The Modulated Dispersion Hypothesis Confirmed in Humans

Abstract

Conventional teaching suggests that the initiation of arrhythmias requires an initiating “trigger” and a suitable “substrate.” Moreover, the hallmark of electro-anatomic substrates for reentrant arrhythmias is spatially heterogeneous structural or electrophysiological properties. The fundamental requirement of heterogeneous refractory properties is not a new concept and was recognized by the early pioneers of cardiac electrophysiology1,2 Under these conditions, an appropriately timed triggering beat will fail to propagate into the most refractory zones, leading to unidirectional block and reentry. One common form of spatially inhomogeneous electric properties is often referred to as “dispersion of repolarization,” in which action potential duration (APD) between neighboring myocytes spanning the epicardial surface2,3 or across the transmural wall4 vary to form spatial gradients of repolarization. It is the differences in ion channel composition and density between myocytes that presumably underlie spatial dispersion of repolarization. Article see p 162 Although the “trigger” and “substrate” for arrhythmias are often considered independent phenomena, Laurita et al5–7 previously demonstrated that a premature trigger can interact with and actively modulate spatial dispersion of repolarization through a process referred to as “modulated dispersion.” According to modulated dispersion, progressive shortening of premature coupling interval will, in turn, progressively reduce dispersion of repolarization, but at very short coupling intervals dispersion of repolarization will again rise sharply. Importantly, the coupling interval–dependent modulation of repolarization gradients directly impacted vulnerability to ventricular arrhythmias, with the heart becoming relatively resistant to arrhythmia when repolarization homogenized (at intermediate …