Pulsed field ablation as a precise approach for cardiac arrhythmia treatment via cardiac microenvironment remodeling

PFA uses short-duration, high-voltage electrical pulses to induce transient or irreversible electroporation on cell membranes, causing cell death. Selective inhibition of chaotic electrical signals in morbid cardiomyocytes significantly aids the treatment of atrial fibrillation, ventricular tachycardia, and other heart arrhythmias. Recent preclinical and clinical studies have only investigated physical changes, such as lesion size and myocardial scar. Compared to radiofrequency ablation and cryoballoon ablation, PFA causes less postoperative myocardial cell fibrosis and inflammatory reaction and does not result in myocardial necrosis or tissue scar formation. However, the regulatory mechanism of cellular stress following PFA treatment remains unknown. This study aimed to analyze the transcriptome of the mouse ventricle after PFA treatment. The animals were subjected to a 225-V electric pulse with a 1.5-mm gap between the positive and negative electrodes. Hearts were harvested at 3, 6, 12, 24 h, and 2, 5 days for myocardial zymogram testing. PFA-treated ventricular regions were selected for single-nucleus sequencing. We discovered that PFA remodeled the cardiac microenvironment as a whole. Further, we discussed the possible stress response and wound-healing mechanism in non-targeted cells. In conclusion, PFA allowed effective and selective ventricular myocardium ablation with controllable inflammation.