Can the rate of mortality and neurological recovery be predicted from the time of onset of symptoms and MRI grade in patients with cerebral fat embolism? : a study of 34 patients.

AIMS: The aim of this study was to assess whether it is possible to predict the mortality, and the extent and time of neurological recovery from the time of the onset of symptoms and MRI grade, in patients with the cerebral fat embolism syndrome (CFES). This has not previously been investigated. METHODS: The study included 34 patients who were diagnosed with CFES following trauma between 2012 and 2018. The clinical diagnosis was confirmed and the severity graded by MRI. We investigated the rate of mortality, the time and extent of neurological recovery, the time between the injury and the onset of symptoms, the clinical severity of the condition, and the MRI grade. All patients were male with a mean age of 29.7 years (18 to 70). The mean follow-up was 4.15 years (2 to 8), with neurological recovery being assessed by the Glasgow Outcome Scale and the Mini-Mental State Examination. RESULTS: In all, seven who had early-onset CFES (< 24 hours), and a severe Takahashi grade on MRI, died. There was a significant association between the time of onset of neurological signs and mortality (p = 0.035). Mortality was also significantly associated with a severe Takahashi grade (p < 0.001). Among the 27 surviving patients, 26 (96.3%) recovered completely. One (3.7%) had a cognitive deficit. The mean time to recovery was 4.7 weeks (2 to 13), with late recovery aftereight eight weeks being recorded in three patients. CONCLUSION: There was a significantly increased rate of mortality in patients with CFES who had an early onset of symptoms and a severe grade on MRI. Complete neurological recovery can be expected in most patients with CFES who survive. Cite this article: Bone Joint J 2022;104-B(1):142-149.

Potential Embolic Sources and Outcomes in Embolic Stroke of Undetermined Source in the NAVIGATE-ESUS Trial.

Background and Purpose- Emboli in embolic stroke of undetermined source (ESUS) may originate from various potential embolic sources (PES), some of which may respond better to anticoagulation, whereas others to antiplatelets. We analyzed whether rivaroxaban is associated with reduction of recurrent stroke compared with aspirin in patients with ESUS across different PES and by number of PES. Methods- We assessed the presence/absence of each PES (atrial cardiopathy, atrial fibrillation, arterial atherosclerosis, left ventricular dysfunction, cardiac valvulopathy, patent foramen ovale, cancer) in NAVIGATE-ESUS (New Approach Rivaroxaban Inhibition of Factor Xa in a Global Trial Versus ASA to Prevent Embolism in Embolic Stroke of Undetermined Source) participants. Prevalence of each PES, as well as treatment effect and risk of event for each PES were determined. Results by number of PES were also determined. The outcomes were ischemic stroke, all-cause mortality, cardiovascular mortality, and myocardial infarction. Results- In 7213 patients (38% women, mean age 67years) followed for a median of 11 months, the 3 most prevalent PES were atrial cardiopathy (37%), left ventricular disease (36%), and arterial atherosclerosis (29%). Forty-one percent of all patients had multiple PES, with 15% having ≥3 PES. None or a single PES was present in 23% and 36%, respectively. Recurrent ischemic stroke risk was similar for rivaroxaban- and aspirin-assigned patients for each PES, except for those with cardiac valvular disease which was marginally higher in rivaroxaban-assigned patients (hazard ratio, 1.8 [95% CI, 1.0-3.0]). All-cause mortality risks were similar across treatment groups for each PES while too few myocardial infarctions and cardiovascular deaths occurred for meaningful assessment. Increasing number of PES was not associated with increased stroke recurrence nor all-cause mortality, and outcomes did not vary between rivaroxaban- and aspirin-assigned patients by number of PES. Conclusions- A large proportion of patients with ESUS had multiple PES which could explain the neutral results of NAVIGATE-ESUS. Recurrence rates between rivaroxaban- and aspirin-assigned patients were similar across the spectrum of PES. Registration- URL: https://www.clinicaltrials.gov; Unique identifier: NCT02313909.

Supraventricular Extrasystoles on Standard 12-lead Electrocardiogram Predict New Incident Atrial Fibrillation after Embolic Stroke of Undetermined Source: The AF-ESUS Study.

BACKGROUND: The diagnosis of covert atrial fibrillation (AF) remains a major challenge to guide secondary prevention of patients with embolic stroke of undetermined source (ESUS). AIMS: We analyzed consecutive ESUS patients from 3 prospective stroke registries to assess whether the presence of supraventricular extrasystoles (SVE) on standard 12-lead electrocardiogram (ECG) is associated with the detection of AF (primary outcome), stroke recurrence and death (secondary outcomes) during follow-up. METHODS: We measured the number of SVEs in all available ECGs of patients hospitalized for ESUS. Multivariate stepwise regression with forward selection of covariates assessed the association between SVE (classified in 4 groups according to their number per 10 seconds of ECG: no SVE, >0-1SVEs, >1-2SVEs, and >2SVEs) and outcomes during follow-up. The Kaplan-Meier product limit method estimated the 10-year cumulative probabilities of outcomes in each SVE group. We calculated the negative prognostic value (NPV) of the presence of any SVE to predict new AF, defined as the probability that AF will not be detected during follow-up if there is no SVE. RESULTS: Among 853 ESUS patients followed for 2857 patient-years (median age: 67 years, 43.0% women), 226 (26.5%) patients had at least 1 SVE at the standard 12-lead ECGs performed during hospitalization. AF was detected in 125 (14.7%) of patients in the overall population during follow-up: 8.9%, 22.5%, 28.1%, and 48.3% in patients with no SVE, greater than 0-1SVE, greater than 1-2SVE and greater than 2SVE respectively. In multivariate regression analysis, compared to patients with no SVEs, the corresponding hazard-ratios were 1.80 [95% confidence intervals (95%CI):1.06-3.05], 2.26 (95%CI:1.28-4.01) and 3.19 (95%CI:1.93-5.27). The NPV of the presence of any SVE for the prediction of new AF was 91.4%. There was no statistically significant association of SVE with the risk of ischemic stroke recurrence and death. CONCLUSIONS: In ESUS patients without SVEs during hospitalization, the probability that AF will not be detected during a follow-up of 3.4 years is more than 91%.

Axillary artery cannulation reduces early embolic stroke and mortality after open arch repair with circulatory arrest.

OBJECTIVE: To evaluate the efficacy of axillary artery cannulation for early embolic stroke and operative mortality, we retrospectively compared the outcomes between patients with or without axillary artery cannulation during open aortic arch repair with circulatory arrest. METHODS: Between January 2004 and December 2017, 468 patients underwent open aortic arch repair with circulatory arrest using antegrade cerebral perfusion and were divided into 2 groups according to the site of arterial cannulation: the axillary artery (axillary group, n = 352) or another site (nonaxillary group, n = 116) groups. Embolic stroke was defined as a physician-diagnosed new postoperative neurologic deficit lasting more than 72 hours, generally confirmed by computed tomography or magnetic resonance imaging. RESULTS: After propensity score matching, the patients' characteristics were comparable between the groups (n = 116 in each). The incidences of acute type A dissection, aortic rupture, shock, or emergency operation were similar between groups. The incidence of early embolic stroke was significantly lower in axillary group (n = 3 [2.6%] vs n = 10 [8.6%]; P = .046). Also, 30-day mortality (n = 3 [2.6%] vs n = 10 [8.6%]; P = .046) and in-hospital mortality (n = 3 [2.6%] vs n = 11 [9.5%]; P = .027) occurred significantly lower in the axillary group. CONCLUSIONS: Axillary artery cannulation reduced the early embolic stroke and early mortality after open arch repair with circulatory arrest. Axillary artery cannulation as the arterial cannulation site during open arch repair with circulatory arrest may be helpful in preventing embolic stroke and reducing early mortality.

Clinical Outcomes of Sentinel Cerebral Protection System Use During Transcatheter Aortic Valve Replacement: A Systematic Review and Meta-Analysis.

OBJECTIVE: To compare the clinical outcomes following transcatheter aortic valve replacement (TAVR) with and without the use of the Sentinel Cerebral Protection System (Sentinel CPS). BACKGROUND: Stroke occurs in 2-5% of patients at 30 days after TAVR and increases mortality >3 fold. The Sentinel CPS is the only FDA (Food and Drug Administration) approved cerebral embolic protection device. METHODS: The Cochrane Library, PubMed and Web of Science were searched for relevant studies for inclusion in the meta-analysis. Two authors independently screened and included studies comparing the clinical outcomes after TAVR with and without the Sentinel CPS. Risk of bias was assessed using the Cochrane tools (RoB2.0 and ROBINS-I). RESULTS: Four studies comparing 606 patients undergoing TAVR with Sentinel CPS to 724 without any embolic protection device were included. Sentinel CPS use was associated with lower rates of 30-day mortality [0.8% vs 2.7%; RR 0.34 (95% CI 0.12, 0.92) I2 = 0%], 30-day symptomatic stroke [3.5% vs 6.1%; RR 0.51 (95% CI 0.29, 0.90) I2 = 0] and major or life-threatening bleeding [3.3% vs 6.6%; RR 0.50 (0.26, 0.98) I2 = 16%]. There was no significant difference between the two arms in the incidence of acute kidney injury [0.8% vs 1%; RR 0.85 (95% CI 0.22, 3.24) I2 = 0%] and major vascular complications [5.1% vs 6%; RR 0.74 (0.33, 1.67) I2 = 45%]. CONCLUSION: The results suggest that Sentinel CPS use in TAVR is associated with a lower risk of stroke, mortality and major or life-threatening bleeding at 30 days.

Troponin T Predicts Cardioembolic Aetiology and Clinical Outcome in Undetermined Ischaemic Stroke in Hyperacute Phase.

BACKGROUND: Elevated high-sensitivity cardiac troponin T (hs-cTnT) levels have been related to clinical outcome in stroke patients. However, the role of hs-cTnT and its potential as a biomarker in ischaemic stroke (IS) has not been well established. This study aims to determine whether basal hs-cTnT determination in the hyperacute phase of undetermined IS and transient ischaemic attack (TIA) can predict the cardioembolic aetiology and clinical outcome. METHODS: We prospectively studied 110 consecutive patients with undetermined acute IS and TIA. hs-cTnT levels were determined at hospital arrival. Large vessel stenosis/occlusion and previously known aetiologies at admission were exclusion criteria for this study. All patients were subjected to a complete aetiological evaluation. A 12-month follow-up was performed in all patients. The subtype of IS was evaluated following the SSS-TOAST criteria. We established two groups at admission: cardioembolic aetiology (group A) and noncardioembolic aetiologies (group B). RESULTS: The number of patients in each group was similar (group A: 52, 47.27%; group B, 58, 52.73%). Patients in group A had elevated hs-cTnT more frequently (61.54% versus 17.24%; P < .001). Group A patients had significantly higher mortality at 3 months (14.29% versus 1.82%, P = .025). In the multivariate analysis, elevated hs-cTnT was the only independent predictor of cardioembolic aetiology (odds ratio: 14.821; 95% confidence interval: 3.717-59.102, P < .001). CONCLUSION: Baseline hs-cTnT assessment in undetermined strokes and TIA during the hyperacute phase is independently associated with cardioembolic aetiology.

Real-World Experience of the Sentinel Cerebral Protection Device: Insights From the FDA Manufacturer and User Facility Device Experience (MAUDE) Database.

BACKGROUND/PURPOSE: The Sentinel Cerebral Protection System (Boston Scientific, Marlborough, Massachusetts) is indicated for use as a cerebral protection device to capture and remove embolic material during transcatheter aortic valve procedures and was approved by the US Food and Drug Administration (FDA) in 2017. Robust data on the most commonly reported complications and modes of failure associated with the Sentinel device are limited. METHODS/MATERIALS: We analyzed postmarketing surveillance data from the FDA Manufacturer and User Facility Device Experience (MAUDE) database from 2017 through 2019, yielding 43 reports. RESULTS: Of the 43 reports of major complications involving Sentinel devices, 23 involved either death (3) or injury (20) related to the device. The 3 deaths were due to stroke, while 18 of the 20 injuries were reported as stroke. The other 20 reports were related to device modes of failure. Modes of failure were due to damaged device (5), difficulty retrieving/resheathing the device (5); package contamination (4), difficulty deploying the device (3), and, finally, complications with preparation (3). CONCLUSIONS: Our analysis of the MAUDE database demonstrates that in real-world practice, the Sentinel Cerebral Protection System may be associated with complications, including death, stroke, vascular injury, and difficulties with the device itself. The MAUDE database serves as an important tool for both physicians and manufacturers to optimize performance and clinical outcomes.

Factores pronósticos de muerte en pacientes con infarto cerebralcardioembólico / Prognostic factors of death in patients with cardioembolic cerebral infarction

Objetivo: Determinar los factores pronósticos de muerte en el infarto cerebral cardioembólico.Métodos: Se realizó un estudio observacional, analítico, tipo cohorte, en el Hospital “Dr. Carlos J. Finlay”, de enero de 2016 a diciembre de 2017, cuya muestra estuvo representada por63 pacientes. Se tuvieron en cuenta variables como la edad, sexo, gravedad y tamaño del infarto, complicaciones neurológicas y no neurológicas, latencia al ingreso, uso de antitrombóticos yestado al egreso. Se realizó el análisis estadístico univariado mediante el test de Chi cuadrado, y aquellas variables con valor de p< 0,05 fueron sometidas a un estudio de regresión logísticamultivariada binomial.Resultados: El análisis univariado evidenció asociación significativa con el fallecimiento en los pacientes con ictus severo, inicio tardío de la anticoagulación y presencia de complicaciones no neurológicas. En el procesamiento multivariado se obtuvo que los pacientes con insuficienciarespiratoria tuvieron 17 veces más posibilidades de fallecer, seguido por la insuficiencia cardiaca compensada con la que el riesgo de morir fue casi 8 veces mayor. Igualmente, en los pacientes con trastorno del medio interno el riesgo aumentó 6 veces.Conclusiones: Constituyeron factores pronósticos de muerte la insuficiencia respiratoria, la insuficiencia cardiaca descompensada y los trastornos del medio interno, principalmente,la acidosis respiratoria(AU)

Objective: To determine the prognostic factors of death in cardioembolic cerebral infarction.Methods: An observational, analytical, cohort type study was carried out at the Dr. Carlos J. Finlay hospital, from January 2016 to December 2017, whose sample was represented by63 patients. Variables such as age, sex, severity and size of the infarction, neurological and nonneurological complications, latency at admission, use of antithrombotic drugs and status atdischarge were taken into account. Univariate statistical analysis was performed using the Chisquare test, and those variables with value of p <0.05 were subjected to a binomial multivariate logistic regression study.Results: Univariate analysis showed a significant association with death in patients with severe stroke, late onset of anticoagulation and the presence of non-neurological complications. Inmultivariate processing it was obtained that patients with respiratory failure were 17 times more likely to die, followed by decompensated heart failure with which the risk of dying was almost 8 times higher. Likewise, in patients with internal disorder, the risk increased 6 times.Conclusions: Prognostic factors of death were respiratory failure, decompensated heart failureand internal disorders, mainly respiratory acidosis(AU)

Embolic Stroke of Undetermined Source in Saudi Arabia: Prevalence, Patient Characteristics, and Outcomes.

BACKGROUND: Embolic stroke of undetermined source (ESUS) is a newly introduced clinical construct to better characterize cryptogenic stroke. It is associated with considerable morbidity and mortality and a high recurrence rate. It has not previously been investigated in Saudi stroke patients. We aimed to conduct a descriptive analysis of ESUS in Saudi Arabia, including its frequency among patients with acute stroke, characteristics, and outcomes. METHODS: We reviewed all ischemic stroke patients admitted to the stroke unit at King Abdulaziz Medical City-Riyadh, Saudi Arabia, from February 2016 to July 2018. We applied the criteria proposed by the Cryptogenic Stroke/ESUS International Working Group, which defines ESUS as a radiologically confirmed nonlacunar brain infarct without (a) extracranial or intracranial atherosclerosis causing ≥50% stenosis in arteries supplying the ischemic area, (b) a major-risk cardioembolic source, (c) any other specific cause of stroke. We compared ESUS patients with the other stroke patients. Study was approved by local institutional review board. RESULTS: Of the 736 patients admitted with ischemic stroke, 147 (20%) had ESUS. Patients with ESUS had fewer vascular risk factors compared to patients without ESUS. Nearly third were either dead or dependent at discharge. There were no significant differences between ESUS and other types of ischemic strokes in mortality rate and independence at discharge. CONCLUSION: ESUS is common in Saudi stroke patients. Despite of the lack of definite etiology, it is associated with considerable morbidity and mortality.

Aortic Arch Atherosclerosis in Patients With Embolic Stroke of Undetermined Source: An Exploratory Analysis of the NAVIGATE ESUS Trial.

Background and Purpose- Aortic arch atherosclerosis (AAA) is a possible source of embolism in patients with embolic stroke of undetermined source. Previous studies reported high rates of embolic events in patients with AAA, especially those with high-risk AAA. This exploratory analysis of NAVIGATE ESUS (New Approach Rivaroxaban Inhibition of Factor Xa in a Global Trial Versus ASA to Prevent Embolism in Embolic Stroke of Undetermined Source) focused on patients with AAA and assessed their characteristics, stroke recurrence rates, and response to treatment. Methods- The detection of AAA and the assessment of its features were based on transesophageal echocardiography that was done in 19% of participants. AAA plaques were considered to have complex features when reported as complex or ulcerated or were ≥4 mm in thickness or had a mobile thrombus present. Results- Among 1382 participants who had transesophageal echocardiography, 397 (29%) had AAA and 112 (8%) had complex AAA. Mean (SD) age (63 [10] versus 67 [9] versus 69 [9]; P<0.001), prevalence of diabetes mellitus (19% versus 26%, versus 32%; P=0.002), and aortic valvulopathy (10 versus 20 versus 20; P<0.001) increased across no versus noncomplex versus complex AAA, respectively. In multivariable analyses, increasing age, diabetes mellitus, aortic valvulopathy, statin use before randomization, chronic infarcts on imaging, and region were independently associated with any AAA versus no AAA and also with complex AAA versus no AAA. Multiterritorial qualifying infarcts rather than single-territory infarcts were observed in 21% with complex AAA versus 17% noncomplex versus 13% no AAA (P=0.07). Annualized rates of ischemic stroke recurrence were 7.2% versus 4.2% versus 5.6% for complex versus noncomplex versus no AAA, respectively. While prevalence of complex AAA increased with increasing risk score, after adjusting for risk score, we did not observe increased risk of recurrent stroke for patients with complex AAA (hazard ratio, 1.1; 95% CI, 0.53-2.4), although the number of outcomes was limited. In patients with complex AAA, 4 strokes occurred among rivaroxaban-assigned patients and 4 strokes among aspirin-assigned patients. Conclusions- Complex AAA is prevalent in embolic stroke of undetermined source patients and is associated with atherosclerotic burden. Whether complex AAA independently increases recurrent stroke risk and whether a non-vitamin-K oral anticoagulant as compared with aspirin may be effective for reducing recurrent stroke requires additional study. Clinical Trial Registration- URL: https://www.clinicaltrials.gov. Unique identifier: NCT02313909.

Association between Bilateral Infarcts Pattern and Detection of Occult Atrial Fibrillation in Embolic Stroke of Undetermined Source (ESUS) Patients with Insertable Cardiac Monitor (ICM).

BACKGROUND AND AIMS: Increasingly, insertable cardiac monitors (ICM) have been used to detect Atrial Fibrillation (AF) in patients with cryptogenic stroke or embolic strokes of undetermined source (ESUS). We aim to examine the characteristics of these patients who were subsequently found to have AF. METHODS: We studied 83 consecutive patients who were comprehensively evaluated using neuroimaging and vessel imaging (computed tomography angiography, magnetic resonance angiography, or transcranial and extracranial Doppler sonography) to have met the previously established ESUS criteria. All 83 patients had ICM implanted between 2015 and 2017. All patients were followed up for at least 1 year, with a median follow-up period of 1.5 ± .5 years. We compared the baseline clinical, laboratory, echocardiographic, neuro-imaging profiles, and clinical outcomes in terms of functional recovery, recurrent stroke, and mortality in patients with and without detected AF. RESULTS: AF detection rate in this ESUS cohort was 12% over the study period. Patients with detected AF were associated with bilateral infarcts pattern at presentation (30% versus 5.5%, P = .035). Infarcts involving multiple vascular territories was not significantly associated with the detection of AF. There were no significant differences in the other clinical characteristics and outcomes between the AF group compared to the group without detected AF. Echocardiographic parameters including left ventricular ejection fraction and left atrial diameter were also not shown to be significantly different. CONCLUSION: Our study found that a neuroimaging profile of bilateral infarcts was associated with AF detection using insertable cardiac monitor in ESUS patients. Larger prospective studies are needed to validate our findings.

Temporal Trends in Ischemic Stroke Incidence in Younger Adults in the Framingham Study.

Background and Purpose- Stroke at midlife has a disproportionately large impact on disability-adjusted life-years lost. Ischemic stroke incidence may be increasing at this age. We investigated long-term trends in ischemic stroke incidence and changes in stroke risk factors in a community sample stratified by stroke onset at middle and older age. Methods- In the Framingham Study, surveillance for incident stroke is ongoing since 1948. We examined age-adjusted and sex-adjusted 10-year incidence of ischemic stroke using Cox models in persons aged 35 to 54 and ≥55 years at start of follow-up. Tests for linear trend were performed over 4 epochs, controlling for the distance in time between intervals. Further, we calculated the mean 10-year risk of stroke at each epoch and for both age groups, based on vascular risk factors from the Framingham Stroke Risk Profile. Results- There were 153, 197, 176, and 165 incident ischemic strokes within each epoch beginning in 1962 (n=3966), 1971 (n=5779), 1987 (n=5133), and 1998 (n=6964). Most ischemic strokes at midlife (n=71) were because of atherosclerotic brain infarction (n=50) or cardioembolism (n=19). Using the risk in the 1962 epoch as the reference, the risk of ischemic stroke at midlife did not significantly decline (hazard ratio, 0.87; 95% CI, 0.74-1.02; P trend =0.09). Incidence of ischemic stroke declined in the older group (hazard ratio, 0.82; 95% CI, 0.77-0.88; P trend <0.001). Between epochs 1 and 4, the average 10-year risk of stroke, as estimated by the Framingham Stroke Risk Profile, declined by 0.7% at midlife and 1.1% at older age. Conclusions- Long-term rates of ischemic stroke declined in our community sample; the decline was greater in older as compared with younger adults. Early prevention, focused on modification of cardiovascular risk factors, is important to see sustained declines in stroke incidence and mortality at midlife.

The safety of antithrombotic therapy in patients with cerebral microbleeds and cardiogenic cerebral embolism due to nonvalvular atrial fibrillation.

BACKGROUND: The impact of cerebral microbleeds on the safety of antithrombotic therapy has recently received considerable attention. We investigated the safety of antithrombotic therapy in patients with cerebral microbleeds and cardiogenic cerebral embolism caused by nonvalvular atrial fibrillation. METHODS: This retrospective study enrolled patients with acute cardiogenic cerebral embolism due to nonvalvular atrial fibrillation in the stroke unit of the Department of Neurology at the Beijing Tiantan Hospital, the Capital Medical University, from January 2015 to January 2018. General clinical data, magnetic resonance imaging data, and data regarding the use of antithrombotic medications were collected. The main adverse events were cerebral hemorrhage and all-cause death. RESULTS: According to the susceptibility-weighted imaging sequence, patients were divided into a cerebral microbleeds group and a non-cerebral microbleeds group. Patients with cerebral microbleeds were more likely to be male and to have a history of hypertension and diabetes, and they were less likely to have received anticoagulant therapy (49.1% vs. 71.3%, P = 0.001). However, no significant differences were found in the event-free time, the occurrence of cerebral hemorrhage events and all-cause death. Cox regression analysis showed that the risk of all-cause death in patients with a cerebral hemorrhage history and cerebral microbleeds increased 2.773-fold (HR = 2.773, 95%CI 1.056-7.280, P = 0.019), and the risk of a cerebral hemorrhage event in patients with cerebral microbleeds and a hypertension history (HR = 3.451, 95%CI 1.947-6.119, P = 0.045) or a cerebral hemorrhage history (HR = 2.443, 1.078-5.536, P = 0.006) was increased 3.451-fold and 2.443-fold, respectively. CONCLUSIONS: Antithrombotic therapy in patients with CMBs and cardiogenic cerebral embolism due to nonvalvular atrial fibrillation did not have increased risks of a cerebral hemorrhage event and all-cause death. CMBs were probably not a crucial predictor of whether patients were prescribed antithrombotic medicine. Patients with CMBs and a hypertension history or cerebral hemorrhage history should receive a close follow-up after antithrombotic therapy.

Double Filtration During Carotid Artery Stenting Using a Novel Post-Dilation Balloon With Integrated Embolic Protection.

OBJECTIVES: This study evaluated the safety and performance of the Paladin System, a novel angioplasty balloon with an integrated embolic protection filter designed to increase embolic protection during post-dilation. BACKGROUND: The risk of major adverse events during carotid artery stenting (CAS) is equivalent to carotid endarterectomy. However, the risk of minor stroke remains higher with CAS. Much of this risk occurs during post-stent dilation. METHODS: A total of 106 patients were enrolled in 5 centers in Germany. The study's primary endpoint was all-cause death, myocardial infarction, and stroke at 30 days post-procedure. Pre- and post-procedural diffusion-weighted magnetic resonance imaging evaluated new ischemic lesions in 30 subjects. Filter histomorphometric analysis was performed in 23 patients. Retrospective analyses compared outcome rates to historical controls. RESULTS: Device and procedural success rates were 100%. The combined major adverse event rate (death, myocardial infarction, and stroke) at discharge and at 30 days was 0% and 1.0%, respectively. The single adverse event was a stroke, which occurred at day 12 and was believed unrelated to the device or procedure. New ischemic lesions were found in 11 (36.7%) patients in the diffusion-weighted magnetic resonance imaging subset. New ipsilateral lesions were seen in 9 (30.0%) patients. Mean lesion volume per patient was 0.010 cm3. Debris was present in all filters, and approximately 90% of captured particles were <100 µm. CONCLUSIONS: Use of the Paladin System for post-stent dilation during CAS appears safe, and it may effectively decrease the number of embolic particles reaching the brain, which may help reduce the risk of procedure-related stroke. (A Multi-Center Study to Evaluate Acute Safety and Clinical Performance of Paladin® Carotid Post-Dilation Balloon System With Integrated Embolic Protection; NCT02501148).

Comparison of Triflusal with Aspirin in the Secondary Prevention of Atherothrombotic Events; Α Randomised Clinical Trial.

BACKGROUND: Triflusal has demonstrated an efficacy similar to aspirin in the prevention of vascular events in patients with acute myocardial infarction (ΜΙ) and ischaemic stroke but with less bleeding events. OBJECTIVE: We performed a randomised, multicentre, phase 4 clinical trial to compare the clinical efficacy and safety of triflusal versus aspirin, administered for 12 months in patients eligible to receive a cyclooxygenase-1 (COX-1) inhibitor. METHODS: Patients with stable coronary artery disease or with a history of non-cardioembolic ischaemic stroke were randomly assigned to receive either triflusal 300 mg twice or 600 mg once daily or aspirin 100 mg once daily for 12 months. The primary efficacy endpoint was the composite of: (a) ΜΙ, (b) stroke (ischaemic or haemorrhagic), or, (c) death from vascular causes for the entire follow-up period. The primary safety endpoints were the rate of bleeding events as defined by Bleeding Academic Research Consortium (BARC) criteria. RESULTS: At 12-month follow-up, an equivalent result was revealed between the triflusal (n=559) and aspirin (n=560) in primary efficacy endpoint. Specifically, the combined efficacy outcome rate (i.e. MI, stroke or death from vascular causes) difference was equal to -1.3% (95% confidence interval -1.1 to 3.5) and lied within the a-priori defined equivalence interval (p<0.001). Regarding the primary safety endpoints, patients on triflusal treatment were 50% less likely to develop bleeding events according to the BARC criteria, and especially any clinically overt sign of haemorrhage that requires diagnostic studies, hospitalisation or special treatment (BARC type 2). CONCLUSION: The efficacy of triflusal in the secondary prevention of vascular events is similar to aspirin when administered for 12 months. Importantly, triflusal significantly reduced the incidence of ΜΙ and showed a better safety profile compared with aspirin. (ASpirin versus Triflusal for Event Reduction In Atherothrombosis Secondary prevention, ASTERIAS trial; Clinical Trials.gov Identifier: NCT02616497).

Balloon protection of the left subclavian artery in debranching thoracic endovascular aortic repair.

OBJECTIVES: Since 2012, we have routinely applied balloon protection of the proximal left subclavian artery to prevent embolic events through the left vertebral artery during debranching thoracic endovascular aortic repair. This study aimed to study the effectiveness of balloon protection of the proximal left subclavian artery. METHODS: We reviewed the medical records of 157 patients who underwent debranching thoracic endovascular aortic repair between 2007 and 2017. Of these, 71 patients for whom balloon protection of the proximal left subclavian artery was used were assigned to the balloon protection of the proximal left subclavian artery group (58 men; age: 78 ± 6.7 years), and 86 patients were assigned to the control group (66 men; age: 78 ± 8.9 years). A total of 51 patients from each group were matched by their propensity scores to adjust for differences in the patients' characteristics. RESULTS: Perioperative stroke was significantly lower in the balloon protection of the proximal left subclavian artery group than in the control group (0%: 0/71 vs 7.9%: 7/86, P = .014). Freedom from all causes of mortality at 2 and 4 years was significantly higher in the balloon protection of the proximal left subclavian artery group compared with the control group (93%/76% vs 77%/59%, P = .015). Freedom from aortic death at 2 and 4 years was similar in both groups (97%/97% vs 91%/86%, P = .094). Propensity score matching yielded similar results of better freedom from all causes of mortality in the balloon protection of the proximal left subclavian artery group (93%/93% vs 81%/63%, P = .017) and equivalent aortic death in both groups (95%/95% vs 92%/88%, P = .30). CONCLUSIONS: Debranching thoracic endovascular aortic repair using balloon protection of the proximal left subclavian artery demonstrated more appropriate early and late outcomes. Evaluation using propensity score matching enhanced the efficacy of balloon protection of the proximal left subclavian artery.

Association of Transthoracic Echocardiography Findings and Long-Term Outcomes in Patients Undergoing Workup of Stroke.

BACKGROUND: Transthoracic echocardiography (TTE) has become routine as part of initial stroke workup to assess for sources of emboli. Few studies have looked at other TTE findings such as ejection fraction, wall motion abnormalities, valve disease, pulmonary hypertension and left ventricular hypertrophy and their association with various subtypes of stroke, long-term outcomes of recurrent stroke, and all-cause mortality. METHODS AND RESULTS: Computed tomography and magnetic resonance imaging brain imaging and TTE reports were reviewed for 2464 consecutive patients referred for TTE as part of a workup for acute stroke between 1/1/01 and 9/30/07. Study patients were 67 ± 15years, 60% female, 75% minorities and had hypertension (76%), diabetes (41%), chronic kidney disease (27%) and atrial fibrillation (18%). On TTE, a mass, thrombus, or vegetation was identified in only 4 cases (0.2%), whereas a clinically significant abnormality (ejection fraction < 50%, left ventricle or right ventricle wall motion abnormalities, severe valve disease, pulmonary hypertension, or left ventricular hypertrophy) was identified in 16%. Those with an abnormal TTE had increased risk for death at 10years (hazard ratio [HR] 1.8; 95% confidence interval [CI]: 1.6, 2.0; P < .01), although risk for readmission with stroke was not increased. Abnormal TTE remained associated with increased risk of death at 10years after adjustment for age, sex, race, and cardiovascular risk factors (HR 1.4; 95% CI: 1.2, 1.7; P < .01). CONCLUSIONS: TTE performed as part of an initial workup for stroke had minimal yield for identifying sources of embolism. Clinically important abnormalities found on TTE were independently associated with increased long-term mortality, but not recurrent stroke.

Anterior cerebral artery embolism during thrombectomy increases disability and mortality.

OBJECTIVE: During thrombectomy, thromboembolic migration in previously unaffected territory may occur and is not systematically notified. We report our data on the incidence, predictors, and clinical outcome of anterior cerebral artery emboli (ACAE). METHODS: From a prospectively collected thrombectomy database of consecutive patients with anterior circulation stroke between January 2012 and December 2016, 690 angiographic images were analyzed to assess ACAE. The primary outcome was a favorable outcome, defined as a 3 month modified Rankin Scale score of 0-2 or equal to the pre-stroke score. RESULTS: ACAE occurred in 65 patients (9.4%; 95% CI 7.2% to 11.6%). Internal carotid artery occlusion (tandem or terminal), Alberta Stroke Program Early CT Score <7, increasing number of passes, and use of stent retriever alone (compared with distal aspiration alone or combined with stent retriever) were found to be independent predictors of ACAE. Compared with patients without ACAE, patients with ACAE had lower rates, with an adjusted OR (95% CI) of 0.48 (0.25 to 0.92; P=0.027) for favorable outcome and 0.49 (0.25 to 0.96; P=0.038) for early neurologic improvement. ACAE was significantly associated with a higher mortality (adjusted OR 1.93; 95% CI 1.03 to 3.61; P=0.039) and intracranial hemorrhagic complications (adjusted OR 2.45; 95% CI 1.33 to 4.47; P=0.004). Despite a successful reperfusion modified Thrombolysis in Cerebral Infarction score of 2b-3 at the end of the procedure, a favorable outcome was reached in 30% of patients with ACAE compared with 52.4% in the other patients (OR 0.39; 95% CI 0.19 to 0.78; P=0.008). CONCLUSIONS: Procedural ACAE was not an uncommon condition, and was associated with increased mortality and disability rates, regardless of the success of reperfusion.

Endovascular Therapy in Ischemic Stroke With Acute Large-Vessel Occlusion: Recovery by Endovascular Salvage for Cerebral Ultra-Acute Embolism Japan Registry 2.

BACKGROUND: Endovascular therapy has been shown to be effective in patients with acute cerebral large-vessel occlusion, but real-world efficacies are unknown. METHODS AND RESULTS: We conducted a prospective registry at 46 centers between October 2014 and January 2017. Eligible patients were those who were aged 20 years or older, with acute cerebral large-vessel occlusion, and who were hospitalized within 24 hours of the onset. We enrolled both consecutive patients who were treated with or without endovascular therapy. Endovascular therapy included thrombectomy, balloon angioplasty, stenting, local fibrinolysis, and piercing. The primary outcome was a favorable outcome as defined by a modified Rankin Scale of 0 to 2 at 90 days after onset. Secondary outcomes were modified Rankin Scale of 0 to 1 and mortality. Safety outcomes were intracerebral hemorrhage or a recurrence of ischemic stroke. We constructed the 2242 (1121 each) propensity score-matched patients cohort based on a propensity score for endovascular therapy and estimated the adjusted odds ratio, followed by sensitivity analyses on original 2399 (1278 in endovascular therapy versus 1121 in no endovascular therapy) patients. In the propensity score-matched cohort, favorable outcomes were observed in 35.3% and 30.7% of patients in the endovascular therapy and no endovascular therapy groups, respectively (P=0.02). The adjusted odds ratio for the favorable outcome was 1.44 (95% confidence interval, 1.10-1.86, P=0.007). The efficacy of endovascular therapy in achieving favorable outcomes did not differ between our subgroups and in the sensitivity analyses. CONCLUSIONS: Endovascular therapy decreased disabilities at 90 days in real-world patients with acute cerebral large-vessel occlusion. CLINICAL TRIAL REGISTRATION: URL: http://www.clinicaltrials.gov. Unique identifier: NCT02419794.

Safety and efficacy of cerebral protection devices in transcatheter aortic valve replacement: A clinical end-points meta-analysis.

BACKGROUND: Stroke after transcatheter aortic valve replacement (TAVR) occurs with an incidence of 4-11% and is a particularly devastating adverse event associated with the procedure. Several cerebral protection devices (CPD) have been developed to prevent cerebrovascular events during TAVR. While most studies have shown CPD to be associated with decreased number and volume of lesions on diffusion weighted magnetic resonance imaging, the clinical benefit of these devices remains uncertain. METHODS: We aimed to use meta-analysis techniques to study the clinical safety and efficacy of these CPD in prospective randomized and non-randomized studies. Data was summarized as Mantel-Haenszel relative risk (RR) and 95% confidence intervals (CI). We used the Higgins' I2 statistic to evaluate heterogeneity. RESULTS: We found no evidence of difference between patients with and without CPD [RR 0.70 (95% CI 0.40-1.21)] for the primary composite outcome of stroke and mortality at 30 days. The two groups were also comparable in peri-procedural strokes [RR 0.53 (95% CI 0.27-1.07)], stroke at 30 days [RR 0.69(95% CI 0.38-1.26)], mortality [RR 0.59 (95% CI 0.22-1.59) at 30 days, AKI [RR 0.68(95% CI 0.28-1.62)], major bleeding [RR 0.56 (95% CI 0.26-1.18)], life threating bleeding [0.54 (95% CI 0.19-1.53)] and major vascular complications [RR 0.80 (95% CI 0.52-1.24)]. The risk of strokes within the first week of TAVR was significantly lower in the CPD group [0.56(95% CI 0.33-0.96)]. CONCLUSION: CPD are associated with a decreased incidence of strokes within 1 week of follow-up without showing any evidence of increased risk of other peri-procedural adverse events.