EP Tips & Techniques

Don’t Stop the Warfarin: A Case of Left Atrial Appendage Closure Device Thrombus

Siri Kadire, MD1; Benjamin Maatman, MD2; Abhishek Khemka, MD3; Mithilesh Das, MD3; Anjan Sinha, MD3
1
Resident, Indiana University School of Medicine, Indianapolis, Indiana; 2Fellow, Krannert Institute of Cardiology, Indianapolis, Indiana; 3Faculty, Krannert Institute of Cardiology, Indianapolis, Indiana

Siri Kadire, MD1; Benjamin Maatman, MD2; Abhishek Khemka, MD3; Mithilesh Das, MD3; Anjan Sinha, MD3
1
Resident, Indiana University School of Medicine, Indianapolis, Indiana; 2Fellow, Krannert Institute of Cardiology, Indianapolis, Indiana; 3Faculty, Krannert Institute of Cardiology, Indianapolis, Indiana

Introduction

Left atrial appendage closure (LAAC) devices are implanted to reduce thromboembolic risk in patients with atrial fibrillation (AFib) intolerant to anticoagulation (AC). Long-term complication data remains limited; however, device-related thrombus (DRT) is one of the most commonly reported. If not recognized and treated appropriately, DRT negates the intended stroke risk reduction with LAAC device implantation. Although there is currently no standard protocol for management of this complication, many strategies are available for consideration. Here we present a case of a 79-year-old male with DRT following device implant that successfully resolved with anticoagulation without significant adverse clinic events.

Case Description

Our patient had a history of paroxysmal AFib with a CHA2DS2-VASc score of 5 and HAS-BLED score of 4, which was managed on long-term warfarin until this was discontinued due to a traumatic subarachnoid hemorrhage. Long-term AC was felt to be contraindicated by his primary providers and per patient preference. He was cleared for short-term AC and referred for a LAAC procedure.

A LAAC device was implanted under fluoroscopic and transesophageal echocardiogram (TEE) guidance without complication (Figure 1). Periprocedural TEE showed a well-seated device with 17-20% compression and no residual flow into the left atrial appendage. The 45-day post-procedure TEE showed a well-seated device with no thrombus or peri-device leak as well. After completing 45 days of warfarin with therapeutic INRs, he was transitioned to aspirin 325 mg plus clopidogrel 75 mg, with a planned duration of 6 months post implant. Clopidogrel was discontinued prematurely at 41 days due to epistaxis, and he was continued on aspirin 325 mg thereafter.

The 6-month follow-up TEE revealed a large echo-dense mass seated on the LAAC device consistent with DRT (Figures 2 and 3). The patient was restarted on warfarin for a duration of 6 additional months without significant bleeding. The subsequent TEE at 12 months post-LAAC implant showed complete thrombus resolution (Figures 4 and 5). He currently remains on an aspirin 325 mg single antiplatelet regimen, with a planned repeat TEE 18 months post implant, which is pending.

Discussion

Patients and operators involved in LAAC device implantation should be aware of the low but present risk of multiple periprocedural complications (e.g., tamponade, vascular complication, embolism) as well as late complications such as DRT. LAAC device-related thrombus is a known but uncommon complication with a reported incidence of 3-7%.1 However, when present, it is associated with a three-fold increased risk of ischemic as well as an increase in bleeding events.1-4 Fauchier et al reported stroke in 4 of 26 patients in their series found to have DRT, with an adjusted hazard ratio of 4.4.5 The majority of DRTs are incidentally detected on surveillance imaging beyond 45 days post implant, but have been reported at any time period post implant.1 It has been argued that the incidence of DRT needs to be measured in the context of a reported 0.3-3.6% rate of LAA thrombus found in patients on therapeutic anticoagulation undergoing TEE prior to ablation.6

The main risk factors for DRT appear to include permanent atrial fibrillation, large left atrial appendages, prior stroke, higher CHA2DS2-VASc and HAS-BLED scores, chronic kidney disease, and reduced ejection fraction.1,7 Deep device implantation with residual appendage, defined as incomplete coverage of the pulmonary ridge between the LAA and upper left pulmonary vein, has been associated with DRT as well.8,9 DRT is thought to be highest risk during the sealing process before complete endothelialization has occurred. A prior animal model showed that endothelialization takes approximately 45 days.10 Time to complete endothelialization differs for each individual patient, but extrapolated from this animal model, it generally is felt to be completed by 45 days.

Currently, there is no standardized treatment strategy for DRT given its low incidence and relative infancy of the technology. There are multiple treatment strategies that can be considered, including use of a single antiplatelet agent, dual antiplatelet therapy, resumption of warfarin, or a direct oral anticoagulant. Lempereur et al reported a meta-analysis with 45.5% of cases treated with low molecular weight heparin (LMWH), with 100% resolution in the LMWH group and 89.5% for other forms of anticoagulation.11 Median treatment time was 45 days; however, the optimal duration remains unclear. The duration of anticoagulation should be individualized to the patient’s relative bleeding and ischemic risk balance. If the patient is intolerant to anticoagulation, which may be optimal, then a short duration of a one-month single or dual antiplatelet regimen may suffice. Cardiac computed tomography (CCT) may provide information regarding incomplete endothelialization to guide AC duration, described as persistent contrast filling of the LAA despite no peri-device leak by Doppler flow on TEE.12 Additionally, CCT can identify DRT in patients unable or reluctant to undergo serial TEE procedures.

Summary

This case highlights the importance of strict adherence to a post-implantation monitoring program with serial TEEs and a focused assessment for DRT. Recognition is important, given the up to threefold elevated risk of thromboembolic events. Optimal treatment strategy at this time is unclear, and antithrombotic regimen as well as duration should be tailored to the individual’s perceived balance regarding ischemic and bleeding risks. This can further be guided by imaging assessment of endothelialization. In absence of a significant mechanical issue such as a deep implantation of the device or residual gap along the face of the device, the risk of DRT should decrease with time as endothelialization and sealing of the device is completed. 

Disclosures: The authors have no conflicts of interest to report regarding the content herein. Outside the submitted work, Dr. Sinha reports personal fees from Boston Scientific.   

References
  1. Dukkipati SR, Kar S, Holmes DR, et al. Device-related thrombus after left atrial appendage closure. Circulation. 2018;138(9):874-885.
  2. Holmes DR Jr, Kar S, Price MJ, et al. Prospective randomized evaluation of the Watchman Left Atrial Appendage Closure device in patients with atrial fibrillation versus long-term warfarin therapy: the PREVAIL trial. J Am Coll Cardiol. 2014;64(1):1-12.
  3. Reddy VY, Doshi SK, Kar S, et al. 5-year outcomes after left atrial appendage closure: from the PREVAIL and PROTECT AF Trials. J Am Coll Cardiol. 2017;70(24):2964-2975.
  4. Reddy VY, Doshi SK, Sievert H, et al. Percutaneous left atrial appendage closure for stroke prophylaxis in patients with atrial fibrillation: 2.3-year follow-up of the PROTECT AF (Watchman Left Atrial Appendage System for Embolic Protection in Patients with Atrial Fibrillation) Trial. Circulation. 2013;127(6):720-729.
  5. Fauchier L, Cinaud A, Brigadeau F, et al. Device-related thrombosis after percutaneous left atrial appendage occlusion for atrial fibrillation. J Am Coll Cardiol. 2018;71(14):1528-1536.
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  7. Alkhouli M, Buru T, Shah K, et al. Incidence and clinical impact of device-related thrombus following percutaneous left atrial appendage occlusion: a meta-analysis. JACC Clin Electrophysiol. 2018;4(12):1629-1637.
  8. Meier B. What lies beneath left atrial appendage occlusion: know your enemy. Circ Cardiovasc Interv. 2018;11(3):e006360.
  9. Pracon R, Bangalore S, Dzielinska Z, et al. Device thrombosis after percutaneous left atrial appendage occlusion is related to patient and procedural characteristics but not to duration of postimplantation dual antiplatelet therapy. Circ Cardiovasc Interv. 2018;11(3):e005997.
  10. Schwartz RS, Holmes DR, Van Tassel RA, et al. Left atrial appendage obliteration: mechanisms of healing and intracardiac integration. JACC Cardiovasc Interv. 2010;3(8):870-777.
  11. Lempereur M, Aminian A, Freixa X, et al. Device-associated thrombus formation after left atrial appendage occlusion: A systematic review of events reported with the Watchman, the Amplatzer Cardiac Plug and the Amulet. Catheter Cardiovasc Interv. 2017;90(5):E111-E121.
  12. Granier M, Laugaudin G, Massin F, et al. Occurrence of incomplete endothelialization causing residual permeability after left atrial appendage closure. J Invasive Cardiol. 2018;30(7):245-250.
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