Abstract
Background
An early catheter ablation treatment strategy is effective for rhythm control in patients with atrial fibrillation (AF). In clinical practice, most patients undergo catheter ablation as a second-line treatment, following a trial of antiarrhythmic drugs (AADs). We aimed to investigate the effectiveness and safety of AF catheter ablation performed as a first-line vs a second-line approach, based on data from the nationwide, multicentre Israeli Catheter Ablation Registry.
Methods
Following AF catheter ablation, patients were stratified into 2 groups—first-line vs second-line therapy approaches. The second-line group included AF patients who were referred for catheter ablation following treatment with at least one AAD. The primary endpoint was the 1-year freedom from AF recurrence. The secondary endpoints included 1-year hospitalizations, death, cerebrovascular events, and the composite of adverse cardiac events.
Results
The 923 participants had a mean age of 66 ± 4.5 years. Catheter ablation was performed as a first-line therapy in 192 patients (20.8%). Median times from AF diagnosis to catheter ablation were 1.5 and 3 years in the first- and second-line groups, respectively. Patients in the first-line group were younger, had a shorter AF duration, and more frequently had a normal left atrial size prior to the procedure. The primary endpoint of AF recurrence at 1 year did not differ significantly between the groups (24.9% vs 30%, P = 0.205). No significant differences in the incidence of secondary outcomes occurred.
Conclusions
Mildly delayed AF catheter ablation for patients with AF did not compromise the procedure’s efficacy or safety.
Résumé
Contexte
L’ablation précoce par cathéter est une stratégie efficace pour corriger le rythme chez les patients atteints de fibrillation auriculaire (FA). Dans la pratique clinique, la plupart des patients subissent une ablation par cathéter en deuxième intention, après un essai de médicaments antiarythmiques. Nous avons évalué l’efficacité et l’innocuité de l’ablation par cathéter de la FA pratiquée en première plutôt qu’en deuxième intention, à partir des données d’un registre national multicentrique israélien de l’ablation par cathéter.
Méthodologie
Les patients ayant subi l’ablation par cathéter d’une FA ont été répartis en deux groupes selon que l’intervention avait été pratiquée en première ou en deuxième intention. Les patients du groupe traité en deuxième intention avaient reçu au moins un antiarythmique avant d’être orientés vers l’ablation par cathéter. Le paramètre d’évaluation principal était l’absence de récurrence de la FA à 1 an. Les paramètres d’évaluation secondaires comprenaient l’hospitalisation à 1 an, le décès, les événements cérébrovasculaires et un critère composite combinant diversévénements indésirables cardiaques.
Résultats
L’âge moyen des 923 participants était de 66 ± 4,5 ans. L’ablation par cathéter a été pratiquée en première intention chez 192 patients (20,8 %). Le délai médian entre le diagnostic de FA et l’ablation par cathéter était de 1,5 an dans le groupe traité en première intention et de 3 ans dans le groupe traité en deuxième intention. Les patients appartenant au groupe traité en première intention étaient plus jeunes, étaient atteints de FA depuis moins longtemps et présentaient plus souvent une oreillette gauche de taille normale avant l’intervention. Les résultats au regard du paramètre d’évaluation principal, soit la récurrence de la FA à 1 an, ne différaient pas beaucoup entre les groupes (24,9 % vs 30 %; p = 0,205). Aucune différence significative au niveau de l’incidence des paramètres d’évaluation secondaires n’a été observée.
Conclusions
Retarder légèrement l’ablation par cathéter chez les patients atteints de FA n’a compromis ni l’efficacité ni l’innocuité de l’intervention.
Atrial fibrillation (AF) is the most common cardiac arrhythmia among adults worldwide. AF is associated with an increased incidence of morbidity and mortality, posing a significant healthcare burden.1 In the past decade, the management of AF has evolved, with an emphasis on rhythm control as an initial approach, rather than rate control, for its potential superiority in improving prognosis and quality of life.2,3 Antiarrhythmic drugs (AADs) have been used traditionally to restore and maintain sinus rhythm in patients with AF. However, the efficacy of this approach is limited and has been associated with a wide range of side effects.4,5
AF catheter ablation is an effective and well-accepted long-term rhythm control strategy for patients with AF. The European Society of Cardiology guidelines provide a 1A recommendation for AF patients with tachycardia-induced cardiomyopathy and following failure of AAD use to improve symptoms and outcomes.4,5 Early performance of AF catheter ablation, before remodelling changes and with smaller left atrial size, improves clinical outcomes by interrupting the rapid progression of the pathophysiological changes of the left atrium.3,6 Recently, the superiority of AF catheter ablation, compared to AAD therapy, as a first-line therapy for patients with paroxysmal AF has been demonstrated.7 However, in clinical practice, most AF catheter ablations are conducted as a second-line strategy, following AAD treatment.
The aim of the current study was to compare the effectiveness and safety of AF catheter ablation performed as either a first-line or second-line therapy, using a nationwide survey.
Methods
The Israeli Catheter Ablation Registry is a national multicentre prospective observational registry that includes patients who underwent any type of AF catheter ablation therapy between 2019 and 2021. The registry includes all catheter ablations performed at participating centres during the study period, ensuring comprehensive data collection. Study physicians recorded all clinical and demographic data, including information regarding AAD treatment, and peri-, intra-, and post-procedural details. The diagnosis and classification of AF were based on clinical and electrocardiographic criteria.4 Patients were managed at the discretion of each medical centre.
Patients were divided into 2 groups—first-line and second-line AF catheter ablation. The second-line group included patients with prior AAD use, aside from beta-blockers, regardless of whether AAD failure was documented. Baseline characteristics, procedural and medical therapy, and clinical outcomes were compared between the 2 groups. All patients underwent transesophageal echocardiography or cardiac computed tomography prior to the AF ablation, to exclude the presence of left atrial appendage thrombus.
The analysis included data on demographic, clinical, and procedural characteristics, peri- and post-procedural complications, and safety. Follow-up was conducted at 1 year, through clinical and telemedicine visits.
The primary outcome of the study was 1-year freedom from AF recurrence. The secondary outcomes were comprised of 1-year redo AF catheter ablation, rehospitalization, and major adverse cardiac events (including acute coronary syndrome, cardiovascular rehospitalization, and death).
AF recurrence was defined as any documented AF episode that lasted longer than 30 seconds. The diagnosis of AF recurrence was made by analyzing either electrocardiograms (ECGs) from medical charts during hospitalizations, or medical records and ambulatory-performed ECG and Holter ECG monitoring. Patient follow-up was conducted as part of a clinic evaluation 1 year after the procedure. Rhythm surveillance included a review of the patient's complaints over the year, an assessment of medical visits documenting AF recurrence, an evaluation of ECG or Holter ECG recordings performed in various medical settings during the year, and a review of relevant hospitalizations during the follow-up period.
The study was approved by the local institutional ethics committee of each medical centre, in accordance with the principles of the Declaration of Helsinki. Participants provided written informed consent before their enrollment, according to ministry of health regulations.
Statistical analysis
Patients' characteristics were presented as n (%) for categorical variables, and as mean (± standard deviation) or median (interquartile range [IQR]) for normally and non-normally distributed continuous variables. The cohort was divided into 2 groups based on the AF catheter ablation approach. Baseline characteristics, treatment, and clinical outcomes were compared between the groups using χ2 tests for categorical variables and t-tests or Mann–Whitney–Wilcoxon tests for normally and non-normally distributed continuous variables. Statistical significance was considered to be a P value < 0.05 in univariable tests. Missing values in the included covariates were < 10% and were not imputed. All analyses were performed using R (R-studio, version 4.0.3, Vienna, Austria).
Results
The 923 AF patients who underwent AF catheter ablation had a median age of 66 years (IQR: 58-72), and 62.8% were male. Paroxysmal AF was the most common indication for the procedure (65.7% of all patients). Catheter ablation as a first-line therapy was performed in 192 patients (20.8%). Baseline characteristics for the 2 groups are presented in Table 1. Patients who underwent AF catheter ablation as a first-line therapy were younger, more frequently male, and had a shorter AF duration. Among the 731 patients in the second-line AF catheter ablation group, 604 patients (82.6%) were being treated with AAD therapy at the time of catheter ablation, and the remaining 127 patients (17.4%) had discontinued AAD therapy before the time of enrollment, due to treatment failure. Amiodarone was the AAD used most commonly, followed by class 1c drugs. All patients underwent pre-procedural echocardiographic assessment.
Table 1.
Baseline demographic and clinical parameters
| Parameter | Overall | First-line AF catheter ablation | Second-line AF catheter ablation | P |
|---|---|---|---|---|
| n | 923 | 192 | 731 | |
| Age, y | 66.0 [58.0, 72.0] | 65.0 [54.0, 70.0] | 66.0 [59.0, 73.0] | 0.001 |
| Gender, male | 580 (62.8) | 132 (68.8) | 448 (61.3) | 0.069 |
| AF classification | 0.029 | |||
| Paroxysmal | 604 (65.7) | 132 (69.1) | 472 (64.8) | |
| Persistent | 315 (34.3) | 59 (30.9) | 256 (35.2) | |
| AF duration, y | 3.0 [1.0, 5.0] | 1.5 [1.0, 4.0] | 3.0 [1.0, 6.0] | < 0.001 |
| Prior pharmacological therapy | ||||
| Prior anticoagulation type | 0.178 | |||
| Apixaban | 490 (60.8) | 88 (56.1) | 402 (61.9) | |
| Dabigatran | 90 (11.2) | 15 (9.6) | 75 (11.6) | |
| Rivaroxaban | 197 (24.4) | 49 (31.2) | 148 (22.8) | |
| Warfarin | 29 (3.6) | 5 (3.2) | 24 (3.7) | |
| Prior rate control therapy | 623 (67.6) | 137 (71.4) | 486 (66.7) | 0.251 |
| Prior AADs | 604 (65.4) | 0 (0.0) | 604 (82.6) | < 0.001 |
| Amiodarone | 274 (29.6) | 0 (0.0) | 274 (37.5) | |
| Sotalol | 32 (3.4) | 0 (0.0) | 32 (4.4) | |
| Propafenone | 140 (15.1) | 0 (0.0) | 140 (19.2) | |
| Flecainide | 120 (13.0) | 0 (0.0) | 120 (16.4) | |
| Dronedarone | 44 (4.7) | 0 (0.0) | 44 (6.0) | |
| Disopyramide | 2 (0.2) | 0 (0.0) | 2 (0.3) | |
Data are presented as median [interquartile range], or n (%), unless otherwise indicated.
AAD, anti-arrhythmic drug; AF, atrial fibrillation.
Catheter ablation procedural details are presented in Table 2. The majority of patients (87.9%) underwent cryoablation. Normal left atrial size was more frequent in the first-line catheter ablation group, although the procedure duration was notably longer in the first-line ablation group. No significant differences were present in procedural techniques between the 2 groups. The periprocedural complication rates did not differ significantly between the 2 catheter ablation groups. Postprocedural antiarrhythmic therapy was administered more commonly to patients in the second-line AF catheter ablation group. Postprocedure AAD use had a median duration of 6 months (IQR: 3-9.5 months), with no significant differences between the groups.
Table 2.
Atrial fibrillation (AF) catheter ablation, procedural data, and peri-procedural events
| Parameter | Overall | First-line AF catheter ablation | Second-line AF catheter ablation | P |
|---|---|---|---|---|
| n | 923 | 192 | 731 | |
| Procedure performed | 0.387 | |||
| Radiofrequency ablation | 49 (5.3) | 7 (3.6) | 42 (5.7) | |
| Cryoablation | 811 (87.9) | 174 (90.6) | 637 (87.1) | |
| Both | 63 (6.8) | 11 (5.7) | 52 (7.1) | |
| Left atriumsize∗ | < 0.001 | |||
| Normal | 239 (31.0) | 69 (44.5) | 170 (27.6) | |
| Mild enlargement | 352 (45.7) | 50 (32.3) | 302 (49.1) | |
| Moderate enlargement | 145 (18.8) | 31 (20.0) | 114 (18.5) | |
| Severe enlargement | 34 (4.4) | 5 (3.2) | 29 (4.7) | |
| Procedure duration, min | 85.0 [60.0, 120.0] | 90.0 [61.25, 120.0] | 80.0 [60.0, 120.0] | 0.015 |
| Peri procedural cardiovascular events | 6 (0.7) | 1 (0.5) | 5 (0.7) | 1.00 |
| AADs following catheter ablation | 317 (37.9) | 38 (22.0) | 279 (42.0) | < 0.001 |
| AAD type following catheter ablation | 0.594 | |||
| Class IC | 99 (33.4) | 10 (26.3) | 89 (34.5) | |
| Amiodarone | 178 (60.1) | 25 (65.8) | 153 (59.3) | |
| Sotalol | 19 (6.4) | 3 (7.9) | 16 (6.2) | |
| Duration of AAD use following catheter ablation, mo | 6.00 [3.00, 9.50] | 6.00 [2.00, 12.00] | 5.50 [3.00, 8.00] | 0.766 |
The 2 groups had 100% survival at discharge.
Data are presented as median [interquartile range], or n (%), unless otherwise indicated.
AAD, anti-arrhythmic drug.
Normal = left atrial diameter < 4.1 cm in men, and < 3.9 cm in women; mild enlargement = 4.1–4.6 cm in men and 3.9–4.2 cm in women; moderate enlargement = 4.7–5.1 cm in men and 4.3–4.6 cm in women; severe enlargement = ≥ 5.2 cm in men and ≥ 4.7 cm in women.
Figure 1 presents a Kaplan-Meyer curve comparing rates of 1-year survival free of AF recurrence for the 2 catheter ablation groups. The primary endpoint of AF recurrence at 1 year did not differ significantly between the 2 groups (24.9% and 30% in the first- and second-line catheter ablation group, respectively, P = 0.205; Table 3). Moreover, no significant differences were demonstrated in the incidence of adverse cardiac events, including cardiac death, acute coronary syndrome, and cardiovascular rehospitalization. No significant difference occurred in 1-year rehospitalization rates between the 2 groups (Fig. 2).
Figure 1.
Kaplan–Meier curve for 1-year re-atrial fibrillation (AF) event following AF catheter ablation as a first-line vs second-line therapy. 1-year follow-up data available for 864 patients.
Table 3.
Clinical outcomes 1 year following atrial fibrillation (AF) catheter ablation
| Outcome | Overall | First-line AF catheter ablation | Second-line AF catheter ablation | p |
|---|---|---|---|---|
| n | 864 | 181 | 683 | |
| Primary outcome | ||||
| Recurrent AF | 250 (28.9) | 45 (24.9) | 205 (30.0) | 0.205 |
| Symptomatic | 225 (84.6) | 42 (84.0) | 183 (84.7) | 1.00 |
| Secondary outcomes | ||||
| Re-ablation | 81 (9.6) | 14 (8.0) | 67 (10.0) | 0.505 |
| Rehospitalization | 192 (22.8) | 33 (18.9) | 159 (23.8) | 0.198 |
| Adverse cardiac events | 18 (2.1) | 2 (1.1) | 16 (2.3) | 0.457 |
Data are presented as median (interquartile range), unless otherwise indicated. Follow-up data were missing for 29 patients.
Figure 2.
Kaplan–Meier curve for 1-year rehospitalization following AF catheter ablation as a first-line vs second-line therapy. 1-year follow-up data available for 864 patients.
During the 1-year follow-up period, only 1 of 10 patients underwent an additional catheter ablation, with no significant differences between the 2 groups in this regard (Table 3).
Discussion
AF catheter ablation is a well-established treatment for the prevention of AF recurrence. Accordingly, the European Society of Cardiology guidelines indicate a class IIA recommendation for AF catheter ablation for symptomatic patients with paroxysmal AF, and a class I recommendation for patients with heart failure.4 The choice between AF catheter ablation and AAD therapy as a first-line therapy was determined by patients' preference. Several randomized controlled studies have demonstrated that when performed by appropriately trained operators, AF catheter ablation as a first-line treatment is a safe and superior alternative to use of AADs, for maintenance of sinus rhythm and symptom improvement.7, 8, 9, 10 The EARLY-AF (Early Aggressive Invasive Intervention for Atrial Fibrillation) trial enrolled 303 patients, with a mean age of 57.4 years and symptomatic AF, who either underwent cryoablation or received AADs as an initial therapy.7 Use of first-line cryoablation therapy showed a significant reduction in atrial tachyarrhythmia recurrence in the 12-month follow-up, with no difference in the incidence of major adverse events. The “Cryoablation as initial therapy for atrial fibrillation” (STOP AF) study included 203 patients who had paroxysmal AF for which they had not previously received rhythm-control therapy.8 Patients were randomly assigned to receive treatment with AADs (class I or III agents) or AF catheter ablation with cryoablation. AF catheter ablation as an initial therapy was superior to drug therapy for the prevention of atrial arrhythmia recurrence.
In clinical practice, catheter ablation is performed most commonly as a second-line strategy, due to either patients' choice or the failure or intolerability of AAD use. Surprisingly, studies comparing the efficacy and safety of AF catheter ablation as a first-line therapy or following AAD therapy are lacking.
The present study was based on a nationwide clinical practice cohort of consecutive AF patients who underwent their first catheter ablation. In our study no significant differences occurred in AF recurrence rates at 1 year, for the early vs delayed catheter ablation groups. We demonstrated similar 1-year AF recurrence rates and adverse cardiovascular events in both AF catheter ablation groups. Furthermore, no significant differences occurred in procedural complications. We did not find a difference in outcomes despite the presence of well-known factors of AF recurrence after ablation in the delayed ablation group.11, 12, 13, 14 Patients in the second-line AF catheter ablation group were older, had a longer AF duration and a larger left atrial size, compared to those in the first-line AF catheter ablation group. The lack of difference can probably be explained by the relatively short duration of AF, even in the second-line AF catheter ablation group (median of 3 years). The lack of significant differences in 1-year AF recurrence rates between the 2 groups suggests that as long as AF catheter ablation is conducted early in the course of the arrhythmia, procedural success rates remain high, regardless of the treatment strategy.
Compared to patients in previous trials, patients in our study in the second-line AF catheter ablation group were more frequently treated with amiodarone before the ablation procedure. Despite this difference, when AAD therapy was initiated or continued after the procedure, the proportion of patients taking amiodarone and the time from ablation to AAD discontinuation were similar in the 2 groups, with no significant differences observed. Therefore, the type of antiarrhythmic treatment does not fully explain the lack of a significant difference in 1-year AF recurrence rates between the 2 groups. Moreover, as previously demonstrated, short-term AAD treatment (eg, 2-3 months) following ablation reduces early recurrences of AF but does not affect late recurrences or 1-year clinical outcomes.15,16
The similarity in outcomes between the groups suggest that AAD use may play a role in maintaining sinus rhythm in patients awaiting ablation, whether delays are due to patient or physician preference, referral logistics, or procedural wait times.
The main clinical implication of our study is that when AF catheter ablation is not performed as a first-line strategy, due to either patient preference or procedural unavailability, initiation of AAD therapy appears to be a reasonable approach. Delayed AF catheter ablation may have similar outcomes as long as it is performed within a reasonable time from diagnosis. Nevertheless, our findings should be further validated.
Our study has several limitations that warrant consideration. First, this study is uncontrolled and observational; therefore, other confounding parameters could account for the lack of association between early ablation and clinical outcomes. However, our cohort was based on a multicentre national registry that includes a relatively large population and provides real-life data. Second, our study did not include data on several important outcomes, including stroke and AF symptoms. Third, our study did not include data on AF burden, which limits the interpretation of rhythm control outcomes. AF burden was not evaluated, as it cannot be addressed within the framework of an observational study. Nevertheless, AF burden remains one of the key factors influencing the success of treatment. Finally, AF recurrence was diagnosed mostly clinically and not by monitoring devices.
In conclusion, in patients with AF, a reasonably delayed catheter ablation following AAD therapy did not reduce the efficacy and safety of the procedure, as compared to the first-line AF catheter ablation approach.
Acknowledgments
Ethics Statement
The study was approved by the local institutional ethics committee of each medical centre, in accordance with the principles of the Declaration of Helsinki.
Patient Consent
The authors confirm that a patient consent form(s) has been obtained for this article
Funding Sources
The authors have no funding sources to declare.
Disclosures
The authors have no conflicts of interest to disclose.
Footnotes
See page 434 for disclosure information.
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