In vivo analysis of the origin and characteristics of gaseous microemboli during catheter-mediated irreversible electroporation

Aims: Irreversible electroporation (IRE) ablation is a non-thermal ablation method based on the application of direct current between a multi-electrode catheter and skin electrode. The delivery of current through blood leads to electrolysis. Some studies suggest that gaseous (micro)emboli might be associated with myocardial damage and/or (a)symptomatic cerebral ischaemic events. The aim of this study was to compare the amount of gas generated during IRE ablation and during radiofrequency (RF) ablation. Methods and results: In six 60-75 kg pigs, an extracorporeal femoral shunt was outfitted with a bubble-counter to detect the size and total volume of gas bubbles. Anodal and cathodal 200 J IRE applications were delivered in the left atrium (LA) using a 14-electrode circular catheter. The 30 and 60 s 40 W RF point-by-point ablations were performed. Using transoesophageal echocardiography (TOE), gas formation was visualized. Average gas volumes were 0.6 ± 0.6 and 56.9 ± 19.1 μL (P < 0.01) for each anodal and cathodal IRE application, respectively. Also, qualitative TOE imaging showed significantly less LA bubble contrast with anodal than with cathodal applications. Radiofrequency ablations produced 1.7 ± 2.9 and 6.7 ± 7.4 μL of gas, for 30 and 60 s ablation time, respectively. Conclusion: Anodal IRE applications result in significantly less gas formation than both cathodal IRE applications and RF applications. This finding is supported by TOE observations

Characteristics and time course of acute and chronic myocardial lesion formation after electroporation ablation in the porcine model

Introduction: Electroporation ablation creates deep and wide myocardial lesions. No data are available on time course and characteristics of acute lesion formation. Methods: For the acute phase of myocardial lesion development, seven pigs were investigated. Single 200 J applications were delivered at four different epicardial right ventricular sites using a linear suction device, yielding a total of 28 lesions. Timing of applications was designed to yield lesions at seven time points: 0, 10, 20, 30, 40, 50, and 60 min, with four lesions per time point. After killing, lesion characteristics were histologically investigated. For the chronic phase of myocardial lesion development, tissue samples were used from previously conducted studies where tissue was obtained at 3 weeks and 3 months after electroporation ablation. Results: Acute myocardial lesions induce a necrosis pattern with contraction band necrosis and interstitial edema, immediately present after electroporation ablation. No further histological changes such as hemorrhage or influx of inflammatory cells occurred in the first hour. After 3 weeks, the lesions consisted of sharply demarcated loose connective tissue that further developed to more fibrotic scar tissue after 3 months without additional changes. Within the scar tissue, arteries and nerves were unaffected. Conclusion: Electroporation ablation immediately induces contraction band necrosis and edema without additional tissue changes in the first hour. After 3 weeks, a sharply demarked scar has been developed that remains stable during follow-up of 3 months. This is highly relevant for clinical application of electroporation ablation in terms of the electrophysiological endpoint and waiting period after ablation

Multielectrode Contact Measurement Can Improve Long-Term Outcome of Pulmonary Vein Isolation Using Circular Single-Pulse Electroporation Ablation

Background: Irreversible electroporation (IRE) ablation is generally performed with multielectrode catheters. Electrode-tissue contact is an important predictor for the success of pulmonary vein (PV) isolation; however, contact force is difficult to measure with multielectrode ablation catheters. In a preclinical study, we assessed the feasibility of a multielectrode impedance system (MEIS) as a predictor of long-term success of PV isolation. In addition, we present the first-in-human clinical experience with MEIS. Methods: In 10 pigs, one PV was ablated based on impedance (MEIS group), and the other PV was solely based on local electrogram information (EP group). IRE ablations were performed at 200 J. After 3 months, recurrence of conduction was assessed. Subsequently, in 30 patients undergoing PV isolation with IRE, MEIS was evaluated and MEIS contact values were compared to local electrograms. Results: In the porcine study, 43 IRE applications were delivered in 19 PVs. Acutely, no reconnections were observed in either group. After 3 months, 0 versus 3 (P=0.21) PVs showed conduction recurrence in the MEIS and EP groups, respectively. Results from the clinical study showed a significant linear relation was found between mean MEIS value and bipolar dV/dt (r2=0.49, P<0.001), with a slope of 20.6 mV/s per Ohm. Conclusions: Data from the animal study suggest that MEIS values predict effective IRE applications. For the long-term success of electrical PV isolation with circular IRE applications, no significant difference in efficacy was found between ablation based on the measurement of electrode interface impedance and ablation using the classical EP approach for determining electrode-tissue contact. Experiences of the first clinical use of MEIS were promising and serve as an important basis for future research

Multi-national survey on the methods, efficacy, and safety on the post-approval clinical use of pulsed field ablation (MANIFEST-PF).

AIMS Pulsed field ablation (PFA) is a novel atrial fibrillation (AF) ablation modality that has demonstrated preferential tissue ablation, including no oesophageal damage, in first-in-human clinical trials. In the MANIFEST-PF survey, we investigated the 'real world' performance of the only approved PFA catheter, including acute effectiveness and safety-in particular, rare oesophageal effects and other unforeseen PFA-related complications. METHODS AND RESULTS This retrospective survey included all 24 clinical centres using the pentaspline PFA catheter after regulatory approval. Institution-level data were obtained on patient characteristics, procedure parameters, acute efficacy, and adverse events. With an average of 73 patients treated per centre (range 7-291), full cohort included 1758 patients: mean age 61.6 years (range 19-92), female 34%, first-time ablation 94%, paroxysmal/persistent AF 58/35%. Most procedures employed deep sedation without intubation (82.1%), and 15.1% were discharged same day. Pulmonary vein isolation (PVI) was successful in 99.9% (range 98.9-100%). Procedure time was 65 min (38-215). There were no oesophageal complications or phrenic nerve injuries persisting past hospital discharge. Major complications (1.6%) were pericardial tamponade (0.97%) and stroke (0.4%); one stroke resulted in death (0.06%). Minor complications (3.9%) were primarily vascular (3.3%), but also included transient phrenic nerve paresis (0.46%), and TIA (0.11%). Rare complications included coronary artery spasm, haemoptysis, and dry cough persistent for 6 weeks (0.06% each). CONCLUSION In a large cohort of unselected patients, PFA was efficacious for PVI, and expressed a safety profile consistent with preferential tissue ablation. However, the frequency of 'generic' catheter complications (tamponade, stroke) underscores the need for improvement

Safety of pulsed field ablation in more than 17,000 patients with atrial fibrillation in the MANIFEST-17K study

Pulsed field ablation (PFA) is an emerging technology for the treatment of atrial fibrillation (AF), for which pre-clinical and early-stage clinical data are suggestive of some degree of preferentiality to myocardial tissue ablation without damage to adjacent structures. Here in the MANIFEST-17K study we assessed the safety of PFA by studying the post-approval use of this treatment modality. Of the 116 centers performing post-approval PFA with a pentaspline catheter, data were received from 106 centers (91.4% participation) regarding 17,642 patients undergoing PFA (mean age 64, 34.7% female, 57.8% paroxysmal AF and 35.2% persistent AF). No esophageal complications, pulmonary vein stenosis or persistent phrenic palsy was reported (transient palsy was reported in 0.06% of patients; 11 of 17,642). Major complications, reported for ~1% of patients (173 of 17,642), were pericardial tamponade (0.36%; 63 of 17,642) and vascular events (0.30%; 53 of 17,642). Stroke was rare (0.12%; 22 of 17,642) and death was even rarer (0.03%; 5 of 17,642). Unexpected complications of PFA were coronary arterial spasm in 0.14% of patients (25 of 17,642) and hemolysis-related acute renal failure necessitating hemodialysis in 0.03% of patients (5 of 17,642). Taken together, these data indicate that PFA demonstrates a favorable safety profile by avoiding much of the collateral damage seen with conventional thermal ablation. PFA has the potential to be transformative for the management of patients with AF.Peer reviewe

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

Epicardial Ablation: Prevention of Phrenic Nerve Damage by Pericardial Injection of Saline and the Use of a Steerable Sheath

Because of the close proximity of the phrenic nerve to the pericardium, phrenic nerve damage caused by epicardial ablation can easily occur. We report two cases of epicardial VT ablation where pericardial injection of saline, combined with the use of a steerable sheath, successfully prevents the phrenic nerve from being damaged

Balloon Catheter Position and its Relationship with Esophageal Temperature during Pulmonary Vein Isolation using High-Intensity Focused Ultrasound

Background: HIFU can achieve PVI, but severe esophageal complications have happened. We analyzed relative position of HIFU balloon catheter (BC) to esophageal temperature (ET) probe and correlated it to ET changes. Methods and Results: Before each ablation relative position of HIFU BC to ET probe was recorded in RAO 30° and LAO 40°. We compared ablations where ET at end of ablation was <38.5°C or ≥38.5°C and <40.0°C or ≥40.0°C. A total of 600 images from 311 ablations in 28 patients (18 male, age 63±7 years), were analyzed. ET ≥38.5°C was reached when distance from BC to ET probe was: <20 mm in LAO for RSPV and <29 mm in LAO for RIPV. For RIPV ET ≥38.5°C was reached when angle between BC and ET probe was significantly smaller in LAO and RAO. ET ≥40.0°C was reached when distance of BC to ET probe was: <20 mm in LAO for RIPV, <14 mm in RAO for RIPV, <18 mm in RAO for LIPV. ET increased to ≥40.0°C when distance from BC to ET probe was significantly longer in LAO for LIPV. For RIPV ET ≥40.0°C was reached when angle between BC and ET probe was significantly smaller in LAO. Conclusions: There is a relationship between distance/angle of HIFU BC to ET probe and ET: shorter distances and smaller angles can cause higher ET