnerability to ventricular tachycardi and sudden cardiac death. These findings have implications regarding the definition of QT prolongation and its use in predicting arrhythmias and sudden death.