Adaptation of ventricular repolarization dispersion during heart rate increase in humans: A roller coaster process

Regional differences in ventricular activation sequence and action potential duration and morphology result in dispersion in ventricular repolarization (VR). VR dispersion is a key factor in arrhythmogenesis. We studied the adaptation of global VR dispersion in humans during normal and abnormal ventricular activation, and the relation to the QT adaptation (hysteresis).

We measured global VR dispersion as T amplitude, T area, and ventricular gradient (VG), using continuous Frank vectorcardiography, in response to abrupt and sustained atrial (AP) or ventricular pacing (VP) aiming at 120 bpm, in 21 subjects with permanent pacemakers.

Following pacing start, VR adaptation showed an initially rapid and complex tri-phasic pattern, most pronounced for T amplitude. There were major differences in the patterns of VR dispersion adaptation following abrupt AP vs VP, confirming that the adaptation pattern is activation dependent. In response to AP, an instantaneous decrease in VR dispersion occurred, followed by an increase and then a slow decrease, all at a lower level than baseline. In contrast, following VP there was an immediate increase to ~4× baseline in T amplitude and T area (but not in VG), with a subsequent biphasic adaptation lasting longer during VP than AP. The initial rapid changes occurred within the time for QT adaptation to reach steady-state.

Our results corroborate and expand data from animal and invasive human studies, showing similarities of the adaptation pattern on different scales. The initial rapidly changing VR adaptation phase presumably reflects a window of increased vulnerability to arrhythmias.