Management of an acute cerebral embolic infarct with thrombolysis and mechanical thrombectomy in the presence of an aortic arch floating thrombus

Abstract

An aortic arch floating thrombus is a rare cause of embolic ischaemic cerebral infarction. Previously, thrombolysis or mechanical thrombectomy has been used to treat acute cerebral infarction in this context; however, combination therapy using both modalities is yet to be published. The optimal management of aortic arch floating thrombi is debated. Endovascular removal, thrombolysis, vitamin K antagonists and recently, direct oral anticoagulants have been utilised to treat aortic arch floating thrombi. Herein, we highlight the case of a patient presenting with dense hemiparesis, dysphasia and chest pain. CT imaging revealed a left middle cerebral artery thrombus and concurrent aortic arch floating thrombus. He was successfully treated with acute thrombolysis and subsequent mechanical thrombectomy of the cerebral thrombus resulting in resolution of his neurological symptoms. Repeat imaging demonstrated persistence of the aortic arch floating thrombus despite thrombolysis. The aortic arch floating thrombus was managed successfully with direct oral anticoagulant therapy.

Background

An aortic arch floating thrombus (AAFT), present without discernible atherosclerotic disease, is a rare phenomenon and an important source of systemic emboli. It is believed that primary atherosclerotic pathways and cardiovascular risk factors are implicated in the pathophysiology of AAFTs.¹ Few case reports document embolic cerebral infarction secondary to an AAFT. As such, optimal management is debated. Combined therapy with thrombolysis and subsequent cerebral mechanical thrombectomy in the presence of an AAFT has not been reported.

There is a lack of consensus regarding the effective management of AAFTs. Treatment options used include open surgical² or endovascular removal³ and anticoagulation therapy. For patients who received anticoagulation therapy, vitamin K antagonists and heparin have been used.⁴ Recently, successful resolution of aortic floating thrombi has been reported with the use of direct oral anticoagulant therapy.^{5 6}

This case details favourable outcomes following management of an acute cerebral thrombus with thrombolysis and mechanical thrombectomy in the presence of an AAFT. We also report complete resolution of the AAFT after several months of direct oral anticoagulant therapy.

Case presentation

A man in his mid-50s presented with dense right-sided hemiparesis, expressive dysphasia and persistent chest pain for the hour preceding presentation.⁷ Exact time of onset could be ascertained from discussion with the patient’s next of kin. His medical history included hypothyroidism subsequent to radioiodine therapy for hyperthyroidism. He was on daily oral levothyroxine. The patient was not from the local area and had recently been investigated at his base hospital for episodes of transient loss of consciousness with suspected tonic–clonic seizures. Initial investigations which had been performed including CT head, electroencephalogram and transthoracic echocardiogram were unremarkable and he had not been prescribed any antiplatelet or antiepileptic medication. An implantable loop recorder had recently been inserted to capture possible cardiac arrhythmias. He denied any personal or family history of vascular disease or thrombophilia but had a 10 pack-year smoking history. Neurological examination revealed Medical Research Council (MRC) grade 0 power in the right upper and right lower limbs with positive ipsilateral Babinski’s reflex. Power in the left upper and lower limbs was recorded as MRC grade 5. Mild right-sided facial droop was seen. He had marked right hemisensory loss. The patient had receptive and expressive dysphasia. Visual field examination was normal but he had partial right-sided gaze palsy. Initial NIHSS (National Institutes of Health Stroke Scale) score was 18/42. Glasgow coma scale score was 12/15 (E4, V3, M5). Radio-femoral delay was noted. Clinical examination was otherwise unremarkable.

Investigations

Significant variation in blood pressure in the upper extremities was observed. Blood pressure in the left and right upper limbs was recorded as 163/92 and 146/87, respectively. Twelve-lead ECG demonstrated sinus rhythm with features of early repolarisation. Routine blood tests including glycated haemoglobin and lipid profile were unremarkable. Troponin level was within normal range. Initial non-contrast CT head demonstrated complete occlusion of the M1 segment of the left middle cerebral artery (MCA) in keeping with acute thrombus (figure 1). The Alberta stroke programme early CT score was 10. CT angiography (CTA) of the intracranial vasculature and aortic arch demonstrated restricted flow of contrast within the distal left internal carotid artery extending up to the M1 segment of the left MCA consistent with an acute thrombus (figure 2). CTA also revealed an incidental 4 cm mural thrombus within the proximal aortic arch, inferior to the bifurcation of the brachiocephalic artery and extending into the lumen of the aortic arch (figure 3). The major branches arising from the aortic arch demonstrated normal opacification and patency.

Figure 1.

Initial non-contrast CT head demonstrates an area of focal hyperdensity and occlusion within the M1 segment of the left middle cerebral artery (see arrow) in keeping with acute thrombus. This is consistent with the hyperdense middle cerebral artery sign.

Figure 2.

Subsequent CT angiography highlights paucity of contrast distal to the bifurcation of the left common carotid artery (A). The left ICA (internal carotid artery) is not visualised in the region of the cavernous sinus (B). As the left ICA divides into its terminal branches, no contrast is visualised within the left middle cerebral artery (C).

Figure 3.

CT angiography of the aortic arch revealed a 40 mm intramural thrombus inferior to the bifurcation of the brachiocephalic artery and extending into the lumen of the aortic arch. The major branches arising from the aortic arch demonstrated normal opacification.

Treatment

He was diagnosed with an acute ischaemic stroke secondary to a left MCA embolic thrombus, deemed to arise from the AAFT. Door-to-needle (DTN) time was 75 min; the slightly longer DTN time was due to an initial delay in acquiring the CT head and CTA. He received thrombolysis with alteplase (a recombinant tissue plasminogen activator). Post-thrombolysis, power in his right leg improved to MRC grade 4. Speech and comprehension also improved. Repeat NIHSS score was 15/42. He was transferred to a neurointerventional radiology centre where he underwent successful cerebral mechanical thrombectomy. Door-to-groin puncture was 239 min. Good recanalisation was achieved; the patient’s thrombolysis in cerebral infarction score was grade 2b (figure 4). NIHSS score 2 hours post thrombectomy was 6/42. The patient demonstrated no clinical evidence of recurrent embolic phenomena following treatment. Repeat CTA revealed persistence of the AAFT despite thrombolysis.

Figure 4.

Cerebral digital subtraction angiography demonstrates a distal left ICA occlusion with no contrast visualised within the left middle cerebral artery (MCA) arterial system prior to mechanical thrombectomy (A). Post thrombectomy, there is significantly improved contrast flow and visualisation within the left ICA and MCA territories, thrombolysis in cerebral infarction grade 2b (B).

MRI head revealed multiple foci of restricted diffusion in the left frontal lobe, left basal ganglia and left posterior parietal lobe on diffusion weighted imaging with similar hypointense foci on the apparent diffusion coefficient sequence in keeping with multiple embolic infarcts of the left MCA territory (figure 5). Corresponding changes were also seen in the T2 and T2-FLAIR (Fluid-attenuated inversion recovery) sequences. Transthoracic echocardiography did not reveal any evidence of left ventricular thrombus. His case was discussed in the joint cardiology and cardiothoracic surgery multidisciplinary team meeting. Due to his recent ischaemic infarct, they highlighted that an invasive approach would be associated with significant anaesthetic and perioperative risk and thus, medical management was advised. The option of a long-term vitamin K antagonist or direct oral anticoagulant therapy was discussed with the patient. Due to paucity of cases, the evidence base for either treatment option was limited. The patient opted for direct oral anticoagulant therapy. He was commenced on dabigatran 150 mg twice daily and atorvastatin 40 mg nocte.

Figure 5.

MRI head performed on day 2 post thrombectomy, reveals hyperdense lesions within the basal ganglia on the diffusion-weighted sequence (A) and corresponding hypodense changes on the apparent diffusion coefficient map (B) suggestive of a recent ischaemic infarct. Changes are also noted in the T2 and T2-FLAIR sequence in parallel regions, consistent with a recent infarct (C, D). There is no evidence of haemorrhage on the T2*(gradient echo) sequence (E).

Outcome and follow-up

The patient’s expressive dysphasia resolved and hemiparesis improved considerably following thrombectomy. NIHSS score 24 hours after initial presentation was 3/42. With physiotherapy, only marginal right sided weakness was elicited on examination when discharged. Repeat CTA of the aortic arch at 4-month follow-up revealed complete resolution of the AAFT. Analysis of his implantable loop recorder found no evidence of atrial fibrillation. He completed 6 months of direct oral anticoagulant therapy. He was advised to commence single antiplatelet therapy (clopidogrel) lifelong. We have requested an acquired thrombophilia screen be performed by his local hospital following completion of his direct oral anticoagulant course.

Discussion

An AAFT, without associated atherosclerotic disease, is a rare occurrence; it is likely many remain undiagnosed. Thrombi may be a significant source of idiopathic systemic emboli. Several authors have implicated primary atherosclerotic processes in the pathophysiology of AAFT, supported by histological inspection of specimens demonstrating cholesterol-rich plaques at the thrombus insertion site.^{1 8} Cardiovascular risk factors including smoking and hypercoagulable syndromes may also predispose to AAFT.^{1 3} AAFTs have been detected on echocardiography and CTA however, CTA appears to facilitate improved detection and enhanced characterisation of the thrombus.^{1 3} CT also permits superior depiction of the proximal branching vessels of the aorta.

Few cases in literature depict patients diagnosed with acute ischaemic stroke secondary to an AAFT. Systemic thrombolysis or mechanical thrombectomy has been used to treat the acute cerebral thrombus in this context.^{1 9} Thrombolysis poses a potential risk of partial lysis of the AAFT and recurrent embolisation. Krüger et al¹⁰ describe this complication but also highlight that systemic thrombolysis may treat recurrent thromboembolism. It is likely the recurrent thromboembolic risk is low. The recent third international stroke trial demonstrated that the risk of recurrent ischaemic stroke after thrombolysis is <1%.¹¹ The decision was made to proceed with thrombolysis in our patient as the advantages of salvaging viable brain tissue and limiting the size of the core infarct in a young patient likely outweighed the early recurrent ischaemic risk from partial lysis of the AAFT. There was no clinical evidence of recurrent thromboembolism in our patient after thrombolysis; the patient demonstrated observable clinical improvement in the immediate period following thrombolysis. It is probable that the AAFT was well organised and firmly adherent to the aortic wall which may explain why the thrombus persisted despite systemic thrombolysis.

There is no consensus on the definitive management of AAFT. Surgical resection,² mechanical thrombectomy¹ and systemic thrombolysis¹⁰ have been used. Consideration of surgical management should encompass review of the patient’s performance status, key characteristics of the AAFT such as size and location and the patient’s operative risk. Poor pre-existing functional baseline, high operative risk or considerable morbidity following the initial embolic event may mandate a conservative approach. For our patient, his high operative risk was deemed a deterrent to surgical management.

There are no robust randomised controlled trials and limited evidence available to evaluate the efficacy and adverse effects of warfarin versus direct oral anticoagulants in treating thrombus in the aortic arch or left ventricle and thus, insufficient evidence to calculate the ischaemic risk of vascular events due to fragmented emboli. Several authors have detailed complete resolution of an AAFT with either heparin or warfarin^{4 12 13}; however, recurrent embolisation despite anticoagulation has been reported.¹ Recent reports have used direct oral anticoagulants such as apixaban, rivaroxaban and dabigatran as an alternative conservative option in treating mural and floating thrombi of the aorta.^{5 6 14} The Randomised Evaluation of Long-Term Anticoagulation Therapy trial demonstrated lower rates of stroke and systemic embolism when patients received 150 mg of dabigatran two times per day compared with warfarin in patients with atrial fibrillation.¹⁵ In our case, the patient had a good premorbid functional baseline and optimal renal function hence, also owing to patient preference, dabigatran was used. The minimum duration of anticoagulant therapy and, if coumarins are advised, the target international normalised ratio in patients with AAFT is undetermined.

A hypercoagulable state secondary to thrombophilia has been noted in some patients with AAFT.¹ When investigating the aetiology of an AAFT, a thrombophilia screen should be performed. Direct oral anticoagulants can interfere with the coagulation pathways reviewed in a thrombophilia screen.^{16 17} Consequently, in our patient, the thrombophilia screen was delayed until completion of his anticoagulant course.

To conclude, acute ischaemic stroke secondary to an AAFT is rare. Thrombolysis and mechanical thrombectomy should be considered if the patient presents within the appropriate time window. If the AAFT persists despite systemic thrombolysis, direct oral anticoagulants may be considered as an alternative conservative management option due to their non-inferiority to warfarin.

Learning points.

• An aortic arch floating thrombus without discernible atherosclerotic disease is a rare cause of embolic ischaemic stroke.

• Aortic arch floating thrombi may present with critical cardiovascular symptoms such as chest pain, radiofemoral delay and blood pressure variation in the upper extremities.

• Management of an acute embolic stroke secondary to an aortic arch floating thrombus can include combination therapy with systemic thrombolysis and mechanical thrombectomy.

• Direct oral anticoagulant therapy is an alternative conservative management option for aortic arch floating thrombi.

• Further discussion and review of cases depicting acute ischaemic strokes secondary to an aortic arch floating thrombus are required to facilitate consensus on optimal management.