Electrophysiology, Pathology, and Imaging of Pulsed Field Ablation of Scarred and Healthy Ventricles in Swine.

BACKGROUND: Pulsed field ablation (PFA) has recently been shown to penetrate ischemic scar, but details on its efficacy, risk of arrhythmias, and imaging insights are lacking. In a porcine model of myocardial scar, we studied the ability of ventricular PFA to penetrate scarred tissue, induce ventricular arrhythmias, and assess the influence of QRS gating during pulse delivery. METHODS: Of a total of 6 swine, 5 underwent coronary occlusion and 1 underwent radiofrequency ablation to create infarct scar and iatrogenic scar models, respectively. Two additional swine served as healthy controls. An 8 Fr focal PFA catheter was used to deliver bipolar, biphasic PFA (2.0 kV) lesions guided by electroanatomical mapping, fluoroscopy, and intracardiac echocardiography over both scarred and healthy myocardium. Swine underwent magnetic resonance imaging 2-7 days post-PFA. RESULTS: PFA successfully penetrated scar without significant difference in lesion depth between lesion at the infarct border (5.9±1.0 mm, n=41) and healthy myocardium (5.7±1.3 mm, n=26; P=0.53). PFA penetration of both infarct and iatrogenic radiofrequency abalation scar was observed in all examined sections. Sustained ventricular arrhythmias requiring defibrillation occurred in 4 of 187 (2.1%) ungated applications, whereas no ventricular arrhythmias occurred during gated PFA applications (0 of 64 [0%]). Dark-blood late-gadolinium-enhanced sequences allowed for improved endocardial border detection as well as lesion boundaries compared with conventional bright-blood late-gadolinium-enhanced sequences. CONCLUSIONS: PFA penetrates infarct and iatrogenic scar successfully to create deep lesions. Gated delivery eliminates the occurrence of ventricular arrhythmias observed with ungated porcine PFA. Optimized magnetic resonance imaging sequences can be helpful in detecting lesion boundaries.

Effect of Epicardial Pulsed Field Ablation Directly on Coronary Arteries.

BACKGROUND: The unique tissue selectivity of pulsed field ablation (PFA) allows for minimizing collateral damage to the nerves/esophagus. However, the safety profile of epicardial PFA on coronary arteries (CAs) has not been well defined. OBJECTIVES: This study sought to evaluate the effect of epicardial PFA directly on CAs in a swine model. METHODS: In 4 swine, an 8-F linear quadripolar PFA catheter (FARAPULSE Inc) was introduced into the pericardial space via a subxiphoid puncture. After coronary angiography (Angio), QRS synchronized, biphasic, bipolar PFA was delivered directly on the left anterior descending artery, left circumflex artery, or normal myocardium (control) (2.0 kV × 4 applications per site). Angio was repeated immediately after ablation and repeated every 5 minutes to quantify the degree of CA narrowing. After 4- or 8-week survival, repeat Angio was performed followed by gross and histologic lesion analyses. RESULTS: A total of 15 lesions were delivered (8 left anterior descending arteries, 3 left circumflexes, and 4 controls). Target site Angio revealed median of 47% (IQR: 38%-69%) acute luminal narrowing immediately after PFA, which gradually resolved over 30 minutes. Epicardial PFA lesions extended into the myocardium with a median depth of 4.1 mm (IQR: 3.6-5.6 mm) passing across the CAs and adipose tissue. However, 87.5% of the CAs demonstrated minimal to mild CA stenosis associated with neointimal hyperplasia and tunica media fibrosis. CONCLUSIONS: In a swine model, epicardial PFA directly on CAs allowed the creation of myocardial lesions but led to a CA response characterized by acute moderate spasm and chronic mild stenosis via neointimal hyperplasia.

Pulsed Field Ablation Versus Radiofrequency Ablation: Esophageal Injury in a Novel Porcine Model.

BACKGROUND: Pulsed field ablation (PFA) can be myocardium selective, potentially sparing the esophagus during left atrial ablation. In an in vivo porcine esophageal injury model, we compared the effects of newer biphasic PFA with radiofrequency ablation (RFA). METHODS: In 10 animals, under general anesthesia, the lower esophagus was deflected toward the inferior vena cava using an esophageal deviation balloon, and ablation was performed from within the inferior vena cava at areas of esophageal contact. Four discrete esophageal sites were targeted in each animal: 6 animals received 8 PFA applications/site (2 kV, multispline catheter), and 4 animals received 6 clusters of irrigated RFA applications (30 W×30 seconds, 3.5 mm catheter). All animals were survived to 25 days, sacrificed, and the esophagus submitted for pathological examination, including 10 discrete histological sections/esophagus. RESULTS: The animals weight increased by 13.7±6.2% and 6.8±6.3% (P=0.343) in the PFA and RFA cohorts, respectively. No PFA animals (0 of 6, 0%) developed abnormal in-life observations, but 1 of 4 RFA animals (25%) developed fever and dyspnea. On necropsy, no PFA animals (0 of 6, 0%) demonstrated esophageal lesions. In contrast, esophageal injury occurred in all RFA animals (4 of 4, 100%; P=0.005): a mean of 1.5 mucosal lesions/animal (length, -21.8±8.9 mm; width, -4.9±1.4 mm) were observed, including one esophago-pulmonary fistula and deep esophageal ulcers in the other animals. Histological examination demonstrated tissue necrosis surrounded by acute and chronic inflammation and fibrosis. The necrotic RFA lesions involved multiple esophageal tissue layers with evidence of arteriolar medial thickening and fibrosis of periesophageal nerves. Abscess formation and full-thickness esophageal wall disruptions were seen in areas of perforation/fistula. CONCLUSIONS: In this novel porcine model of esophageal injury, biphasic PFA induced no chronic histopathologic esophageal changes, while RFA demonstrated a spectrum of esophageal lesions including fistula and deep esophageal ulcers and abscesses.

Endocardial ventricular pulsed field ablation: a proof-of-concept preclinical evaluation.

AIMS: Pulsed field ablation (PFA) is a novel, non-thermal modality that selectively ablates myocardium with ultra-short electrical impulses while sparing collateral tissues. In a proof-of-concept study, the safety and feasibility of ventricular PFA were assessed using a prototype steerable, endocardial catheter. METHODS AND RESULTS: Under general anaesthesia, the left and right ventricles of four healthy swine were ablated using the 12-Fr deflectable PFA catheter and a deflectable sheath guided by electroanatomic mapping. Using the study catheter, electrograms were recorded for each site and pre-ablation and post-ablation pacing thresholds (at 2.0 ms pulse width) were recorded in two of four animals. After euthanasia at 35.5 days, the hearts were submitted for histology. The PFA applications (n = 39) resulted in significant electrogram reduction without ventricular arrhythmias. In ablation sites where it was measured, the pacing thresholds increased by >16.8 mA in the right ventricle (3 sites) and >16.1 mA in the left ventricle (7 sites), with non-capture at maximum amplitude (20 mA) observable in 8 of 10 sites. Gross measurements, available for 28 of 30 ablation sites, revealed average lesion dimensions to be 6.5 ± 1.7 mm deep by 22.6 ± 4.1 mm wide, with a maximum depth and width of 9.4 mm and 28.6 mm, respectively. In the PFA lesions, fibrous tissue homogeneously replaced myocytes with a narrow zone of surrounding myocytolysis and no overlying thrombus. When present, nerve fascicles and vasculature were preserved within surrounding fibrosis. CONCLUSION: We demonstrate that endocardial PFA can be focally delivered using this prototype catheter to create homogeneous, myocardium-specific lesions.

Preclinical Evaluation of Pulsed Field Ablation: Electrophysiological and Histological Assessment of Thoracic Vein Isolation.

BACKGROUND: Pulsed field ablation (PFA) is a uniquely tissue-selective, nonthermal cardiac ablation modality. Delivery parameters such as the electrical waveform composition and device design are critical to PFA's efficacy and safety, particularly tissue specificity. In a series of preclinical studies, we sought to examine the electrophysiological and histological effects of PFA and compare the safety and feasibility of durable pulmonary vein and superior vena cava (SVC) isolation between radiofrequency ablation and PFA waveforms. METHODS: A femoral venous approach was used to gain right and left atrial access under general anesthesia in healthy swine. Baseline potentials in right superior pulmonary and inferior common vein and in SVC were assessed. Bipolar PFA was performed with monophasic (PFAMono) and biphasic (PFABi) waveforms in 7 and 7 swine sequentially and irrigated radiofrequency ablation in 3 swine. Vein potentials were then assessed acutely, and at ≈10 weeks; histology was obtained. RESULTS: All targeted veins (n=46) were successfully isolated on the first attempt in all cohorts. The PFABi waveform induced significantly less skeletal muscle engagement. Pulmonary vein isolation durability was assessed in 28 veins: including the SVC, durability was significantly higher in the PFABi group (18/18 PFABi, 10/18 PFAMono, 3/6 radiofrequency, P=0.002). Transmurality rates were similar across groups with evidence of nerve damage only with radiofrequency. Pulmonary vein narrowing was noted only in the radiofrequency cohort. The phrenic nerve was spared in all cohorts but at the expense of incomplete SVC encirclement with radiofrequency. CONCLUSIONS: In this chronic porcine study, PFA-based pulmonary vein and SVC isolation were safe and efficacious with demonstrable sparing of nerves and venous tissue. This preclinical study provided the scientific basis for the first-in-human endocardial PFA studies.