Is a single lethal electric field threshold sufficient to characterize the lesion size in computational modeling of cardiac pulsed-field ablation?

Background: Pulsed-field ablation (PFA) is a novel cardiac ablation technology based on irreversible electroporation (IRE). PFA computational models rely on identification of a lethal electric field threshold to predict the IRE area. However, the predicted lesion anisotropy ratios (width over depth) vary extensively among recent studies, and these discrepancies remain a subject of discussion. Objective: This work aims to evaluate the predicted lesion anisotropy ratios using a PFA computational model by applying it to an open-chest in vivo porcine model geometry. Methods: Six domestic swine underwent epicardial PFA applications using a previously described waveform protocol. Animals were killed at least 3 hours after the last ablation, and lesions were assessed using triphenyltetrazolium chloride (TTC) staining. Numeric simulations were performed on a segmented and meshed porcine thoracic computed tomography (CT) scan, mimicking the open-chest experimental setup. Results: The maximum width of all simulated lesions was observed at the epicardial surface. The anisotropy ratios (AR) of the experimental lesions were smaller than the simulated ones (AR experimental vs simulated, 1.0-1.7 vs 2-2.7; Q1-Q3 quartiles). Increasing the peak voltage resulted in larger lesions; however, the computational model clearly underestimated the increase in lesion depth compared with the experimental data. Conclusion: Our computational model shows that a single lethal electric field threshold is insufficient to accurately predict both lesion depth and width in cardiac PFA. Our study suggests that for the given PFA waveforms, a threshold between 270 and 500 V/cm provides satisfactory lesion depth estimations, and a higher threshold between 790 and 1000 V/cm better captures the lesion width.