Electroporation and its Relevance for Cardiac Catheter Ablation

Irreversible electroporation can be used as a nonthermal energy source to ablate tissue. Cardiac catheter ablation by irreversible electroporation may be a safe and effective alternative for thermal ablation techniques such as radiofrequency or cryoablation. Total applied current, not delivered power (watts), energy (joules), or voltage, is the parameter that most directly relates to the local voltage gradient that causes electroporation. Electroporation can be achieved with various modalities: direct current, alternating current, pulsed direct current, or any combination of these. Experimental cardiac and noncardiac studies have demonstrated tissue specificity with survival of arteries and nerves in large lesions. In addition, porcine data suggest that application inside a pulmonary vein does not lead to pulmonary vein stenosis and that the esophagus is remarkably insensitive to electroporation. Therefore, irreversible electroporation is a very promising technique for cardiac catheter ablation and especially for electrical pulmonary vein isolation

In-vitro analysis of the origin and characteristics of gaseous micro-emboli during catheter electroporation ablation

Introduction: Recent studies demonstrated that irreversible electroporation (IRE) ablation may be an alternative method for thermal ablation for pulmonary vein isolation. Development of gaseous microemboli during catheter ablation might lead to asymptomatic ischemic events and is therefore an important research topic. Gas formation during arcing with direct current catheter ablation has been studied in the past, however not for nonarcing IRE-ablation. Objective: The aim of the present study was to visualize, quantify, and characterize gas formation during nonarcing millisecond IRE-pulses using a multielectrode circular catheter. Methods: In vitro, gas formation during IRE-pulses was studied using a high-speed imaging, direct volume measurements, and a bubble counter. Gas formation was compared between cathodal and anodal IRE-pulses and between a small and large catheter hoop diameter. Results: High-speed images showed the location and dynamics of gas formation during cathodal and anodal millisecond IRE-pulses. The direct volume measurements demonstrated a significantly larger volume for cathodal than for anodal IRE-pulses (P <.001), and no significant difference between small and large hoop diameters. A strong linear relationship was found between delivered charge and total gas volume (r = 0.99). Bubble counter measurements showed that cathodal IRE-pulses produced more and larger gas bubbles than anodal IRE-pulses. The ratio of total gas volume between cathodal and anodal IRE-pulses is different as predicted from electrolysis theory. Conclusion: In vitro, millisecond anodal IRE-pulses produce significantly less and smaller gas bubbles than millisecond cathodal IRE-pulses. In vivo experiments are required to investigate the clinical implication of these observations

Low vulnerability of the right phrenic nerve to electroporation ablation

BACKGROUND Circular electroporation ablation is a novel ablation modality for electrical pulmonary vein isolation. With a single 200-3 application, deep circular myocardial lesions can be created. However, the acute and chronic effects of this energy source on phrenic nerve (PN) function are unknown. OBJECTIVE The purpose of this study was to analyze nerve vulnerability to electroporation ablation in a porcine model. METHODS In 20 animals (60-75 kg), the course of the right PN was pace-mapped inside the superior caval vein (SCV). Thereafter, a single 200-3 circular electroporation ablation was performed via a multipolar circular catheter in firm contact with the inner SCV wall. RESULTS In 19 of 20 animals, the PN could be captured along an estimated 6-8 cm trajectory above the right atrial contour. Directly after the application, the PN could be captured above the ablation Level in 17 of 19 animals and after maximally 30 minutes in all animals. Fifteen animals were restudied after 3-13 weeks, and PN functionality was unaffected in all. Histological analysis in 5 animals in which the application had been delivered in the muscular sleeve just above the right atrium showed a transmural circular lesion. However, no lesion was found in the other animals in which the application had been delivered in the fibrous section more cranial in the SCV. CONCLUSIONS Electroporation ablation at an energy Level that may create deep myocardial Lesions may spare the targeted right PN. These animal data suggest that electroporation may be a safe ablation modality near the right PN

Low vulnerability of the right phrenic nerve to electroporation ablation

BACKGROUND Circular electroporation ablation is a novel ablation modality for electrical pulmonary vein isolation. With a single 200-3 application, deep circular myocardial lesions can be created. However, the acute and chronic effects of this energy source on phrenic nerve (PN) function are unknown. OBJECTIVE The purpose of this study was to analyze nerve vulnerability to electroporation ablation in a porcine model. METHODS In 20 animals (60-75 kg), the course of the right PN was pace-mapped inside the superior caval vein (SCV). Thereafter, a single 200-3 circular electroporation ablation was performed via a multipolar circular catheter in firm contact with the inner SCV wall. RESULTS In 19 of 20 animals, the PN could be captured along an estimated 6-8 cm trajectory above the right atrial contour. Directly after the application, the PN could be captured above the ablation Level in 17 of 19 animals and after maximally 30 minutes in all animals. Fifteen animals were restudied after 3-13 weeks, and PN functionality was unaffected in all. Histological analysis in 5 animals in which the application had been delivered in the muscular sleeve just above the right atrium showed a transmural circular lesion. However, no lesion was found in the other animals in which the application had been delivered in the fibrous section more cranial in the SCV. CONCLUSIONS Electroporation ablation at an energy Level that may create deep myocardial Lesions may spare the targeted right PN. These animal data suggest that electroporation may be a safe ablation modality near the right PN

Pulmonary Vein Isolation With Single Pulse Irreversible Electroporation: A First in Human Study in 10 Patients With Atrial Fibrillation

BACKGROUND: Irreversible electroporation (IRE) is a promising new nonthermal ablation technology for pulmonary vein (PV) isolation in patients with atrial fibrillation. Experimental data suggest that IRE ablation produces large enough lesions without the risk of PV stenosis, artery, nerve, or esophageal damage. This study aimed to investigate the feasibility and safety of single pulse IRE PV isolation in patients with atrial fibrillation. METHODS: Ten patients with symptomatic paroxysmal or persistent atrial fibrillation underwent single pulse IRE PV isolation under general anesthesia. Three-dimensional reconstruction and electroanatomical voltage mapping (EnSite Precision, Abbott) of left atrium and PVs were performed using a conventional circular mapping catheter. PV isolation was performed by delivering nonarcing, nonbarotraumatic 6 ms, 200 J direct current IRE applications via a custom nondeflectable 14-polar circular IRE ablation catheter with a variable hoop diameter (16-27 mm). A deflectable sheath (Agilis, Abbott) was used to maneuver the ablation catheter. A minimum of 2 IRE applications with slightly different catheter positions were delivered per vein to achieve circular tissue contact, even if PV potentials were abolished after the first application. Bidirectional PV isolation was confirmed with the circular mapping catheter and a post ablation voltage map. After a 30-minute waiting period, adenosine testing (30 mg) was used to reveal dormant PV conduction. RESULTS: All 40 PVs could be successfully isolated with a mean of 2.4±0.4 IRE applications per PV. Mean delivered peak voltage and peak current were 2154±59 V and 33.9±1.6 A, respectively. No PV reconnections occurred during the waiting period and adenosine testing. No periprocedural complications were observed. CONCLUSIONS: In the 10 patients of this first-in-human study, acute bidirectional electrical PV isolation could be achieved safely by single pulse IRE ablation

Efficacy of multi-electrode linear irreversible electroporation

AIMS: We investigated the efficacy of linear multi-electrode irreversible electroporation (IRE) ablation in a porcine model. METHODS AND RESULTS: The study was performed in six pigs (weight 60-75 kg). After median sternotomy and opening of the pericardium, a pericardial cradle was formed and filled with blood. A linear seven polar 7-Fr electrode catheter with 2.5 mm electrodes and 2.5 mm inter-electrode spacing was placed in good contact with epicardial tissue. A single IRE application was delivered using 50 J at one site and 100 J at two other sites, in random sequence, using a standard monophasic defibrillator connected to all seven electrodes connected in parallel. The pericardium and thorax were closed and after 3 weeks survival animals were euthanized. A total of 82 histological sections from all 18 electroporation lesions were analysed. A total of seven 50 J and fourteen 100 J epicardial IRE applications were performed. Mean peak voltages at 50 and 100 J were 1079.2 V ± 81.1 and 1609.5 V ± 56.8, with a mean peak current of 15.4 A ± 2.3 and 20.2 A ± 1.7, respectively. Median depth of the 50 and 100 J lesions were 3.2 mm [interquartile range (IQR) 3.1-3.6] and 5.5 mm (IQR 4.6-6.6) (P < 0.001), respectively. Median lesion width of the 50 and 100 J lesions was 3.9 mm (IQR 3.7-4.8) and 5.4 mm (IQR 5.0-6.3), respectively (P < 0.001). Longitudinal sections showed continuous lesions for 100 J applications. CONCLUSION: Epicardial multi-electrode linear application of IRE pulses is effective in creating continuous deep lesions

Pulmonary vein ostium geometry - Analysis by magnetic resonance angiography

Background-During a catheter ablation procedure for selective electrical isolation of pulmonary vein (PV) ostia, the size of these ostia is usually estimated using fluoroscopic angiography. This measurement may be misleading, however, because only the projected supero/inferior ostium diameters can be measured. In this study, we analyzed 3-dimensional magnetic resonance angiographic (MRA) images to measure the minimal and maximal cross-sectional diameter of PV ostia in relation to the diameter that would have been projected on fluoroscopic angiograms during a catheter ablation procedure. Methods and Results-In 42 patients with idiopathic atrial fibrillation who were scheduled for selective electrical isolation of PV ostia, the minimal and maximal diameters of these ostia were measured from 3-dimensional MRA images. Thereafter, these images were oriented in a 45 right or left anterior oblique direction and the projected diameter of the PV ostia were measured again. The average ratio between maximal and minimal diameter was 1.5+/-0.4 for the left and 1.2+/-0.1 for the right pulmonary vein ostia. Because of the orientation and oval shape of especially the left pulmonary vein ostia, their minimal diameters were significantly smaller than the projected diameters. Conclusion-Pulmonary vein ostia, especially those at the left, are oval with the short axis oriented approximately in the antero/posterior direction. Consequently, PV ostia may sometimes be very narrow despite a rather normal appearance on angiographic images obtained during a catheter ablation procedur

Irreversible Electroporation of the Pancreas Using Parallel Plate Electrodes in a Porcine Model: A Feasibility Study.

Irreversible electroporation (IRE) with needle electrodes is being explored as treatment option in locally advanced pancreatic cancer. Several studies have shown promising results with IRE needles, positioned around the tumor to achieve tumor ablation. Disadvantages are the technical difficulties for needle placement, the time needed to achieve tumor ablation, the risk of needle track seeding and most important the possible occurrence of postoperative pancreatic fistula via the needle tracks. The aim of this experimental study was to evaluate the feasibility of a new IRE-technique using two parallel plate electrodes, in a porcine model.Twelve healthy pigs underwent laparotomy. The pancreas was mobilized to enable positioning of the paddles. A standard monophasic external cardiac defibrillator was used to perform an ablation in 3 separate parts of the pancreas; either a single application of 50 or 100J or a serial application of 4x50J. After 6 hours, pancreatectomy was performed for histology and pigs were terminated.Histology showed necrosis of pancreatic parenchyma with neutrophil influx in 5/12, 11/12 and 12/12 of the ablated areas at 50, 100, and 4x50J respectively. The electric current density threshold to achieve necrosis was 4.3, 5.1 and 3.4 A/cm2 respectively. The ablation threshold was significantly lower for the serial compared to the single applications (p = 0.003). The content of the ablated areas differed between the applications: areas treated with a single application of 50 J often contained vital areas without obvious necrosis, whereas half of the sections treated with 100 J showed small islands of normal looking cells surrounded by necrosis, while all sections receiving 4x 50 J showed a homogeneous necrotic lesion.Pancreatic tissue can be successfully ablated using two parallel paddles around the tissue. A serial application of 4x50J was most effective in creating a homogeneous necrotic lesion