A Very Late and Persistent Thrombosis after Left Atrial Appendage Occlusion.

Atrial fibrillation (AF) is the most common cardiac arrhythmia and ischemic stroke represents the most important complication. When the oral anticoagulation cannot be taken due to bleeding problems and considerations, the percutaneous occlusion of the left atrial appendage (LAA) is a possible solution. We present a case of a very late thrombosis of the LAA-Occluder device. The thrombus was diagnosed only after the patient suffered a stroke and a regression could not be achieved, neither with apixaban nor with warfarin alone. A successful result could be observed with the combination of high dose warfarin with aspirin 100mg/day. The possible etiology of this rare complication is an incomplete endothelialization of the device. Copyright:

INTRODUCTION

Cerebral ischemic stroke represents the most important fatal complication of atrial fibrillation (AF) with a stroke-related mortality rate of about 20%.[1]

In autopsy and echocardiography studies, the left atrial appendage (LAA) was shown to be the source of thrombin in >90% of patients with nonvalvular AF and a recent embolic event.[1]

Oral anticoagulation (OAC) is recommended in patients with CHA2DS2-VA2Sc score ≥1 to reduce stroke risk in these patients. However, OAC is associated with severe hemorrhagic complications.[2]

Percutaneous LAA closure has emerged as an alternative to OAC, and after the implantation of the device, a dual antiplatelet therapy (DAPT) should be considered for a minimum duration of 3 months.[2] No clear recommendation is mentioned in the current European guidelines on the duration of DAPT.[3]

The latest European guidelines classify the percutaneous LAA occlusion with IIb class of recommendation for stroke prevention in patients with AF and contraindications for long-term anticoagulant treatment[3] and point out the need for adequately powered controlled trials to inform the best use of these devices.

The presence of a thrombus on the device is a possible complication. Older age and history of stroke are known predictors of thrombus formation on the devices. An incomplete occlusion as etiology of a thrombus has also been speculated.[45] Pracon et al.[6] have divided the device related thrombosis (DRT) as early (at 1.5 month), late (at 3–6 months), or very late (at 12-month follow-up). A successful treatment of the thrombus with OAC has been previously published.[4]

CASE PRESENTATION

A 83-year-old female patient presented in our clinic for further evaluation after having an ischemic stroke. She has a a past history of chronic heart failure with reduced ejection fraction (25%–30%). She also has two-vessel coronary artery disease, chronic renal failure with glomerular filtration rate 44 ml/min/1.73 m2, type 2 diabetes mellitus, and arterial hypertension. A persistent AF was diagnosed 5 years ago, and an OAC with warfarin was initiated (CHA2DS2 VASc score was 7). Shortly after the initiation of OAC, she suffered a life-threatening esophagus bleeding due to varices. As the LAA was free of thrombus, an Amplatzer Cardiac Plug (ACP) Occluder 24 mm was implanted without complications. A DAPT with aspirin (100 mg/day) and clopidogrel (75 mg/day) was initiated. A transoesophageal echocardiogram (TOE) at the 2nd and 90th days showed a very good result with no signs of blood flow in the LAA. Clopidogrel was then stopped and a monotherapy with aspirin was given.

At the time of the new presentation shortly after the stroke and over 4 years after the implantation of the LAA Occluder, a new TOE was performed. In the TOE, a large thrombus (20 mm × 11 mm) on the Amplatzer Occluder device was diagnosed.

With the proof of thrombus, the treatment was switched from aspirin to apixaban (10 mg/day), and a new TOE was performed after 8 weeks. As the thrombus was consistent, a treatment with warfarin instead of apixaban was initiated (target international normalized ratio: 3.0). In the new TOE after 3 months of effective anticoagulation, there was no further improvement, and aspirin of 100 mg was added. With the combined treatment of aspirin and warfarin a regression of the thrombus was finally achieved. The patient was then left on monotherapy with warfarin, and in the last TOE after 8 weeks, a device related thrombosis (DRT) was no longer present [Figure 1].

Figure 1

Transoesophageal echocardiography shortly after the presentation with stroke and over 4 years after the implantation of the left atrial appendage occlude (a) and transoesophageal echocardiogram after initiation of a combination therapy with warfarin and aspirin (b), showing regression of the device-related thrombosis. Red arrow is the thrombosis

From the initial presentation and up to now, the patient suffered no further ischemic or bleeding events.

DISCUSSION

In the current case report, we present a patient with a large and persistent DRT. The risk factors in the development of a thrombus are presented here (older age and history of stroke). The implanted device was an ACP Occluder device, and in the PLAATO study,[7] device thrombosis was reported (the WATCHMAN study[3] on the contrary showed no thrombosis during the follow up), but the hypothesis of a device-induced thrombosis has been questioned in registries and meta-analysis.[5]

In contrast to the previous reported cases, a single anticoagulation did not resolve the problem. We observed a persistence of the thrombus under apixaban and with high-dosed warfarin,[8] and only after the introduction of a combination therapy with aspirin and warfarin, there was an improvement.

In addition, in the TOE after the implantation (days 2 and 90 and under DAPT), there were no signs of DRT. The most possible explanation for these observations is a missing or incomplete endothelialization of the LAA occluder device, which became clinic manifest after withdrawing the DAPT.

In the vast majority of cases, the thrombus formation on the ACP Occluder is on the central screw of the device,[9] as it has happened in our case. The material used for the ACP is mostly Nitinol, except from the central screw, which is made from stainless steel.[9] The second-generation LAA occluder devices do not have the central screw, and a significant reduction on device thrombosis has been well-documented.[10]

The fact that a reduction of the thrombus was possible only after the addition of aspirin to the OAC is also a sign of the incomplete endothelialization and platelet aggregation as a cause of the thrombosis. The absence of an incomplete endothelialization has been also previously proposed as a possible cause of device thrombosis,[7] although this scenario was tested neither in the PLAATO nor in the PROTECT AF study.

CONCLUSION

The percutaneous occlusion of LAA is an attractive solution concerning patients with AF with anticoagulation and bleeding problems. Nevertheless, the possibility of early, late, or very late DRT should be taken into account, especially in patients with known risk factors (age and history of stroke). The management of such a complication is not standardized, and a combination of warfarin and aspirin may be needed.

Declaration of patient consent

The authors certify that they have obtained all appropriate patient consent forms. In the form the patient(s) has/have given his/her/their consent for his/her/their images and other clinical information to be reported in the journal. The patients understand that their names and initials will not be published and due efforts will be made to conceal their identity, but anonymity cannot be guaranteed.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.