Cardioembolic Origin Research Articles

Sindrome de Wallenberg en adulto joven

Introducción: La Enfermedad Cerebrovascular es el conjunto de afecciones clínicas caracterizadas por un déficit neurológico de inicio súbito secundario a la oclusión total o parcial de una arteria cerebral la misma que durante los últimos años en países en vías de desarrollo ha provocado un incremento en la mortalidad. 
 Objetivo: Describir un caso clínico de Síndrome de Wallenberg en un adulto joven, sus manifestaciones clínicas, diagnóstico y manejo.
 Material y métodos: Estudio descriptivo retrospectivo, presentación de caso clínico de Síndrome de Wallenberg en un adulto joven.
 Resultados: Se presenta el caso de un adulto joven que ingresa a hospitalización por presentar cuadro clínico compatible con Síndrome de Wallenberg de origen cardioembólico (fibrilación auricular paroxística) fuera del periodo ventana para administración de activador tisular del plasminógeno indicándose cardioversión farmacológica exitosa, y mostrando mejoría clínica evidente de déficit neurológico al mes de tratamiento médico domiciliario y rehabilitador.
 Conclusiones: La escasa frecuencia de presentación del Síndrome de Wallenberg, así como la necesidad de realizar un diagnóstico precoz y brindar un tratamiento oportuno para evitar las secuelas neurológicas hacen que sea importante conocer acerca de su situación actual y manejo.

Author response: Optimizing in-hospital triage for large vessel occlusion using a novel clinical scale (GAI2AA).

We appreciate the comments and insights of Grewal and Goldstein on our article.1 As for atrial fibrillation (AF), it has the weakest relation with large vessel occlusion (LVO) (logit [probability of the occlusion] = 3.3 [gaze palsy, aphasia, or inattention [GAI]] + 1.5 [arm paresis] + 1.3 [AF] − 4.4 + e), and the prevalence may vary between the patient groups. In our GAI2AA scale (pronounced “gaia,” who is the Greek goddess of the earth), the addition of AF was intended to reinforce the diagnosis of LVO. If the patients with hemispheric symptoms and arm paresis also have the sign of AF, it not only shows the more probability of an LVO but also with typical cardioembolic origin.

Editors' note: Optimizing in-hospital triage for large vessel occlusion using a novel clinical scale (GAI 2 AA)

Editors' note: Optimizing in-hospital triage for large vessel occlusion using a novel clinical scale (GAI ₂ AA)

Management of Stroke in Patients with Left Ventricular Assist Devices

IntroductionThe number of patients with left ventricular assist devices (LVAD) is rapidly growing in industrialized countries. While cerebrovascular events comprise a significant complication, data on stroke etiology, clinical management and functional outcome are scarce. MethodsConsecutive LVAD patients with ischemic or hemorrhagic stroke receiving treatment at an university stroke center between 2010 and 2018 were included into an institutional registry. Clinical characteristics, causes, management and functional outcome of stroke occurring within this cohort are reported. Acceptable functional outcome was defined as mRS 0-3. ResultsN = 30 acute strokes occurred in 20 patients (77% ischemic, 23% hemorrhagic, mean age 57 ± 13 years, 10% female, 8 patients (40%) had more than one event). 87% of all events happened with non-pulsatile devices, on average 9 (IQR 3-22) months after the implantation. All patients used oral anticoagulation with a Vitamin-K antagonist in combination with anti-platelets. The international normalized ratio (INR)-values were outside the therapeutic range in 39% of ischemic strokes and in 57% of hemorrhagic strokes. Ischemic strokes were predominantly of cardioembolic origin (92%) and of mild to moderate clinical severity (median NIHSS 6 (IQR 4-10). None qualified to receive intravenous thrombolysis or intra-arterial endovascular therapy. 61% of IS-patients showed an acceptable functional outcome after three months. 4/7 patients with hemorrhagic stroke received immediate reversal of anticoagulation without any thrombotic complications. ConclusionThe majority of LVAD patients with ischemic stroke had an acceptable functional outcome after three months. Future clinical research is warranted to improve therapeutic strategies for acute care and stroke prevention.

Sleep breathing disorders in ischemic stroke: relationship with the localization and toast classification subtypes

Stroke is one of the leading causes of death and disability worldwide, despite successful strategies to manage the main risk factors for ischemic stroke (hypertension, atrial fibrillation, diabetes mellitus and others). Sleep-disordered breathing (SDB) is poorly studied, but potentially significant and modifiable risk factor for stroke, so it draws attention of investigators. In this review we have focused on some aspects and analyzed the relationship of different variants of SBD with the lesions localization and the type of acute ischemic stroke according to TOAST criteria. During the analysis, it was shown that in the early period after cerebrovascular accident, the frequency and severity of respiratory disturbances in sleep were higher, mainly due to the presence of central apnea, which develops when the vertebro-basilar pool is involved in the blood supply zone. However, impaired cerebral circulation of supratentorial localization can also be a factor contributing to the appearance or exacerbation of respiratory failure in a dream. With regard to the relationship of respiratory disorders in a dream with a type of cerebrovascular accident according to the TOAST classification, we can talk about the likely relationship of obstructive sleep apnea with a cerebrovascular accident of cardioembolic and atherothrombotic origin.

Infarct in new territory after endovascular stroke treatment: A diffusion-weighted imaging study

Data on infarcts in new territory (INT) in patients undergoing endovascular stroke treatment for acute large-vessel occlusions are sparse. Aim of this study was to assess the prevalence, risk factors, and clinical relevance of INT. For this purpose, all patients in a single-center prospective registry who underwent endovascular stroke treatment and received pre- and post-interventional diffusion-weighted imaging were included (N = 259). Using an established scoring system, INT were classified according to size (I-III, ≤2 mm, >2 mm ≤20 mm, >20 mm) and likelihood of being related to the intervention (A, high likelihood; B, low likelihood). Additionally, a new type of infarct, that occurred in a territory distal to the occlusion, but was initially not hypoperfused, was defined as an infarct in initially not hypoperfused territory (IINHT). A total of 180 INT and 38 IINHT were observed in 32.8% (N = 85/259) of patients. In most patients, INT were angiographically occult (90.2%), and 13 patients had INT/IINHT larger than 2 cm (type III). Absence of protection during stent-retrieval and a cardio-embolic stroke origin were associated with higher incidence of INT/IINHT, whereas pretreatment with IV tPA showed no association, even when different bolus timing was considered. INT/IINHT were associated with lower rates of functional independence with increasing size type after adjusting for confounders (adjusted Odds Ratio per size group increase 0.63, 95% confidence interval 0.46–0.86). In conclusion, INT and IINHT are not rare, are associated with poor outcome with increasing size, and they may serve as a surrogate endpoint for safety evaluation of new devices and endovascular techniques. Further research on associated factors is warranted.

Abstract TP317: Utility and Cost of Inpatient Thrombophilia Testing in Ischemic Stroke Patients Aged 18-60

Introduction: Patients (pts) <60 years with ischemic stroke (IS) are commonly tested for thrombophilias (TP) due to the perception that there could be underlying hypercoagulable states. However, inherited TPs are largely not a risk factor for IS; and testing for acquired TPs in an acute inpatient setting may yield erroneous results that increase health care costs. We reviewed the frequency and cost of TP testing at our institution as part of a plan-do-study act cycle for improving the utilization of inpatient TP testing in young pts after IS. Methods: We performed a retrospective review of 18-60 year old pts admitted for IS to our comprehensive stroke center between 11/2016 and 7/2018. Pts discharged with a stroke etiology not attributed to large vessel (LV), small vessel (SV), or cardioembolic (CE) origin and the initial hospital TP testing monitored. Pts seen subsequently in clinic or later admissions in our system were monitored. Results: Of 1,162 pts, 104 without diagnosed LV/SV/CE etiologies were identified. At least one TP test was performed in 82 (79%) pts (Table 1). In 70 pts testing was done in the initial 24 hrs of hospitalization. One test abnormality was seen in 42 (51%) pts but anticoagulation was initiated in only one 1 patient at discharge. Forty-seven (45%) pts were followed in our outpatient clinic, with a mean follow up of 5 (0.2 – 24) months. TP was confirmed in 3 pts in clinic – two with heterozygous FVL mutation and one with known homozygous FVL mutation. The total charges of the initial inpatient testing is estimated to be as high as $222,150 for 82 patients. Conclusion: Frequent inpatient TP testing in young pts with cryptogenic stroke does not change management and can be costly to the hospital. Based on these results, we created a practice guideline to improve utilization of TP testing starting January 2019. A one year analysis of the effectiveness, safety, and cost for these changes is ongoing.

Abstract WP268: Von Willebrand Factor Expression in Various Subtypes of Acute Ischemic Stroke

Introduction: Von Willebrand factor (VWF) is a key component of acute ischemic stroke (AIS) thrombi. The aim of our prospective study was to investigate the immunohistochemical expression of VWF in clots and to evaluate whether VWF is associated with certain subtypes of AIS. Methods: VWF immunostaining was performed on 79 thrombi collected as part of the multi-center Stroke Thromboembolism Registry of Imaging and Pathology (STRIP) registry. The cases were classified according to TOAST criteria. The VWF expression was quantified using Orbit Image Analysis (www.Orbit.bio) machine learning software. IBM SPSS statistics 25 was used to assess the relationship between the VWF levels and different etiology subtypes. Results: A cardioembolic stroke was defined in 39 cases (49.4%) whereas an atherosclerotic origin was identified in 13 patients (16.5%). Other causes accounted for 12 cases (15.1%). Unknown etiology was reported in 15 cases (19%). The mean VWF content in the clots was 12.8%. According to the Mann-Whitney U-test, the level of VWF was significantly higher in the cases with unknown etiology compared to cardioembolic origin (p=0.044). We found also that patients with unknown etiology of stroke had higher VWF expression as compared to the other two subtypes, although this difference was not statistically significant. Conclusions: Among the patients with ischemic stroke included in this study, the VWF expression was significantly increased in those with unknown etiology compared to the group with cardioembolic stroke. Our finding provides new insights into clot composition in cryptogenic stroke and may influence the treatment and secondary prevention in these cases.

Long-term incidence of cardioembolic events after cryoballoon pulmonary vein isolation

Long-term outcomes in term of cardioembolic events (CE) is poorly described after cryoballoon pulmonary vein isolation (cryo-PVI) for atrial fibrillation (AF). To evaluate the long-term incidence of CE after cryo-PVI. All consecutive patients who underwent cryo-PVI for paroxysmal or persistent AF between November 2012 and October 2017 were included. They were prospectively followed at least 12 months in the ablation center, and then by their cardiologist. Decision of oral anticoagulation (OAC) discontinuation was let at the appreciation of the referent cardiologist. All ischemic events (stroke, transient ischemic attack (TIA), systemic embolism) were collected. Four hundred and fifty patients (78% men, median age 61 years) were included, among which 208 (46%) were initially in persistent AF. Median CHA 2 DS 2 -VASc score was 1 (IQR 1), and 26 patients (6%) had a history of stroke/TIA before the procedure. Two hundred and seventy patients (60%) were in sinus rhythm after one procedure and a median follow-up of 26 months (IQR 23). OAC was discontinued for 75 patients (17%) after the procedure, among which 50 (67%) had no indication for long-term anticoagulation. Six patients presented an ischemic event, all considered as cardioembolic origin: 3 stroke, 2 TIA, 1 acute lower limb ischemia. Mean follow-up was 30 months, therefore incidence of CE was 0.53%/year. Three out of six of the patient who presented CE had no recurrence documented before or at the time of the event. All patients who presented a CE had class I or class IIa indication for long-term anticoagulation. In our cohort, long-term incidence of CE after cryo-PVI was 0.53%/year. Absence of documented recurrence could not be an argument for stopping OAC, decision who need to be guided only by CHA 2 DS 2 -VASc score.

Etiology of recurrent large vessel occlusions treated with repeated thrombectomy.

Repeated mechanical thrombectomy for acute stroke treatment in individual patients has been proven feasible. However, less is known about the etiology of recurrent vessel occlusions after prior thrombectomy. We aimed to understand if the etiology of such recurrent events differs from the first stroke. Retrospectively, we identified all patients at our center who received a repeated mechanical thrombectomy between 2007 and 2019. Clinical data were retrieved from medical records. Etiology of stroke was evaluated retrospectively, and angiographic studies were revisited. Twenty-three patients (1.5%) were identified. Median age was 68 years (IQR 56-77). Median NIHSS at first admission was 11 points (IQR 5-15). In nine cases (39.1%), the recurrent vessel occlusion was located exactly at the same position as the prior occlusion. Overall, five (21.7%) patients had a remarkable extracranial pathology as likely cause of stroke recurrence. In 16 patients (69.6%), the etiology of the first stroke and its recurrence was considered as likely being the same, mostly of cardioembolic or unknown origin. In the seven remaining patients (30.4%), the cause of stroke possibly differed from the first event, with five patients (21.7%) having a postinterventional intracranial intimal lesion as possible cause of stroke. Incidence of repeated thrombectomy was low. However, the high number of patients with known origin of stroke etiology raises the question how their monitoring may be optimized. The number of patients with remarkable extracranial pathologies or intracranial endothelial lesions supports current clinical practice to pay attention to final angiographic series.

FTIR, Raman and AFM characterization of the clinically valid biochemical parameters of the thrombi in acute ischemic stroke

The significance and utility of innovative imaging techniques in arterial clot analysis, which enable far more detailed and automated analysis compared to standard methods, are presented. The examination of two types of human thrombi is shown, representing the main ischemic stroke etiologies: fibrin–predominant clot of large vessel origin and red blood cells–rich clot of cardioembolic origin. The synergy effect of Fourier–transform infrared spectroscopy (FTIR), Raman spectroscopy (RS) and atomic force microscopy (AFM) techniques supported by chemometrics in comparison with reference histological staining was presented. The main advantage of such approach refers to free–label and non–destructive quantitative imaging of clinically valid, biochemical parameters in whole sample (FTIR–low resolution) and selected regions (RS–ultra–high resolution). We may include here analysis of lipid content, its distribution and total degree of unsaturation as well as analysis of protein content (mainly fibrin and hemoproteins). The AFM studies enhanced the vibrational data, showed clearly shape and thickness of clot features as well as visualized the fibrin framework. The extraordinary sensitivity of FTIR and RS imaging toward detection and discrimination of clinically valid parameters in clot confirms its applicability in assessment of thrombi origin.

Age-related burden and characteristics of embolic stroke of undetermined source in the real world clinical practice.

Few data are available on age-related burden and characteristics of embolic stroke of undetermined source (ESUS) in the real world clinical practice. The aim of our study was to provide information about it. We retrospectively analyzed data of patients consecutively admitted to our Stroke Unit along 1year (2017, November 1st-2018, October 31st). The etiology of ischemic stroke was defined at hospital discharge; ESUS was considered as a subset of cryptogenic stroke, and defined according to the 2014 international criteria. In the analyzed period, 306 patients, 52.3% females, mean age ± SD 77.9 ± 11.9years, were discharged with diagnosis of ischemic stroke. Ischemic strokes of cardioembolic and lacunar origin were the most frequent subtypes: 30.1% and 29.4%, respectively. Cardioembolic strokes were particularly frequent in patients ≥ 75years, and almost always associated with atrial fibrillation. Overall, in 80 patients (26.1%) the etiology of stroke was undetermined; in 25 (8.2%) it remained undefined because of death or severe comorbidity, making further diagnostic work-up not worthy. Cryptogenic stroke occurred in 55 patients (18%), and ESUS criteria were satisfied in 39 of them (12.7%). According to age, cryptogenic stroke was diagnosed in 21.1% (21.1% ESUS) of patients < 65years, 24.2% (19.4% ESUS) of patients aged 65-74years, 15.5% (9.2% ESUS) of patients ≥ 75years. After diagnostic work-up, patent foramen ovale was most commonly associated with ESUS (17.9%), especially in patients < 65years (62.5%); covert paroxysmal atrial fibrillation was detected in 10.5% of ESUS patients ≥ 75years. In the real world clinical practice, the frequency of ischemic strokes of undetermined etiology, and of those satisfying ESUS criteria, is not negligible, especially in younger patients. A thorough diagnostic work-up, with an age-specific approach, is therefore necessary and of the utmost importance for the identification of stroke etiology, in order to optimize secondary stroke prevention strategies.

Clinical and Neuroimaging Characteristics in Embolic Stroke of Undetermined versus Cardioembolic Origin: A Population-Based Study.

Evidence suggests that cardioembolism represents the underlying mechanism in the minority of embolic strokesofundeterminedsource(ESUS). In this population-based study, we sought to compare the clinical and imaging characteristics as well as outcomes in patients with ESUS and cardioembolic stroke (CE). We included consecutive patients with first-ever ischemic stroke (IS) from the previously published population-based Evros-Stroke-Registry identified as ESUS or CE according to standardized criteria. Baseline characteristics, admission NIHSS scores, cerebral edema, hemorrhagic transformation, stroke recurrence, functional outcomes (determined by modified Rankin Scale [mRS] scores), and mortality rates were recorded during the 1-year follow-up period. We identified 21 ESUS (3.7% of IS) and 211 CE (37.1% of IS) cases. Patients with ESUS were younger (median age: 68 years [interquartile range [IQR]: 61-75] vs 80 years [IQR: 75-84]; P<.001), had lower median admission NIHSS scores (4 points [IQR: 2-8] vs 10 points [IQR: 5-17]; P<.001), and lower prevalence of cerebral edema on neuroimaging studies (0 vs. 33.3%, P = .002). Functional outcomes were more favorable in ESUS at 28 (median mRS score: 2 [IQR: 1-3] vs 4 [IQR: 4-5]; P<.001), 90 (median mRS score: 1 [IQR: 0-2] vs 4 [IQR: 3-5]; P<.001), and 365 days (median mRS score: 1 [IQR: 0-2] vs 4 [IQR: 2-4]; P<0.001). At 1-year, the mortality rate was lower in ESUS (0% [95% confidence interval [CI]: 0-13.5%] vs 34.6% [95% CI: 28.2-41.0%]; P<.001); the 1-year recurrent rate was also lower numerically (0% [95% CI: 0-13.5%] vs 9.5% [95% CI: 5.5-13.4%]; P = .140) but this difference failed to reach statistical significance due to the small study population. The clinical and neuroimaging profiles as well as clinical outcomes vary substantially between ESUS and CE indicating different underlying mechanisms.

P.036 Stroke in people with Down Syndrome: a retrospective study

Background: There are only few studies approaching the prevalence and cause of stroke in children and adults with Down Syndrome (DS). Methods: We did a retrospective study of our cohort of 4962 patients of Jerome Lejeune Institute since 2007. We collected age of stroke, clinical presentation, cause (TOAST classification), treatment and clinical course. Results: We identified 20 patients from 6 to 56 years old .In all cases, it was a stroke of ischemic origin.: 8 children with a prevalence of 0.33%. 4 had a cardio-embolic origin, 3 secondary to Moya-Moya syndrome and one of undetermined origin. 12 adults (21 to 52 years old) with a prevalence of 0.46%.The majority of the causes of these ischemic strokes are indeterminate (9 of 12), Conclusions: We found a low prevalence and an ischemic cause in all cases of stroke, which differs from the general population. For pediatric stroke, the causes are expected thromboembolic in a context of heart disease most often or secondary to a Moya-Moya syndrome. For adult strokes, the average age is younger than that in the general population and the cause is indeterminate in most cases. We must better explore our patients to identify the risk factors in DS population.

Small obliquely oriented cortical cerebellar infarctions are associated with cardioembolic stroke

BackgroundA revised classification of cerebellar infarctions (CI) may uncover unrecognized associations with etiologic stroke subtypes. We hypothesized that obliquely oriented small cortical cerebellar infarction (SCCI) representing end zone infarctions on MRI would be associated with cardiac embolism.MethodsWe retrospectively analyzed consecutive stroke patients recruited between January–December 2016 in our center. Analyzed baseline characteristics: sex, age, cardiovascular risk factors, history of stroke or atrial fibrillation (AF). TOAST classification was used for determining stroke subtype. Acute infarction location (anterior/posterior/mixed anterior-posterior circulation), acute uni- or multiterritorial infarction, and acute or chronic CI/SCCI/non-SCCI were assessed by MRI, and vertebrobasilar stenosis/occlusion by vessel imaging. Pre-specified analysis was also performed in patients without known high cardioembolic risk (known AF history or acute multiterritorial infarction).ResultsWe included 452 patients (CI in 154, isolated SCCI in 55, isolated non-SCCI in 50, and mixed SCCI/non-SCCI in 49). Both SCCI and non-SCCI were associated with AF history (SCCI, p = 0.021; non-SCCI, p = 0.004), additional acute posterior circulation infarction (p < 0.001 both CI-subtypes), multiterritorial infarctions (SCCI, p = 0.003; non-SCCI, p < 0.001) and cardioembolic more frequent than large-artery atherosclerosis origin (p < 0.001 for both CI-subtypes). SCCI was associated with older age (p < 0.001), whereas non-SCCI was associated with stroke history (p = 0.036) and vertebrobasilar stenosis/occlusion (p = 0.002). SCCI were older (p = 0.046) than non-SCCI patients, had less frequently prior stroke (p < 0.001), and more frequent cardioembolic infarction (p = 0.025).In patients without known high cardioembolic risk (n = 348), SCCI was strongly associated with subsequent cardioembolism diagnosis (OR 3.00 [CI 1.58–5.73, p < 0.001]). No such association was present in non-SCCI.ConclusionsAcute or chronic SCCI are strongly associated with a cardioembolic origin.

Serum Troponin Level in Acute Ischemic Stroke Identifies Patients with Visceral Infarcts

Background and Purpose: Patients with ischemic stroke of cardioembolic origin are at risk of visceral (renal or splenic) infarction. We hypothesized that serum troponin level at time of ischemic stroke would be associated with presence of visceral infarction. Methods: Data were abstracted from a single center prospective stroke database over 18 months and included all patients with ischemic stroke who underwent contrast-enhanced computerized tomography (CT) of the abdomen and pelvis for clinical purposes within 1 year of stroke. The primary predictor was troponin concentration ≥.1ng/mL. The primary outcome was visceral infarct (renal and/or splenic) on CT abdomen and pelvis. Univariate and multivariable logistic regression models were used to estimate the odds ratio and 95% confidence intervals (OR, 95% CI) for the association of troponin with visceral infarction. Results: Of 1233 patients with ischemic stroke, 259 patients had a qualifying visceral CT. Serum troponin level on admission was measured in 237 of 259 patients (93.3%) and 41 of 237 (17.3%) had positive troponin. There were 25 patients with visceral infarcts: 16 renal, 7 splenic, and 2 both. In univariate models, patients with a positive troponin level (versus negative) were more likely to have visceral infarcts (39.1% [9/23] versus 15.0% [32/214], P = .008) and this association persisted in multivariable models (adjusted OR 3.83; 95% CI 1.42-10.31, P = .006). Conclusions: In ischemic stroke patients, elevated serum troponin levels may help identify patients with visceral infarcts. This suggests that troponin in the acute stroke setting is a biomarker of embolic risk. Larger studies with systematic visceral imaging are needed to confirm our findings.

The role of Holter Monitor in the Detection of Atrial Fibrillation in Transient Ischaemic Attack and Acute Ischaemic Stroke

Background: Ischaemic stroke of cardioembolic origin is associated with profound morbidity and mortality, of which atrial fibrillation (AF) accounts for a significant proportion. Holter monitoring remains the first line investigation in identifying patients with underlying AF in stroke patients. Methods: We conducted a retrospective review of all patients undergoing Holter monitoring between August 2017 and February 2019 at an urban teaching hospital, to identify incidence of AF (defined as episodes lasting longer than 30 seconds) in patients presenting with transient ischaemic attack (TIA) or confirmed acute ischaemic stroke (AIS). Results: 193 eligible patients, 15 excluded due to known history of AF. Remaining 178 patients had mean 23.5 hours of Holter monitoring. Baseline demographics data: mean age 64.1 years, male gender 55.6%. TIA accounted for 41.6%, and AIS accounted for the remaining 58.4% of cases. AF was detected in 5 patients (2.8%). An additional 6 patients had AF identified on ward telemetry, which was not detected during Holter monitoring. Nine of these 11 patients were commenced on anticoagulation. A further 7 patients were commenced on anticoagulation due to suspected cardioembolic source based on cerebral imaging in the absence of confirmed AF. In a separate analysis of patients excluded for known AF, 8 of the15 patients had AF detected during Holter monitoring (53.3%). Discussion: Holter monitor alone is an insensitive method for detecting atrial fibrillation. Longer duration of monitoring should be considered in patients with cryptogenic stroke as suggested by recent trials with detection rate of 30% at 36 months.

Thrombus Permeability in Admission Computed Tomographic Imaging Indicates Stroke Pathogenesis Based on Thrombus Histology.

Background and Purpose- Intracranial thrombi can be characterized according to their permeability as measured by contrast agent penetration. Thrombus composition and its associated pathogenesis are important factors affecting treatment and secondary prevention. We aimed to explore the histopathologic factors explaining the heterogeneity of thrombus permeability measures and evaluated potential correlations with stroke pathogenesis. Methods- Thrombus densities were measured in thin-slice noncontrast computed tomography and automatically aligned computed tomographic angiography images of 133 patients with large-vessel occlusions of the middle cerebral artery. Change in thrombus attenuation (Δt) and corrected void fraction (ε; attenuation increase corrected for contralateral artery densities) were calculated. First, these thrombus perviousness measures were correlated with histological thrombus components (especially fractions of fibrin-platelet accumulation and red blood cells) and stroke pathogenesis (n=32). For validation, an association between perviousness and pathogenesis was assessed in a second, independent cohort (n=101). Results- Thrombus perviousness estimates were correlated with both fibrin/platelets fractions (Δt: r=0.43, P=0.016/ε: r=0.45, P=0.01) and inversely with red blood cells counts (Δt: r=-0.46, P=0.01/ε: r=-0.49, P=0.006). In the first cohort, Δt was substantially higher in samples from patients with cardioembolic stroke pathogenesis as compared with noncardioembolic-derived thrombi ( P=0.026). In the validation cohort, thrombus perviousness measures differed significantly between cardioembolic (Δt: median [ interquartile range]=12.53 [8.70-17.90]; ε: median [interquartile range]=0.054 [0.036-0.082]) and noncardioembolic thrombi (Δt: median [interquartile range]=3.2 [2.17-6.44], P<0.001; ε: median [interquartile range]=0.020 [0.011-0.027], P<0.001) and were associated with pathogenesis (Δt: β=0.45, P=0.016/ε: β=83.6, P=0.013) in a binary logistic regression model. Conclusions- Permeable thrombi showed a strong correlation with lower fractions of red blood cells counts and more fibrin/platelets conglomerations, concurrent with an association with cardioembolic origin. This novel information about thrombus perviousness may be valuable as a new and simple to acquire imaging marker for identifying stroke pathogenesis using early and readily available imaging.

Differential MicroRibonucleic Acid Expression in Cardioembolic Stroke

BackgroundMicroRNAs (miRNA) are a class of small, endogenous (17-25 nucleotide) noncoding ribonucleic acids implicated in the transcriptional and post-transcriptional regulation of gene expression. This study examines stroke-specific miRNA expression in large vessel territory cardioembolic stroke. MethodsPeripheral blood was collected from controls and ischemic stroke patients 24 hours after stroke onset. Whole blood miRNA was isolated and analyzed for differential expression. A total of 16 patients with acute middle cerebral artery territory strokes of cardioembolic origin were included in this pilot study. MiRNA profiling was conducted by miRCURY LNA™ microRNA Array. ResultsIn patients with cardioembolic stroke, significant differential expression of 14 miRNAs was observed when compared to controls. Ten of these miRNA had not previously been associated with ischemic stroke (miR-664a-3p, -2116-5pp, -4531, -4765-5p, -647, -4709-3p, -4742-3p, -5584-3p, -4756-3p, and -5187-3p). Subanalysis of severe strokes (NIHSS > 10) identified an additional 5 differentially expressed miRNA. No significant effects of sex or tissue plasminogen activator treatment were seen on miRNA expression. ConclusionsIschemic stroke patients show a differential miRNA expression profile as compared to controls. These new associations between circulating miRNAs and ischemic stroke may help to refine stroke subtype diagnosis and identify novel therapeutic miRNA targets for the treatment of ischemic stroke.

Occurrence and Classification of Cerebrovascular Events after Isolated Bioprosthetic Surgical Aortic Valve Replacement: A Competing Risk Analysis of the CAREAVR Study

ABSTRACTBackground: The long-term incidence of stroke and the proportion of cardioembolic events after bioprosthetic surgical aortic valve replacement (SAVR) remain largely unknown.Methods: The CAREAVR study sought to assess the rate of stroke and transient ischemic attack (TIA) in patients who underwent isolated surgical aortic valve replacement with a bioprosthesis at four Finnish university hospitals between 2002 and 2014. Data was collected retrospectively and included 721 patients. Median follow-up time was 4.8 [3.0–7.0] years.Results: At 5 years, freedom from stroke was 89.0%, from TIA 94.1%, and from stroke and TIA 83.7%. The median time between index procedure and stroke or TIA was 1.7 years [29 days–3.9 years]. Stroke was of cardioembolic origin in 44.4% of patients. In multivariable competing risk analysis, increased age (HR 1.03, 95%CI 1.00–1.06, p = 0.022), previous stroke or TIA (HR 1.75, 95%CI 1.14–2.70, p = 0.010), New York Heart Association (NYHA) class III or more (HR 1.51, 95%CI 1.01–2.24, p = 0.044) and insulin treatment at discharge (HR 1.20, 95%CI 1.09–3.64, p = 0.024) were independent predictors of stroke or TIA. Cerebrovascular events occurred in 47.2% of patients with ongoing anticoagulation therapy.Conclusion: In this study, the incidence of stroke in the early postoperative period after bioprosthetic SAVR was higher than previously documented. Almost half of strokes were of cardioembolic etiology. These findings highlight the need for the better prevention strategies for cardioembolic events after bioprosthetic SAVR.