In vivopulsed-field ablation in healthy vs. chronically infarcted ventricular myocardium: biophysical and histologic characterization

Abstract

Aims Data on ventricular pulsed-field ablation (PFA) are sparse in the setting of chronic myocardial infarction (MI). The objective of this study was to compare the biophysical and histopathologic characteristics of PFA in healthy and MI swine ventricular myocardium. Methods and results Myocardial infarction swine (n = 8) underwent coronary balloon occlusion and survived for 30 days. We then performed endocardial unipolar, biphasic PFA of the MI border zone and a dense scar with electroanatomic mapping and using an irrigated contact force (CF)-sensing catheter with the CENTAURI System (Galaxy Medical). Lesion and biophysical characteristics were compared with three controls: MI swine undergoing thermal ablation, MI swine undergoing no ablation, and healthy swine undergoing similar PFA applications that included linear lesion sets. Tissues were systematically assessed by gross pathology utilizing 2,3,5-triphenyl-2H-tetrazolium chloride staining and histologically with haematoxylin and eosin and trichrome. Pulsed-field ablation in healthy myocardium generated well-demarcated ellipsoid lesions (7.2 ± 2.1 mm depth) with contraction band necrosis and myocytolysis. Pulsed-field ablation in MI demonstrated slightly smaller lesions (depth 5.3 ± 1.9 mm, P = 0.0002), and lesions infiltrated into the irregular scar border, resulting in contraction band necrosis and myocytolysis of surviving myocytes and extending to the epicardial border of the scar. Coagulative necrosis was present in 75% of thermal ablation controls but only in 16% of PFA lesions. Linear PFA resulted in contiguous linear lesions with no gaps in gross pathology. Neither CF nor local R-wave amplitude reduction correlated with lesion size. Conclusion Pulsed-field ablation of a heterogeneous chronic MI scar effectively ablates surviving myocytes within and beyond the scar, demonstrating promise for the clinical ablation of scar-mediated ventricular arrhythmias.

Opportunities and Challenges in Catheter-Based Irreversible Electroporation for Ventricular Tachycardia

“…Langendorff and whole-animal studies have been completed in swine [ 52 , 53 , 54 , 55 , 56 , 57 ], canine [ 58 ], ovine [ 59 ], and even rabbit [ 60 ] models using various PFA catheter types and methodologies. Consensus findings include the creation of transmural lesions via concentrated apoptosis with no evidence of thermal-based tissue damage.…”

“…Unfortunately, no pre-clinical data assessing the safety, efficacy, or reproducibility of PFA for VT exist in animal models of human cardiac disease. However, pre-clinical reports on the efficacy of ventricular PFA [ 53 , 56 , 57 , 61 ], as well as the safety of ventricular PFA [ 62 ], are increasing. All five studies were conducted in swine [ 53 , 56 , 57 , 61 , 62 ] and had short-term endpoints (ranging from 2 to 7 days [ 57 ] to 6 to 8 weeks [ 53 ]).…”

“…However, pre-clinical reports on the efficacy of ventricular PFA [ 53 , 56 , 57 , 61 ], as well as the safety of ventricular PFA [ 62 ], are increasing. All five studies were conducted in swine [ 53 , 56 , 57 , 61 , 62 ] and had short-term endpoints (ranging from 2 to 7 days [ 57 ] to 6 to 8 weeks [ 53 ]). Sample sizes were small (ranging from 4 to 10 swine), though appropriate for preliminary de novo safety study designs.…”

25 years of basic and translational science in EP Europace: novel insights into arrhythmia mechanisms and therapeutic strategies

“… 4 Moreover, they showed that late recovery of electrical conduction in individual lesions can lead to arrhythmia recurrence—consistent with the clinical observation of the association between loss of bi-directional conduction block and arrhythmia recurrence. Other studies investigated the differences in scar/lesion formation in healthy and diseased myocardium (low- to intermediate-voltage areas), 5 , 6 identifying differences in the depth, width, and homogeneity of the lesions, which has clinical implications for performing ablations in diseased myocardium.…”

Effects of Electroporation on the Function of Sarco/Endoplasmic Reticulum Ca2+-ATPase and Na+,K+-ATPase in H9c2 Cells

“…Pulsed field ablation (PFA), based on irreversible electroporation, is a promising new intervention for the treatment of atrial fibrillation (AF), which isolates electric triggers in pulmonary veins from entering the left atrium and, thus, stops the arrhythmic beating of the heart [3][4][5][6]. As PFA is being rapidly introduced into clinical practice, there is growing interest for its use in ventricular tissue as well [7][8][9][10][11][12][13]. Electroporation occurs when cells are exposed to short, high-voltage electric pulses [14], which leads to a transient increase in cell membrane permeability and may result in cell death.…”