Heterogeneity of cellular repolarization in LQTS: the role of M cells

QT prolongation, whether congenital or acquired, is commonly associated wit h life-threatening torsade de pointes (TdP) arrhythmias that develop as a c onsequence of the amplification of electrical heterogeneities intrinsic to the ventricular myocardium. Electrophysiologic distinctions among the three predominant cell types that comprise the ventricular myocardium. are respo nsible for the normal dispersion of repolarization and transmural voltage g radients that inscribe the J and T waves of the ECG. Differences in the res ponse of epicardial, endocardial and M cells to pharmacologic agents and/or pathophysiological states result in amplification of these intrinsic elect rical heterogeneities, thus providing a substrate and trigger for the devel opment of reentrant arrhythmias. Transmural dispersion of repolarization se condary to disproportionate prolongation of the action potential of M cells in response to a reduction in net repolarizing current often leads to the development of a vulnerable window, long QT intervals, abnormal T waves as well as to the induction of polymorphic VT resembling torsade de pointes. T he decrease in net repolarizing current also predisposes M cells and Purkin je fibres to develop early afterdepolarization-induced triggered activity, which is responsible for the generation of extrasystoles thought to precipi tate TdP. Agents that prolong the QT interval but do not increase transmura l dispersion of repolarization are not capable of inducing TdP. Thus, the a vailable data suggest that that the principal problem with the long QT synd rome is not long QT intervals, but rather the dispersion of repolarization that often accompanies prolongation of the QT interval. (Eur Heart J Supple ments 2001; 3 (Suppl K): K2-K16) (C) 2001 The European Society of Cardiolog y.