Abstract
Background
Pulsed field ablation (PFA) is a non-thermal modality for pulmonary vein isolation (PVI) in atrial fibrillation (AF). While effective, hemolysis and renal effects may occur, potentially modulated by catheter design.
Methods
In this prospective, non-randomized, single-center study, patients underwent PFA-based PVI using either a balloon-in-basket catheter or a pentaspline catheter. Hemolysis (LDH, bilirubin, haptoglobin, myoglobin) and renal markers (creatinine, eGFR) were assessed immediately before and the morning after ablation.
Results
Eighty-one patients were included (balloon-in-basket: n=35; pentaspline: n=46), with comparable baseline characteristics. Both groups achieved acute 100% first-pass PVI. The pentaspline group received more PFA applications (32 [32–40] vs. 16 [16–18], p<0.001). Hemolytic markers increased significantly in both groups but were more pronounced in the pentaspline group: LDH Δ+99 [76–121] vs. +59 [43–69] U/L, bilirubin Δ+5.2 [2.4–8.5] vs. +2.4 [0.2–5.1] µmol/L, haptoglobin Δ−28 [−39 to −18] vs. −6 [−17 to +5] mg/dL (all p<0.001). Myoglobin increased modestly in both groups: Δ+12.0 [0–26.0] vs. +11.0 [0–21.5] ng/mL (p=0.696). Only the pentaspline group exhibited a significant renal function decline: creatinine Δ+6.0 [2.2–11.5] vs. +2.0 [−4.0–4.4] µmol/L (p=0.009); eGFR Δ−4.5 [−10.8 to −1.3] vs. −1.0 [−3.5–5.0] mL/min (p=0.002).
Conclusion
The pentaspline catheter induced more hemolysis and a measurable decline in renal function. Myoglobin increases were similar in both groups and unlikely to explain the renal findings. Catheter design and energy delivery appear to shape the systemic impact profile of PFA.
Graphical abstract
Keywords: Pulsed field ablation, Pulmonary vein isolation, Hemolysis, Renal function, Catheter design, Balloon-in-basket, Pentaspline
Introduction
Pulsed field ablation (PFA) has quickly gained attention as a novel and non-thermal energy source for pulmonary vein isolation (PVI), offering selective myocardial ablation with the potential to spare surrounding non-cardiac tissue [1, 2]. While the safety profile of PFA is generally favorable, accumulating clinical data suggest that hemolysis may be a frequent byproduct of the procedure, particularly when using the widely adopted pentaspline PFA catheter system.
Several studies and multicenter clinical experiences have reported that a significant proportion of patients undergoing PVI with the pentaspline catheter develop biochemical signs of hemolysis, including elevated plasma free hemoglobin, lactate dehydrogenase (LDH), and related markers of red blood cell destruction [3, 4]. In some cases, this hemolytic burden has been associated with signs of pigment-induced acute kidney injury (AKI), highlighting the need to better understand the systemic effects of PFA energy delivery [5, 6].
These observations raise the question of whether hemolysis is an intrinsic feature of PFA or if it is influenced by catheter-specific factors. Catheter design—particularly electrode configuration, tissue contact, and the dynamics of energy application—may play a pivotal role in determining the degree of red blood cell injury. The balloon-in-basket PFA catheter (VOLT) represents a newer generation of PFA technology, designed to allow for real-time assessment of tissue contact and potentially more controlled energy delivery [7]. Recently published data using this system demonstrated no clinically relevant hemolysis or renal impairment following PVI, supporting the hypothesis that catheter design can significantly influence hemolytic outcomes [8, 9].
To date, no study has directly compared hemolysis and renal safety between these two PFA catheter systems. The present study aims to close this gap by performing a head-to-head comparison of a balloon-in-basket and a pentaspline PFA catheter, evaluating their impact on hemolysis and renal function following PVI.
Methods
Study population and trial design
This prospective, non-randomized, single-center study aimed to compare hemolysis-related renal safety following PFA-based PVI using either a balloon-in-basket or a pentaspline PFA catheter. Between January 2024 and April 2025, consecutive patients with symptomatic atrial fibrillation (AF) undergoing PFA-based PVI with either a pentaspline catheter (FARAWAVE™, Boston Scientific) or a balloon-in-basket catheter (VOLT™ PFA system, Abbott) were prospectively enrolled. All participants were included in the Lübeck Ablation Registry, and 27 of the 35 patients treated with the balloon-in-basket system were additionally enrolled in the VOLT CE Mark study, sponsored by Abbott. The study protocol was approved by the institutional ethics committee (Lübeck Ablation Registry, approval number WF-028/15), and written informed consent was obtained from all participants. The study conformed to the ethical principles of the Declaration of Helsinki. Eligible patients were >18 years of age, had symptomatic paroxysmal or persistent AF, and provided written informed consent. Patients with known hematologic disorders predisposing to hemolysis or with hepatic dysfunction associated with elevated bilirubin levels were excluded.
General procedural management
All patients underwent preprocedural evaluation according to institutional standards. In patients with elevated stroke risk, intracardiac thrombi were excluded by transesophageal echocardiography. In patients receiving vitamin K antagonists, ablation was performed with a therapeutic international normalized ratio (INR) of 2–3. In patients on direct oral anticoagulants (DOACs), the morning dose was withheld on the day of the procedure. All ablations were performed under deep sedation using propofol, midazolam, and fentanyl, in accordance with national recommendations [7, 10]. One or two ultrasound-guided 8 Fr femoral venous access sites were obtained. A diagnostic catheter was positioned in the coronary sinus, and a single transseptal puncture (TSP) was performed under fluoroscopic guidance using a modified Brockenbrough technique. After TSP, intravenous heparin was administered to maintain an activated clotting time (ACT) >300 s. An SL1 sheath (Abbott) was used to access the left atrium. Contrast dye was administered both to guide transseptal puncture and for selective pulmonary vein angiography prior to ablation.
PFA procedure—pentaspline catheter
To prevent vagal responses, 1 mg of atropine was administered intravenously prior to energy delivery. The 12-Fr, over-the-wire pentaspline catheter (FARAWAVE™, Boston Scientific) was positioned at the ostium of each pulmonary vein. In general, eight to ten pulse trains (2 kV, 2.5 s each; bipolar, biphasic waveform) were delivered per pulmonary vein, typically consisting of four applications in the “basket” and four to six in the “flower” configuration, starting with the left-sided veins in accordance with institutional protocols [11]. Flower applications were angulated to target broader anterior and posterior antral segments.
PFA procedure—balloon-in-basket catheter
The procedure was performed as defined in the VOLT CE mark study protocol [7]. In 27 out of the 35 VOLT™ cases, pre-ablation three-dimensional voltage mapping of the left atrium was performed using a high density mapping catheter. In subsequent cases, the VOLT™ catheter was used for anatomical reconstruction. Following mapping, the transseptal sheath was exchanged for a steerable 13 Fr sheath (Agilis™ NxT, Abbott). A 0.035-inch guidewire was used to access the pulmonary veins and provide catheter stability. PFA energy was delivered at nominal (1800 V) or reduced (1400 V) waveform settings. At nominal energy, at least two applications with device rotation were performed per vein; at reduced energy, three applications were used. A maximum of eight applications per vein were delivered. For right-sided veins, phrenic nerve capture was assessed by pacing from the splines of the VOLT™ catheter. If capture occurred, ablation was performed using the low-voltage waveform (minimum of three times 1400 V). Phrenic testing was repeated following each repositioning. A maximum of eight applications was permitted per vein. In two patients treated with the balloon-in-basket system, additional posterior wall isolation was performed using four supplemental applications at 1700 V with deselection of not-in-contact splines. Following ablation, a 20-min waiting period was applied prior to post-ablation voltage remapping and final confirmation of phrenic nerve integrity by pacing from the superior vena cava.
Postprocedural management
Hemostasis was achieved using either vascular closure devices or a figure-of-eight suture combined with a pressure bandage. The pressure bandage was removed after 2–4 h, depending on the closure method, and the suture was removed on the following day. Transthoracic echocardiography was performed immediately post-procedure, at 1 h, and on the first post-ablation day to exclude pericardial effusion. Intravenous fluid administration was not standardized, but patients with an eGFR below 60 mL/min routinely received 500 mL of a fully electrolyte-balanced solution on the day of the intervention and the following day. No systematic intergroup differences were present. Oral anticoagulation was resumed 6 h after the procedure and continued for a minimum of 2 months. Long-term anticoagulation was guided by the individual CHA₂DS₂-VASc/CHA₂DS₂-VA score.
Blood sampling and analysis
Venous blood samples were obtained at two time points: (1) immediately after femoral venous access at the start of the procedure and (2) on the morning of the first post-procedural day. All patients were in a fasting state at the time of sampling. Hemoglobin was measured from lithium heparinized whole blood using visible photometry on the IL GEM4000 analyzer. LDH, total bilirubin, creatinine, eGFR, and haptoglobin were measured from lithium heparin plasma using photometric and immunoturbidimetric assays on the Cobas pro c503 analyzer (Roche Diagnostics). eGFR was calculated using the CKD-EPI formula. All analyses were performed in the central clinical chemistry laboratory of the University Hospital Schleswig-Holstein according to standardized protocols.
Statistical analysis
Continuous variables are presented as mean ± standard deviation (SD) for normally distributed data or as median and interquartile range (25th–75th percentile) for non-normally distributed data, as assessed by the Shapiro–Wilk test. Categorical variables are reported as absolute numbers and percentages. Intra-group comparisons of continuous variables were performed using the paired-samples t-test or Wilcoxon signed-rank test, as appropriate. Between-group comparisons were conducted using the unpaired t-test or Mann–Whitney U test, depending on the distribution. Normality was evaluated based on the distribution of raw values for independent comparisons and the distribution of differences for paired comparisons. If normality assumptions were not met in either group, non-parametric tests were applied (e.g., Mann–Whitney U test for between-group comparisons of age). Categorical variables were compared using Fisher’s exact test. A two-sided p-value <0.05 was considered statistically significant. To assess associations between the number of PFA impulses and laboratory parameters (e.g., LDH, creatinine), Spearman’s rank correlation coefficient was used due to non-normal distribution of the variables, as determined by the Shapiro–Wilk test. All analyses were performed using IBM SPSS Statistics for Mac, Version 29.0.2.0 (IBM Corp., Armonk, NY, USA).
Results
Baseline characteristics
A total of 81 consecutive patients undergoing PFA-based PVI were prospectively included, with 35 patients treated using a balloon-in-basket PFA catheter and 46 patients treated using a pentaspline PFA catheter (Table 1) Fig. 1. The median age was 66.0 [61.0; 72.3] years in the balloon-in-basket group and 69.5 [61.0; 75.0] years in the pentaspline group (p = 0.307). Female patients accounted for 40.0% and 52.2% of the groups, respectively (p = 0.277). Body mass index and AF type were similarly distributed, with paroxysmal AF present in 48.6% of balloon-in-basket patients and 63.0% of those in the pentaspline group (p = 0.246). The prevalence of cardiovascular comorbidities, including arterial hypertension, diabetes mellitus, coronary artery disease, heart failure, and prior stroke or TIA, was comparable between groups. Median CHA₂DS₂-VASc score was 2.0 [1.0; 3.8] in the balloon-in-basket group and 2.5 [2.0; 3.8] in the pentaspline group (p = 0.715). Echocardiographic parameters showed preserved left ventricular ejection fraction in both groups (median 55.0% [51.0; 60.0] vs. 55.0% [53.0; 55.0], p = 0.392), and similar left atrial volume indices. Use of class I or III antiarrhythmic drugs at baseline was more frequent in the pentaspline group (58.7% vs. 28.6%, p = 0.007).
Table 1.
Baseline characteristics of the study population
| Balloon-in-basket PFA PVI group (n=35) | Pentaspline PFA PVI group (n=46) | p-value | |
|---|---|---|---|
| Age (years) | 66.0 [61.0; 72.3] | 69.5 [61.0; 75.0] | 0.307 |
| Sex (female), n (%) | 14 (40.0%) | 24 (52.2%) | 0.277 |
| BMI (kg/m2) | 26.0 [23.9; 29.4] | 27.3 [24.8; 28.7] | 0.249 |
| AF Type, n (%): | 0.246 | ||
| - Paroxysmal | 17 (48.6%) | 29 (63.0%) | |
| - Persistent | 18 (51.4%) | 17 (37%) | |
| Arterial hypertension, n (%) | 18 (51.4%) | 30 (65.2%) | 0.211 |
| Diabetes mellitus, n (%) | 6 (17.1%) | 3 (6.5%) | 0.165 |
| Coronary artery disease, n (%) | 5 (14.3%) | 10 (21.7%) | 0.392 |
| Heart failure, n (%) | 6 (17.2%) | 8 (17.4%) | 0.977 |
| Stroke/TIA, n (%) | 2 (5.7%) | 4 (8.7%) | 0.694 |
| OSAS, n (%) | 2 (6.7%) | 2 (4.4) | 1.0 |
| CHA₂DS₂-VASc Score | 2.0 [1.0; 3.8] | 2.5 [2.0; 3.8] | 0.715 |
| LAVI (mL/m2) | 33.0 [27.7; 47.5] | 34.0 [34.0; 42.5] | 0.436 |
| LVEF (%) | 55.0 [51.0; 60] | 55.0 [53.0; 55.0] | 0.392 |
| Class I/III AAD at baseline, n (%) | 10 (28.6%) | 27 (58.7%) | 0.007 |
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
Fig. 1.
Study PRISMA (STROBE format). AF, atrial fibrillation; LDH, lactate dehydrogenase; PFA, pulsed field ablation; PVI, pulmonary vein isolation
Procedural characteristics
All patients achieved successful acute PVI, and first-pass isolation of all pulmonary veins was achieved in 100% of procedures in both groups. Procedure time was significantly shorter in the pentaspline PFA group (30.5 [27.3; 40.0] min) compared to the balloon-in-basket group (69.0 [64.3; 76.8] min, p < 0.001; Table 2). Left atrial dwell time and contrast volume were also lower in the pentaspline group (22.5 [18.0; 29.0] min vs. 58.0 [54.3; 64.8] min, and 40 [30; 40] mL vs. 50 [40; 50] mL, both p < 0.001). Patients in the pentaspline group received more PFA applications overall (32 [32; 40] vs. 16 [16; 18], p < 0.001) and per pulmonary vein (all p < 0.001). Dose area product was modestly lower in the pentaspline group (308 [176; 405] vs. 361 [271; 483] cGy·cm2, p = 0.033), while fluoroscopy time and the number of periprocedural cardioversions were similar between groups.
Table 2.
Procedural characteristics of the study population
| Variable | Balloon-in-basket PFA PVI group (n=35) | Pentaspline PFA PVI group (n=46) | p-value |
|---|---|---|---|
| Procedure time (min) | 69.0 [64.3; 76.8] | 30.5 [27.3; 40.0] | <0.001 |
| Fluoroscopy time (min) | 8.5 [6.2; 10.0] | 7.4 [5.5; 10.0] | 0.147 |
| Dose area product (cGy·cm2) | 361 [271; 483] | 308 [176; 405] | 0.033 |
| Left atrial dwell time (min) | 58 [54.3; 64.8] | 22.5 [18.0; 29.0] | <0.001 |
| Number of cardioversions, n | 0 [0; 1] | 0 [0; 1] | 1 |
| Contrast amount (mL) | 50 [40; 50] | 40 [30; 40] | <0.001 |
| Successful acute PVI, n (%) | 35 (100) | 46 (100) | 1 |
| First-pass PVI, n (%) | 35 (100) | 46 (100) | 1 |
| PFA applications per subject, n | 16 [16; 18] | 32 [32; 40] | <0.001 |
| PFA applications LSPV n | 4 [4; 4] | 8 [8; 10] | <0.001 |
| PFA applications LIPV, n | 4 [4; 4] | 8 [8; 10] | <0.001 |
| PFA applications RSPV, n | 4 [4; 4.8] | 8 [8; 10] | <0.001 |
| PFA applications RIPV, n | 4 [4; 4] | 8 [8; 10] | <0.001 |
| Major adverse events | 0 (0) | 0 (0) | 1 |
Values are presented as median [interquartile range]
LSPV left superior pulmonary vein, LIPV left inferior pulmonary vein, RSPV right superior pulmonary vein, RIPV right inferior pulmonary vein
Hemolysis and renal function—pre/post comparisons
Markers of hemolysis changed significantly from baseline to 24 h post-ablation in both groups (Table 3). LDH increased in the balloon-in-basket group from 197 [165; 236] to 248 [228; 269] U/L (p < 0.001), and in the pentaspline group from 189 [169; 219] to 285 [260; 318] U/L (p < 0.001). Haptoglobin decreased in both groups, with a post-procedural median of 105 [72; 145] mg/dL in the balloon-in-basket group (p = 0.037) and 65 [34; 98] mg/dL in the pentaspline group (p < 0.001). Total bilirubin increased in both groups (balloon-in-basket: from 8.6 [7.1; 10.8] to 9.9 [8.1; 15.1] µmol/L; pentaspline: from 9.5 [7.5; 12.1] to 13.1 [10.8; 20.2] µmol/L; both p < 0.001). Myoglobin levels also rose post-ablation: from 42.0 [35.0; 50.0] to 50.0 [45.0; 71.0] ng/mL in the balloon-in-basket group (p < 0.001), and from 46.0 [36.0; 66.0] to 69.0 [46.0; 81.5] ng/mL in the pentaspline group (p < 0.001). Renal markers remained stable in the balloon-in-basket group, with no significant changes in serum creatinine or GFR. In contrast, the pentaspline group showed a statistically significant increase in creatinine (80.4 [70.3; 88.4] to 86.2 [75.5; 94.0] µmol/L, p < 0.001) and a decrease in GFR (82.5 [61.5; 90.0] to 71.0 [59.5; 81.0] mL/min, p < 0.001). No standardized hydration protocol was applied, urine output was not monitored, and no cases of macroscopic hemoglobinuria occurred.
Table 3.
Comparison of pre- and post-procedural values for hemolysis and renal function markers in the balloon-in-basket and pentaspline PFA PVI groups
| Timing | Balloon-in-basket PFA PVI group (n=35) | p-value | Pentaspline PFA PVI group (n=46) | p-value | |
|---|---|---|---|---|---|
| Hemoglobin (g/dL) | Pre | 14.1 [13.2; 15.0] | 0.002 | 12.8 [11.9; 13.6] | 0.415 |
| Post | 13.5 [12.7; 14.1] | 13.2 [12.6; 13.7] | |||
| Haptoglobin (mg/dL) | Pre | 128 [75; 154] | 0.037 | 97 [76; 124] | <0.001 |
| Post | 105 [72; 145] | 65 [34; 98] | |||
| LDH (U/L) | Pre | 197 [165; 236] | <0.001 | 189 [169; 219] | <0.001 |
| Post | 248 [228; 269] | 285 [260; 318] | |||
| Total Bilirubin (µmol/L) | Pre | 8.6 [7.1; 10.8] | <0.001 | 9.5 [7.5; 12.1] | <0.001 |
| Post | 9.9 [8.1; 15.1] | 13.1 [10.8; 20.2] | |||
| Myoglobin | Pre | 42.0 [35.0; 50.0] | <0.001 | 46.0 [36.0; 66.0] | <0.001 |
| ng/mL | Post | 50.0 [45.0; 71.0] | 69.0 [46.0; 81.5] | ||
| Creatinine (µmol/L) | Pre | 79.0 [71.2; 99.5] | 0.651 | 80.4 [70.3; 88.4] | <0.001 |
| Post | 86.0 [74.6; 101.5] | 86.2 [75.5; 94.0] | |||
| GFR (ml/min) | Pre | 75.0 [65.0; 90.5] | 0.888 | 82.5 [61.5; 90.0] | <0.001 |
| Post | 79.0 [65.5; 87.0] | 71.0 [59.5; 81.0] |
Values are presented as median [interquartile range]
Intergroup comparison of delta values
Periprocedural delta values (Table 4) revealed significantly larger changes in markers of hemolysis and renal function in the pentaspline group Fig 2. LDH increased by 99 [76; 121] U/L compared to 59 [43; 69] U/L in the balloon-in-basket group (p < 0.001). Haptoglobin decreased by −28 [−39; −18] mg/dL in the pentaspline group and −6 [−17; 5] mg/dL in the balloon-in-basket group (p < 0.001). Bilirubin increased by 5.2 [2.4; 8.5] µmol/L vs. 2.4 [0.2; 5.1] µmol/L, respectively (p < 0.001). Myoglobin also increased in both groups, but the delta values did not differ significantly (12.0 [0; 26.0] ng/mL vs. 11.0 [0; 21.5] ng/mL, p = 0.696). Renal markers showed greater periprocedural changes in the pentaspline group. Creatinine increased by 6.0 [2.2; 11.5] µmol/L versus 2.0 [−4.0; 4.4] µmol/L in the balloon-in-basket group (p = 0.009), while GFR declined by −4.5 [−10.8; −1.3] vs. −1.0 [−3.5; 5.0] mL/min (p = 0.002). Hemoglobin levels decreased in the balloon-in-basket group (−0.71 ± 1.13 g/dL) and remained unchanged in the pentaspline group (+0.12 ± 0.98 g/dL, p = 0.042).
Table 4.
Comparison of periprocedural changes (delta values) in hemolysis and renal function markers between balloon-in-basket and Pentaspline PFA PVI
| Marker | Balloon-in-basket PFA PVI group | Pentaspline PFA PVI group | p-value |
|---|---|---|---|
| Δ Hemoglobin (g/dL) | −0.71 ± 1.13 | 0.12 ± 0.98 | 0.042 |
| Δ Haptoglobin (mg/dL) | −6 [−17; 5] | −28 [−39; −18] | <0.001 |
| Δ LDH (U/L) | 59 [43; 69] | 99 [77; 121] | <0.001 |
| Δ Myoglobin (ng/L) | 11.0 [0; 21.5] | 12.0 [0; 26.0] | 0.696 |
| Δ Total Bilirubin (mg/dL) | 2.4 [0.2; 5.1] | 5.2 [2.4; 8.5] | <0.001 |
| Δ Creatinine (mg/dL) | 2.0 [−4.0; 4.4] | 6.0 [2.2; 11.5] | 0.009 |
| Δ GFR (mL/min) | −1 [−3.5; 5.0] | −4.5 [−10.8; −1.3] | 0.002 |
Values are presented as mean and standard deviation or median [interquartile range]. Delta = post-procedural minus pre-procedural value
Fig. 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 (IQR) of changes from baseline to 24 h post-procedure. P-values were calculated using the Wilcoxon rank-sum test; p < 0.05 was considered statistically significant.
Correlation between number of PFA applications and hemolysis
In the pentaspline PFA group, there was no significant correlation between the number of impulses and bilirubin (ρ = 0.020, p = 0.906), LDH (ρ = −0.093, p = 0.601), creatinine (ρ = −0.165, p = 0.278), or GFR (ρ = −0.174, p = 0.252). However, a significant negative correlation was observed with haptoglobin (ρ = −0.341, p = 0.039). In contrast, in the balloon-in-basket PFA group, no significant correlations were found between the number of impulses and any of the laboratory parameters, including haptoglobin (ρ = −0.186, p = 0.374), bilirubin (ρ = −0.071, p = 0.718), LDH (ρ = −0.060, p = 0.765), myoglobin (ρ = −0.107, p = 0.595), creatinine (ρ = −0.125, p = 0.474), and GFR (ρ = −0.019, p = 0.916).
Discussion
This prospective study compared the periprocedural impact of two PFA systems—a balloon-in-basket catheter (VOLT™, Abbott) and a pentaspline catheter (FARAWAVE™, Boston Scientific)—on markers of hemolysis and renal function in patients undergoing PVI. The main findings were as follows:
The pentaspline catheter induced significantly greater hemolysis across all measured markers compared to the balloon-in-basket system.
Only the pentaspline group exhibited a significant post-procedural decline in renal function.
Myoglobin increases were similar in both groups, arguing against muscle injury as the cause of renal impairment.
Hemolysis after PFA: catheter design and energy delivery matter
Hemolysis has emerged as a biologically relevant phenomenon associated with PFA procedures. The application of high-voltage electric fields, while intended to induce irreversible electroporation of myocardial cells, can also exert non-selective effects on circulating erythrocytes. Several recent studies—including a multicenter analysis by Popa et al.—have reported consistent elevations in LDH and bilirubin, along with reductions in haptoglobin following PFA, particularly in systems requiring a higher number of energy applications [12, 13]. These findings were corroborated in our study, where patients treated with the pentaspline catheter exhibited significantly greater changes in all hemolysis markers compared to those in the balloon-in-basket group.
The most plausible contributors to this difference include (1) catheter design and electrode geometry, (2) the number of PFA applications, (3) contact-dependent electrode activation, and (4) waveform configuration.
First, the balloon-in-basket system features a semi-compliant balloon that ensures stable, circumferential apposition to the pulmonary vein wall, promoting uniform lesion formation. Critically, its flat electrode splines are embedded around the balloon periphery and oriented laterally, directing the electric field directly into the adjacent myocardial tissue. This configuration enables targeted electroporation of the tissue interface while minimizing exposure to the intravascular blood volume. In addition, the saline-filled balloon itself displaces blood volume within the vein, which may further reduce the exposure of circulating blood to the electric field and thereby mitigate hemolysis. In contrast, the pentaspline catheter consists of multiple independently maneuvered splines that extend into the vein without a stabilizing and potentially isolating balloon structure. These splines are more susceptible to variable or suboptimal contact, increasing the likelihood that energy is delivered across blood-filled spaces rather than exclusively into the tissue. As a result, a greater proportion of the electric field may interact with circulating erythrocytes, thereby amplifying intravascular hemolysis.
Second, the balloon-in-basket system includes an integrated contact indicator within the electroanatomical mapping system, which provides real-time feedback on tissue contact quality. Furthermore, the operator can selectively deactivate electrode splines that are directed toward the blood pool and lack wall contact—an important safety feature to avoid off-target energy delivery. In contrast, the pentaspline system activates all electrodes simultaneously, regardless of their orientation or contact quality. This inability to tailor energy delivery based on contact may contribute substantially to unnecessary exposure of blood to high-voltage fields.
Third, the number of PFA applications was significantly higher in the pentaspline group (32 vs. 16 per patient). While hemolysis is expected to scale with energy exposure, the more pronounced hemolytic response in the pentaspline group likely reflects not only cumulative dose but also less efficient energy delivery due to inconsistent tissue contact. Importantly, there is currently no established consensus or gold standard regarding the exact number of PFA applications required for effective pulmonary vein isolation (PVI). Most protocols are based on the manufacturer’s recommendation for a minimum of four applications in both the basket and flower configurations, totaling eight per vein [14]. No studies to date have suggested that fewer applications are sufficient. Notably, some centers opt for higher numbers of applications, whereas our institution adheres to a protocol with a relatively low number of applications. For the balloon-in-basket system, the manufacturer recommends a minimum of two applications per vein. To investigate whether energy burden alone was associated with hemolysis or renal impairment, we performed a correlation analysis. Unlike prior studies suggesting dose-dependent effects [15, 16], no significant associations were found. This may be due to limited variability in impulse counts, especially in the balloon-in-basket group (clustered around 16), and protocol-driven standardization in both cohorts, reducing statistical power to detect subtle relationships.
Fourth, differences in waveform architecture may further influence hemolytic potential. The balloon-in-basket catheter uses a biphasic waveform with lower overall voltage requirements due to improved energy focus and tissue coupling. As demonstrated by recent modeling works [17], lower peak voltages, reduced pulse duration, and spatial targeting can substantially reduce hemolytic potential without compromising lesion efficacy. These principles are embodied in the balloon-in-basket system, which combines energy to tissue targeted catheter design with waveform engineering thereby minimizing systemic energy dispersion.
Taken together, our findings indicate that the degree of hemolysis observed with PFA is determined not solely by the amount of energy delivered, but more critically by how and where that energy is applied. Optimizing catheter design, energy directionality, and contact-sensing integration may be essential for minimizing hemolysis and its downstream consequences.
Renal function and hemolysis: a causal link
In this study, a transient but statistically significant decline in renal function was observed exclusively in the pentaspline PFA group, as reflected by a post-procedural rise in serum creatinine and a corresponding reduction in estimated GFR. In contrast, renal function remained stable in patients treated with the balloon-in-basket system. These findings are clinically relevant given emerging evidence linking PFA-induced hemolysis to AKI [6, 18]. The likely mechanism involves nephrotoxicity from circulating heme-containing compounds—particularly free hemoglobin—released during intravascular hemolysis. These molecules can cause oxidative damage and tubular obstruction within the kidney [19]. In our cohort, the extent of renal function decline closely mirrored the hemolytic burden: patients in the pentaspline group exhibited significantly greater increases in LDH and bilirubin, and more pronounced haptoglobin depletion. Notably, this difference is not attributable to contrast exposure. The balloon-in-basket group, despite receiving significantly higher contrast volumes (median 50 vs. 40 mL, p < 0.001), did not exhibit renal impairment. This strongly supports hemolysis, rather than contrast-induced nephropathy, as the dominant factor underlying renal dysfunction in the pentaspline group. These findings align with case reports and small series describing hemolysis-driven AKI following high-energy PFA procedures [5, 18].
We also evaluated changes in myoglobin, a muscle-derived protein with established nephrotoxic potential. Myoglobin levels increased modestly in both groups following ablation, with no significant difference between the systems (delta +12.0 vs. +11.0 ng/mL, p = 0.696). This indicates that skeletal or myocardial muscle injury occurred to a similar extent in both groups and is unlikely to account for the selective renal impairment observed with the pentaspline catheter. Interestingly, the comparable rise in myoglobin is unexpected, as visible muscle contractions are markedly reduced in patients treated with the balloon-in-basket catheter. In fact, contractions are often barely perceptible, enabling performance of balloon-in-basket PFA procedures under significantly lighter sedation. These findings support the hypothesis that hemolysis—rather than myoglobinemia—was the primary contributor to the observed renal dysfunction.
Taken together, our findings suggest that catheter design and energy dispersion into the blood pool not only influence hemolysis but also have downstream effects on renal function. In addition to optimizing waveform configuration and catheter-tissue interaction, supportive measures such as adequate hydration may help mitigate hemoglobin-mediated renal injury [20]. Future mechanistic studies, including the use of urinary biomarkers of tubular stress, may further clarify the pathophysiology of PFA-associated renal effects.
Limitations
This study has several important limitations. First, it was a prospective but non-randomized, single-center observational study, and patient allocation to PFA systems was not randomized, which introduces the possibility of selection bias. Second, although baseline characteristics were largely comparable, a larger proportion of patients in the pentaspline group were concurrently enrolled in the VOLT CE Mark study, which may have introduced subtle protocol-related differences despite uniform registry data collection. Third, the number of PFA applications, particularly for the pentaspline catheter, was limited due to institutional standards, potentially influencing the extent of hemolysis and renal function changes observed. Fourth, our study only assessed acute changes in hemolysis and renal function; no long-term data are available to determine whether these laboratory changes translate into sustained clinical consequences. Fourth, we could not compare the actual amount of energy delivered to the tissue between the two systems, as detailed waveform and current parameters remain proprietary and undisclosed by the manufacturers. Thus, pulse count was used as a pragmatic surrogate, although it does not fully capture differences in effective tissue energy deposition. Fifth, intravenous fluid administration was not fully standardized, with a general policy of giving 500 mL of electrolyte solution to patients with reduced renal function, but without a uniform protocol across all patients. Finally, although the balloon and pentaspline systems are both classified as PFA, their waveforms differ substantially in configuration and delivery, limiting the direct comparability of their biological effects.
Conclusion
In this prospective study, the pentaspline PFA catheter was associated with significantly greater hemolysis and a transient decline in renal function, indicating a measurable systemic impact. In contrast, the balloon-in-basket system caused minimal, clinically irrelevant hemolysis without affecting renal parameters. These findings highlight the influence of catheter design and energy delivery on the biological footprint of PFA and underscore the importance of optimizing ablation strategies to preserve hematologic and renal integrity.
Funding
The VOLT CE Mark study was sponsored by Abbott.
Data Availability
The data that support the findings of this study are available from the corresponding author upon reasonable request.
Declarations
Ethics approval
The present study was approved by the local ethics committee and was performed in accordance with the ethical standards laid down in the 1964 Declaration of Helsinki and its later amendments. The VOLT CE Mark study was sponsored by Abbott.
Consent for publication
The manuscript “Catheter Design Matters: Hemolysis and Renal Function After Pulsed Field Ablation With Balloon-in-Basket vs. Pentaspline 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.
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. JV received travel grants from Abbott, Bayer, Biosense Webster and Daiichi Sankyo, speaker’s honoraria from Abbott, Astra Zeneca, Boston Scientific, Doctrina Med, EHRA, Medtronic, Daiichi Sankyo, and Novartis and is a proctor for Boston Scientific. KHK reports grants and personal fees from Abbott Vascular, Medtronic, and Biosense Webster outside the submitted work. MK received travel and congress grants from Abbott Medical 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. All other authors have no relevant disclosures.
Footnotes
Clinical Perspective
What is Known?
• PFA is a promising non-thermal ablation energy source, but hemolysis and renal effects have been reported.
• The extent of these effects may depend on catheter design and energy delivery patterns.
What the Study Adds
• In a head-to-head comparison, the pentaspline catheter caused significantly more hemolysis and renal function decline than the balloon-in-basket system.
• Myoglobin increased modestly in both groups but did not differ significantly, suggesting muscle injury was not the driver of renal impairment.
• Catheter geometry, tissue contact, and waveform configuration are key determinants of the systemic impact of PFA.
Publisher's Note
Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.
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Associated Data
This section collects any data citations, data availability statements, or supplementary materials included in this article.
Data Availability Statement
The data that support the findings of this study are available from the corresponding author upon reasonable request.