Spatial heterogeneity in refractoriness as a proarrhythmic substrate: theoretical evaluation by numerical simulation

Spatial heterogeneity in the refractoriness of the ventricular myocardium due to a regionally prolonged refractory period has often been observed in patients with cardiovascular disease as the substrate for functional reentrant tachyarrhythmias. The present study sought to determine how functional reentrant activity could occur due to the spatial heterogeneity, using numerical simulation. Spatial heterogeneity in the refractoriness was introduced into a two-dimensional array by the regionally prolonged refractory period expressed as a square cluster. Double stimulation, conducted from a single source, was introduced into 4 types of matrices, which differed in their level of spatial heterogeneity. A pseudoelectrocardiogram was calculated from these matrices. Spiral waves were initiated in all the matrices except for the lowest heterogeneous matrix. A vulnerable window of the coupling interval, which induced spiral waves, was observed and was wider in proportion to the level of the heterogeneity. A higher level of heterogeneity and more limited range of coupling intervals were required to sustain the spiral waves. Furthermore, in the pseudoelectrocardiogram, sustained spiral waves exhibited a waveform like that in torsades de pointes (TdP) and their transformation into ventricular fibrillation (VF). Spatial heterogeneity in refractoriness due to a regionally prolonged refractory period could be a substrate for functional reentrant tachyarrhythmias, possibly including TdP and VF.