Variability in pulmonary vein electrophysiology and fibrosis determines arrhythmia susceptibility and dynamics

Success rates for catheter ablation of persistent atrial fibrillation patients are currently low; however, there is a subset of patients for whom electrical isolation of the pulmonary veins alone is a successful treatment strategy. It is difficult to identify these patients because there are a multitude of factors affecting arrhythmia susceptibility and maintenance, and the individual contributions of these factors are difficult to determine clinically. We hypothesised that the combination of pulmonary vein (PV) electrophysiology and atrial body fibrosis determine driver location and effectiveness of pulmonary vein isolation (PVI). We used bilayer biatrial computer models based on patient geometries to investigate the effects of PV properties and atrial fibrosis on arrhythmia inducibility, maintenance mechanisms, and the outcome of PVI. Short PV action potential duration (APD) increased arrhythmia susceptibility, while longer PV APD was found to be protective. Arrhythmia inducibility increased with slower conduction velocity (CV) at the LA/PV junction, but not for cases with homogeneous CV changes or slower CV at the distal PV. Phase singularity (PS) density in the PV region for cases with PV fibrosis was increased. Arrhythmia dynamics depend on both PV properties and fibrosis distribution, varying from meandering rotors to PV reentry (in cases with baseline or long APD), to stable rotors at regions of high fibrosis density. Measurement of fibrosis and PV properties may indicate patient specific susceptibility to AF initiation and maintenance. PV PS density before PVI was higher for cases in which AF terminated or converted to a macroreentry; thus, high PV PS density may indicate likelihood of PVI success.Author summary: Atrial fibrillation is the most commonly encountered cardiac arrhythmia, affecting a significant portion of the population. Currently, ablation is the most effective treatment but success rates are less than optimal, being 70% one-year post-treatment. There is a large effort to find better ablation strategies to permanently cure the condition. Pulmonary vein isolation by ablation is more or less the standard of care, but many questions remain since pulmonary vein ectopy by itself does not explain all of the clinical successes or failures. We used computer simulations to investigate how electrophysiological properties of the pulmonary veins can affect rotor formation and maintenance in patients suffering from atrial fibrillation. We used complex, biophysical representations of cellular electrophysiology in highly detailed geometries constructed from patient scans. We heterogeneously varied electrophysiological and structural properties to see their effects on rotor initiation and maintenance. Our study suggests a metric for indicating the likelihood of success of pulmonary vein isolation. Thus either measuring this clinically, or running patient-specific simulations to estimate this metric may suggest whether ablation in addition to pulmonary vein isolation should be performed. Our study provides motivation for a retrospective clinical study or experimental study into this metric.