Intravascular Hemolysis and the Spectrum of Tissue Injury Following Pulsed Field Ablation for Atrial Fibrillation: A Systematic Review of Clinical Markers, Catheter Designs, and Renal Outcomes

Pulsed field ablation (PFA) is a novel treatment option for atrial fibrillation (AF) that offers myocardial selectivity and tissue-specific ablation.However, its systemic effects, particularly intravascular hemolysis and potential downstream renal injury, remain incompletely characterized.This systematic review aimed to synthesize the available evidence regarding hemolysis biomarkers, renal outcomes, tissue injury, and the influence of PFA catheter design.A comprehensive literature search of PubMed, the Cochrane Library, Embase, and Scopus was conducted from inception through April 2026.Prospective, retrospective, cohort, registry-based, and cross-sectional studies evaluating systemic or renal effects following PFA for AF, including intravascular hemolysis and catheter-related outcomes, were eligible for inclusion.Outcomes of interest included hemolysis biomarkers (lactate dehydrogenase (LDH), haptoglobin, free plasma hemoglobin (fHb), and bilirubin), acute kidney injury (AKI), hemoglobinuria, and markers of tissue injury.The risk of bias in the included studies was assessed using the Risk Of Bias In Non-randomized Studies of Interventions (ROBINS-I) tool.A quantitative meta-analysis was not feasible because of substantial clinical and methodological heterogeneity and the limited availability of comparable numerical data across studies.Therefore, the findings were synthesized narratively using a qualitative synthesis approach.Nine studies involving 18,439 patients were included in the qualitative synthesis.All studies demonstrated evidence of postprocedural intravascular hemolysis.LDH increased by 63-160 U/L (p < 0.001), while haptoglobin decreased by up to 1.22 g/L (p < 0.001).fHb increased approximately 5-to 12-fold, and bilirubin levels consistently increased following PFA.Biochemical AKI occurred in 3.2-7.0% of patients and demonstrated a dose-dependent association with PFA exposure, whereas clinically severe AKI was rare (0.03%).Hemoglobinuria was reported in up to 75% of dehydrated patients in the reported study; however, the available evidence is insufficient to determine whether adequate periprocedural hydration prevents hemoglobinuria or AKI.Neurological assessments and cerebral imaging revealed limited evidence of clinically overt neurological events or radiologically detected acute cerebral ischemic injury, whereas biomarkers of myocardial injury increased following the procedure.Pentaspline catheter systems were associated with greater degrees of hemolysis and renal injury than balloon-based, circular-array, and monopolar systems, suggesting that catheter design may substantially influence systemic outcomes.PFA is consistently associated with substantial but predictable intravascular hemolysis, while clinically severe renal complications remain uncommon.The magnitude of hemolysis and renal effects appears to be influenced by procedural dose, catheter design, and hydration status.Optimization of these procedural factors, particularly adequate hydration and catheter selection, may reduce systemic effects and improve the safety profile of PFA.