Systemic embolism with left atrial thrombus occurring four years after left atrial appendage closure in a patient with atrial fibrillation

Zhi-hong Zhao, Sai-hua Wang, Qiang Huan, Luo-ning Zhu, Zhong-ping Ning

Department of Cardiology, Shanghai Pudong New Area Zhoupu Hospital, Shanghai University of Medicine & Health Sciences Affiliated Zhoupu Hospital, Shanghai 201318, China

Dear editor,

The left atrial appendage (LAA) is the most common site for thrombus formation in patients with atrial fibrillation (AF).We present the case of a patient with AF who underwent LAA closure (LAAC) with Watchman (Atritech, Boston Scientific, USA), in whom extracranial systemic embolic events (SEEs) with left atrial thrombus were observed after 4 years, and discuss relevant literature to improve the understanding of SEEs.

CASE

A 78-year-old woman was admitted to our hospital on September 18, 2016, with AF accompanied by palpitations and dyspnoea while climbing stairs, and this symptom had been persistent for the past month. The physical examination results were unremarkable; she had a history of cerebral infarction for 1 year, limb weakness,and a 10-year history of hypertension. Transthoracic echocardiography (TTE) showed a left atrial diameter of 55 mm and a left ventricular ejection fraction of 45%. Transesophageal echocardiography (TEE) showed left atrial spontaneous echo contrast, but no thrombus was detected. The ostial diameters of the LAA were 15.8 mm at 45°, 20.7 mm at 90°, and 22.6 mm at 135°;LAA emptiness time was 37.1 cm/s; the filling speed was 23.7 cm/s. She had a history of cerebral infarction due to the inability to tolerate long-term anticoagulation therapy, with congestive heart failure, hypertension, age≥75 years (doubled), diabetes mellitus, stroke (doubled)-vascular disease, age 65-74 years and sex category(female) (CHADS-VAS) score of 7 and Hypertension,Abnormal renal/liver function, Stroke, Bleeding history or predisposition, Labile international normalized ratio, Elderly, Drugs/alcohol (HAS-BLED) score of 5.The patient underwent LAAC with Watchman, with the residual leak at 1 mm and the compression ratio at 20%. The patient was advised to take warfarin daily(international normalized ratio [INR] 2-3). Three months after LAAC, TEE was performed, and no thrombus was detected on the Watchman device. The patient resumed dual antiplatelet therapy with aspirin 100 mg plus clopidogrel 75 mg daily for 6 months, followed by life-long aspirin. No bleeding-related complications developed. On December 18, 2020 (4 years after LAAC), the patient was readmitted with sudden chest pain and dyspnoea, with D-dimer ＞10 mg/L (normal value ＜0.5 mg/L), troponin I ＜0.025 ng/mL, N-terminal brain natriuretic peptide 1,837 pg/mL, urea nitrogen 16.00 mmol/L, creatinine 136 μmol/L, and uric acid 578 μmol/L. Electrocardiography showed AF rhythm. Brain magnetic resonance imaging revealed multiple lacunar ischaemic infarcts. Cardiac computed tomography angiography (CTA) showed left atrial spontaneous echo contrast, and a thrombus was found in the anterior wall of the left atrium (Figure 1A), which was unrelated to the Watchman (Figures 1 B and C). TTE revealed the left atrium diameter to be 46 mm × 70 mm × 56 mm; a hypoechoic mass of 40 mm × 15 mm was found in the anterior wall of the left atrium, and the left ventricular ejection fraction was 50%. Lower extremity vascular ultrasonography showed bilateral lower extremity arterial plaques, left lower extremity artery thrombus,and normal blood flow in the deep veins of the lower extremities. TEE revealed left atrium spontaneous echo contrast, Watchman device in a good position,endothelialisation echo on the surface of occluder,1-mm residual leak, and a hypoechoic mass of 46 mm× 20 mm on the anterior wall of the left atrium, with no obvious motion (Figures 1 E and F). On aortic CTA,atherosclerosis was found in the aorta and branches, left internal iliac artery, superior mesenteric artery, and left renal artery in moderate stenosis conditions. Remarkable atherosclerosis was observed on the descending aorta with thrombus, and there was more thrombus with lumen occluded in the right common iliac artery, the proximal segment of the right anterior internal iliac artery and external iliac artery (Figure 1D). Pulmonary artery CTA did not reveal filling defects in left or right pulmonary arteries. After 10 d of anticoagulation therapy with low-molecular-weight heparin, the patient’s chest pain and dyspnoea were relieved, and the D-dimer level returned to normal. The antithrombotic regimen was changed to 100 mg aspirin daily combined with warfarin(INR 2.0-2.5). Two months later, TEE re-examination showed that the left atrium hypoechoic mass disappeared.Aspirin combined with warfarin was used for a long time, and follow-up was closely performed.

DISCUSSION

AF is associated with adverse complications such as ischemic strokes, systemic thromboembolisms, and heart failure.LAA is the most common anatomical site for thromboembolic AF. Our patient with AF was admitted to the hospital with sudden chest tightness and shortness of breath 4 years after LAAC. She had left intraatrial thrombus, atherosclerosis of the aorta and major branches, and moderate stenosis of the left internal iliac artery, superior mesenteric artery and left renal artery.There were more thrombi with lumen occlusion in the right common iliac artery, the proximal segment of the right anterior internal iliac artery and the external iliac artery,which were consistent with the diagnosis of SEEs.

Figure 1. Examination images of the patient. A: thrombus in the left anterior atrial wall (red arrow) (CTA review); B: Watchman in favorable shape and position (black arrow), with no relationship to the thrombus (red arrow) (CTA review); C: the upper left sealing disc of Watchman device localized filling contrast (red arrow) (CTA review); D: thrombus noted in the right common iliac artery (red arrow), proximal segment of the right anterior internal iliac artery, and external iliac artery occlusion (CTA review); E: hypoechoic mass on the anterior wall of the left atrium (red arrow) (TTE review); F: the surface of Watchman device (red arrow) was endothelialised, and no thrombus was observed (TEE review). CTA:computed tomography angiography; TTE: transthoracic echocardiography; TEE: transesophageal echocardiography.

SEEs occurring in patients with AF in contemporary anticoagulation trials accounted for at least 11.5% of all thromboembolic events and were associated with considerable morbidity,with the incidence of SEEs in the near and middle term after LAAC being 0.24%-0.29%.

LAAC prevents LAA thrombus. We emphasized that intensive anticoagulation 2-3 months after LAAC could prevent device-related thrombus (DRT) before the endothelialization of the sealed disc, although there is no clear diagnosis of the endothelialization process. In this case, the atrial thrombus does not belong to the category of DRT. For patients with long-term persistent AF, the pathogenesis of intracardiac thrombus formation in AF is related to each component of Virchow’s triad, including atrial stasis, endothelial dysfunction, and a systemic hypercoagulable state. The administration of only aspirin could not alleviate hypercoagulability after LAAC, left atrial enlargement and persistent AF as risk factors for left atrial thrombus/spontaneous echo contrast.

In our patient with chest pain and dyspnoea, the D-dimer level increased significantly. Although lower extremity deep venous system thrombus and pulmonary artery embolism were excluded, transient pulmonary embolism was not excluded. In fact, the elevated D-dimer level was associated with not only left atrial thrombus but also aortic plaque rupture.

We analyzed the results of aortic CTA and ruled out the possibility of embolism below the abdominal aorta, where the thrombus was considered to occur in situ, suggesting that long-term oral aspirin after LAAC in patients with AF could not prevent the occurrence of SEEs and left atrial thrombus. In this case, the left atrium thrombus was the result of a systemic hypercoagulable state triggered by SEEs, indicating that the patients with the LAAC need close follow-up and its long-term efficacy remains to be further understood.

CONCLUSIONS

This report shows the case of a patient with AF who took aspirin for 4 years after LAAC and developed SEEs,accompanied by left atrial thrombus (non-DRT), in whom long-term oral warfarin and aspirin administration caused the disappearance of left atrium thrombus.

This study was supported by grants from the Clinical Plateau Discipline of Pudong New Area Health Committee(PWYgy2018-03) and the General Project of Science and Technology Committee of Pudong New Area (PKJ2019-Y40).

Not needed.

The authors declare no conflicts of interest regarding the publication of this paper.

All authors had substantial contributions to the acquisition, analysis, or interpretation of data for the work. All authors have read and approved the final version of the submitted manuscript.