Frequency dependency of pacing determinants of an IK1-mediated rotor drift in the posterior left atrial wall toward the pulmonary veins

Maintenance of paroxysmal atrial fibrillation (AF) by fast rotors near or at the pulmonary veins (PVs) is not fully understood. We believe that heterogeneous distribution of transmembrane currents in the PVs and LA junction (PV-LAJ) play a major in the localization of rotors in the PVs. We seek for pacing protocols and measurements that could be used to predict drift direction. Experimentally observed heterogeneities in the PV-LAJ were incorporated into 2D and pseudo-3D models of Courtemanche-Ramirez-Nattel-Kneller human atrial kinetics to simulate various conditions and investigate rotor drifting mechanisms and electrophysiological pacing predictors. Simulations with various IK1 gradient conditions and various current-voltage relationships, substantiated its major role in the rotor drift. Among various action potential properties tested, only MDP gradient was found to be a pacing-rate independent predictor of rotor drift direction. Our simulations suggest that IK1 heterogeneity is dominant in conveying the drift direction through its impact on the global excitability and refractoriness gradients and more importantly it is only reflected in pacing studies in a frequency dependent manner. Our results call out for precaution when extrapolating results determined from pacing studies, commonly performed at 2 Hz.