Comparing High-Frequency With Monophasic Electroporation Protocols in an In Vivo Beating Heart Model

Heller, Eyal; García-Sánchez, Tomás; Moshkovits, Yonatan; Rabinovici, R.; Grynberg, Dvora; Segev, Amit; Asirvatham, Samuel J.; Ivorra, Antoni; Maor, Elad

doi:10.1016/j.jacep.2021.05.003

Cited by 14 publications

(32 citation statements)

References 10 publications

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“…In this study we decided to model a biphasic protocol based on recent published data on cardiac tissue of rats 57 and similar to another study in a swine model 58 . The protocol consisted of 20 bursts of biphasic pulses (150 kHz internal frequency, this means 15 biphasic pulses with no delay between pulses), with a conventional duration of 100 µs per burst at a repetition frequency of 1 Hz between consecutive bursts.…”

Section: Methodsmentioning

confidence: 99%

A computational comparison of radiofrequency and pulsed field ablation in terms of lesion morphology in the cardiac chamber

Gómez-Barea

García-Sánchez

Ivorra

2022

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Pulsed Field Ablation (PFA) has been developed over the last years as a novel electrical ablation technique for treating cardiac arrhythmias. It is based on irreversible electroporation which is a non-thermal phenomenon innocuous to the extracellular matrix and, because of that, PFA is considered to be safer than the reference technique, Radiofrequency Ablation (RFA). However, possible differences in lesion morphology between both techniques have been poorly studied. Simulations including electric, thermal and fluid physics were performed in a simplified model of the cardiac chamber which, in essence, consisted of a slab of myocardium with blood in motion on the top. Monopolar and bipolar catheter configurations were studied. Different blood velocities and catheter orientations were assayed. RFA was simulated assuming a conventional temperature-controlled approach. The PFA treatment was assumed to consist in a sequence of 20 biphasic bursts (100 µs duration). Simulations indicate that, for equivalent lesion depths, PFA lesions are wider, larger and more symmetrical than RFA lesions for both catheter configurations. RFA lesions display a great dependence on blood velocity while PFA lesions dependence is negligible on it. For the monopolar configuration, catheter angle with respect to the cardiac surface impacted both ablation techniques but in opposite sense. The orientation of the catheter with respect to blood flow direction only affected RFA lesions. In this study, substantial morphological differences between RFA and PFA lesions were predicted numerically. Negligible dependence of PFA on blood flow velocity and direction is a potential important advantage of this technique over RFA.

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Section: Methodsmentioning

confidence: 99%

A computational comparison of radiofrequency and pulsed field ablation in terms of lesion morphology in the cardiac chamber

Gómez-Barea

García-Sánchez

Ivorra

2022

Sci Rep

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“…The surface ECG was continuously monitored and acquired throughout the whole procedure. A surgical window was created by a left thoracotomy to gain access to the epicardial surface as previously described, 17,18 and the return patch electrode was fixed to the lower back of the animal in a previously shaved area. The monopolar electrode was positioned on the epicardium of the lateral wall of the left ventricle.…”

Section: What the Study Addsmentioning

confidence: 99%

Parametric Study of Pulsed Field Ablation With Biphasic Waveforms in an In Vivo Heart Model: The Role of Frequency

García-Sánchez

Amorós-Figueras

Jorge

et al. 2022

Circ: Arrhythmia and Electrophysiology

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Background: Pulsed field ablation (PFA) is a novel nonthermal cardiac ablation technology based on irreversible electroporation. Unfortunately, the characteristics of the electric field waveforms used in clinical and experimental PFA are not typically reported. This study examines the effect of the frequency of biphasic waveforms and compares biphasic to monophasic waveforms. Methods: A total of 29 Sprague-Dawley rats were treated with PFA using an epicardial monopolar electrode. Biphasic waveforms with three different frequencies, 90, 260, and 450 kHz (10 bursts of 100 µs duration at 500 V or 800 V) and monophasic waveforms (10 pulses of 100 µs duration at 500 V) were studied. Collateral neuromuscular stimulation and temperature increase in the point of application were directly measured. Lesion formation was assessed 3 weeks after treatment by histopathologic analysis. Computer simulations were used to estimate the electric field lethal threshold for each condition. A previous in vitro study was performed to draw a complete characterization of the studied dependencies. Results: Morphometric analysis demonstrated a significant association between chronic lesion size and waveform characteristics. For the same voltage level, monophasic waveforms yielded the largest lesions compared with any of the biphasic protocols ( P <0.05). Increasing PFA frequency was associated with reduced neuromuscular stimulation but also with reduced ablation efficacy. Maximum absolute temperature increase recorded along a complete treatment was 3 °C. Vascular structures inside the lesions were preserved for all conditions. Computer simulation-based analysis showed that waveform frequency had a graded effect on the lethal electric field threshold, with threshold of 600 V/cm for monophasic waveforms versus 2000 V/cm for biphasic waveforms with a frequency of 450 kHz. Conclusions: Frequency is a major determinant of efficacy in biphasic PFA. Our results highlight the critical need of disclosing waveform characteristics when reporting the results of different PFA systems.

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“…Preclinical studies aimed at quantifying the electric field threshold (EFT) for cardiac electroporation used various PEF parameters and animal models ( Xie et al, 2015 ; Xie and Zemlin, 2016 ; Semenov et al, 2018 ; Azarov et al, 2019 ; Neuber et al, 2019 ; Heller et al, 2021 ). These publications suggest that EFTs for electroporation are treatment dependent.…”

Section: Introductionmentioning

confidence: 99%

Human in vitro assay for irreversible electroporation cardiac ablation

et al. 2023

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Introduction: Pulsed electric field (PEF) cardiac ablation has been recently proposed as a technique to treat drug resistant atrial fibrillation by inducing cell death through irreversible electroporation (IRE). Improper PEF dosing can result in thermal damage or reversible electroporation. The lack of comprehensive and systematic studies to select PEF parameters for safe and effective IRE cardiac treatments hinders device development and regulatory decision-making. Human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) have been proposed as an alternative to animal models in the evaluation of cardiac electrophysiology safety.Methods: We developed a novel high-throughput in vitro assay to quantify the electric field threshold (EFT) for electroporation (acute effect) and cell death (long-term effect) in hiPSC-CMs. Monolayers of hiPSC-CMs were cultured in high-throughput format and exposed to clinically relevant biphasic PEF treatments. Electroporation and cell death areas were identified using fluorescent probes and confocal microscopy; electroporation and cell death EFTs were quantified by comparison of fluorescent images with electric field numerical simulations.Results: Study results confirmed that PEF induces electroporation and cell death in hiPSC-CMs, dependent on the number of pulses and the amplitude, duration, and repetition frequency. In addition, PEF-induced temperature increase, absorbed dose, and total treatment time for each PEF parameter combination are reported.Discussion: Upon verification of the translatability of the in vitro results presented here to in vivo models, this novel hiPSC-CM-based assay could be used as an alternative to animal or human studies and can assist in early nonclinical device development, as well as inform regulatory decision-making for cardiac ablation medical devices.

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Comparing High-Frequency With Monophasic Electroporation Protocols in an In Vivo Beating Heart Model

Cited by 14 publications

References 10 publications

A computational comparison of radiofrequency and pulsed field ablation in terms of lesion morphology in the cardiac chamber

A computational comparison of radiofrequency and pulsed field ablation in terms of lesion morphology in the cardiac chamber

Parametric Study of Pulsed Field Ablation With Biphasic Waveforms in an In Vivo Heart Model: The Role of Frequency

Human in vitro assay for irreversible electroporation cardiac ablation

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