Fully automated initiation of simulated episodes of atrial arrhythmias

AIMS: To develop computational tools for automatically initiating a large number of independent episodes of atrial arrhythmias in electro-anatomical computer models of the atria and therefore facilitating the design of in silico experiments. METHODS AND RESULTS: A biophysical model of the atria was constructed from segmented medical images of the human atria of a patient with atrial fibrillation (AF). A set of 40 initial conditions were generated based on a priori knowledge about wavefront propagation and the number and location of reentries (1-6 randomly distributed over the atrial epicardium). Simulations were run from each of these initial conditions in three substrates representing different forms of AF dynamics (stable rotors; multiple unstable meandering wavelets; and wavelets broken by repolarization heterogeneities). To demonstrate the applicability of the initiation method for testing clinical of therapeutic interventions, the channel I(Kr) was blocked after 2 s of simulation and its effect on the number of functional reentries was documented. The use of pre-computed initial conditions enabled to successfully generate episodes of simulated AF in each substrate. Blockade of I(Kr) channel prolonged action potential duration, resulting in a reduction of the number of functional reentries. In the substrate with unstable spiral waves, the effect was sufficiently large to terminate AF in about two-thirds of the cases. In the two other substrates, the effect was minor. CONCLUSION: These new simulation tools may help investigate in computer models therapeutic interventions in different substrates in order to identify substrate-specific optimal therapy.