BACKGROUND: Pulsed-field ablation (PFA) has emerged as a potentially safer alternative to radiofrequency ablation (RFA). However, recent studies have raised concerns that PFA may induce hemolysis, which could contribute to the development of acute kidney injury (AKI). METHODS: The PubMed, Embase, Scopus, and Cochrane databases were searched for randomized clinical trials (RCTs) and non-RCTs that reported AKI incidence and hemolysis biomarkers after PFA. Random-effects models were used to calculate pooled odds ratio (OR) and mean differences (MDs) with 95% confidence intervals (CIs). Substantial heterogeneity was defined as I2 > 25%. RESULTS: Ten studies, including one RCT, comprising a total of 3,843 patients, were included, with 1,859 in the PFA group and 1,994 in the RFA group. In the primary endpoint analysis related to AKI and renal function, no significant differences were found between the PFA and RFA groups, with PFA having a total prevalence of 2.1% (95% CI [0.90; 4.84]). The leave-one-out analysis, specifically the exclusion of one outlier study, led to the comparative results having statistical significance statistical significance (OR 3.70, 95% CI [2.49; 5.51], p = 0.0019; I² = 0%), indicating no heterogeneity, and with the total prevalence increasing to 2.4% (95% CI [0.96; 5.93]). Regarding hemolysis, all evaluated biomarkers were significantly elevated in the PFA group, although with high heterogeneity. CONCLUSION: PFA appears to be associated with a slightly higher risk of AKI than RFA. Renal injury is mostly mild-degree and transient. PFA is associated with significant peri-procedural hemolysis.

Cardiocenter University Hospital Kralovske Vinohrady Prague Czech Republic

Charles University Prague Czech Republic

Department of Biomedicine and Prevention Division of Cardiology University of Tor Vergata Rome Italy

Department of Internal Medicine Case Western Reserve University Cleveland OH United States of America

Medicine Department Medical Faculty Federal University of Goiás Goiânia Goiás Brazil

Medicine Department Medical Sciences and Life School Pontifical Catholic University of Goiás Goiânia Goiás Brazil

Texas Cardiac Arrhythmia Institute St David's Medical Center Austin TX United States of America

Zobrazit více v PubMed

Linz D, Gawalko M, Betz K, et al. Atrial fibrillation: epidemiology, screening and digital health. The Lancet Regional Health - Europe. 2024;37:100786. PubMed DOI PMC

Van Gelder IC, Rienstra M, Bunting KV, et al. 2024 ESC guidelines for the management of atrial fibrillation developed in collaboration with the European Association for Cardio-Thoracic Surgery (EACTS). Eur Heart J. 2024;45:3314–414. PubMed DOI

Tzeis S, Gerstenfeld EP, Kalman J, et al. European Heart Rhythm Association/Heart Rhythm Society/Asia Pacific Heart Rhythm Society/Latin American Heart Rhythm Society expert consensus statement on catheter and surgical ablation of atrial fibrillation. Europace. 2024;2024:26.

Reddy VY, Gerstenfeld EP, Natale A, et al. Pulsed field or conventional thermal ablation for paroxysmal atrial fibrillation. N Engl J Med. 2023;389:1660–71. PubMed DOI

Shtembari J, Shrestha DB, Pathak BD, et al. Efficacy and safety of pulsed field ablation in atrial fibrillation: a systematic review. J Clin Med. 2023;12:719. PubMed DOI PMC

Popa MA, Venier S, Menè R, et al. Characterization and Clinical Significance of Hemolysis After Pulsed Field Ablation for Atrial Fibrillation: Results of a Multicenter Analysis. Circ Arrhythm Electrophysiol. 2024;17.

de Campos MCAV, Moraes VRY, Daher RF, et al. Pulsed-field ablation versus thermal ablation for atrial fibrillation: a meta-analysis. Heart Rhythm O2. 2024;5:385–95. PubMed DOI PMC

Xu Y, Gulburak TK, Lu Y, et al. Hemolysis after pulsed-field ablation of atrial fibrillation. Heart Rhythm. 2025. https://doi.org/10.1016/j.hrthm.2025.01.021 . PubMed DOI

Venier S, Vaxelaire N, Jacon P, et al. Severe acute kidney injury related to haemolysis after pulsed field ablation for atrial fibrillation. Europace. 2023. https://doi.org/10.1093/europace/euad371 . PubMed DOI PMC

Osmancik P, Bacova B, Herman D, et al. Periprocedural intravascular hemolysis during atrial fibrillation ablation. JACC: Clinical Electrophysiology. 2024;10:1660–71. PubMed

Mohanty S, Casella M, Compagnucci P, et al. Acute kidney injury resulting from hemoglobinuria after pulsed-field ablation in atrial fibrillation. JACC: Clinical Electrophysiology. 2024;10:709–15. PubMed

Page MJ, McKenzie JE, Bossuyt PM, The PRISMA, et al. statement: an updated guideline for reporting systematic reviews. BMJ. 2020;2021: n71.

Tawfik GM, Dila KAS, Mohamed MYF, et al. A step by step guide for conducting a systematic review and meta-analysis with simulation data. Trop Med Health. 2019;47:46. PubMed DOI PMC

Ouzzani M, Hammady H, Fedorowicz Z, Elmagarmid A. Rayyan—a web and mobile app for systematic reviews. Syst Rev. 2016;5:210. PubMed DOI PMC

Section 2: AKI Definition. Kidney Int Suppl. (2011) 2012; 2:19–36.

Sterne JAC, Hernán MA, Reeves BC, et al. ROBINS-I: a tool for assessing risk of bias in non-randomised studies of interventions. BMJ. 2016;i4919-4919.

Sterne JAC, Savović J, Page MJ et al. RoB 2: a revised tool for assessing risk of bias in randomised trials. BMJ 2019;:l4898–4898.

McGuinness LA, Higgins JPT. Risk-of‐bias visualization (robvis): an R package and Shiny web app for visualizing risk‐of‐bias assessments. Res Synth Methods. 2021;12:55–61. PubMed DOI

Lin L, Chu H. Quantifying publication bias in meta-analysis. Biometrics. 2018;74:785–94. PubMed DOI

van Enst WA, Ochodo E, Scholten RJ, Hooft L, Leeflang MM. Investigation of publication bias in meta-analyses of diagnostic test accuracy: a meta-epidemiological study. BMC Med Res Methodol. 2014;14:70. PubMed DOI PMC

Higgins JPT. Measuring inconsistency in meta-analyses. BMJ. 2003;327:557–60. PubMed DOI PMC

Higgins JPT, Thomas J, Chandler J, et al editors. Cochrane Handbook for Systematic Reviews of Interventions. Wiley; 2019.

Hozo SP, Djulbegovic B, Hozo I. Estimating the mean and variance from the median, range, and the size of a sample. BMC Med Res Methodol. 2005;5:13. PubMed DOI PMC

Balduzzi S, Rücker G, Schwarzer G. How to perform a meta-analysis with R: a practical tutorial. Evid Based Ment Health. 2019;22:153–60. PubMed DOI PMC

Wan X, Wang W, Liu J, Tong T. Estimating the sample mean and standard deviation from the sample size, median, range and/or interquartile range. BMC Med Res Methodol. 2014;14:135. PubMed DOI PMC

Luo D, Wan X, Liu J, Tong T. Optimally estimating the sample mean from the sample size, median, mid-range, and/or mid-quartile range. Stat Methods Med Res. 2018;27:1785–805. PubMed DOI

auf der Heiden C, Bejinariu AG, Kelm M, Spieker M, Rana O. Hemolysis after pulsed-field ablation in pulmonary vein isolation for atrial fibrillation: A prospective controlled trial. Heart Rhythm. 2025.

Lakkireddy D, Katapadi A, Garg J, et al. NEMESIS-PFA. JACC: Clinical Electrophysiology. 2025. https://doi.org/10.1016/j.jacep.2025.04.017 . PubMed DOI

Jordan F, Knecht S, Isenegger C, et al. Acute kidney injury after catheter ablation of atrial fibrillation: comparison between different energy sources. Heart Rhythm. 2024;21:1248–9. PubMed DOI

De Smet MAJ, François C, De Becker B, et al. Intravascular haemolysis and acute kidney injury following atrial fibrillation ablation: a report using two different systems for pulsed field ablation. Europace. 2024. https://doi.org/10.1093/europace/euae251 . PubMed DOI PMC

Kawamura I, Miyazaki S, Kato R, et al. Comparison of Hemolysis with Different Pulsed Field Ablation Systems. Heart Rhythm. 2025.

Stojadinović P, Ventrella N, Alfredová H, et al. Prediction of major intravascular hemolysis during pulsed electric field ablation of atrial fibrillation using a pentaspline catheter. J Cardiovasc Electrophysiol. 2024;35:2405–10. PubMed DOI PMC

Sochorová V, Kunštátová V, OsmanČík P, et al. COnventional vs. Optimized PERiprocedural Analgosedation vs. Total IntraVEnous Anesthesia for Pulsed-Field Ablation: a Three-Arm Randomized Controlled Trial (COOPERATIVE-PFA). Circulation. 2025.

Gowda S, Desai PB, Kulkarni SS, Hull VV, Math AAK, Vernekar SN. Markers of renal function tests. N Am J Med Sci. 2010;2:170–3. PubMed PMC

Wasung ME, Chawla LS, Madero M. Biomarkers of renal function, which and when? Clin Chim Acta. 2015;438:350–7. PubMed DOI

van Veldhuisen DJ, Ruilope LM, Maisel AS, Damman K. Biomarkers of renal injury and function: diagnostic, prognostic and therapeutic implications in heart failure. Eur Heart J. 2016;37:2577–85. PubMed DOI

Hsu RK, Hsu C, McCulloch CE, et al. Research-based versus clinical serum creatinine measurements and the association of acute kidney injury with subsequent kidney function: findings from the Chronic Renal Insufficiency Cohort study. Clin Kidney J. 2020;13:55–62. PubMed DOI

Jiang S, Qian F, Ji S, et al. Pulsed field ablation for atrial fibrillation: mechanisms, advantages, and limitations. Rev Cardiovasc Med. 2024;25:138. PubMed DOI PMC

Pereira L, Nascimento P, Domingos C, blood markers related to intravascular hemolysis and pain crises in sickle cell anemia. Hematol Transfus Cell Ther. 2024;46:S84. DOI

Barcellini W, Fattizzo B. Clinical applications of hemolytic markers in the differential diagnosis and management of hemolytic anemia. Dis Markers. 2015;2015:1–7. DOI

Htay PN, Aung MH, Sin TM, et al. Pulsed field ablation: a systematic review. Health Sci Rep. 2025. https://doi.org/10.1002/hsr2.70439 . PubMed DOI PMC

Deepan N, Sripusanapan A, Prasitlumkum N, et al. Comparing efficacy and safety between pulsed field ablation, cryoballoon ablation and high-power short duration radiofrequency ablation in atrial fibrillation: a systematic review and network meta-analysis. J Interv Card Electrophysiol. 2025. https://doi.org/10.1007/s10840-025-02033-8 . PubMed DOI

Zylla MM, Mages C, Rahm A-K, et al. Comparative evaluation of 2 pulsed field ablation systems for atrial fibrillation: insights from real-world clinical implementation and short-term outcomes. Heart Rhythm. 2024.

Sugrue A, Shabtaie S, Tan NY, Maor E, Kapa S, Asirvatham SJ. Considerations regarding safety with pulsed field ablation for atrial fibrillation. Heart Rhythm O2. 2024;5:655–61. PubMed DOI PMC

Pierucci N, Mariani MV, Laviola D, et al. Pulsed field energy in atrial fibrillation ablation: from physical principles to clinical applications. J Clin Med. 2024;13:2980. PubMed DOI PMC

Ekanem E, Neuzil P, Reichlin T, et al. Safety of pulsed field ablation in more than 17,000 patients with atrial fibrillation in the MANIFEST-17K study. Nat Med. 2024;30:2020–9. PubMed DOI PMC

Van Avondt K, Nur E, Zeerleder S. Mechanisms of haemolysis-induced kidney injury. Nat Rev Nephrol. 2019;15:671–92. PubMed DOI

Lu PC, Lai HC, Liu JS. A reevaluation and discussion on the threshold limit for hemolysis in a turbulent shear flow. J Biomech. 2001;34:1361–4. PubMed DOI

Luft FC. Biomarkers and predicting acute kidney injury. Acta Physiol. 2021. https://doi.org/10.1111/apha.13479 . DOI

Strauß C, Booke H, Forni L, Zarbock A. Biomarkers of acute kidney injury: from discovery to the future of clinical practice. J Clin Anesth. 2024;95:111458. PubMed DOI