Recurrent Embolic Stroke Research Articles

Updates on Patent Foramen Ovale (PFO) Closure.

Patent foramen ovale (PFO) has been previously linked to left circulation thromboembolism and stroke. This review article aims to discuss the latest evidence, updated societal guidelines, diagnostic algorithms and novel therapeutic devices for PFO closure. PFO closure for cryptogenic stroke and systemic embolization is supported by a large body of evidence and has a strong societal recommendation. Limited data are available for platypnea-orthodeoxia syndrome, although closure appears to be beneficial. Current data do not support routine closure for migraines and decompression Illness. Development of heart-brain teams can improve identification of patients most likely to benefit from closure, utilizing a combination of imaging test and risk score algorithms. Multiple novel devices aiming at reducing complications and improving the long-term impact of current available devices are being evaluated. PFO closure has significantly progressed over the last years, with new data supporting its superiority in reducing risk of recurrent embolic stroke in patients with PFO-related stroke. Additional clinical data are required to provide further refinements on patient selection and guidance on treatment of specific subgroups.

Fighter Pilot Syndrome: A Bow Hunter Syndrome Variant Identified With Dynamic Cerebral Angiography

Background Dynamic compression of extracranial arteries in the cervicocerebral circulation is a rare phenomenon of ischemic stroke. Methods Retrospective chart review. Results Here, we present a young fighter pilot who presented with recurrent embolic strokes of undetermined source. He endorsed flying fighter jets for 6 years, during which he was subject to high G‐force loads and extensive in‐flight head maneuvers. Extensive workup identified dynamic arterial compression of his right vertebral artery, which entered the transverse foramen at the C4 level. Dynamic cerebral angiography was used to reveal the specific vessel location and provocative maneuver leading to dynamic occlusion of his right vertebral artery. Conclusion This case highlights the utility of dynamic cerebral angiography in identifying previously unexplored causes of arteriogenic emboli formation, particularly in patients with predisposing anatomic and clinical risk factors.

Abstract 089: A Case of Complicated Dissection: Vertebral Artery Sacrifice for Recurrent Stroke Prevention

Introduction Posterior circulation strokes account for 20% of ischemic strokes (1). Optimal management for posterior circulation strokes has been studied less than for anterior circulation strokes (2). Endovascular parent vessel sacrifice is an established technique used to treat vascular pathologies. There is limited evidence for parent artery sacrifice for recurrent strokes and there is no current guideline for standard of care. Methods '‐ Results 51‐year‐old gentleman with history of tobacco use presented with left homonymous hemianopsia, onset 1.5 hours prior to arrival. CT brain showed no bleed and patient received IV tissue‐plasminogen activator (tPA). CT angiography (CTA) demonstrated occlusion of the right posterior cerebral artery (PCA) and dissection of the left vertebral artery (V2 segment) with distal reconstitution. He underwent emergent thrombectomy for right P2 thrombus with complete reperfusion TICI 3 (Thrombolysis in Cerebral Infarction Score). Less than 24 hours later, he developed a right homonymous hemianopsia, and was found to have a new occlusion of the left P1 segment of the left PCA. Emergent thrombectomy was performed with complete reperfusion (TICI3). MRI brain demonstrated bilateral PCA territory infarcts. Within 12 hours of the second thrombectomy, his neurological exam deteriorated, and interval imaging revealed a basilar trunk thrombus, for which he underwent a successful endovascular thrombectomy complete reperfusion (TICI3). His antiplatelet regimen was optimized with Aspirin. Heparin was considered as treatment but was not provided because of the hemorrhagic conversion of his ischemic strokes. Given the persistent recurrence of thromboemboli in the posterior circulation despite being on optimal medical management, and evidence of hemorrhagic conversion, a decision was made to perform endovascular coil embolization of the left vertebral artery V2 segment at the site of dissection. Angiographic imaging demonstrated antegrade blood flow through the dissection as the source of recurrent embolic strokes. Six Stryker Target coils were deployed spanning the region of dissection within the left V2 segment via a right radial access with the guide catheter in the right vertebral artery. Post coil embolization angiographic runs demonstrated complete occlusion of the left vertebral V2 segment at the region of dissection which was confirmed via a left vertebral injection from a left femoral arterial access. There was preservation of ascending cervical collaterals beyond the dissection with patency of the contralateral vertebral artery supplying the intracranial circulation. Following embolization, repeat imaging showed no new infarcts and no new or worsening hemorrhage. He was continued on Aspirin monotherapy. It is notable that though his neurological exam deteriorated during each recurrent thromboembolic event, his neurologic exam at the time of discharge significantly improved with NIHSS of 3. He is currently being followed at our neuroscience institute. Conclusion Cervical arterial dissections pose increased risk for ischemic strokes (3). Vertebral artery dissection accounts for approximately 2%, of which, 10‐25% occur in middle‐aged and younger patients (4). This is a case of a young patient that exemplifies a successful role for vertebral artery sacrifice with coil embolization to prevent recurrent thromboembolic posterior circulation strokes. However controlled studies are needed for safety and efficacy of these interventions.

Elongated Styloid Process Can be Made Responsible for Recurrent Embolic Stroke Only if Eagle Syndrome is Present

With interest we read the article by Xu et al. on a 59 year-old male with recurrent episode of left hemispheric, embolic stroke [1]. Elongated styloid process (ESP) and carotid web pocket were identified as causes of recurrent stroke [1]. After resection of the ESP and resection of the carotid web, the patient became asymptomatic during a 6 months follow-up [1]. The study is excellent but has limitations that are cause of concerns and should be discussed. The main limitation of the study is that alternative causes of embolic stroke were not entirely ruled out. We should know whether there were any indications for alternative causes of embolic stroke, such as heart failure, atrial fibrillation, Takotsubo syndrome. noncompaction, endocarditis, valve abnormalities, or myocarditis. Missing in this respect are echocardiography and ultrasound of vertebral arteries. As long as all these alternative sources of embolism were not adequately ruled out, ESP and carotid web pocket cannot be made responsible for recurrent stroke with certainty. There is also no mention of inflammatory parameters, blood coagulation parameters, platelet counts, troponin values, and pro brain-natriuretic peptide (proBNP). A strong argument against the ESP as the cause of recurrent stroke is that ESP presumably existed already for a long time. No explanation is provided why it became symptomatic just at age 58 years. Where there ever any sudden neurological deficits recognised during previous years (>1.5 years before)? Another argument against ESP as the cause of recurrent stroke is that the index patient did not present with typical Eagle syndrome also referred as stylohyoid syndrome, styloid syndrome, or styloid–carotid artery syndrome [2]. Eagle syndrome is clinically characterised by orofacial and cervical pain often triggered by neck movements, by dysphagia, facial palsy, slurred speech, and vertigo [2]. Eagle syndrome can be associated with ankyloting spondylitis [3], which should have been ruled out in the index patient. The diffusion weighted imaging (DWI) lesions shown in figure 1 panel A do not explain right-sided weakness of the upper limb and amaurosis. The precentral lesions are too small and not directly in the area of the cortical upper limb representation to explain limb weakness. Regarding unilateral amaurosis, we should know whether ophthalmologists ever documented occlusion of the central retinal artery. Amaurosis triggered by head flexion suggests that each time the head is flexed embolization into the left central retinal artery occurs, which is rather unlikely. Clamping of the carotid artery by head flexion is unlikely since no cerebral symptoms with head flexion were reported [1]. Another argument against amaurosis as a manifestation of ESP is that no such cases have been previously reported. Overall, the interesting study has limitations that call the results and their interpretation into question. Addressing these issues would strengthen the conclusions and could improve the status of the study. Before attributing recurrent embolic stroke to ESP and carotid web, it is crucial to adequately rule out all alternative causes of embolic stroke. Recurrent unilateral amaurosis triggered by head flexion cannot be easily explained by ESP.

Vertebral Stump Syndrome and Recurrent Embolic Stroke in Posterior Circulation: Surgical Treatment of Complex Cases

Vertebral Stump Syndrome and Recurrent Embolic Stroke in Posterior Circulation: Surgical Treatment of Complex Cases

Recurrent embolic stroke associated with adenomyosis: A single case report and literature review.

Uterine adenomyosis is a benign disorder in which endometrial glands and stroma are present within the myometrium. There have been several case reports of cerebral infarction associated with adenomyosis, but their clinical characteristics, optimal treatment, and prognosis have not been systematically reviewed. A case of cerebral infarction with adenomyosis is reported, and a comprehensive systematic literature search using the PubMed database was conducted. A 42-year-old woman, previously diagnosed with adenomyosis, developed multiple cerebral infarctions during menstruation. Her CA125 level was 293 U/mL, and treatment with edoxaban 30mg was started. Seven days after hospital discharge, she had her subsequent menstrual period and then developed a recurrent stroke. Her CA125 level was 743 U/mL on readmission. A hysterectomy was performed, and the patient has had no further stroke recurrence. A systematic review identified 19 cases with cerebral infarction associated with adenomyosis, including the present case. The patients' clinical characteristics included young age (44.7 ± 6.2years), stroke development during menstruation (85%), multiple infarctions affecting ≥ 3 vessel territories (39%), and high levels of CA125 and D-dimer (810.6 ± 888.4 U/mL, and 10.3 ± 18.6μg/mL, respectively). Antithrombotic therapy was given to 14 patients, but recurrent stroke occurred in 5 (36%) patients. Hysterectomy was conducted in 5 and 4 patients with initial and recurrent stokes, respectively, and there were no further recurrences thereafter. Cerebral infarction associated with adenomyosis has specific clinical characteristics. Antithrombotic therapy was insufficient, and hysterectomy should particularly be considered in cases of recurrent stroke.

Abstract 13392: 3D TEE Aids in Assessment of Embolic Stroke Due to Aortic Atherosclerotic Plaque

Case Presentation: A 69-year-old right-handed man presented with new left-sided weakness and recurrent ischemic strokes. His had history of coronary artery disease, diabetes mellitus, hypertension, dyslipidemia, chronic kidney disease stage 3, obstructive sleep apnea and obesity. Plasma low-density lipoprotein was 127 mg/dL. Brain MRI showed diffusion restriction in the left caudate head, left corona radiata, left anterior lentiform nucleus, and left periventricular white matter from acute to subacute infarction. CT angiogram showed diffuse atheromatous disease in the anterior and posterior circulation, bilateral mild cervical internal carotid artery stenosis, and calcifications in the aortic arch ( Figure 1 ). Transthoracic echocardiogram (TTE) showed mild generalized left ventricular hypokinesis (ejection fraction 45%) without thrombus. Transesophageal echocardiogram (TEE) showed complex mobile atherosclerotic plaques in the aortic arch ( Figure 2 ) after which Apixaban & Clopidogrel were started and statins increased. At 1-year follow-up there was no recurrent stroke. Discussion: This case highlights the role of 3D TEE in the detection of complex aortic arch atherosclerotic plaque with mobile components as the etiology of recurrent embolic stroke. 2D TTE & TEE and CT chest were unable to show mobile components in the aortic arch plaque. Many patients identified as having “cryptogenic stroke” after 2D TTE & TEE may in fact have mobile aortic arch plaques which can only be delineated by 3D TEE, thus reducing the need for further workup and expediting appropriate treatment.

S2671 Upper Gastrointestinal Bleeding Due to Duodenal Ischemia: A Case Series

Introduction: Duodenal ischemia is a rare entity given dual blood supply from branches of the Celiac axis and Superior Mesenteric artery. However, it may present with clinically significant GI bleeding. We present three cases of duodenal ischemia diagnosed on EGD. Case Description/Methods: Case 1: An 84-year-old lady with heart failure presented with abdominal pain and melena. Vitals were BP 90/55, HR 112. She was cachectic with a mildly tender abdomen. Labs were notable for hemoglobin 6.6 g/dL from baseline of 8.2; BUN 65 mg/dL. CT abdomen noted bowel wall edema involving the duodenum. EGD revealed 5 duodenal ulcers with surrounding erythematous and friable mucosa consistent with ischemia (FigureA). She was discharged in stable condition on pantoprazole BID. Case 2: A 63-year-old lady presented with chest pain and was diagnosed with an inferior STEMI. On presentation vitals were BP 76/50 mmHg and HR 43 bpm. Cardiac catheterization was performed with two drug-eluting stents placed in the right coronary artery. Patient was started on aspirin and clopidogrel and developed melena 3 days later. Hemoglobin dripped from 12.4 to 8.4 g/dL. EGD noted pallor of the gastric body with areas of patchy erythema and erosions within the antrum, in addition to several clean based ulcers with erythema within the duodenal bulb through the second portion (FigureB). Admission CT abdomen showed moderate celiac narrowing. Patient was continued on pantoprazole BID and did not have further bleeding episodes prior to discharge. Case 3: A 63-year-old man with ESRD was admitted with endocarditis, MSSA bacteremia and embolic strokes. On day 9, he suffered PEA arrest and was resuscitated. He subsequently developed melena and shock. Hemoglobin dropped from 9.8 g/dL to 6.6 g/dL. Urgent EGD revealed a diffusely hemorrhagic stomach and the duodenum was noted to have spotty areas of necrosis, erosions and ulcerations within the bulb and second portion ( FigureC). CTA revealed moderate to severe stenosis in the proximal SMA and celiac axis. The patient was transitioned to comfort measures after suffering recurrent embolic strokes during admission. Discussion: Clinicians should maintain a high index of suspicion for duodenal ischemia in patients presenting with upper GI bleeding in the setting of a low-flow state, as illustrated in the above three cases. Management is typically supportive; however prognosis may be poor reflecting patients’ systemic illnesses leading to the process.Figure 1.: Endoscopic images demonstrating duodenal ischemia.

Two Strokes of Luck: Unusual Recurrent Paradoxical Embolic Stroke and Patent Foramen Ovale

Stroke is a leading cause of neurologic disability in the United States with the majority of cases a consequence of ischemia.

A Case of Recurrent Embolic Strokes in a Young Female With a Patent Foramen Ovale and Presumed Fibroelastoma

Patent foramen ovale (PFO) occurs in about 25% of the population. PFO closure has been shown to decrease the risk of stroke in patients with recurrent strokes as compared to those treated with medical therapy alone, with more benefit in those with larger PFO sizes. Percutaneous PFO closure, although minimally invasive, does carry surgical risks, which must also be taken into account. We present a case of a 31-year-old female presenting with a left middle cerebellar artery (MCA) stroke and persistent deficits who was found to have both a PFO and presumed fibroelastoma on her aortic valve. She was treated with aspirin and apixaban and advised to follow up with cardiothoracic surgery once she recovered from her stroke for ultimate PFO closure and removal of the fibroelastoma. Unfortunately, she presented again less than one month later with recurrent cerebrovascular accidents (CVA) requiring urgent PFO closure. Our case stresses the importance of tools such as the Risk of Paradoxical Embolism (RoPE) score index when determining treatment plans for patients with PFO, and possible confounding factors such as the presence of an aortic valve fibroelastoma.

Use of intravascular optical coherence tomography to confirm the diagnosis of a carotid web in a patient with recurrent ipsilateral embolic strokes and evaluate the response to stenting.

A Carotid web (CaW) is defined as a focal shelf-like projection of non-atheromatous, fibrous tissue along the posterior wall of the carotid bulb. CaW are rare and commonly overlooked lesions increasingly recognized as a cause of stroke in otherwise healthy patients. Intravascular imaging modalities such as intravascular ultrasound and optical coherence tomography (OCT) have been proposed as an adjunct to digital subtraction angiography for the evaluation of CaW. However, the use of OCT in CaW has yet to be described. This report investigated the utility of OCT as an adjunct imaging modality in the evaluation of CaW morphology in a young patient with recurrent ischemic strokes.

Abstract TP193: Atrial Fibrillation Burden Is Not Associated With Recurrent Cerebrovascular Events In Anticoagulated Stroke Patients: An Arest Trial Sub-study

Introduction: The burden of Atrial Fibrillation (AF) has previously been associated with a higher stroke risk in non-anticoagulated patients. We aim to find whether there is also an association between AF burden and recurrent cerebrovascular events in anticoagulated AF patients after their initial acute ischemic stroke (AIS) or transient ischemic attacks (TIA). Methods: The AREST study (Apixaban for Early Prevention of Recurrent Embolic Stroke and Hemorrhagic Transformation) was a multi-center, randomized controlled trial of early apixaban versus warfarin at one week post-TIA or two weeks post-AIS, in AF patients from 2015 to 2019. Subjects received either 30-day continuous electrocardiographic monitoring or an implantable device (i.e., pacemaker, loop recorder, or defibrillator). Logistic regression and Kendall's tau-b test were utilized to identify an association between AF burden and the proportion of subjects who developed recurrent cerebrovascular events. Results: Of 91 subjects enrolled into AREST, heart rhythm monitoring was assessed in 49 (54%); over half (59%) clustered at the extreme ends of the distribution, at either low (≤1%) or high (≥99%) AF burden. Higher AF burden was not significantly correlated with an increased risk of recurrent stroke or TIA (Odds Ratio = 0.99 [95% confidence interval (CI), 0.98-1.0]; p=0.518). Moreover, there was no statistically significant association between AF burden and the composite outcomes after adjusting for either apixaban or warfarin. Conclusions: AF Burden was not found to be associated with recurrent cerebrovascular events in patients taking oral anticoagulant after an AIS or TIA. Further research is needed to confirm these findings.

ニボルマブ奏効中に非細菌性血栓性心内膜炎による脳梗塞を発症した肺癌の 1 例

ニボルマブ奏効中に非細菌性血栓性心内膜炎による脳梗塞を発症した肺癌の 1 例

D-dimer Level as a Predictor of Recurrent Stroke in Patients With Embolic Stroke of Undetermined Source.

This study aimed to investigate the value of d-dimer levels in predicting recurrent stroke in patients with embolic stroke of undetermined source. We also evaluated the underlying causes of recurrent stroke according to d-dimer levels. A total of 1431 patients with undetermined source were enrolled in this study and divided into quartiles according to their baseline plasma d-dimer levels. The primary outcome measure was the occurrence of recurrent stroke (ischemic or hemorrhagic) in the year following the stroke event. The risk of recurrent stroke increased significantly with the increasing d-dimer quartile (log-rank P=0.001). Patients in the higher d-dimer quartiles had a higher probability of recurrent embolic stroke because of covert atrial fibrillation, hidden malignancy, or undetermined sources. Most recurrent strokes in Q3 and Q4 were embolic but not in Q1 or Q2. Multivariate analysis revealed that patients in Q3 and Q4 had a significantly increased risk of recurrent stroke compared with those in Q1 (hazard ratio, 3.12 [95% CI, 1.07−9.07], P=0.036; hazard ratio, 7.29 [95% CI, 2.59−20.52], P<0.001, respectively; Ptrend<0.001). Binary analyses showed a significant association between a high d-dimer level above normal range and the risk of recurrent stroke (hazard ratio, 2.48 [95% CI, 1.31−4.70], P=0.005). In subgroup analyses, a high d-dimer level was associated with a significantly higher risk of recurrent stroke in men than in women (P=0.039). Our findings suggest that d-dimer levels can be a useful risk assessment biomarker for predicting recurrent stroke, especially embolic ischemic stroke, in patients with undetermined source.

Early Apixaban Use Following Stroke in Patients With Atrial Fibrillation: Results of the AREST Trial.

It is unknown when to start anticoagulation after acute ischemic stroke (AIS) from atrial fibrillation (AF). Early anticoagulation may prevent recurrent infarctions but may provoke hemorrhagic transformation as AF strokes are typically larger and hemorrhagic transformation-prone. Later anticoagulation may prevent hemorrhagic transformation but increases risk of secondary stroke in this time frame. Our aim was to compare early anticoagulation with apixaban in AF patients with stroke or transient ischemic attack (TIA) versus warfarin administration at later intervals. AREST (Apixaban for Early Prevention of Recurrent Embolic Stroke and Hemorrhagic Transformation) was an open-label, randomized controlled trial comparing the safety of early use of apixaban at day 0 to 3 for TIA, day 3 to 5 for small-sized AIS (<1.5 cm), and day 7 to 9 for medium-sized AIS (≥1.5 cm, excluding full cortical territory), to warfarin, in a 1:1 ratio at 1 week post-TIA, or 2 weeks post-AIS. Although AREST ended prematurely after a national guideline focused update recommended direct oral anticoagulants over warfarin for AF, it revealed that apixaban had statistically similar yet generally numerically lower rates of recurrent strokes/TIA (14.6% versus 19.2%, P=0.78), death (4.9% versus 8.5%, P=0.68), fatal strokes (2.4% versus 8.5%, P=0.37), symptomatic hemorrhages (0% versus 2.1%), and the primary composite outcome of fatal stroke, recurrent ischemic stroke, or TIA (17.1% versus 25.5%, P=0.44). One symptomatic intracerebral hemorrhage occurred on warfarin, none on apixaban. Five asymptomatic hemorrhagic transformation occurred in each arm. Early initiation of anticoagulation after TIA, small-, or medium-sized AIS from AF does not appear to compromise patient safety. Potential efficacy of early initiation of anticoagulation remains to be determined from larger pivotal trials. Registration: URL: https://www.clinicaltrials.gov/; Unique identifier: NCT02283294.

Closure of the patent foramen ovale in patients with embolic stroke of undetermined source: A clinical expert opinion and consensus statement for the Asian-Pacific region.

Recently published long-term data from randomized controlled trials have provided evidence for the prevention of recurrent embolic stroke of undetermined source by percutaneous closure of the patent foramen ovale. However, most data were obtained from Caucasian populations and evidence on patent foramen ovale closure in Asian-Pacific patients is limited. The relative paucity in clinical data from this population, as well as the fact that Asian-Pacific patients may have higher bleeding risks than Caucasians, complicates clinical decision-making. This document, resulting from a consensus meeting of Asian-Pacific clinical experts, states the consensus among these experts about how to treat Asian-Pacific patients who had an embolic stroke of undetermined source and have a patent foramen ovale, based on currently available evidence and expert opinions. In addition, uncertainties and the need for clinical data regarding patent foramen ovale closure for prevention of recurrent embolic stroke of undetermined source in general, and specifically for Asian-Pacific patients, are identified.

Usefulness of P Wave Duration in Embolic Stroke of Undetermined Source.

The investigation of the potential association between ischemic stroke and subclinical atrial fibrillation (SCAF) is important for secondary prevention. We aimed to determine whether SCAF can be predicted by atrial substrate measurement with P wave signal-averaged electrocardiography (SAECG). We recruited 125 consecutive patients with embolic stroke of undetermined source (ESUS) and 125 patients with paroxysmal atrial fibrillation as controls. All participants underwent P wave SAECG at baseline, and patients with ESUS were followed up with Holter monitoring and electrocardiography at baseline, 3, 6, and 12 months after discharge and every 6 months thereafter. In the ESUS group, 32 (25.6%) patients were diagnosed with SCAF during follow-up. There were no significant differences between the groups regarding atrial substrate. P wave duration (PWD) was a significant predictor of SCAF. Stroke recurrence occurred in 22 patients (17.6%), and prolonged PWD (≥ 135 ms) predicted stroke recurrence more robustly than SCAF detection. In ESUS patients, PWD can be a useful biomarker to predict SCAF and to identify patients who are more likely to have a recurrent embolic stroke associated with an atrial cardiopathy. Further research is needed for supporting the utility and applicability of PWD.

Cardiac papillary fibroelastomas: A 10-year single-center surgical experience and long-term echocardiographic follow-up study.

Limited contemporary data are available on the clinical and echocardiographic outcomes after surgery for cardiac papillary fibroelastoma (CPF). The aim of this study was to review the clinical manifestations, pathological characteristics, surgical management, and prognoses of patients with histologically verified CPF, who underwent surgery at our cardiac surgery center from 2008 to 2018. Twelve patients of median age 62 years (28 to 77 years) were treated. Embolic stroke or transient ischemic attack (five patients, 42%) were the only CPF clinical manifestations. Eleven (92%) tumors were localized on the valves, with the aortic valve being the most common tumor site (seven patients; 58%). Multiple factor analysis revealed no independent predictor of CPF-related embolization. Simple shave tumor excision was sufficient in most patients (10 patients, 83%). No operative or tumor-related late mortality during the median follow-up period of 4.7 years (1.1 to 10.2 years) was recorded. Asymptomatic metachronous valve tumor recurrence (in a location different from that of the original tumor) was revealed in two patients (17%) by transesophageal echocardiography (TEE), not detected by transthoracic echocardiography (TTE). One of these two patients underwent repeated surgery for CPF but later suffered a recurrent embolic stroke, due to another tumor recurrence. CPF can be safely and effectively treated surgically. TEE is superior to the TTE option in CPF post-operative recurrence detection. There is a clear need for a prospective study to determine criteria for embolization risk stratification and optimum management in patients with CPF.

Ischemic Stroke Secondary to Left Ventricular Noncompaction

Left ventricular noncompaction (LVNC) is a rare cause of cardiomyopathy that can lead to systemic embolism and ischemic stroke. LVNC results from the arrest of ventricular myocardium compaction during embryogenesis. Multiple other cardiac complications coexist with this cardiomyopathy, and one of the potential consequences is cardioembolic events causing ischemic stroke. This condition can be underdiagnosed or misdiagnosed as hypertrophic or dilated cardiomyopathy. We report a patient who presented with recurrent embolic ischemic stroke secondary to LVNC that was overlooked on initial transthoracic echocardiographic studies. After an unremarkable laboratory workup, transesophageal echocardiogram (TEE) revealed noncompaction of the myocardium within the apex of the left ventricle, confirmed by cardiac magnetic resonance imaging (MRI). The patient was anticoagulated with warfarin and discharged to a rehabilitation facility. Increased understanding and awareness of the diagnosis, clinical manifestations, and management of LVNC are advised, particularly in patients with recurrent embolic stroke of undetermined source. Screening of all first-degree relatives with this familial condition is recommended as well, as appropriate treatment can prevent cardiac complications and sudden death. J Neurol Res. 2019;9(4-5):75-80 doi: https://doi.org/10.14740/jnr553

Protocol for AREST: Apixaban for Early Prevention of Recurrent Embolic Stroke and Hemorrhagic Transformation-A Randomized Controlled Trial of Early Anticoagulation After Acute Ischemic Stroke in Atrial Fibrillation.

Background: Optimal timing to initiate anticoagulation after acute ischemic stroke (AIS) from atrial fibrillation (AF) is currently unknown. Compared to other stroke etiologies, AF typically provokes larger infarct volumes and greater concern of hemorrhagic transformation, so seminal randomized trials waited weeks to months to begin anticoagulation after initial stroke. Subsequent data are limited and non-randomized. Guidelines suggest anticoagulation initiation windows between 3 and 14 days post-stroke, with Class IIa recommendations, and level of evidence B in the USA and C in Europe.Aims: This open-label, parallel-group, multi-center, randomized controlled trial AREST (Apixaban for Early Prevention of Recurrent Embolic Stroke and Hemorrhagic Transformation) is designed to evaluate the safety and efficacy of early anticoagulation, based on stroke size, secondary prevention of ischemic stroke, and risks of subsequent hemorrhagic transformation.Methods: Subjects are randomly assigned in a 1:1 ratio to receive early apixaban at day 0–3 for transient ischemic attack (TIA), 3–5 for small-sized AIS (<1.5 cm), and 7–9 for medium-sized AIS (1.5 cm or greater but less than a full cortical territory), or warfarin at 1 week post-TIA or 2 weeks post-stroke. Large AISs are excluded.Study Outcomes: Primary: recurrent ischemic stroke, TIA, and fatal stroke; secondary: intracranial hemorrhage (ICH); hemorrhagic transformation (HT) of ischemic stroke; cerebral microbleeds (CMBs); neurologic disability [e.g., modified Rankin Scores (mRS), National Institutes of Health Stroke Scale (NIHSS), Stroke Specific Quality of Life scale (SS-QOL)]; and cardiac biomarkers [e.g., AF burden, transthoracic echo (TTE)/transesophageal echo (TEE) abnormalities].Sample Size Estimates: Enrollment goal was 120 for 80% power (two-sided type I error rate of 0.05) to detect an absolute risk reduction of 16.5% postulated to occur with apixaban in the primary composite outcome of fatal stroke/recurrent ischemic stroke/TIA within 180 days. Enrollment was suspended at 91 subjects in 2019 after a focused guideline update recommended direct oral anticoagulants (DOACs) over warfarin in AF, excepting valvular disease (Class I, level of evidence A).Discussion: AREST will offer randomized controlled trial data about timeliness and safety of anticoagulation in AIS patients with AF.Clinical Trial Registration: www.ClinicalTrials.gov, identifier NCT02283294.