Abstract
BACKGROUND
In patients with persistent atrial fibrillation (PerAF), antiarrhythmic drugs (AADs) are considered a first-line rhythm-control strategy, whereas catheter ablation is a reasonable alternative.
OBJECTIVES
This study sought to examine the prevalence, patient characteristics, and clinical outcomes of patients with PerAF who underwent catheter ablation as a first or second-line strategy.
METHODS
This multicenter observational study included consecutive patients with PerAF who underwent first-time ablation between January 2020 and September 2021 in 9 medical centers in the United States. Patients were divided into those who underwent ablation as first-line therapy and those who had ablation as second-line therapy. Patient characteristics and clinical outcomes were compared between the groups.
RESULTS
A total of 2,083 patients underwent first-time ablation for PerAF. Of these, 1,086 (52%) underwent ablation as a first-line rhythm-control treatment. Compared with patients treated with AADs as first-line therapy, these patients were predominantly male (72.6% vs 68.1%; P = 0.03), with a lower frequency of hypertension (64.0% vs 73.4%; P < 0.001) and heart failure (19.1% vs 30.5%; P < 0.001). During a mean follow-up of 325.9 ± 81.6 days, arrhythmia-free survival was similar between the groups (HR: 1.13; 95% CI: 0.92-1.41); however, patients in the second-line ablation strategy were more likely to continue receiving AAD therapy (41.5% vs 15.9%; P < 0.001).
CONCLUSIONS
A first-line ablation strategy for PerAF is prevalent in the United States, particularly in men with fewer comorbidities. More data are needed to identify patients with PerAF who derive benefit from an early intervention strategy.
Keywords: antiarrhythmic drugs, atrial fibrillation, catheter ablation, clinical outcomes, rhythm control, treatment strategy
Catheter ablation is an effective rhythm control strategy in patients with atrial fibrillation (AF).1–4 Because the success rate of catheter ablation is higher in paroxysmal AF (PAF) compared with persistent AF (PerAF), the guidelines for the management of AF grant Class I and IIa indications for catheter ablation in PAF and PerAF, respectively.5,6 As such, patients with PAF are increasingly referred for catheter ablation as a first-line rhythm control strategy, whereas patients with PerAF often undergo catheter ablation as a second-line strategy after treatment with class I or III antiarrhythmic drugs (AADs) fails. Furthermore, the Food and Drug Administration excludes patients with PerAF who have not yet experienced failed AAD therapy from participating in investigational device exemption ablation studies, and thus the studied populations may not accurately represent real-world patients.
Although catheter ablation is superior to AAD therapy in patients with PAF, there is growing evidence that catheter ablation may also outperform AADs in PerAF.7–9 Furthermore, continuous advancements in catheter ablation technologies compared with the largely stagnated field of pharmacologic therapy and a growing patient awareness of potential drug-related side effects may contribute to a contemporary shift in the pendulum toward earlier use of catheter ablation as a first-line therapy in patients with PerAF.
However, the real-world prevalence of using catheter ablation as the initial treatment for PerAF remains unreported. The present study sought to evaluate the prevalence of AF ablation as first-line therapy in PerAF. It also compared the clinical characteristics and outcomes after ablation between patients with PerAF who underwent ablation as first-line therapy and as second-line therapy after AAD treatment failure.
METHODS
STUDY DESIGN AND PATIENTS.
This multicenter retrospective study included consecutive patients with PerAF who underwent their first catheter-based ablation procedure between January 1, 2020, and September 31, 2021, across 9 medical centers in the United States with different geographies, academic profiles, and procedural volume, as detailed in Supplemental Table 1. The definition of PerAF was based on the 2017 Heart Rhythm Society guidelines and included those patients with AF lasting more than 7 days and <12 months.6 All participating institutions had an AF ablation registry containing the following information: age, sex, presence of hypertension, diabetes mellites, left ventricular ejection fraction (LVEF), heart failure (defined as NYHA functional class ≥II), CHA2DS2-VASc score, history of AAD use, ablation technology, and procedure-related complications. Follow-up data included a minimum of 2 continuous ambulatory Holter monitor sessions performed after the 90-day blanking period during the first year after ablation, use of AAD therapy, redo ablation procedures, arrhythmia-related hospital admissions, and all-cause mortality. Follow-up was planned for at least 12 months after ablation to assess the intermediate-term clinical outcomes. AF burden, quality of life, and ablation strategy beyond pulmonary vein isolation (PVI) were unavailable for all registries and therefore were not included in the analysis. A center procedural volume was categorized as “high” if the total number of first-time AF ablation procedures (for PAF and PerAF) was higher than the median in the participating centers and as “low” if it was lower than the median. The study protocol was approved by the Institutional Review Board at each participating center.
DATA ANALYSIS AND CLINICAL OUTCOMES.
To analyze clinical outcomes, patients were categorized according to whether they underwent catheter ablation as their initial approach to rhythm control or as a secondary option following unsuccessful AAD treatment before the ablation intervention. AAD therapy was defined as treatment with class I or III agents (beta-blockers or calcium-channel blockers were not considered AADs). Clinical outcomes included freedom from sustained (>30 seconds) atrial tachyarrhythmias after the 90-day blanking period, atrial arrhythmia-related hospital admissions, need for redo ablation procedures, and all-cause mortality. Periprocedural complications were analyzed as a composite outcome of vascular complications, pericardial effusion (requiring pericardiocentesis), phrenic nerve palsy, cerebrovascular strokes (transient and permanent), and 30-day mortality.
STATISTICAL ANALYSIS.
Continuous variables were presented as mean ± SD, and categorical variables were presented as number (%). Statistical comparisons were conducted using t-tests for continuous variables and using Pearson chi-square tests for categorical variables. Time-to-event analyses for clinical outcomes were performed using the Cox proportional hazards model, and the results were presented as HRs with 95% CIs, along with Kaplan-Meier plots. Multivariable analysis was conducted using Cox and logistic regression models, adjusting for prespecified confounders, including age, sex, hypertension, diabetes mellitus, heart failure, CHA2DS2-VASc score, and type of AAD. The regression analysis results are represented using ORs and 95% CIs. Three-way associations were evaluated with the Mantel-Haenszel chi-square test. HRs for antiarrhythmic medications were compared with amiodarone, which was the most frequent AAD used. A sensitivity analysis was performed to evaluate the clustering effect of treatment centers. This analysis assessed whether the interactions among treatment centers and treatment strategies significantly affected clinical outcomes in Cox regression models. This interaction was not a significant predictor (P > 0.05 for all centers). Statistical significance was defined as P < 0.05. All statistical analyses were performed using R software version 4.3.0 (R Foundation for Statistical Computing).
RESULTS
A total of 2,083 patients with PerAF underwent first-time AF ablation during the study period. Of the total cohort, 1,086 (52%) patients underwent catheter ablation as a first-line rhythm control strategy, whereas in 997 (48%) patients, catheter ablation was a second-line treatment after exposure to AADs. The most frequent AAD used was amiodarone (39.4%), followed by flecainide (17.8%) and dofetilide (16.4%). Table 1 summarizes the baseline clinical characteristics for both groups. Most patients in both groups were treated with atrioventricular nodal agents before ablation (86.5%). The rates for beta-blocker prescription were higher for the second-line ablation group (68.6% vs 62.9%; P = 0.007), whereas there was no difference in calcium-channel blocker use (22.3% vs 19.7%; P = 0.17).
TABLE 1.
Baseline Patient Characteristics
| Total (N = 2,083) |
First-Line Ablation (n = 1,086) |
Second-Line Ablation (n = 997) |
P Value | |
|---|---|---|---|---|
| Age, y | 67 ± 9.9 | 66.9 ± 9.9 | 67.1 ± 9.9 | 0.64 |
|
| ||||
| Male | 1,467 (70.4) | 788 (72.6) | 679 (68.1) | 0.03 |
|
| ||||
| Hypertension | 1,427 (68.5) | 695 (64) | 732 (73.4) | <0.001 |
|
| ||||
| Diabetes mellitus | 415 (19.9) | 202 (18.6) | 213 (21.4) | 0.13 |
|
| ||||
| Heart failure | 511 (24.5) | 207 (19.1) | 304 (30.5) | <0.001 |
|
| ||||
| CHA2DS2-VASc | 2.6 ± 1.5 | 2.4 ± 1.5 | 2.8 ± 1.5 | <0.001 |
|
| ||||
| LVEF, % | 53.8 ± 11.2 | 54.5 ± 10.6 | 53 ± 11.6 | 0.004 |
|
| ||||
| Antiarrhythmic drugs | ||||
| Amiodarone | 391 (39.4) | 0 (0) | 391 (39.4) | – |
| Flecainide | 177 (17.8) | 0 (0) | 177 (17.8) | – |
| Dofetilide | 163 (16.4) | 0 (0) | 163 (16.4) | – |
| Sotalol | 95 (9.6) | 0 (0) | 95 (9.6) | – |
| Other | 70 (7.1) | 0 (0) | 70 (7.1) | – |
| Propafenone | 64 (6.5) | 0 (0) | 64 (6.5) | – |
| Dronedarone | 32 (3.2) | 0 (0) | 32 (3.2) | – |
|
| ||||
| AV nodal agents | ||||
| Beta-blockers | 1,367 (65.6) | 683 (62.9) | 684 (68.6) | 0.007 |
| Calcium-channel blockers | 436 (20.9) | 214 (19.7) | 222 (22.3) | 0.17 |
Values are mean ± SD or n (%).
AV = atrioventricular; LVEF = left ventricular ejection fraction.
CATHETER ABLATION AS FIRST- OR SECOND-LINE TREATMENT: PATIENT CHARACTERISTICS.
The patient’s age at the time of the ablation procedure was comparable between the groups undergoing catheter ablation as first- or second-line treatment (mean 67 ± 9.9; P = 0.64). Most patients in both groups were men, although male predominance was higher in the first-line ablation group (72.6% vs 68.1%; P = 0.03).
Patients referred for ablation as a first-line rhythm control strategy tended to have fewer comorbidities with lower rates of hypertension (64.0% vs 73.4%; P < 0.001) and heart failure (19.1% vs 30.5%; P < 0.001), as well as a lower CHA2DS2-VASc score (P < 0.001), as shown in Table 1.
In addition to the clinical characteristics, there was significant variation among centers in patients who were referred for catheter ablation as a first- or second-line rhythm control strategy. This variability ranged from 29% to 72% and was associated with the center’s procedural volume. The average number of first-time AF ablation procedures per year in the participating centers was 445 ± 393, with a median of 304 (Q1-Q3: 126-1,347). Higher-volume centers were more likely to offer ablation as a first-line strategy (OR: 1.63; 95% CI: 1.31-2.04). Figure 1 shows the percentage of patients treated with first-line catheter ablation stratified by the center’s AF ablation procedural volume.
FIGURE 1. Association Between the Proportion of Catheter Ablations as a First-Line Strategy and a Center’s Procedural Volume.
The proportion of patients treated with a first-line catheter ablation strategy stratified by the participating medical center (CNTR) and its volume. Procedural volume was dichotomized at the median procedure number reported during the study period. Participating centers are randomly anonymized.
To investigate variables associated with catheter ablation as first- or second-line therapy, a univariable analysis was used to compare rhythm control strategies. The variables of female sex (OR: 1.23; 95% CI: 1.03-1.49), hypertension (OR: 1.55; 95% CI: 1.29-1.88), LVEF <40% (OR: 1.59; 95% CI: 1.19-2.15), heart failure (OR: 1.86; 95% CI: 1.52-2.28), CHA2DS2-VASc score ≥3 (OR: 1.48; 95% CI: 1.24-1.75), and low center volume (OR: 1.78; 95% CI: 1.45-2.2) were associated with a greater likelihood of AAD therapy use before catheter ablation (Figure 2A). In a multivariable analysis, female (OR: 1.32; 95% CI: 1.06-1.64), hypertension (OR: 1.54; 95% CI: 1.22-1.93), heart failure (OR: 1.60; 95% CI: 1.25-2.06), and low center volume (OR: 1.63; 95% CI: 1.31-2.04) remained independently associated with an initial AAD strategy (Figure 2B).
FIGURE 2. Univariable and Multivariable Analysis for Rhythm Control Strategy.
Forest plots of (A) univariable and (B) multivariable analysis of variables associated with ablation as a first-line rhythm control strategy. LVEF = left ventricular ejection fraction.
ABLATION PROCEDURE AND COMPLICATIONS.
Table 2 summarizes the procedural characteristics and periprocedural complications. The most common energy source was radiofrequency (95.7%), followed by cryothermy (4.1%). Acute PVI was achieved in all patients. The combined result of periprocedural complications was comparable between the 2 groups (first-line catheter ablation approach: 1.1% vs 1.0% in the second-line catheter ablation strategy; P = 0.82). The most common complications were peripheral vascular (6 [0.5%] vs 9 [0.9%]; P = 0.41), stroke (4 [0.4%] vs 1 [0.1%]; P = 0.19), and tamponade (2 [0.2%] vs 0 [0%]; P = 0.33) for first-line and second-line treatment, respectively. The 30-day postprocedural mortality was identical between rhythm control strategies (0.2%; P = 1.00).
TABLE 2.
Procedural Characteristics, Periprocedural Complications, and Clinical Outcomes
| Total (N = 2,083) |
First-Line Ablation (n = 1,086) |
Second-Line Ablation (n = 997) |
P Value | |
|---|---|---|---|---|
| Energy type | ||||
| Radiofrequency | 1,912 (95.7) | 1,006 (96.3) | 906 (95.1) | 0.21 |
| Cryotherapy | 81 (4.1) | 38 (3.6) | 43 (4.5) | 0.50 |
| Other | 5 (0.3) | 1 (0.1) | 4 (0.4) | – |
|
| ||||
| Periprocedural complications | ||||
| Total | 22 (1.1) | 12 (1.1) | 10 (1.0) | 0.82 |
| Peripheral vascular | 15 (0.7) | 6 (0.5) | 9 (0.9) | 0.41 |
| Stroke | 5 (0.2) | 4 (0.4) | 1 (0.1) | 0.19 |
| Tamponade | 2 (0.1) | 2 (0.2) | 0 (0) | 0.33 |
| 30-d mortality | 4 (0.2) | 2 (0.2) | 2 (0.2) | 1.00 |
|
| ||||
| Clinical outcomes | ||||
| Follow-up duration, d | 325.9 ± 81.6 | 326.0 ± 79.4 | 325.9 ± 83.9 | 0.98 |
| Arrhythmia recurrencea | 333 (16.0) | 164 (15.1) | 169 (17.0) | 0.25 |
| Paroxysmal | 75 (22.5) | 26 (15.9) | 49 (29.0) | – |
| Persistent | 177 (53.2) | 90 (54.9) | 87 (51.5) | – |
| Unspecified | 81 (24.3) | 48 (29.7) | 33 (19.5) | – |
| Hospitalizationa | 123 (5.9) | 72 (6.6) | 51 (5.1) | 0.25 |
| Redo ablationa | 68 (3.3) | 33 (3.0) | 35 (3.5) | 0.15 |
| All-cause mortality | 17 (0.8) | 8 (0.7) | 9 (0.9) | 0.68 |
Values are n (%) or mean ± SD.
Reported outcomes exclude 90-day blanking period.
CLINICAL OUTCOMES.
Clinical outcomes are summarized in Table 2. The mean follow-up duration was 325.9 ± 81.6 days and was similar between the groups (P = 0.98). During the follow-up period, recurrence of atrial arrhythmias was detected in 164 of 1,086 (15.1%) patients in the first-line ablation group and in 169 of 997 (17.0%) patients in the second-line catheter ablation group (P = 0.26). Figure 3 shows the Kaplan-Meyer survival curve for the atrial arrhythmia recurrence rate. There was no difference between the groups as indicated by an HR of 1.13 (95% CI: 0.92-1.41; P = 0.25).
FIGURE 3. Arrhythmia-Free Survival Stratified by Catheter Ablation as First- or Second-Line Therapy.
Kaplan-Meier estimates of freedom from recurrence of any atrial tachyarrhythmia during the first year after ablation.
The multivariable model did not identify a single clinical parameter that predicted arrhythmia recurrence after ablation in either the first-line ablation group or the second-line ablation group (Figures 4A and 4B). However, in the group undergoing catheter ablation as second-line therapy, treatment with amiodarone was associated with a lower recurrence rate compared with any other AAD in both univariable and multivariable analyses (all other AADs are compared with amiodarone).
FIGURE 4. Multivariable Analysis of Variables Associated With Atrial Arrhythmia Recurrence.
Forest plots of multivariable analysis of clinical variables association with atrial arrhythmia recurrence in the group that underwent catheter ablation as a (A) first-line and (B) second-line rhythm-control strategy. Data are represented as HRs along with 95% CIs. AADs = antiarrhythmic drugs; LVEF = left ventricular ejection fraction.
At 12 months after ablation, patients in the second-line ablation strategy group were more likely to be receiving AAD therapy (41.5% vs 15.9%; P < 0.001). The most frequently prescribed agent was amiodarone (35.6%), followed by dofetilide (27.5%) and flecainide (15.8%). Figure 5 shows bar graphs of AAD use before and after ablation for both groups. Supplemental Table 2 shows the frequency of AADs usage in each group after the 90-day blanking period.
FIGURE 5. Comparison of Antiarrhythmic Drug Therapy Between Groups That Underwent Catheter Ablation as First- or Second-Line Therapy.
The bar graphs display the use of antiarrhythmic drug therapy before and 12 months after catheter ablation for the groups that underwent ablation as (left) first-line and (right) second-line therapy.
The first-line and second-line ablation rhythm control groups had similar rates of arrhythmia-related hospitalizations (3.1% vs 4.1%, respectively; P = 0.35), redo ablation procedures (3.0% vs 3.5%, respectively; P = 0.15), and all-cause mortality rates (1.1% vs 1.3%, respectively; P = 0.97), as shown in Table 2.
DISCUSSION
This study evaluated the prevalence of catheter ablation as a first-line rhythm-control strategy in patients with PerAF. It also compared the clinical characteristics and outcomes between those patients who underwent ablation as a first-line or second-line rhythm control strategy. The main findings include the following:
Catheter ablation as a first-line rhythm-control strategy for PerAF is relatively common in the United States, with just over one-half of patients undergoing ablation without a previous attempt of class I or III AAD therapy.
Patients with PerAF who were referred for catheter ablation as a first-line rhythm control strategy were largely men with fewer comorbidities compared with patients initially treated with AADs.
The rates of arrhythmia-free survival after ablation were similar among patients who underwent catheter ablation as first- or second-line treatment.
RHYTHM CONTROL IN PATIENTS WITH PerAF.
Several studies compared rhythm control with rate control in patients with PerAF. The EAST-AFNET 4 (Early Rhythm-Control Therapy in Patients With Atrial Fibrillation-Atrial Fibrillation Network) trial reported that early rhythm control with AADs or catheter ablation was associated with improved cardiovascular outcomes in patients with PAF or PerAF compared with usual care.9 The EAST-AFNET 4 trial included a primary composite endpoint of cardiovascular death, stroke, or hospitalization for heart failure or acute coronary syndrome (HR: 0.79; 96% CI: 0.66-0.94; P = 0.01) and the individual components of cardiovascular death (HR: 0.72; 96% CI: 0.52-0.98) and stroke (HR: 0.65; 96% CI: 0.44-0.97) at a median follow-up of 5 years. This study contributed to the evidence that early rhythm control is preferable over usual care in patients with either PAF or PerAF. However, catheter ablation was used in only ~20% of patients.
The SARA study (Study of Ablation Versus antiaRrhythmic Drugs in Persistent Atrial Fibrillation) randomized patients with PerAF to AADs or catheter ablation.10 The primary endpoint was atrial arrhythmia recurrence at 3 to 12 months after ablation. In an intention-to-treat analysis, the proportion of patients free of atrial tachyarrhythmias was significantly higher in the ablation group (70.4% vs 43.7%; P = 0.002), with an absolute risk reduction difference of 26.6% (95% CI: 10.0-43.3) favoring the ablation group.
These findings are also consistent with the recently published substudy of the CABANA trial (Catheter Ablation Versus Anti-arrhythmic Drug Therapy for Atrial Fibrillation Trial). The primary analysis was performed in 1,240 patients with AF recurrence; the baseline AF type was paroxysmal in 43.0% and persistent in 57.0% of these patients. In this analysis, ablation was effective in reducing AF recurrence by ~50% compared with AADs in all patients, regardless of AF type.3
REAL-WORLD PROPORTIONS OF CATHETER ABLATION AS FIRST-LINE STRATEGY IN PerAF.
Professional society guidelines for the treatment of AF grant a Class IIa indication for catheter ablation in PerAF.5,6 This recommendation largely stems from insufficient clinical evidence and is based on expert consensus. In this multicenter observational report, approximately 50% of all patients with PerAF were referred for catheter ablation as a first-line rhythm-control strategy without a trial of class I or III AADs. This relatively high proportion of patients with PerAF who were undergoing catheter ablation as a first-line treatment is consistent with the proportion of patients with PerAF in the CABANA trial (47%).3 In comparison, in the older RAAFT-1 (First Line Radiofrequency Ablation Versus Antiarrhythmic Drugs for Atrial Fibrillation Treatment) trial, only 3% of patients had PerAF.7
This trend in referring patients with PerAF to catheter ablation before a trial of AADs may be influenced by the increased availability of catheter ablation, the constantly improving safety and efficacy profiles of catheter ablation procedures, and the greater awareness of patients of potential AAD-related side effects.11,12 This trend may have also been affected by recent studies demonstrating that early rhythm control with catheter ablation is superior to AAD therapy in progression from PAF to PerAF.8,13,14 These studies, although largely including patients with PAF, may have indirectly contributed to earlier referral of patients with PerAF because of some phenotypic overlap between PAF and early PerAF. The increased safety profile of catheter ablation procedures may have also influenced the concept that catheter ablation may serve as an adjunctive tool to increase the effect of AAD therapy. In this report, early referral to catheter ablation was associated with a two-thirds reduction in the need for continuous AAD therapy after ablation.
Despite recent data suggesting that catheter ablation may be particularly beneficial in sicker patients, including those with heart failure,15,16 in this study, patients referred for catheter ablation as a first-line rhythm control strategy were relatively healthier, with less hypertension, less heart failure, and a lower CHA2DS2-VASc score. It is conceivable that these healthier patients resembled patients with PAF, who experience a better clinical outcome of catheter ablation. Furthermore, in this study, women were less likely to be referred for catheter ablation as a first-line rhythm control strategy despite similar clinical characteristics and comorbidities. This finding is particularly interesting given the higher prevalence of side effects of AADs in women.17 These data highlight the need for prospective and randomized data to help identify the patients with PerAF who may derive the maximal benefit from an early intervention strategy.
STUDY LIMITATIONS.
The major limitation of this study is inherent in its retrospective observational design, with data derived from few selected sites rather than from a national registry. We included sites that maintained an AF registry and agreed to share their data. Although national registries have significant advantages, this study provides new real-world data that may help focus the questions for a larger study. Another limitation is the potential selection bias in the distribution of patients in each group. It is conceivable that patients who underwent ablation after failed AAD therapy had more advanced disease with a longer history and burden of disease. This may explain the increased use of AAD therapy after ablation. However, this limitation is unlikely to affect the primary objective of this study, to evaluate the proportion of patients referred for catheter ablation as a first-line rhythm control strategy. Additionally, this study did not compare AADs with catheter ablation, thus limiting the validity of these data regarding the efficacy of AAD therapy vs catheter ablation.
CONCLUSIONS
First-line catheter ablation for PerAF is common in the United States, particularly in higher-volume centers. The patients tend to be men with fewer medical comorbidities. The clinical outcome of ablation appears to be similar between patients undergoing catheter ablation as first-line treatment and those having ablation as second-line treatment. However, ablation as a first-line rhythm control strategy lowered the risk of long-term AAD exposure (Central Illustration).
CENTRAL ILLUSTRATION. Catheter Ablation as First or Second Line Therapy in Persistent AF.
The figure summarizes the study design and results. AAD = antiarrhythmic drug; AF = atrial fibrillation; PerAF = persistent atrial fibrillation.
Supplementary Material
PERSPECTIVES.
COMPETENCY IN MEDICAL KNOWLEDGE:
In patients with persistent PerAF, AADs are considered a first-line rhythm-control strategy, whereas catheter ablation is considered a reasonable alternative. Although recent data suggest that catheter ablation is at least as effective as AADs in in patients with PerAF, the prevalence of AF catheter ablation as a first-line rhythm-control strategy for PerAF is unknown.
TRANSLATIONAL OUTLOOK:
Catheter ablation as a first-line rhythm-control strategy for PerAF is common in the United States, with just over one-half of these patients undergoing ablation without a previous trial of AADs. Patients with PerAF who were referred for catheter ablation as a first-line rhythm control strategy were predominantly men with fewer comorbidities. The rates of arrhythmia-free survival after ablation were similar among patients who underwent catheter ablation as first or second-line treatment. More data are needed to identify patients with PerAF who derive benefit from an early intervention strategy.
FUNDING SUPPORT AND AUTHOR DISCLOSURES
Dr Barkagan has received consulting fees from Biosense Webster and Cardiodet. Dr Gerstenfeld has received research grants and speaking honoraria from Abbott Medical; has served on the advisory board of Biosense Webster; and has served on the data safety monitoring board of Abbott Medical. Dr Narayan has served as a consultant for Abbott, LifeSignals, and TDK. Dr Tzou has served as a consultant for Abbott, Biosense Webster, Boston Scientific, and Medtronic. Dr Siddiqui has received consulting fees from Abbott, Biosense Webster, Boston Scientific, Medtronic, and Stereotaxis. Dr Natale has served as a consultant for Abbott, Baylis, Biosense Webster, Biotronik, Boston Scientific, and Medtronic. Dr Anter has received research grants and speaking honoraria from Biosense Webster and Boston Scientific; and has previously held stock in Affera Inc. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose.
ABBREVIATIONS AND ACRONYMS
- AAD
antiarrhythmic drugs
- AF
atrial fibrillation
- LVEF
left ventricular ejection fraction
- PAF
paroxysmal atrial fibrillation
- PerAF
persistent atrial fibrillation
- PVI
pulmonary vein isolation
Footnotes
The authors attest they are in compliance with human studies committees and animal welfare regulations of the authors’ institutions and Food and Drug Administration guidelines, including patient consent where appropriate. For more information, visit the Author Center.
APPENDIX For a supplemental and tables, please see the online version of this paper.
REFERENCES
- 1.Packer DL, Mark DB, Robb RA, et al. , CABANA Investigators. Effect of catheter ablation vs antiarrhythmic drug therapy on mortality, stroke, bleeding, and cardiac arrest among patients with atrial fibrillation: the CABANA randomized clinical trial. JAMA. 2019;321:1261–1274. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 2.Morillo CA, Verma A, Connolly SJ, et al. , RAAFT-2 Investigators. Radiofrequency ablation vs antiarrhythmic drugs as first-line treatment of paroxysmal atrial fibrillation (RAAFT-2): a randomized trial. JAMA. 2014;311:692–700. [DOI] [PubMed] [Google Scholar]
- 3.Poole JE, Bahnson TD, Monahan KH, et al. , CABANA Investigators and ECG Rhythm Core Lab. Recurrence of atrial fibrillation after catheter ablation or antiarrhythmic drug therapy in the CABANA trial. J Am Coll Cardiol. 2020;75:3105–3118. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 4.Andrade JG, Deyell MW, Badra M, et al. Randomised clinical trial of cryoballoon versus irrigated radio frequency catheter ablation for atrial fibrillation-the effect of double short versus standard exposure cryoablation duration during pulmonary vein isolation (CIRCA-DOSE): methods and rationale. BMJ Open. 2017;7:e017970. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 5.Hindricks G, Potpara T, Dagres N, et al. Corrigendum to: 2020 ESC guidelines for the diagnosis and management of atrial fibrillation developed in collaboration with the European Association for Cardio-Thoracic Surgery (EACTS): the Task Force for the Diagnosis and Management of Atrial Fibrillation of the European Society of Cardiology (ESC) developed with the special contribution of the European Heart Rhythm Association (EHRA) of the ESC. Eur Heart J. 2021;42:4194. [DOI] [PubMed] [Google Scholar]
- 6.Calkins H, Hindricks G, Cappato R, et al. 2017 HRS/EHRA/ECAS/APHRS/SOLAECE expert consensus statement on catheter and surgical ablation of atrial fibrillation. Heart Rhythm. 2017;14:e275–e444. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 7.Wazni OM, Marrouche NF, Martin DO, et al. Radiofrequency ablation vs antiarrhythmic drugs as first-line treatment of symptomatic atrial fibrillation: a randomized trial. JAMA. 2005;293:2634–2640. [DOI] [PubMed] [Google Scholar]
- 8.Andrade JG, Deyell MW, Khairy P, et al. Atrial fibrillation progression after cryoablation versus radiofrequency ablation: the CIRCA-DOSE trial. Eur Heart J. 2024;45(7):510–518. [DOI] [PubMed] [Google Scholar]
- 9.Kirchhof P, Camm AJ, Goette A, et al. EAST-AFNET 4 Trial Investigators. Early rhythm-control therapy in patients with atrial fibrillation. N Engl J Med. 2020;383:1305–1316. [DOI] [PubMed] [Google Scholar]
- 10.Mont L, Bisbal F, Hernandez-Madrid A, et al. , SARA Investigatorsl. Catheter ablation vs. antiarrhythmic drug treatment of persistent atrial fibrillation: a multicentre, randomized, controlled trial (SARA study). Eur Heart J. 2014;35:501–507. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 11.Mansour M, Calkins H, Osorio J, et al. Persistent atrial fibrillation ablation with contact force-sensing catheter: the prospective multicenter PRECEPT trial. J Am Coll Cardiol EP. 2020;6:958–969. [DOI] [PubMed] [Google Scholar]
- 12.Reddy VY, Peichl P, Anter E, et al. A focal ablation catheter toggling between radiofrequency and pulsed field energy to treat atrial fibrillation. J Am Coll Cardiol EP. 2023;9(8 Pt 3):1786–1801. [DOI] [PubMed] [Google Scholar]
- 13.Andrade JG, Deyell MW, Macle L, et al. , EARLY-AF Investigators. Progression of atrial fibrillation after cryoablation or drug therapy. N Engl J Med. 2023;388:105–116. [DOI] [PubMed] [Google Scholar]
- 14.Andrade JG, Champagne J, Dubuc M, et al. , CIRCA-DOSE Study Investigators. Cryoballoon or radiofrequency ablation for atrial fibrillation assessed by continuous monitoring: a randomized clinical trial. Circulation. 2019;140:1779–1788. [DOI] [PubMed] [Google Scholar]
- 15.Marrouche NF, Brachmann J, Andresen D, et al. , CASTLE-AF Investigators. Catheter ablation for atrial fibrillation with heart failure. N Engl J Med. 2018;378:417–427. [DOI] [PubMed] [Google Scholar]
- 16.Sohns C, Fox H, Marrouche NF, et al. , CASTLE HTx Investigators. Catheter ablation in end-stage heart failure with atrial fibrillation. N Engl J Med. 2023;389(15):1380–1389. [DOI] [PubMed] [Google Scholar]
- 17.Tamargo J, Rosano G, Walther T, et al. Gender differences in the effects of cardiovascular drugs. Eur Heart J Cardiovasc Pharmacother. 2017;3:163–182. [DOI] [PubMed] [Google Scholar]
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