Cerebral Embolic Protection during Transcatheter Aortic-Valve Replacement.

BACKGROUND: Transcatheter aortic-valve replacement (TAVR) for the treatment of aortic stenosis can lead to embolization of debris. Capture of debris by devices that provide cerebral embolic protection (CEP) may reduce the risk of stroke. METHODS: We randomly assigned patients with aortic stenosis in a 1:1 ratio to undergo transfemoral TAVR with CEP (CEP group) or without CEP (control group). The primary end point was stroke within 72 hours after TAVR or before discharge (whichever came first) in the intention-to-treat population. Disabling stroke, death, transient ischemic attack, delirium, major or minor vascular complications at the CEP access site, and acute kidney injury were also assessed. A neurology professional examined all the patients at baseline and after TAVR. RESULTS: A total of 3000 patients across North America, Europe, and Australia underwent randomization; 1501 were assigned to the CEP group and 1499 to the control group. A CEP device was successfully deployed in 1406 of the 1489 patients (94.4%) in whom an attempt was made. The incidence of stroke within 72 hours after TAVR or before discharge did not differ significantly between the CEP group and the control group (2.3% vs. 2.9%; difference, -0.6 percentage points; 95% confidence interval, -1.7 to 0.5; P = 0.30). Disabling stroke occurred in 0.5% of the patients in the CEP group and in 1.3% of those in the control group. There were no substantial differences between the CEP group and the control group in the percentage of patients who died (0.5% vs. 0.3%); had a stroke, a transient ischemic attack, or delirium (3.1% vs. 3.7%); or had acute kidney injury (0.5% vs. 0.5%). One patient (0.1%) had a vascular complication at the CEP access site. CONCLUSIONS: Among patients with aortic stenosis undergoing transfemoral TAVR, the use of CEP did not have a significant effect on the incidence of periprocedural stroke, but on the basis of the 95% confidence interval around this outcome, the results may not rule out a benefit of CEP during TAVR. (Funded by Boston Scientific; PROTECTED TAVR ClinicalTrials.gov number, NCT04149535.).

Performance of Thrombectomy-Capable, Comprehensive, and Primary Stroke Centers in Reperfusion Therapies for Acute Ischemic Stroke: Report From the Get With The Guidelines-Stroke Registry.

BACKGROUND: The thrombectomy-capable stroke center (TSC) is a recently introduced intermediate tier of accreditation for hospitals at which patients with acute ischemic stroke receive care. The comparative quality and clinical outcomes of reperfusion therapies at TSCs, primary stroke centers (PSCs), and comprehensive stroke centers (CSCs) have not been well delineated. METHODS: We conducted a retrospective, observational, cohort study from 2018 to 2020 that included patients with acute ischemic stroke who received endovascular thrombectomy (EVT) and intravenous thrombolysis reperfusion therapies at CSCs, TSCs, or PSCs. Participants were recruited from Get With The Guidelines-Stroke registry. Study end points included timeliness of intravenous thrombolysis and EVT, successful reperfusion, discharge destination, discharge mortality, and functional independence at discharge. RESULTS: Among 84 903 patients, 48 682 received EVT, of whom 73% were treated at CSCs, 22% at PSCs, and 4% at TSCs. The median annual EVT volume was 76 for CSCs, 55 for TSCs, and 32 for PSCs. Patient differences by center status included higher National Institutes of Health Stroke Scale score, longer onset-to-arrival time, and higher transfer-in rates for CSCs, TSCs, and PSCs, respectively. In adjusted analyses, the likelihood of achieving the goal door-to-needle time was higher in CSCs compared with PSCs (odds ratio [OR], 1.39 [95% CI, 1.17-1.66]) and in TSCs compared with PSCs (OR, 1.45 [95% CI, 1.08-1.96]). Likewise, the odds of achieving the goal door-to-puncture time were higher in CSCs compared with PSCs (OR, 1.58 [95% CI, 1.13-2.21]). CSCs and TSCs also demonstrated better clinical efficacy outcomes compared with PSCs. The odds of discharge to home or rehabilitation were higher in CSCs compared with PSCs (OR, 1.18 [95% CI, 1.06-1.31]), whereas the odds of in-hospital mortality or discharge to hospice were lower in both CSCs compared with PSCs (OR, 0.87 [95% CI, 0.81-0.94]) and TSCs compared with PSCs (OR, 0.86 [95% CI, 0.75-0.98]). There were no significant differences in any of the quality-of-care metrics and clinical outcomes between TSCs and CSCs. CONCLUSIONS: In this study representing national US practice, CSCs and TSCs exceeded PSCs in key quality-of-care reperfusion metrics and outcomes, whereas TSCs and CSCs demonstrated a similar performance. With more than one-fifth of all EVT procedures during the study period conducted at PSCs, it may be desirable to explore national initiatives aimed at facilitating the elevation of eligible PSCs to a higher certification status.

Twenty Years of Get With The Guidelines-Stroke: Celebrating Past Successes, Lessons Learned, and Future Challenges.

The Get With The Guidelines-Stroke program which, began 20 years ago, is one of the largest and most important nationally representative disease registries in the United States. Its importance to the stroke community can be gauged by its sustained growth and widespread dissemination of findings that demonstrate sustained increases in both the quality of care and patient outcomes over time. The objectives of this narrative review are to provide a brief history of Get With The Guidelines-Stroke, summarize its major successes and impact, and highlight lessons learned. Looking to the next 20 years, we discuss potential challenges and opportunities for the program.

World Stroke Organization Brain & hEart globAl iniTiative Program.

INTRODUCTION: The World Stroke Organization (WSO) Brain & Heart Task Force developed the Brain & hEart globAl iniTiative (BEAT), a pilot feasibility implementation program to establish clinical collaborations between cardiologists and stroke physicians who work at large healthcare facilities. METHODS: The WSO BEAT pilot project focused on atrial fibrillation (AF) and patent foramen ovale (PFO) detection and management, and poststroke cardiovascular complications known as the stroke-heart syndrome. The program included 10 sites from 8 countries: Brazil, China, Egypt, Germany, Japan, Mexico, Romania, and the USA The primary composite feasibility outcome was the achievement of the following 3 implementation metrics (1) developing site-specific clinical pathways for the diagnosis and management of AF, PFO, and the stroke-heart syndrome; (2) establishing regular Neurocardiology rounds (e.g., monthly); and (3) incorporating a cardiologist to the stroke team. The secondary objectives were (1) to identify implementation challenges to guide a larger program and (2) to describe qualitative improvements. RESULTS: The WSO BEAT pilot feasibility program achieved the prespecified primary composite outcome in 9 of 10 (90%) sites. The most common challenges were the limited access to specific medications (e.g., direct oral anticoagulants) and diagnostic (e.g., prolonged cardiac monitoring) or therapeutic (e.g., PFO closure devices) technologies. The most relevant qualitative improvement was the achievement of a more homogeneous diagnostic and therapeutic approach. CONCLUSION: The WSO BEAT pilot program suggests that developing neurocardiology collaborations is feasible. The long-term sustainability of the WSO BEAT program and its impact on quality of stroke care and clinical outcomes needs to be tested in a larger and longer duration program.

Door-in-Door-out Times for Interhospital Transfer of Patients With Stroke.

Importance: Treatments for time-sensitive acute stroke are not available at every hospital, often requiring interhospital transfer. Current guidelines recommend hospitals achieve a door-in-door-out time of no more than 120 minutes at the transferring emergency department (ED). Objective: To evaluate door-in-door-out times for acute stroke transfers in the American Heart Association Get With The Guidelines-Stroke registry and to identify patient and hospital factors associated with door-in-door-out times. Design, Setting, and Participants: US registry-based, retrospective study of patients with ischemic or hemorrhagic stroke from January 2019 through December 2021 who were transferred from the ED at registry-affiliated hospitals to other acute care hospitals. Exposure: Patient- and hospital-level characteristics. Main Outcomes and Measures: The primary outcome was the door-in-door-out time (time of transfer out minus time of arrival to the transferring ED) as a continuous variable and a categorical variable (≤120 minutes, >120 minutes). Generalized estimating equation (GEE) regression models were used to identify patient and hospital-level characteristics associated with door-in-door-out time overall and in subgroups of patients with hemorrhagic stroke, acute ischemic stroke eligible for endovascular therapy, and acute ischemic stroke transferred for reasons other than endovascular therapy. Results: Among 108 913 patients (mean [SD] age, 66.7 [15.2] years; 71.7% non-Hispanic White; 50.6% male) transferred from 1925 hospitals, 67 235 had acute ischemic stroke and 41 678 had hemorrhagic stroke. Overall, the median door-in-door-out time was 174 minutes (IQR, 116-276 minutes): 29 741 patients (27.3%) had a door-in-door-out time of 120 minutes or less. The factors significantly associated with longer median times were age 80 years or older (vs 18-59 years; 14.9 minutes, 95% CI, 12.3 to 17.5 minutes), female sex (5.2 minutes; 95% CI, 3.6 to 6.9 minutes), non-Hispanic Black vs non-Hispanic White (8.2 minutes, 95% CI, 5.7 to 10.8 minutes), and Hispanic ethnicity vs non-Hispanic White (5.4 minutes, 95% CI, 1.8 to 9.0 minutes). The following were significantly associated with shorter median door-in-door-out time: emergency medical services prenotification (-20.1 minutes; 95% CI, -22.1 to -18.1 minutes), National Institutes of Health Stroke Scale (NIHSS) score exceeding 12 vs a score of 0 to 1 (-66.7 minutes; 95% CI, -68.7 to -64.7 minutes), and patients with acute ischemic stroke eligible for endovascular therapy vs the hemorrhagic stroke subgroup (-16.8 minutes; 95% CI, -21.0 to -12.7 minutes). Among patients with acute ischemic stroke eligible for endovascular therapy, female sex, Black race, and Hispanic ethnicity were associated with a significantly higher door-in-door-out time, whereas emergency medical services prenotification, intravenous thrombolysis, and a higher NIHSS score were associated with significantly lower door-in-door-out times. Conclusions and Relevance: In this US registry-based study of interhospital transfer for acute stroke, the median door-in-door-out time was 174 minutes, which is longer than current recommendations for acute stroke transfer. Disparities and modifiable health system factors associated with longer door-in-door-out times are suitable targets for quality improvement initiatives.

Basilar artery bifurcation anatomy as a determinant of recanalization and stroke outcome: Basilar artery bifurcation anatomy and stroke outcome.

OBJECTIVES: Thrombectomy improves outcomes in patients with basilar artery (BA) occlusion. We hypothesized that the anatomic configuration of the BA bifurcation, classified as T- or Y-shaped, may impact the outcome as a T-shaped BA would involve more deep penetrating arteries of the midbrain and thalamus. MATERIALS AND METHODS: In this 2-center retrospective cohort study, we included patients with stroke due to distal BA occlusion and performed blinded classification of their BA distal bifurcation as either T- or Y-shaped. The primary outcomes were favorable outcome at 90-days (modified Rankin Scale 0 - 2) and successful recanalization (TICI scores 2B or 3). RESULTS: 70 patients (mean age 66 years, 36% women) were included. 38 had T- and 32 had Y-shaped bifurcations. Baseline characteristics were similar for both groups, including demographics, onset to arterial puncture time, baseline NIHSS, THRIVE score, posterior circulation collateral score, and presence of tandem occlusion. Comparing the T- to the Y- shape, there was no difference in the likelihood of successful recanalization (RR: 1.02, CI: [0.86-1.21], p=1.00) nor 90-day favorable mRS (0-2) score (RR: 0.58, CI: [0.25-1.32]; p=0.18). Similarly, mortality at 30 and 90-days were not significantly affected by the type of bifurcation. CONCLUSIONS: The configuration of the basilar artery does not significantly impact on recanalization success or stroke outcome in our study. Further studies are needed to confirm our observations.

Perioperative Neurological Evaluation and Management to Lower the Risk of Acute Stroke in Patients Undergoing Noncardiac, Nonneurological Surgery: A Scientific Statement From the American Heart Association/American Stroke Association.

Perioperative stroke is a potentially devastating complication in patients undergoing noncardiac, nonneurological surgery. This scientific statement summarizes established risk factors for perioperative stroke, preoperative and intraoperative strategies to mitigate the risk of stroke, suggestions for postoperative assessments, and treatment approaches for minimizing permanent neurological dysfunction in patients who experience a perioperative stroke. The first section focuses on preoperative optimization, including the role of preoperative carotid revascularization in patients with high-grade carotid stenosis and delaying surgery in patients with recent strokes. The second section reviews intraoperative strategies to reduce the risk of stroke, focusing on blood pressure control, perioperative goal-directed therapy, blood transfusion, and anesthetic technique. Finally, this statement presents strategies for the evaluation and treatment of patients with suspected postoperative strokes and, in particular, highlights the value of rapid recognition of strokes and the early use of intravenous thrombolysis and mechanical embolectomy in appropriate patients.

Frequency and Patterns of Brain Infarction in Patients With Embolic Stroke of Undetermined Source: NAVIGATE ESUS Trial.

BACKGROUND AND PURPOSE: The spectrum of brain infarction in patients with embolic stroke of undetermined source (ESUS) has not been well characterized. Our objective was to define the frequency and pattern of brain infarcts detected by magnetic resonance imaging (MRI) among patients with recent ESUS participating in a clinical trial. METHODS: In the NAVIGATE ESUS trial (New Approach Rivaroxaban Inhibition of Factor Xa in a Global Trial Versus ASA to Prevent Embolism in Embolic Stroke of Undetermined Source), an MRI substudy was carried out at 87 sites in 15 countries. Participants underwent an MRI using a specified protocol near randomization. Images were interpreted centrally by those unaware of clinical characteristics. RESULTS: Among the 918 substudy cohort participants, the mean age was 67 years and 60% were men with a median (interquartile range) of 64 (26-115) days between the qualifying ischemic stroke and MRI. On MRI, 855 (93%) had recent or chronic brain infarcts that were multiple in 646 (70%) and involved multiple arterial territories in 62% (401/646). Multiple brain infarcts were present in 68% (510/755) of those without a history of stroke or transient ischemic attack before the qualifying ESUS. Prior stroke/transient ischemic attack (P<0.001), modified Rankin Scale score >0 (P<0.001), and current tobacco use (P=0.01) were associated with multiple infarcts. Topographically, large and/or cortical infarcts were present in 89% (757/855) of patients with infarcts, while in 11% (98/855) infarcts were exclusively small and subcortical. Among those with multiple large and/or cortical infarcts, 57% (251/437) had one or more involving a different vascular territory from the qualifying ESUS. CONCLUSIONS: Most patients with ESUS, including those without prior clinical stroke or transient ischemic attack, had multiple large and/or cortical brain infarcts detected by MRI, reflecting a substantial burden of clinical stroke and covert brain infarction. Infarcts most frequently involved multiple vascular territories. Registration: URL: https://www.clinicaltrials.gov; Unique identifier: NCT02313909.

A randomized evaluation of the TriGuard™ HDH cerebral embolic protection device to Reduce the Impact of Cerebral Embolic LEsions after TransCatheter Aortic Valve ImplanTation: the REFLECT I trial.

AIMS: The REFLECT I trial investigated the safety and effectiveness of the TriGuard™ HDH (TG) cerebral embolic deflection device in patients undergoing transcatheter aortic valve replacement (TAVR). METHODS AND RESULTS: This prospective, multicentre, single-blind, 2:1 randomized (TG vs. no TG) study aimed to enrol up to 375 patients, including up to 90 roll-in patients. The primary combined safety endpoint (VARC-2 defined early safety) at 30 days was compared with a performance goal. The primary efficacy endpoint was a hierarchical composite of (i) all-cause mortality or any stroke at 30 days, (ii) National Institutes of Health Stroke Scale (NIHSS) worsening at 2-5 days or Montreal Cognitive Assessment worsening at 30 days, and (iii) total volume of cerebral ischaemic lesions detected by diffusion-weighted magnetic resonance imaging at 2-5 days. Cumulative scores were compared between treatment groups using the Finkelstein-Schoenfeld method. A total of 258 of the planned, 375 patients (68.8%) were enrolled (54 roll-in and 204 randomized). The primary safety outcome was met compared with the performance goal (21.8% vs. 35%, P < 0.0001). The primary hierarchical efficacy endpoint was not met (mean efficacy score, higher is better: -5.3 ± 99.8 TG vs. 11.8 ± 96.4 control, P = 0.31). Covert central nervous system injury was numerically lower with TG both in-hospital (46.1% vs. 60.3%, P = 0.0698) and at 5 days (61.7 vs. 76.2%, P = 0.054) compared with controls. CONCLUSION: REFLECT I demonstrated that TG cerebral protection during TAVR was safe in comparison with historical TAVR data but did not meet the predefined effectiveness endpoint compared with unprotected TAVR controls.

Delays in the Identification and Assessment of in-Hospital Stroke Patients.

OBJECTIVES: In-hospital stroke is associated with poor outcomes. Reasons for delays, use of interventions, and presence of large vessel occlusion are not well characterized. MATERIALS AND METHODS: A retrospective single center cohort of 97 patients with in-hospital stroke was analyzed to identify factors associated with delays from last known normal to symptom identification and to stroke team alerting. Stroke interventions and presence of large vessel occlusion were also assessed. RESULTS: Strokes were predominantly on surgery services (70%), ischemic (82%), and severe (median NIHSS 16; interquartile range [IQR] 6-24). There were long delays from last known normal to symptom identification (median 5.1 hours, IQR 1.0-19.7 hours), symptom identification to stroke team alerting (median 2.1 hours, IQR 0.5-9.9 hours), and total time from last known normal to alerting (median 11.4 [IQR 2.7-34.2] hours). In univariable analysis, being on a surgical service, in an ICU, intubated, and higher NIHSS were associated with delays. In multivariable analysis only intubation was independently associated with time from last known normal to symptom identification (coefficient 20 hours, IQR 0.2 - 39.8, p=0.047). Interventions were given to 17/80 (21%) ischemic stroke patients; 3 (4%) received IV tPA and 14 (18%) underwent thrombectomy. Vascular imaging occurred in 57/80 (71%) ischemic stroke patients and 21/57 (37%) had large vessel occlusion. CONCLUSIONS: Hospitalized patients with stroke experience long delays from symptom identification to stroke team alerting. Intubation was strongly associated with delay to symptom identification. Although stroke severity was high and large vessel occlusion common, many patients did not receive acute interventions.

Considerations for Reduction of Risk of Perioperative Stroke in Adult Patients Undergoing Cardiac and Thoracic Aortic Operations: A Scientific Statement From the American Heart Association.

Perioperative stroke is one of the most severe and feared complications of cardiac surgery. Based on the timing of onset and detection, perioperative stroke can be classified as intraoperative or postoperative. The pathogenesis of perioperative stroke is multifactorial, which makes prediction and prevention challenging. However, information on its incidence, mechanisms, diagnosis, and treatment can be helpful in minimizing the perioperative neurological risk for individual patients. We herein provide suggestions on preoperative, intraoperative, and postoperative strategies aimed at reducing the risk of perioperative stroke and at improving the outcomes of patients who experience a perioperative stroke.

Vessel Wall Magnetic Resonance Imaging Biomarkers of Symptomatic Intracranial Atherosclerosis: A Meta-Analysis.

BACKGROUND AND PURPOSE: Intracranial atherosclerotic disease is a common cause of stroke worldwide. Intracranial vessel wall magnetic resonance imaging may be able to identify imaging biomarkers of symptomatic plaque. We performed a meta-analysis to evaluate the strength of association of imaging features of symptomatic plaque leading to downstream ischemic events. Effects on the strength of association were also assessed accounting for possible sources of bias and variability related to study design and magnetic resonance parameters. METHODS: PubMed, Scopus, Web of Science, EMBASE, and Cochrane databases were searched up to October 2019. Two independent reviewers extracted data on study design, vessel wall magnetic resonance imaging techniques, and imaging end points. Per-lesion odds ratios (OR) were calculated and pooled using a bivariate random-effects model. Subgroup analyses, sensitivity analysis, and evaluation of publication bias were also performed. RESULTS: Twenty-one articles met inclusion criteria (1750 lesions; 1542 subjects). Plaque enhancement (OR, 7.42 [95% CI, 3.35-16.43]), positive remodeling (OR, 5.60 [95% CI, 2.23-14.03]), T1 hyperintensity (OR, 2.05 [95% CI, 1.27-3.32]), and surface irregularity (OR, 4.50 [95% CI, 1.39-8.57]) were significantly associated with downstream ischemic events. T2 signal intensity was not significant (P=0.59). Plaque enhancement was significantly associated with downstream ischemic events in all subgroup analyses and showed stronger associations when measured in retrospectively designed studies (P=0.02), by a radiologist as a rater (P<0.001), and on lower vessel wall magnetic resonance imaging spatial resolution sequences (P=0.02). CONCLUSIONS: Plaque enhancement, positive remodeling, T1 hyperintensity, and surface irregularity emerged as strong imaging biomarkers of symptomatic plaque in patients with ischemic events. Plaque enhancement remained significant accounting for sources of bias and variability in both study design and instrument. Future studies evaluating plaque enhancement as a predictive marker for stroke recurrence with larger sample sizes would be valuable.

Patent Foramen Ovale Closure Decreases the Incidence but Not the Size of New Brain Infarction on Magnetic Resonance Imaging: An Analysis of the REDUCE Trial.

Background and Purpose: Randomized patent foramen ovale closure trials have used open-label end point ascertainment which increases the risk of bias and undermines confidence in the conclusions. The Gore REDUCE trial prospectively performed baseline and follow-up magnetic resonance imaging (MRIs) for all subjects providing an objective measure of the effectiveness of closure. Methods: We performed blinded evaluations of the presence, location, and volume of new infarct on diffusion-weighted imaging of recurrent clinical stroke or new infarct (>3 mm) on T2/fluid attenuated inversion recovery from baseline to follow-up MRI at 2 years, comparing closure to medical therapy alone. We also examined the effect of shunt size and the development of atrial fibrillation on infarct burden at follow-up. Results: At follow-up, new clinical stroke or silent MRI infarct occurred in 18/383 (4.7%) patients who underwent closure and 19/177 (10.7%) medication-only patients (relative risk, 0.44 [95% CI, 0.24­0.81], P=0.02). Clinical strokes were less common in closure patients compared with medically treated patients, 5 (1.3%) versus 12 (6.8%), P=0.001, while silent MRI infarcts were similar, 13 (3.4%) versus 7 (4.0%), P=0.81. There were no differences in number, volumes, and distribution of new infarct comparing closure patients to those treated with medication alone. There were also no differences of number, volumes, and distribution comparing silent infarcts to clinical strokes. Infarct burden was also similar for patients who developed atrial fibrillation and for those with large shunts. Conclusions: The REDUCE trial demonstrates that patent foramen ovale closure prevents recurrent brain infarction based on the objective outcome of new infarcts on MRI. Only clinical strokes were reduced by closure while silent infarctions were similar between study arms, and there were no differences in infarct volume or location comparing silent infarcts to clinical strokes. Registration: URL: https://www.clinicaltrials.gov; Unique identifier: NCT00738894.

Patent foramen ovale and stroke: current evidence and treatment options.

PURPOSE OF REVIEW: Recent data have changed the landscape of patent foramen ovale (PFO) closure for secondary stroke prevention. This review synthesizes the data and provides a framework for optimal management of stroke patients with PFO. RECENT FINDINGS: The cumulative evidence indicates that PFO closure reduces the risk of recurrent stroke in carefully selected young cryptogenic stroke patients, with an annualized risk reduction of ∼0.6%. The benefit of PFO closure is particularly evident in patients with embolic appearing strokes, large right-to-left shunt, or an associated atrial septal aneurysm. There may be little or no benefit in patients with small deep infarcts, a small PFO, or an indication for long-term anticoagulation. Closure is accompanied by a small risk of major procedural complication and atrial fibrillation. SUMMARY: The annual risk of stroke from PFO is low relative to other stroke mechanisms, but the life-time cumulative risk in young patients who have experienced a prior stroke may be substantial, in which case the absolute benefit of closure is likely impactful. PFO is highly prevalent in the general population, present in about one in four adults, and should not be considered to be the cause of the stroke until a thorough workup has excluded alternative mechanisms.

Improved Carotid Stenosis Quantification on Novel 4D/3D-Doppler Ultrasonography Indexing to the Common Carotid Artery.

PURPOSE: The accuracy of internal carotid artery stenosis (ICAS) quantification depends on the method of stenosis measurement, impacting therapeutic decisions and outcomes. The NASCET method references the stenotic to the distal ICAS lumen, the ECST method to the local outer and the common carotid artery (CC) method to the CC diameter. Direct morphometric stenosis measurement with four-dimensionally guided three-dimensional ultrasonography (4D/3DC-US) demonstrated good validity for the commonly used NASCET method. The NASCET definition has clinically relevant drawbacks. Our purpose was to investigate the validity of the ECST and CC methods. MATERIALS AND METHODS: 4D/3DC-US percent-stenosis measures of 103 stenoses (80 patients) were compared to quantitative catheter angiography and duplex ultrasonography (DUS) in a blinded fashion. RESULTS: The 4D/3DC-US versus angiography intermethod standard deviation of differences (SDD, n = 103) was lower for the CC method (5.7 %) compared to the NASCET (8.1 %, p < 0.001) and ECST methods (9.1 %, p < 0.001). Additionally, it was lower than the NASCET angiography interrater SDD of 52 stenoses (SDD 7.2 %, p = 0.047) and non-inferior for the ECST method (p = 0.065). Interobserver analysis of equivalent grading methods showed no differences for the SDDs between angiography and 4D/3DC-US observers (p > 0.076). Binary comparison to angiography showed equal Kappa values > 0.7 and an accuracy ≥ 85 % for the NASCET and CC methods, higher than for the ECST method. The binary accuracy of ICAS grading did not differ from DUS for all methods. CONCLUSION: The new 4D/3DC-US CC method is an accurate and well reproducible alternative to the NASCET and ECST methods and offers potential for clinical application.

D-dimer and Body CT to Identify Occult Malignancy in Acute Ischemic Stroke.

BACKGROUND AND AIM: Patients with acute ischemic stroke associated with cancer have D-dimer elevations greater than those with acute ischemic stroke or cancer alone. While D-dimer has been proposed as a screening tool to identify such patients, its use in clinical practice to identify malignancy and to inform the use of CT scanning has not been well characterized. METHODS: We conducted a retrospective cohort study of patients with acute ischemic stroke to evaluate how D-dimer levels and CT chest, abdomen, and pelvis scanning were used in practice to screen for occult malignancy. Patients were excluded if they had known active cancer and or received tPA. RESULTS: Of 480 patients, 254 (53%) had D-dimer measured, 49 (10%) underwent CT screening for cancer, and 11 (2%) had findings concerning for malignancy. There was no difference in D-dimer level between patients who underwent CT evaluation for cancer and those who did not (median 1.01 vs 0.85 p = 0.19). Patients with CT concerning for cancer had higher D-dimer levels than those with a negative CT (median 2.52 vs 0.74 p = 0.01). D-dimer demonstrated moderate discrimination with a c-statistic of 0.77. Selecting a cut point of >1.2 ug/mL (60th percentile of our cohort and 2.4-times the upper limit of normal for our institution's D-dimer assay) provided a sensitivity of 85% and specificity of 65%, a positive likelihood ratio of 2.32, and an odds ratio of 9.6 (95% confidence interval 2.1-44.1, p = 0.004) for having a CT scan concerning for malignancy. CONCLUSIONS: Elevated D-dimer levels are suggestive of occult malignancy in acute ischemic stroke patients and should inform selective use of CT to screen for cancer.

Anticoagulation Choice and Timing in Stroke Due to Atrial Fibrillation: A Survey of US Stroke Specialists (ACT-SAFe).

OBJECTIVE: Risk of early recurrent ischemic stroke in patients with atrial fibrillation may be high. ASA/AHA guidelines provide imprecise recommendations on the timing and anticoagulant choice for this indication. We assessed current opinions of stroke neurologists. METHODS: Case scenarios describing patients with acute ischemic stroke (AIS) due to paroxysmal atrial fibrillation (AF) were presented to US board-certified stroke neurologists in an internet-based questionnaire. Questions assessed timing and choice of anticoagulation for secondary stroke prevention, factors prompting earlier anticoagulation, reasons for specific anticoagulant choice, and alternatives to anticoagulation in ineligible patients. Open-ended comments were also solicited. RESULTS: Responses were available from 238/1239 stroke neurologists surveyed. In patients with small AIS without hemorrhagic transformation (HT), 51% elected to start anticoagulation within 96 hours. With increased stroke severity and asymptomatic HT, only 29% and 26% respectively chose to anticoagulate within 7 days. Few requested stability imaging before starting anticoagulation. With symptomatic HT the majority (79%) waited >14 days. 93% would anticoagulate earlier if left atrium/left atrial appendage or acute left ventricular thrombi, or mechanical heart valve were present. Direct oral anticoagulants (DOACs) were the preferred anticoagulation strategy (64%), and the remaining 38% preferred Warfarin. Aspirin was preferred by 57% in anticoagulation ineligible. CONCLUSION: Apart from AIS with symptomatic HT, there is a remarkable lack of consensus among stroke neurologists regarding the timing of anticoagulation for secondary stroke prevention in patients with AIS due to PAF. DOACs are the preferred anticoagulation strategy. More studies are required to clarify anticoagulant management in this patient population.

Cardiovascular Events after New-Onset Atrial Fibrillation in Adults with CKD: Results from the Chronic Renal Insufficiency Cohort (CRIC) Study.

BACKGROUND: Atrial fibrillation (AF), the most common sustained arrhythmia in CKD, is associated with poor clinical outcomes in both patients without CKD and patients with dialysis-treated ESRD. However, less is known about AF-associated outcomes in patients with CKD who do not require dialysis. METHODS: To prospectively examine the association of new-onset AF with subsequent risks of cardiovascular disease events and death among adults with CKD, we studied participants enrolled in the Chronic Renal Insufficiency Cohort Study who did not have AF at baseline. Outcomes included heart failure, myocardial infarction, stroke, and death occurring after diagnosis of AF. We used Cox regression models and marginal structural models to examine the association of incident AF with subsequent risk of cardiovascular disease events and death, adjusting for patient characteristics, laboratory values, and medication use. RESULTS: Among 3080 participants, 323 (10.5%) developed incident AF during a mean 6.1 years of follow-up. Compared with participants who did not develop AF, those who did had higher adjusted rates of heart failure (hazard ratio [HR], 5.17; 95% confidence interval [95% CI], 3.89 to 6.87), myocardial infarction (HR, 3.64; 95% CI, 2.50 to 5.31), stroke (HR, 2.66; 95% CI, 1.50 to 4.74), and death (HR, 3.30; 95% CI, 2.65 to 4.12). These associations remained robust with additional adjustment for biomarkers of inflammation, cardiac stress, and mineral metabolism; left ventricular mass; ejection fraction; and left atrial diameter. CONCLUSIONS: Incident AF is independently associated with two- to five-fold increased rates of developing subsequent heart failure, myocardial infarction, stroke, or death in adults with CKD. These findings have important implications for cardiovascular risk reduction.

Proposed Standardized Neurological Endpoints for Cardiovascular Clinical Trials: An Academic Research Consortium Initiative.

Surgical and catheter-based cardiovascular procedures and adjunctive pharmacology have an inherent risk of neurological complications. The current diversity of neurological endpoint definitions and ascertainment methods in clinical trials has led to uncertainties in the neurological risk attributable to cardiovascular procedures and inconsistent evaluation of therapies intended to prevent or mitigate neurological injury. Benefit-risk assessment of such procedures should be on the basis of an evaluation of well-defined neurological outcomes that are ascertained with consistent methods and capture the full spectrum of neurovascular injury and its clinical effect. The Neurologic Academic Research Consortium is an international collaboration intended to establish consensus on the definition, classification, and assessment of neurological endpoints applicable to clinical trials of a broad range of cardiovascular interventions. Systematic application of the proposed definitions and assessments will improve our ability to evaluate the risks of cardiovascular procedures and the safety and effectiveness of preventive therapies.

Prevalence of Nonstenotic Carotid Plaque in Stroke Due to Atrial Fibrillation Compared to Embolic Stroke of Undetermined Source.

BACKGROUND: Embolic stroke of undetermined source (ESUS) accounts for about 20% of strokes. Nonstenotic cervical arterial plaque may be a mechanism of stroke in a subset of these patients. METHODS: A cohort of consecutive patients with ischemic stroke was retrospectively identified from a stroke registry. Patients with unilateral anterior circulation embolic stroke due to atrial fibrillation (AF) or consistent with ESUS who underwent computed tomographic neck angiography were included. The prespecified primary outcome was a comparison of the prevalence of carotid plaque greater than or equal to 3 mm thickness ipsilateral versus contralateral to the infarct side. RESULTS: Of 772 screened patients, 96 patients with ESUS and 99 patients with AF were included. Plaque greater than or equal to 3 mm was more frequently ipsilateral than contralateral to the infarct in patients with ESUS (41% versus 29%, P = .03), and plaque thickness was greater ipsilateral compared to contralateral (median 2.5 versus 2.2 mm, P = .02). No significant differences in plaque characteristics ipsilateral compared to contralateral were found in patients with AF. The prevalence of ipsilateral versus contralateral plaque was greater in ESUS patients less than or equal to 65 years old (48% versus 19%, P < .01), but no different in patients greater than 65 years old (35% versus 39%, P = .57). CONCLUSIONS: Nonstenotic cervical carotid plaque is more common ipislateral to the infarction in patients with ESUS, but not in patients with AF, supporting an underlying atheroembolic mechanism in a subset of ESUS patients. This association might be greater in younger ESUS patients.