Author + information
- Received January 29, 2017
- Revision received May 8, 2017
- Accepted May 22, 2017
- Published online December 4, 2017.
- Shunsuke Kubo, MDa,b,
- Yukiko Mizutani, MDa,
- Krissada Meemook, MDa,
- Yoshifumi Nakajima, MDa,
- Asma Hussaini, PAa and
- Saibal Kar, MDa,∗ ()
- aHeart Institute, Cedars-Sinai Medical Center, Los Angeles, California
- bDepartment of Cardiology, Kurashiki Central Hospital, Kurashiki, Japan
- ↵∗Address for correspondence:
Dr. Saibal Kar, Heart Institute, Cedars-Sinai Medical Center, 8631 West Third Street, Suite 415-E, Los Angeles, California 90048.
Objectives This study investigated characteristics and clinical impact of device-related thrombus formation after Watchman device implantation in atrial fibrillation (AF) patients.
Background Left atrial appendage occlusion using the Watchman device is an effective alternative to anticoagulation for stroke prevention in AF patients. However, device-related thrombus formation remains an important concern after Watchman implantation.
Methods From 2006 to 2014, 119 consecutive AF patients underwent Watchman implantation. Transesophageal echocardiographic (TEE) follow-up was scheduled at 45 days, at 6 months, and at 12 months after the procedure. The incidence, characteristics, and clinical course of device-related thrombus formation detected by TEE were assessed.
Results Follow-up TEE identified thrombus formation on the Watchman device in 4 patients (3.4%). The prevalence of chronic AF was 100% in patients with thrombus, which was higher than that for patients without thrombus (40.0%). Deployed device size was numerically larger in patients with thrombus (29.3 ± 3.8 mm vs. 25.7 ± 3.2 mm, respectively). All patients with thrombus discontinued any of the anticoagulant/antiplatelet therapy which was required under the study protocol. After restarting or continuing warfarin and aspirin therapy, complete resolution of the thrombus was achieved in all patients at subsequent follow-up TEE. Warfarin therapy was discontinued within 6 months for all cases, and there was no thrombus recurrence. The mean follow-up duration was 1,456 ± 546 days, with no death, stroke, or systemic embolization events in patients with thrombus.
Conclusions AF burden, device size, and anticoagulant/antiplatelet regimens can be associated with device-related thrombus after Watchman device implantation. Short-term warfarin therapy was effective, and the clinical outcomes were favorable.
- device-related thrombus
- left atrial appendage
- percutaneous left atrial appendage occlusion
- Watchman device
Embolic stroke is a serious and often debilitating complication of atrial fibrillation (AF). Oral anticoagulation using warfarin therapy has long been the gold standard for the prevention of embolic stroke (1). The left atrial appendage (LAA) is the primary source (>90%) of thromboembolism in nonvalvular AF (2,3). Percutaneous occlusion of the LAA has emerged as a device-based treatment alternative to long-term anticoagulation therapy in the prevention of AF-associated stroke. The PROTECT-AF (Watchman Left Atrial Appendage System for Embolic Protection in Patients With AF) trial demonstrated the efficacy of the Watchman device (Boston Scientific, Marlborough, Massachusetts) to prevent stroke, systemic embolism, and cardiovascular death, compared to warfarin therapy (4,5). In the United States, the Watchman device is the only LAA occlusion device approved by the U.S. Food and Drug Administration.
Residual peri-device leakage and unexpected device-related thrombus after implantation of the Watchman device are important clinical concerns. A previous study reported that residual leakage was not associated with risk for thromboembolism (6). There have been some reports of device-related thrombus formation associated with the Watchman device (7–9); however, patient characteristics and clinical implications of the device-related thrombus are still unknown. In this study, the incidence, characteristics, and clinical courses of left atrial thrombus associated with the Watchman device were investigated.
This study population included 119 consecutive AF patients who underwent Watchman implantation from June 2006 to March 2014 at our institution. All patients received the Watchman device as participants in the PROTECT-AF clinical trial (n = 10), the CAP (Continued Access Protocol) registry (n = 61), the PREVAIL (Prospective Randomized Evaluation of the Watchman LAA Closure Device In Patients With Atrial Fibrillation Versus Long Term Warfarin Therapy) clinical trial (n = 22), or the CAP 2 Registry (n = 26). Inclusion and exclusion criteria of the PROTECT AF and PREVAIL trials have been described previously (4,10). The Watchman device was successfully deployed in all patients. All data for this study were collected from an established interventional cardiology laboratory database approved by the Cedars-Sinai Medical Center Institutional Review Board.
Transthoracic and transesophageal echocardiography (TEE) was performed prior to Watchman device implantation to calculate left ventricular ejection fraction and exclude patients with intracardiac thrombus. Baseline LAA flow velocity was measured, and spontaneous echocardiographic contrast (SEC) was graded by a score of 0+ (none) to 3+ (severe) (11). The severity of mitral regurgitation was also evaluated according to previous reports (12).
Watchman device implantation
The Watchman device implantation was performed as previously described (4). The procedure was performed with the patient under general anesthesia. Intravenous heparin was given as a bolus dose to achieve an activated clotting time of >250 s in all patients. The TEE and an LAA angiogram were used to determine optimal device size (there are 5 sizes ranging from 21 to 33 mm in maximum diameter). All patients were placed on warfarin (international normalized ratio: 2 to 3) and aspirin (81 to 325 mg daily) therapy and discharged the next day.
After the procedure, clinical and TEE follow-up were scheduled at 45 days, at 6 months, and at 12 months during the first year, as dictated by the trial protocol (5). In patients within the CAP or CAP-2 registry, follow-up TEE at 6 months was not planned. Thrombus formation and residual leakage into the LAA were evaluated during each follow-up TEE. Device-related thrombus was defined as thrombus formation attached to the Watchman device.
Warfarin therapy was discontinued if the TEE at 45 days showed complete closure of the LAA, no residual peri-device flow (jet >5 mm in width), or no device-related thrombus. After warfarin treatment was stopped, aspirin therapy was continued and daily clopidogrel (75 mg) was started until the 6-month follow-up was completed. After that point, only aspirin therapy was continued indefinitely. Patients who deviated from the above-described prescribed anticoagulation and antiplatelet regimen were defined as off-protocol patients. When the device-related thrombus is detected, warfarin and aspirin therapy is maintained, and follow-up TEE is scheduled for 3 or 6 months after the detection of thrombus. After the first year, clinical follow-up was scheduled semiannually by clinic visit or telephone interview. Clinical events included death, stroke, and systemic embolism.
Data are mean ± SD for continuous variables. Categorical variables are numbers with relative percentages. The SPSS statistical software version 20 (IBM Corp., Armonk, New York) was used for all statistical calculations.
Follow-up TEE was performed in 117 patients (98.3%) at 45 days, 66 patients (55.4%) at 6 months, and 101 patients (84.9%) at 12 months. Follow-up TEE identified thrombus attached to the Watchman device (device-related thrombus) in 4 patients (3.4%), 2 patients at 45 days, 1 patient at 6 months, and 1 patient at 12 months. No intracardiac thrombus formation was detected in the other patients. The patient characteristics with and without thrombus formation were shown in Table 1. The prevalence of chronic AF was 100% in the thrombus group, which was higher than in the nonthrombus group (40.0%). Mean age was lower in the thrombus group (age 66.5 ± 9.9 years vs. 76.1 ± 9.2 years, respectively). The CHADS2 (congestion, hypertension, age, diabetes, and stroke) score and CHA2DS2-VASC (CHADS2 plus vascular disease and sex) score seemed to be higher in the thrombus group. The baseline LAA flow velocity was not different between the 2 groups (31.7 ± 23.6 m/s vs. 36.7 ± 18.1 m/s, respectively). However, the severity of SEC was much greater in the thrombus group (2.50 ± 0.58) than in the nonthrombus group (0.47 ± 0.65). The severity of mitral regurgitation was similar between the 2 groups.
Mean procedure time was 53.0 ± 11.1 min in the thrombus group and 60.4 ± 21.2 min in the nonthrombus group. The Watchman device size was numerically larger in the thrombus group than in the nonthrombus group (29.3 ± 3.8 mm vs. 25.7 ± 3.2 mm, respectively). There were no other adverse events, including death, myocardial infarction, stroke, and acute renal failure, in either the thrombus or the nonthrombus group during the hospital stay.
Echocardiographic findings in the thrombus group are summarized in Table 2. All thrombi were organized on the polyethylene terephthalate (PET) fabric. The thrombus was mobile in 1 patient and nonmobile in 3 patients. The mobile thrombus was pedunculated and had a neck attached to the fabric (Figure 1A). The cases with nonmobile thrombus encompassed the fabric to various extents (Figure 1B). Residual leakage into the LAA was observed in 2 patients of the thrombus group at the time of thrombus detection (1.3 mm and 1.5 mm, respectively). The prevalence of residual leakage within 12 months (at 45 days, at 6 months, or at 12 months) was 50.0% in the thrombus group and 28.7% in the nonthrombus group. The time course of anticoagulation and antiplatelet therapy in 4 patients with thrombus is illustrated in Figure 2. Of the patients in whom thrombus was detected at 45 days, 1 patient discontinued both warfarin and aspirin therapy due to subdural hematoma at 22 days, and another patient discontinued aspirin therapy by self-judgment before follow-up. The patient with the thrombus at 6 months had discontinued clopidogrel therapy due to nosebleed at 2 months. The patient with thrombus at 12 months discontinued aspirin therapy at 8 months, and clopidogrel was administered at the referring physician’s recommendation. Therefore, all patients deviated from the prescribed anticoagulant/antiplatelet therapy (off-protocol patients). The rate of the off-protocol patients was 27.8% in the nonthrombus group but much lower compared to the thrombus group (100%).
After the detection of thrombi, both warfarin and aspirin therapy were continued or restarted in all patients of the thrombus group. Complete resolution of the thrombus was achieved in all patients at subsequent follow-up TEE (Figures 1A and 1B). Warfarin therapy was able to be discontinued within 6 months after the detection of thrombi in all patients (Figure 2), and no recurrence of thrombus formation was observed. The mean follow-up duration was 1,456 ± 546 days in the thrombus group. There were no instances of death, stroke, and systemic embolism events in all 4 patients during the follow-up period.
The main findings of this study were as follows. First, the incidence of device-related thrombus formation after Watchman implantation was 3.4% for 12 months follow-up. Second, age, AF type, device size, CHADS2 score, SEC grade, and anticoagulation/antiplatelet therapy can be associated with thrombus formation after Watchman device implantation. Third, in patients with device-related thrombus, short-term warfarin therapy was effective, and clinical outcomes were favorable.
The current study is the first to demonstrate the characteristics and clinical course of the device-related thrombus associated with the Watchman device. The observed incidence (3.4% per patient) was consistent with the previous study (7). On the other hand, after implantation of the Amplatzer cardiac plug (ACP) (St. Jude Medical, St. Paul, Minnesota), another device used to occlude the LAA, the incidence of thrombus formation was reported to be 17.6% (13). Although the regimens of anticoagulation/antiplatelet therapy were different among each of the studies, the Watchman device may have a lower incidence of device-related thrombus than the ACP device. As the previous study stated, this result was affected by the smaller surface of the Watchman device (13). Furthermore, in a previous study, there were focal uncovered areas in the ACP device at the screw and inferior edge of the left atrium, although complete endothelial coverage was shown at 28 days after the Watchman implantation (14); therefore, the earlier healing response to the device surface might also have affected the low incidence of thrombus after the Watchman device implantation.
Predictors of LAA thrombus in AF patients have been reported to be CHADS2 score, left ventricular dysfunction, SEC grade, left atrial volume, LAA flow velocity, and LAA morphology (15–17). In the current study, several possible factors were identified to predict device-related thrombus. Notably, chronic AF was seen in all patients with device-related thrombus, and these patients also had higher SEC grades than patients without thrombus. This finding suggests that the blood stasis in the left atrium affects thrombus formation on the device surface after LAA occlusion. Larger Watchman devices were implanted in the thrombus group than in the nonthrombus group. Because all device-related thrombi were organized from fabric space in this study, the fabric area of the larger device might have contributed the incidence of thrombus formation. Furthermore, at the detection of thrombi, all patients had discontinued at least part of the prescribed anticoagulation/antiplatelet therapy. Therefore, the current recommendation for an anticoagulation/antiplatelet regimen under the PROTECT-AF and PREVAIL trial would be reasonable. A previous study reported that the Watchman device could be safely implanted with low incidence of device-related thrombus even without a warfarin transition (18). However, when early discontinuation of anticoagulationt/antiplatelet therapy is considered after the Watchman device implantation, risk assessment for thrombus formation based on the current findings may be useful.
In the current study, complete resolution of device-related thrombus was achieved by warfarin therapy in all patients. The efficacy of warfarin therapy for LAA thrombus has been reported (19). In a previous study, LAA thrombus was resolved in 71% of participants. Due to the exposure of the thrombus to direct left atrial blood flow, warfarin therapy may be more effective in device-related thrombus than in LAA thrombus. Furthermore, the duration of warfarin therapy was <6 months in all patients, and there was no recurrence of thrombus without warfarin therapy. We hypothesize that the risk of thrombus formation may be reduced because endothelial coverage has progressed on the device surface. There were no major adverse events in patients with thrombus in this study. Previous trial data also reported the low incidence of device-related ischemic stroke (0.3%) (7). Therefore, once the thrombus formation is detected attached to the device, it is expected that short-term warfarin therapy is responsive and the subsequent clinical impact of the thrombus is still low. The results of our can be useful for preventing and treating device-related thrombus after the Watchman implantation.
First, this is a retrospective, observational, single-center study. Second, the study population was limited to a low event rate. Due to the limited population of the thrombus group, inferential statistics may not be meaningful and were not calculated. Therefore, our study results need to be confirmed by larger prospective studies. Third, although TEE is the gold standard modality for detecting the left atrial thrombus, small thrombus on the device may not be detected. Fourth, echocardiographic data were not analyzed in an independent core laboratory. Finally, the current study population included several trials which had clinical inclusion and exclusion criteria. Therefore, the current study results may not be generalized.
The incidence of device-related thrombus after the Watchman left appendage occlusion device implantation was 3.4% in our cohort. Atrial fibrillation burden, SEC grade, device size, and anticoagulation/antiplatelet regimen can be associated with thrombus formation. Even after detection of thrombus, short-term warfarin therapy is effective, and the clinical outcomes are favorable.
COMPETENCY IN MEDICAL KNOWLEDGE: Percutaneous left atrial appendage closure using the Watchman device was effective to prevent stroke, systemic embolism, and cardiovascular death in atrial fibrillation patients. However, device-related thrombus was a clinical concern of the Watchman device. Currently, there are no data for characteristics and clinical courses of the device-related thrombus.
TRANSLATIONAL OUTLOOK: This study showed that AF burden, SEC grade, device size, and the anticoagulation/antiplatelet regimen can be associated with the thrombus formation, and short-term warfarin therapy is effective for resolving the thrombus. These characteristics of the thrombus were helpful for the risk assessment of the thrombus in the clinical practice. Our findings should be confirmed in a prospective study with a larger population.
Dr. Kar has received research grants from and is a consultant for Boston Scientific, Abbott Vascular, and Gore Medical. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose.
All authors attest they are in compliance with human studies committees and animal welfare regulations of the authors’ institutions and Food and Drug Administration guidelines, including patient consent where appropriate. For more information, visit the JACC: Clinical Electrophysiology author instructions page.
- Abbreviations and Acronyms
- atrial fibrillation
- left atrial appendage
- spontaneous echocardiographic contrast
- transesophageal echocardiography
- Received January 29, 2017.
- Revision received May 8, 2017.
- Accepted May 22, 2017.
- 2017 American College of Cardiology Foundation
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