Pulsed-field Ablation for Paroxysmal and Persistent Atrial Fibrillation: A Single-center Experience

Abstract

Background:

Atrial fibrillation (AF) increases morbidity and mortality. Traditional catheter ablation techniques have limitations. Pulsed-field ablation (PFA) is a new nonthermal ablation method aiming to eliminate arrhythmogenic tissue while minimizing collateral damage. The study reported the initial experience of the prince sultan cardiac center with PFA and the learning curve.

Patients and Methods:

This retrospective study included 33 patients with paroxysmal or persistent AF who underwent ablation with the PFA technique from 2022 to 2023. The study outcomes included short-term and follow-up complications and AF recurrence.

Results:

The mean age was 48.52 ± 13.97 years, and 24 patients were males (72.73%). Hypertension was the most common comorbidity encountered in 11 patients (33.33%). Thirteen patients (39.39%) were on antiarrhythmic medications, and 26 (78.79%) were on nonvitamin K-dependent oral anticoagulation. The most common indication was symptomatic paroxysmal AF (n = 28; 84.85%). The preprocedural left atrial diameter was 41.82 ± 14.78 mm, and the ejection fraction was 51.36% ±8.41%. The left atrial ablation time was 45.38 ± 17.96 min, the fluoroscopy time was 33.45 ± 15.60 min, and the procedure time was 77.55 ± 19.73 min. No complications were reported postprocedurally or at 3 or 6 months. One patient had recurrent AF; one developed atrial flutter after 9 months and underwent ablation.

Conclusions:

Pulmonary vein isolation using PFA for paroxysmal and persistent AF might be a safe and effective procedure. Future long-term studies comparing PFA with other ablation techniques are recommended.

INTRODUCTION

Pulmonary vein isolation (PVI) is the principal component of catheter ablation for atrial fibrillation (AF), with reported improvements in survival and quality of life in patients with symptomatic AF refractory to medical therapy.[1] However, the long-term effect of PVI is suboptimal, and the reported success rate declined to 50%–70% over long-term follow-up.[1,2] Optimizing the energy source for durable isolation with balanced safety and efficacy is an ongoing battle. PVI is achieved using heating with radiofrequency or cooling with cryoablation.[3] Several modifications were introduced to improve radiofrequency ablation durability, including using irrigated tips[4] and contact force-sensing catheters.[5] Furthermore, cryoablation technology was improved using cryoballoons with comparable results to radiofrequency ablation.[6] Nevertheless, pulmonary vein reconnection and collateral damage are still of concern. Collateral damage was frequently reported after thermal ablation, such as atrioesophageal fistulae, pulmonary vein stenosis, and phrenic nerve injury.[7]

Pulsed-field ablation (PFA) has recently been introduced as a nonthermal approach with selective myocardial ablation and minimal collateral damage.[8] PFA uses electroporation, which increases cell permeability and leads to cell death when applied with a dose above a specific threshold.[9] Additionally, PFA is applied in an ultrarapid fashion compared to conventional energy sources,[10] potentially decreasing collateral damage and procedure times. These characteristics of PFA indicate a potential superiority over other AF ablation methods. However, testing the safety and efficacy of PFA in the clinical setting is still needed. Therefore, this study aimed to assess the safety and efficacy of PFA in managing symptomatic paroxysmal or persistent AF after failure or intolerance to at least one class I or III antiarrhythmic medication. The study reported the initial experience of the Prince Sultan Cardiac Center with PFA and the learning curve in the first 33 cases.

PATIENTS AND METHODS

Sample and study design

We conducted a retrospective analysis on patients who underwent AF ablation between November 2022 and November 2023. The study included patients with symptomatic paroxysmal or persistent AF who received the PFA (Farapulse Inc., Menlo Park, California, USA) technique at a single tertiary referral cardiac center. All patients had documented symptomatic AF, with paroxysmal AF lasting <7 days and persistent AF lasting between 7 and 365 days. These patients received at least one class I or III antiarrhythmic medication with failure or intolerance to medical therapy.

Ethical approval

Data collection for this study was approved by the Local Ethical Committee (IRB number: 1675), and the committee waived the need for patient consent because of the retrospective design.

Pulsed-field ablation procedure

As part of the routine preoperative workup, all patients underwent a baseline cardiac computed tomography (CT) scan before the ablation procedure. A CT scan was performed to rule out left atrial and appendage thrombi, pulmonary vein stenosis, and coronary artery lesions. Preprocedural anticoagulation was continued. The procedure was performed under general anesthesia, transesophageal echocardiography was used in all patients, and systemic heparinization was performed. The PFA system delivers a pulsed electrical waveform through multiple channels. The PFA catheter contains four electrodes over five splines. We advanced the catheter over the guidewire transseptally to ensure circumferential proximity between the splines and the left atrial-pulmonary valve area, and ablative energy was emitted from all electrodes. The third electrode of each spline recorded the pace and electrograms from all pulmonary veins. Four paired applications were used for each vein in the flower and basket poses. In patients with persistent AF, roof lines and posterior lesions were performed. PVI was confirmed by electrocardiogram. At the end of the procedure, diaphragmatic pacing was performed to evaluate phrenic nerve function. After the procedure, patients were admitted to the coronary care unit for 24 h to be monitored for complications.

Follow-up

We followed the patients clinically at the outpatient clinic after 3, 6, 9, and 12 months. At follow-up visits, the patients were assessed for symptoms and AF recurrence. A transtelephonic monitor was performed for patients who could not attend the clinic at the 3- and 6-month follow-ups. A 24-h Holter monitor was used at 3, 6, and 12 months.

Study data and outcomes

Preprocedural data collected for this study were demographics (age, sex, and body mass index), comorbidities (hypertension, congestive heart failure, diabetes mellitus, coronary artery disease, and stroke), medications (antiarrhythmic, Vitamin K antagonist, and nonvitamin K-dependent anticoagulation), indications for ablation (paroxysmal, persistent AF), and echocardiographic parameters (left atrial diameter and left ventricular ejection fraction). The preprocedural CHA2DS2-VASc score was calculated based on age (<65: 0, 65–74: +1, and ≥75 years: +2), sex (female: +1), congestive heart failure history (+1), hypertension (+1), stroke/transient ischemic attack (+2), vascular disease (+1), and diabetes mellitus (+1).

Procedural data included electroanatomical mapping, left atrial, fluoroscopy and procedure times, and PFA applications. Study outcomes were all-cause mortality and procedure-related complications, including esophageal fistula, esophageal dysmotility, pericardial tamponade, pulmonary vein stenosis, percutaneous treatment, surgical treatment, stroke/transient ischemic attack, vascular complications requiring surgery, coronary artery spasm, hematoma, pseudoaneurysm, coronary spasm, persistent phrenic nerve injury, or arteriovenous fistula. Other outcomes included recurrent symptoms and/or AF.

Statistical analysis

The results were presented using descriptive analysis. Continuous variables are expressed as the mean and standard deviation or median (Q1–Q3), while categorical variables are presented as numbers and percentages. Procedure time was compared between patients with paroxysmal and persistent AF using the Mann–Whitney U-test. Kruskal–Wallis was used to compare times between groups. The statistical analysis was performed using Stata 18 software (Stata Corp., College Station, TX, USA).

RESULTS

Preprocedural data

Thirty-three patients were enrolled in the study. The mean age was 48.52 ± 13.97 years, and 24 patients were males (72.73%). Hypertension was the most common comorbidity encountered in 11 (33.33%) patients. Thirteen patients (39.39%) were on antiarrhythmic medications, and 26 (78.79%) were on nonvitamin K-dependent oral anticoagulation (warfarin). The most common indication for ablation was paroxysmal AF (n = 28; 84.85%). The preprocedural left atrial diameter measured by echocardiography was 41.82 ± 14.78 mm, and the left ventricular ejection fraction was 51.36% ±8.41%. No patient needed a preprocedural magnetic resonance imaging. Detailed preprocedural data are presented in Table 1.

Table 1.

Preprocedural data of the study patients who had pulsed-field ablation

Variables	n=33
Demographics
Age (years)	48.52±13.97
Male	24 (72.73)
BMI (kg/m2)	30.01±4.57
CHA2DS2-VASc score
0	9 (27.27)
1	12 (36.36)
2	9 (27.27)
3	2 (6.06)
4	1 (3.03)
Comorbidities
Hypertension	11 (33.33)
Diabetes mellitus	4 (12.12)
Congestive heart failure	10 (30.30)
Coronary artery disease	4 (12.12)
Stroke/transient ischemic attack	1 (3.03)
Medications
Antiarrhythmic medications	13 (39.39)
Vitamin K antagonist	1 (3.03)
NOACs	26 (78.79)
Indications for ablation
Paroxysmal AF	28 (84.85)
Persistent AF	3 (9.09)
Longstanding persistent AF	2 (6.06)
Echocardiographic parameters
LA diameter (mm) (n=25)	41.82±14.78
LVEF (%)	51.36±8.41

Data are presented as the mean±SD or n (%). BMI: Body mass index, LA: Left atrium, LVEF: Left ventricular ejection fraction, NOACs: Non-Vitamin K-dependent oral anticoagulation, SD: Standard deviation, AF: Atrial fibrillation

Procedure data

Intraprocedural transesophageal echocardiography was used in all patients. The left atrial ablation time was 45.38 ± 17.96 min, the fluoroscopy time was 33.45 ± 15.60 min, and the procedure time was 77.55 ± 19.73 min [Figure 1]. There was no difference in procedure time between patients with paroxysmal AF (median 74 [Q1–Q3: 58–92] min) and persistent AF (70 [76–88] min) (P = 0.412). All patients had pulmonary vein ablation while roof and posterior lines ablation were performed in 5 patients (15.15%). PVI was successful in 100% of cases. Procedure details are presented in Table 2.

Figure 1.

Violin graph showing the box plot and density plot of left atrial ablation, fluoroscopy, and procedure times

Table 2.

Procedure details of the study patients who had pulsed-field ablation

	n=33
Electro anatomical mapping
Paroxysmal AF	8 (24.24)
Persistent AF	4 (12.12)
Longstanding persistent AF	2 (6.06)
Times
Left atrial ablation time (min) (n=32)	45.38±17.96
Fluoroscopy time (min) (n=32)	33.45±15.60
Procedure time (min)	77.55±19.73
PFA applications
Left superior pulmonary vein
Basket 4 + flower 4	26 (78.79)
Basket 10 + flower 12	1 (3.03)
Basket 10 + flower 6	1 (3.03)
Basket 4+flower 6	2 (6.06)
Basket 6 + flower 4	1 (3.03)
Basket 6 + flower 6	1 (3.03)
Left inferior pulmonary vein
Basket 4 + flower 4	26 (78.79)
Basket 4 + flower 7	2 (6.06)
Basket 4 + flower 8	3 (9.09)
Basket 5 + flower 6	1 (3.03)
Basket 6 + flower 6	1 (3.03)
Right superior pulmonary vein
Basket 13 + flower 8	1 (3.03)
Basket 4 + flower 4	24 (72.73)
Basket 4 + flower 6	2 (6.06)
Basket 6 + flower 4	1 (3.03)
Basket 6 + flower 6	2 (6.06)
Basket 6 + flower 7	2 (6.06)
Basket 8 + flower 4	1 (3.03)
Right inferior pulmonary vein
Basket 4 + flower 4	30 (90.91)
Basket 4 + flower 5	3 (9.09)
Roofline	5 (15.15)
Lateral mitral isthmus	0
Left atrial posterior wall	5 (15.15)
Anterior line	0
Superior vena cava isolation	0
CFAE area	0
LAA isolation	0
Nonpulmonary vein trigger	0

Data are presented as the mean±SD or n (%). AF: Atrial fibrillation, CFAE: Complex fractionated atrial electrogram, LAA: Left atrial appendage, PFA: Pulsed-field ablation, SD: Standard deviation

Postprocedural complications

There was no reported hospital mortality or complications, including esophageal fistula, esophageal dysmotility, pericardial tamponade, pulmonary vein stenosis, percutaneous treatment, surgical treatment, stroke/transient ischemic attack, vascular complications requiring surgery, coronary artery spasm, hematoma, pseudoaneurysm, coronary spasm, persistent phrenic nerve injury, or arteriovenous fistula. All patients were symptom-free.

Learning curve

Patients were divided into three thirds, and the procedure and ablation times were compared among the first, second, and third 11 patients. The median ablation time in the first 11 patients was 42 min (Q1–Q3: 29–59), 43 (30–57) min in the middle 11 patients, and 42 (36–55) min in the last 11 patients (P = 0.987). There was no significant difference in the procedure time among groups (85 [70–96] vs. 74 [58–94] vs. 70 [57–87] min, P = 0.498).

Follow-up data

All patients completed 3-month follow-up, 23 patients (69.7%) completed 6-month follow-up, and 6 patients (18.2%) completed 1-year follow-up. No complications were reported at the 3-, 6-, or 12-month follow-up. One patient had AF recurrence (3%) after 3 months. One patient developed atrial flutter 9 months after the procedure and underwent atrial flutter ablation.

DISCUSSION

PFA is a new technique introduced for AF ablation. PFA emits electrical pulses to cause nonthermal irreversible electroporation, increasing cell permeability and leading to cell death when applied in specific doses.[11] This mechanism leads to selective myocyte ablation and elimination of arrhythmogenic focus, with minimal collateral damage.[12] We conducted this retrospective study to assess the safety and efficacy of PFA in treating symptomatic persistent or paroxysmal AF. Thirty-three patients were included; 28 (84.85%) had paroxysmal AF, and 5 (15.15%) had persistent AF. No periprocedural morbidity or mortality was reported. One patient had early AF recurrence, and one had atrial flutter after 9 months. The procedure time decreased in recent cases; however, it did not reach a significant value.

The safety and efficacy of PFA were evaluated in several recent studies. Shaheen et al. performed a meta-analysis for studies assessing PFA’s safety and efficacy and reported 16 studies with 485 patients. They reported a mean procedure duration of 94 min, which was longer than our mean procedure duration (78 min); however, we reported a longer average fluoroscopy time (33 vs. 17 min). The AF recurrence rate was 2.84%, comparable to that reported in this study (3%). On the other hand, the reported complication rate was 2.23%, while we did not report any complications in our series.[13] In a review of 6 studies, including 1897 patients who had PFA, the reported success rate of PVI was 100% in four studies. The procedure time ranged from 38 to 215 min, and the procedure time was significantly shorter with PFA than with thermal techniques.[14] In the multinational survey on the methods, efficacy, and safety of the postapproval clinical use of PFA (MANIFEST-PF) study, 1758 patients were included from 24 centers and reported a 99.9% PVI success rate. The study did not report esophageal or phrenic nerve complications; however, pericardial tamponade was reported in 0.97% of patients, and stroke was reported in 0.4%. Other reported complications were vascular injury, transient ischemic attack, coronary spasm, hemoptysis, and transient phrenic nerve paralysis.[15] The 5S study reported a success rate of 100% with no esophageal thermal injury; however, recurrence occurred in 9%.[16]

Cochet et al. compared esophageal injury using cardiac magnetic resonance performed postprocedure and after 3 months in patients who had PFA (n = 18) to thermal ablation patients (n = 23).[17] Esophageal injury was reported in 43% of patients after thermal ablation, and no patient with PFA had esophageal lesions. Regression of the PFA over time was evaluated in another study of 20 patients 3 months after PFA and reported that the level of PVI did not regress.[18] However, Reddy et al. reported left posterior atrial wall scar regression in 3/25 patients without affecting conduction.[19] Lemoine et al. evaluated the 1-year follow-up after PFA in 138 patients and reported a freedom from recurrence in 60% of patients with persistent AF and 90% with paroxysmal AF.[20] The results from this and other studies indicate that PFA has excellent short- and mid-term results; however, data about long-term durability is still lacking.

Study limitations and future perspectives

Several study limitations should be considered. First, the study is retrospective in design. This study design has an inherent selection bias, which could have affected the study results, and clinical randomized trials comparing PFA to other thermal ablation techniques are recommended. Second, the study has no comparative group and presents a single-center experience; therefore, generalization of the results could be an issue. Last, the study is limited by the small sample size. However, the study showed that PFA is a safe procedure with no reported short- or follow-up complications. The study showed that the technique was safe and effective in treating persistent or paroxysmal AF; only one patient had a recurrence of AF postprocedure, and one patient had atrial flutter after 9 months. Future studies are needed to evaluate the long-term effects of PFA compared to thermal ablation techniques.

CONCLUSIONS

PVI using PFA for symptomatic paroxysmal and persistent AF might be a safe and effective procedure. The data suggested that the clinicians were able to maintain consistent procedure times throughout the patient cohort. This might indicate that the learning curve could have been affected by prior ablation experience. Future studies comparing PFA with other ablation techniques are recommended.

Conflicts of interest

There are no conflicts of interest.

Funding Statement

Nil.