Where does heterogeneity exist in ventricular tachyarrhythmias?
Reentry is the most common mechanism for tachyarrhythmias including lethal ventricular tachycardia observed in patients with structural heart diseases, such as an old myocardial or dilated cardiomyopathy. In contrast, torsades de pointes (TdP) is a polymorphic ventricular tachycardia often associated with QT prolongation in patients with long QT syndrome. There is general agreement that the initiating premature ventricular beat (PVB) leading to TdP is due to early afterdepolarization–induced triggered activity; however, the subsequent polymorphic ventricular beats are due to a reentrant mechanism. It is well known that electrical heterogeneity of the action potential duration (APD) or refractoriness is required to establish reentrant arrhythmias. One of the important heterogeneous factors of ventricular repolarization for ventricular tachyarrhythmias is that located across the ventricular wall (ie, transmural heterogeneity). Numerous studies over these past 20 years have mainly highlighted the transmural heterogeneity involved in the response of diverse cell types to pharmacological agents and pathophysiological states. The 3 cell types making up the ventricular wall are epicardial, mid-myocardial (M), and endocardial cells, and they differ principally with respect to their repolarization characteristics. M cells are distinguished by the ability of their action potential to prolong more than those of epicardial and endocardial cells in response to a slowing of the rate and/or in response to drugs with APD/QT prolonging actions, such as fast activating delayed rectifier potassium current blockers or late sodium current (INa-L) enhancers. The ionic basis for these features includes the presence of a smaller slowly activating delayed rectifier potassium current, larger INa-L, 10 and larger electrogenic sodium-calcium exchange current (INa-Ca) 11 in the M region compared with those in the epicardial or endocardial cells. The significant contribution of an enhanced transmural heterogeneity has been reported in experimental models of congenital long QT syndrome employing an arterially perfused canine ventricular wedge preparation. We