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

Abstract

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.

Keywords: Catheter ablation; Electroporation; Pulsed field ablation; Ventricle; Ventricular tachycardia.

Graphical Abstract

Figure 1

(Left panel) Distal aspect of the ablation catheter in deployed position. (Right panel) Fluoroscopic view demonstrating pacing catheters placed in the right ventricle and coronary sinus along with ICE positioned in the RA. A deflectable transseptal sheath is in position with the ablation catheter positioned in the LV. ICE, intracardiac echocardiography; LV, left ventricle; PFA, pulsed field ablation; RA, right atrium.

Figure 2

Distribution of applications across both RV and LV. LV, left ventricle; RV, right ventricle; RVOT, right ventricular outflow tract.

Figure 3

(Left panel) Joint pacing from coronary sinus and right ventricular catheters with synchronized PFA pulses. (Right panel) Figure diagram demonstrating the simulated ablation zone for this specific dose/electrode combination. PFA, pulsed field ablation.

Figure 4

(A) Epicardial aspect of transmural lesions in the RV, inset-zoomed view of a single lesion. (B) Endocardial aspect of the same lesions in the RV, inset-zoomed view of a single lesion. (C) Section demonstrating non-transmural lesions in the LV. LV, left ventricle; RV, right ventricle.

Figure 5

(A) A well-demarcated, non-transmural lesion in the left ventricle (MT, 3×). (B) Junction of fibrotic lesions and normal myocardium (H&E, 10×). (C) Thickening of arteriolar walls (black arrows) with well-preserved endothelial lining and spared lumen as seen within the core of an ablation lesion. Note: no thrombi in the vessels (MT, 10×). D) A transmural fibrotic lesion in right ventricle (MT, 2×). (E) Flat mesothelial cells lining of pericardium are seen to be well-preserved (MT, 40×). (F) Two well-preserved and viable nerve fascicles seen within fibrous tissue of an ablation lesion. H&E, haematoxylin and eosin; MT, masons trichrome.