Cancellation effect is present in high-frequency reversible and irreversible electroporation

Polajžer, Tamara; Dermol–Černe, Janja; Reberšek, Matej; O’Connor, Rodney; Miklavčič, Damijan

doi:10.1016/j.bioelechem.2019.107442

Cited by 48 publications

(24 citation statements)

References 72 publications

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“…Both symmetrical and asymmetrical AC pulses have been proved to ablate ventricular myocardium in an epicardial porcine model with customized applicators (van Es et al, 2019b). From this evidence, symmetrical AC bursts of sufficient duration do not suffer from "cancelation effect", where the effect of the first phase of the pulse is canceled by the second phase (Polajžer et al, 2020). Therefore, AC bursts are a suitable PFA waveform yet to be tested in endocardial settings with commercial catheters.…”

Section: Introductionmentioning

confidence: 99%

AC Pulsed Field Ablation Is Feasible and Safe in Atrial and Ventricular Settings: A Proof-of-Concept Chronic Animal Study

Caluori

Odehnalová

Jadczyk

et al. 2020

Front. Bioeng. Biotechnol.

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IntroductionPulsed field ablation (PFA) exploits the delivery of short high-voltage shocks to induce cells death via irreversible electroporation. The therapy offers a potential paradigm shift for catheter ablation of cardiac arrhythmia. We designed an AC-burst generator and therapeutic strategy, based on the existing knowledge between efficacy and safety among different pulses. We performed a proof-of-concept chronic animal trial to test the feasibility and safety of our method and technology.MethodsWe employed 6 female swine – weight 53.75 ± 4.77 kg – in this study. With fluoroscopic and electroanatomical mapping assistance, we performed ECG-gated AC-PFA in the following settings: in the left atrium with a decapolar loop catheter with electrodes connected in bipolar fashion; across the interventricular septum applying energy between the distal electrodes of two tip catheters. After procedure and 4-week follow-up, the animals were euthanized, and the hearts were inspected for tissue changes and characterized. We perform finite element method simulation of our AC-PFA scenarios to corroborate our method and better interpret our findings.ResultsWe applied square, 50% duty cycle, AC bursts of 100 μs duration, 100 kHz internal frequency, 900 V for 60 pulses in the atrium and 1500 V for 120 pulses in the septum. The inter-burst interval was determined by the native heart rhythm – 69 ± 9 bpm. Acute changes in the atrial and ventricular electrograms were immediately visible at the sites of AC-PFA – signals were elongated and reduced in amplitude (p < 0.0001) and tissue impedance dropped (p = 0.011). No adverse event (e.g., esophageal temperature rises or gas bubble streams) was observed – while twitching was avoided by addition of electrosurgical return electrodes. The implemented numerical simulations confirmed the non-thermal nature of our AC-PFA and provided specific information on the estimated treated area and need of pulse trains. The postmortem chest inspection showed no peripheral damage, but epicardial and endocardial discolorations at sites of ablation. T1-weighted scans revealed specific tissue changes in atria and ventricles, confirmed to be fibrotic scars via trichrome staining. We found isolated, transmural and continuous scars. A surviving cardiomyocyte core was visible in basal ventricular lesions.ConclusionWe proved that our method and technology of AC-PFA is feasible and safe for atrial and ventricular myocardial ablation, supporting their systematic investigation into effectiveness evaluation for the treatment of cardiac arrhythmia. Further optimization, with energy titration or longer follow-up, is required for a robust atrial and ventricular AC-PFA.

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Section: Introductionmentioning

confidence: 99%

AC Pulsed Field Ablation Is Feasible and Safe in Atrial and Ventricular Settings: A Proof-of-Concept Chronic Animal Study

Caluori

Odehnalová

Jadczyk

et al. 2020

Front. Bioeng. Biotechnol.

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“…The pulse duration and the inter-phase delay are the main factors influencing the cancellation effect, and shorter pulses and shorter interphase delay cause more pronounced cancellation. [ 5 ] H-FIRE obviates the need for paralytic agents and eliminates the inherent risk associated with general anesthesia, in doing so, optimizes the surgical procedure and makes the surgery less complicated to provide the possibility for performance in more patients. [ 6 ] The different waveforms and frequencies of IRE and H-FIRE affect the cell death and repair in distinct ways.…”

Section: Introductionmentioning

confidence: 99%

Comparison between high-frequency irreversible electroporation and irreversible electroporation ablation of small swine liver: follow-up of DCE-MRI and pathological observations

Zhang²,

Wang

et al. 2021

Chinese Medical Journal

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Background: High-frequency irreversible electroporation (H-FIRE) is a novel, next-generation nanoknife technology with the advantage of relieving irreversible electroporation (IRE)-induced muscle contractions. However, the difference between IRE and H-FIRE with distinct ablation parameters was not clearly defined. This study aimed to compare the efficacy of the two treatments in vivo . Methods: Ten Bama miniature swine were divided into two group: five in the 1-day group and five in the 7-day group. The efficacy of IRE and H-FIRE ablation was compared by volume transfer constant (Krans), rate constant (Kep) and extravascular extracellular volume fraction (Ve) value of dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI), size of the ablation zone, and histologic analysis. Each animal underwent the IRE and H-FIRE. Temperatures of the electrodes were measured during ablation. DCE-MRI images were obtained 1, 4, and 7 days after ablation in the 7-day group. All animals in the two groups were euthanized 1 day or 7 days after ablation, and subsequently, IRE and H-FIRE treated liver tissues were collected for histological examination. Student's t test or Mann-Whitney U test was applied for comparing any two groups. One-way analysis of variance (ANOVA) test and Welch's ANOVA test followed by Holm-Sidak's multiple comparisons test, one-way ANOVA with repeated measures followed by Bonferroni test, or Kruskal-Wallis H test followed by Dunn's multiple comparison test was used for multiple group comparisons and post hoc analyses. Pearson correlation coefficient test was conducted to analyze the relationship between two variables. Results: Higher Ve was seen in IRE zone than in H-FIRE zone (0.14 ± 0.02 vs. 0.08 ± 0.05, t = 2.408, P = 0.043) on day 4, but no significant difference was seen in Ktrans or Kep between IRE and H-FIRE zones at all time points (all P > 0.05). For IRE zone, the greatest Ktrans was seen on day 7, which was significantly higher than that on day 1 ( P = 0.033). The ablation zone size of H-FIRE was significantly larger than IRE 1 day (4.74 ± 0.88 cm 2 vs. 3.20 ± 0.77 cm 2 , t = 3.241, P = 0.009) and 4 days (2.22 ± 0.83 cm 2 vs. 1.30 ± 0.50 cm 2 , t = 2.343, P = 0.041) after treatment. Apoptotic index (0.05 ± 0.02 vs. 0.73 ± 0.06 vs. 0.68 ± 0.07, F = 241.300, P < 0.001) and heat shock prote...

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“…Sano et al (2017) reported that asymmetric waveforms have significantly lower IRE thresholds compared to equivalent symmetrical waveforms, at least for neuroblastoma cells in vitro [ 64 ]. Both symmetrical and asymmetrical biphasic pulses have proven effective in IRE cardiac ablation procedures in both animals and a small number of pilot human trials [ 45 , 65 , 66 , 67 , 68 ]. Overall, asymmetric waveforms appear to produce more effective pore opening than symmetric pulses, possibly due to the different amplitudes of their phases.…”

Section: Electroporation As An Ablative Approachmentioning

confidence: 99%

Ablation Modalities for Therapeutic Intervention in Arrhythmia-Related Cardiovascular Disease: Focus on Electroporation

McBride

Avazzadeh

Wheatley

et al. 2021

JCM

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Targeted cellular ablation is being increasingly used in the treatment of arrhythmias and structural heart disease. Catheter-based ablation for atrial fibrillation (AF) is considered a safe and effective approach for patients who are medication refractory. Electroporation (EPo) employs electrical energy to disrupt cell membranes which has a minimally thermal effect. The nanopores that arise from EPo can be temporary or permanent. Reversible electroporation is transitory in nature and cell viability is maintained, whereas irreversible electroporation causes permanent pore formation, leading to loss of cellular homeostasis and cell death. Several studies report that EPo displays a degree of specificity in terms of the lethal threshold required to induce cell death in different tissues. However, significantly more research is required to scope the profile of EPo thresholds for specific cell types within complex tissues. Irreversible electroporation (IRE) as an ablative approach appears to overcome the significant negative effects associated with thermal based techniques, particularly collateral damage to surrounding structures. With further fine-tuning of parameters and longer and larger clinical trials, EPo may lead the way of adapting a safer and efficient ablation modality for the treatment of persistent AF.

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Cancellation effect is present in high-frequency reversible and irreversible electroporation

Cited by 48 publications

References 72 publications

AC Pulsed Field Ablation Is Feasible and Safe in Atrial and Ventricular Settings: A Proof-of-Concept Chronic Animal Study

AC Pulsed Field Ablation Is Feasible and Safe in Atrial and Ventricular Settings: A Proof-of-Concept Chronic Animal Study

Comparison between high-frequency irreversible electroporation and irreversible electroporation ablation of small swine liver: follow-up of DCE-MRI and pathological observations

Ablation Modalities for Therapeutic Intervention in Arrhythmia-Related Cardiovascular Disease: Focus on Electroporation

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