Recurrent Ischemic Events Research Articles

Impact of Vascular Service Centralization on the Carotid Endarterectomy Pathway: A Study at the Bedfordshire, Luton, and Milton Keynes Vascular Network.

Introduction Carotid endarterectomy (CEA) is the gold standard intervention for patients experiencing transient ischemic attacks (TIAs) or embolic strokes with >50% internal carotid artery (ICA) stenosis supplying index hemispheric territory. The recommended period for CEA is 14 days post-index event; this period carries a heightened risk for second ischemic events. However, implementation of this stringent timeline often encounters delays stemming from multifaceted factors. The centralization of vascular services, designed to enhance patient care, introduces a paradigm shift. Centralization's efficacy in improving patient outcomes, particularly in the CEA pathway, is a subject of ongoing investigation. Our study aims to discern the impact of centralized services on the timeliness of CEA for symptomatic carotid artery stenosis, shedding light on this complex interplay of factors. Methods This retrospective study analyzed CEA data at the Bedfordshire, Luton, and Milton Keynes Vascular Network between January 2021 and June 2023. Eligible patients exhibited symptomatic carotid artery stenosis, with asymptomatic cases; those unfit for surgery or receiving best medical therapy only were excluded. Patients were categorized by their primary referral location: Hub, Spoke-1, or Spoke-2. Demographic and referral data were collected, and timelines from symptom onset to surgery were recorded. Continuous variables were expressed as means and standard deviations, and categorical variables as counts and percentages. Box plots illustrated the relationship between referral origin and surgery timing, and the Classification and Regression Tree (CART) assessed second events. Statistical significance was determined using Fisher's exact and chi-square tests, with p<0.05 indicating significance. Results A total of 148 patients underwent CEA after implementing exclusion criteria. 35.5% (n=53)of patients were referred from the Hub, while 45.6% (n=67)and 18.8% (n=28)were from Spoke-1 and Spoke-2, respectively. 40% (n=59) received CEA within the recommended timeframe, and 15.4% (n=23) experienced a second ischemic event pre-surgery. Time from TIA clinic review to referral was 5.5±8 days and 16.4±20 days from vascular referral to surgery. Patterns of delays were observed, with Spoke-2 exhibiting the most significant delays. Notably, amaurosis fugax and embolic stroke correlated with recurrent ischemic events, emphasizing the importance of timely care in CEA. Conclusion Our study underscores the significant benefits and challenges of the Hub and Spoke model in vascular surgery. The growing referral delays from Spoke sites are concerning, emphasizing the need for a multi-disciplinary team approach within Spoke sites to ensure efficient and standardized care delivery.

Effect of collateral circulation in patients with multiple craniocervical artery stenoses.

Based on previous findings, collateral circulation in the brain is vital in mitigating cerebral ischemia's effects and influencing stroke risk. This retrospective study examined collateral circulation, admission ischemic stroke status, and long-term recurrence in patients with multiple craniocervical artery stenoses. Consecutive symptomatic internal carotid artery (ICA) stenosis patients from the First Affiliated Hospital of Soochow University were recruited. Baseline data including medical histories and neurological function at admission were collected. Imaging techniques assessed collateral compensative capacity. Multivariate logistic regression analysis was used to investigate the association between collateral circulation and case status. A total of 559 patients with symptomatic ICA stenosis were included, among whom 153 (27.4%) had concurrent moderate to severe vertebro-basilar artery (VBA) stenosis. Dizziness, weakness/numbness, and slurring of speech were the primary symptoms in all patients. Over 36 months, 71 (12.7%) patients experienced a recurrence of acute ischemic stroke (AIS). In multivariate analysis, collateral circulation was found to be negatively associated with AIS (regional leptomeningeal collateral [rLMC] scores: OR: 0.798, 95% CI: 0.743-0.857, p < 0.001; Tan scores: OR: 0.478, 95% CI: 0.336-0.679, p < 0.001). Meanwhile, the collateral circulation scores were significantly associated with the recurrence of AIS within 3 years (rLMC scores: OR: 0.926, 95% CI: 0.860-0.997, p = 0.042; Tan scores: OR: 0.467, 95% CI: 0.306-0.712, p < 0.001). Most associations remained significant in the subgroup of patients with VBA stenosis. Favorable collateral circulation in multiple craniocervical artery stenosis patients reduced long-term ischemic event recurrence. Stratifying treatment risks is essential for optimizing outcomes.

Predictors of recurrent cerebral ischemia after patent foramen ovale closure: A single center observational study

ObjectivesTranscatheter patent foramen ovale closure lowers recurrent stroke in patients with cryptogenic stroke or transient ischemic attack with an indication for closure. However, the incidence of recurrent stroke is not negligible and underlying pathophysiology remains largely unknown. We sought to evaluate the prevalence of recurrent ischemic neurological events and to assess its predictors after transcatheter patent foramen ovale closure. MethodsWe enrolled consecutive patients who underwent patent foramen ovale closure for secondary prevention of neurological ischemic events at the University Hospital of Parma between 2006 and 2021. Clinical and procedure-related features were collected for each patient. The incidence of recurrent ischemic neurological events was assessed at follow-up. ResultsWe enrolled a total of 169 patients with mean Risk of Paradoxical Embolism score at hospital admission of 6.4 ± 1.5. The primary indication was previous cryptogenic stroke (94 [55.6 %] subjects), followed by transient ischemic attack (75 [44.4 %]). Among patients with complete outcome data (n= 154), after a median follow-up of 112 months, recurrent cerebral ischemia occurred in 13 [8.4 %], with an annualized rate of 0.92/100 patients. The presence of obesity [OR 5.268, p = 0.018], Risk of Paradoxical Embolism score < 7 [OR 5.991, p = 0.035] and migraine [OR = 5.932 p = 0.012] were independent positive predictors of recurrent stroke/ transient ischemic attack after patent foramen ovale closure. ConclusionsThe presence of obesity, Risk of Paradoxical Embolism score < 7 and migraine were independent positive predictors of recurrent ischemic neurological events after patent foramen ovale closure.

Characteristics and prognosis of patients with elevated triglycerides in acute myocardial infarction: observational data from a large database over a 17-year period: High triglycerides in acute myocardial infarction

From a large regional registry, we aimed to address the characteristics and prognosis of patients with elevated triglycerides (TG) among patients hospitalized for an acute myocardial infarction (MI). From the multicenter database of the RICO survey, all consecutive patients hospitalized for an acute MI (2001-2017) and alive at discharge were included. Among the 10,667 patients included, 17.7% had elevated TG. When compared with patients with TG ≤ 200 mg/dL, patients with high TG (>200 mg/dL) were 10 years younger, had a higher BMI, were more frequently men, diabetic, and smokers. At 1-year follow-up, recurrent ischemic events were more frequent in elevated TG patients. In multivariate logistic regression analysis, high TG (OR (95%CI): 1.356 (1.095-1.679)) remained an independent estimate for recurrent ischemic events, even after adjustment for confounding factors. In our large population-based cohort, elevated TG are common in acute MI, and associated with residual risk of recurrent ischemic events, beyond traditional prognostic markers.

High-sensitivity troponin-i and risk of heart failure in individuals with suspected acute coronary syndrome

Abstract Background Serial high-sensitivity cardiac troponin-I (hsTnI) concentrations are associated with short- and long-term mortality and recurrent ischemic events in individuals with suspected acute coronary syndrome. However, the relation to subsequent heart failure events is less well established. Purpose To examine the association between single and serial hsTnI concentrations and subsequent hospitalization or outpatient contact for heart failure in subjects with suspected acute coronary syndrome. Methods Using Danish national registries, we identified persons without known heart failure who underwent two hsTnI measurements (Siemens TnI Flex® Reagent, 99th percentile upper reference limit, 45 ng/l) separated by 1-7 hours, during hospitalization for myocardial infarction, unstable angina, observation for suspected myocardial infarction, or chest pain from 2012 through 2019. Individuals were stratified according to their hsTnI concentration pattern from first to second measurement (main groups: normal, rising, persistently elevated, or falling) and the magnitude of hsTnI concentration change (secondary groups: &amp;lt;20%, &amp;gt;20 to 50%, or &amp;gt;50% in either direction). Finally, they were grouped into quantiles based on the first hsTnI measurement (&amp;lt; = 15 ng/l, 16-30 ng/l, 31-44 ng/l, &amp;gt; = 45 ng/l) to explore whether the risk of heart failure was greater with higher hsTnI concentrations. We calculated standardized risks of hospitalization or outpatient contact for heart failure using multivariable logistic regression with average treatment effect modeling. Results A total of 18,939 individuals were included of whom 21.9% were discharged with a diagnosis of myocardial infarction, 4.8% with unstable angina, and 73.3% with observation for suspected myocardial infarction or chest pain. Median age was 61.9 years, and 52.5% were male. With respect to known cardiovascular disease, 17.6% had coronary artery disease, 5.4% had undergone prior coronary revascularization, and 8.0% had atrial fibrillation or flutter. A total of 429 individuals received a diagnosis of heart failure within the first 30 days while an additional 526 were diagnosed from days 31-365. The standardized absolute risk was lowest in subjects with two normal hsTnI values (days 0-30: 0.45%; days 31-365: &amp;lt;0.01%) and highest in those with persistently elevated concentrations (days 0-30: 8.56%; days 31-365: 9.50%) (Figure). The degree of hsTnI within each main group did not appear to affect the risk of heart failure. Conversely, the risk of heart failure was positively associated with hsTnI concentrations measured on the first sample. Conclusions Among individuals with suspected acute coronary syndrome, those with a persistently elevated hsTnI concentration consistently had the highest risk of a subsequent hospitalization or outpatient contact for heart failure. In addition, there appeared to be a dose-response relationship between hsTnI concentrations and the risk of heart failure.Figure

Phenotyping coronary plaque by computed tomography in premature coronary artery disease

Abstract Background Premature coronary artery disease (CAD) is an aggressive chronic disease with multiple recurrences mostly related to the progression or complication of new coronary lesions. Purpose To compare coronary plaque characteristics of individuals with premature CAD with those of incidental plaques found in matched individuals free of overt cardiovascular disease, using coronary computed tomography angiography (CCTA). Methods 106 individuals with premature CAD were matched by age, sex, smoking status, family history of CAD, and dyslipidemia with 106 controls free of overt cardiovascular disease. CCTA were standardly analyzed for CAD-RADS score, plaque composition (calcified, partially or non-calcified), and the following four high-risk plaque (HRP) features : spotty calcification, positive remodeling, napkin-ring sign, and low-attenuation plaque. Results At least one coronary plaque was found in 85% of individuals with premature CAD vs. 62% of matched controls. The prevalence of non-calcified plaques was higher among individuals with premature CAD (65.1% vs. 30.2%, p&amp;lt;0,001), as well as spotty calcification (42.5% vs. 17.9%, p&amp;lt;0.001), positive remodeling (41.5% vs. 9.4%, p&amp;lt;0.001), low-attenuation plaques (24.5% vs. 3.8%, p&amp;lt;0.001) and napkin-ring sign (1.9% vs. 0.0%) (Figure 1). Individuals with premature CAD exhibited an average of 2.2 (±2.7) HRP features per person, while the control group displayed 0.4 (±0.8) HRP per person (p&amp;lt;0.001). Within a median follow-up of 24 [16,34] months, 24 ischemic recurrent events occurred in 24 individuals, all in the in premature CAD group. Individuals with premature CAD and recurrent ischemic event had more high-risk plaque features (4.3±3.9) than those without ischemic recurrence (1.5±1.9). They displayed more frequently non-calcified plaques (91.7% vs. 57.3%) with positive remodeling (75.0% vs. 31.7%) and low-attenuation plaques (45.8% vs. 18.3%) as compared to those without ischemic recurrence (Figure 2). Conclusions Coronary atherosclerosis in individuals with premature CAD is characterized by a high and predominant burden of non-calcified plaque and unusual high prevalence of high-risk plaque features, contributing to disease progression with multiple recurrences in this setting.HRP features in study populationHRP according to ischemic recurrence

Comparison of sodium-glucose co-transporter-2 inhibitors and glucagon-like peptide-1 receptor agonists in myocardial infarction patients with type 2 diabetes

Abstract Background Both sodium–glucose cotransporter 2 inhibitors (SGLT2i) and glucagon-like peptide-1 receptor agonists (GLP1-RA) have been shown to reduce the risk of adverse cardiovascular outcomes in type 2 diabetes mellitus (T2DM) patients with established atherosclerotic cardiovascular disease. Purpose The aim of this study was to assess the comparative effectiveness of SGLT2i and GLP1-RA in myocardial infarction (MI) patients with T2DM. Methods This observational cohort study included MI patients with T2DM who were treated with SGLT2i or GLP1-RA within 180 days of hospital discharge between 2013 and 2021. Data was acquired from the SWEDEHEART registry, a nationwide quality register. The co-primary endpoints of this study were a composite of MI, ischemic stroke and all-cause mortality (MACE) and a composite of heart failure hospitalisation (HHF) and all-cause mortality. Inverse probability of treatment weighting was used to adjust for differences in baseline covariates between the treatment groups. Results This study consisted of 617 patients who were treated with SGLT2i and 543 patients who were treated with GLP1-RA. We observed no statistically significant differences between SGLT2i and GLP1-RA concerning the risk of MACE (adjusted incidence rate 76 vs. 68 events per 1000 person-years; HR 1.09 [95% CI 0.85 - 1.40]) and the risk of HHF or all-cause mortality (adjusted incidence rate 52 vs. 50 events per 1000 person-years; HR 1.04 [95% CI 0.80 - 1.36]). Similarly, we did not observe any statistically significant differences between the treatment groups concerning the secondary outcomes of MI (adjusted incidence rate 63 vs. 53 events per 1000 person-years; HR 1.08 [95% CI 0.83 - 1.40]), stroke (adjusted incidence rate 7 vs. 6 events per 1000 person-years; HR 1.22 [95% CI 0.57 - 2.87]), HHF (adjusted incidence rate 45 vs. 38 events per 1000 person-years; HR 1.06 [95% CI 0.80 - 1.41]) and all-cause mortality (adjusted incidence rate 11 vs. 15 events per 1000 person-years; HR 1.06 [95% CI 0.63 - 1.82]). Conclusions There were no statistically significant differences between SGLT2i and GLP1-RA concerning the risk of recurrent ischemic events, HHF and all-cause mortality in this cohort of MI patients with T2DM.Cumulative incidence of events

Patent foramen ovale: high-risk echocardiographic features related to secondary stroke prevention

Abstract Introduction Patent foramen ovale (PFO) closure has long been a matter of debate concerning the impact of such procedure on preventing ischemic events recurrence. Recent reports support this strategy raising the issue of optimal patient selection based on anatomical high-risk characteristics evaluated by transoesophageal echocardiography (TEE) that may be associated with an increased risk of recurrence. Purpose Characterize PFO-related echocardiographic findings and clinical features of a cohort of Embolic Stroke of Undetermined Source (ESUS) patients (pts). Methods Unicentric, retrospective analysis of pts with ESUS diagnosis who underwent TEE between 1/2014 and 11/2019. Excluded pts aged older than 70 years. Clinical stroke characteristics and echocardiographic PFO features were analysed. Results A total of 124 pts were included in the analysis, presenting a mean age of 50±1.6 [20;68] years and female gender predominance (58.9%). 48.4% of ESUS pts had PFO (53% female). Regarding PFO pts, 38 (62.3%) had significant right-to-left shunt on TEE, which was statistically associated with cortical infarcts (78.9 vs 56.5%,p=0.037). 35pts (58.3%) had shunt occurring at rest and during the Valsalva manoeuvre; when associated to significant shunt there was a correlation with cortical located infarcts (82.1 vs 60.0%, p&amp;lt;0.001). 33 PFOs (54.1%) had tunnel-like morphology. Tunnel-like PFOs were associated with significant right-to-left shunt (78.8 vs 42.9%, p&amp;lt;0.001), atrial septum aneurysm (ASA) presence (68.8 vs 50.0%, p&amp;lt;0.001) and with haemorrhagic transformation of ischemic stroke (15.2 vs 3.6%, p=0.031). 34 PFO pts (60.7%) had ASA. Mean PFO length was 6.42±5.0mm and mean height was 3.2±2.0mm. Conclusion In this cohort, there was a similar number of pts with and without PFO. Regarding ESUS pts with PFO, the majority had significant right-to-left shunt that occurred at rest and during Valsalva manoeuvre and were associated with cortical located infarcts. Tunnel-like morphology and ASA were also frequent. Tunnel-like morphology were associated with haemorrhagic transformation of ischemic strokes. These findings support the proposal that PFO characterization should have an additional role in stratifying pts with ESUS and selecting them for device closure.

Abstract 15274: STEMI as Initial Manifestation of Essential Thrombocythemia

Background: Essential thrombocythemia (ET) is a myeloproliferative neoplasm of myeloid cell expansion, mainly excessive platelet production, associated with thrombotic complications. Myocardial infarction (MI) in the setting of ET can result from thrombosis in the absence of coronary atherosclerosis. Here we present a case of ST elevation MI in the setting of previously undiagnosed ET. Case Report: A 59-year-old male with hypertension presented to the ED with left upper extremity weakness which started upon waking. On exam, he was in acute distress and diaphoretic. EKG revealed sinus rhythm with ST elevation in II, III, aVF, V5, and V6 suggesting inferolateral STEMI (Figure 1A). Labs were notable for Hgb 8.5g/dL, white blood cell count 33k/μL, and platelets 1.9million/μL. Decision Making: He was loaded with aspirin and clopidogrel (dual antiplatelet therapy-DAPT) and taken for coronary angiogram which revealed 80-90% thrombotic occlusion of the left circumflex artery (Figure 1b). Thrombectomy was performed and a drug-eluting stent was placed. A bone marrow biopsy showed JAK2 positive ET with myelofibrosis. He was immediately started on hydroxyurea. Platelets remained elevated, thus pegylated IFN alpha-2a was started which normalized platelet count. He remained on DAPT through discharge with no recurrent ischemic events or in-stent thrombosis during the 45-day hospitalization post stent placement. Conclusion: Patients with ET are at high risk for arterial thrombosis regardless of the presence of traditional atherosclerotic risk factors. High-risk patients, which includes those age over 60 with JAK2 mutation or history of arterial thrombosis, should be treated prophylactically with aspirin and hydroxyurea for cytoreduction. MI may be the first clinical manifestation of ET, even in patients without atherosclerotic risk factors. Initial management in patients with ET presenting with STEMI includes PCI with DAPT and early cytoreductive therapy.

Abstract 16290: Lipoprotein (a) as a Predictor of Recurrent Myocardial Infarction/Coronary Revascularization in Patients With Acute Coronary Syndrome Who Underwent PCI: A Meta-Analysis of Observational Studies

Introduction: Lipoprotein (a) [Lp(a)] has been recognized as an independent predictor of atherosclerotic cardiovascular disease (ASCVD). However, there is limited data on the association between Lp(a) levels and risk of recurrent myocardial infarction (MI)/coronary revascularization in patients with acute coronary syndrome (ACS) who underwent percutaneous coronary intervention (PCI). Methods: PubMed/Medline, EMBASE, and Scopus were searched for studies evaluating the association of Lp(a) with recurrent ischemic events from the year 2000-2023. Patients with coronary artery disease or ACS with baseline Lp(a) who underwent PCI or coronary stenting and had outcomes as recurrent MI/ coronary revascularization were included. Random effects models and I 2 statistics were used for pooled hazard ratios (HR), odds ratio (OR), and heterogeneity assessment. A leave-one-out sensitivity analysis was also performed. Results: The initial search resulted in 651 articles, of which nine studies with 27964 patients (mean age 58-66 years, 74.79% male) were included. Of the nine studies, six were retrospective and three prospective. Mean±SD/Median (IQ) follow-up duration was four years [range 2-7 years]. There was an increased risk of recurrent MI/coronary revascularization associated with Lp(a) ≥30 mg/dL (OR, 1.44, 95% CI: 1.09-1.89, I 2 = 79.24%, p=0.009) (Fig 1a) and Lp(a) ≥10-30 mg/dL (OR, 1.19, 95% CI: 1.009-1.416, I 2 = 0%, p=0.039) (Fig 1b), but failed to reach significance with Lp(a) as a continuous variable (OR, 1.004, 95% CI: 0.998-1.009, I 2 = 85.02%, p=0.221) (Fig 1c). Leave-one-out sensitivity analysis showed an equivalent result for various Lp(a) cutoffs (Fig 1a, 1b, and 1c). Conclusions: Our meta-analysis suggests an association of raised Lp(a) with increased risk of recurrent MI/coronary revascularization in ACS patients who underwent PCI.

Abstract 16802: Disparities in the Prevalence of Atrial Fibrillation and Associated Risk Characteristics Among Black and White Acute Ischemic Stroke Patients Treated With Alteplase

Introduction: Earlier studies addressing racial disparity in patients with acute ischemic stroke (AIS) and atrial fibrillation included significantly lower percentage of blacks. Demographics and post-intervention risk among white vs. black patients with AIS and AF have not been reported in a community hospital setup. Methods: In this retrospective analysis, baseline demographics, procedural characteristics and one-year clinical outcomes were collected from hospital database and compared between blacks and whites who are admitted with AIS and treated with alteplase. Results: 228 and 274 black patients with AIS admitted to our hospital during 2016 to 2021 were included in the analysis. Blacks compared to whites were younger (67 ±13 vs. 74 ± 14 years) and had lower prevalence of cardioembolism (49% vs. 61%), atrial fibrillation (10% vs. 34%), coronary artery disease (17% vs. 26%), prior coronary artery disease or myocardial infarction (17% vs. 26%), depression (16% vs. 25%), dyslipidemia (53% vs. 65%), ischemic risk at admission (6.1 ± 3.6 vs. 8.2 ± 3.8), and NIHSS-obtained (11±11 vs. 14±13), but higher prevalence of small vessel disease (15% vs. 7.9%), cryptogenic stroke (20% vs. 13%), diabetes (39% vs. 25%), smokers (26% vs. 14%), drug/alcohol abuse (21% vs. 9%), prior stroke (24% vs.15%) and one year recurrent ischemic stroke (4.7 % vs. 1.3%) (p&lt;0.05 for all comparisons). Among patients with AF, blacks were of similar age compared to whites (75±13 vs. 79±14 years) and similar prevalence of cardioembolism (99% and 96%), prior myocardial infarction/coronary artery disease (26% vs. 30%) and obesity (59% vs. 48%, p=ns for all), but higher prevalence of prior stroke (48% vs. 20%), diabetes (41% vs. 22%), renal insufficiency 30% vs. 18%) and recurrent ischemic stroke (7.4% vs. 1.3%, p&lt;0.05 for all). Conclusions: Blacks patients with AIS exhibit distinct demographics and higher prevalence of recurrent ischemic events compared to whites. Despite lower prevalence, blacks with AIS have higher prevalence of comorbidities and recurrent stroke events in the presence of AF. These data provide springboard for ongoing biomarker studies at our hospital to understand the racial disparity in the underlying pathophysiology of stroke and associated outcomes in blacks.

Ventricular arrhythmias during ST-segment elevation myocardial infarction and arrhythmic complications during recurrent ischaemic events.

Ventricular arrhythmias during ST-segment elevation myocardial infarction and arrhythmic complications during recurrent ischaemic events.

Hemostasis Biomarkers and Long-Term Risk of Recurrent Cardiovascular Events and Bleeding Complications in Young Patients with an Ischemic Stroke

Background: Patients with ischemic stroke at a young age (18-50 years) have a persistent increased risk of recurrent ischemic cardiovascular events, despite antithrombotic treatment. Additionally, antithrombotic agents result in a higher risk of bleeding complications. Balancing hemostasis to prevent thrombotic events and minimizing the risk of hemorrhagic events is challenging. Previous research observed a hypercoagulable state and a significant degree of inflammation years after an acute ischemic stroke in young adults. It is known that an increased clotting tendency is a risk factor for a first ischemic stroke, especially in young adults. However, the risk profile of a recurrent event in these individuals can be different. To this end, our study aims to investigate the role of plasma pro- and anticoagulation biomarkers, platelet activation markers and thrombin generation parameters in the risk of recurrent ischemic arterial events and bleeding complications after a first ischemic stroke or transient ischemic attack (TIA) at a young age. Method: Patients from a single-center cohort study (the FUTURE cohort) with a first-ever TIA or ischemic stroke event between 1980 and 2010 were included. Blood was collected in 2010 and patients were followed on recurrent ischemic events or bleeding complications between 2010 and 2023. The following coagulation parameters were measured: blood cell count, Von Willebrand factor, active Von Willebrand factor, factor VIII, prothrombin, fragment 1.2, d-dimer, fibrinogen, fibrin degradation products, antithrombin, alpha-2-macroglobulin, serum CXCL-4 and CXCL-7. In addition, thrombin generation (TG) was determined using 1pM and 5pM tissue factor, and thrombomodulin in platelet-poor plasma to assess the functional capacity of plasma to form thrombin. The primary outcome was a composite of recurrent ischemic stroke, TIA, acute coronary syndrome or peripheral artery disease. The secondary outcome was the occurrence of a bleeding complication using the Bleeding Academic Research Consortium (BARC) criteria. We applied Cox proportional hazard models to estimate hazard ratios (HR) with 95% confidence intervals (CI). Results : Among 378 patients (median age 42.1 years, 56% women), 74 experienced a recurrent ischemic event during a mean follow-up of 6.5 years. An increased platelet and leukocyte count, along with elevated levels of fragment 1.2, fibrinogen and D-dimer were associated with a higher risk of ischemic events (table 1). Patients with low plasma antithrombin activity had a higher risk of recurrent ischemic events, especially in women (HR 0.67 [0.47-0.96]). After adjustment for age, sex and traditional risk factors, the association between leukocytes numbers, fragment 1.2 and fibrinogen levels and antithrombin activity and the risk of recurrent ischemic events remained: HR 1.14 [1.05-1.25], 1.07 [1.01-1.14], 0.80 [0.65-0.98], and 1.09 [1.00-1.17], respectively. In patients without vitamin K antagonist treatment, the association between antithrombin activity (HR 0.78 [0.62-0.98]) and leukocytes numbers (HR 1.15 [1.05-1.25]) with recurrent ischemic events were stronger. Thrombin generation parameters were not related to recurrence. Bleeding complications were observed in 16% of patients, mainly among women and predominantly attributable to gynecological bleedings. Hemoglobin, platelets, CXCL-4 and -7, prothrombin, fragment 1.2 and alpha-2-macroglobulin were associated with a bleeding complication (table 2). The association for platelets (HR 0.93 [0.89-0.97]), CXCL-4 (HR 0.90 [0.82-0.99]) and alpha-2-macroglobulin (HR 1.15 [1.03-1.29]) remained after adjustment. Conclusion: Lower antithrombin activity and, higher fragment 1.2, fibrinogen levels, and leukocytes counts were linked to an increased risk of recurrent ischemic events. Bleeding was associated with platelets, CXCL4, and alpha-2-macroglobulin. Overall, especially platelets appear to be significantly involved in the risk of both recurrent arterial thrombosis and bleeding, whereas the observed association with risk of recurrent ischemic events implies a more dominant role of the coagulation system.

Role of Cardiac Risk Scores in Clinical Use to Predict Outcomes of Acute Ischemic Stroke.

Acute coronary syndromes and ischemic stroke have similar risk factors. Risk scores help to identify disease severity in both diseases. We aimed to evaluate if HEART (History, ECG, Age, Risk factors, and Troponin) score could predict re-hospitalization, recurrent cardiac/cerebrovascular events risk, and mortality within 1-year follow-up in patients presenting with acute ischemic stroke. Patients hospitalized with a diagnosis of acute ischemic stroke in our tertiary center between 2019 and 2021 were included in this retrospective study. CHA2DS2-VASc and HEART scores on admission were calculated. In-hospital, 1-month, and 1-year mortalities, as well as re-hospitalization due to recurrent ischemic (cardiac/cerebral), were defined as major adverse cardiac and cerebrovascular events (MACCE), and occurrence of MACCE was accepted as the primary endpoint of the study. Comparative statistical and regression analyses were obtained. A total of 297 patients were included. The mortality rate for 30 days was 7.4% and 1 year was 20.5%. HEART and CHA2DS2-VASc scores were found independent risk factors associated with the occurrence of MACCE. Patients who experienced MACCE had higher HEART and CHA2DS2-VASc scores. Meanwhile, HEART score had better prognostic accuracy than CHA2DS2-VASc score when a cutoff value of 3.5 was set, which is associated with 84.7% sensitivity and 75.2% specificity in the prediction of MACCE. HEART score is effective in determining re-hospitalization and recurrent cerebral ischemic event risk as well as mortality within 30 days and 1 year in patients presenting with acute ischemic stroke. Thus, concomitant use of HEART and CHA2DS2-VASc scores may provide better characterization of worse prognosis in ischemic stroke patients with high sensitivity and specificity.

Different patterns of multiple acute infarctions and long-term prognosis in minor posterior circulation stroke

ObjectivesDifferent classification of multiple acute infarctions (MAIs) existed in minor posterior circulation stroke (PCS). We aimed to explore the association between different patterns of MAIs and long-term prognosis in minor PCS. Materials and methodsWe derived data from Chinese Intracranial Atherosclerosis (CICAS) study. We analyzed the clinical features and outcomes in MAIs among anterior circulation stroke (ACS) and PCS. The patterns of MAIs in PCS were further classified into multiple infarcts, multilevel infarcts, or multiterritorial infarcts. The long-term prognosis included ischemic events recurrence and poor functional outcome (modified Rankin Scale, mRS=2–6) in 1 year. Multivariable Cox and logistic regression were adopted respectively to evaluate the correlation of different patterns of MAIs with recurrence and poor functional outcome. ResultsWe totally enrolled 802 patients with minor stroke in CICAS study, including 484 ACS and 318 PCS. In univariate analysis, MAIs were significantly associated with recurrence in ACS (P<0.01), but were significantly correlated with poor functional outcome in PCS (P=0.044). Among the PCS patients, there were 90 patients with multiple infarcts, 32 patients with multilevel infarcts and 36 patients with multiterritorial infarcts. Multivariable Cox regression showed that multiterritorial infarcts were independently associated with ischemic events recurrence (HR, 3.083; 95 % CI, 1.078–8.813). In multivariable logistic regression, significant correlation with poor functional outcome in 1 year was revealed in multilevel infarcts (OR, 2.788; 95 % CI, 1.144–6.797). ConclusionsDifferent patterns of MAIs provide different predictive performances for PCS prognosis. It is imperative to perform more detailed image interpretation of MAIs in PCS.

Safety and Feasibility of an Emergency Department-to-Outpatient Pathway for Patients With TIA and Nondisabling Stroke.

Evaluation of transient ischemic attack/nondisabling ischemic strokes (TIA/NDS) in the emergency department (ED) contributes to capacity issues and increasing health care expenditures, especially high-cost duplicative imaging. As an institutional quality improvement project, we developed a novel pathway to evaluate patients with TIA/NDS in the ED using a core set of laboratory tests and CT-based neuroimaging. Patients identified as 'low risk' through a safety checklist were discharged and scheduled for prompt outpatient tests and stroke clinic follow-up. In this prespecified analysis designed to assess feasibility and safety, we abstracted data from patients consecutively enrolled in the first 6 months. We compared data from 106 patients with TIA/NDS enrolled in the new pathway from April through September 2020 (age 67.9 years, 45% female), against 55 unmatched historical controls with TIA encountered from April 2016 through March 2017 (age 68.3 years, 47% female). Both groups had similar median NIHSS scores (pathway and control 0) and ABCD2 scores (pathway and control 3). Pathway-enrolled patients had a 44% decrease in mean ED length of stay (pathway 13.7 hours, control 24.4 hours, p < 0.001) and decreased utilization of ED MRI-based imaging (pathway 63%, control 91%, p < 0.001) and duplicative ED CT plus MRI-based brain and/or vascular imaging (pathway 35%, control 53%, p = 0.04). Among pathway-enrolled patients, 89% were evaluated in our stroke clinic within a median of 5 business days; only 5.5% were lost to follow-up. Both groups had similar 90-day rates of ED revisits (pathway 21%, control 18%, p = 0.84) and recurrent TIA/ischemic stroke (pathway 1%, control 2%, p = 1.0). Recurrent ischemic events among pathway-enrolled patients were attributed to errors in following the safety checklist before discharge. Our TIA/NDS pathway, implemented during the initial outbreak of COVID-19, seems feasible and safe, with significant positive impact on ED throughput and ED-based high-cost duplicative imaging. The safety checklist and option of virtual telehealth follow-up are novel features. Broader adoption of such pathways has important implications for value-based health care.

Propensity-score matched analysis of patent foramen ovale closure in real-world study cohort with cryptogenic ischemic stroke

IntroductionPatent foramen ovale (PFO) occurs in 25% of the general population and in 40% of cryptogenic ischemic stroke patients. Recent trials support PFO closure in selected patients with cryptogenic stroke. We examined the outcomes of transcatheter PFO closure in a real-world study cohort with cryptogenic stroke. MethodsConsecutive ischemic stroke patients who were classified as cryptogenic on the TOAST aetiology and diagnosed with a PFO were included. All patients underwent either transcatheter PFO closure or medical therapy. A 2:1 propensity score matching by sex and Risk-of-Paradoxical-Embolism (RoPE) score was performed. Multivariable regression models adjusted for sex and RoPE score. ResultsOur cohort comprised 232 patients with mean age 44.3 years (SD 10.8) and median follow-up 1486.5 days. 33.2% were female. PFO closure (n=84) and medical therapy (n=148) groups were well-matched with <10% mean-difference in sex and RoPE score. Two patients in the treated group (2.4%) and seven in the control group (4.7%) had a recurrent ischemic stroke event. Multivariable Cox regression demonstrated a hazard-ratio of 0.26 (95%CI 0.03-2.13, P=0.21) for PFO closure compared to control. The incidence of atrial fibrillation (AF) detected post-PFO closure was similar between the treated and control (1.19% vs 1.35%, multivariable logistic regression odds-ratio 0.90, 95%CI 0.04-9.81, P=0.94). There were no major periprocedural complications documented. The difference in restricted mean survival-time free from stroke at two years between treated and control was 26.2 days (95%CI 5.52-46.85, P=0.013). ConclusionsIn this Asian cohort, we report a low incidence of ischemic stroke recurrence and new-onset AF in patients who underwent PFO closure. When compared to the medical therapy group, there was no significant difference in the incidence of stroke recurrence and new-onset AF. Further studies involving larger real-world cohorts are warranted to identify patients who are more likely to benefit from PFO closure.

Approaches to classification of microembolic signals in patients recovering from ischemic stroke

Introduction. Microembolus detection by transcranial Doppler (TCD) is the only non-invasive modality for visualization of cerebral embolism. Currently, there is no unified classification of recorded microembolic signals (MES) that could be used in clinical practice.&#x0D; The aim of the study is to investigate biophysical MES parameters in patients with ischemic stroke, as well as to assess approaches to microemboli differentiation by structure and origin to improve the diagnostic accuracy of the method and to reduce the risk of recurrent ischemic events.&#x0D; Materials and methods. The inclusion criterion was TCD-detected signs of MES. We analyzed the data of 28 patients with ischemic stroke (9 women and 19 men; mean age was 58 years 13). We recorded power, duration, and frequency for each MES, and calculated an energy index.&#x0D; Results. A total of 938 MES were reported. In patients with cardioembolic stroke and all other pathogenetic stroke subtypes, biophysical parameter limits were as follows: 14.65 dB for the average power, 9.45 ms for the average duration, and 0.16 J for the average energy index. For patients with atrial fibrillation, characteristic MES power was found to be 13 dB. The MES frequency limit was determined to be 650 Hz for microemboli differentiation by acoustic density.&#x0D; Conclusion. The data obtained can be used to further search for optimal limit ranges for biophysical parameters of various MES in order to establish a single MES classification, which will increase the diagnostic value of microembolus detection by TCD in stroke treatment practice.

Who may benefit from low-dose Rivaroxaban plus Aspirin? Practical implications for outpatients with cardiovascular disease.

Despite the availability of effective preventive therapies based on guidelines, patients with vascular diseases continue to be at a high risk for recurrent ischemic events. Therefore, novel therapeutic strategies are required to further reduce the residual risk present in these patients at high risk. Platelet aggregation and fibrin organization are involved in arterial thrombosis, and rivaroxaban is capable of targeting both processes and has a synergistic effect when used in combination with acetylsalicylic acid (ASA), the so-called dual pathway inhibition (DPI). The COMPASS (Cardiovascular Outcomes for People Using Anticoagulation Strategies) trial showed that the DPI (a combination of rivaroxaban 2.5 mg/bid (vascular dose) and ASA 100 mg once daily), reduced cardiovascular death, stroke, or myocardial infarction by 24% in patients with chronic coronary artery disease (CAD) and peripheral artery disease (PAD). Subsequently, the VOYAGER PAD (Vascular Outcomes Study of ASA Along with Rivaroxaban in Endovascular or Surgical Limb Revascularization for PAD) trial confirmed the effectiveness of the vascular dose of rivaroxaban in patients with PAD after lower-extremity revascularization, compared to ASA alone. Therefore, DPI is recommended in patients with CAD (+/- PAD) or symptomatic PAD at high ischaemic risk. The purpose of this review is to examine the clinical benefits and practical implications of DPI in CAD and PAD patients.

Association of culprit plaque enhancement ratio, hypoperfusion and HbA1c with recurrent ischemic stroke in patients with atherosclerotic stenosis of the middle cerebral artery

PurposeTo investigate the differences in intracranial culprit plaque characteristics of the middle cerebral artery (MCA), collateral circulation and hypoperfusion in patients with and without recurrent ischemic stroke and to identify the association with the recurrent ischemic cerebrovascular events. MethodEighty-six patients with acute/subacute ischemic stroke caused by atherosclerotic plaques of the MCA were retrospectively enrolled and grouped into patients with recurrence (n = 36) and without recurrence (n = 50). All patients underwent high-resolution vessel wall imaging and dynamic susceptibility contrast-enhanced perfusion weighted imaging. The differences in culprit plaque characteristics, collateral circulation and hypoperfusion in the territory of the stenotic MCA were assessed between the two groups. The relationship between plaque characteristics and hypoperfusion was evaluated. The independent factors of recurrent ischemic stroke were identified by logistic regression analyses. ResultsHigher HbA1c, culprit plaque enhancement grade, culprit plaque enhancement ratio, and lower time to peak map based on the Alberta Stroke Program Early CT score (TTP-ASPECTS) were observed in the recurrence group(all p < 0.050). Both plaque enhancement grade and enhancement ratio were significantly associated with TTP-ASPECTS (p = 0.030 and 0.039, respectively). HbA1c, culprit plaque enhancement ratio and TTP-ASPECTS were independent factors of the recurrence of ischemic stroke (all p < 0.050). The area under the curve of the combination including the above factors (AUC = 0.819) was significantly higher than that of any variable alone after adjustment (all p < 0.050). ConclusionsCulprit plaque enhancement ratio, TTP-ASPECTS and HbA1c were independent factors of recurrent ischemic stroke. Their combination improved the accuracy in identifying the risk of recurrent ischemic stroke.