Irreversible electroporation for catheter-based cardiac ablation: a systematic review of the preclinical experience

Sugrue, Alan; Vaidya, Vaibhav R.; Witt, Chance M.; DeSimone, Christopher V.; Yasin, Omar; Maor, Elad; Killu, Ammar M.; Kapa, Suraj; McLeod, Christopher J.; Miklavčič, Damijan; Asirvatham, Samuel J.

doi:10.1007/s10840-019-00574-3

Cited by 49 publications

(29 citation statements)

References 65 publications

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“…Cardiac muscle sensitivity has been demonstrated in several in vitro , in vivo ( Sugrue et al, 2019 ), and in pilot clinical studies ( Reddy et al, 2018 ). It represents, with tissue selectivity, the cornerstone of the potential success of PFA in clinical trials.…”

Section: Discussionmentioning

confidence: 99%

“…Pulsed field ablation (PFA) is a recent method for interventional treatment of cardiac arrhythmia. It exploits the localized application of short – nano/microseconds - high-voltage electric fields to induce irreversible electroporation, a prolonged state or pore-induced permeability that triggers non-necrotic deaths ( Davalos et al, 2005 ), in the proximal tissue ( Wittkampf et al, 2018 ; Wojtaszczyk et al, 2018 ; Sugrue et al, 2019 ) with high selectivity ( Miklavčič, 2018 ) and without strict need of contact ( Ramirez et al, 2020 ). These characteristics make the method an excellent candidate to avoid thermal collateral damages observed with radiofrequency and cryo-balloon ablation, among which phrenic/vagal nerve injury/palsy, atrio-esophageal fistula, pulmonary vein stenosis and thrombus formation ( Sugrue et al, 2018 ; Wojtaszczyk et al, 2018 ).…”

Section: Introductionmentioning

confidence: 99%

“…This peculiar sensitivity prompted researchers and physicians to perfect a selective ablation of heart muscle using pulsed irreversible electroporation. Several short-term animal studies have proven how PFA does not affect the coronary vasculature, the local innervation, and the adjacent structures (e.g., esophagus and lungs) ( Sugrue et al, 2019 ). A first in-human trial for paroxysmal atrial fibrillation ablation via pulmonary vein isolation has delivered promising results, with a 12-month Kaplan-Meier estimate of freedom from arrhythmia of 87.4 ± 5.6%, outperforming in the medium term the mentioned radiofrequency (RF) and cryo-balloon studies ( Reddy et al, 2019 ).…”

Section: Introductionmentioning

confidence: 99%

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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: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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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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“…Also, this is the first PFA study to directly measure local temperature of each individual energy delivery electrode immediately after PFA delivery, with the intent of characterizing the non‐thermal nature of PFA deliveries. Although other preclinical studies may have evaluated similar targets, the safety and efficacy of PFA depends on the unique system configuration and electrode array 31,32 …”

Section: Discussionmentioning

confidence: 99%

Safety and chronic lesion characterization of pulsed field ablation in a Porcine model

Stewart

Haines

Miklavčič

et al. 2021

Cardiovasc electrophysiol

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Background Pulsed field ablation (PFA) has been identified as an alternative to thermal‐based ablation systems for treatment of atrial fibrillation patients. The objective of this Good Laboratory Practice (GLP) study was to characterize the chronic effects and safety of overlapping lesions created by a PFA system at intracardiac locations in a porcine model. Methods A circular catheter with nine gold electrodes was used for overlapping low‐ or high‐dose PFA deliveries in the superior vena cava (SVC), right atrial appendage (RAA), and right superior pulmonary vein (RSPV) in six pigs. Electrical isolation was evaluated acutely and chronic lesions were assessed via necropsy and histopathology after 4‐week survival. Acute and chronic safety data were recorded peri‐ and post‐procedurally. Results No animal experienced ventricular arrhythmia during PFA delivery, and there was no evidence of periprocedural PFA‐related adverse events. Lesions created in all anatomies resulted in electrical isolation postprocedure. Lesions were circumferential, contiguous, and transmural, with all converting into consistent lines of chronic replacement fibrosis, regardless of trabeculated or smooth endocardial surface structure. Ablations were non‐thermally generated with only minimal post‐delivery temperature rises recorded at the electrodes. There was no evidence of extracardiac damage, stenosis, aneurysms, endocardial disruption, or thrombus. Conclusion PFA deliveries to the SVC, RAA, and RSPV resulted in complete circumferential replacement fibrosis at 4‐week postablation with an excellent chronic myocardial and collateral tissue safety profile. This GLP study evaluated the safety and efficacy of a dosage range in preparation for a clinical trial and characterized the non‐thermal nature of PFA.

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“…When the electric field increases further, the electroporation becomes irreversible and leads to cell death. This technique is also used in medicine, for example in the treatment of tumors, or more recently proposed for the ablation of atrial fibrillation [ 64 ]. In myocardial tissue, the lethal dose 50 (to kill 50% of the cell population) corresponds to a potential gradient of about 80 V/cm for a biphasic electric shock [ 65 ].…”

Section: Pathophysiology Of Defibrillationmentioning

confidence: 99%

The Defibrillation Conundrum: New Insights into the Mechanisms of Shock-Related Myocardial Injury Sustained from a Life-Saving Therapy

Clémenty

Bodin

Bisson

et al. 2021

IJMS

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Implantable cardiac defibrillators (ICDs) are recommended to prevent the risk of sudden cardiac death. However, shocks are associated with an increased mortality with a dose response effect, and a strategy of reducing electrical therapy burden improves the prognosis of implanted patients. We review the mechanisms of defibrillation and its consequences, including cell damage, metabolic remodeling, calcium metabolism anomalies, and inflammatory and pro-fibrotic remodeling. Electrical shocks do save lives, but also promote myocardial stunning, heart failure, and pro-arrhythmic effects as seen in electrical storms. Limiting unnecessary implantations and therapies and proposing new methods of defibrillation in the future are recommended.

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Irreversible electroporation for catheter-based cardiac ablation: a systematic review of the preclinical experience

Cited by 49 publications

References 65 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

Safety and chronic lesion characterization of pulsed field ablation in a Porcine model

The Defibrillation Conundrum: New Insights into the Mechanisms of Shock-Related Myocardial Injury Sustained from a Life-Saving Therapy

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