Intravascular Hemolysis and Pulsed-Field Ablation: State of the Art Review

Intravascular hemolysis (IH) has emerged as a potential complication of pulsed-field ablation (PFA), yet reported incidence varies widely. This review synthesizes the clinical and preclinical literature, using an empirical framework to provide practical recommendations. We systematically evaluated all available human and translational PFA-IH studies from 2020 to 2025 according to 3 physiologic criteria: 1) biomarker kinetics; 2) determinants of energy delivery; and 3) clinical workflow. Each study was assigned an interpretability rating based on timing of sampling and biomarkers used to define IH (green, yellow, or red). Of the 53 studies reviewed, 34 were excluded, leaving 19 (16 in vivo, 3 in vitro) for assessment. Most (8) studies assessed received a yellow interpretability rating, 2 a red interpretability rating , and 6 a green interpretability rating. Although laboratory-defined severe IH (free plasma hemoglobin >100 mg/dL) was noted, the incidence of complications, namely, acute renal failure, remained low. IH following PFA is common but rarely clinically consequential, and its impact appears modifiable. Technology selection should align with ablation strategy, reserving large-footprint catheters for pulmonary vein isolation and favoring smaller footprint catheters for focal or linear ablation to minimize unintended energy delivery. A dose-dependent relationship underscores the need to limit applications to those required for acute success and ensure tissue contact with each delivery. Patient-specific vulnerability, particularly in those with renal dysfunction or hemodynamic compromise, should guide procedural planning and periprocedural optimization. Routine biomarker testing is not warranted, but selective screening in higher-risk scenarios may help identify clinically relevant IH.