Abstract Pulsed field ablation (PFA) is emerging as a major advance in cardiac ablation because it induces irreversible electroporation rather than relying primarily on thermal injury. This article provides an overview of the core biophysical principles underlying PFA, focusing on concepts broadly relevant across systems and clinical applications. Externally applied pulsed electric fields interact with biological tissues and affect their transmembrane potential. When a critical threshold is exceeded, nanoscale aqueous pores form in the lipid bilayer, initiating electroporation. Depending on pulse amplitude, duration, number, repetition frequency, waveform, and tissue characteristics, membrane permeabilization may remain reversible or progress to irreversible injury and cell death. This article focuses on the fundamental biophysical principles of electroporation that underpin PFA. The article outlines how membrane charging, cell geometry, and tissue heterogeneity influence electric field distribution and biological response and explains why lesion formation depends on both field intensity and exposure conditions. It also summarizes the molecular basis of pore formation, the potential contribution of lipid peroxidation and membrane proteins, and the downstream processes linking sustained permeability to loss of homeostasis and delayed cell death. Finally, it places cardiac PFA in the broader context of electroporation-based therapies developed in oncology, drug delivery, and gene transfer, while highlighting the remaining need for cardiomyocyte-specific mechanistic evidence to further optimize safety, precision, and durability.
Abstract Pulsed field ablation (PFA) has emerged as a transformative technology in cardiac electrophysiology, offering a potentially superior safety profile compared with thermal ablation due to its non-thermal mechanism of irreversible electroporation. Clinical experience confirms a substantial reduction in traditional complications such as pulmonary vein stenosis, atrio-oesophageal fistula, and permanent phrenic nerve injury, though PFA introduces a distinct spectrum of physiologic effects requiring consideration. Coronary vasospasm is the most characteristic phenomenon, ranging from transient, subclinical constriction to rare ischaemic or arrhythmic events; mitigation relies on coronary anatomical awareness, optimized lesion placement, and prophylactic vasodilators. Haemolysis, caused by red blood cell electroporation, varies with catheter design and pulse burden and is typically mild, though high exposure and inadequate hydration may rarely lead to acute kidney injury. Silent cerebral lesions could result from procedural and/or energy-related factors, including gas formation, air ingress, catheter manipulation, and anticoagulation management, with uncertain long-term clinical impact but opportunities for technique-driven reduction. Interactions between PFA and cardiac implantable electronic devices are system- and context-dependent, with monopolar configurations and catheter-lead proximity influencing the risk of transient interference and rare permanent damage.
