Assessment of Complex Flow Patterns in Patients With Carotid Webs, Patients With Carotid Atherosclerosis, and Healthy Subjects Using 4D Flow MRI.

BACKGROUND: Carotid webs (CaWs) are fibromuscular projections in the internal carotid artery (ICA) that cause mild luminal narrowing (<50%), but may be causative in up to one-third of seemingly cryptogenic strokes. Understanding hemodynamic alterations caused by CaWs is imperative to assessing stroke risk. Time-Average Wall Shear Stress (TAWSS) and Oscillatory Shear Index (OSI) are hemodynamic parameters linked to vascular dysfunction and thrombosis. PURPOSE: To test the hypothesis: "CaWs are associated with lower TAWSS and higher OSI than mild atherosclerosis or healthy carotid bifurcation." STUDY TYPE: Prospective study. POPULATION: A total of 35 subjects (N = 14 bifurcations with CaW, 11F, age: 49 ± 10, 10 mild atherosclerosis 6F, age: 72 ± 9, 11 healthy 9F, age: 42 ± 13). FIELD STRENGTH/SEQUENCE: 4D flow/STAR-MATCH/3D TOF/3T MRI, CTA. ASSESSMENT: 4D Flow velocity data were analyzed in two ways: 1) 3D ROI in the ICA bulbar segment (complex flow patterns are expected) was used to quantify the regions with low TAWSS and high OSI. 2) 2D planes were placed perpendicular to the centerline of the carotid bifurcation for detailed analysis of TAWSS and OSI. STATISTICAL TESTS: Independent-samples Kruskal-Wallis-H test with 0.05 used for statistical significance. RESULTS: The percent surface area where low TAWSS was present in the ICA bulb was 12.3 ± 8.0% (95% CI: 7.6-16.9) in CaW subjects, 1.6 ± 1.9% (95% CI: 0.2-2.9) in atherosclerosis, and 8.5 ± 7.7% (95% CI: 3.6-13.4) in healthy subjects, all differences were statistically significant (ƞ2 = 0.3 [95% CI: 0.05-0.5], P-value CaW vs. healthy = 0.2). OSI had similar values in the CCA between groups (ƞ2 = 0.07 [95% CI: 0.0-0.2], P-value = 0.5), but OSI was significantly higher downstream of the bifurcation in CaW subjects compared to atherosclerosis and normal subjects. OSI returned to similar values between groups 1.5 diameters distal to the bifurcation (ƞ2 = 0.03 [95% CI: 0.0-0.2], P-value = 0.7). CONCLUSION: Lower TAWSS and higher OSI are present in the ICA bulb in patients with CaW when compared to patients with atherosclerotic or healthy subjects. EVIDENCE LEVEL: 2 TECHNICAL EFFICACY: Stage 2.

Carotid Web Phenotype Is Uncommonly Associated With Classic Fibromuscular Dysplasia: A Retrospective Observational Study.

BACKGROUND AND PURPOSE: Carotid web (CaW) is an intimal form of fibromuscular dysplasia (FMD) involving the carotid bulb which has been increasingly recognized as a potential cause of recurrent ischemic strokes. It is overlooked as a separate entity and often dismissed if no coexistent signs of classic FMD changes are observed. We aim to evaluate the frequency of classic FMD in high-yield vascular territories in patients with symptomatic CaW. METHODS: This was a retrospective analysis of a symptomatic CaW database of 2 comprehensive stroke centers (spanning September 2014-October 2020). The diagnosis of a CaW during a stroke workup was defined as the presence of a shelf-like linear filling defect in the posterior aspect of the carotid bulb on computed tomography angiography in patients with acute ischemic stroke or transient ischemic attack of undetermined cause after a thorough evaluation. Neck computed tomography angiography and renal conventional angiography images were independently evaluated by two readers blinded to the laterality and clinical details to inspect the presence of underlying classic FMD. RESULTS: Sixty-six patients with CaW were identified. Median age was 51 years (interquartile range, 42-57), and 74% were women. All patients had neck computed tomography angiography (allowing for bilateral vertebral and carotid evaluation), whereas 47 patients had additional digital subtraction angiography (which evaluated 47 carotids ipsilateral to the stroke and 10 contralateral carotids). Internal carotid artery classic FMD changes were noted in only 6 out of 66 (9%) in the ipsilateral carotids. No contralateral carotid or vertebral artery classic FMD changes were observed. Renal artery catheter-based angiography was obtained in 16 patients/32 arteries and only 1 patient/2 renal arteries demonstrated classic FMD changes. CONCLUSIONS: CaW phenotype is uncommonly associated with classic FMD changes. Coexistent classic FMD does not constitute a useful marker to corroborate or exclude CaW diagnosis.

Baseline Characteristics of Patients with Symptomatic Carotid Webs: A Matched Case Control Study.

BACKGROUND AND PURPOSE: The baseline characteristics of patients with symptomatic carotid web (CaW) are unclear. We investigate demographic and cerebrovascular risk factors in patients with this overlooked stroke etiology. METHODS: We identified consecutive patients diagnosed with symptomatic CaW at a comprehensive stroke center from July 2014-December 2018. These patients were matched at a 1:4 ratio (based on age and NIHSS scores) to create a control group of acute ischemic stroke (AIS) patients with non-CaW etiologies from the local GetWithTheGuidelines stroke database. RESULTS: Thirty patients with symptomatic CaW were compared to 120 AIS patients with non-CaW etiologies. Symptomatic CaW patients were more likely to be female (73.3 vs. 44.2%; p = 0.004) and black (86.7 vs. 64.2%; p = 0.02). Symptomatic CaWs patients had a fewer absolute number of modifiable cerebrovascular risk factors (1.7±1.1 vs. 2.5±1.2; p = 0.002), lower rates of hypertension (43.4 vs. 63.3%; p = 0.04), and a more favorable lipid profile with lower average LDL (89.5±30.3 vs. 111.2±43.7 mg/dL; p = 0.01) and higher average HDL (47.9±11.3 vs. 42.2±13.8 mg/dL; p = 0.01) as compared to strokes with non-CaW etiology. Symptomatic CaW patients were more likely to have a large vessel occlusion (80.0 vs. 51.7%; p = 0.005), despite similar e-ASPECTS between the groups (8.1±2.1 vs. 8.3±2.2; p = 0.30). On multivariable analysis, symptomatic CaW was an independent predictor of independence at discharge (OR 3.72; 95%CI 1.27-10.94). CONCLUSION: A gender and racial predilection of symptomatic CaWs may exist as females and blacks were were found to be more likely affected. Symptomatic CaW patients have a more benign cerebrovascular risk factor profile corroborating the proposed mechanism of local stasis and thromboembolism. Despite presenting more commonly with LVO, symptomatic CaW was associated with good functional outcome, warranting further studies.

Learning From Alarms: A Robust Learning Approach for Accurate Photoplethysmography-Based Atrial Fibrillation Detection Using Eight Million Samples Labeled With Imprecise Arrhythmia Alarms.

Atrial fibrillation (AF) is a common cardiac arrhythmia with serious health consequences if not detected and treated early. Detecting AF using wearable devices with photoplethysmography (PPG) sensors and deep neural networks has demonstrated some success using proprietary algorithms in commercial solutions. However, to improve continuous AF detection in ambulatory settings towards a population-wide screening use case, we face several challenges, one of which is the lack of large-scale labeled training data. To address this challenge, we propose to leverage AF alarms from bedside patient monitors to label concurrent PPG signals, resulting in the largest PPG-AF dataset so far (8.5 M 30-second records from 24,100 patients) and demonstrating a practical approach to build large labeled PPG datasets. Furthermore, we recognize that the AF labels thus obtained contain errors because of false AF alarms generated from imperfect built-in algorithms from bedside monitors. Dealing with label noise with unknown distribution characteristics in this case requires advanced algorithms. We, therefore, introduce and open-source a novel loss design, the cluster membership consistency (CMC) loss, to mitigate label errors. By comparing CMC with state-of-the-art methods selected from a noisy label competition, we demonstrate its superiority in handling label noise in PPG data, resilience to poor-quality signals, and computational efficiency.

Subjects with carotid webs demonstrate pro-thrombotic hemodynamics compared to subjects with carotid atherosclerosis.

Carotid artery webs (CaW) are non-atherosclerotic projections into the vascular lumen and have been linked to up to one-third of cryptogenic strokes in younger patients. Determining how CaW affects local hemodynamics is essential for understanding clot formation and stroke risk. Computational fluid dynamics simulations were used to investigate patient-specific hemodynamics in carotid artery bifurcations with CaW, bifurcations with atherosclerotic lesions having a similar degree of lumen narrowing, and with healthy carotid bifurcations. Simulations were conducted using segmented computed tomography angiography geometries with inlet boundary conditions extracted from 2D phase contrast MRI scans. The study included carotid bifurcations with CaW (n = 13), mild atherosclerosis (n = 7), and healthy bifurcation geometries (n = 6). Hemodynamic parameters associated with vascular dysfunction and clot formation, including shear rate, oscillatory shear index (OSI), low velocity, and flow stasis were calculated and compared between the subject groups. Patients with CaW had significantly larger regions containing low shear rate, high OSI, low velocity, and flow stasis in comparison to subjects with mild atherosclerosis or normal bifurcations. These abnormal hemodynamic metrics in patients with CaW are associated with clot formation and vascular dysfunction and suggest that hemodynamic assessment may be a tool to assess stroke risk in these patients.

Retrospective Analyses Associate Hemostasis Activation Biomarkers With Poor Outcomes in Patients With COVID-19.

OBJECTIVES: Patients with coronavirus disease 2019 (COVID-19) have thromboembolic complications. Assessment of coagulation and other markers could be useful to understand their coagulopathy. METHODS: We performed a retrospective study of inflammatory and coagulation parameters, including prothrombin fragment 1.2 (PF1.2), thrombin-antithrombin complexes (TATs), fibrin monomers, and D-dimer, in hospitalized patients with COVID-19. We compared the markers in patients with thrombosis, admission to the intensive care unit (ICU), and poor outcome. RESULTS: Of the 81 patients, 9 (11%) experienced an acute thrombotic event (4 with pulmonary embolism, 3 with venous thrombosis, and 2 with stroke). PF1.2 was elevated in 32 (39%) patients, TATs in 54 (67%), fibrin monomers in 49 (60%), and D-dimer in 76 (94%). Statistically significant elevation in PF1.2 and TATs was seen in patients admitted to the ICU, while D-dimer and fibrin monomers were significantly elevated in patients with poor outcomes. The presence of multiple abnormal coagulation parameters was associated with ICU admission. Other parameters with statistically significant results included abnormal WBC counts and elevated C-reactive protein, which were associated with ICU admission and poor outcomes. CONCLUSIONS: Our data demonstrate that abnormalities of biomarkers of hemostasis activation and inflammatory markers are associated with poor outcomes in patients with COVID-19.

C-Reactive protein as a prognostic indicator in hospitalized patients with COVID-19.

Recent studies have reported that CRP levels are elevated in patients with COVID-19 and may correlate with severity of disease and disease progression. We conducted a retrospective cohort analysis of the medical records of 268 adult patients, who were admitted to one of the six cohorted COVID ICUs across Emory Healthcare System and had at least two CRP values within the first seven days of admission to study the temporal progression of CRP and its association with all-cause in-hospital mortality. The median CRP during hospitalization for the entire cohort was 130 mg/L (IQR 82-191 mg/L), and the median CRP on ICU admission was 169 (IQR 111-234). The hospitalization-wide median CRP was significantly higher amongst the patients who died, compared to those who survived [206 mg/L (157-288 mg/L) vs 114 mg/L (72-160 mg/L), p<0.001]. CRP levels increased in a linear fashion during the first week of hospitalization and peaked on day 5. Compared to patients who died, those who survived had lower peak CRP levels and earlier declines. CRP levels were significantly higher in patients who died compared to those who survived (p<0.001). Our findings support the utility of daily CRP values in hospitalized COVID-19 patients and provide early thresholds during hospitalization that may facilitate risk stratification and prognostication.

Dietary and Serum Omega-6/Omega-3 Fatty Acids Are Associated with Physical and Metabolic Function in Stroke Survivors.

The purpose of this study was to quantify habitual dietary and systemic omega-6 and omega-3 fatty acids and their ratios and to determine their relationship with physical and metabolic function in a cohort of chronic adult stroke survivors. Twenty-five older chronic stroke survivors (age: 63 ± 8 years; BMI: 31 ± 7 kg/m2; mean ± SD) were assessed for fitness (VO2peak), gait speed (GS), 3 m timed up and go (TUG), and six-minute walk distance (6MWD). Plasma lipid and glucose profiles were measured, and HOMA-IR calculated. Dietary (5-day food records) and serum (mass spectrometry) omega-6/omega-3 profiles were assessed. Participants were severely deconditioned (VO2peak: 19 ± 4 mL/kg/min; GS: 0.88 ± 0.28 m/s; TUG: 12.6 ± 5.9 s; 6MWD: 295 ± 121 m) and at elevated metabolic risk (HOMA-IR: 6.3 ± 4.5). The dietary intake ratio of omega-6/omega-3 fatty acids averaged 12.6 ± 7.1 and the serum concentration ratio was 1.21 ± 0.37, which were correlated (r = 0.88, p < 0.01). Higher dietary intake and serum concentrations of omega-6/omega-3 fatty acids were associated with lower 6MWD and higher HOMA-IR, while a higher serum omega-6/omega-3 concentration index was associated with lower VO2peak (p's < 0.05). These preliminary data suggest that both dietary omega-6 and omega-3 fatty acids (quantitated as their intake ratio) and the serum concentration ratio of omega-6/omega-3 may be important indices of physical dysfunction and insulin resistance in chronic stroke survivors.

Trends and diagnostic value of D-dimer levels in patients hospitalized with coronavirus disease 2019.

Coronavirus disease 2019 (COVID-19) has been associated with increased incidence of venous thromboembolic events (VTE) as well as mortality. D-dimer is a marker of fibrinolysis and has been used as a diagnostic and prognostic marker in VTE among other diseases. The purpose of our study is to describe outcomes from out center and to examine trends in D-dimer levels as it relates to VTE and mortality.Patients admitted with confirmed COVID-19 cases to Emory Healthcare from March 12, 2020 through April 6, 2020 with measured plasma D-dimer levels were included in our retrospective analysis. Relevant data about comorbidities, hospitalization course, laboratory results, and outcomes were analyzed.One hundred fifteen patients were included in our study. Mean age was 64 ±â€Š15 years, 47 (41%) females and 84 (73%) African-American. Hypertension was present in 83 (72%) and diabetes in 60 (52%). Mean duration of hospitalization was 19 ±â€Š11 days with 62 (54%) patients intubated (mean duration of 13 ±â€Š8 days). VTE was diagnosed in 27 (23%) patients (mean time to diagnosis 14 ±â€Š9 days). Median D-dimer within the first 7 days of hospitalization was higher (6450 vs. 1596 ng/mL, p < 0.001) in VTE cases compared to non-VTE cases, and was predictive of VTE (area under the curve [AUC] = 0.72, optimal threshold 2500 ng/mL) although not of mortality (AUC 0.55, P = .34). Change in D-dimer level (AUC = 0.72 P = .004) and rate of D-dimer rise (AUC = 0.75 P = .001) were also predictive of VTE, though neither predicted death (P > .05 for all). Within the first 7 days of hospitalization, peak D-dimer level of >2500 ng/mL and a rate of change exceeding 150 ng/mL/d were predictive of future diagnosis of VTE. Rise in D-dimer >2000 ng/mL within any 24 hour period through hospital day 10 had 75% sensitivity and 74% specificity for diagnosis of VTE.We found that both magnitude and rate of rise in d-dimer within the first 10 days of hospitalization are predictive of diagnosis of VTE but not mortality. These parameters may aid in identifying individuals with possible underlying VTE or at high risk for VTE, thereby guiding risk stratification and anticoagulation policies in COVID-19 patients.

Long-term outcomes after percutaneous patent foramen ovale closure.

Percutaneous patent foramen ovale (PFO) closure is a treatment for cryptogenic stroke and migraine headache. The goal of this study was to assess long-term outcomes of patients treated with percutaneous PFO closure. Records of patients with percutaneous PFO closure at Emory University Hospital from February 2002 to July 2009 were reviewed. Follow-up telephone questionnaire and chart review assessed recurrent stroke, migraine, and complications. Data was reviewed on 414 consecutive patients. Long-term follow-up was obtained in 207 of patients, and mean follow up was 4.6 ± 2.0 years. Cryptogenic stroke was the primary indication for intervention in 193 (93%) patients. Thirteen (7%) patients had a recurrent neurologic event post closure. In patients with multiple neurological events at baseline, 17% (n = 11) had a recurrent event, compared with 2% (n = 2) of patients with a single neurological event prior to PFO-closure (P < 0.002). Post closure, migraine frequency and severity declined from 4.5 to 1.1 migraine/month (P < 0.01) and 7.2 to 3.6 out of 10 (P < 0.01) in patients with history of migraine (n = 60). Thirty-day mortality was 1% (n = 2). One patient had device erosion 5 years post-procedure requiring emergent surgery. Atrial fibrillation was newly diagnosed in 8 (4%) patients within 6 months. In conclusion, the long-term rate of recurrent stroke after PFO closure is low in patients with a single neurological event at baseline. Serious long-term complications after PFO closure are rare. PFO closure may decrease the frequency and severity of migraine.

Long-term neurocognitive and neuroimaging outcomes in posterior reversible encephalopathy syndrome: two case reports and implications.

Posterior reversible encephalopathy syndrome (PRES) is a neurotoxic and neurometabolic state associated with a distinct appearance on computed tomography and magnetic resonance imaging, as well as particular clinical features. While PRES is defined as a reversible condition, instances of irreversible or persisting cytotoxic edema have been reported and appear to be associated with poor outcomes. Studies addressing the post-acute neurocognitive findings in persisting/irreversible PRES are lacking. We report two cases of persisting PRES with associated neurocognitive deficits and functional limitations following acute presentation. Neuroimaging revealed abnormalities within the posterior parietal lobes, along with bilateral involvement of the occipital and frontal lobes. The results from the neuropsychological examination revealed a pattern of impairment generally affecting spatial-perceptual and related functions and aspects of executive function. These cases document instances of irreversible/persisting PRES with associated neurocognitive deficits and functional limitations generally corresponding with the areas implicated on neuroimaging. Studies addressing the post-acute neurocognitive presentation and functional outcomes of PRES are needed.