Determination of lethal electric field threshold for pulsed field ablation in ex vivo perfused porcine and human hearts

Abstract

IntroductionPulsed field ablation is an emerging modality for catheter-based cardiac ablation. The main mechanism of action is irreversible electroporation (IRE), a threshold-based phenomenon in which cells die after exposure to intense pulsed electric fields. Lethal electric field threshold for IRE is a tissue property that determines treatment feasibility and enables the development of new devices and therapeutic applications, but it is greatly dependent on the number of pulses and their duration.MethodsIn the study, lesions were generated by applying IRE in porcine and human left ventricles using a pair of parallel needle electrodes at different voltages (500–1500 V) and two different pulse waveforms: a proprietary biphasic waveform (Medtronic) and monophasic 48 × 100 μs pulses. The lethal electric field threshold, anisotropy ratio, and conductivity increase by electroporation were determined by numerical modeling, comparing the model outputs with segmented lesion images.ResultsThe median threshold was 535 V/cm in porcine ((N = 51 lesions in n = 6 hearts) and 416 V/cm in the human donor hearts ((N = 21 lesions in n = 3 hearts) for the biphasic waveform. The median threshold value was 368 V/cm in porcine hearts ((N = 35 lesions in n = 9 hearts) cm for 48 × 100 μs pulses.DiscussionThe values obtained are compared with an extensive literature review of published lethal electric field thresholds in other tissues and were found to be lower than most other tissues, except for skeletal muscle. These findings, albeit preliminary, from a limited number of hearts suggest that treatments in humans with parameters optimized in pigs should result in equal or greater lesions.

Pulsed electric field performance calculator tool based on an in vitro human cardiac model

“…This curated set of pulse parameters can subsequently undergo validation on a limited number of animal models. Furthermore, when coupled with numerical modeling that incorporates the specific electrode geometry and anatomical target site, the user will be empowered to estimate alterations in ablation volume ( Kos et al, 2023 ), corresponding to changes in pulse parameters, utilizing EFTs obtained from this tool.…”

“…Moreover, limited data are available regarding the impact of waveform parameter selection on cardiac lesion formation, largely due to medical device developers with proprietary waveform characteristics leading the PFA development. Only a handful of nonclinical studies have published the waveform parameters used ( Stewart et al, 2019 ; van Es et al, 2019 ; Caluori et al, 2020 ; Loh et al, 2020 ), or investigated the impact of these parameters on treatment effectiveness in diverse animal models ( Zager et al, 2016 ; Heller et al, 2021 ; Yavin et al, 2021 ; García-Sánchez et al, 2022 ; Kos et al, 2023 ).…”

The Effects of Interphase and Interpulse Delays and Pulse Widths on Induced Muscle Contractions, Pain and Therapeutic Efficacy in Electroporation-Based Therapies

“…This also means that the area of ablation by irreversible electroporation will be the smallest, surrounded by reversible electroporation, and affecting/stimulating the nerves passing through the surrounding zone (Figure 10). It is important to note that the spatial distribution of the electric field depends on the biophysical properties of the cardiac tissue, including the inhomogeneity and anisotropy of electric (i.e., conductivity and dielectricity) attributes, as well as on the electrode's shape, i.e., the catheter design, and whether the pulses are delivered in a unipolar or bipolar fashion [57,58]. During a PFA treatment using specific waveforms, the electrical pulses are delivered to a treatment site using an ablation therapy delivery device composed of a pulse generator and a catheter.…”

A pilot clinical assessment of biphasic asymmetric pulsed field ablation catheter for pulmonary vein isolation

“…PFA is based on irreversible electroporation technology, which applies electric field intensity above the lethal electric field threshold for cell death to disrupt cell membranes and induce cell death. The lethal electric field threshold for cell death not only depends on tissue type but also on pulse parameters and other factors ( 7 ). Recent in vitro studies have only partially confirmed the tissue specificity of PFA.…”

“…Apart from skeletal muscle ( 8 ), myocardial cells have a lower lethal electric field threshold for cell death, especially compared to esophageal smooth muscle cells and phrenic nerve cells. Myocardial cells are more susceptible to electroporation injury, with a lower threshold for cell death than other tissues ( 7 , 9 , 10 ). This selectivity is a fundamental cellular characteristic ( 11 ).…”