Variable-Loop Circular vs. Pentaspline Catheter: Hemolysis Outcomes in Pulsed-Field Ablation Procedures for Atrial Fibrillation

Variable-Loop Circular vs. Pentaspline Catheter: Hemolysis Outcomes in Pulsed-Field Ablation Procedures for Atrial Fibrillation | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Advisory Board Help Center Sign In Submit a Preprint Cite Share Download PDF Research Article Variable-Loop Circular vs. Pentaspline Catheter: Hemolysis Outcomes in Pulsed-Field Ablation Procedures for Atrial Fibrillation Marek Hozman, Pavel Osmančík, Barbora Bačová, Jakub Karch, Jana Veselá, and 6 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-7897511/v1 This work is licensed under a CC BY 4.0 License Status: Published Journal Publication published 19 Feb, 2026 Read the published version in Journal of Interventional Cardiac Electrophysiology → Version 1 posted You are reading this latest preprint version Abstract Purpose To compare the extent of intravascular hemolysis, quantified by red blood cell microparticles (RBCµs), between patients undergoing pulsed-field ablation (PFA) for atrial fibrillation (AF) with a variable-loop circular catheter (VLCC) and those treated with a pentaspline catheter (PSC). Methods This prospective, single-center observational study included three cohorts of patients undergoing first-time AF ablation: (1) pulmonary vein isolation (PVI) by the PSC (PSC PVI), (2) PVI plus posterior wall and/or mitral isthmus by the PSC (PSC PVI+), and (3) PVI plus posterior wall by the VLCC (VLCC PVI+). Blood samples were collected at baseline, immediately post-ablation, and 24 hours after the procedure to measure RBCµs and other biochemical markers. Results The study included 77 patients (64.2 ± 9.5 years, 42.9% female): 22, 25 and 30 in the PSC PVI, PSC PVI+, and VLCC PVI + groups, respectively. All groups exhibited a significant transient rise in RBCµs concentration immediately after ablation (p < 0.001), returning to baseline within 24 hours. Peak RBCµs levels were highest in the PSC PVI + group, followed by PSC PVI and VLCC PVI+ (all pairwise comparisons p < 0.001). The total number of applications was highest in the PS PVI + group and lowest in the VLCC PVI + group, correlating with the magnitude of hemolysis. Conclusions The VLCC used in persistent AF ablation was linked to lower levels of intravascular hemolysis compared to the PS catheter employed in cases of paroxysmal and persistent AF. atrial fibrillation pulsed-field ablation hemolysis red blood cell microparticles Figures Figure 1 1. Introduction Pulsed-field ablation (PFA) is the latest modality of nonpharmacological treatment for atrial fibrillation (AF). Unlike conventional thermal energy sources like radiofrequency or cryoablation, it increases cell membrane permeability through a high-intensity electrical field, ultimately leading to cell death. PFA has been shown to be non-inferior in efficacy compared to conventional modalities. Moreover, it causes less collateral damage due to its partial tissue selectivity 1 . However, several energy-specific safety concerns, including hemolysis, coronary spasms, and silent cerebral lesions, need to be addressed in PFA procedures. In vitro studies demonstrated cell disruption at the electrical field of 1,000 V/cm for erythrocytes compared to 1,500 V/cm for cardiomyocytes 2 . A positive correlation exists between the extent of intravascular hemolysis and the number of pulsed-field (PF) applications 3 . Importantly, due to the toxicity of free heme, severe hemolysis might even cause acute renal failure 4 . Patients with persistent AF who require more applications and frequently have preexisting renal impairment are at the highest risk 5 . There is a notable difference in pulse configuration among vendors of PFA systems, which affects the level of red blood cell destruction. Hemolysis has long been quantified using traditional markers, such as lactate dehydrogenase (LDH) and haptoglobin concentrations. However, the levels of both markers can be influenced by conditions other than hemolysis—LDH can be elevated due to myocardial damage, while haptoglobin levels can be affected by inflammation. In contrast, measuring circulating red blood cell microparticles (RBCµs) using flow cytometry provides a specific and sensitive method for detecting red blood cell destruction, making it one of the most reliable indicators of intravascular hemolysis. It's important to note that the pulse configuration of PFA systems varies among different vendors, which may lead to differing effects on red blood cell destruction. The main goal of this analysis was to compare the extent of intravascular hemolysis in patients with persistent AF who underwent ablation using a variable-loop circular catheter (VLCC), with two groups of patients treated with a pentaspline catheter (PSC): those with paroxysmal and those with persistent AF. 2. Methods 2.1. Study Design This study was a prospective, non-randomized, observational research conducted at a single center. The patient population consisted of two cohorts. The first group included patients with paroxysmal and persistent AF who underwent ablation using a PSC, enrolled from October 2023 to May 2024. The second group included patients with persistent AF who underwent ablation using a VLCC, enrolled from January to June 2025 due to the delayed availability of the VLCC. The study was approved by the Ethics Committee of the University Hospital Kralovské Vinohrady and was conducted in accordance with the Declaration of Helsinki. Each participant provided informed consent. The study was registered before the enrolment phase on clinicaltrials.gov (NCT06801392). 2.2. Study Population Patients with symptomatic paroxysmal or non-paroxysmal AF indicated for a first-ever AF ablation procedure were recruited. Inclusion criteria were the presence of symptomatic paroxysmal or non-paroxysmal AF, age above 18 years, and signed informed consent. Exclusion criteria were as follows: symptomatic heart failure with a left ventricular ejection fraction of < 30%; untreated chronic obstructive pulmonary disease; history of left atrial (LA) ablation; and the presence of any malignant, significant hematologic, or chronic hepatic disease. Only patients with persistent AF were included in the VLCC cohort, as the VLCC was primarily utilized for ablation of persistent AF during the study period. Patients were divided into three groups based on the ablation modality and lesion set used during the procedure: PSC PVI (PVI only by PSC), PSC PVI+ (PVI with additional LA lesions by PSC), VLCC PVI+ (PVI and posterior wall by VLCC). 2.3. Ablation Procedures All patients had been on anticoagulation for at least one month, with only the morning dose withheld on the day of ablation. Femoral venous access was achieved under ultrasound guidance, and all procedures were performed under intracardiac echocardiography guidance (AcuNav, Siemens, Erlangen, Germany). An initial 5,000 IU heparin bolus was administered before the transseptal puncture, followed by 10,000–15,000 IU (depending on body weight) after the puncture, aiming to maintain an activated clotting time above 350 seconds throughout the procedure. 2.3.1. Pentaspline Catheter Groups Ablation was conducted using the FARAPULSE™ system (Boston Scientific, MA, US). The dedicated FARASTAR™ generator operates at a 2 kV output, and each ablation consists of five biphasic bipolar trains of pulses, each lasting 200 ms, separated by 300 ms pauses. In all cases, a 31 mm PSC was utilized. Paroxysmal AF patients (PSC PVI group) received PVI only (four “basket” and four “flower” applications per vein). If an entrance or exit block was not present, additional PF applications were delivered. In patients with non-paroxysmal AF (PSC PVI + group), PVI was combined with LA posterior wall and, in selected cases, with mitral isthmus ablation. LA posterior wall ablation consisted of at least two rows of overlapping lesions that connected the left and right pulmonary veins and was verified by the loss of signals on the PSC or by exit block. The mitral isthmus was ablated between the posterior aspect of the left atrial appendage and the mitral annulus. Conduction block across the mitral line was assessed by differential pacing. In patients with documented typical atrial flutter, a cavotricuspid isthmus line was also performed by PFA. 2.3.2. Variable-Loop Circular Catheter Group In the VLCC PVI + group, the procedures were conducted using the VARIPULSE™ system (Biosense Webster, CA, USA). The variable-loop circular catheter was utilized for both mapping and ablation. During one ablation, the electrical field of 1.8 kV is delivered in a bipolar, biphasic configuration with three 250-ms trains of pulses separated by 10-second pauses. An electroanatomical map (CARTO 3™, Biosense Webster, CA, USA) was created before the ablation phase. Each pulmonary vein received four ablations: two in “closed loop” and two in “open loop” configurations. Caution was taken to cover the gaps between the proximal and distal electrodes by rotating the catheter. Following PVI, a left atrial posterior wall ablation was performed in all cases, with one ablation per site and a lesion overlap of approximately 20%. After a 20-minute observation period, the durability of the lesions was assessed using electroanatomic remapping, with additional ablation performed if necessary. If touch-up applications were utilized, another 20-minute reassessment of lesion durability was conducted. 2.4. Blood Samples and Laboratory Analysis 2.4.1. Blood Sampling Blood samples were collected from fasting patients at three points: (T1) baseline (from the F-11 sheath), (T2) post-ablation (from the same sheath), and (T3) one day after the ablation (from the antecubital vein). The first 5 mL of blood was discarded for each sample. Samples from antecubital veins were drawn without tourniquets. The concentration of red blood cell microparticles (RBCµs) was measured at all three time points, whilst other hemolytic markers (lactate dehydrogenase [LDH], haptoglobin) were assessed at baseline and 24 hours later (T1 and T3). For safety reasons, creatinine concentration was measured at timepoints T1 and T3 in every patient. Flow cytometry, biochemistry, and hematology were performed within three hours of collection. 2.4.2. Flow Cytometry The concentration of RBCµs (fragments of damaged erythrocytes) was assessed from samples of citrated whole blood using flow cytometry (identified as CD235a- and annexin V–positive events). 2.5. Statistical Considerations Since there were no prior reports on the extent of hemolysis associated with the VLCC at the start of the study, the sample size was determined based on the initial results from the first 10 patients in the VLCC PVI + and PSC PVI groups. Our calculations (Cohen's d = 0.95) indicate that a sample size of 22 patients per group would provide 80% power to detect a 2.5% (Bonferroni correction for a three-group design) two-tailed significance level. Data were reported as mean and standard deviation (SD) or median and interquartile range (IQR) for normal or skewed distributions, respectively. Paired samples were compared using the Friedman test, followed by the pairwise comparison using the Dunn’s test with the Bonferroni correction. Non-paired samples were analyzed using either the Kruskal-Wallis test or a one-way analysis of variance (ANOVA), depending on the data distribution. A two-sided P-value < 0.05 was considered significant. For statistical computations, we used the R software 6 . 3. Results 3.1. Patient Population and Procedural Characteristics A total of 77 patients were included in the study: 22 in the PSC PVI group, 25 in the PSC PVI + group, and 30 in the VLCC PVI + group. The mean age of the participants was 64.2 years (SD 9.5), with 33 individuals (42.9%) being female. The median CHA 2 DS 2 -VASc score was 3.0 (IQR 2.0–3.0). As expected, patients with persistent atrial fibrillation (AF) in both the PSC PVI + and VLCC groups had a higher incidence of previous electrical cardioversion, as well as a greater number of patients with heart failure with preserved ejection fraction. Consequently, LA diameter was significantly smaller in the PSC PVI group compared to the other two groups. Other baseline characteristics were comparable among the study groups (see Table 1 ). Table 1 Baseline characteristics; BMI = body mass index, CHA 2 DS 2 -VASc = Congestive Heart Failure, Hypertension, Age, Diabetes, Stroke, Vascular Disease, Sex Category (stroke risk score), LA = left atrium, LVEF – Left Ventricular Ejection Fraction, LVEDd – Left Ventricular End-Diastolic Diameter PSC PVI No. 22 PSC PVI + No. 25 VLCC PVI + No. 30 p-value Age (years) 59.8 (± 9.4) 66.3 (± 9.5) 65.6 (± 8.7) 0.18 Female sex 10 (45.5%) 9 (36.0%) 14 (46.7%) 0.71 BMI (kg/m 2 ) 28.5 (± 4.2) 31.2 (± 5.5) 30.9 (± 6.2) 0.45 Heart failure 2 (9.1%) 6 (24.0%) 18 (60.0%) < 0.001 Diabetes 2 (9.1%) 7 (28.0%) 5 (16.7%) 0.24 Coronary artery disease 0.0 (± 0.0) 0.1 (± 0.3) 0.0 (± 0.2) 0.49 CHA 2 DS 2 -VASc 2.0 (1.0–3.0) 2.0 (2.0–3.0) 3.0 (2.0–4.0) 0.06 Cardioversion 2 (9.1%) 20 (80.0%) 27 (90.0%) < 0.001 Previous ablation 0 (0.0%) 3 (12.0%) 2 (6.7%) 0.31 N of antiarrhythmic drugs 0.12 0 6 (27.3%) 1 (4.0%) 2 (6.7%) 1 11 (50.0%) 13 (52.0%) 19 (63.3%) 2 5 (22.7%) 10 (40.0%) 9 (30.0%) 3 0 (0.0%) 1 (4.0%) 0 (0.0%) LVEDd (mm) 49.2 (± 4.7) 51.4 (± 5.8) 50.5 (± 5.6) 0.36 LVEF (%) 60.5 (± 2.6) 57.7 (± 7.2) 56.0 (± 6.2) 0.11 LA diameter (mm) 39.0 (± 4.2) 44.6 (± 5.4) 46.1 (± 5.8) 0.01 Hemoglobin (g/L) 140.4 (± 9.6) 141.7 (± 9.9) 138.6 (± 13.2) 0.51 Creatinine (µmol/L) 82.0 (± 15.4) 100.2 (± 23.8) 82.0 (± 19.9) 0.41 Categorical data displayed as counts (percentage) and continuous data as mean (SD) or median (IQR) in parametric or skewed data, respectively The procedure data are summarized in Table 2 . There were significant differences among all groups in terms of the total number of applications (p < 0.001 for all comparisons), with the highest count in the PSC PVI + cohort and the lowest in the VLCC PVI + cohort. Additionally, the PSC PVI + group exhibited a higher prevalence of mitral isthmus ablation compared to both the VLCC PVI + group and the PSC PVI group. Furthermore, the shortest procedure duration was recorded in the PSC PVI group Table 2 Procedure characteristics; LA = left atrium, PV = pulmonary veins PSC PVI No. 22 PSC PVI + No. 25 VLCC PVI + No. 30 p-value Procedure duration (min) 49.7 (± 14.2) 63.4 (± 13.5) 103.1 (± 21.8) 0.04 Fluoroscopy time (s) 5.9 (± 2.3) 8.1 (± 3.4) 5.8 (± 3.6) 0.42 LA dwell time (min) 30.3 (± 10.6) 41.0 (± 14.2) 84.3 (± 18.5) 0.04 PV applications 33.0 (32.0–38.5) 33.0 (32.0–34.0) 16.0 (16.0–16.0) < 0.001 Total N of ablations 32.0 (25.0–59.0) 64.0 (60.0–74.0) 24.0 (20.0–25.0) < 0.001 Mitral isthmus ablation 0 (0.0%) 24 (96.0%) 0 (0.0%) < 0.001 Categorical data displayed as counts (percentage) and continuous data as mean (SD) or median (IQR) in parametric or skewed data, respectively 3.2. Laboratory Parameters Red Blood Cell Microparticles All groups exhibited a significant increase in RBCµs count immediately after ablation (T2 sample), returning to baseline levels within 24 hours post-procedure (p < 0.001 for all groups). The peak RBCµs count was highest in the PSC PVI + cohort, followed by the PSC PVI and VLCC PVI + groups, with all comparisons between the groups being statistically significant (Table 3 ). Table 3 Red Blood Cell Microparticles Group RBCµs / µL p–value (T1 vs. T2) p–value (T2 vs. T3) p–value (T1 vs. T3) T1 T2 T3 PSC PVI 65.3 (42.6–85.8) 657.0 (505.6–998.0) 53.9 (41.0–84.5) < 0.001 0.9 PSC PVI+ 74.9 (62.7–102.5) 924.1 (758.6–1355.5) 66.1 (47.8–81.9) < 0.001 < 0.001 0.22 VLCC PVI+ 43.4 (24.1–49.4) 403.4 (315.2–530.3) 42.6 (25.2–66.2) < 0.001 0.9 Data displayed as median (IQR) Other Markers of Intravascular Hemolysis A significant increase (p < 0.001 for all groups) in LDH levels after ablation was observed in all three groups when comparing T1 and T3 measurements (Table 4 ). When comparing the T3 values among the study groups, the PSC PVI + group had significantly higher LDH levels compared to both the PSC PVI group (p = 0.003) and the VLCC PVI + group (p 0.9). Table 4 Lactate Dehydrogenase Levels; LDH = lactate dehydrogenase Group LDH (µkat/L) p–value (T1 vs. T3) T1 T3 PSC PVI 2.6 (2.4–2.8) 4.2 (3.8–4.6) < 0.001 PSC PVI+ 2.8 (2.5–2.9) 5.2 (4.4–5.9) < 0.001 VLCC PVI+ 2.8 (2.4–3.0) 3.9 (3.7–4.3) < 0.001 When comparing T1 haptoglobin levels to post-ablation T3 levels, all groups showed a significant decline (Table 5 ). However, the differences in the minimal values among the study groups did not reach statistical significance (p = 0.06). Table 5 Haptoglobin Levels Group Haptoglobin (g/L) p–value (T1 vs. T3) T1 T3 PSC PVI 1.1 (0.9–1.4) 0.6 (0.3–0.9) < 0.001 PSC PVI+ 1.2 (0.9–1.6) 0.4 (0.2–0.6) < 0.001 VLCC PVI+ 1.0 (0.8–1.4) 0.5 (0.3–0.9) < 0.001 Creatinine Concentration The T3 creatinine levels showed no significant difference from baseline values in either group. The mean differences (T3 minus T1) observed in the PSC PVI, PSC PVI+, and VLCC PVI + cohorts were − 2.4 (± 17.2), -5.44 (± 13.8), and − 4.07 (± 6.22) µmol/L, respectively. 4. Discussion In this observational study involving 77 patients, we found that the use of a VLCC resulted in less intravascular hemolysis compared to the PSC. Notably, the level of intravascular hemolysis was lower even when the VLCC was used for PVI combined with posterior wall ablation, as compared to a strategy using only PVI with the PSC. It is important to highlight that VLCC usage was linked to the fewest applications. The number of applications is a widely acknowledged predictor of intravascular hemolysis 7 8 . However, focusing solely on this aspect would be a mistake, as other factors—such as pulse configuration, catheter design, and catheter-tissue contact—may also influence the degree of hemolysis associated with a specific PFA system. All PFA systems have different pulse configuration settings. Specifically, while the voltage and pulse train duration are similar in the PSC and the VLCC (2 kV and 200ms vs. 1.8 kV and 250ms), the applications differ in the number and duration of pulses, as well as the time interval between them (5 pulses and 300ms vs. 3 pulses and 10s). The threshold for pulsed electric fields is lower in erythrocytes compared to cardiomyocytes, with values of 1000 V/cm and 1500 V/cm, respectively, as recently demonstrated in vitro by Fišerová and colleagues 2 . This indicates that any pulse capable of causing cell death in cardiomyocytes should also lead to red blood cell disruption. However, variations in the number of pulses and the interval between them could potentially affect the volume of blood impacted and, consequently, the level of hemolysis. Another important issue is catheter-tissue contact. Nies et al. demonstrated in a swine model that, even after just four no-contact PF applications, the level of intravascular hemolysis (measured by cell-free hemoglobin) was significantly greater compared to lesions with good catheter-tissue contact 9 . Platforms with integrated electroanatomical mapping systems can provide superior catheter-tissue contact compared to those guided solely by sciascopy or intracardiac echocardiography. The VARIPULSE™ system, part of the CARTO™ environment, enables tissue contact assessment through a real-time impedance indicator called TPI (Tissue Proximity Indicator). During patient enrollment for this trial, the FARAPULSE™ system was utilized without electroanatomical mapping. PFA systems vary significantly in catheter design, which adds another key variable to consider. Differences exist in electrode size, distribution, and spacing, significantly affecting the electrical field during procedures. Belalcazar and Heist conducted an insightful in silico simulation on this subject, comparing various catheter designs 10 . They measured the proportion of energy delivered to the target tissue during application. A lower percentage indicates that more energy is absorbed by non-target tissues, such as blood. The authors concluded that the energy delivered to the target tissue is 3% for the PS basket and 6% for the variable loop design. Although all previously mentioned variables likely contribute to the lower hemolysis level associated with the VLCC when compared to the PSC, the most significant factor appears to be the total number of applications. Several clinical trials have demonstrated that the number of applications is a key predictor of intravascular hemolysis 3 , 5 , 7 , 8 . Two important factors account for the significant difference between the two tested catheters: first, the minimum recommended number of applications for PVI alone is lower for the VLCC (16 versus 32). Second, the design of the PSC allows for more non-PV ablations, such as mitral isthmus, significantly increasing the total number of ablations in this cohort. The difference in intravascular hemolysis levels between the two PFA systems emphasizes a key point in the current era of catheter ablations: PFA systems can differ greatly in various aspects. Therefore, further direct comparisons in both efficacy and safety are essential. 4.1. Study limitations Several limitations of the study should be noted. The most important one is the significant difference in the total number of PF applications between the study groups, which was influenced by the recommended workflow for each system. This discrepancy makes it challenging to assess the impact of other variables that may affect hemolysis levels. Additionally, the absence of a paroxysmal VLCC cohort is another limitation. Analyzing this cohort with the lowest number of applications could provide important data relevant to the topic. 5. Conclusions In this single-center observational study, the use of a variable-loop circular catheter for pulsed-field ablation was associated with a significantly lower degree of intravascular hemolysis compared with the pentaspline catheter. This finding was observed despite the inclusion of posterior wall ablation in all variable-loop circular catheter cases, suggesting that factors beyond ablation extent—such as pulse configuration, catheter design, and the total number of applications—play a substantial role in determining hemolytic burden. Abbreviations AF – Atrial Fibrillation ANOVA – Analysis of Variance BMI – Body Mass Index CARTO – Electroanatomical Mapping System (CARTO 3™) CHA 2 DS 2 -VASc – Congestive Heart Failure, Hypertension, Age, Diabetes, Stroke, Vascular Disease, Sex Category (stroke risk score) CTI – Cavotricuspid Isthmus IQR – Interquartile Range LA – Left Atrium / Left Atrial LDH – Lactate Dehydrogenase LVEF – Left Ventricular Ejection Fraction LVEDd – Left Ventricular End-Diastolic Diameter PFA – Pulsed-Field Ablation PF – Pulsed-Field PSC – Pentaspline Catheter PVI – Pulmonary Vein Isolation RBCµs – Red Blood Cell Microparticles SD – Standard Deviation TPI – Tissue Proximity Indication VLCC – Variable-Loop Circular Catheter Declarations Disclosures The authors declare no conflict of interest related to the topic. Author Contribution M.H. wrote the main manuscript, while D.H. and P.O. reviewed it. B.B. performed the laboratory analyses, and J.K., L.P., J.V., V.F., S.H., and J. Hornof conducted the procedures. J. Hoznamová handled the data analysis. 6. Sources of Funding The work was supported by the Charles University Research program “Cooperatio–Cardiovascular Science,” and 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. References Koruth J, Kuroki K, Iwasawa J, Enomoto Y, Viswanathan R, Brose R, et al. Preclinical Evaluation of Pulsed Field Ablation. Circ Arrhythm Electrophysiol Am Heart Association. 2019;12:e007781. Fiserova I, Fiser O, Novak M, Trnka J, Gibalova A, Kvapil D, et al. Significant hemolysis is present during irreversible electroporation of cardiomyocytes in vitro. Heart Rhythm Elsevier; 2025;22:466–74. Stojadinović P, Ventrella N, Alfredová H, Wichterle D, Peichl P, Čihák R et al. Prediction of major intravascular hemolysis during pulsed electric field ablation of atrial fibrillation using a pentaspline catheter. J Cardiovasc Electrophysiol John Wiley and Sons Inc; 2024;35:2405. Mohanty S, Casella M, Compagnucci P, Torlapati PG, Rocca DG, Della, Fazia VM, La, et al. Acute Kidney Injury Resulting From Hemoglobinuria After Pulsed-Field Ablation in Atrial Fibrillation: Is it Preventable? JACC Clin Electrophysiol Elsevier Inc. 2024;10:709–15. Lakkireddy D, Katapadi A, Garg J, Herink E, Klotz M, Ganta J, et al. NEMESIS-PFA: Investigating Collateral Tissue Injury Associated With Pulsed Field Ablation. Clinical Electrophysiology American College of Cardiology FoundationWashington D.C.; 2025. R Core Team. (2025). R: A Language and Environment for Statistical Computing. R Foundation for Statistical Computing, Vienna, Austria.; 2025. Osmancik P, Bacova B, Herman D, Hozman M, Fiserova I, Hassouna S, et al. Periprocedural Intravascular Hemolysis During Atrial Fibrillation Ablation: A Comparison of Pulsed Field With Radiofrequency Ablation. Volume 10. JACC Clin Electrophysiol Elsevier Inc.; 2024. pp. 1660–71. Popa MA, Venier S, Menè R, Rocca DG, Della, Sacher F, Derval N, et al. Characterization and Clinical Significance of Hemolysis After Pulsed Field Ablation for Atrial Fibrillation: Results of a Multicenter Analysis. Volume 17. Circ Arrhythm Electrophysiol Lippincott Williams & WilkinsHagerstown, MD;; 2024. p. e012732. Nies M, Koruth JS, Mlček M, Watanabe K, Tibenská VC, Královec Š, et al. Hemolysis After Pulsed Field Ablation: Impact of Lesion Number and Catheter-Tissue Contact. Circ Arrhythm Electrophysiol Circ Arrhythm Electrophysiol. 2024;17:e012765. Belalcazar A, Heist EK. Comparison of efficiency of PFA catheter designs by computer modeling. J Cardiovasc Electrophysiol J Cardiovasc Electrophysiol. 2024;35:2382–93. Additional Declarations No competing interests reported. Cite Share Download PDF Status: Published Journal Publication published 19 Feb, 2026 Read the published version in Journal of Interventional Cardiac Electrophysiology → Version 1 posted You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. As a division of Research Square Company, we’re committed to making research communication faster, fairer, and more useful. We do this by developing innovative software and high quality services for the global research community. Our growing team is made up of researchers and industry professionals working together to solve the most critical problems facing scientific publishing. Also discoverable on Platform About Our Team In Review Editorial Policies Advisory Board Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {"props":{"pageProps":{"initialData":{"identity":"rs-7897511","acceptedTermsAndConditions":true,"allowDirectSubmit":true,"archivedVersions":[],"articleType":"Research Article","associatedPublications":[],"authors":[{"id":539307331,"identity":"20bd3f6c-bfef-4a89-9720-dff616bba171","order_by":0,"name":"Marek Hozman","email":"","orcid":"","institution":"Charles University Prague and University Hospital Kralovske Vinohrady","correspondingAuthor":false,"prefix":"","firstName":"Marek","middleName":"","lastName":"Hozman","suffix":""},{"id":539307332,"identity":"07ba26fe-707c-4ff8-a0d7-20d2869a1bfd","order_by":1,"name":"Pavel Osmančík","email":"","orcid":"","institution":"Charles University Prague and University Hospital Kralovske Vinohrady","correspondingAuthor":false,"prefix":"","firstName":"Pavel","middleName":"","lastName":"Osmančík","suffix":""},{"id":539307333,"identity":"5b16eab4-9c0c-44cd-a3e8-f024b067b61d","order_by":2,"name":"Barbora Bačová","email":"","orcid":"","institution":"The Institute of Hematology and Blood Transfusion","correspondingAuthor":false,"prefix":"","firstName":"Barbora","middleName":"","lastName":"Bačová","suffix":""},{"id":539307334,"identity":"bfc5059e-4bac-4603-b04c-0fa000520341","order_by":3,"name":"Jakub Karch","email":"","orcid":"","institution":"Charles University Prague and University Hospital Kralovske Vinohrady","correspondingAuthor":false,"prefix":"","firstName":"Jakub","middleName":"","lastName":"Karch","suffix":""},{"id":539307335,"identity":"c2efd312-bdc8-43a4-804b-36d46a5a195d","order_by":4,"name":"Jana Veselá","email":"","orcid":"","institution":"Charles University Prague and University Hospital Kralovske 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Vinohrady","correspondingAuthor":false,"prefix":"","firstName":"Jana","middleName":"","lastName":"Hozmanová","suffix":""},{"id":539307339,"identity":"8d74257f-ef58-42c6-b0f6-941611e353a1","order_by":8,"name":"Sabri Hassouna","email":"","orcid":"","institution":"Charles University Prague and University Hospital Kralovske Vinohrady","correspondingAuthor":false,"prefix":"","firstName":"Sabri","middleName":"","lastName":"Hassouna","suffix":""},{"id":539307340,"identity":"0f7fc6d0-4770-4d8a-acaf-41036e064547","order_by":9,"name":"Josef Hornof","email":"","orcid":"","institution":"Charles University Prague and University Hospital Kralovske Vinohrady","correspondingAuthor":false,"prefix":"","firstName":"Josef","middleName":"","lastName":"Hornof","suffix":""},{"id":539307341,"identity":"c37fda01-b80c-4687-a93d-91fd641f26ff","order_by":10,"name":"Dalibor Heřman","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAAA6UlEQVRIie3QvQrCMBDA8ZNCXFpd46DPcJMiiM8SEToLLk5SETK1u4/h6BgJ2CXataXgx6Cbk4uCgoof6GB0dMh/CRl+HHcAJtM/JixPXl+8fWt5sL+SzBtxC94vxHoh8jvJheOebHXmUMkG6+FhFNGKrRD2x8+koBqeHKg2VP2wnAQqpdXAx4yvGYXiQhzOAGOXxA5PuxgRZgHVkGh1J4sNSU58Rm8ENSR+TiEkdbigOO0LC5hml3h13YXZqFySFnmTopJi7IvPJBc15a7VYSUMJyTZ8vqFNHpL3cUevV9IM8NkMplMv3QGMEBZrS31hL4AAAAASUVORK5CYII=","orcid":"","institution":"Charles University Prague and University Hospital Kralovske Vinohrady","correspondingAuthor":true,"prefix":"","firstName":"Dalibor","middleName":"","lastName":"Heřman","suffix":""}],"badges":[],"createdAt":"2025-10-19 09:08:23","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-7897511/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-7897511/v1","draftVersion":[],"editorialEvents":[{"content":"https://doi.org/10.1007/s10840-026-02244-7","type":"published","date":"2026-02-19T15:59:04+00:00"}],"editorialNote":"","failedWorkflow":false,"files":[{"id":95173146,"identity":"823460cd-fa74-44bc-8159-154f9e6de96a","added_by":"auto","created_at":"2025-11-05 06:41:08","extension":"docx","order_by":0,"title":"","display":"","copyAsset":false,"role":"acdc-reference","size":276610,"visible":true,"origin":"","legend":"","description":"","filename":"manuscriptfinal.docx","url":"https://assets-eu.researchsquare.com/files/rs-7897511/v1/fa61875c360f166e1480f5b9.docx"},{"id":95173144,"identity":"2c33a9a9-ab09-4ffd-8986-fedf57045b50","added_by":"auto","created_at":"2025-11-05 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06:41:08","extension":"html","order_by":6,"title":"","display":"","copyAsset":false,"role":"acdc-reference","size":80484,"visible":true,"origin":"","legend":"","description":"","filename":"earlyproof.html","url":"https://assets-eu.researchsquare.com/files/rs-7897511/v1/108db24229c5f7b639fc355d.html"},{"id":95226604,"identity":"31e1bc5e-111e-4235-ab9f-5f23c7f239a3","added_by":"auto","created_at":"2025-11-05 16:31:27","extension":"jpeg","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":433291,"visible":true,"origin":"","legend":"\u003cp\u003eTop - Red Blood Cell microparticles Per Study Group; Bottom: Number of Pulsed-Field Applications per Study Group, PF = pulsed-field\u003c/p\u003e","description":"","filename":"floatimage1.jpeg","url":"https://assets-eu.researchsquare.com/files/rs-7897511/v1/538f3b94ee49b0d4e91d2d7c.jpeg"},{"id":103251582,"identity":"9d4cc93f-e9ef-4395-a452-ca5cd22d2ea5","added_by":"auto","created_at":"2026-02-23 16:10:55","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":1292550,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-7897511/v1/ace79fe4-f7de-4a71-9e94-247cd49afdd9.pdf"}],"financialInterests":"No competing interests reported.","formattedTitle":"Variable-Loop Circular vs. Pentaspline Catheter: Hemolysis Outcomes in Pulsed-Field Ablation Procedures for Atrial Fibrillation","fulltext":[{"header":"1. Introduction","content":"\u003cp\u003ePulsed-field ablation (PFA) is the latest modality of nonpharmacological treatment for atrial fibrillation (AF). Unlike conventional thermal energy sources like radiofrequency or cryoablation, it increases cell membrane permeability through a high-intensity electrical field, ultimately leading to cell death. PFA has been shown to be non-inferior in efficacy compared to conventional modalities. Moreover, it causes less collateral damage due to its partial tissue selectivity\u003csup\u003e\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e\u003c/sup\u003e. However, several energy-specific safety concerns, including hemolysis, coronary spasms, and silent cerebral lesions, need to be addressed in PFA procedures.\u003c/p\u003e\u003cp\u003e\u003cem\u003eIn vitro\u003c/em\u003e studies demonstrated cell disruption at the electrical field of 1,000 V/cm for erythrocytes compared to 1,500 V/cm for cardiomyocytes\u003csup\u003e\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e\u003c/sup\u003e. A positive correlation exists between the extent of intravascular hemolysis and the number of pulsed-field (PF) applications\u003csup\u003e\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e\u003c/sup\u003e. Importantly, due to the toxicity of free heme, severe hemolysis might even cause acute renal failure \u003csup\u003e\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e\u003c/sup\u003e. Patients with persistent AF who require more applications and frequently have preexisting renal impairment are at the highest risk \u003csup\u003e\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e\u003c/sup\u003e.\u003c/p\u003e\u003cp\u003eThere is a notable difference in pulse configuration among vendors of PFA systems, which affects the level of red blood cell destruction.\u003c/p\u003e\u003cp\u003eHemolysis has long been quantified using traditional markers, such as lactate dehydrogenase (LDH) and haptoglobin concentrations. However, the levels of both markers can be influenced by conditions other than hemolysis\u0026mdash;LDH can be elevated due to myocardial damage, while haptoglobin levels can be affected by inflammation.\u003c/p\u003e\u003cp\u003eIn contrast, measuring circulating red blood cell microparticles (RBC\u0026micro;s) using flow cytometry provides a specific and sensitive method for detecting red blood cell destruction, making it one of the most reliable indicators of intravascular hemolysis.\u003c/p\u003e\u003cp\u003eIt's important to note that the pulse configuration of PFA systems varies among different vendors, which may lead to differing effects on red blood cell destruction.\u003c/p\u003e\u003cp\u003eThe main goal of this analysis was to compare the extent of intravascular hemolysis in patients with persistent AF who underwent ablation using a variable-loop circular catheter (VLCC), with two groups of patients treated with a pentaspline catheter (PSC): those with paroxysmal and those with persistent AF.\u003c/p\u003e"},{"header":"2. Methods","content":"\u003cdiv id=\"Sec3\" class=\"Section2\"\u003e\u003ch2\u003e2.1. Study Design\u003c/h2\u003e\u003cp\u003eThis study was a prospective, non-randomized, observational research conducted at a single center. The patient population consisted of two cohorts. The first group included patients with paroxysmal and persistent AF who underwent ablation using a PSC, enrolled from October 2023 to May 2024. The second group included patients with persistent AF who underwent ablation using a VLCC, enrolled from January to June 2025 due to the delayed availability of the VLCC.\u003c/p\u003e\u003cp\u003e The study was approved by the Ethics Committee of the University Hospital Kralovsk\u0026eacute; Vinohrady and was conducted in accordance with the Declaration of Helsinki. Each participant provided informed consent. The study was registered before the enrolment phase on clinicaltrials.gov (NCT06801392).\u003c/p\u003e\u003c/div\u003e\u003cdiv id=\"Sec4\" class=\"Section2\"\u003e\u003ch2\u003e2.2. Study Population\u003c/h2\u003e\u003cp\u003ePatients with symptomatic paroxysmal or non-paroxysmal AF indicated for a first-ever AF ablation procedure were recruited. Inclusion criteria were the presence of symptomatic paroxysmal or non-paroxysmal AF, age above 18 years, and signed informed consent. Exclusion criteria were as follows: symptomatic heart failure with a left ventricular ejection fraction of \u0026lt;\u0026thinsp;30%; untreated chronic obstructive pulmonary disease; history of left atrial (LA) ablation; and the presence of any malignant, significant hematologic, or chronic hepatic disease.\u003c/p\u003e\u003cp\u003eOnly patients with persistent AF were included in the VLCC cohort, as the VLCC was primarily utilized for ablation of persistent AF during the study period.\u003c/p\u003e\u003cp\u003ePatients were divided into three groups based on the ablation modality and lesion set used during the procedure: PSC PVI (PVI only by PSC), PSC PVI+ (PVI with additional LA lesions by PSC), VLCC PVI+ (PVI and posterior wall by VLCC).\u003c/p\u003e\u003c/div\u003e\u003cdiv id=\"Sec5\" class=\"Section2\"\u003e\u003ch2\u003e2.3. Ablation Procedures\u003c/h2\u003e\u003cp\u003eAll patients had been on anticoagulation for at least one month, with only the morning dose withheld on the day of ablation. Femoral venous access was achieved under ultrasound guidance, and all procedures were performed under intracardiac echocardiography guidance (AcuNav, Siemens, Erlangen, Germany). An initial 5,000 IU heparin bolus was administered before the transseptal puncture, followed by 10,000\u0026ndash;15,000 IU (depending on body weight) after the puncture, aiming to maintain an activated clotting time above 350 seconds throughout the procedure.\u003c/p\u003e\u003cdiv id=\"Sec6\" class=\"Section3\"\u003e\u003ch2\u003e2.3.1. Pentaspline Catheter Groups\u003c/h2\u003e\u003cp\u003eAblation was conducted using the FARAPULSE\u0026trade; system (Boston Scientific, MA, US). The dedicated FARASTAR\u0026trade; generator operates at a 2 kV output, and each ablation consists of five biphasic bipolar trains of pulses, each lasting 200 ms, separated by 300 ms pauses. In all cases, a 31 mm PSC was utilized.\u003c/p\u003e\u003cp\u003eParoxysmal AF patients (PSC PVI group) received PVI only (four \u0026ldquo;basket\u0026rdquo; and four \u0026ldquo;flower\u0026rdquo; applications per vein). If an entrance or exit block was not present, additional PF applications were delivered.\u003c/p\u003e\u003cp\u003eIn patients with non-paroxysmal AF (PSC PVI\u0026thinsp;+\u0026thinsp;group), PVI was combined with LA posterior wall and, in selected cases, with mitral isthmus ablation. LA posterior wall ablation consisted of at least two rows of overlapping lesions that connected the left and right pulmonary veins and was verified by the loss of signals on the PSC or by exit block. The mitral isthmus was ablated between the posterior aspect of the left atrial appendage and the mitral annulus. Conduction block across the mitral line was assessed by differential pacing.\u003c/p\u003e\u003cp\u003eIn patients with documented typical atrial flutter, a cavotricuspid isthmus line was also performed by PFA.\u003c/p\u003e\u003c/div\u003e\u003cdiv id=\"Sec7\" class=\"Section3\"\u003e\u003ch2\u003e2.3.2. Variable-Loop Circular Catheter Group\u003c/h2\u003e\u003cp\u003eIn the VLCC PVI\u0026thinsp;+\u0026thinsp;group, the procedures were conducted using the VARIPULSE\u0026trade; system (Biosense Webster, CA, USA). The variable-loop circular catheter was utilized for both mapping and ablation. During one ablation, the electrical field of 1.8 kV is delivered in a bipolar, biphasic configuration with three 250-ms trains of pulses separated by 10-second pauses.\u003c/p\u003e\u003cp\u003eAn electroanatomical map (CARTO 3\u0026trade;, Biosense Webster, CA, USA) was created before the ablation phase. Each pulmonary vein received four ablations: two in \u0026ldquo;closed loop\u0026rdquo; and two in \u0026ldquo;open loop\u0026rdquo; configurations. Caution was taken to cover the gaps between the proximal and distal electrodes by rotating the catheter. Following PVI, a left atrial posterior wall ablation was performed in all cases, with one ablation per site and a lesion overlap of approximately 20%. After a 20-minute observation period, the durability of the lesions was assessed using electroanatomic remapping, with additional ablation performed if necessary. If touch-up applications were utilized, another 20-minute reassessment of lesion durability was conducted.\u003c/p\u003e\u003c/div\u003e\u003c/div\u003e\u003cdiv id=\"Sec8\" class=\"Section2\"\u003e\u003ch2\u003e2.4. Blood Samples and Laboratory Analysis\u003c/h2\u003e\u003cdiv id=\"Sec9\" class=\"Section3\"\u003e\u003ch2\u003e2.4.1. Blood Sampling\u003c/h2\u003e\u003cp\u003eBlood samples were collected from fasting patients at three points: (T1) baseline (from the F-11 sheath), (T2) post-ablation (from the same sheath), and (T3) one day after the ablation (from the antecubital vein). The first 5 mL of blood was discarded for each sample. Samples from antecubital veins were drawn without tourniquets. The concentration of red blood cell microparticles (RBC\u0026micro;s) was measured at all three time points, whilst other hemolytic markers (lactate dehydrogenase [LDH], haptoglobin) were assessed at baseline and 24 hours later (T1 and T3). For safety reasons, creatinine concentration was measured at timepoints T1 and T3 in every patient. Flow cytometry, biochemistry, and hematology were performed within three hours of collection.\u003c/p\u003e\u003c/div\u003e\u003cdiv id=\"Sec10\" class=\"Section3\"\u003e\u003ch2\u003e2.4.2. Flow Cytometry\u003c/h2\u003e\u003cp\u003eThe concentration of RBC\u0026micro;s (fragments of damaged erythrocytes) was assessed from samples of citrated whole blood using flow cytometry (identified as CD235a- and annexin V\u0026ndash;positive events).\u003c/p\u003e\u003c/div\u003e\u003c/div\u003e\u003cdiv id=\"Sec11\" class=\"Section2\"\u003e\u003ch2\u003e2.5. Statistical Considerations\u003c/h2\u003e\u003cp\u003eSince there were no prior reports on the extent of hemolysis associated with the VLCC at the start of the study, the sample size was determined based on the initial results from the first 10 patients in the VLCC PVI\u0026thinsp;+\u0026thinsp;and PSC PVI groups. Our calculations (Cohen's d\u0026thinsp;=\u0026thinsp;0.95) indicate that a sample size of 22 patients per group would provide 80% power to detect a 2.5% (Bonferroni correction for a three-group design) two-tailed significance level.\u003c/p\u003e\u003cp\u003eData were reported as mean and standard deviation (SD) or median and interquartile range (IQR) for normal or skewed distributions, respectively. Paired samples were compared using the Friedman test, followed by the pairwise comparison using the Dunn\u0026rsquo;s test with the Bonferroni correction. Non-paired samples were analyzed using either the Kruskal-Wallis test or a one-way analysis of variance (ANOVA), depending on the data distribution. A two-sided P-value\u0026thinsp;\u0026lt;\u0026thinsp;0.05 was considered significant. For statistical computations, we used the R software\u003csup\u003e\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e\u003c/sup\u003e.\u003c/p\u003e\u003c/div\u003e"},{"header":"3. Results","content":"\u003cdiv id=\"Sec13\" class=\"Section2\"\u003e\u003ch2\u003e3.1. Patient Population and Procedural Characteristics\u003c/h2\u003e\u003cp\u003eA total of 77 patients were included in the study: 22 in the PSC PVI group, 25 in the PSC PVI\u0026thinsp;+\u0026thinsp;group, and 30 in the VLCC PVI\u0026thinsp;+\u0026thinsp;group. The mean age of the participants was 64.2 years (SD 9.5), with 33 individuals (42.9%) being female. The median CHA\u003csub\u003e2\u003c/sub\u003eDS\u003csub\u003e2\u003c/sub\u003e-VASc score was 3.0 (IQR 2.0\u0026ndash;3.0). As expected, patients with persistent atrial fibrillation (AF) in both the PSC PVI\u0026thinsp;+\u0026thinsp;and VLCC groups had a higher incidence of previous electrical cardioversion, as well as a greater number of patients with heart failure with preserved ejection fraction. Consequently, LA diameter was significantly smaller in the PSC PVI group compared to the other two groups. Other baseline characteristics were comparable among the study groups (see Table\u0026nbsp;\u003cspan refid=\"Tab1\" class=\"InternalRef\"\u003e1\u003c/span\u003e).\u003c/p\u003e\u003cp\u003e\u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab1\" border=\"1\"\u003e\u003ccaption language=\"En\"\u003e\u003cdiv class=\"CaptionNumber\"\u003eTable 1\u003c/div\u003e\u003cdiv class=\"CaptionContent\"\u003e\u003cp\u003eBaseline characteristics; BMI\u0026thinsp;=\u0026thinsp;body mass index, CHA\u003csub\u003e2\u003c/sub\u003eDS\u003csub\u003e2\u003c/sub\u003e-VASc\u0026thinsp;=\u0026thinsp;Congestive Heart Failure, Hypertension, Age, Diabetes, Stroke, Vascular Disease, Sex Category (stroke risk score), LA\u0026thinsp;=\u0026thinsp;left atrium, LVEF \u0026ndash; Left Ventricular Ejection Fraction, LVEDd \u0026ndash; Left Ventricular End-Diastolic Diameter\u003c/p\u003e\u003c/div\u003e\u003c/caption\u003e\u003ccolgroup cols=\"5\"\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c5\" colnum=\"5\"\u003e\u003c/div\u003e\u003cthead\u003e\u003ctr\u003e\u003cth align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/th\u003e\u003cth align=\"left\" colname=\"c2\"\u003e\u003cp\u003ePSC PVI\u003c/p\u003e\u003cp\u003eNo. 22\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c3\"\u003e\u003cp\u003ePSC PVI\u0026thinsp;+\u0026thinsp;\u003c/p\u003e\u003cp\u003eNo. 25\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c4\"\u003e\u003cp\u003eVLCC PVI\u0026thinsp;+\u0026thinsp;\u003c/p\u003e\u003cp\u003eNo. 30\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c5\"\u003e\u003cp\u003ep-value\u003c/p\u003e\u003c/th\u003e\u003c/tr\u003e\u003c/thead\u003e\u003ctbody\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eAge (years)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e59.8 (\u0026plusmn;\u0026thinsp;9.4)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e66.3 (\u0026plusmn;\u0026thinsp;9.5)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e65.6 (\u0026plusmn;\u0026thinsp;8.7)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e0.18\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eFemale sex\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e10 (45.5%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e9 (36.0%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e14 (46.7%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e0.71\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eBMI (kg/m\u003csup\u003e2\u003c/sup\u003e)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e28.5 (\u0026plusmn;\u0026thinsp;4.2)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e31.2 (\u0026plusmn;\u0026thinsp;5.5)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e30.9 (\u0026plusmn;\u0026thinsp;6.2)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e0.45\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eHeart failure\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e2 (9.1%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e6 (24.0%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e18 (60.0%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e\u0026lt;\u0026thinsp;0.001\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eDiabetes\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e2 (9.1%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e7 (28.0%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e5 (16.7%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e0.24\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eCoronary artery disease\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e0.0 (\u0026plusmn;\u0026thinsp;0.0)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e0.1 (\u0026plusmn;\u0026thinsp;0.3)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e0.0 (\u0026plusmn;\u0026thinsp;0.2)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e0.49\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eCHA\u003csub\u003e2\u003c/sub\u003eDS\u003csub\u003e2\u003c/sub\u003e-VASc\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e2.0 (1.0\u0026ndash;3.0)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e2.0 (2.0\u0026ndash;3.0)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e3.0 (2.0\u0026ndash;4.0)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e0.06\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eCardioversion\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e2 (9.1%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e20 (80.0%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e27 (90.0%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e\u0026lt;\u0026thinsp;0.001\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003ePrevious ablation\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e0 (0.0%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e3 (12.0%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e2 (6.7%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e0.31\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eN of antiarrhythmic drugs\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colspan=\"3\" nameend=\"c4\" namest=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e\u003cb\u003e0.12\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e0\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e6 (27.3%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e1 (4.0%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e2 (6.7%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e1\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e11 (50.0%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e13 (52.0%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e19 (63.3%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e2\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e5 (22.7%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e10 (40.0%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e9 (30.0%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e3\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e0 (0.0%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e1 (4.0%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e0 (0.0%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eLVEDd (mm)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e49.2 (\u0026plusmn;\u0026thinsp;4.7)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e51.4 (\u0026plusmn;\u0026thinsp;5.8)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e50.5 (\u0026plusmn;\u0026thinsp;5.6)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e0.36\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eLVEF (%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e60.5 (\u0026plusmn;\u0026thinsp;2.6)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e57.7 (\u0026plusmn;\u0026thinsp;7.2)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e56.0 (\u0026plusmn;\u0026thinsp;6.2)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e0.11\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eLA diameter (mm)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e39.0 (\u0026plusmn;\u0026thinsp;4.2)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e44.6 (\u0026plusmn;\u0026thinsp;5.4)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e46.1 (\u0026plusmn;\u0026thinsp;5.8)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e0.01\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eHemoglobin (g/L)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e140.4 (\u0026plusmn;\u0026thinsp;9.6)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e141.7 (\u0026plusmn;\u0026thinsp;9.9)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e138.6 (\u0026plusmn;\u0026thinsp;13.2)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e0.51\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eCreatinine (\u0026micro;mol/L)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e82.0 (\u0026plusmn;\u0026thinsp;15.4)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e100.2 (\u0026plusmn;\u0026thinsp;23.8)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e82.0 (\u0026plusmn;\u0026thinsp;19.9)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e0.41\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colspan=\"5\" nameend=\"c5\" namest=\"c1\"\u003e\u003cp\u003eCategorical data displayed as counts (percentage) and continuous data as mean (SD) or median (IQR) in parametric or skewed data, respectively\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003c/tbody\u003e\u003c/colgroup\u003e\u003c/table\u003e\u003c/div\u003e\u003c/p\u003e\u003cp\u003eThe procedure data are summarized in Table\u0026nbsp;\u003cspan refid=\"Tab2\" class=\"InternalRef\"\u003e2\u003c/span\u003e. There were significant differences among all groups in terms of the total number of applications (p\u0026thinsp;\u0026lt;\u0026thinsp;0.001 for all comparisons), with the highest count in the PSC PVI\u0026thinsp;+\u0026thinsp;cohort and the lowest in the VLCC PVI\u0026thinsp;+\u0026thinsp;cohort. Additionally, the PSC PVI\u0026thinsp;+\u0026thinsp;group exhibited a higher prevalence of mitral isthmus ablation compared to both the VLCC PVI\u0026thinsp;+\u0026thinsp;group and the PSC PVI group. Furthermore, the shortest procedure duration was recorded in the PSC PVI group\u003c/p\u003e\u003cp\u003e\u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab2\" border=\"1\"\u003e\u003ccaption language=\"En\"\u003e\u003cdiv class=\"CaptionNumber\"\u003eTable 2\u003c/div\u003e\u003cdiv class=\"CaptionContent\"\u003e\u003cp\u003eProcedure characteristics; LA\u0026thinsp;=\u0026thinsp;left atrium, PV\u0026thinsp;=\u0026thinsp;pulmonary veins\u003c/p\u003e\u003c/div\u003e\u003c/caption\u003e\u003ccolgroup cols=\"5\"\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c5\" colnum=\"5\"\u003e\u003c/div\u003e\u003cthead\u003e\u003ctr\u003e\u003cth align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/th\u003e\u003cth align=\"left\" colname=\"c2\"\u003e\u003cp\u003ePSC PVI\u003c/p\u003e\u003cp\u003eNo. 22\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c3\"\u003e\u003cp\u003ePSC PVI\u0026thinsp;+\u0026thinsp;\u003c/p\u003e\u003cp\u003eNo. 25\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c4\"\u003e\u003cp\u003eVLCC PVI\u0026thinsp;+\u0026thinsp;\u003c/p\u003e\u003cp\u003eNo. 30\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c5\"\u003e\u003cp\u003ep-value\u003c/p\u003e\u003c/th\u003e\u003c/tr\u003e\u003c/thead\u003e\u003ctbody\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eProcedure duration (min)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e49.7 (\u0026plusmn;\u0026thinsp;14.2)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e63.4 (\u0026plusmn;\u0026thinsp;13.5)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e103.1 (\u0026plusmn;\u0026thinsp;21.8)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e0.04\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eFluoroscopy time (s)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e5.9 (\u0026plusmn;\u0026thinsp;2.3)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e8.1 (\u0026plusmn;\u0026thinsp;3.4)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e5.8 (\u0026plusmn;\u0026thinsp;3.6)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e0.42\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eLA dwell time (min)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e30.3 (\u0026plusmn;\u0026thinsp;10.6)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e41.0 (\u0026plusmn;\u0026thinsp;14.2)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e84.3 (\u0026plusmn;\u0026thinsp;18.5)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e0.04\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003ePV applications\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e33.0 (32.0\u0026ndash;38.5)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e33.0 (32.0\u0026ndash;34.0)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e\u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"No\" id=\"Taba\" border=\"1\"\u003e\u003ccolgroup cols=\"2\"\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e\u003ctbody\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e16.0 (16.0\u0026ndash;16.0)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003c/tbody\u003e\u003c/colgroup\u003e\u003c/table\u003e\u003c/div\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e\u0026lt;\u0026thinsp;0.001\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eTotal N of ablations\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e32.0 (25.0\u0026ndash;59.0)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e64.0 (60.0\u0026ndash;74.0)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e24.0 (20.0\u0026ndash;25.0)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e\u0026lt;\u0026thinsp;0.001\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eMitral isthmus ablation\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e0 (0.0%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e24 (96.0%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e0 (0.0%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e\u0026lt;\u0026thinsp;0.001\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colspan=\"5\" nameend=\"c5\" namest=\"c1\"\u003e\u003cp\u003eCategorical data displayed as counts (percentage) and continuous data as mean (SD) or median (IQR) in parametric or skewed data, respectively\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003c/tbody\u003e\u003c/colgroup\u003e\u003c/table\u003e\u003c/div\u003e\u003c/p\u003e\u003c/div\u003e\u003cdiv id=\"Sec14\" class=\"Section2\"\u003e\u003ch2\u003e3.2. Laboratory Parameters\u003c/h2\u003e\u003cp\u003e\u003cb\u003eRed Blood Cell Microparticles\u003c/b\u003e\u003c/p\u003e\u003cp\u003eAll groups exhibited a significant increase in RBC\u0026micro;s count immediately after ablation (T2 sample), returning to baseline levels within 24 hours post-procedure (p\u0026thinsp;\u0026lt;\u0026thinsp;0.001 for all groups). The peak RBC\u0026micro;s count was highest in the PSC PVI\u0026thinsp;+\u0026thinsp;cohort, followed by the PSC PVI and VLCC PVI\u0026thinsp;+\u0026thinsp;groups, with all comparisons between the groups being statistically significant (Table\u0026nbsp;\u003cspan refid=\"Tab3\" class=\"InternalRef\"\u003e3\u003c/span\u003e).\u003c/p\u003e\u003cp\u003e\u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab3\" border=\"1\"\u003e\u003ccaption language=\"En\"\u003e\u003cdiv class=\"CaptionNumber\"\u003eTable 3\u003c/div\u003e\u003cdiv class=\"CaptionContent\"\u003e\u003cp\u003eRed Blood Cell Microparticles\u003c/p\u003e\u003c/div\u003e\u003c/caption\u003e\u003ccolgroup cols=\"7\"\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c5\" colnum=\"5\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c6\" colnum=\"6\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c7\" colnum=\"7\"\u003e\u003c/div\u003e\u003cthead\u003e\u003ctr\u003e\u003cth align=\"left\" colname=\"c1\" morerows=\"1\" rowspan=\"2\"\u003e\u003cp\u003eGroup\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colspan=\"3\" nameend=\"c4\" namest=\"c2\"\u003e\u003cp\u003eRBC\u0026micro;s / \u0026micro;L\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c5\" morerows=\"1\" rowspan=\"2\"\u003e\u003cp\u003ep\u0026ndash;value \u003c/p\u003e\u003cp\u003e(T1 vs. T2)\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c6\" morerows=\"1\" rowspan=\"2\"\u003e\u003cp\u003ep\u0026ndash;value \u003c/p\u003e\u003cp\u003e(T2 vs. T3)\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c7\" morerows=\"1\" rowspan=\"2\"\u003e\u003cp\u003ep\u0026ndash;value \u003c/p\u003e\u003cp\u003e(T1 vs. T3)\u003c/p\u003e\u003c/th\u003e\u003c/tr\u003e\u003ctr\u003e\u003cth align=\"left\" colname=\"c2\"\u003e\u003cp\u003eT1\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c3\"\u003e\u003cp\u003eT2\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c4\"\u003e\u003cp\u003eT3\u003c/p\u003e\u003c/th\u003e\u003c/tr\u003e\u003c/thead\u003e\u003ctbody\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003ePSC PVI\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e65.3 (42.6\u0026ndash;85.8)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e657.0 (505.6\u0026ndash;998.0)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e53.9 (41.0\u0026ndash;84.5)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e\u0026lt;\u0026thinsp;0.001\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e\u0026lt;\u0026thinsp;0.001\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u003cp\u003e\u0026gt;\u0026thinsp;0.9\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003ePSC PVI+\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e74.9 (62.7\u0026ndash;102.5)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e924.1 (758.6\u0026ndash;1355.5)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e66.1 (47.8\u0026ndash;81.9)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e\u0026lt;\u0026thinsp;0.001\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e\u0026lt;\u0026thinsp;0.001\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u003cp\u003e0.22\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eVLCC PVI+\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e43.4 (24.1\u0026ndash;49.4)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e403.4 (315.2\u0026ndash;530.3)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e42.6 (25.2\u0026ndash;66.2)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e\u0026lt;\u0026thinsp;0.001\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e\u0026lt;\u0026thinsp;0.001\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u003cp\u003e\u0026gt;\u0026thinsp;0.9\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colspan=\"7\" nameend=\"c7\" namest=\"c1\"\u003e\u003cp\u003eData displayed as median (IQR)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003c/tbody\u003e\u003c/colgroup\u003e\u003c/table\u003e\u003c/div\u003e\u003c/p\u003e\u003cp\u003e\u003cb\u003eOther Markers of Intravascular Hemolysis\u003c/b\u003e\u003c/p\u003e\u003cp\u003eA significant increase (p\u0026thinsp;\u0026lt;\u0026thinsp;0.001 for all groups) in LDH levels after ablation was observed in all three groups when comparing T1 and T3 measurements (Table\u0026nbsp;\u003cspan refid=\"Tab4\" class=\"InternalRef\"\u003e4\u003c/span\u003e). When comparing the T3 values among the study groups, the PSC PVI\u0026thinsp;+\u0026thinsp;group had significantly higher LDH levels compared to both the PSC PVI group (p\u0026thinsp;=\u0026thinsp;0.003) and the VLCC PVI\u0026thinsp;+\u0026thinsp;group (p\u0026thinsp;\u0026lt;\u0026thinsp;0.001). However, no significant difference was observed between the PSC PVI group and the VLCC PVI\u0026thinsp;+\u0026thinsp;group (p\u0026thinsp;\u0026gt;\u0026thinsp;0.9).\u003c/p\u003e\u003cp\u003e\u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab4\" border=\"1\"\u003e\u003ccaption language=\"En\"\u003e\u003cdiv class=\"CaptionNumber\"\u003eTable 4\u003c/div\u003e\u003cdiv class=\"CaptionContent\"\u003e\u003cp\u003eLactate Dehydrogenase Levels; LDH\u0026thinsp;=\u0026thinsp;lactate dehydrogenase\u003c/p\u003e\u003c/div\u003e\u003c/caption\u003e\u003ccolgroup cols=\"4\"\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e\u003cthead\u003e\u003ctr\u003e\u003cth align=\"left\" colname=\"c1\" morerows=\"1\" rowspan=\"2\"\u003e\u003cp\u003eGroup\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colspan=\"2\" nameend=\"c3\" namest=\"c2\"\u003e\u003cp\u003eLDH (\u0026micro;kat/L)\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c4\"\u003e\u003cp\u003ep\u0026ndash;value \u003c/p\u003e\u003cp\u003e(T1 vs. T3)\u003c/p\u003e\u003c/th\u003e\u003c/tr\u003e\u003ctr\u003e\u003cth align=\"left\" colname=\"c2\"\u003e\u003cp\u003eT1\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c3\"\u003e\u003cp\u003eT3\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/th\u003e\u003c/tr\u003e\u003c/thead\u003e\u003ctbody\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003ePSC PVI\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e2.6 (2.4\u0026ndash;2.8)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e4.2 (3.8\u0026ndash;4.6)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e\u0026lt;\u0026thinsp;0.001\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003ePSC PVI+\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e2.8 (2.5\u0026ndash;2.9)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e5.2 (4.4\u0026ndash;5.9)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e\u0026lt;\u0026thinsp;0.001\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eVLCC PVI+\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e2.8 (2.4\u0026ndash;3.0)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e3.9 (3.7\u0026ndash;4.3)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e\u0026lt;\u0026thinsp;0.001\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003c/tbody\u003e\u003c/colgroup\u003e\u003c/table\u003e\u003c/div\u003e\u003c/p\u003e\u003cp\u003eWhen comparing T1 haptoglobin levels to post-ablation T3 levels, all groups showed a significant decline (Table\u0026nbsp;\u003cspan refid=\"Tab5\" class=\"InternalRef\"\u003e5\u003c/span\u003e). However, the differences in the minimal values among the study groups did not reach statistical significance (p\u0026thinsp;=\u0026thinsp;0.06).\u003c/p\u003e\u003cp\u003e\u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab5\" border=\"1\"\u003e\u003ccaption language=\"En\"\u003e\u003cdiv class=\"CaptionNumber\"\u003eTable 5\u003c/div\u003e\u003cdiv class=\"CaptionContent\"\u003e\u003cp\u003eHaptoglobin Levels\u003c/p\u003e\u003c/div\u003e\u003c/caption\u003e\u003ccolgroup cols=\"4\"\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e\u003cthead\u003e\u003ctr\u003e\u003cth align=\"left\" colname=\"c1\" morerows=\"1\" rowspan=\"2\"\u003e\u003cp\u003eGroup\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colspan=\"2\" nameend=\"c3\" namest=\"c2\"\u003e\u003cp\u003eHaptoglobin (g/L)\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c4\"\u003e\u003cp\u003ep\u0026ndash;value \u003c/p\u003e\u003cp\u003e(T1 vs. T3)\u003c/p\u003e\u003c/th\u003e\u003c/tr\u003e\u003ctr\u003e\u003cth align=\"left\" colname=\"c2\"\u003e\u003cp\u003eT1\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c3\"\u003e\u003cp\u003eT3\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/th\u003e\u003c/tr\u003e\u003c/thead\u003e\u003ctbody\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003ePSC PVI\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e1.1 (0.9\u0026ndash;1.4)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e0.6 (0.3\u0026ndash;0.9)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e\u0026lt;\u0026thinsp;0.001\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003ePSC PVI+\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e1.2 (0.9\u0026ndash;1.6)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e0.4 (0.2\u0026ndash;0.6)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e\u0026lt;\u0026thinsp;0.001\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eVLCC PVI+\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e1.0 (0.8\u0026ndash;1.4)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e0.5 (0.3\u0026ndash;0.9)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e\u0026lt;\u0026thinsp;0.001\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003c/tbody\u003e\u003c/colgroup\u003e\u003c/table\u003e\u003c/div\u003e\u003c/p\u003e\u003cp\u003e\u003cb\u003eCreatinine Concentration\u003c/b\u003e\u003c/p\u003e\u003cp\u003eThe T3 creatinine levels showed no significant difference from baseline values in either group. The mean differences (T3 minus T1) observed in the PSC PVI, PSC PVI+, and VLCC PVI\u0026thinsp;+\u0026thinsp;cohorts were \u0026minus;\u0026thinsp;2.4 (\u0026plusmn;\u0026thinsp;17.2), -5.44 (\u0026plusmn;\u0026thinsp;13.8), and \u0026minus;\u0026thinsp;4.07 (\u0026plusmn;\u0026thinsp;6.22) \u0026micro;mol/L, respectively.\u003c/p\u003e\u003c/div\u003e"},{"header":"4. Discussion","content":"\u003cp\u003eIn this observational study involving 77 patients, we found that the use of a VLCC resulted in less intravascular hemolysis compared to the PSC. Notably, the level of intravascular hemolysis was lower even when the VLCC was used for PVI combined with posterior wall ablation, as compared to a strategy using only PVI with the PSC. It is important to highlight that VLCC usage was linked to the fewest applications.\u003c/p\u003e\u003cp\u003eThe number of applications is a widely acknowledged predictor of intravascular hemolysis \u003csup\u003e7 8\u003c/sup\u003e. However, focusing solely on this aspect would be a mistake, as other factors\u0026mdash;such as pulse configuration, catheter design, and catheter-tissue contact\u0026mdash;may also influence the degree of hemolysis associated with a specific PFA system.\u003c/p\u003e\u003cp\u003eAll PFA systems have different pulse configuration settings. Specifically, while the voltage and pulse train duration are similar in the PSC and the VLCC (2 kV and 200ms vs. 1.8 kV and 250ms), the applications differ in the number and duration of pulses, as well as the time interval between them (5 pulses and 300ms vs. 3 pulses and 10s). The threshold for pulsed electric fields is lower in erythrocytes compared to cardiomyocytes, with values of 1000 V/cm and 1500 V/cm, respectively, as recently demonstrated \u003cem\u003ein vitro\u003c/em\u003e by Fišerov\u0026aacute; and colleagues \u003csup\u003e\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e\u003c/sup\u003e. This indicates that any pulse capable of causing cell death in cardiomyocytes should also lead to red blood cell disruption. However, variations in the number of pulses and the interval between them could potentially affect the volume of blood impacted and, consequently, the level of hemolysis.\u003c/p\u003e\u003cp\u003eAnother important issue is catheter-tissue contact. Nies et al. demonstrated in a swine model that, even after just four no-contact PF applications, the level of intravascular hemolysis (measured by cell-free hemoglobin) was significantly greater compared to lesions with good catheter-tissue contact \u003csup\u003e\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e\u003c/sup\u003e. Platforms with integrated electroanatomical mapping systems can provide superior catheter-tissue contact compared to those guided solely by sciascopy or intracardiac echocardiography. The VARIPULSE\u0026trade; system, part of the CARTO\u0026trade; environment, enables tissue contact assessment through a real-time impedance indicator called TPI (Tissue Proximity Indicator). During patient enrollment for this trial, the FARAPULSE\u0026trade; system was utilized without electroanatomical mapping.\u003c/p\u003e\u003cp\u003ePFA systems vary significantly in catheter design, which adds another key variable to consider. Differences exist in electrode size, distribution, and spacing, significantly affecting the electrical field during procedures. Belalcazar and Heist conducted an insightful \u003cem\u003ein silico\u003c/em\u003e simulation on this subject, comparing various catheter designs \u003csup\u003e\u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e\u003c/sup\u003e. They measured the proportion of energy delivered to the target tissue during application. A lower percentage indicates that more energy is absorbed by non-target tissues, such as blood. The authors concluded that the energy delivered to the target tissue is 3% for the PS basket and 6% for the variable loop design.\u003c/p\u003e\u003cp\u003eAlthough all previously mentioned variables likely contribute to the lower hemolysis level associated with the VLCC when compared to the PSC, the most significant factor appears to be the total number of applications. Several clinical trials have demonstrated that the number of applications is a key predictor of intravascular hemolysis\u003csup\u003e\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e,\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e,\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e,\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e\u003c/sup\u003e. Two important factors account for the significant difference between the two tested catheters: first, the minimum recommended number of applications for PVI alone is lower for the VLCC (16 versus 32). Second, the design of the PSC allows for more non-PV ablations, such as mitral isthmus, significantly increasing the total number of ablations in this cohort.\u003c/p\u003e\u003cp\u003eThe difference in intravascular hemolysis levels between the two PFA systems emphasizes a key point in the current era of catheter ablations: PFA systems can differ greatly in various aspects. Therefore, further direct comparisons in both efficacy and safety are essential.\u003c/p\u003e\u003cdiv id=\"Sec16\" class=\"Section2\"\u003e\u003ch2\u003e4.1. Study limitations\u003c/h2\u003e\u003cp\u003eSeveral limitations of the study should be noted. The most important one is the significant difference in the total number of PF applications between the study groups, which was influenced by the recommended workflow for each system. This discrepancy makes it challenging to assess the impact of other variables that may affect hemolysis levels. Additionally, the absence of a paroxysmal VLCC cohort is another limitation. Analyzing this cohort with the lowest number of applications could provide important data relevant to the topic.\u003c/p\u003e\u003c/div\u003e"},{"header":"5. Conclusions","content":"\u003cp\u003eIn this single-center observational study, the use of a variable-loop circular catheter for pulsed-field ablation was associated with a significantly lower degree of intravascular hemolysis compared with the pentaspline catheter. This finding was observed despite the inclusion of posterior wall ablation in all variable-loop circular catheter cases, suggesting that factors beyond ablation extent\u0026mdash;such as pulse configuration, catheter design, and the total number of applications\u0026mdash;play a substantial role in determining hemolytic burden.\u003c/p\u003e"},{"header":"Abbreviations","content":"\u003cul type=\"disc\"\u003e\n \u003cli\u003e\u003cstrong\u003eAF\u003c/strong\u003e \u0026ndash; Atrial Fibrillation\u003c/li\u003e\n \u003cli\u003e\u003cstrong\u003eANOVA\u003c/strong\u003e \u0026ndash; Analysis of Variance\u003c/li\u003e\n \u003cli\u003e\u003cstrong\u003eBMI\u003c/strong\u003e \u0026ndash; Body Mass Index\u003c/li\u003e\n \u003cli\u003e\u003cstrong\u003eCARTO\u003c/strong\u003e \u0026ndash; Electroanatomical Mapping System (CARTO 3\u0026trade;)\u003c/li\u003e\n \u003cli\u003e\u003cstrong\u003eCHA\u003csub\u003e2\u003c/sub\u003eDS\u003csub\u003e2\u003c/sub\u003e-VASc\u003c/strong\u003e \u0026ndash; Congestive Heart Failure, Hypertension, Age, Diabetes, Stroke, Vascular Disease, Sex Category (stroke risk score)\u003c/li\u003e\n \u003cli\u003e\u003cstrong\u003eCTI\u003c/strong\u003e \u0026ndash; Cavotricuspid Isthmus\u003c/li\u003e\n \u003cli\u003e\u003cstrong\u003eIQR\u003c/strong\u003e \u0026ndash; Interquartile Range\u003c/li\u003e\n \u003cli\u003e\u003cstrong\u003eLA\u003c/strong\u003e \u0026ndash; Left Atrium / Left Atrial\u003c/li\u003e\n \u003cli\u003e\u003cstrong\u003eLDH\u003c/strong\u003e \u0026ndash; Lactate Dehydrogenase\u003c/li\u003e\n \u003cli\u003e\u003cstrong\u003eLVEF\u003c/strong\u003e \u0026ndash; Left Ventricular Ejection Fraction\u003c/li\u003e\n \u003cli\u003e\u003cstrong\u003eLVEDd\u003c/strong\u003e \u0026ndash; Left Ventricular End-Diastolic Diameter\u003c/li\u003e\n \u003cli\u003e\u003cstrong\u003ePFA\u003c/strong\u003e \u0026ndash; Pulsed-Field Ablation\u003c/li\u003e\n \u003cli\u003e\u003cstrong\u003ePF\u003c/strong\u003e \u0026ndash; Pulsed-Field\u003c/li\u003e\n \u003cli\u003e\u003cstrong\u003ePSC\u003c/strong\u003e \u0026ndash; Pentaspline Catheter\u003c/li\u003e\n \u003cli\u003e\u003cstrong\u003ePVI\u003c/strong\u003e \u0026ndash; Pulmonary Vein Isolation\u003c/li\u003e\n \u003cli\u003e\u003cstrong\u003eRBC\u0026micro;s\u003c/strong\u003e \u0026ndash; Red Blood Cell Microparticles\u003c/li\u003e\n \u003cli\u003e\u003cstrong\u003eSD\u003c/strong\u003e \u0026ndash; Standard Deviation\u003c/li\u003e\n \u003cli\u003e\u003cstrong\u003eTPI\u003c/strong\u003e \u0026ndash; Tissue Proximity Indication\u003c/li\u003e\n \u003cli\u003e\u003cstrong\u003eVLCC\u003c/strong\u003e \u0026ndash; Variable-Loop Circular Catheter\u003c/li\u003e\n\u003c/ul\u003e"},{"header":"Declarations","content":"\u003ch2\u003eDisclosures\u003c/h2\u003e\u003cp\u003eThe authors declare no conflict of interest related to the topic.\u003c/p\u003e\u003c/p\u003e\u003ch2\u003eAuthor Contribution\u003c/h2\u003e\u003cp\u003eM.H. wrote the main manuscript, while D.H. and P.O. reviewed it. B.B. performed the laboratory analyses, and J.K., L.P., J.V., V.F., S.H., and J. Hornof conducted the procedures. J. Hoznamov\u0026aacute; handled the data analysis.\u003c/p\u003e\n\u003ch3\u003e6. Sources of Funding\u003c/h3\u003e\n\u003cp\u003eThe work was supported by the Charles University Research program \u0026ldquo;Cooperatio\u0026ndash;Cardiovascular Science,\u0026rdquo; and by the project National Institute for Research of Metabolic and Cardiovascular Diseases (CarDia), Programme EXCELES, ID Project No. LX22NPO5104.\u003c/p\u003e\u003cp\u003eFunded by the European Union \u0026ndash; Next Generation EU.\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\u003cli\u003e\u003cspan\u003eKoruth J, Kuroki K, Iwasawa J, Enomoto Y, Viswanathan R, Brose R, et al. Preclinical Evaluation of Pulsed Field Ablation. Circ Arrhythm Electrophysiol Am Heart Association. 2019;12:e007781.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eFiserova I, Fiser O, Novak M, Trnka J, Gibalova A, Kvapil D, et al. Significant hemolysis is present during irreversible electroporation of cardiomyocytes in\u0026nbsp;vitro. \u003cem\u003eHeart Rhythm\u003c/em\u003e Elsevier; 2025;22:466\u0026ndash;74.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eStojadinović P, Ventrella N, Alfredov\u0026aacute; H, Wichterle D, Peichl P, Čih\u0026aacute;k R et al. Prediction of major intravascular hemolysis during pulsed electric field ablation of atrial fibrillation using a pentaspline catheter. \u003cem\u003eJ Cardiovasc Electrophysiol\u003c/em\u003e John Wiley and Sons Inc; 2024;35:2405.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eMohanty S, Casella M, Compagnucci P, Torlapati PG, Rocca DG, Della, Fazia VM, La, et al. Acute Kidney Injury Resulting From Hemoglobinuria After Pulsed-Field Ablation in Atrial Fibrillation: Is it Preventable? JACC Clin Electrophysiol Elsevier Inc. 2024;10:709\u0026ndash;15.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eLakkireddy D, Katapadi A, Garg J, Herink E, Klotz M, Ganta J, et al. NEMESIS-PFA: Investigating Collateral Tissue Injury Associated With Pulsed Field Ablation. Clinical Electrophysiology American College of Cardiology FoundationWashington D.C.; 2025.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eR Core Team. (2025). R: A Language and Environment for Statistical Computing. R Foundation for Statistical Computing, Vienna, Austria.; 2025.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eOsmancik P, Bacova B, Herman D, Hozman M, Fiserova I, Hassouna S, et al. Periprocedural Intravascular Hemolysis During Atrial Fibrillation Ablation: A Comparison of Pulsed Field With Radiofrequency Ablation. Volume 10. JACC Clin Electrophysiol Elsevier Inc.; 2024. pp. 1660\u0026ndash;71.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003ePopa MA, Venier S, Men\u0026egrave; R, Rocca DG, Della, Sacher F, Derval N, et al. Characterization and Clinical Significance of Hemolysis After Pulsed Field Ablation for Atrial Fibrillation: Results of a Multicenter Analysis. Volume 17. Circ Arrhythm Electrophysiol Lippincott Williams \u0026amp; WilkinsHagerstown, MD;; 2024. p. e012732.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eNies M, Koruth JS, Mlček M, Watanabe K, Tibensk\u0026aacute; VC, Kr\u0026aacute;lovec Š, et al. Hemolysis After Pulsed Field Ablation: Impact of Lesion Number and Catheter-Tissue Contact. Circ Arrhythm Electrophysiol Circ Arrhythm Electrophysiol. 2024;17:e012765.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eBelalcazar A, Heist EK. Comparison of efficiency of PFA catheter designs by computer modeling. J Cardiovasc Electrophysiol J Cardiovasc Electrophysiol. 2024;35:2382\u0026ndash;93.\u003c/span\u003e\u003c/li\u003e\u003c/ol\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":true,"highlight":"","institution":"","isAcceptedByJournal":true,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true},"keywords":"atrial fibrillation, pulsed-field ablation, hemolysis, red blood cell microparticles","lastPublishedDoi":"10.21203/rs.3.rs-7897511/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-7897511/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003ch2\u003ePurpose\u003c/h2\u003e\u003cp\u003eTo compare the extent of intravascular hemolysis, quantified by red blood cell microparticles (RBC\u0026micro;s), between patients undergoing pulsed-field ablation (PFA) for atrial fibrillation (AF) with a variable-loop circular catheter (VLCC) and those treated with a pentaspline catheter (PSC).\u003c/p\u003e\u003ch2\u003eMethods\u003c/h2\u003e\u003cp\u003eThis prospective, single-center observational study included three cohorts of patients undergoing first-time AF ablation: (1) pulmonary vein isolation (PVI) by the PSC (PSC PVI), (2) PVI plus posterior wall and/or mitral isthmus by the PSC (PSC PVI+), and (3) PVI plus posterior wall by the VLCC (VLCC PVI+). Blood samples were collected at baseline, immediately post-ablation, and 24 hours after the procedure to measure RBC\u0026micro;s and other biochemical markers.\u003c/p\u003e\u003ch2\u003eResults\u003c/h2\u003e\u003cp\u003eThe study included 77 patients (64.2\u0026thinsp;\u0026plusmn;\u0026thinsp;9.5 years, 42.9% female): 22, 25 and 30 in the PSC PVI, PSC PVI+, and VLCC PVI\u0026thinsp;+\u0026thinsp;groups, respectively. All groups exhibited a significant transient rise in RBC\u0026micro;s concentration immediately after ablation (p\u0026thinsp;\u0026lt;\u0026thinsp;0.001), returning to baseline within 24 hours. Peak RBC\u0026micro;s levels were highest in the PSC PVI\u0026thinsp;+\u0026thinsp;group, followed by PSC PVI and VLCC PVI+ (all pairwise comparisons p\u0026thinsp;\u0026lt;\u0026thinsp;0.001). The total number of applications was highest in the PS PVI\u0026thinsp;+\u0026thinsp;group and lowest in the VLCC PVI\u0026thinsp;+\u0026thinsp;group, correlating with the magnitude of hemolysis.\u003c/p\u003e\u003ch2\u003eConclusions\u003c/h2\u003e\u003cp\u003eThe VLCC used in persistent AF ablation was linked to lower levels of intravascular hemolysis compared to the PS catheter employed in cases of paroxysmal and persistent AF.\u003c/p\u003e","manuscriptTitle":"Variable-Loop Circular vs. Pentaspline Catheter: Hemolysis Outcomes in Pulsed-Field Ablation Procedures for Atrial Fibrillation","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2025-11-05 06:41:03","doi":"10.21203/rs.3.rs-7897511/v1","editorialEvents":[{"type":"communityComments","content":0}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"709e3ebd-5078-4c75-a1b5-64d9f860f180","owner":[],"postedDate":"November 5th, 2025","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"posted","subjectAreas":[],"tags":[],"updatedAt":"2026-02-23T16:07:51+00:00","versionOfRecord":{"articleIdentity":"rs-7897511","link":"https://doi.org/10.1007/s10840-026-02244-7","journal":{"identity":"journal-of-interventional-cardiac-electrophysiology","isVorOnly":false,"title":"Journal of Interventional Cardiac Electrophysiology"},"publishedOn":"2026-02-19 15:59:04","publishedOnDateReadable":"February 19th, 2026"},"versionCreatedAt":"2025-11-05 06:41:03","video":"","vorDoi":"10.1007/s10840-026-02244-7","vorDoiUrl":"https://doi.org/10.1007/s10840-026-02244-7","workflowStages":[]},"version":"v1","identity":"rs-7897511","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-7897511","identity":"rs-7897511","version":["v1"]},"buildId":"8U1c8b4HqxoKbykW_rLl7","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}