Abstract
Purpose Atherosclerotic vascular disease remains a leading cause of morbidity and mortality worldwide. Current treatments such as angioplasty, stenting, and atherectomy are invasive and limited by restenosis, thrombosis, and incomplete long-term efficacy. Pulsed field ablation (PFA), a nonthermal electroporation-based modality, has demonstrated safety in other cardiovascular applications, but it has not been applied for the treatment of endoluminal vascular diseases. We investigated whether pulsed electric fields could be delivered within the coronary artery and if PFA could selectively ablate the cellular components of atherosclerotic plaques. Methods An endoluminal bipolar PFA probe was fabricated using a balloon catheter with flexible electrodes and evaluated in potato and ex vivo porcine hearts. The electrical conductivities of human atherosclerotic plaques were derived from previous impedance measurements for patient-specific multi-tissue and single-cell electroporation modeling. PFA was then evaluated for selective decellularization within an electrical conductivity-matched 3D fibrotic atherosclerosis tissue mimic using high concentrations of human macrophages and aggregated oxidized low-density lipoproteins, encapsulated within a collagen matrix. Results Endoluminal probe positioning and high-voltage pulsed electric field delivery feasibility was established within the porcine left coronary arteries, with susequent potato lesions experiments demonstrating maximum ablations (6.99 cm 2 ) and current (13 A) with equal treatment parameters. The multi-tissue model then indicated that endoluminal PFA can effectively cover > 95% of severe and thick plaques with irreversible electroporation, with single-cell modeling supporting the electroporation of foam cells within the plaque. The 3D atherosclerosis mimic validated the ability of PFA to completely ablate the foam cells with fibrotic tissue at > 1000 V/cm. Conclusions This study provides practical demonstration of PFA for the treatment of atherosclerotic vascular disease. By combining experimental validation with computational modeling, we establish proof-of-concept that endoluminal PFA can selectively ablate diseased cells while preserving extracellular architecture, laying the groundwork for future translational development of this therapy.