The impact of basic atrial rhythm during catheter ablation of atrial fibrillation on clinical outcomes: Lessons from the German Ablation Registry

The impact of basic atrial rhythm (sinus rhythm [SR] vs. atrial fibrillation [AF]) during AF ablation on efficacy and safety is unknown.


| INTRODUCTION
Atrial fibrillation (AF) is the most common arrhythmia worldwide and catheter ablation of AF is an established and effective treatment option. 1,2 Different ablation tools for pulmonary vein isolation (PVI) such as radiofrequency (RF) current in conjunction with a three-dimensional (3D) mapping system or the cryoballoon (CB), as well as different ablation strategies such as stand-alone PVI or PVI plus additional substrate modification have already been evaluated. [3][4][5][6] However, limited data are available on the impact of the basic intraprocedural atrial rhythm (sinus rhythm [SR] or AF) on procedural efficacy and safety as well as on long-term clinical outcomes. In general, left atrial contraction and diastolic compliance are significantly reduced during AF, which on the other hand might enhance catheter stability and more efficacious lesion creation. 7 Therefore, the index atrial rhythm might play an important role with regard to acute efficacy as well as for clinical long-term results of AF ablation. 8,9 The study reports on the impact of catheter ablation of AF according to the basic periprocedural atrial rhythm from a real-world multicentre prospective registry.

| German ablation registry structure
The German Ablation Registry is a prospective, multicenter non-profit registry led by the "Institut für Herzinfarktforschung" (IHF, Ludwigshafen, Germany). Project development and management, data acquisition, and clinical monitoring were organized by the IHF. Out of 55 participating German centers, 41 provided cases with AF catheter ablation.
The study was approved by local ethics boards. Patients gave written informed consent for registry participation. Data acquisition was conducted on a web-based platform.

| Preprocedural assessment, ablation procedures, and postprocedural care
Ablation procedures were performed according to institutional standards. Before the procedure, transthoracic and transoesophageal echocardiography was performed to rule out intracardiac thrombi and to assess the LA diameter. In patients on vitamin-K antagonists, anticoagulation was stopped before ablation and bridging was performed with low molecular-weight heparin. Periprocedural activated clotting times (ACT) of 250 to 300 s were targeted. Procedures were performed under deep sedation using midazolam, sufentanyl, and/or continuous propofol infusion. Performance of pre-interventional imaging, the use of a 3D mapping system and selection of the ablation system (RF or cryoballoon [CB] ablation) were at the discretion of the operators. PV isolation (PVI) was the cornerstone of all ablation procedures. Additional ablation strategies including the creation of right atrial (RA) and LA linear lesions, or ablation of complex fractionated atrial electrograms (CFAEs) were at the discretion of the operator. The postprocedural anticoagulation F I G U R E 1 Flow-diagram of patient classification. AF, atrial fibrillation; PAF, paroxysmal atrial fibrillation; SR, sinus rhythm management and antiarrhythmic drug therapy (AAD) were conducted according to local institutional standards.

| Registry management and clinical follow-up
Physicians and study nurses at participating sites entered data for baseline characteristics, and procedural details during hospital stay (see Supplement 1 for further details). A centralized telephone follow-up was conducted after 12 months applying a standardized protocol (see Supplement 2 for further details). Adverse events during follow-up together with dates of severe events, data on arrhythmia recurrencescategorized either as clinical recurrence with typical symptoms and evidence by either ECG or documented initiation of medical treatment, or arrhythmia recurrence with reliable ECG-documentation (defined as any documented episode of atrial tachycardia or tachyarrhythmia lasting > 30 s), and repeat ablations were collected. Information about the incidence and type of symptoms, patient satisfaction, and patient safety was obtained in the personal interview. Patient satisfaction was categorized as "improved," "unchanged," and "worsened." Patients not reached at their given address were traced with the help of local municipal authorities.

| Endpoints
In-hospital outcomes of interest were acute procedural success (defined as successful PV isolation) and safety. Long-term outcomes of interest were a long-term procedural success (defined as the absence of arrhythmia recurrence during the follow-up period), patient survival and long-term safety as well as patient satisfaction (defined as subjective patient well-being).
Potential periprocedural complications were categorized as severe, moderate, and minor (see Table S1 for further details).
Adverse events (AE) during follow-up were categorized as serious, moderate and minor (see Table S2 for details).
Long-term safety was specified as 12-month MACE rate (composite endpoint of death and myocardial infarction), MACCE rate (composite endpoint of death, myocardial infarction, and stroke) and a quadruple endpoint (composite endpoint of death, myocardial infarction, stroke, and major bleeding).

| Statistical analysis
Continuous data are described as means ± standard deviation (SD), if normally distributed, or as medians and interquartile range (IQR; first and third quartile). Categorical data are described as absolute and relative frequencies.
Differences in categorical variables were compared between the patient groups with the Pearson χ 2 test, those of continuous variables with Mann-Whitney-Wilcoxon test. For rates of in-hospital complications, Fisher's exact test was used.
The Kaplan-Meier method was used to estimate the 12-month MACE rate (composite endpoint of death and myocardial infarction), MACCE rate (composite endpoint of death, myocardial infarction, and stroke) and a quadruple endpoint (composite endpoint of death, myocardial infarction, stroke, and major bleeding), based on the reported event dates. The aforementioned outcomes were compared between patient groups using the log-rank test.
Statistical calculations were based on available data and cases at the time of follow-up. Documentation of baseline and procedural characteristics was more than 99% complete unless indicated in the tables.
All statistical comparisons were two-sided, and a p value < .05 was considered statistically significant. Analyses were performed using the Statistical Analysis System (SAS, Version 9.4, SAS Institute Inc.).  of cardiomyopathy or valvular heart disease was more often documented in patients of group Ib than in patients of group Ia.

| Patient cohorts and baseline parameters
In total patients with persistent AF were older and suffered from cardiac comorbidities more often when compared to patients with paroxysmal AF.
Detailed patients' baseline characteristics are provided in Tables 1, 2, and 3.

| DISCUSSION
The present study analyzes the impact of the intraprocedural atrial rhythm (SR or AF) on the acute and long-term efficacy and safety of catheter ablation of AF in a prospective multicenter registry. Our main findings are as follows: 1. At the beginning of the ablation procedure, patients suffering from paroxysmal AF presented in SR more often than did patients suffering from persistent AF (85% vs. 32%).
2. Patients presenting in SR were more often treated with the CB, regardless of the underlying type of AF (paroxysmal vs. persistent AF), whereas RF ablation was more often performed in patients presenting in AF.
3. In general, basic atrial rhythm did neither affect total procedure time, nor fluoroscopy time, nor cumulative radiation dosage.
4. There was no significant difference in arrhythmia-free survival during 1-year follow-up between patients presenting in SR and those presenting in AF.

For patients suffering from persistent AF and ablated in SR a
more favorable acute and long-term safety profile was observed when compared to ablation in AF.

| Procedural parameters and acute procedurerelated complications
In patients with persistent AF, the overall acute procedurerelated complication rate was higher when ablated in AF (54 In general, mortality is higher in patients with persistent AF than in patients with PAF 17 and is mainly driven by comorbidities and age. 18 Interestingly, in our analysis, numerically more deaths were documented for patients suffering from persistent AF when ablated in AF compared with patients ablated during SR, although this difference was not statistically significant. However, for patients with persistent AF ablated in AF, poorer results were found for MACCE (death, myocardial infarction, and stroke) and quadruple endpoints (death, myocardial infarction, stroke, and major bleeding). These differences in safety outcomes are among others driven by the increased incidence of stroke in this cohort. Stroke is mainly influenced by increased age and distinct comorbidities, which are both known to be more common in patients with persistent AF and patients with an increased AF burden. 17,19 However, the CHA 2 DS 2 -VASc score, which is currently the recommended risk score for anticoagulation assessment in AF patients, 1 was similar in groups IIa and IIb. Another aspect might be a higher rate of electrical cardioversions during the ablation procedure in patients of group IIb. Electrical cardioversion is associated with potential stunning of the left atrial appendage 20,21 and therefore might lead-at least transiently-to a higher stroke risk even when treated with anticoagulants. 21

| Limitations
Data acquisition was conducted in this prospective registry based on voluntary participation of centers and patients, and in a nonrandomized fashion. Moreover, the follow-up was carried out according to local standards and therefore data acquisition might affect the study findings.

| CONCLUSIONS
Patients undergoing AF ablation in SR were more often treated with the CB, regardless of the underlying type of AF (paroxysmal vs. persistent), whereas in patients in AF at the beginning of the ablation procedure RF-based ablation including (right and/or left atrial) substrate modification was more often performed. However, basic atrial rhythm did not affect total procedure time, fluoroscopy time, and cumulative radiation dosage. Regarding arrhythmia-free survival during 1-year follow-up, there was no difference between patients presenting in SR and those presenting in AF at the beginning of an AF-ablation procedure. However, for patients suffering from persistent AF a more favorable acute and long-term safety profile was observed when ablated in SR.

ACKNOWLEDGMENT
The ablation registry, especially the long-term follow-up, was partially supported by unrestricted grants from Medtronic, Biosense Webster, and Biotronik.