Different approaches to persistent and long-standing persistent atrial fibrillation ablation using pulsed field ablation: impact of procedural workflows on arrhythmia termination

Introduction

Over the past two decades, catheter ablation has become a cornerstone in the management of persistent (PerAF) and long-standing persistent AF (LSPAF).¹ In contrast to paroxysmal AF, PerAF is characterized by a more advanced and heterogeneous atrial substrate promoting arrhythmia perpetuation and contributing to higher recurrence rates after ablation.^1,2

In this evolving landscape, pulsed field ablation (PFA) has emerged as a promising energy modality.³ Limited data suggest that arrhythmia termination during PFA-based procedures may be achievable in patients with PerAF/LSPAF when ablation strategies incorporate extensive atrial substrate modification.^4,5

The present study evaluated acute safety and efficacy of different workflows using either a pentaspline PFA or a large-footprint dual-energy catheter in PerAF/LSPAF.

Methods

Patients

This dual-centre observational cohort study included all consecutive patients undergoing catheter ablation for PerAF > 6 months/LSPAF using either pentaspline PFA catheters (Farawave or FarawaveNAV) or a large-footprint, nitinol/lattice-tip, dual-energy catheter (Sphere-9) at Italian referral centres. The study complied with the Declaration of Helsinki and was conducted using an institutional review board–approved database.

Study groups and ablation strategy

Patients were categorized into three groups according to ablation technology and workflow (Figure 1A–B):

Figure 1.

Main study findings. P values in panel B were derived from pairwise χ² tests with Holm correction. * Percentages were calculated considering the number of patients who underwent a redo procedure. ** Among the seven patients receiving CTI ablation in Group-A, RF energy alone with 8 mm linear catheters was used in five cases (71%). PFA alone was used at all other LA/RA sites in Group-A and Group-B. † In Group-C, among the 45 (92%) patients who received RF ablation combined with PFA, the median number of RF applications was 11 (6–18). Among the 37 patients who underwent posterior–lateral MI ablation in Group-C, 25 (68%) received RF in combination with PFA in the region, with RF specifically applied at the lateral MI; one patient (3%) underwent ablation of the lateral MI using RF alone. ‡ Among the 21 patients who underwent CTI ablation in Group-C, 20 (95%) received RF alone, whereas the remaining patient (5%) underwent CTI ablation using PFA alone. § Among the 40 patients who underwent LA anterior wall ablation in Group-C, 29 (73%) received RF applications close to the MV, with PFA delivered at LA anterior wall sites distant from the MV. || Among the seven patients who underwent LAA base ablation in Group-C, two (29%) received RF in combination with PFA in the region, while one patient (14%) received RF alone. # Per unit increase. AF, atrial fibrillation; AKI, acute kidney injury; AV, atrioventricular; BMI, body mass index; CS, coronary sinus; CTI, cavotricuspid isthmus; ICE, intracardiac echocardiography; iLAV, indexed left atrial volume; IQR, interquartile range; LA, left atrial; LAA, left atrial appendage; MI, mitral isthmus; MV, mitral valve; PFA, pulsed field ablation; PV, pulmonary vein; PW, posterior wall; RF, radiofrequency energy; SD, standard deviation; SVC, superior vena cava.

1. Group-A: non-integrated pentaspline PFA (Farawave)

2. Group-B: integrated pentaspline PFA (FarawaveNAV)

3. Group-C (Ancona approach): large-footprint, nitinol/lattice-tip dual-energy catheter

Patient allocation to the study groups depended on operator preference and technology availability.^3,5–7 The lesion set included pulmonary vein (PV) and left atrial posterior wall (LA-PW) ablation, with electroanatomical mapping-guided substrate modification in Group-B and Group-C. If AF organized into intermediate atrial tachycardia (AT), activation mapping and ablation were performed to restore sinus rhythm (SR). Cavotricuspid isthmus (CTI) ablation was performed for prior or inducible typical atrial flutter.

Endpoints and statistics

The primary efficacy endpoint was AF termination without cardioversion, defined as restoration of SR or organization into AT. The primary safety endpoint was a composite of any procedure-related complications.

Descriptive statistics were used, and comparisons among the three groups performed with χ², ANOVA, or Kruskal–Wallis tests, as appropriate. Factors associated with AF termination were evaluated using logistic regression. A two-tailed P < 0.05 indicated statistical significance; all analyses were performed using R4.2.0.

Results

Clinical/procedural characteristics

A total of 151 consecutive patients were included (Group-A, n = 69; Group-B, n = 33; Group-C, n = 49). Baseline clinical characteristics by group are reported in Figure 1B.

Compared with Group-A/Group-B, procedural workflows in Group-C more frequently incorporated ablation at other left atrial (LA) and right atrial (RA) sites.

Arrhythmia termination

The primary efficacy endpoint of AF termination occurred most frequently in Group-C [Group-A: n = 24 (35%); Group-B: n = 14 (42%); Group-C: n = 34 (69%); P < 0.001; Figure 1C]. Results were consistent in the index procedure subgroup [Group-A: n = 13 (33%); Group-B: n = 14 (45%); Group-C: n = 25 (76%); P < 0.001]. Termination sites most commonly involved the PVs and the central LA-PW (Group-A), the LA roof and the lateral–mitral isthmus (MI; Group-B), or the inferior LA-PW adjacent to the CS and the LA anterior wall near the mitral valve (MV; Group-C; Figure 1C).

Among the 24 patients achieving AF termination in Group-A, direct restoration of SR occurred in nine patients (38%), whereas the remaining 15 (62%) organized into ATs, all of which were successfully terminated with ablation, mostly at the inferior LA-PW and central LA-PW (n = 5 each). In Group-B, direct restoration of SR occurred in seven patients (50%), whereas the remaining seven (50%) organized into ATs; five of these (71%) were successfully terminated with ablation, most commonly at the LA anterior wall (n = 2). In Group-C, direct restoration of SR occurred in 13 (39%), whereas 21 (62%) organized into 25 intermediate ATs. Of the 25 ATs, 24 (96%) were successfully terminated with ablation, most commonly at the CTI (n = 9), lateral MI (n = 5), LA appendage base, LA roof, CS, or intercaval line (n = 2 each).

In multivariable logistic regression, the use of the large-footprint catheter [adjusted odds ratio (aOR), 3.42; 95% CI, 1.24–9.98; P = 0.020] and AF episode duration (aOR, 0.96/month; 95% CI, 0.92–0.98; P = 0.007) were independently associated with AF termination after adjustment for several covariates, including electroanatomical integration (Figure 1D).

Safety

Acute procedural complications occurred in two patients (3%) in Group-A, none in Group-B, and five patients (10%) in Group-C, with a nonsignificant trend towards a higher rate in Group-C (P = 0.064; Figure 1B). After excluding vascular complications (Group-A, n = 2; Group-C, n = 1), non-vascular adverse events in Group-C included one transient atrioventricular block after PFA applications at the proximal CS, one acute kidney injury with spontaneous and complete recovery (baseline creatinine 1.45 mg/dL; peak creatinine 2.72 mg/dL; n = 177 PFA applications), and two transient ST-segment elevations (STEs) occurring after PFA delivery within the CS or near the anterior MV annulus, which resolved promptly with intravenous nitroglycerin and without sequelae. Notably, STEs occurred among the first three Group-C patients without nitrate pretreatment. In subsequent patients, continuous intravenous nitroglycerin (4 mg/h), initiated after LA mapping and maintained throughout ablation, together with the use of radiofrequency ablation close to the mitral/tricuspid annuli, was associated with no further STEs.

Discussion

This study provides the first comparative evaluation of workflow strategies and acute outcomes in PerAF/LSPAF ablation using different PFA platforms. Three principal findings emerge.

First, an extensive workflow incorporating electroanatomical mapping-guided substrate modification achieved a high rate of AF termination. This finding confirms recent reports showing AF termination rates up to 96% with extensive LA substrate modification using pentaspline PFA,⁴ compared with lower rates (33%) adopting more limited lesion sets.⁵ In our series, termination rates were lowest with the non-integrated pentaspline catheter, intermediate with the integrated pentaspline catheter, and highest with the dual-energy catheter, which enabled the most extensive ablation strategy and remained associated with AF termination in multivariable analysis.⁴

Second, the large-footprint nitinol/lattice-tip catheter may provide technical advantages for complex substrate modification.⁸ Its focal design facilitates navigation to critical sites at the anterior LA wall near the MV and the inferior LA-PW, where ablation can terminate AF.^4,5 The deformable tip may improve catheter–tissue contact, while dual-energy capability may enhance safety near coronary arteries, supporting its versatility.⁸ These observations extend prior stepwise radiofrequency experiences reporting high AF termination rates, with shorter procedural times in the present series.^9,10

Third, despite the extensive lesion set, the safety profile was acceptable. Early transient STEs were no longer observed after implementation of systematic intraprocedural nitroglycerin pretreatment, a simple workflow adjustment.⁸

Limitations include the non-randomized study design. Furthermore, in the absence of long-term rhythm outcome data, the significance of acute AF termination in PerAF/LSPAF as a measure of procedural efficacy should be considered hypothesis generating.⁵

Conclusions

In patients with PerAF/LSPAF, an extensive dual-energy ablation strategy targeting non-PV sites was associated with a high rate of acute arrhythmia termination, underscoring the potential importance of procedural workflow in this challenging population. However, heterogeneity among study groups precludes definitive comparisons between different catheter platforms.

Patient consent statement

The authors confirm that patient consent forms have been obtained for this article.

Funding

This research did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors.

Data availability

The data underlying this article will be shared on reasonable request to the corresponding author.