Postural Change-associated Alterations in QT/QTc Intervals on Electrocardiograms

In a new drug development, regulatory authorities recommend the “thorough QT/QTc study”, in which the use of a positive control group was recommended for evaluating assay sensitivity that allows the detection of a QT/QTc interval prolongation about 5 msec. The effects of postural change on the QT/QTc intervals were examined to determine its potential usefulness as a nonpharmacological positive control. Standard 12-lead electrocardiograms of 72 healthy male subjects (mean age: 22.6 ± 2.0 years) were recorded in the morning and evening in 6 positions (supine, 30-degree semisitting, standing, supine, 90-degree sitting, and standing). The QT-RR relationships during postural changes seemed to be similar in the morning and the evening. The QTc interval calculated by the Fridericia's or Framingham's formula shortened in the sitting (7 to 10 msec) and the standing position (11 to 14 msec) compared to that in the supine position. On the other hand, the QTc interval calculated by the Bazett's formula prolonged by nearly 4 msec in the sitting position and by nearly 9 msec in the standing position. The results suggest that the difference in QTc interval during postural change, especially from supine to sitting position, could be useful as a nonpharmacological positive control.