Cellular basis for QT dispersion

The cellular basis for the dispersion of the QT interval recorded at the body surface is incompletely understood. Contributing to QT dispersion are heterogeneities of repolarization time in the three-dimensional structure of the ventricular myocardium, which are secondary to regional differences in action potential duration (APD) and activation time. While differences in APD occur along the apicobasal and anteroposterior axes in both epicardium and endocardium of many species, transitions are usually gradual. Recent studies have also demonstrated important APD gradients along the transmural axis. Because transmural heterogeneities in repolarization time are more abrupt than those recorded along the surfaces of the heart, they may represent a more onerous substrate for the development of arrhythmias, and their quantitation may provide a valuable tool for evaluation of arrhythmia risk. Our data, derived from the arterially perfused canine left ventricular wedge preparation, suggest that transmural gradients of voltage during repolarization contribute importantly to the inscription of the T wave. The start of the T wave is caused by a more rapid decline of the plateau, or phase 2 of the epicardial action potential, creating a voltage gradient across the wall. The gradient increases as the epicardial action potential continues to repolarize, reaching a maximum with full repolarization of epicardium; this juncture marks the peak of the T wave. The next region to repolarize is endocardium, giving rise to the initial descending limb of the upright T wave. The last region to repolarize is the M region, contributing to the final segment of the T wave. Full repolarization of the M region marks the end of the T wave. The time interval between the peak and the end of the T wave therefore represents the transmural dispersion of repolarization. Conditions known to augment QTc dispersion, including acquired long QT syndrome (class IA or III antiarrhythmics) lead to augmentation of transmural dispersion of repolarization in the wedge, due to a preferential effect of the drugs to prolong the M cell action potential. Antiarrhythmic agents known to diminish QTc dispersion, such as amiodarone, also diminish transmural dispersion of repolarization in the wedge by causing a preferential prolongation of APD in epicardium and endocardium. While exaggerated transmural heterogeneity clearly can provide the substrate for reentry, a precipitating event in the form of a premature beat that penetrates the vulnerable window is usually required to initiate the reentrant arrhythmia. In long QT syndrome, the trigger is thought to be an early afterdepolarization (EAD)-induced triggered beat. The likelihood of developing EADs and triggered activity is increased when repolarizing forces are diminished, making for a slower and more gradual repolarization of phases 2 and 3 of the action potential, which translates into broad, low amplitude and sometimes bifurcated T waves in the electrocardiogram. Our findings suggest that regional differences in the duration of the M cell action potential may be the basis for QT dispersion measured at the body surface under normal and long QT conditions. The data indicate that the interval delimited by the peak and the end of the T wave represents an accurate measure of regional dispersion of repolarization across the ventricular wall and as such may be a valuable index for assessment of arrhythmic risk. The presence of low amplitude, broad and/or bifurcated T waves, particularly under conditions of long QT syndrome, is indicative of diminished repolarizing forces and may represent an independent variable of arrhythmic risk, forecasting the development of EAD-induced triggered beats that can precipitate torsade de pointes. Although the QT interval, QT dispersion, the T wave peak-to-end interval, and the width and amplitude of the T wave often change in parallel, they contain different information and should not be expected to be equivalent in their ability to forecast arrhythmic risk.