Abstract
Background
Pulsed field ablation (PFA) is a nonthermal technique for pulmonary vein isolation (PVI) in atrial fibrillation, offering lesion selectivity with minimal collateral damage. Despite its nonthermal nature, systemic inflammatory and myocardial responses may occur. Catheter design could modulate these effects.
Objective
The purpose of this study was to compare inflammatory and myocardial biomarker responses after PFA using balloon-in-basket vs pentaspline catheter systems.
Methods
This prospective, nonrandomized, single-center study involved venous blood sampling before and the morning after PFA-based PVI using either catheter type. Biomarkers analyzed included leukocytes, C-reactive protein (CRP), platelets, troponin T, creatine kinase (CK), CK-MB, and myoglobin.
Results
Eighty patients were included (balloon-in-basket: n = 40; pentaspline: n = 40). Baseline characteristics were comparable. All patients achieved acute and first-pass PVI. The balloon-in-basket group required fewer PFA applications (16 vs 32; P < .001). Leukocyte and CRP rose in both groups, more so with the pentaspline catheter (Δ leukocytes: 0.6 × 109/L vs 1.9 × 109/L, P = .026; Δ CRP: 3.4 mg/L vs 5.1 mg/L, P = .074). Platelet count decreased more in the balloon-in-basket group (Δ platelets −11 × 109/L vs −1 × 109/L; P = .005), while CK increased more in this group (Δ CK 219.5 U/L vs 97.0 U/L; P < .001). Troponin T, CK-MB, and myoglobin changes were similar.
Conclusion
Balloon-in-basket and pentaspline PFA catheters induce distinct inflammatory and myocardial biomarker profiles after PVI. The observed differences in leukocyte, CRP, and platelet responses highlight design-specific biological effects. These findings may support informed catheter selection and help guide postprocedural monitoring strategies.
Keywords: Pulsed field ablation, Pulmonary vein isolation, Inflammation, Myocardial injury, Platelets, Catheter design, Atrial fibrillation
Graphical abstract
Key Findings.
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Both balloon-in-basket and pentaspline pulsed field ablation catheters induced significant elevations in inflammatory and myocardial biomarkers after pulmonary vein isolation.
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The pentaspline catheter was associated with a more pronounced inflammatory response, with significantly greater increases in leukocytes and a trend toward higher C-reactive protein levels compared with the balloon-in-basket catheter.
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The balloon-in-basket catheter showed significantly higher creatine kinase elevations, suggesting differences in mechanical interaction and myocardial impact.
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Renal function remained stable in the balloon-in-basket group but significantly declined in the pentaspline group, indicating distinct systemic effects between catheter designs.
Introduction
Pulsed field ablation (PFA) is an emerging nonthermal modality for pulmonary vein isolation (PVI) in patients with atrial fibrillation (AF), using irreversible electroporation to ablate myocardial tissue with minimal collateral injury.1 Clinical studies have demonstrated high acute success rates and favorable safety profiles.2,3
Despite its nonthermal nature, PFA may elicit systemic biological effects. Postprocedural elevations of inflammatory and myocardial biomarkers such as leukocytes, C-reactive protein (CRP), troponin-T, and creatine kinase (CK) have been reported, indicating an acute tissue response.4 These biomarkers can reflect myocardial injury and systemic inflammation, offering insight into procedural impact beyond lesion efficacy.
Inflammatory markers, such as CRP, have been linked to arrhythmia recurrence and atrial remodeling, highlighting their clinical relevance.5, 6, 7 Myocardial injury markers, such as troponin-T and CK, also rise consistently after ablation, although their prognostic value remains debated.4,8,9
Among available PFA catheters, the pentaspline design (FARAWAVE, Boston Scientific) is currently the most widely used.10 The balloon-in-basket system (VOLT, Abbott) represents a newer alternative, differing in electrode layout, balloon-mediated contact mechanics, and energy dispersion strategy.2 These technical distinctions may affect inflammatory or myocardial response, yet direct comparisons are lacking.
Evaluating systemic biomarkers post-PFA can help characterize acute biological effects and identify device-specific profiles. Such data may inform catheter selection and refine postprocedural care.
This study aimed to compare biomarker responses after PFA using balloon-in-basket and pentaspline catheter systems.
Methods
Study population and trial design
This prospective, single-center, nonrandomized study evaluated systemic biomarker responses after PFA-based PVI with 2 catheter systems: a pentaspline catheter (FARAWAVE) and a balloon-in-basket catheter (VOLT). Between January 2024 and May 2025, 80 consecutive patients with paroxysmal or persistent AF were enrolled. All procedures were performed at the Heart Center Lübeck and recorded in the institutional ablation registry. A subset of balloon-in-basket patients (n = 27) also participated in the VOLT CE Mark Study.
Eligibility criteria included age ≥18 years, diagnosis of AF, and informed consent. Exclusion criteria were active infection, autoimmune or chronic inflammatory disease, recent myocardial infarction, neuromuscular disorders, or severe hepatic dysfunction, to minimize biomarker confounding.
The study protocol was approved by the institutional ethics committee (Lübeck Ablation Registry, approval number WF-028/15) and was conducted in accordance with the Declaration of Helsinki.11
General procedural management
All patients underwent standardized preprocedural assessment according to the institutional protocol. In patients with elevated thromboembolic risk, transesophageal echocardiography was performed to exclude intracardiac thrombi.
Vitamin K antagonists were continued at a therapeutic international normalized ratio (2.0–3.0), while direct oral anticoagulants were withheld on the morning of the procedure.
Ablation was performed under deep sedation using propofol, midazolam, and fentanyl. In selected cases, continuous propofol was omitted to maintain patient responsiveness. A multimodal analgesic regimen (metamizole, midazolam, fentanyl, and lidocaine) was administered in those patients.
Femoral vein access was obtained via 1 or 2 ultrasound-guided punctures (8-F sheaths). A diagnostic catheter was placed in the coronary sinus. Transseptal puncture was performed under fluoroscopic guidance using the modified Brockenbrough technique.
After transseptal access, intravenous unfractionated heparin was given to maintain an activated clotting time >300 seconds. Left atrial access was established using an SL1 sheath (Abbott).
Catheter assignment was time-based and followed the clinical availability of each system. While not strictly sequential, devices were used during defined periods independent of patient characteristics or operator preference, thereby minimizing selection bias due to anatomy or procedural complexity.
Pentaspline catheter
To prevent vagal reactions, 1 mg of intravenous atropine was administered before the first energy application. The 12-F over-the-wire pentaspline catheter (FARAWAVE) was positioned at the pulmonary vein ostia via the FARADRIVE sheath. For each vein, 8–10 biphasic, bipolar pulses (2 kV, 2.5 seconds each) were delivered, including 4 “basket” and 4–6 “flower” applications, typically beginning with the left pulmonary veins.
Balloon-in-basket catheter
Procedures with the balloon-in-basket system followed the VOLT CE Mark protocol. In 30 cases, left atrial voltage mapping was performed using a high-density catheter; in later cases, anatomical reconstruction was done with the VOLT catheter alone. After mapping, the transseptal sheath was exchanged for a steerable 13-F sheath (Agilis NxT, Abbott), and pulmonary vein access was obtained using a 0.035-in guidewire. PFA was delivered at 1800 V (≥2 rotated applications per vein) or 1400 V (typically 3); up to 8 applications per vein were permitted. For right-sided veins, phrenic nerve capture was assessed via spline pacing. If diaphragmatic stimulation occurred, ablation proceeded at 1400 V with ≥3 applications. Testing was repeated after each repositioning.
Postprocedural management
Hemostasis was achieved using either vascular closure systems or figure-of-eight sutures with a compression bandage. The bandage was removed after 1 to 4 hours and sutures on the following day. Transthoracic echocardiography was routinely performed postprocedure, at 1 hour and on the first postoperative day, to exclude pericardial effusion. Oral anticoagulation was resumed 6 hours after ablation and continued for at least 2 months. Long-term therapy was based on individual thromboembolic risk (CHA2DS2-VASc or CHA2DS2-VA score), in line with current guidelines.12,13
Blood sampling and analysis
Venous blood samples were collected at 2 time points: (1) after femoral access before ablation and (2) on the morning of the first postprocedural day. All samples were obtained fasting. Biomarkers were selected to assess inflammatory, myocardial, and systemic responses to PFA. Leukocyte count and CRP served as markers of systemic inflammation and were analyzed using fluorescence flow cytometry (XN-9000, Sysmex) and immunoturbidimetry (Cobas c 503, Roche), respectively. Platelet count, reflecting potential consumption or endothelial activation, was also measured via flow cytometry. Troponin T and myoglobin, as indicators of myocardial injury, were quantified using electrochemiluminescence immunoassay (Cobas 801, Roche). CK and CK-MB, markers of general and cardiac-specific muscle damage, were determined enzymatically using UV photometry (Cobas c 702, Roche). CK-MB was assessed only in patients with elevated baseline values. Serum creatinine was measured on Cobas c 503 (Roche), and estimated glomerular filtration rate (eGFR) was calculated using the Chronic Kidney Disease Epidemiology Collaboration formula to monitor renal function. All analyses were performed in the central laboratory of the University Hospital Schleswig-Holstein under validated, certified protocols.
Statistical analysis
Continuous data were tested for normality using Shapiro-Wilk tests and are presented as mean ± standard deviation or median (Q1, Q3), as appropriate. Between-group comparisons were made 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 PFA applications were analyzed using Pearson or Spearman coefficients, depending on data distribution. Categorical variables are reported as absolute and relative frequencies and were compared using Fisher exact or χ2 tests, depending on sample size. All analyses were performed using IBM SPSS Statistics version 29.0.1.0 (IBM Corporation). Two-sided P values <.05 were considered statistically significant.
Results
Baseline characteristics
A total of 80 patients were included: 40 treated with the balloon-in-basket catheter and 40 with the pentaspline catheter (Figure 1). The median age was 65.0 years; 22 (50%) were female; and 46 (57.5% ) had paroxysmal AF. Cardiovascular risk factors were similarly distributed between the 2 groups, with no significant differences (Table 1). The median CHA2DS2-VASc score was 2.0 (P = .801). Left ventricular ejection fraction was preserved, and left atrial size was mildly increased in both groups. At the time of ablation, AF was present in 30 (37.5%) patients (P = .134).
Figure 1.
Study flowchart (PRISMA/STROBE format. AF = atrial fibrillation; CK = creatine kinase; CK-MB = creatine kinase-MB; CRP = C-reactive protein; eGFR = estimated glomerular filtration rate; PFA = pulsed field ablation; STROBE = strengthening the reporting of observationl studies in epidemiology; PVI = pulmonary vein isolation.
Table 1.
Baseline characteristics of the study population
| Variable | Total (n = 80) | Balloon-in-basket PFA-PVI group (n = 40) | Pentaspline PFA-PVI group (n = 40) | P |
|---|---|---|---|---|
| Age (y) | 65.0 (59.0–73.3) | 65 (59.8–71.3) | 68 (58.8–75.0) | .275 |
| Sex: female | 40 (50) | 22 (55) | 18 (45) | .371 |
| BMI (kg/m2) | 27.2 (24.4–28.9) | 27.4 (24.6–29.1) | 26.3 (24.3–28.9) | .692 |
| AF type | .245 | |||
| Paroxysmal | 46 (57.5) | 21 (52.5) | 25 (62.5) | |
| Persistent | 34 (42.5) | 19 (47.5) | 15 (37.5) | |
| Arterial hypertension | 46 (57.5) | 21 (52.5) | 25 (62.5) | .407 |
| Diabetes mellitus | 7 (8.8) | 5 (12.5) | 2 (5) | .301 |
| Coronary artery disease | 15 (18.8) | 6 (15) | 9 (22.5) | .476 |
| Heart failure | 11 (13.8) | 4 (10) | 7 (17.5) | .438 |
| Stroke/TIA | 5 (6.3) | 2 (5) | 3 (7.5) | .542 |
| OSAS | 4 (5) | 1 (2.5) | 3 (5) | .585 |
| CHA2DS2-VASc score | 2.0 (1.0–3.0) | 2.0 (1.0–3.0) | 2.0 (2.0–3.0) | .801 |
| LAVI (mL/m2) | 36.8 ± 16.1 | 36.3 ± 13.8 | 33.2 ± 14.7 | .500 |
| LVEF (%) | 55.0 (54.3–59) | 55.0 (55.0–60) | 55.0 (55.0–55.0) | .229 |
| OAC | 67 (83.8) | 33 (82.5) | 34 (85) | .801 |
| Class I/III AAD at baseline | 33 (41.3) | 11 (27.5) | 23 (57.5) | .099 |
| AF at the time of the procedure | 30 (37.5) | 17 (42.5) | 13 (32.5) | .356 |
| NT-proBNP (ng/L) | 365 (138–996) | 306 (79–1309) | 382 (184–967) | .413 |
Values are presented as mean ± standard deviation, median (Q1, Q3), or n (%).
AAD = antiarrhythmic drug; AF = atrial fibrillation; BMI = body mass index; LAVI = left atrial volume index; LVEF = left ventricular ejection fraction; NT-proBNP = N-terminal prohormone of brain natriuretic peptide; OAC = oral anticoagulation; OSAS = obstructive sleep apnea syndrome; PFA = pulsed field ablation; PVI = pulmonary vein isolation; TIA = transient ischemic attack.
Procedural characteristics
Acute PVI was achieved in all procedures, with 100% first-pass isolation in both groups. The median procedure time was longer in the balloon-in-basket group (P < .001), as was the left atrial dwell time (P < .001).
In the balloon-in-basket group, the first 30 procedures involved high-density voltage mapping while the last 10 used anatomical reconstruction with the VOLT catheter alone. This change reduced procedure time (71.5–40.5 minutes), fluoroscopy time (9.3–7.8 minutes), and dwell time (60.0–30.5 minutes). The balloon-in-basket group required fewer PFA applications (P < .001), consistent across all pulmonary veins (P < .001 for all). Fluoroscopy time was slightly longer (P = .052), and both dose-area product (P = .034) and contrast volume (P < .001) were higher in the balloon-in-basket group. No major acute complications occurred in either group (Table 2).
Table 2.
Procedural characteristics of the study population
| Variable | Total (n = 80) | Balloon-in-basket PFA-PVI group (n = 40) | Pentaspline PFA-PVI group (n = 40) | P |
|---|---|---|---|---|
| Procedure time (min) | 43.0 (30.0–69.0) | 68.0 (61.3–77.5) | 30.0 (27.5–38.0) | <.001 |
| Fluoroscopy time (min) | 8.2 (6.0–10.0) | 8.8 (6.3–10.5) | 7.34 (5.5–9.4) | .052 |
| Dose-area product (cGy·cm2) | 330.5 (239.5–464.3) | 364 (263–577.8) | 320 (192–404) | .034 |
| Left atrial dwell time (min) | 29.5 (20.5–55.75) | 57 (43.5–65.3) | 22.0 (18.0–27.0) | <.001 |
| Number of cardioversions | 0 (0–1) | 0 (0–1) | 0 (0–1) | .827 |
| Contrast amount (mL) | 40 (40.0–50.0) | 50 (40; 50) | 40 (30–40) | <.001 |
| Successful acute PVI | 80 (100) | 40 (100) | 40 (100) | >.999 |
| First-pass PVI | 80 (100) | 40 (100) | 40 (100) | >.999 |
| Number of PFA applications per subject | 26.5 (16–32) | 16 (15.8–17) | 32 (32–40) | <.001 |
| Number of PFA applications at the LSPV | 5 (4–8) | 4 (4–4) | 8 (8–10) | <.001 |
| Number of PFA applications at the LIPV | 5 (4–8) | 4 (4–4) | 8 (8–10) | <.001 |
| Number of PFA applications at the RSPV | 5 (4–8) | 4 (3–4) | 8 (8–10) | <.001 |
| Number of PFA applications at the RIPV | 5 (4–8) | 4 (4–4) | 8 (8–10) | <.001 |
Values are presented as median (Q1, Q3) or n (%).
LIPV = left inferior pulmonary vein; LSPV = left superior pulmonary vein; PFA = pulsed field ablation; PVI = pulmonary vein isolation; RIPV = right inferior pulmonary vein; RSPV = right superior pulmonary vein.
Biomarkers—Pre- and postprocedural comparisons
Inflammatory and myocardial biomarkers showed significant periprocedural changes in both groups (Table 3). Leukocyte counts increased significantly in both the balloon-in-basket (P = .005) and pentaspline (P < .001) groups.
Table 3.
Comparison of pre- and postprocedural values in inflammation and myocardial biomarkers in the balloon-in-basket and pentaspline PFA-PVI groups
| Marker | Timing | Total (n = 80) |
P | Balloon-in-basket PFA-PVI group (n = 40) | P | Pentaspline PFA-PVI group (n = 40) | P |
|---|---|---|---|---|---|---|---|
| Leukocytes (×109/L) | Pre | 5.7 (4.7–7.6) | <.001 | 6.2 (5.4–8.2) | .005 | 5.0 (4.5–6.5) | <.001 |
| Post | 7.6 (6.6–9.3) | 8.3 (7.2–9.3) | 7.4 (6.5–9.2) | ||||
| Platelets (×109/L) | Pre | 203.0 (169.8–245.3) | .107 | 212.5 (179.5–258.0) | .003 | 200.0 (165.5–241.3) | .363 |
| Post | 195.5 (171.8–247.6) | 200.0 (164.5–244.8) | 193.0 (175.3–246.3) | ||||
| CRP (mg/L) | Pre | 1.1 (0.7–2.4) | <.001 | 1.1 (0.6–2.0) | <.001 | 1.1 (0.8–2.8) | <.001 |
| Post | 6.8 (4.1–10.9) | 7.3 (3.5–10.1) | 6.3 (4.6–12.3) | ||||
| Creatinine (μmol/L) | Pre | 83.9 ± 21.2 | .002 | 87.1 ± 18.8 | .835 | 75.4 (68.5–86.3) | <.001 |
| Post | 87.6 ± 20.4 | 87.0 ± 18.3 | 85.0 (74.1–97.2) | ||||
| GFR (mL/min) | Pre | 77.5 ± 18.4 | <.001 | 77.2 ± 19.8 | .734 | 77.8 ± 18.4 | <.001 |
| Post | 73.6 ± 17.1 | 76.9 ± 17.9 | 70.6 ± 17.2 | ||||
| Myoglobin (ng/mL) | Pre | 44.5 (36.0–63.8) | <.001 | 42.0 (35.5–50.8) | .001 | 48.0 (36.0–66.3) | <.001 |
| Post | 54.0 (44.5–77.5) | 49.0 (44.0–71.0) | 65.0 (45.5–79.8) | ||||
| CK-MB (n = 9/5/4) (U/L) | Pre | 16.6 (14.5–34.6) | .022 | 15.2 (14.5–16.6) | .181 | 30.5 (23.1–43.1) | .020 |
| Post | 41.7 (34.5–48.1) | 39.1 (32.4–48.5) | 44.1 (36.1–47.9) | ||||
| CK (U/L) | Pre Post |
88.0 (65.8–134.3) 355 (236.0–447.0) |
<.001 | 85.0 (72.3–120.5) 316.0 (229.0–398.0) |
<.001 | 97.0 (63.0–143.3) 376.0 (282.0–492.0) |
<.001 |
| Troponin T (ng/L) | Pre Post |
10.2 (7.2–17.0) 1194.0 (747.0–1710) |
<.001 | 8.9 (6.1–12.0) 1089.5 (697.0–1422.0) |
<.001 | 11.7 (8.6–19.4) 1370 (879–2047.5) |
<.001 |
Values are presented as mean ± standard deviation or median (Q1, Q3). CM MB was available in 9 patients total, 5 in Ballon in basket group, 4 in pentaspline.
CK = creatine kinase; CK-MB = creatine kinase-MB; CRP = C-reactive protein; GFR = glomerular filtration rate; PFA = pulsed field ablation; PVI = pulmonary vein isolation.
Platelet counts decreased in the balloon-in-basket group (P = .003) but remained unchanged in the pentaspline group (P = .363). CRP rose markedly in both groups (P < .001 for both).
Troponin T and CK increased significantly in both groups (P < .001). Myoglobin also rose in both groups (P < .001).
CK-MB increased significantly in the pentaspline group (P = .020) but not in the balloon-in-basket group (P = .181).
Renal function remained stable in the balloon-in-basket group (creatinine: P = .835; eGFR: P = .734) but deteriorated significantly in the pentaspline group (creatinine and eGFR: P < .001 for both).
Intergroup comparisons of delta values
Intergroup comparisons of delta values (Figure 2 and Table 4) showed significant differences in leukocyte (P = .026) and platelet count (P = .005) changes, with a greater leukocyte increase in the pentaspline group and a more pronounced platelet decline in the balloon-in-basket group. CRP rose in both groups, with a nonsignificant trend toward higher values in the pentaspline group (P = .074). Troponin T and CK-MB increased in both groups, with numerically higher deltas in the pentaspline cohort, though without statistical significance (P = .542 and P = .268). In contrast, CK rose significantly more in the balloon-in-basket group (P < .001). Myoglobin changes did not differ between the 2 groups (P = .980). Serum creatinine increased and eGFR decreased significantly in the pentaspline group compared with the balloon-in-basket group (P < .001 and P = .002, respectively).
Figure 2.
Comparison of delta values between the balloon-in-basket PFA-PVI group and the pentaspline PFA-PVI group. Box plots represent the median and interquartile range of changes from baseline to 18–24 hours postprocedure. CK = creatine kinase; CRP = C-reactive protein; PFA = pulsed field ablation; PVI = pulmonary vein isolation.
Table 4.
Comparison of periprocedural changes (delta values) in inflammation and myocardial biomarkers between balloon-in-basket and pentaspline PFA-PVI groups
| Variable | Total (n = 40) |
Balloon-in-basket PFA-PVI group (n = 40) | Pentaspline PFA-PVI group (n = 40) | P |
|---|---|---|---|---|
| Δ Leukocytes (×109/L) | 1.9 (0.0-3.0) | 0.6 (−0.4-3.1) | 1.9 (1.5-3.1) | .026 |
| Δ Platelets (×109/L) | −3.5 (−16.25-11.0) | −11 (−24.5-−1) | −1 (−10.5-20.5) | .005 |
| Δ CRP (mg/L) | 4.2 (2.7-6.9) | 3.4 (2.3-6.0) | 5.1 (3.4-8.2) | .074 |
| Δ Creatinine (μmol/L) | 3.0 (−3.0-9.75) | 1.0 (−5.3-4.8) | 7.2 (3-12.2) | <.001 |
| Δ GFR (mL/min) | −2.0 (−8.8-1.75) | −1.0 (−4.3-3.0) | −6.0 (−12-−2) | .002 |
| Δ Myoglobin (ng/mL) | 11.0 (0.0-25.3) | 10.0 (0.0-25.8) | 12.0 (−2.5-25.0) | .980 |
| Δ CK-MB (U/L) | 26.6 ± 23.5 | 19.6 ± 15.9 | 35.7 ± 23.5 | .268 |
| Δ CK (U/L) | 132 (79.0-217) | 219.5 (132.3-313.8) | 97.0 (63.0-142.5) | <.001 |
| Δ Troponin T (ng/L) | 1173.6 (722.6-1723) | 1189.0 (875.6-1711.3) | 1402.4 (862.9-2050.1) | .542 |
Values are presented as mean ± standard deviation or median (Q1, Q3).
Δ = postprocedural minus preprocedural value; CK = creatine kinase; CK-MB = creatine kinase-MB; CRP = C-reactive protein; GFR = glomerular filtration rate; PFA = pulsed field ablation; PVI = pulmonary vein isolation.
Correlation matrix
Correlation analyses for each catheter group are summarized in Tables 5 and 6. In both groups, there was no statistically significant correlation between the number of PFA applications and changes in evaluated laboratory values. Subgroup analysis in the balloon-in-basket group showed no correlation between procedural time and changes in evaluated laboratory values.
Table 5.
Correlation between the amount of PFA impulses and inflammation/myocardial biomarkers changes in balloon-in-basket and pentaspline PFA-PVI groups
| Marker | Correlation in the balloon-in-basket PFA-PVI group (n = 40) | P | Correlation in the pentaspline PFA-PVI group (n = 40) | P |
|---|---|---|---|---|
| Leukocytes | 0.083 | .418 | −0.172 | .260 |
| Platelets | 0.025 | .824 | −0.085 | .583 |
| CRP | −0.010 | .656 | 0.004 | .982 |
| Creatinine | 0.026 | .915 | 0.039 | .151 |
| GFR | −0.016 | .776 | −0.260 | .199 |
| Myoglobin | −0.255 | .245 | 0.035 | .824 |
| CK-MB | −0.151 | .808 | 0.347 | .360 |
| CK | 0.193 | .774 | 0.157 | .307 |
| Troponin T | 0.108 | .797 | 0.072 | .769 |
CK = creatine kinase; CK-MB = creatine kinase-MB; CRP = C-reactive protein; GFR = glomerular filtration rate; PFA = pulsed field ablation; PVI = pulmonary vein isolation.
Table 6.
Correlation between procedure time and inflammation/myocardial biomarkers changes in balloon-in-basket PVI
| Marker | Correlation in the balloon-in-basket PFA-PVI group (n = 40) | P |
|---|---|---|
| Leukocytes | 0.111 | .503 |
| Platelets | −0.245 | .127 |
| CRP | −0.245 | .170 |
| Creatinine | 0.005 | .975 |
| GFR | −0.094 | .564 |
| Myoglobin | 0.055 | .771 |
| CK-MB | 0.345 | .570 |
| CK | 0.244 | .165 |
| Troponin T | 0.048 | .804 |
CK = creatine kinase; CK-MB = creatine kinase-MB; CRP = C-reactive protein; GFR = glomerular filtration rate; PFA = pulsed field ablation; PVI = pulmonary vein isolation.
Discussion
This prospective study examined inflammatory and myocardial marker changes during PVI with balloon-in-basket vs pentaspline PFA systems. The central findings were as follows:
-
1.
Inflammatory markers, particularly leukocytes and CRP, increased significantly in both groups after ablation.
-
2.
Biomarkers of myocardial injury—troponin T, CK, and CK-MB—rose substantially in both groups.
-
3.
Intergroup analyses revealed significantly greater increases in leukocytes and a trend toward higher CRP in the pentaspline group.
Inflammatory response to PFA: Device design and interface dynamics
Cardiac ablation, irrespective of energy modality, triggers an inflammatory response due to cellular disruption and immune activation. In this study, both PFA systems led to significant increases in leukocyte count and CRP, consistent with prior reports.4,14 While radiofrequency ablation induces widespread inflammation via coagulative necrosis, PFA is believed to provoke a more localized and attenuated response through nonthermal electroporation.4,14, 15, 16
The more pronounced inflammatory response observed with the pentaspline system likely results from a combination of factors: (1) catheter design and contact geometry, (2) field orientation and current dispersion, and (3) lack of contact-specific energy modulation.
The balloon-in-basket system uses a semi-compliant balloon to stabilize electrode-tissue contact, enabling uniform circumferential lesion formation. Laterally oriented electrodes embedded in the balloon surface focus electroporation at the myocardial interface while limiting energy dispersion beyond the target zone. In contrast, the pentaspline catheter deploys independent splines without balloon support, resulting in variable contact with the pulmonary vein wall and potentially less consistent energy coupling, which may amplify systemic inflammatory signaling.17,18
Although a higher number of applications may imply greater cumulative energy, the absence of correlation between impulse count and biomarker elevation likely reflects protocol constraints—specifically, fixed dosing of 16 impulses per vein in the balloon-in-basket group and 32 in the pentaspline group—limiting variability for detecting dose-response effects. Despite shorter procedure and dwell times in the pentaspline group, the stronger inflammatory response suggests that qualitative aspects of energy delivery—rather than procedural duration—may drive biomarker dynamics. Interestingly, platelet counts declined more markedly in the balloon-in-basket group. This may reflect shear stress or endothelial activation. The balloon-in-basket design, with its larger diameter and expansion mechanism, likely causes more mechanical interaction with the endocardial surface than does the pentaspline catheter. Together, these findings underscore that catheter architecture, energy precision, and contact control—not only impulse count or procedure time—are key determinants of the systemic inflammatory response to PFA. Further studies should explore whether refining catheter design and energy modulation can enhance procedural biocompatibility without compromising efficacy.
Myocardial injury after PFA: Reflections on energy delivery and tissue response
Consistent with prior studies on myocardial injury postablation, this study showed significant increases in troponin-T, CK, and CK-MB in both PFA groups. These established injury markers consistently rise after myocardial energy delivery.4,19 Troponin-T rose in both groups, with a nonsignificant trend toward higher levels in the pentaspline group.
CK and CK-MB also rose significantly, with total CK elevation greater in the balloon-in-basket group. Although CK is not entirely cardiac-specific, this may suggest broader or more confluent lesions.4,20 Still, in the absence of direct lesion visualization, this remains speculative. Variations in contact quality or catheter stability may offer alternative explanations.
No correlation was observed between impulse count and myocardial biomarker elevation. However, because of fixed-dosing protocols with limited variability, a potential dose-response relationship cannot be excluded.
Despite its nonthermal nature, PFA can result in substantial myocardial injury.21, 22, 23 Magnetic resonance imaging (MRI) studies have demonstrated larger lesion volumes with PFA than with radiofrequency ablation, likely reflecting system-specific features and reduced reliance on contact force.20
Elevated troponin-T —particularly with single-shot devices—support the hypothesis of broader myocardial engagement. Yet, the clinical significance remains unclear.4,16,23, 24, 25 The extent to which measured injury reflects irreversible electroporation vs transient membrane effects remains unclear. Only irreversible damage is expected to cause fibrosis and functional consequences. Imaging and tissue characterization studies are needed to assess lesion permanence and viability.
Myoglobin rose significantly in both groups, without intergroup differences, suggesting limited sensitivity to catheter-specific factors. Despite more prominent skeletal muscle contractions with the pentaspline system, no additional myoglobin release was observed, arguing against extracardiac sources.
The comparable myoglobin response contrasts with the eGFR decline seen only in the pentaspline group, supporting a device-related rather than myoglobin-mediated mechanism. Overall, both systems induced robust myocardial biomarker release, likely driven by lesion size, tissue properties, catheter mechanics, and release kinetics.16,20,23,25 Further studies integrating biomarkers, imaging, and histology are warranted to determine clinical impact.
Renal function and myoglobin
Transient reductions in renal function are known to occur after ablation, but the underlying mechanisms remain unclear. While both groups showed similar myoglobin elevations, eGFR decline occurred only in the pentaspline arm. This dissociation may reflect catheter- or procedure-related effects beyond tubular stress, although other unmeasured factors cannot be excluded.
Clinical relevance and outlook
Periprocedural biomarker changes after PFA may reflect procedural burden and offer insight into safety, procedural quality, and long-term outcomes. Although no overt complications occurred, these patterns raise concerns about subclinical injury and cumulative tissue stress.
The findings suggest that PFA systems may elicit different biological effects, potentially influenced by design, energy delivery, or procedural parameters. Geometry and mapping integration may also contribute. Whether these differences are clinically relevant remains uncertain. The single postablation time point (18–24 hours) limited assessment of dynamic biomarker kinetics, such as onset, peak, and resolution. Sequential monitoring may improve interpretability and support protocol optimization. Future studies should link biomarkers to imaging, rhythm outcomes, and tissue remodeling. Cardiac MRI and molecular tools may provide further insight. In the long term, machine learning could support personalized strategies. A multicenter randomized trial is needed to confirm these results and reduce bias from the single-center nonrandomized design.
Limitations
This study has limitations. First, it was conducted at a single high-volume center with a limited sample size, restricting generalizability and statistical power, especially for exploratory analyses.
Second, biomarkers were assessed only once (18–24 hours postablation), limiting insight into temporal dynamics such as onset, peak, and resolution. Also, no apoptosis-related biomarkers were assessed.
Third, no MRI was performed to directly assess lesion characteristics; conclusions were inferred from biomarkers.
Fourth, fixed protocol specifications (16 applications vs 32 applications) limited variability in energy delivery, reducing sensitivity to dose-response effects.
Finally, most balloon-in-basket cases were part of the VOLT CE Mark Study, introducing possible protocol-related bias.
Conclusion
To the best of our knowledge, this is the first study to compare the periprocedural inflammatory and myocardial responses of pentaspline and balloon-in-basket PFA systems during PVI. Both catheters induced significant biomarker elevations, with the pentaspline group showing greater increases in leukocytes, CRP, and myocardial injury markers, suggesting a stronger systemic response.
Although not correlated with impulse count, the observed biomarker differences may reflect the impact of catheter design, supporting further refinement of PFA technologies.
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. After using this tool/service, the authors reviewed and edited the content as needed and take full responsibility for the content of the publication.
Disclosures
Dr Wenzel has received funding from the German Foundation of Heart Research (F/29/19), speaker fees from Abbott and Doctrina Med, and travel support from Boston Scientific. Dr Eitel has received research/travel grants and speaker fees from Abbott, Boston Scientific, LifeTech, Biosense Webster, CardioFocus, CTI GmbH, and Doctrina Med. Dr Nikorowitsch has received speaker fees from Abbott. Dr de Waha has received consulting fees from Zoll/Therox and speaker fees from Edwards Lifesciences. Dr Kuck has received grants/personal fees from Abbott, Medtronic, and Biosense Webster. Dr Tilz has received speaker fees from Pfizer, Abbott, Biosense Webster, Boston Scientific, Doctrina Med, cme4u, Medtronic, Radcliffe, and Wikonect; consulting/advisory fees from Boston Scientific, Biosense Webster, Capvision, Guidepoint, Haemonetics, Medtronic, Philips, and Abbott; institutional research support from Biotronik, Abbott, Boston Scientific, Medtronic, LifeTech, and J&J; and travel support from Biosense Webster, Abbott, Boston Scientific, Medtronic, and Philips. The rest of the authors have no conflicts of interest.
Acknowledgments
Funding Sources
This research did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors.
Authorship
All authors attest they meet the current ICMJE criteria for authorship.
Patient Consent
Eligibility criteria included informed consent.
Ethics Statement
The study protocol was approved by the institutional ethics committee (Lübeck Ablation Registry, approval number WF-028/15) and conducted in accordance with the Declaration of Helsinki.
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