Differential Biomarker Responses of Hemolysis, Inflammation, and Myocardial Injury after Pulsed-Field Pulmonary Vein Isolation: Balloon-in-Basket versus Circular Catheter Systems

Differential Biomarker Responses of Hemolysis, Inflammation, and Myocardial Injury after Pulsed-Field Pulmonary Vein Isolation: Balloon-in-Basket versus Circular Catheter Systems | Authorea try { document.documentElement.classList.add('js'); } catch (e) { } var _gaq = _gaq || []; _gaq.push(['_setAccount', 'G-8VDV14Y67G']); _gaq.push(['_trackPageview']); (function() { var ga = document.createElement('script'); ga.type = 'text/javascript'; ga.async = true; ga.src = ('https:' == document.location.protocol ? 'https://ssl' : 'http://www') + '.google-analytics.com/ga.js'; var s = document.getElementsByTagName('script')[0]; s.parentNode.insertBefore(ga, s); })(); Skip to main content Preprints Collections Wiley Open Research IET Open Research Ecological Society of Japan All Collections About About Authorea FAQs Contact Us Quick Search anywhere Search for preprint articles, keywords, etc. Search Search ADVANCED SEARCH SCROLL This is a preprint and has not been peer reviewed. Data may be preliminary. 25 September 2025 V1 Latest version Share on Differential Biomarker Responses of Hemolysis, Inflammation, and Myocardial Injury after Pulsed-Field Pulmonary Vein Isolation: Balloon-in-Basket versus Circular Catheter Systems Authors : Jan-Per Wenzel , Charlotte Eitel , Sorin Popescu , Suzanne de Waha , Tanja Zeller , Karl-Heinz Kuck , Roland Tilz , and Sascha Hatahet 0000-0002-3061-2249 Authors Info & Affiliations https://doi.org/10.22541/au.175882522.29307085/v1 262 views 149 downloads Contents Abstract Tables Supplementary Material Information & Authors Metrics & Citations View Options References Figures Tables Media Share Abstract Background Pulsed-field ablation (PFA) has emerged as a promising non-thermal energy source for pulmonary vein isolation (PVI) in atrial fibrillation (AF). However, data comparing the biological impact of novel PFA technologies remain limited. This study assessed changes in biomarkers of hemolysis, inflammation, and myocardial injury following PVI using two PFA systems: a balloon-in-basket (BiB; VOLT™, Abbott) and a circular catheter (PS; PulseSelect™, Medtronic). Methods This prospective, single-center, non-randomized study enrolled consecutive patients undergoing first-time PVI. Biomarkers, including leukocytes, C-reactive protein (CRP), platelets, lactate dehydrogenase (LDH), haptoglobin, total bilirubin, troponin T, creatine kinase (CK), myoglobin, creatinine, and estimated glomerular filtration rate (eGFR), were measured before and 16-18h after ablation. Results: Forty patients were included (BiB n=20, PS n=20). Patients treated with PS were older (73 vs. 63, p=0.016) and had higher incidence of persistent AF (80% vs. 30%, p = 0.001). Acute PVI was achieved in all cases. BiB required fewer applications (13.5 vs. 32, p<0.001) but a higher contrast agent volume (40 vs. 30 mL, p<0.001). Both systems resulted in significant increases in leukocytes, CRP, troponin, and CK without inter-group differences. Haptoglobin decreased significantly with PS but remained stable with BiB (Δ –0.13 vs. +0.035 g/L, p<0.001), while LDH increased similarly in both groups. Renal function remained stable. In BiB group, ΔLDH correlated with application number (p < 0.001). In PS group, Δtroponin and ΔCK correlated with application number (p < 0.05). Conclusion: Despite comparable overall biomarker responses between the two PFA systems, the distinct haptoglobin patterns highlight possible differences in biological tissue interaction, warranting further investigation in larger studies. Differential Biomarker Responses of Hemolysis, Inflammation, and Myocardial Injury after Pulsed-Field Pulmonary Vein Isolation: Balloon-in-Basket versus Circular Catheter Systems Jan-Per Wenzel 1,2# , Raed Abdessadok 1# , Charlotte Eitel 1,2 , Sorin Popescu 1 , Suzanne de Waha 1,2 , Tanja Zeller 2,3 , Karl-Heinz Kuck 1 , Roland Richard Tilz 1,2* , Sascha Hatahet 1* # JPW and RA contributed equally and share first authorship * RRT and SH contributed equally and share last authorship Affiliations 1 Department of Rhythmology, Heart Center Lübeck, University Hospital Schleswig-Holstein, Lübeck, Germany 2 German Center for Cardiovascular Research (DZHK), Partner Site Lübeck, Germany 3 Institute for Cardiogenetics, University Hospital Schleswig-Holstein, Lübeck, Germany Corresponding Authors: Jan-Per Wenzel Ratzeburger Allee 160 23562 Lübeck [email protected] Conflicts of interest : JPW received funding of the German Foundation of Heart Research (F/29/19), speaker fees from Abbott and Doctrina Med, and travel grants from Boston Scientific in each case unrelated to this project. CE received travel grants and research grants from Abbott, Boston Scientific, Lifetech, Biosense Webster and Cardiofocus and speaker honoraria from Abbott, Boston Scientific, Biosense Webster, Cardiofocus and C.T.I. GmbH and Doctrina Med. KHK reports grants and personal fees from Abbott Vascular, Medtronic, Biosense Webster outside the submitted work. RRT is a consultant for Abbott, Boston Scientific, Biotronik and Biosense Webster and received speaker honoraria from Biosense Webster, Medtronic, Boston Scientific and Abbot Medical. SSP is a medical consultant by Active Health; and has received travel grants and congress grants from Lifetech and educational grants and a speaker grant from Abbott Medical. SH received travel, congress and educational grants from Abbott Medical outside of the submitted work. All other authors have no relevant disclosures. Total word count: 5683 Ethics approval The study was approved by the local ethics committee (Lübeck Ablation Registry, approval number WF-028/15) and conducted in accordance with the Declaration of Helsinki (1964) and its later amendments. Consent for publication The manuscript „Differential Biomarker Responses of Hemolysis, Inflammation, and Myocardial Injury after Pulsed-Field Pulmonary Vein Isolation: Balloon-in-Basket versus Circular Catheter Systems“ is not under consideration for publication elsewhere. None of the paper’s contents has been previously published. All authors have read and approved the manuscript. Abstract Background Pulsed-field ablation (PFA) has emerged as a promising non-thermal energy source for pulmonary vein isolation (PVI) in atrial fibrillation (AF). However, data comparing the biological impact of novel PFA technologies remain limited. This study assessed changes in biomarkers of hemolysis, inflammation, and myocardial injury following PVI using two PFA systems: a balloon-in-basket (BiB; VOLT™, Abbott) and a circular catheter (PS; PulseSelect™, Medtronic). Methods This prospective, single-center, non-randomized study enrolled consecutive patients undergoing first-time PVI. Biomarkers, including leukocytes, C-reactive protein (CRP), platelets, lactate dehydrogenase (LDH), haptoglobin, total bilirubin, troponin T, creatine kinase (CK), myoglobin, creatinine, and estimated glomerular filtration rate (eGFR), were measured before and 16-18h after ablation. Results: Forty patients were included (BiB n=20, PS n=20). Patients treated with PS were older (73 vs. 63, p=0.016) and had higher incidence of persistent AF (80% vs. 30%, p = 0.001). Acute PVI was achieved in all cases. BiB required fewer applications (13.5 vs. 32, p<0.001) but a higher contrast agent volume (40 vs. 30 mL, p<0.001). Both systems resulted in significant increases in leukocytes, CRP, troponin, and CK without inter-group differences. Haptoglobin decreased significantly with PS but remained stable with BiB (Δ –0.13 vs. +0.035 g/L, p<0.001), while LDH increased similarly in both groups. Renal function remained stable. In BiB group, ΔLDH correlated with application number (p < 0.001). In PS group, Δtroponin and ΔCK correlated with application number (p < 0.05). Conclusion: Despite comparable overall biomarker responses between the two PFA systems, the distinct haptoglobin patterns highlight possible differences in biological tissue interaction, warranting further investigation in larger studies. Keywords: pulsed-field ablation, atrial fibrillation, pulmonary vein isolation, VOLT, PulseSelect, hemolysis, inflammation, myocardial injury What’s new? • Both PFA catheters were associated with increases in inflammatory and myocardial biomarkers. • Haptoglobin levels decreased significantly with PS but remained stable with BiB • Renal function was preserved in both groups, and no acute kidney injury was observed. • These findings indicate that overall biomarker responses are comparable, with hemolysis differing between PFA catheter types Graphical Abstract. Introduction: Pulsed-field ablation (PFA) has emerged as an innovative approach in atrial fibrillation (AF) therapy, providing a non-thermal method for pulmonary vein isolation. Using high-voltage electric pulses, PFA induces irreversible electroporation of cardiomyocytes, thereby creating durable lesions while minimizing collateral injury to surrounding structures. Recent multicenter studies have confirmed its high procedural efficacy and superior safety profile when compared to thermal energy sources 1-3 . Beyond lesion formation, PFA induces systemic effects, most notably intravascular hemolysis, characterized by increased LDH and bilirubin with reduced haptoglobin, and in rare cases progression to pigment-induced acute kidney injury. In addition, elevations in inflammatory and myocardial injury markers, including C-reactive protein (CRP), leukocytes, troponin, and creatine kinase (CK), have been reported after ablation. While CRP has been linked to atrial remodeling and arrhythmia recurrence 4-7 , troponin and CK might primarily reflect the extent of myocardial damage, though their prognostic value for long-term outcomes remains debated. Among PFA technologies, the VOLT™ balloon-in-basket catheter (BiB; Abbott) represents a novel approach, characterized by its balloon-in-basket configuration, distinct electrode arrangement, and balloon-mediated energy dispersion 3 . In contrast, the PulseSelect™ PFA catheter (PS; Medtronic) is a multipolar loop-based system advanced over a guidewire that delivers energy via a biphasic pulse waveform 8 . Such differences in design and energy application may modulate systemic responses. To date, no studies have directly compared the systemic effects of the recently released BiB (limited market release in Europe) catheter and the circular PS system with respect to hemolysis, inflammation, and myocardial injury. This study therefore aimed to characterize and contrast acute biomarker responses between both platforms to provide the first device-specific insights into the biological impact of PFA. Study Population and Trial Design This prospective, single-center, non-randomized study investigated systemic biomarker changes after PFA-based PVI using two catheter platforms: the PS and the BiB catheter. From April 2025 to July 2025, consecutive patients with paroxysmal or persistent AF were enrolled. All procedures were carried out at the Heart Center Lübeck and documented within the institutional ablation registry. Inclusion criteria were age ≥18 years, documented AF, and written informed consent. Patients with active infection, autoimmune or chronic inflammatory disease, recent myocardial infarction, neuromuscular disorders, or severe hepatic dysfunction were excluded to avoid biomarker confounding. The study was approved by the institutional ethics committee (Lübeck Ablation Registry, WF-028/15) and conducted in accordance with the Declaration of Helsinki. General Procedural Management All patients underwent standardized preprocedural evaluation according to institutional protocols. In those with elevated thromboembolic risk, transesophageal echocardiography was performed to rule out intracardiac thrombus. Anticoagulation with vitamin K antagonists was maintained at a therapeutic INR (2.0–3.0), while direct oral anticoagulants (DOACs) were withheld on the morning of the procedure. Ablation was conducted under deep sedation using propofol, midazolam, and fentanyl. In selected cases, continuous propofol infusion was omitted to preserve patient responsiveness, and a multimodal analgesic regimen consisting of metamizole, midazolam, fentanyl, and lidocaine was applied. Femoral venous access was obtained via one or two ultrasound-guided punctures with 8 Fr sheaths, followed by placement of a diagnostic catheter in the coronary sinus. Transseptal puncture was performed under fluoroscopic guidance using the modified Brockenbrough technique. After entry into the left atrium, intravenous unfractionated heparin was administered to maintain an activated clotting time >300 seconds, and left atrial access was secured with an SL1 sheath (Abbott). Patients were allocated to either the BiB or PS PFA system according to device availability and operator practice during the respective study period, without selection based on patient characteristics. Circular PFA -Catheter Procedure The PS catheter (9F) was advanced into the left atrium over a guidewire following transseptal puncture. The catheter delivers a controlled biphasic, bipolar waveform via a circular array of nine 3-mm gold electrodes. Secure wall contact was achieved by advancing the circular array to the pulmonary vein (PV) ostium, where fluoroscopy was used to assess changes in catheter angulation upon contact with the PV wall. Each application consisted of four biphasic, bipolar pulse trains lasting 100–200 ms. After each application, the catheter was rotated in a systematic sequence to achieve full circumferential lesion sets: starting at the roof position, followed by 45° clockwise or counterclockwise rotations to target the anterior, inferior, and posterior PV aspects. Initially, four applications were delivered at the ostium, followed by four additional applications at the antral level. For the posterior aspect, sheath manipulation involved clockwise torque for left-sided PVs and counterclockwise torque for right-sided PVs. Conversely, for the anterior aspect, the sheath was turned counterclockwise for left-sided PVs and clockwise for right-sided PVs. Balloon-In-Basket PFA-Catheter Procedure The catheter was introduced into the left atrium via a steerable 13 Fr Agilis™ NxT sheath (Abbott) over a 0.035-inch guidewire. The expandable balloon incorporates eight active spline electrodes, enabling single-shot circumferential PFA delivery. Pulses were applied at 1800 V with at least two rotated applications per vein, or at 1400 V with typically three applications, with a maximum of four applications per vein. Phrenic nerve pacing was routinely performed during right-sided PV ablation. In cases with diaphragmatic capture, ablation was performed at 1400 V with ≥3 applications. Electroanatomical mapping was conducted using the EnsiteX system (Abbott), with the BiB catheter employed for map acquisition both before and after PVI. The integrated contact indicator was used to verify secure PV wall contact during ablation. Acute procedural success was confirmed by demonstration of entrance block in all targeted PVs. Postprocedural Management Hemostasis was achieved using either vascular closure devices or figure-of-eight sutures combined with compression bandage. Compression bandages were removed after 1–4 hours, whereas sutures were removed on the following day. Transthoracic echocardiography was routinely performed 1 hour post-procedure and again on the first postoperative day to rule out pericardial effusion. Oral anticoagulation was restarted 6 hours after ablation and continued for a minimum of two months. Long-term anticoagulation was guided by individual thromboembolic risk (CHA₂DS₂-VA score) in accordance with current guideline recommendations. Blood Sampling and Analysis Venous blood samples were obtained at two predefined time points: (1) after femoral venous access and prior to ablation, and (2) on the morning of the first postoperative day. All samples were collected in the fasting state. The biomarker panel included leukocytes, platelets, C-reactive protein (CRP), high-sensitivity troponin T, creatine kinase (CK), CK-MB, myoglobin, serum creatinine, and estimated glomerular filtration rate (eGFR). Leukocytes and platelets were measured in EDTA blood by fluorescence flow cytometry (Sysmex XN-9000). CRP was determined by immunoturbidimetry (Cobas c503). Troponin T and myoglobin were quantified using electrochemiluminescence immunoassay (Cobas 801). CK and CK-MB were measured enzymatically by UV photometry (Cobas c702), creatinine by Cobas c503, and eGFR was calculated using the CKD-EPI formula. CK-MB was analyzed only in patients with elevated baseline values. All laboratory analyses were performed at the central laboratory of the University Hospital Schleswig-Holstein in compliance with certified, validated protocols. Statistical Analysis Continuous data were tested for normality using the Shapiro–Wilk test and are presented as mean ± SD or median (Q1, Q3), as appropriate. Between-group comparisons were performed using independent-samples t-tests or Mann–Whitney U tests. Within-group comparisons used paired t-tests or Wilcoxon signed-rank tests. Correlations between biomarker changes and ablation parameters were analyzed with Pearson or Spearman coefficients, depending on distribution. Categorical variables are reported as absolute and relative frequencies and compared using Fisher’s exact or Chi-square tests. Analyses were conducted using IBM SPSS Statistics v29.0.1.0 (IBM Corp., Armonk, NY, USA). A two-sided p-value <0.05 was considered statistically significant. Results Baseline Characteristics A total of 40 patients were included, 20 treated with the BiB system and 20 with the PS system. Patients in the PS group were significantly older (median 73 vs. 63 years, p = 0.016) and more frequently presented with persistent AF (80.0% vs. 30.0%, p = 0.001). Hypertension (85.0% vs. 55.0%, p = 0.038) and heart failure (30.0% vs. 5.0%, p = 0.037) were also more prevalent in the PS cohort. The median CHA₂DS₂-VA score was higher in the PS group (4.0 vs. 1.0, p = 0.022). Other baseline variables, including sex distribution, diabetes, coronary artery disease, prior stroke/TIA, obstructive sleep apnea, and left ventricular ejection fraction, did not differ significantly between groups (Table 1). Procedural Characteristics Acute PVI was achieved in all patients (100%). Left atrial dwell time was significantly longer with BiB compared to PS (30.0 vs. 23.0 min, p = 0.007), and contrast volume was higher in the BiB group (40.0 vs. 30.0 mL, p < 0.001). PS required a substantially greater number of applications across all PV (median total 32.0 vs. 13.5, p < 0.001). Procedure duration and fluoroscopy time did not differ between groups. No major acute complications were observed (Table 2). Biomarkers — Pre/Post Comparisons In the BiB group, leukocytes, CRP, bilirubin, LDH, myoglobin, CK, and troponin increased significantly, whereas haptoglobin, creatinine, and eGFR showed no relevant changes. In the PS group, similar increases in leukocytes, CRP, bilirubin, LDH, myoglobin, CK, and troponin were observed, accompanied by a significant decrease in haptoglobin, while renal markers remained stable (Table 3). Intergroup Comparison of Delta Values Between-group analysis showed a significantly greater reduction in haptoglobin with PS compared to BiB (–0.130 vs. +0.035 g/L, p 0.05; Table 4). Correlation Between Number of PFA Applications and Biomarker Changes In the BiB group, the number of PFA applications correlated strongly with LDH increase (r = 0.800, p 0.05). In the PS group, the number of applications correlated positively with troponin (r = 0.496, p = 0.036) and CK (r = 0.563, p = 0.019), whereas no significant relationships were found for other biomarkers (all p > 0.05; Table 5). Discussion This prospective study compared systemic biological effects during PVI among two PFA technologies – the BiB catheter and the PS system. The main findings are: 1. Both platforms induced significant increases in markers of inflammation, hemolysis, and myocardial injury. 2. Only the PS catheter produced a significant decline in haptoglobin, indicating greater hemolytic activity. 3. Both groups exhibited correlations between application number and biomarker changes, albeit with marker-specific patterns (LDH with BiB; troponin and CK with PS), consistent with a dose–response relationship. Myocardial Injury: Comparable in Magnitude, Distinct in Correlation Patterns Both systems were associated with significant increases in troponin, CK, and myoglobin, consistent with substantial myocardial injury and were in line with prior PFA studies 9,10,13,17 . Intergroup comparisons showed no significant differences, although BiB required fewer applications. Similar troponin and CK rises despite fewer BiB applications suggest higher per-application efficacy of this system, whereas PS compensates with more pulses. The correlation of troponin and CK with application number in the PS group, but not in the BiB group, supports this interpretation. Whether these biomarker elevations reflect irreversible necrosis or partly reversible electroporation remains uncertain. Their prognostic significance for long-term atrial function or arrhythmia recurrence warrants further study. Inflammation: Comparable and Modest Systemic Inflammatory Activation Both PFA systems induced a significant rise in leukocytes and CRP after ablation, reflecting a systemic inflammatory response. The magnitude of these changes was comparable between BiB and PS, indicating no relevant influence of catheter design on inflammatory burden in this study. No correlation with pulse count was observed, suggesting that the inflammatory response was not dose-dependent within the applied energy range. Overall, PFA-induced inflammation appears to be a uniform biological effect of electroporation rather than a catheter-specific phenomenon in this study. The modest and comparable response in both groups underscores the similar biocompatibility of the two catheters and aligns with prior reports that PFA causes only limited systemic inflammation compared with thermal ablation techniques 11,12,17 . Hemolysis: Evidence of Device-Specific Signatures Markers of hemolysis increased after ablation with both platforms. LDH and bilirubin rose significantly, while hemoglobin changes were minor and clinically irrelevant. The greater haptoglobin decline observed with PS likely reflects less consistent wall contact and greater blood-pool interaction at the PV ostium, whereas BiB ensures circumferential tissue apposition and lateral energy directionality, limiting exposure of circulating erythrocytes. Despite biochemical signs of hemolysis, no patient developed acute kidney injury, consistent with prior studies showing PFA-related hemolysis to be largely subclinical 14,15,18 . Catheter design features likely underlie these differences. BiB incorporates a semi-compliant balloon that stabilizes circumferential wall contact, with flat splines oriented laterally to direct the electric field into adjacent myocardium while shielding circulating blood. It also includes an integrated contact indicator within the electroanatomical mapping system, providing real-time feedback on tissue contact quality. This allows selective deactivation of splines directed toward the blood pool, avoiding unnecessary intravascular energy delivery. In contrast, PS deploys forward-facing electrodes without balloon support or selective deactivation, activating all electrodes simultaneously regardless of orientation, which increases the probability of off-target energy dispersion. Application number is also relevant: hemolysis generally scales with pulse burden, but the higher counts in the PS group may reflect not only cumulative exposure but also less efficient energy transfer due to inconsistent tissue coupling. In our study, the narrow dosing protocol in the BiB cohort (≤4 per vein) restricted variability, limiting correlations, though prior multicenter datasets have confirmed a clear dose–response between pulse count and hemolysis 16,19,20 . Waveform design may further contribute. BiB uses a biphasic waveform with lower voltage requirements due to improved tissue coupling, reducing hemolytic potential without compromising lesion efficacy. Together, these features provide a mechanistic explanation for the greater hemolytic signal observed with PS. Dose–Response Considerations The marker-specific correlations identified here align with broader evidence that hemolysis and myocardial injury scale with pulse burden and application count across PFA systems. In the present study, standardized dosing – particularly the narrow range in the BiB cohort – and a modest sample size limited variability and statistical power, likely biasing correlation estimates toward the null. Larger cohorts and wider dosing ranges will likely reveal a clearer and more consistent dose–response across biomarkers, as demonstrated in recent multicenter studies 16,20 . Clinical Implications Systemic biological effects of PFA are shaped by catheter design and dosing. While inflammation and myocardial injury appear to be generic consequences of electroporation, hemolysis is more pronounced with PS, likely due to less consistent wall contact. These observations indicate that catheter-related hemolysis may be more relevant in patients with anemia or renal dysfunction, and that dosing strategies should be adapted to the specific design of each system rather than applied uniformly across platforms. Limitations Several limitations must be acknowledged. First, the study was non-randomized, and baseline characteristics differed between groups, with patients treated using PS being older and more often having persistent AF and comorbidities. Such differences may have influenced biomarker kinetics and limit the ability to ascribe findings solely to catheter design. Second, the sample size was modest, reducing statistical power and limiting subgroup analyses. Third, protocol-driven dosing – especially the restricted pulse range in the BiB cohort – curtailed variability and likely attenuated observable dose–response signals. Fourth, biomarker sampling was confined to the first 24 hours. Thus, delayed changes or recovery trajectories could not be assessed. Fifth, analysis was restricted to routine clinical markers. Additional parameters such as cytokine panels, oxidative stress markers, or urinary indices of renal tubular injury would have provided deeper mechanistic insight. Finally, both catheters represent early-generation devices, and their systemic profiles may not fully reflect future iterations or other PFA technologies. Conclusion Both BiB and PS induced systemic effects characterized by inflammation, myocardial injury, and hemolysis. Similar troponin and CK rises despite fewer BiB applications indicate higher per-application efficacy, while the greater haptoglobin decline with PS probably reflects less consistent wall contact. Together with prior evidence, our findings support a dose–response relationship between pulse burden and biomarker changes, highlighting that not only the quantity but also the quality of energy delivery shapes the systemic effects of PFA. \sout Declaration of generative AI and AI-assisted technologies in the writing process During the preparation of this work the authors used ChatGPT in order to improve language. 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PMID: 38175788; PMCID: PMC10776308. 15. Martinez J, Challapalli M, Hutchinson M, Ibrahim M, Shen C, Klewer J, et al. Renal safety of high-dose pulsed field ablation of atrial fibrillation: a prospective real-world analysis. Heart Rhythm. 2025 Jul 22:S15475271(25)02700-6. doi:10.1016/j.hrthm.2025.07.026. PMID: 40706736. 16. Popa MA, Venier S, Menè R, Della Rocca DG, Sacher F, Derval N, Hocini M, Dulucq S, Caluori G, Combes S, Albenque JP, Saitta F, Haller B, Chierchia GB, de Asmundis C, Defaye P, Boveda S, Jaïs P. Characterization and clinical significance of hemolysis after pulsed field ablation for atrial fibrillation: results of a multicenter analysis. Circ Arrhythm Electrophysiol. 2024 Oct;17(10):e012732. doi:10.1161/CIRCEP.124.012732. PMID: 39212069. 17. Wenzel JP, Hatahet S, Abdessadok R, Eitel C, Traub A, Popescu S, Mamaev R, Nikorowitsch J, de Waha S, Zeller T, Kuck KH, Tilz RR. Differential inflammatory and myocardial biomarker response after pulsed field ablation for atrial fibrillation using using balloon-in-basket versus pentaspline catheter. Heart Rhythm O2. 2025 Sep 2. Epub ahead of print. doi:10.1016/j.hroo.2025.09.003 18. auf der Heiden C, Bejinariu A, Kelm M, Spieker M, Rana O. Hemolysis after Pulsed Field Ablation in Pulmonary Vein Isolation for Atrial Fibrillation: A Prospective Controlled Trial. Heart Rhythm [Internet]. 2025 [cited 2025 May 19];Available from: https://linkinghub.elsevier.com/retrieve/pii/S1547527125023860 19. Nies M, Koruth JS, Mlček M, Watanabe K, Tibenská VC, Královec Š, Tejkl L, Neuzil P, Reddy VY. Hemolysis after Pulsed Field Ablation: Impact of Lesion Number and Catheter-Tissue Contact. Circ Arrhythm Electrophysiol DOI: 10.1161/CIRCEP.124.012765 20. Wenzel JP, Abdessadok R, Hatahet S, Eitel C, Nikorowitsch J, Mamaev R, Popescu S, Reincke S, Traub A, Subin B, de Waha S, Zeller T, Kuck KH, Tilz RR. Balloon vs. Balloon – Comparison of hemolysis and renal markers after cryoballoon vs. balloon-in-basket pulsed field pulmonary vein isolation. Front Cardiovasc Med. 2025;12:1681098. doi:10.3389/fcvm.2025.1681098. Figures Figure 1: Study PRISMA (STROBE format). BiB = Balloon-in-basket; PS = PulseSelect; AF = atrial fibrillation; PFA = pulsed field ablation; PVI = pulmonary vein isolation, CK = creatine kinase; CRP = C-reactive protein; eGFR = estimated glomerular filtration rate. Figure 2. Figure 2. Comparison of delta values between the balloon-in-basket PFA-PVI group and the PulseSelect PFA-PVI group . Boxplots represent the median with interquartile ranges (IQR) of changes from baseline to 16–18 hours after the procedure. CRP = C-reactive protein, CK = creatine kinase. Figure 3. Figure 3. Comparison of delta values between the balloon-in-basket PFA-PVI group and the PulseSelect PFA-PVI group . Boxplots represent the median with interquartile ranges (IQR) of changes from baseline to 16–18 hours after the procedure. LDH = Lactate dehydrogenase, eGFR = estimated glomerular filtration rate. Tables Table (1): Baseline characteristics of the study population. Values are presented as median [interquartile range], mean ± standard deviation or number (percentage), as appropriate. AF = atrial fibrillation; AAD = antiarrhythmic drug; LAVI = left atrial volume index; LVEF = left ventricular ejection fraction; OSAS = obstructive sleep apnea syndrome; TIA = transient ischemic attack. Female sex (, n (%) 7 (35%) 10 (50%) 0.337 Age (years) 63 (41.5–70.5) 73 (70–80) 0.016 Persistent AF, n (%) 6 (30%) 16 (80%) 0.001 Paroxysmal AF, n (%) 14 (70%) 4 (20%) 0.001 Arterial hypertension, n (%) 11 (55%) 17 (85%) 0.038 Diabetes, n (%) 1 (5%) 3 (15%) 0.292 Coronary artery disease, n (%) 3 (15%) 3 (15%) 1 Heart failure, n (%) 1 (5%) 6 (30%) 0.037 TIA/Stroke, n (%) 1 (5%) 3 (15%) 0.292 OSAS, n (%) 1 (5%) 3 (15%) 0.292 OAC: DOAC, n (%) 16 (80%) 19 (95%) 0.072 Class I/III AAD at baseline, n (%) 4 (20%) 3 (15%) 0.677 LVEF (%) 55.0 (55–56.5) 55.0 (52–57) 0.598 LAVI (mL/m²) 30.0 (24–51) 40.0 (21–44) 1 CHA₂DS₂-VA score 1.0 (0–3.5) 4.0 (3–5) 0.022 BMI (kg/m²) 24.91 (21.86–28.58) 26.73 (23.3–31.21) 0.144 Table (2): Procedural characteristics of the study population. Values are presented as median [interquartile range], mean ± standard deviation or number (percentage), as appropriate. LSPV = left superior pulmonary vein; LIPV = left inferior pulmonary vein; RSPV = right superior pulmonary vein; RIPV = right inferior pulmonary vein. Dose Area Product (Gy·cm²) 324.0 (207.0–516.0) 427.5 (291.5–628.8) 0.166 Fluoroscopy time (min) 7.4 (5.18–11.25) 8.75 (7.13–10.38) 0.365 Successful acute PVI, n(%) 20 (100) 20 (100) 1 First-pass PVI, n(%) 20 (100) 20 (100) 1 Left atrial dwell time (min) 30.0 (20.0–41.0) 23.0 (18.0–28.0) 0.007 Procedure duration (min) 41.0 (35.25–60.50) 37.5 (34.25–44.50) 0.140 Cardioversions (n) 0 (0–0) 0 (0–1.0) 0.161 Contrast amount (mL) 40.0 (40.0–47.5) 30.0 (26.25–37.5) <0.001 Intraprocedural complications (n) 0 (0) 0 (0) 1. LSPV applications (n) 4.0 (2.0–4.0) 8.0 (8.0–9.0) <0.001 LIPV applications (n) 3.0 (2.0–4.0) 8.0 (8.0–10.0) <0.001 RIPV applications (n) 3.5 (2.0–4.0) 8.0 (8.0–9.0) <0.001 RSPV applications (n) 3.0 (2.0–4.0) 8.0 (8.0–8.75) <0.001 Total number of applications (n) 13.5 (8.5–16.0) 32.0 (32.0–36.0) <0.001 Table (3): Comparison of pre- and post-procedural biomarker values in the Balloon-in-basket and PulseSelect PFA-PVI groups. Values are presented as median [interquartile range] or mean ± standard deviation. CK = creatine kinase; CRP = C-reactive protein; eGFR = estimated glomerular filtration rate Leukocytes (×10⁹/L) Pre Post 5.09 ± 1.90 8.43 ± 2.46 0.002 6.02 ± 1.96 7.57 ± 2.38 0.010 Hemoglobin (g/dL) Pre Post 13.17 ± 1.00 13.27 ± 1.05 0.267 12.82 ± 1.64 12.52 ± 1.67 0.113 Platelets (×10⁹/L) Pre Post 157.0 (144.5–225.5) 191.0 (150.5–230.0) 0.950 168.0 ± 55.4 170.3 ± 53.7 0.694 CRP (mg/L) Pre Post 0.99 (0.60–1.92) 5.79 (4.23–7.17) <0.001 1.55 (0.94–3.49) 5.85 (3.34–11.97) <0.001 Haptoglobin (g/L) Pre Post 0.78 ± 0.54 0.84 ± 0.54 0.131 0.75 (0.55–1.26) 0.63 (0.43–1.26) 0.011 Total Bilirubin (µmol/L) Pre Post 12.10 ± 6.12 15.56 ± 7.51 0.002 11.85 (8.90–15.70) 15.05 (10.43–25.15) 0.015 LDH (U/L) Pre Post 157.7 ± 20.3 201.3 ± 28.6 <0.001 202.9 ± 34.3 253.6 ± 55.9 <0.001 Creatinine (µmol/L) Pre Post 72.0 (68.5–84.9) 80.5 (68.3–97.4) 0.443 101.9 (91.0–112.8) 100.5 (87.2–118.8) 0.776 GFR (mL/min) Pre Post 88.4 ± 19.4 81.6 ± 22.7 0.366 54.5 (50.0–60.8) 52.0 (48.0–63.0) 0.410 Myoglobin (µg/L) Pre Post 36.0 (30.0–44.0) 44.0 (40.0–78.5) 0.008 69.0 (38.0–79.8) 75.0 (47.0–93.3) 0.024 CK (U/L) Pre Post 75.0 (61.0–220.5) 361.0 (263.0–428.0) 0.002 91.5 (41.8–128.0) 214.5 (140.3–307.8) <0.001 Troponin (ng/L) Pre Post 5.0 (5.0–13.5) 1183.0 (1075.0–1408.5) 0.001 16.3 (6.6–19.3) 1289.0 (625.5–1873.3) <0.001 Table (4): Comparison of periprocedural biomarker changes (delta values) between the Balloon-in-basket and PulseSelect PFA-PVI groups. Values are presented as mean and standard deviation or median [interquartile range]. Delta = post-procedural minus pre-procedural value. CK = creatine kinase; CRP = C-reactive protein; eGFR = estimated glomerular filtration rate Δ Leukocytes (10⁹/L) 2.86 (–0.55 – 5.88) 1.06 (0.5 – 1.92) 0.157 Δ Haptoglobin (g/L) 0.035 (–0.03 – 0.123) –0.13 (–0.185 – –0.085) <0.001 Δ Myoglobin (ng/mL) 10.5 (4.75 – 64.5) 11.5 (2.25 – 23.5) 0.586 Δ Hemoglobin (g/dL) –0.5 (–0.88 – 0.33) –0.5 (–0.7 – 0.33) 0.780 Δ CRP (mg/L) 3.59 (1.16 – 5.56) 4.19 (1.64 – 5.59) 0.808 Δ Bilirubin (µmol/L) 4.1 (0.70 – 9.63) 2.1 (0.30 – 6.90) 0.442 Δ GFR (mL/min) –2.00 (–15.00 – 4.00) 0.00 (–4.50 – 1.50) 0.576 Δ LDH (U/L) 40. ± 27.6 43.5 ± 35.1 0.762 Δ Creatinine (µmol/L) 4.0 ± 15.3 –0.61 ± 8.3 0.316 Δ Troponin (ng/L) 1203 ± 601.9 1417 ± 645.8 0.352 Δ CK total (U/L) 193 ± 112.2 178.5 ± 117 0.437 Table (5): Correlation Between Number of PFA impulses and Biomarker Changes in the Balloon-in-basket and PulseSelect PFA-PVI groups. CK = creatine kinase; CRP = C-reactive protein; eGFR = estimated glomerular filtration rate Leucocytes r = 0.371 0.157 r = –0.066 0.801 Platelets r = 0.321 0.226 r = –0.056 0.831 CRP r = 0.053 0.856 r = –0.249 0.320 Creatinine r = –0.037 0.895 r = 0.020 0.944 GFR r = 0.207 0.460 r = 0.213 0.413 Myoglobin ρ = –0.220 0.542 r = –0.080 0.770 CK r = 0.075 0.807 r = 0.563 0.019 Troponin T r = 0.252 0.405 r = 0.496 0.036 LDH r = 0.800 <0.001 r = 0.167 0.522 Haptoglobin r = 0.249 0.392 r = –0.269 0.297 Hemoglobin r = –0.136 0.616 r = 0.056 0.836 Total Bilirubin r = –0.336 0.240 r = 0.020 0.936 Supplementary Material File (image1.emf) Download 2.23 MB File (image2.emf) Download 1.92 MB File (image3.emf) Download 1.56 MB File (image4.emf) Download 1.59 MB Information & Authors Information Version history V1 Version 1 25 September 2025 Copyright This work is licensed under a Non Exclusive No Reuse License. Keywords basic: activation mapping of arrhythmias basic: atrial fibrillation/atrial arrhythmias clinical: catheter ablation – atrial fibrillation clinical: catheter ablation – non-rf energy sources clinical: electrophysiology – atrial arrhythmias Authors Affiliations Jan-Per Wenzel Universitatsklinikum Schleswig-Holstein Universitares Herzzentrum Lubeck View all articles by this author Charlotte Eitel Universitatsklinikum Schleswig-Holstein Universitares Herzzentrum Lubeck View all articles by this author Sorin Popescu Universitatsklinikum Schleswig-Holstein Universitares Herzzentrum Lubeck View all articles by this author Suzanne de Waha Universitatsklinikum Schleswig-Holstein Universitares Herzzentrum Lubeck View all articles by this author Tanja Zeller Universitatsklinikum Schleswig-Holstein Universitares Herzzentrum Lubeck View all articles by this author Karl-Heinz Kuck Universitatsklinikum Schleswig-Holstein Universitares Herzzentrum Lubeck View all articles by this author Roland Tilz Universitatsklinikum Schleswig-Holstein Universitares Herzzentrum Lubeck View all articles by this author Sascha Hatahet 0000-0002-3061-2249 Universitatsklinikum Schleswig-Holstein Universitares Herzzentrum Lubeck View all articles by this author Metrics & Citations Metrics Article Usage 262 views 149 downloads .FvxKWukQNSOunydq8rnd { width: 100px; } Citations Download citation Jan-Per Wenzel, Charlotte Eitel, Sorin Popescu, et al. 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