Hemolysis in Pulsed Field Ablation: A Mathematical–Physical Model

Pulsed Field Ablation (PFA) is an emerging technique for the treatment of cardiac arrhythmias based on the irreversible electroporation of cardiomyocytes. It is rapidly replacing conventional thermal ablation owing to its tissue selectivity. However, its widespread clinical adoption has also highlighted several procedure-related complications. Although PFA is generally regarded as tissue-selective, increasing evidence indicates that exposing circulating blood to intense electric fields may induce red blood cell (RBC) damage and hemolysis. In this work, we develop a physics-based mathematical model to predict the extent of hemolysis during PFA procedures. The model combines a simplified representation of the electric field generated by a bipolar PFA catheter with experimentally derived hemolysis– response relationships, allowing the volume of damaged blood and free hemoglobin (fHb) release to be predicted as functions of pulse amplitude, pulse number, and device geometry. The proposed framework is consistent with both classical electroporation theory and recent clinical observations reporting a dose-dependent increase in hemolysis following PFA. The results provide a mechanistic interpretation of blood damage during PFA. Despite several simplifying assumptions, the proposed framework yields a quantitative tool for assessing hemolytic risk and may support the optimization of future PFA protocols.