Comprehensive characterization of waveform-dependent cardiac tissue electroporation for pulsed field ablation

Pulsed field ablation (PFA) has emerged as an alternative to thermal techniques in treating cardiac arrhythmias due to the better safety profile and similar efficacy. However, lack of deep electric field penetration has led to incomplete transmural lesions and 1-year recurrence rates of ∼30 %. Electroporation induces non-linear increases in tissue electrical conductivity, influencing the electric field distribution and subsequent ablation. Characterization of the electroporation-dependent properties across PFA waveforms would improve the accuracy of predicting the electric field distribution through tissue for different patients and catheter designs. Utilizing a neural network trained on electroporation finite element models, we characterized the first electroporation-dependent conductivity curves for the complete range of clinically relevant pulse widths (0.5-100 μs) and electric fields (100-2500 V/cm) in cardiac tissue. We then evaluated the lethal electric field thresholds of human cardiomyocytes in a tissue-mimicking hydrogel. We used both the derived conductivity curves and the lethal thresholds to simulate the non-linear electric field distribution in atrial tissue using a bipolar probe configuration and in ventricular tissue using a monopolar probe configuration, analyzing how waveforms affect ablation depth. As the pulse width increased, the bulk electrical conductivity and the electric field threshold decreased, while the electroporated conductivity remained the same. We found a strong linear correlation between the tissue and the in vitro electric field thresholds. The results provide a rationale for incorporating electroporation effects within PFA modeling, and the characterized curves provide paramount information for predicting complete transmural lesion development with different electrode and treatment designs.