Computational probabilistic quantification of pro-arrhythmic risk from scar and left-to-right heterogeneity in the human ventricles

Both scar and left-to-right ventricular (LV/RV) differences in repolarization properties have been implicated as risk factors for lethal arrhythmias. As a possible mechanism for the initiation of re-entry, a recent study has indicated that LV/RV heterogeneities in the adaptation of action potential duration (APD) to changes in heart rate can cause a transient increase in APD dispersion following rate acceleration, promoting unidirectional block of conduction at the LV/RV junction. In the presence of an ischemic region and ectopic stimulation, a pathological dispersion in repolarization has been suggested to increase the risk of electrical re-entry. However, the exact location and timing of the ectopic activation play a crucial role in initiation of re-entry, and certain combinations may lead to re-entry even under normal LV/RV dispersion in repolarization. This suggests that the phenomenon needs to be investigated in a probabilistic way. In this study we employ a computationally efficient, phenomenological model to quantify the pro-arrhythmic effects associated with a range of combinations of position and timing of an ectopic activation. This allows us to probabilistically study how increasing interventricular dispersion of repolarization increases arrhythmic risk. Results indicate that a larger LV/RV dispersion more than doubles the length of the time window during which the ventricles are vulnerable to re-entry, and leads to a four-fold increase in the probability of re-entry within the vulnerable window.