Incidence, clinical course, and risk factors in the development of femoral pseudoaneurysm after atrial fibrillation ablation

Abstract Background Previous studies have revealed the risk factors for femoral pseudoaneurysms (FPA). Most data on FPA are based on coronary and peripheral interventions, with limited studies focusing on atrial fibrillation (AF) ablation. However, patient backgrounds, anticoagulation regimens, and vascular access methods differ. In addition, a standard for managing FPA after AF ablation remains elusive due to the difficult nature of achieving thrombosis in pseudoaneurysms. Methods This single‐center, retrospective, observational study included 2805 consecutive patients who underwent AF ablation between January 2016 and December 2021. All patients underwent femoral artery and vein punctures. Puncture sites were checked 1 day post‐procedure. Results A total of 23 FPA patients were identified during the study period. Multivariate logistic regression analysis showed that hypertension (odds ratio 4.66, 95% confidence interval: 1.38–15.71; p = .0032) and warfarin use (odds ratio 3.83, 95% confidence interval: 1.40–10.45; p = .021) were significantly associated with the occurrence of FPA. The compression success rate was low (22%). There were nine and six patients in the endovascular treatment (EVT) and ultrasound‐guided thrombin injection (UGTI) groups, respectively. The success rates were 100% and 84% in the EVT and UGTI groups, respectively. The length of hospital stay after FPA treatment was 2.1 days in the EVT group and 1.3 days in the thrombin group. Conclusion We must be careful about post‐procedural FPA, especially for hypertension and warfarin‐using patients. Treatment of pseudoaneurysms with anticoagulants is unlikely to achieve hemostasis, and an early switch to invasive treatments, such as EVT, should be considered.


| INTRODUC TI ON
Atrial fibrillation (AF) ablation is performed worldwide, with the number of AF ablations performed seeing a significant increase over the last decade. 1Due to the use of multiple sheaths and the need for anticoagulation during and after ablation, vascular complications are common adverse events associated with AF ablation.One of these complications includes femoral pseudoaneurysms (FPA), which has a reported incidence of 0.53%-0.93%. 2 Previous studies have reported on the risk factors for FPA, such as older age, obesity, and hypertension. 3However, most of these are reported after coronary intervention and differ from AF ablation regarding patient background, anticoagulation regimen, and vascular access.In addition, a standardized treatment of FPA with anticoagulant therapy remains undefined.Hence, this study aimed to investigate the risk factors, incidence, and treatment of pseudoaneurysms after AF ablation.

| Study population
Between January 2016 and December 2021, 2806 consecutive patients who underwent AF ablation at Shonan Kamakura General Hospital were included in this single-center, retrospective, observational study.The hospital's Ethics Committee approved this retrospective study, which did not require written informed consent.
Patient data and clinical outcomes were obtained from medical records.The surgeons examined the puncture site the day after the procedure.In cases where findings such as tenderness, vascular murmur, or swelling were confirmed, Doppler sonography was performed to diagnose a pseudoaneurysm.

| Anticoagulation therapy
All patients underwent anticoagulation therapy using either warfarin or a direct oral anticoagulant (DOAC) for at least 3 weeks prior to catheter ablation, regardless of their CHADS2 score or the presence or absence of sinus rhythm.While most patients took DOACs as their anticoagulation therapy, warfarin was the preferred choice in cases of severely compromised renal function or when the patient was undergoing dialysis.For those who were administered warfarin before the procedure, the international normalized ratio was consistently maintained within a range of 1.6-2.6. 4 Anticoagulation with both DOAC and warfarin was uninterrupted during the periprocedural period.Heparinized saline was infused to maintain an activated clotting time of at least 300 s.

| Vascular access
Vascular access was obtained using the standard landmarks and palpations of the femoral artery pulse.For cryoballoon ablation, two femoral vein punctures were performed, introducing a 6 Fr sheath and a 15 Fr sheath (FlexCath Advance, Medtronic, Dublin, Ireland).
In radiofrequency ablation, three femoral vein punctures were performed with the introduction of 8, 8.5, and 6 Fr sheaths.All patients underwent arterial puncture for blood pressure monitoring, utilizing a 3 Fr sheath in the femoral artery.Preoperative computed tomography evaluated the coronary arteries; should stenosis be present, a 4 Fr sheath was inserted into the femoral artery to facilitate coronary angiography.

| Ablation procedures
The procedure was performed under moderate propofol sedation.
Pulmonary vein isolation was performed using either a 28-mm cryoballoon (Arctic Front Advance, Medtronic, Ireland), an 8-mm tip ablation catheter (Japan Lifeline, Inc., Tokyo, Japan), TactiCathTM Quartz (Abbott, Ravenswood, Chicago, IL, USA), or a SmartTouch ThermoCool Surround Flow irrigated-tip ablation catheter (Biosense Webster, Irvine, CA, USA).After the procedure, hemostasis of the vascular entry site was achieved using manual compression after intravenous injection of protamine and figure-of-eight sutures.

| Treatment strategy for pseudoaneurysms
Anticoagulation therapy continued after confirmation of FPA because the damaged endocardium and low atrial contraction might cause thrombotic complication.If there was only severe anemia, we temporarily stopped anticoagulants.
All patients initially underwent conventional manual or ultrasound-guided compression therapy (UGCT).The treating physician determined the appropriate timing for transitioning from manual compression, or UGCT, to thrombin injection, considering patient tolerance and therapeutic efficacy.Before 2019, the primary modality for treating compression-resistant pseudoaneurysms was ultrasound-guided thrombin injection (UGTI).Surgical intervention was selected in cases where the pseudoaneurysm was large or accompanied by an arteriovenous fistula.After 2019, we refined our protocol to incorporate combined endovascular treatment (EVT) with percutaneous thrombin injection as the first-line therapy for pseudoaneurysms unresponsive to compression.

| Echo-guided thrombin injection
Treatment was administered using either convex or linear transducers, selected between 5 and 7.5 MHz based on the depth of the pseudoaneurysm.Prior to injection, the site was meticulously prepared, and a local anesthetic, typically 1%-2% lidocaine, was applied to both the skin and underlying tissue.A solution containing 1000 IU/mL thrombin was prepared by combining 5000 IU thrombin with 5 mL of normal saline.This solution was transferred to a 1 mL syringe and introduced under the precise guidance of ultrasound imaging.A 21-gauge needle was carefully inserted adjacent to the pseudoaneurysm sac in the neck region, followed by the deliberate injection of thrombin solution into the sac.The utmost caution was exercised to ensure that the thrombus remained confined within the sac.Thrombin was consistently administered until the pseudoaneurysm was nearly entirely thrombosed, accompanied by the disappearance of color Doppler flow within the sac.After needle withdrawal from the pseudoaneurysm, an ultrasound assessment was performed to verify the absence of thrombosis around the originating artery.Following this procedure, all patients were instructed to maintain a supine posture for a minimum of 12 h.

| RE SULTS
The patient demographics are shown in Table 1.A total of 23 FPA cases were identified during the study period.The prevalence of hypertension, chronic kidney disease, and warfarin use was higher in the FPA group than in the non-FPA group.No significant differences were observed between the two groups in terms of other clinical characteristics.Multivariate logistic regression analysis revealed that hypertension and warfarin use were significantly associated with FPA occurrence (Table 2).
In 23 patients, FPA was initially treated with manual compression, or UGCT, which was successful in five patients (22%).Before 2019, surgical procedures were conducted on three patients: two exhibited a diameter exceeding 50 mm, while the other presented a 9 mm diameter concomitant with an arteriovenous fistula.For the other six pseudoaneurysms that were unresponsive to compression, UGTI was selected for treatment.After 2019, nine cases of pseudoaneurysms unresponsive to compression were treated with EVT (Figure 2).
Table 3 shows the clinical outcomes associated with FPA.One case was unsuccessfully treated with UGTI and subsequently underwent surgical intervention.The success rates of EVT and surgery were 100%.No complications were observed in any of the treatment modalities.The average diameter of the pseudoaneurysms in the invasively treated groups was 30-40 mm.The average hospitalization duration after FPA treatment was 2.1 days for the EVT group, 1.3 days for the UGTI, and 4.7 days for the surgical group.
It is evident that the surgical group had the longest hospitalization.Some pseudoaneurysms originate from both the SFA and the deep femoral artery (DFA).

| DISCUSS ION
The present study demonstrates the clinical experience of FPA in a large cohort of patients.The main findings of the study were as follows: (a) the incidence of FPA after AF ablation was 0.82%, (b) hypertension and warfarin therapy were associated with a higher incidence of FPA, (c) the manual compression success rate for FPA was only 22%, and (d) the treatment outcomes of UGTI, EVT, and surgery were favorable.
Several patient and procedural characteristics predict FPA formation following percutaneous coronary intervention (PCI). 3However, these predictors have not been studied in post-AF ablation populations.A valid comparison between the predictors of FPA and those complicating PCI is difficult because the patient characteristics, preoperative medications, and catheter tools are different.In multivariate analysis, we found that hypertension and warfarin use were independent risk factors for FPA formation.Hypertension elevates intravascular pressure and causes continuous bleeding at the puncture point.It has been reported that patients with systolic blood pressure >180 mmHg during the procedure were eight times more likely to develop vascular complications than other groups. 5The use of antihypertensive drugs may help reduce systolic blood pressure during ablation, possibly reducing the incidence of vascular complications.Anticoagulation Strategy) trial showed a greater incidence of major bleeding events (such as cardiac tamponade and inguinal hematoma) in the warfarin group. 6In the VENTURE-AF trial, which compared rivaroxaban with warfarin, bleeding events were comparable between the two groups. 7However, the limitations of the VENTURE-AF trial were its small sample size (n = 248) and low number of events.These studies and the results of our study suggest that preoperative warfarin may be more likely than DOAC to cause pseudoaneurysms.

TA B L E 1 Patient clinical characteristics and risk factors in relation to femoral pseudoaneurysm.
The factors contributing to pseudoaneurysms include not only patient characteristics and anticoagulation drugs but also the puncture technique employed and the puncture site chosen.Among the physicians in this study, 80% (2244 cases) were fellows, and 20% (561 cases) were attending physicians who performed vascular punctures.There was no notable difference in the incidence of pseudoaneurysms between fellows and attending physicians (0.75% vs. 1.5%; p = .10).Our study suggests that less experienced doctors do not necessarily experience a heightened occurrence of FPAs.The risk of femoral artery pseudoaneurysms increased when the puncture site was not in the common femoral artery but in the superficial, DFA, or the external iliac artery. 8Utilizing real-time ultrasound-guided puncture can help visualize the common femoral artery and determine the optimal route of access. 9In our study, some pseudoaneurysms originated from superficial or deep femoral arteries.Thus, the use of ultrasound-guided punctures may reduce the prevalence of pseudoaneurysms.
Prior research has shown that the occurrence of pseudoaneurysms was significantly lower in trans-radial approach than in trans-femoral approach. 10Trans-radial route might decrease hemorrhagic complication even in AF ablation procedure, but the trans-femoral approach is the preferred and most commonly used access for mechanical circulatory support, such as percutaneous cardiopulmonary support. 8In our institution, the arterial pressure This study had several limitations.First, this was a retrospective, non-randomized, single-center study.A large-scale, prospective, randomized trial is warranted to confirm the study outcomes.
Second, not all punctures were performed under echo guidance.
Recently, angiography and duplex ultrasound guidance have become common during puncture procedures.The puncture method may also affect the occurrence of pseudoaneurysms.Third, the number of FPA cases was small; therefore, regression analysis was limited.
Fourth, treatment selection was not randomly allocated, and there could be a selection bias in the treatment choice.Randomization is warranted to confirm the effects of each treatment.

CO N FLI C T O F I NTER E S T S TATEM ENT
Authors declare no conflict of interests for this article.

DATA AVA I L A B I L I T Y S TAT E M E N T
The data that support the findings of this study are available from the corresponding author, TK, upon reasonable request.

E TH I C S S TATEM ENT
Authorization for the use of case information and materials was

A 4 .
5 or 6 Fr 120 cm guiding sheath was inserted into the radial artery.The guiding sheath was advanced into the external iliac artery, and angiography was performed to confirm the location of the pseudoaneurysm.A 0.014-inch guidewire was advanced to the distal part of the superficial femoral artery (SFA), and the vessel diameter was confirmed by intravascular ultrasound examination.The balloon was then inflated to stop blood flow to the pseudoaneurysm.Next, thrombin was delivered to the aneurysm under fluoroscopic guidance.After balloon deflation, angiography confirmed the absence of blood flow into the pseudoaneurysm (Figure 1).
All statistical analyses were performed using JMP, version 14.0 (SAS Institute, Cary, NC, USA).Continuous data are expressed as means ± standard deviation and were compared using the Student's t-test.Categorical variables were compared using the χ 2 test.Parameters with statistically significant differences (less than .05 in the univariate analysis) were entered into a multiple logistic regression analysis to explore factors associated with FPA incidence.F I G U R E 1 Angiographic imaging of a typical endovascular treatment process with percutaneous thrombin injection for a pseudoaneurysm of the femoral artery.(A) Angiography showing a pseudoaneurysm originating from the common femoral artery.The white arrow indicates the body of the pseudoaneurysm.(B) The guiding wire was advanced to the iliac artery from the right radial artery.(C) We used IVUS to measure the artery diameter.IVUS revealed a pseudoaneurysm in the common femoral artery.The white arrow indicates a pseudoaneurysm.(D) The balloon is inflated to achieve hemostasis inside the artery.Angiography showed that blood flow to the pseudoaneurysm was completely blocked.(E) Thrombin was injected into the pseudoaneurysm under fluoroscopic guidance.(F) The final angiogram showed complete hemostasis.IVUS, intravascular ultrasound.

Therefore, treating the
development of post-AF ablation FPA should be completed carefully, especially in individuals with hypertension and warfarin users.FPA on oral anticoagulants makes achieving hemostasis difficult using compression.Because of this, we would encourage an early switch to EVT.AUTH O R CO NTR I B UTI O N S Takafumi Koyama was responsible for the clinical design and conceptualization.Takafumi Koyama, Kazuki Tobita, and Masato Murakami were involved in the acquisition of clinical data.Takafumi Koyama, Kazuki Tobita, and Masato Murakami analyzed and interpreted the data, and Takafumi Koyama wrote the manuscript.All the authors have discussed, read, and approved the submission of this manuscript to the journal.
obtained from the Institutional Review Board of Shonan Kamakura General Hospital on April 4, 2023 (Approval No. TGE02165-024).D ECL A R ATI O N S Approval of the Research Protocol: Authorization for the use of case information and materials was obtained from the Institutional Review Board of Shonan Kamakura General Hospital (TGE02165-024).Registry and the Registration No: N/A.Animal Studies: N/A.
Univariate and multivariate predictors of femoral pseudoaneurysm.
14cause the EVT method occludes blood flow into the aneurysm using a balloon until hemostasis is achieved, thrombosis is unlikely to occur, and treatment can be performed regardless of the morphology of the neck and aneurysm.14Ourstudy demonstrated the feasibility of EVT for treating FPAs through our high procedural success rate, lack of complications, and short hospital stays.As he- mostasis of pseudoaneurysms is challenging with anticoagulants, we recommend switching to EVT as soon as possible if hemostasis is difficult to achieve with compression.