Ischemic Cerebrovascular Events Research Articles

Predictive Value of Supraventricular Short Runs for New-Onset Atrial Fibrillation in Patients with Ischemic Stroke.

The clinical importance of supraventricular run (SVR) is uncertain in the management of patients with previous cerebrovascular events. We aim to evaluate the role of SVRs in the development of future atrial fibrillation (AF) in patients diagnosed with ischemic stroke. We retrospectively evaluated patients who underwent 24-h Holter monitoring for the evaluation of possible AF after ischemic cerebrovascular events. The presence and duration of SVR were noted. Subsequent diagnosis of AF was searched in patients with sinus rhythm. A total of 694 patients were included in the analysis. SVR was detected in 104 (14.9%) patients in the study group. Seventy-one (10.2%) patients were diagnosed with AF in the follow-up. SVRs were more prevalent among patients with AF (P < 0.001). The median atrial run duration was 5.96 (2.02-17.84) s in the AF absent group vs. 8.76 (3.78-17.62) s in the AF present group (P < 0.001). The best predictive cut-off duration of an atrial run was 8 s (sensitivity = 61.5% and specificity = 74.4%, Area Under Curve (AUC) = 0.708). Cox regression analysis showed that age (odds ratio [OR]: 1.03, 95% confidence interval [CI]: 1.00-1.060, P = 0.020), presence of short supraventricular run (OR: 2.53, 95% CI 1.40-4.57, P = 0.002), and left atrial diameter (OR: 1.13 95% CI: 1.07-1.19, P < 0.001) were the independent predictors of AF development in the follow-up. Age, left atrial diameter, and the presence of SVRs are associated with an increased risk of future AF after ischemic stroke. SVR duration may be an important parameter in risk stratification.

Complication Rate After Carotid Endarterectomy Comparing Patch Angioplasty and Primary Closure: Long-Term Outcome

Objective: In patients with symptomatic or asymptomatic severe internal carotid artery stenosis, carotid endarterectomy (CEA) has been shown to reduce risk for stroke. The optimal surgical technique remains subject of debate. In the latest European Society of Vascular Surgery (ESVS) guidelines on the management of atherosclerotic carotid disease, routine patching is preferred to routine primary closure. However, there are no RCT’s evaluating selective patching strategies. This follow-up study aimed to assess long term complication rate and restenosis after carotid endarterectomy with selective patching. Methods: Two hundred thirteen consecutive carotid endarterectomies over a 3-year period from January 5th 2011 to December 19th 2013 were prospectively analyzed in a follow-up study over 5 years (mean 4.6, range 3.17-6.17). Patient population consisted of 141 procedures on males and 72 on females with mean age 73 years at the time of surgery (standard deviation (SD) 8.57, range 53-95). There was a follow-up of 89%. Postoperative risk factors were assessed such as hypertension, diabetes mellitus, coronary artery disease and smoking. Postoperative symptoms of cranial nerve injury, transient ischemic events, cerebrovascular events and mortality were evaluated. Duplex ultrasound was performed by a radiologist blinded to the operative technique to evaluate patency of the carotid artery after carotid endarterectomy. Results: Primary closure was used in 110 operations, and patch angioplasty in 103 procedures (Dacron patch). Primary closure was performed when the carotid artery had a diameter above 5 mm, when there was a high carotid bifurcation or when the contralateral carotid artery was occluded. There were no significant differences among groups' baseline characteristics at the time of surgery. Primary closure was performed significantly more in male patients (P= .02). Overall complication rate was 3.76% postoperatively (1.8% after primary closure, 5.8% after patch angioplasty) and after 5 years 5.29% (2.0% after primary closure, 9.1% after patch angioplasty). There are no significant differences in results between the two groups (P= .09 and P= .05). In four cases patients experienced symptoms of cranial nerve damage postoperatively, two in each group. In one of the two cases in each group, the patient fully recovered and the other had persistent complaints (P-value= 1). None of the patients experienced amaurosis fugax during the 5-year follow up period. In five cases a patient had an ipsilateral cerebrovascular thrombosis in the group after patch angioplasty compared to zero in the primary closure group (P-value= .02). In the group of primary closure there was a mortality of 26 patients (23.6%) compared to 26 (25.2%) patients after patch angioplasty (P-value = .70). One was caused by cerebral hyperperfusion syndrome within one month postoperative after patch angioplasty and none were caused by an ipsilateral ischemic stroke. Objective duplex ultrasound showed no significant difference comparing restenosis in both groups (P-value= .43). In twelve cases patients showed a restenosis between 50-70% (6 primary closure and 6 patch angioplasty), none of the patients had high grade restenosis of more than 70%. Patient characteristics did not show a significant effect on long term outcomes. There was a correlation between postoperative use of antihypertensive medication and long-term stroke (P-value= .006), restenosis (P-value= .01) and mortality (P-value= .003). Conclusion: After long-term follow-up we found primary closure and patch angioplasty to be equivalent with respect to complication rate and restenosis when used in selected cases. Best medical treatment and especially the use of antihypertensive medication should be emphasized.

Increased circulating levels of MIP-1α and CD14 are associated with the presence of severe stenosis and hypoechoic plaques in patients with carotid atherosclerosis.

Carotid atherosclerosis, a major cause of ischemic cerebrovascular events, is characterized by a pro-inflammatory and pro-oxidant vascular microenvironment. The current risk score models based on traditional risk factors for cardiovascular risk assessment have some limitations. The identification of novel blood biomarkers could be useful to improve patient management. The aim of the study was to evaluate the association of selected inflammation- and oxidative stress-related markers with the presence of severe stenosis and/or vulnerable plaques. Circulating levels of soluble CD40 ligand, interleukin-10, macrophage inflammatory protein (MIP)-1α, endoglin, CD163, CD14, E-selectin, tumor necrosis factor-α, monocyte chemoattractant protein-1, C-Reactive protein, CD40L + T lymphocytes, total antioxidant capacity, glutathione reductase activity, and protein carbonyl content were determined in patients with carotid atherosclerosis. Multiparametric analysis showed significantly higher levels of MIP-1α in patients with stenosis ≥70% than in patients with stenosis <70%, and significantly higher levels of CD14 in patients with hypoechoic (vulnerable) lesions compared to those with hyperechoic (stable) ones. The area under the curve obtained by the receiver operating characteristic curve analysis was 0.7253 for MIP-1α and 0.6908 for CD14. Our data suggest that circulating MIP-1α and CD14 levels are associated with the presence of advanced stenosis and of vulnerable carotid plaques.

Relationship between circulating adipokines and cholesterol efflux in subjects with severe carotid atherosclerosis

AimsCholesterol efflux capacity (CEC) as a measure of high-density lipoprotein functionality is independently and inversely associated with increased risk of cardiovascular events and mortality, and advanced plaque morphology. Adipokines, adipose tissue-derived factors, can influence systemic lipoprotein metabolism, and participate in the regulation of vascular function and inflammation. We aimed to investigate the association between CEC and circulating adipokine levels (anti-inflammatory adiponectin, and pro-inflammatory chemerin and resistin) in subjects with severe carotid atherosclerotic disease and evaluate its impact on post-surgical outcomes. Methods and resultsThis is a cross-sectional study with a 5-year follow-up component. Consecutive patients with severe carotid atherosclerosis scheduled for a carotid endarterectomy were recruited from hospital-based centres in Montreal, Canada (n = 285). Fasting blood samples were collected pre-operatively and used to measure plasma total and high-molecular weight (HMW) adiponectin, chemerin, and resistin, and to perform cholesterol efflux assays in J774 macrophage-like cells. Five-year post-surgery outcomes were obtained through medical chart review. Subjects had a mean age of 70.1 ± 9.4, were 67.0 % male, had various comorbidities (hypercholesterolemia [85.3 %], hypertension [83.5 %], type 2 diabetes [34.5 %], coronary artery disease [38.6 %]), and previously experienced cerebrovascular symptomatology (77.9 %). CEC was independently and positively associated with total and HMW adiponectin levels (ß [95 % confidence interval]; 0.216 [0.134–0.298] and 0.107 [0.037–0.176], respectively) but not with chemerin or resistin. Total adiponectin had the greatest association accounting for 8.3 % of the variance in CEC. Interaction regression models demonstrated a significant interaction between adiponectin and chemerin in increasing CEC. Notably, with each unit increase in CEC there was a 93.9 % decrease in the odds of having an ischemic cerebrovascular event 5 years post-surgery (0.061 [0.007–0.561]). ConclusionsOur findings demonstrated circulating adiponectin to have a strong association with increased CEC in subjects with severe carotid atherosclerosis and high CEC to be associated with more favourable post-surgical outcomes. These findings reflect the importance of adipose tissue health in influencing CEC levels and atherosclerotic cardiovascular disease risk.

Correlations among peripheral blood markers, white matter hyperintensity, and cognitive function in patients with non-disabling ischemic cerebrovascular events.

Both inflammation and cerebral white matter injury are closely associated with vascular cognitive impairment (VCI). The aim of this study was to analyze the correlation between peripheral serological markers, white matter injury, and cognitive function in patients with non-disabling ischemic cerebrovascular events (NICE); to identify potential biological markers for the diagnosis and prediction of VCI; and to provide a basis for the early diagnosis and intervention of VCI. We collected clinical data, along with demographic and medical history data, from 151 NICE patients. Fasting venous blood samples were collected. Based on the Montreal Cognitive Assessment (MoCA) after admission, we divided the patients into normal cognitive function (NCF) and VCI groups, and then classified them into mild white matter hyperintensity (mWMH) and severe white matter hyperintensity (sWMH) based on Fazekas scores. The differences in serological marker levels were compared between the cognitive function groups and the white matter hyperintensity groups. Binary logistic regression models and receiver operating characteristic curves were used to analyze the diagnostic predictive value of serological markers for VCI in patients with NICE and in the white matter hyperintensity subgroups. Among 151 patients with NICE, 95 were male and 56 were female. Lymphocyte count (OR = 0.405, p = 0.010, 95% CI [0.201, 0.806]), red blood cell count (OR = 0.433, p = 0.010, 95% CI [0.228, 0.821]), and hemoglobin level (OR = 0.979, p = 0.046, 95% CI [0.958, 0.999]) were protective factors for cognitive function in patients with NICE. The sWMH group had a higher age, granulocyte/lymphoid ratio (NLR), and neutrophil percentage but a lower MoCA score, hemoglobin level, and lymphocyte count than the mWMH group. In the mWMH group, lymphocyte count (AUC = 0.713, p = 0.003, 95% CI [0.593, 0.833]) had an acceptable predictive value for the diagnosis of VCI, whereas white blood cell count (AUC = 0.672, p = 0.011, 95% CI [0.545, 0.799]), red blood cell count (AUC = 0.665, p = 0.014, 95% CI [0.545, 0.784]), and hemoglobin level (AUC = 0.634, p = 0.047, 95% CI [0.502, 0.765]) had marginal predictive value for the diagnosis of VCI. In the sWMH group, no significant differences were found in serological markers between the NCF and VCI groups. Lymphocyte count, red blood cell count, and hemoglobin level were independent protective factors for cognitive function in patients with NICE; they can be used as potential biological markers to distinguish VCI in patients with NICE and are applicable to subgroups of patients with mWMH.

EE498 Cost of Follow-Up After an Ischemic Cerebrovascular Event in Patients With Atherosclerotic Cardiovascular Disease in Spain: Results from the Reality Study

Ischemic cerebrovascular events stroke and transient ischemic attack (TIA) are a cause of morbidity and mortality in developed countries and entails a high resources consumption and costs for health systems. These patients have an increased risk of suffering a new event with the consequent additional resource consumption and an increased follow-up cost.

Multi-institutional patterns of clopidogrel response among patients undergoing transcarotid artery revascularization.

Current guidelines recommend dual antiplatelet therapy (DAPT) in patients undergoing carotid artery stenting. The most common DAPT regimen is aspirin and clopidogrel, a P2Y12 receptor antagonist; however, the prevalence of clopidogrel resistance (CR) in patients undergoing percutaneous coronary interventions may exceed 60%. Few studies have investigated the prevalence and impact of CR in patients undergoing extracranial carotid artery stenting, particularly transcarotid artery revascularization (TCAR). Consecutive high-risk patients ≥ 18years who underwent TCAR for high grade (≥70%) and/or symptomatic (≥50%) carotid stenosis with preoperative P2Y12 testing between August 2019 and December 2021 were identified across five institutions. Preoperative platelet reactivity was measured with the VerifyNow P2Y12 Reaction Unit (PRU) Test (Instrumentation Laboratory, Bedford, MA), with CR defined as PRU ≥ 194 and hyper-response as PRU <70. Patients without preoperative P2Y12 testing within 30days prior to TCAR or those on a non-clopidogrel P2Y12 inhibitor preoperatively were excluded. The primary outcome of interest was prevalence of CR. Secondary outcomes of interest included the incidence of ischemic and hemorrhagic complications. Of 92 patients identified, the majority were male (59%) and Caucasian (75%) with a mean age of 75years (±8, range 56-92). Preoperatively, 93% of patients were on aspirin, 100% on clopidogrel, and 13% on therapeutic anticoagulation. At presentation, 36% were symptomatic. The mean preoperative P2Y12 was 156 PRU (±76, range 6-349). In total, 30 (33%) patients met criteria for CR (mean PRU 240 ± 37; range 197-349), and 15 (16%) met criteria for hyper-responder (mean PRU 38 ± 20; range 6-68). There was no significant difference by clopidogrel response phenotype in terms of sex (p = 0.246), race (p = 0.384), or symptomatic presentation (p = 0.956). Postoperatively, the cumulative incidence of stroke and MI was 2.1%, with no statistically significant difference in the incidence of in-hospital stroke (PRU 238, p = 0.489) or MI (PRU 168, p = 1) between clopidogrel phenotypes. Three (3.3%) patients, one CR (PRU 240) and two responders (PRU 119 and PRU 189), experienced postoperative access site hematomas that required no subsequent intervention. No other index hospitalization hemorrhagic complications occurred. Using preoperative P2Y12 testing with a threshold PRU ≥ 194 to define CR, we identified a high prevalence of CR in patients undergoing TCAR similar to that in the pre-existing coronary literature. We found no significant differences in postoperative ischemic or hemorrhagic complications by clopidogrel response phenotype, although complication rates in the overall study cohort were low. CR may be a spectrum from responder to partial responder to complete non-responder, and this may account for the differences in our CR cohort compared to the ROADSTER 2 protocol deviation cohort. Further investigation is warranted to determine if a quantitative assessment of CR is sufficient to identify patients at risk of developing secondary cerebrovascular ischemic events in this patient population.

Atrial cardiomyopathy markers predict ischemic cerebrovascular events independent of atrial fibrillation in patients with acute myocardial infarction.

Contemporary data on atrial cardiomyopathy (ACM) markers and ischemic cerebrovascular events (ICVE) in patients with acute myocardial infarction (AMI) is lacking. We aimed to examine whether ACM markers predict ICVE among AMI patients. A total of 4,206 AMI cases diagnosed in clinical examinations between January 2016 and June 2021 were assessed for markers of ACM including B-type natriuretic peptide (BNP), P-wave terminal force in ECG lead V1 (PTFV1), and left atrium diameter (LAD). Left atrial enlargement (LAE) and abnormal PTFV1 were defined by previously published cut-off points. The primary outcome was incident ICVE composed of ischemic stroke (IS) and transient ischemic attack (TIA). Receiver operating curve analyses were used to compare the predictive performance of the CHA2DS2-VASc score combined with ACM markers to the CHA2DS2-VASc score alone. During a median follow-up of 44.0 months, 229 (5.44%) ICVE occurred. Of these, 156 individuals developed IS and the remaining 73 cases were diagnosed with TIAs. The ICVE group showed larger PTFV1 and increased LAD as well as elevated BNP levels at baseline. In the multivariate analysis, we found significant associations with ICVE for PTFV1 (HR per 1,000 μV*ms, 1.143; 95% CI, 1.093-1.196), LAD (HR per millimeter, 1.148; 95% CI, 1.107-1.190), but not BNP after adjusting for known ICVE risk factors and interim atrial fibrillation (AF). The addition of abnormal PTFV1 and LAE improved the predictive accuracy of the CHA2DS2-VASc score with C-statistic increasing from 0.708 to 0.761 (p < 0.001). Atrial cardiomyopathy markers including PTFV1 and LAD were associated with incident ICVE independent of well-established risk factors and AF occurrence. The addition of ACM markers with CHA2DS2-VASc score may well discriminate individuals at high risk of ICVE in AMI patients.

Factors affecting self-reported bleeding acceptance in acute ischemic stroke survivors on various types of antithrombotic therapy

ObjectivesPrior ischemic cerebrovascular event and younger age have been shown to increase bleeding acceptance among anticoagulated outpatients with atrial fibrillation (AF). We sought to determine factors affecting bleeding acceptance in acute ischemic stroke (AIS) survivors on various types of antithrombotic therapy. Materials and MethodsWe enrolled 173 consecutive patients hospitalized for AIS (aged 68.2±11.7 years, 54.9% male), including 54 (31.2%) with AF, who had favorable functional outcome. On discharge, the Bleeding ratio, defined as the declared maximum number of major bleedings that a patient is willing to accept to prevent one major stroke, was evaluated. We assessed the predicted bleeding risk in non-cardioembolic and cardioembolic stroke survivors using S2TOP-BLEED and HAS-BLED scores, respectively. ResultsPatients with the low Bleeding ratio, defined as 5 (median) or less accepted bleeds (n=92; 53.2%), were older and more likely to receive thrombolysis and/or thrombectomy, with no impact of previous stroke. Prior major bleed (odds ratio [OR] 4.67; 95% confidence interval [CI] 0.92-23.72), AF with use of oral anticoagulants (OR 2.35, 95% CI 1.12-4.93), reperfusion treatment (OR 1.95, 95% CI 1.02-3.76), and hospitalization ≤10 days (OR 4.56; 95% CI 1.50-13.87) were associated with the low Bleeding Ratio. Prior use of anticoagulants or aspirin as well as HAS-BLED and S2TOP-BLEED scores did not affect the bleeding acceptance. ConclusionsLower bleeding acceptance declared on discharge by AIS survivors is determined by prior bleeding, anticoagulation in AF, reperfusion treatment, and duration of hospitalization, which might affect medication adherence. The results might help optimize post-discharge management and educational efforts in patients on antithrombotic therapy.

Prevalence of the JAK2V617F Mutation in Patients with Ischemic Stroke

Introduction: Patients with the Philadelphia negative myeloproliferative neoplasms (MPN) have an increased risk of thromboembolic events, ischemic cerebrovascular events in particular. The somatic mutation JAK2V617F is associated with MPN with a prevalence of 96% in polycythemia vera (PV), 55% in essential thrombocythemia (ET), and 65% in primary myelofibrosis (PMF). The JAK2V617F mutation is found to be an independent risk factor for thrombosis in patients with MPN. However, whether the JAK2V617F mutation is a risk factor for arterial thrombosis in the absence of an MPN diagnosis is still uncertain. The sensitivity of the assay used for detection is crucial when assessing the presence of the JAK2V617F mutation. A higher sensitivity enables detection of lower allele burdens. This is illustrated by the varying prevalences (0.1-3.1%) in background population studies. In the Danish population study GESUS of approximately 20.000 individuals, the JAK2V617F mutation was detected by droplet digital PCR (ddPCR) with an assay sensitivity of 0.009%. The GESUS study found a JAK2V617F prevalence of 3.1%. Similarly, prevalence studies of JAK2V617F mutation in stroke have varying detection limits from 0.01-5% mutant alleles. The vast majority of these studies are retrospective studies in younger subpopulations of stroke patients. We aimed to investigate the prevalence of the JAK2V617F mutation in a prospective design of consecutively enrolled unselected patients with ischemic stroke or transient ischemic attack by the highly sensitive ddPCR. Method: We recruited 90 consecutive patients with ischemic stroke or transient ischemic attack during admission at the Department of Neurology, Zealand University Hospital, Denmark. A blood sample was taken within 7 days of the onset of symptoms and screened for the JAK2V617F mutation by ddPCR. Patients unable to give informed consent were excluded from the study. Results: Out of 90 patients (mean age 71, range 46-92; female 37%) with ischemic stroke or transient ischemic attack, the JAK2V617F mutation was found in 11 patients (12.2%). Allele burdens ranged from 0.0021 to 24. All 11 patients suffered an ischemic stroke. Six out of 11 patients with the JAK2V617F mutation had elevated blood cell levels i.e. erythrocytosis, thrombocytosis, and/or leukocytosis at the time of recruitment. Only three patients had continuously elevated blood cell levels after 1 month. Patient no. 6 with a JAK2V617F mutation allele burden of 34% had blood cell levels meeting the diagnostic criteria for MPN and was diagnosed with ET. Patient no. 2 had a JAK2V617F allele burden of 14% and increased levels of hemoglobin and platelet count, which both normalized spontaneously after 1 month. The patient was referred for a hematological workup and was found to have mild splenomegaly and a bone marrow biopsy showing myeloproliferative features. In light of the normal blood cell parameters, patient no. 2 was diagnosed with MPN-U. The patients with a JAK2V617F mutation are presented in table 1. Additional data will be presented at ASH. Conclusion and implications: The present study reveals a JAK2V617F mutation prevalence (12.2%) in a stroke population that is substantially higher compared to the background population (GESUS) in the same region of Denmark, using the same assay. The GESUS study showed a JAK2V617F mutationprevalence of 3.1% and for individuals above age 60 a prevalence of 4.1%. Given the fact that the JAK2V617F mutation is present in patients with and without cytosis, our results highly suggest that the JAK2V617F mutation per se is a thrombogenic factor in ischemic stroke. This calls for an exploration of the pathophysiological mechanisms and potential treatments to prevent future thrombotic events in individuals with and without cytosis. Table legend: Clinical and paraclinical characteristics of ischemic stroke patients with the JAK2V617F mutation. IS, ischemic stroke; TIA, transient ischemic attack; HTN, hypertension; HLP, hyperlipidemia; AF, atrial fibrillation; IHD, ischemic heart disease; DM2, diabetes mellitus type 2; Hb, hemoglobin; PLT, platelet count; WBC, white blood cells. Figure 1View largeDownload PPTFigure 1View largeDownload PPT Close modal

Acute Venous and Arterial Thromboembolic Events in Patients with Monoclonal Gammopathy of Undetermined Significance: A Nation Wide Analysis

Introduction: Monoclonal Gammopathy of Undetermined Significance (MGUS) is a premalignant plasma cell disorder. It is found in over 3% of patients who are 50 years of age or older (Kyle et al., 2006). MGUS is usually asymptomatic; however, it carries an increased risk of certain comorbidities. Some literature suggests an increased risk of venous and arterial thromboembolism in MGUS patients. We sought to examine this relationship using data from the National Inpatient Sample (NIS). Methods: We conducted a cross-sectional study using data from the NIS from the year 2016. We evaluated the frequencies of composite venous and composite arterial thromboembolism outcomes in adult patients with MGUS compared with those who had no history of the disease. IBM SPSS 26.0 was used for analysis. We constructed several logistic regression models to adjust for common confounding variables, including age, sex, race, and expected primary payer. Adjusted odds ratios and confidence intervals were calculated for each composite and component variable. Chi-square tests were used for comparing categorical variables. Results: We identified a total of 8500 patients with the diagnosis of MGUS. Among patients with MGUS, 135 patients (1.6%) had the primary diagnosis of a venous thromboembolic event. These included 55 patients (0.65%) who had acute deep vein thromboembolic events and 80 patients (0.94%) who had pulmonary embolism. Also, 374 patients (4.4%) had the primary diagnosis of an arterial thromboembolic event. These arterial events were divided into 3 categories as follows: 171 discharges (2.01%) were acute thrombo-embolic cardiac events, 190 discharges (2.24%) were acute cerebrovascular ischemic events, and 13 discharges (0.15%) with other arterial thromboembolic events. Patients with MGUS had an increased risk of the composite venous thromboembolism outcome (adjusted odds ratio [OR] 1.271, 95% CI 1.069-1.512). Analysis of the individual components showed a significant increase in the risk of acute deep vein thrombosis (adjusted OR 1.366, 95% CI 1.047-1.782) but failed to show a significant association with the risk of pulmonary embolism (adjusted OR 1.207, 95% CI 0.962-1.513). On the other hand, we found a reduced risk of composite arterial thromboembolism outcome in patients with MGUS (adjusted OR 0.617, 95% CI 0.555-0.685). Individual components analysis showed a reduction in the risk of acute thromboembolic cardiac events (adjusted OR 0.636, 95% CI 0.546-741) and acute ischemic cerebrovascular events (adjusted OR 0.595, 95% CI 0.514-689), but no significant difference was noted in the third group which included other arterial thromboembolic events (adjusted OR 1.343, 95% CI 0.779-2.317). Conclusion: Patients with MGUS had increased odds of developing acute venous thromboembolism, especially deep vein thrombosis, when compared to patients who had no history of MGUS. Interestingly, MGUS patients had reduced odds of developing acute cardiac and cerebrovascular arterial thromboembolic events. More research is required to assess the optimal approach for venous thromboembolism prophylaxis in MGUS patients.

Associations of Warfarin Use with Risks of Ischemic Cerebrovascular Events and Major Bleeding in Patients with Hyperthyroidism-Related Atrial Fibrillation.

The use of oral anticoagulants for patients with new-onset hyperthyroidism-related atrial fibrillation (AF) is controversial. We aimed to evaluate the clinical benefits of warfarin therapy in this population. This retrospective cohort study used a data-cut of Taiwan Health and Welfare Database between 2000 and 2016. We compared warfarin users and nonusers among AF patients with hyperthyroidism. We used 1:2 propensity score matching to balance covariates and Cox regression model to calculate hazard ratios (HRs). The primary outcome was risk of ischemic stroke/transient ischemic attack (TIA), and the secondary outcome was major bleeding. After propensity score matching, we defined 90 and 168 hyperthyroidism-related AF patients with mean (SD) age of 59.9 ± 13.5 and 59.2 ± 14.6 in the warfarin-treated group and untreated group separately. The mean (SD) CHA2DS2-VASc scores for the two groups were 2.1 ± 1.6 and 1.8 ± 1.5, respectively. Patients with hyperthyroidism-related AF receiving warfarin had no significant risk of ischemic stroke/TIA (adjusted HR: 1.16, 95% confidence interval [CI]: 0.52-2.56, p = 0.717) compared to nonusers. There was a comparable risk of major bleeding between those receiving warfarin or not (adjusted HR: 0.91, 95% CI: 0.56-1.47, p = 0.702). The active-comparator design also demonstrated that warfarin use had no significant association with the risk of stroke/TIA versus aspirin use (adjusted HR: 2.43; 95% CI: 0.68-8.70). In conclusion, anticoagulation therapy did not have a statistically significant benefit on ischemic stroke/TIA nor risk of bleeding, among patients with new-onset hyperthyroidism-related AF under a low CHA2DS2-VASc score, by comparing those without use.

Localized Elevation of Wall Shear Stress Is Linked to Recent Symptoms in Patients with Carotid Stenosis

Background: Estimation of symptomatic and asymptomatic carotid atherosclerosis differences can be the basis for prevention and management of carotid artery stenosis disease. In clinical practice, carotid plaque vulnerability is assessed only on the basis of luminal stenosis. However, the evolution of carotid plaque from an asymptomatic state to a symptomatic one is a complex process and the underlying hemodynamic mechanisms are unknown. We aimed to investigate the differences in hemodynamic parameters between patients with recently symptomatic carotid stenosis and asymptomatic ones. Methods: Hemodynamic simulations were performed on 26 carotid plaques from 25 patients with carotid artery stenosis ≥50%, 16 of whom had recent cerebrovascular ischemic events. Using human-specific flow parameters and 3D reconstruction of carotid computed tomography angiography images, we assessed hemodynamic characteristics such as wall shear stress (WSS), time-averaged WSS (TAWSS), oscillatory shear index, and relative residence time (RRT) during the cardiac cycle in patients with and without symptoms. Results: We found that symptomatic carotid stenosis patients had greater local TAWSS (99.59 ± 26.29 vs. 60.40 ± 20.46 dyn/cm², p = 0.0007) and maximal WSS (116.65 ± 39.11 vs. 68.28 ± 23.67 dyn/cm², p = 0.003), but lower RRT (0.019 ± 0.006 vs. 0.013 ± 0.069 s, p = 0.049), than asymptomatic patients, but this hemodynamic difference was not associated with carotid stenosis severity (p = 0.70). Patients with transient ischemic attack (TIA) or stroke had higher local TAWSS and WSSmax than patients with asymptomatic stenosis (p < 0.05). Subgroup analysis showed that there was no statistical difference in local hemodynamic variables between TIA and stroke patients with carotid artery stenosis. Conclusions: Patients with carotid artery stenosis are more likely to experience acute ischemic cerebrovascular accidents if they have higher WSS. Simultaneous assessment with hemodynamic parameters like WSS along with stenosis severity may aid risk stratification in patients with asymptomatic carotid artery stenosis.

Colchicine pre-treatment and post-treatment does not worsen bleeding or functional outcome after collagenase-induced intracerebral hemorrhage.

Patients with intracerebral hemorrhage (ICH) are at increased risk for major ischemic cardiovascular and cerebrovascular events. However, the use of preventative antithrombotic therapy can increase the risk of ICH recurrence and worsen ICH-related outcomes. Colchicine, an anti-inflammatory agent, has the potential to mitigate inflammation-related atherothrombosis and reduce the risk of ischemic vascular events. Here we investigated the safety and efficacy of colchicine when used both before and acutely after ICH. We predicted that daily colchicine administration would not impact our safety measures but would reduce brain injury and improve functional outcomes associated with inflammation reduction. To test this, 0.05 mg/kg colchicine was given orally once daily to rats either before or after they were given a collagenase-induced striatal ICH. We assessed neurological impairments, intra-parenchymal bleeding, Perls positive cells, and brain injury to gauge the therapeutic impact of colchicine on brain injury. Colchicine did not significantly affect bleeding (average = 40.7 μL) at 48 hrs, lesion volume (average = 24.5 mm3) at 14 days, or functional outcome (median neurological deficit scale score at 2 days post-ICH = 4, i.e., modest deficits) from 1-14 days after ICH. Colchicine reduced the volume of Perls positive cells in the perihematomal zone, indicating a reduction in inflammation. Safety measures (body weight, food consumption, water consumption, hydration, body temperature, activity, and pain) were not affected by colchicine. Although colchicine did not confer neuroprotection or functional benefit, it was able to reduce perihematomal inflammation after ICH without increasing bleeding. Thus, our findings suggest that colchicine treatment is safe, unlikely to worsen bleeding, and is unlikely but may reduce secondary injury after an ICH if initiated early post ICH to reduce the risk of ischemic vascular events. These results are informative for the ongoing CoVasc-ICH phase II randomized trial (NCT05159219).

Amiloidosis cardiaca y cierre de aurícula izquierda. Estudio CAMYLAAC

Introduction and objectivesTransthyretin cardiac amyloidosis (ATTR-CA) patients often have atrial fibrillation and increased bleeding/thrombogenic risks. We aimed to evaluate outcomes of left atrial appendage closure (LAAC) compared with patients without a known diagnosis of CA. MethodsComparison at long-term of patients diagnosed with ATTR-CA who underwent LAAC between 2009 and 2020 and those without a known diagnosis of CA. ResultsWe studied a total of 1159 patients. Forty patients (3.5%) were diagnosed with ATTR-CA; these patients were older and had more comorbidities, higher HAS-BLED and CHA2DS2-VASc scores, and lower left ventricular function. Successful LAAC was achieved in 1137 patients (98.1%) with no differences between groups. Regarding in-hospital and follow-up complications, there were no differences between the groups in ischemic stroke (5% vs 2.5% in those without a known diagnosis of CA; P=.283), hemorrhagic stroke (2.5% and 0.8% in the control group; P=.284), major or minor bleeding. At the 2-year follow-up, there were no significant differences in mortality (ATTR-CA: 20% vs those without known CA: 13.6%, 0.248); however, the at 5-year follow-up, ATTR-CA patients had higher mortality (40% vs 19.2%; P <.001) but this difference was unrelated to hemorrhagic complications or ischemic stroke. ConclusionsLAAC could reduce the risk of bleeding complications and ischemic cerebrovascular events without increasing the rate of early or mid-term complications. Although long-term survival was impaired in ATTR-CA patients, it was comparable to that of patients without a known diagnosis of CA at the 2-year follow-up, suggesting that LAAC for patients with ATTR-CA might not be futile.Full English text available from:www.revespcardiol.org/en

Variations in atrial fibrillation screening after ischemic stroke or transient ischemic attack in Sweden

Abstract Background/Introduction The risk of recurrent stroke and mortality is high among patients with ischemic stroke or transient ischemic attack (TIA) and untreated atrial fibrillation (AF). Hence, AF screening after an event has high priority in national and international guidelines. Despite the abundance of evidence on AF detection using different AF screening modalities, there is still no evidence on a prognostic benefit of ECG monitoring post ischemic stroke. There is a risk for variations in clinical practice for AF screening after ischemic cerebrovascular events due to this gap of evidence. Purpose The aim of this study was to investigate the clinical practice of AF screening after TIA or ischemic stroke at Swedish stroke units. Methods In collaboration with the stakeholders of the Swedish stroke register (Riksstroke) important fields to study were identified, e.g. AF screening method, first choice of method (multiple answers possible), monitoring duration, clinical follow-up etc. A draft for a digital survey was constructed and then tested and revised by 5 stroke consultants. The survey consisted of 18 multiple choice questions with free text comments and was sent by e-mail to the medical supervisors at all stroke units in Sweden in November 2021. Results All 72 stroke units in Sweden responded to the survey. Almost all (69/72) stroke units reported that ≥75% of ischemic stroke patients are screened for AF. Of the stroke units 81% had inpatient telemetry as their first choice of AF screening method (Figure 1), but 7% had no access to inpatient telemetry. In case of inpatient telemetry, 30% reported 0–24 hours and 54% reported 24–48 hours as their standard monitoring time. Most had the attending physician at the stroke unit as the primary ECG reader, some with access to support from cardiologist. Different standard monitoring durations for Holter were used (Figure 2) and 17% reported Holter as their first choice of AF screening method. Approximately 85% reported repeated ECG monitoring if high suspicion of cardiac embolization, preferably with repeated Holter (73%) or handheld ECG (49%). Implantable loop recorder (6%), event loop recorder (14%) and 2 weeks registration with ECG-patch (3%) was more infrequently used for this purpose. Conclusions Clinical practice for AF screening after ischemic stroke or TIA at Swedish stroke units showed considerable variations with a range of different AF screening methods and monitoring durations. Further, the standards and quality of inpatient ECG monitoring is unknown. There is an urgent need for evidence and evidence-based recommendations in this field, the present situation also implies inequality in care. Funding Acknowledgement Type of funding sources: Foundation. Main funding source(s): Stiftelsen Hjartat

Telemedicine use and outcomes after transient ischemic attack and minor stroke during the COVID-19 pandemic: a population-based cohort study.

Background:The COVID-19 pandemic has led to an increase in telemedicine use. We compared care and outcomes in patients with transient ischemic attack (TIA) or minor ischemic stroke before and after the widespread adoption of telemedicine in Ontario, Canada, in 2020.Methods:In a population-based cohort study using linked administrative data, we identified patients with TIA or ischemic stroke discharged from any emergency department in Ontario before the widespread use of telemedicine (Apr. 1, 2015, to Mar. 31, 2020) and after (Apr. 1, 2020, to Mar. 31, 2021). We measured care, including visits with a physician, investigations and medication renewal. We compared 90-day death before and after 2020 using Cox proportional hazards models, and we compared 90-day admission using cause-specific hazard models.Results:We identified 47 601 patients (49.3% female; median age 73, interquartile range 62–82, yr) with TIA (n = 35 695, 75.0%) or ischemic stroke (n = 11 906, 25.0%). After 2020, 83.1% of patients had 1 or more telemedicine visit within 90 days of emergency department discharge, compared with 3.8% before. The overall access to outpatient visits within 90 days remained unchanged (92.9% before v. 94.0% after; risk difference 1.1, 95% confidence interval [CI] −1.3 to 3.5). Investigations and medication renewals were unchanged. Clinical outcomes were also similar before and after 2020; the adjusted hazard ratio was 0.97 (95% CI 0.91 to 1.04) for 90-day all-cause admission, 1.06 (95% CI 0.94 to 1.20) for stroke admission and 1.07 (95% CI 0.93 to 1.24) for death.Interpretation:Care and short-term outcomes after TIA or minor stroke remained stable after the widespread implementation of telemedicine during the COVID-19 pandemic. Our findings suggest that telemedicine is an effective method of health care delivery that can be complementary to in-person care for minor ischemic cerebrovascular events.

Natural history of carotid artery free-floating thrombus—A single center, consecutive cohort analysis

IntroductionCarotid free-floating thrombus (CFFT) is a rare cause of stroke and is thought to be associated with a high risk of recurrent cerebrovascular ischaemic events. The existing data on the natural history and optimal treatment modalities of CFFT is scanty and no clear recommendations exist.ObjectiveA retrospective analysis, single-center cohort of consecutive patients diagnosed with CFFT was conducted, investigating the risk for recurrent cerebrovascular ischaemic events.MethodsWe performed a single-center retrospective analysis including all patients presenting at our tertiary center between January 2005 and December 2020 with symptoms consistent with ischaemic stroke and/or transient ischaemic attack. Digital subtraction angiography (DSA), computed tomography angiography (CTA) or magnetic resonance angiography (MRA) were used to diagnose CFFT. In all included patients, CFFT was confirmed with a second imaging modality. CFFT was defined on imaging as a defect in contrast filling extending into the carotid lumen. We gathered information on vascular risk factors, diagnosis and follow-up methods, modality of treatment and neurological outcome. A survival analysis was performed, assessing the risk for recurrent cerebrovascular events.ResultsIn total, N = 62 patients presenting with symptomatic CFFT were included. Mean age was 68 years, 69% (43/62) of patients were male, 52% (32/62) current or previous smokers, 76% (47/62) suffered from arterial hypertension, 68% (42/62) from dyslipidaemia, and 31% (19/62) from diabetes mellitus. Overall, 71% (44/62) of patients received any kind of intervention [endovascular or surgical carotid thrombo-endartectomy (CEA)] at any time point during follow-up. Sixteen percent of patients (10/62) received intervention within 48 h after diagnosis of CFFT. The survival analysis and Kaplan-Meier model censoring patients at the time of intervention or last follow-up showed that the risk for any recurrent ischaemic stroke was 19.7% within the first 7 days and 27.4% within 3 months after diagnosis. No patients experienced a new ischaemic stroke beyond 11 days after diagnosis of CFTT (n = 17).ConclusionThe risk of recurrent ischaemic events in patients with CFFT is high, especially in the first week after diagnosis. Prospective studies are needed to further investigate the optimal management of these patients.

Effective Therapeutic Intervention for Left Atrial Appendage Thrombus: Percutaneous Left Atrial Appendage Closure

Objective: The thrombus formation in the left atrial appendage (LAA) can be challenging for operators and increases periprocedural complication risk. However, recent consensus documents discuss that left atrial appendage closure is a potential therapeutic option for malign left atrial appendage. This clinical study aimed to evaluate the procedural safety and early efficacy outcomes of left atrial appendage closure in patients with left atrial appendage thrombus. Methods: This observational single-center clinical trial included 18 patients with left atrial appendage thrombus. Transesophageal echocardiography was performed before and during the left atrial appendage closure in all patients. All procedures were performed using the Amplatzer Amulet left atrial appendage closure device (Abbott Medical Inc.). Results: Ten of the patients were male (55.6%). The mean ages were 69.6 ± 7.5 years. CHA2DS2-VASc and HAS-BLED scores were calculated at 5 (2-8) and 3 (1-6), respectively. In 4 patients (22.2%), left atrial appendage occlusion was indicated due to malign left atrial appendage. The significant bleeding event under oral anticoagulant treatment was the main indication in 12 patients (66.7%). All patients were referred to Transthoracic Echocardiography (TTE) and transesophageal echocardiography 30 days after the procedure. There were no major or minor adverse clinical events during the first month of follow-up. Also, no patient faced ischemic cerebrovascular events, including transient ischemic attack, hospitalization due to heart failure, or significant bleeding events. Neither device-related thrombus nor peridevice leak was observed in the Transesophageal echocardiography evaluation. Conclusions: Left atrial appendage closure in patients with left atrial appendage thrombus is a feasible and effective method to reduce thromboembolic risk. It can be performed as an alternative therapy to oral anticoagulants (OACs) in patients with contraindications to OACs or malign left atrial appendage.

Ischemic and Hemorrhagic Cerebrovascular Events Related to COVID-19 Coagulopathy and Hypoxemia.

Since the very beginning of the COVID-19 pandemic, numerous researchers have made an effort to determine the molecular composition of the SARS-CoV-2 virus, and the exact pathomechanism through which the virus exerts such a devastating effect on the host/infected organism. Recent scientific evidence highlights the affinity of the virus towards ACE2 receptors, which are widespread in multiple human systems, including the central nervous system (CNS) and cerebral vessels. Such an affinity may explain endothelial dysfunction and damage that is observed in COVID-positive patients in histopathological studies, with subsequent dysregulation of the cerebral circulation leading to transient or acute cerebrovascular accidents. In this paper, we aimed to evaluate the effects of COVID-related hypoxemia and direct viral invasion on the cerebral circulation, with special respect to the postulated pathomechanism, vulnerable groups of patients, clinical course and outcomes, as well as diagnostic imaging findings.