Safety of catheter ablation of atrial fibrillation without pre‐ or peri‐procedural imaging for the detection of left atrial thrombus in the era of uninterrupted anticoagulation

Abstract Background The need for pre‐ or peri‐procedural imaging to rule out the presence of left atrial thrombus in patients undergoing catheter ablation of atrial fibrillation (AF) is unclear in the era of uninterrupted direct oral anticoagulant (DOAC) regimen. We sought to examine the safety of catheter ablation in appropriately selected patients with paroxysmal AF without performing screening for left atrial thrombus. Patients and Methods Consecutive patients planned for radiofrequency AF catheter ablation between January 2016 and June 2020 were enrolled, and prospectively studied. All subjects were receiving uninterrupted anticoagulation with DOACs for at least 4 weeks before the procedure. All subjects were in sinus rhythm the day of the procedure. The primary outcome of the study was ischemic stroke or transient ischemic attack (TIA) during at 30 days. Results A total of 451 patients (age 59.7 ± 10.2 years, 289 males) with paroxysmal AF were included in the study. The mean CHA2DS2‐VASc score was 1.4 ± 1.2. The mean left ventricular ejection fraction and left atrial diameter were 60 ± 5% and 39.3 ± 4 mm, respectively. Regarding the anticoagulation regimen, apixaban was used in 197 (43.6%) patients, rivaroxaban in 148 (32.8%) patients, and dabigatran in 106 (23.5%) patients. None of the patients developed clinical ischemic stroke or TIA during the 30‐day post‐discharged period. Conclusions Catheter ablation can be safely performed in low‐risk patients with paroxysmal AF without imaging for the detection of left atrial thrombus in the era of uninterrupted DOAC anticoagulation.


| INTRODUC TI ON
Transesophageal echocardiography (TOE) is considered the gold standard for the assessment of preexisting left atrial (LA) thrombus in the setting of atrial fibrillation (AF) catheter ablation (CA). 1 Intracardiac echocardiography or cardiac computed tomography are also used, but less commonly, for this reason. [2][3][4] Based on the most recent expert consensus statement on AF CA, TOE is reasonable in patients who present in sinus rhythm and have not been anticoagulated prior to CA and in patients who are in AF and have been receiving anticoagulation for at least 3 weeks before the procedure (Class IIa indication). 1 However, in this consensus statement, only 51% of the Task Force members perform TOE in all patients undergoing AF CA, irrespective of the presenting rhythm and the anticoagulation treatment. 1 Initial AF CA studies with an interrupted periprocedural anticoagulation strategy with vitamin K antagonists (VKAs) question the use of preprocedural TOE in patients undergoing AF CA. 5,6 Recent randomized trials have demonstrated the safety of uninterrupted direct oral anticoagulants (DOACs) as compared to uninterrupted VKAs in patients undergoing AF CA. [7][8][9] In a recent meta-analysis, uninterrupted periprocedural DOACs have been associated with a lower incidence of cerebrovascular events as compared with uninterrupted VKAs. 10 Whether adoption of an uninterrupted anticoagulation strategy with DOACs obviates the need of TOE or other imaging to screen for the presence of LA thrombus in adequately anticoagulated patients undergoing AF CA remains a knowledge gap. Previous reports addressing this issue have incorporated intracardiac echocardiography or cardiac computed tomography. [2][3][4] In this prospective study, we sought to examine the safety of paroxysmal AF CA in adequately anticoagulated patients with DOACs without performing pre-or peri-procedural screening for left atrial thrombus.

| Patient population
Consecutive patients planned for radiofrequency AF CA between January 2016 and June 2020 were enrolled, and prospectively studied. Patient demographics, medical history, medications, and echocardiographic data (ie, left ventricular ejection fraction [LVEF], LA diameter, and the presence of valvular heart disease) were collected in all cases. The thromboembolic risk was estimated with the CHA 2 DS 2 -VASc score. Written informed consent was obtained from all participants, according to institutional guidelines.

| Exclusion criteria
Study exclusion criteria included AF as the presenting rhythm at the day of the procedure, persistent or long-standing persistent AF, previous LA ablation procedures, inadequate anticoagulation for ≥4 weeks prior to the ablation procedure, VKAs use, history of LA thrombus, previous stroke or transient ischemic attack (TIA), history of end-stage renal disease, structural heart disease (LVEF <45%, hypertrophic cardiomyopathy, severe valvular heart disease, and congenital heart disease), and LA enlargement >45 mm. Patients that did not complete the predefined follow-up were also excluded from the analysis.

| Periprocedural anticoagulation and catheter ablation procedure
All subjects were receiving uninterrupted anticoagulation with DOACs (apixaban 5 mg twice daily, rivaroxaban 20 mg once daily, or dabigatran 150 mg twice daily) for at least 4 weeks before the procedure. Reduced doses of DOACs were prescribed according to drug-dosage instructions. The last dose of rivaroxaban was taken on the evening prior to the procedure, whereas the last doses of apixaban and dabigatran were taken on the morning of the procedure. During the procedure, we maintained an activated clotting time between 300 and 400 seconds using intravenous administration of unfractionated heparin. Sheaths were irrigated with heparinized normal saline throughout the procedure. DOACs were readministered 3-4 hours after the procedure and continued for at least 3 months or longer, based on the CHA 2 DS 2 -VASc score.
The ablation procedure has been described in details elsewhere. 11 In brief, following a single transseptal puncture, the three-dimensional geometry of the LA was reconstructed using the CARTO 3 navigation system (Biosense Webster, Inc). All subjects underwent the same ablation protocol including wide circumferential pulmonary vein antral isolation (PVAI) around ipsilateral pulmonary veins (PVs) using a Thermocool SmartTouch irrigated-tip contact force-sensing ablation catheter (Biosense Webster, Inc).

| Post-ablation care and follow-up
Patients were hospitalized for 24 hours after CA. Transthoracic echocardiography was performed after the procedure to rule out the presence of pericardial effusion. A detailed neurological examination was performed in all subjects before discharge in order to exclude ischemic stroke or TIA. Additionally, a postdischarged 30-day outpatient clinic examination was carried out.

| Outcomes
The primary outcome was incident ischemic stroke (defined as a neurologic deficit lasting >24 hours due to acute focal injury of the

| Statistical analysis
Continuous variables were presented as mean values ± standard deviation, while categorical ones were presented as absolute and relative frequencies (percentages). Analyses were done with SPSS (version 17.0, SPSS Inc).

| RE SULTS
The initial study population included 1280 patients referred for AF CA. After applying the exclusion criteria, a total of 451 patients with paroxysmal AF (mean age 59.7 ± 10.2 years old, 289 males) were enrolled in a prospective manner. The clinical, echocardiographic, procedural, and medication data of the study cohort are depicted in Table 1

| D ISCUSS I ON
This single-center study demonstrated the proof-of-concept that AF CA can be safely performed without preprocedural imaging in patients with paroxysmal AF in the setting of uninterrupted DOAC anticoagulation. None of the patients meeting these criteria developed an ischemic stroke or TIA during 30-days of follow-up.
The utility of preprocedural imaging with TOE in patients undergoing AF CA has been initially investigated in studies incorporating an interrupted anticoagulation strategy. In a study of interrupted anticoagulation strategy (warfarin with periprocedural bridging therapy with enoxaparin), the incidence of LA thrombus detected by TOE was 1.47%. 5   Intracardiac echocardiography was performed in all patients to exclude LA thrombus, but in only 71% of them the LA appendage was visualized. In the rest of the patients (29%), AF ablation was per- In conclusion, AF CA can be safely performed without pre-or peri-procedural imaging in the era of uninterrupted DOAC anticoagulation in carefully selected patients with paroxysmal AF.

| Limitations
The present report has potential limitations. First, the presence of thromboembolic events was assessed based on clinical examination.
Cerebral magnetic resonance imaging was not routinely performed.
Second, the number of patients is relatively small. Further studies in larger number of patients are needed to validate our findings. Finally, although patients with AF as the presenting rhythm at the day of the procedure were excluded, LA stunning may be present after recent restoration of sinus rhythm even in the case of paroxysmal AF predisposing these patients to thromboembolic events. Adequate anticoagulation for ≥4 weeks prior to the ablation procedure may overcome this limitation.

D I SCLOS U R E
The authors declare no conflicts of interest.