Peri-Procedural Intravascular Hemolysis during Atrial Fibrillation Ablation: A Comparison of Pulsed-Field with Radiofrequency Ablation

Background Despite the favorable safety profile of pulsed-field (PF) energy during ablation of atrial fibrillation (AF), infrequent cases of renal failure, probably caused by hemolysis, have been recently described. The aim was to analyze hemolysis in patients undergoing pulmonary vein isolation (PVI) with PF ablation (PFA) or radiofrequency ablation (RFA). Methods In consecutive patients, PVI was performed with PFA or RFA. Blood samples were drawn pre-procedure, immediately post-ablation, and one day post-ablation. The concentration of red blood cell microparticles (RBCµ, fragments of damaged erythrocytes) in blood was assessed using flow cytometry (identified as CD235a and annexin V positive events). Lactate-dehydrogenase (LDH), haptoglobin and indirect bilirubin were measured at baseline and at 24 hours. Results Seventy patients (age 64.7±10.2, 47% women, 36 [51.4%] paroxysmal AF) were enrolled, 47 patients in the PFA group (22 PVI only, 36.4±5.5 PF applications vs. 25 PVI plus additional ablations, 67.3±12.4 PF applications). Twenty-three patients underwent RFA. Compared to baseline, the RBCµ concentration increased ∼ 12-fold post-PFA, and returned to baseline by 24 h (70.8 Nr/µL; 51.8-102.5 vs. 846.6; 639.2-1,215.5 vs. 59.3; 42.9-86.5 Nr/µL, p<0.001); this increase was greater in PVI-plus compared to PVI-only patients (p=0.007). There was also a significant albeit substantially smaller peri-procedural increase in RBCµ with RFA (77.7; 39.2-92.0 vs. 149.6; 106.6-180.8 vs. 89.0; 61.2-123.4,p<0.001). At 24 h with PFA, the concentration of LDH and indirect bilirubin increased, and of haptoglobin decreased highly-significantly (all p<0.001). Only smaller changes in LDH and haptoglobin concentrations (p=0.03), and no change in bilirubin concentrations were present with RFA. Conclusion PFA was associated with significant peri-procedural hemolysis. The number of PF applications should be minimized. ### Competing Interest Statement The authors have declared no competing interest. ### Clinical Trial NCT06096428 ### Funding Statement The study was supported by the project National Institute for Research of Metabolic and Cardiovascular Diseases (CarDia), Programme EXCELES, ID Project No. LX22NPO5104, funded by the European Union ? Next Generation EU, and by the Charles University Research Program ?Cooperatio ? Cardiovascular Science?. The authors declare no conflict of interest. ### Author Declarations I confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained. Yes The details of the IRB/oversight body that provided approval or exemption for the research described are given below: The study was approved by the Ethics Committee of the University Hospital Kralovske Vinohrady and was conducted in accordance with the Declaration of Helsinki. I confirm that all necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived, and that any patient/participant/sample identifiers included were not known to anyone (e.g., hospital staff, patients or participants themselves) outside the research group so cannot be used to identify individuals. Yes I understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance). Yes I have followed all appropriate research reporting guidelines, such as any relevant EQUATOR Network research reporting checklist(s) and other pertinent material, if applicable. Yes Data will be available upon reasonable request when the manuscript is published * PFA : pulsed-field ablation PVI : pulmonary vein isolation RFA : radiofrequency ablation AF : atrial fibrillation NOAC : non-vitamin K anticoagulants ICE : intracardiac echocardiography CS : coronary sinus Act : activated clotting time LIPV : left inferior pulmonary vein LA : left atrium CTI : cavotricuspid isthmus ELISA : enzyme-linked immunoassay RBC : red blood cell PFP : platelet-free plasma CD : cluster of differentiation PE : phycoerythrin FITC : fluorescein isothiocyanate FSC : forward scatter SSC : side scatter LDH : lactate dehydrogenase EDTA : ethylenediamine tetraacetic acid IQR : interquartile ranges MHz : mega Herz