A retrospective observational study was performed of consecutive patients referred for catheter ablation of persistent or long-standing persistent AF between May 2016 and October 2018 in a tertiary referral center. Procedural endpoints and one-year follow-up results were assessed.

All patients provided written informed consent and the study complied with the Declaration of Helsinki.

Patients were eligible for inclusion in the study if they presented drug-refractory persistent or long-standing persistent AF or intolerance to antiarrhythmic drug (AAD) therapy, and had undergone radiofrequency (RF) catheter ablation.

Persistent AF was defined as AF lasting between seven days and one year, and long-standing persistent AF as AF lasting for >1 year before a decision to attempt rhythm control was made.5

Exclusion criteria were age <18 years and the presence of thrombus.

Data required for cohort characterization were collected from patients’ clinical records.

Electrical cardioversion was performed in all patients before intervention to reduce the time in AF, and consequently a significant number of patients were in sinus rhythm (SR) at the time of intervention.

All procedures were conducted under general anesthesia and patients suspended AAD therapy at least five half-lives before the procedure. All patients were under oral anticoagulation for at least two months prior to the procedure. In patients under vitamin K antagonists (VKAs), the medication was continued in the periprocedural period with an international normalized ratio within the 2.0-3.0 range. In patients taking non-VKAs the last drug dose was omitted. The presence of intracardiac thrombus was excluded prior to the procedure by either transesophageal echocardiography or computed tomography (CT). During the procedure, unfractionated heparin was administered immediately after transseptal puncture and adjusted as needed for a target activated clotting time >300 s. Anatomical mapping data were collected using a 3D mapping system with CARTO 3 (Biosense Webster, Irvine, CA, USA), or NavX Precision (Abbott, IL, USA) and integrated with a CT imaging reconstruction of the left atrium, when available. Ablation lines were created with point-by-point RF energy using an irrigated tip contact force-sensing catheter, in power-controlled mode with temperature limited to 43°C. Power settings varied according to the targeted region.

During the study period, patients underwent two different AF ablation strategies: PVI plus complex fractionated atrial electrogram (CFAE) ablation (Group 1), from May 2016 to June 2017; and a tailored approach (Group 2), from July 2017 to October 2018.

The primary endpoint was one-year arrhythmia recurrence in patients referred for non-paroxysmal AF ablation, defined by the documentation of at least 30 s of atrial arrhythmia, irrespective of symptoms, in accordance with the expert consensus statement on catheter and surgical ablation of atrial fibrillation.16

We also assessed one-year freedom from arrhythmia according to the strategy employed and the AF pattern (persistent or long-standing persistent).

After the index procedure, patients were followed for a minimum of 12 months. Patients were assessed before discharge and at three, six and 12 months after the procedure. Transthoracic echocardiography and 24-hour Holter monitoring were performed before discharge. Information collected during follow-up included a 12-lead electrocardiogram and a 24-hour Holter at each appointment. Seven-day Holter monitoring was performed at least once per year and a transthoracic echocardiogram at six or 12 months. At discharge AAD therapy was prescribed according to patient characteristics and operators’ decision. The first three months post-procedure were considered as a blanking period. Recurrence of atrial fibrillation was defined as the documentation of at least 30 s of atrial fibrillation, atrial tachycardia, or atrial flutter, irrespective of symptoms, in accordance with the expert consensus statement on catheter and surgical ablation of atrial fibrillation16 and a previously ineffective but tolerated class I or class III (sotalol) drug was the preferred option. Anticoagulation strategy after the first three months was based on the CHA2DS2Vasc and HAS-BLED scores.

Statistical analysis was performed using IBM SPSS Statistics version 25 (IBM, Armonk, New York). Categorical variables are expressed as frequencies and percentages and continuous variables are expressed as mean ± standard deviation or median and interquartile range (IQR) for variables with or without normal distribution, respectively. The chi-square test was used to assess differences between categorical variables and the Student's t test or the Wilcoxon test were used to compare continuous variables with or without normal distribution, respectively. The Kolmogorov-Smirnov test was used to test for normality of distribution of continuous variables. Cox regression was used to assess hazard ratios of variables regarding atrial fibrillation recurrence. Multivariate analysis was performed using the forward stepwise method. Kaplan-Meier curves and the log-rank test were used to assess and compare freedom from arrhythmia recurrence during follow-up. Statistical significance was accepted for p values <0.05.

During the enrollment period, a total of 67 patients fulfilled our inclusion criteria and were included in this study (58% male, mean age 59±11 years). Their main baseline characteristics and echocardiographic parameters are described in Table 1. Forty percent of the patients had long-standing persistent AF. Mean LA volume index was 45±10 ml/m2 and mean left ventricular ejection fraction was 49±14%.

Although electrical cardioversion had been performed before ablation, 57% of patients were in AF at the beginning of the procedure. Low voltage areas beyond the pulmonary veins were present in 52% of patients, covering a median area of 14.5 (IQR 3.2-27.1) cm2. Almost one third of patients (31%) only underwent PVI. At the end of the procedure, 73% of patients were in SR and the others required electrical cardioversion to restore SR. Approximately half of the patients (49%) were discharged without AAD. Procedural details are presented in Table 2.

Mean follow-up was 16±6 months. After one procedure, atrial arrhythmia recurrence was observed in 27% of the patients (60% of them under AAD) (Figure 1). The majority of the recurrences were in atrial fibrillation (55%).

Figure 1.

Freedom from atrial arrhythmia over time. Recurrence was observed in 27% of patients at 16±6 months of follow-up. AF: atrial fibrillation.

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Patients with long-standing persistent AF had a longer history of AF (85 vs. 18 months, p<0.001), longer continuous AF duration (20 vs. 8 months, p<0.001), more hypertension (77.8% vs. 57.5%, p=0.028), more HF (63% vs. 35%, p=0.033), an enlarged left atrium (49 ml/m2 vs. 42 ml/m2, p=0.004) and a higher HASBLED score (1.7 vs. 1.1, p=0.002) compared with patients with persistent AF (Table 1). There were no differences between the groups concerning the presence of low-voltage areas beyond the pulmonary veins (53% for persistent AF vs. 52% for long-standing persistent AF, p=0.73). Although the proportion of patients who underwent PVI only was numerically higher in the persistent group, this did not reach statistical significance (35% for persistent AF vs. 26% for long-standing persistent AF, p=0.07).

During follow-up, patients with long-standing persistent AF had a higher recurrence rate (44.4% vs. 15%, p=0.006) than patients with persistent AF. (Figure 2).

Figure 2.

Freedom from atrial arrhythmia over time, according to strategy employed (A) and to type of atrial fibrillation (B). AF: atrial fibrillation; PVI+CFAE: pulmonary vein isolation plus complex fractionated atrial electrogram ablation.

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There were no significant differences between the baseline characteristics of patients treated by the different ablation strategies, including in the proportion of long-standing persistent AF patients (44.4% for PVI plus CFAE vs. 37.5% for a tailored strategy, p=0.57), the proportion of patients who underwent PVI only (33% for PVI plus CFAE vs. 30% for a tailored strategy, p=0.32) and the presence of low-voltage areas (44% for PVI plus CFAE vs. 58% for a tailored strategy, p=0.15) (Table 1).

Patients undergoing a tailored approach had a lower arrhythmia recurrence rate than patients treated by PVI plus CFAE (17.5% vs. 40.7%, p=0.024) (Figure 2).

The predictors of recurrence are detailed in Table 3. Multivariate modeling indicated that continuous duration of AF (hazard ratio [HR] 1.191 [1.043-1.259], p=0.010), ablation strategy (HR 6.457 [1.399-29.811], p=0.017) and LA volume index (HR 1.160 [1.054-1.276], p=0.002) were associated with a higher risk of arrhythmia recurrence.

There was one case of moderate pericardial effusion, without need for pericardiocentesis, only requiring more days of hospitalization.

We acknowledge several limitations of our work. First, this was a retrospective study involving a relatively small number of patients, and therefore comparisons between subgroups and multivariate analysis may be underpowered. However, our main goal was to assess one-year arrhythmia recurrence in patients with non-paroxysmal AF ablation. Second, although both ablation strategies were clearly defined, we recognize that scar homogenization and, more importantly, CFAE ablation can be operator-dependent and these results may not be reproduced in other centers. Third, as mentioned above, the different AF strategies were performed at different times, therefore we cannot rule out that developments in AF technology in recent years may have contributed to the results obtained in this study. Fourth, systematic monitoring using implantable loop recorders could have documented a higher rate of asymptomatic atrial fibrillation recurrence. However, to minimize this possibility, every patient underwent seven-day Holter monitoring. Also, the proportion of patients with exclusively asymptomatic AF is not expected to be consistently different between the groups.