Clinical Advantages and Pitfalls of Pulsed Field Ablation: How to Prevent ALH Syndrome

Catheter ablation for tachyarrhythmias was first introduced in the early 1980s using direct-current (DC) energy. Following the clinical introduction of radiofrequency (RF) ablation in the late 1980s, thermal ablation technologies became the foundation of catheter ablation because of their superior controllability, efficacy, and safety. In 2014, Wittkampf developed a DC-energy-delivery catheter system preventing electrical arcing, thereby initiating a modern "revival of DC-ablation" based on catheter ablation using electroporation. Subsequent development of high-voltage, short-duration pulse-train delivery led to the emergence of pulsed field ablation (PFA). Exposure of myocytes to high-voltage electric fields induces reversible electroporation through nanoscale pore formation within the lipid bilayer, whereas higher electric-field delivery produces irreversible electroporation, resulting in permanent membrane disruption, apoptosis, and durable lesion formation. PFA is regarded as a predominantly nonthermal and potentially tissue-selective ablation modality. Nevertheless, clinical trials of pulmonary vein isolation for atrial fibrillation have demonstrated that PFA is noninferior to conventional thermal ablation strategies, although clear superiority-other than shorter procedural times-has not yet been established. Importantly, recent studies suggest that electrode-tissue contact remains a critical determinant of durable lesion formation. Accumulating evidence indicates that PFA is associated with new complications not commonly observed with thermal ablation, including acute kidney injury, stroke, coronary vasospasm, myocardial ischemia, ventricular fibrillation, and sudden cardiac death. Although the mechanisms remain incompletely understood, hemolysis-related injury induced by high-voltage pulse delivery may represent an important contributing mechanism. Development of PFA systems capable of real-time prediction of irreversible lesion size may be essential for optimizing both procedural efficacy and safety.