Sonothrombolysis for Ischemic Stroke.

Stroke is a major cause of death and disability globally, with ischemic stroke being the predominant mechanism. While spontaneous recanalization may occur, significant neuronal injury would have occurred in the interim. Intravenous thrombolysis administered within the first 4.5 h after stroke onset and endovascular thrombectomy within 24 h in patients with a salvageable penumbra improves functional independence. Ultrasound has been shown in both in vivo and in vitro models to enhance clot lysis, even more-so in the presence of thrombolytic agents. The use of transcranial Doppler and transcranial color-coded Doppler ultrasound in acute IS has been reported in case series, case-controlled studies, and clinical trials. While ultrasound at a frequency of 300 kHz increases the risk of intracranial hemorrhage, the 2 MHz range ultrasound aids thrombolysis and improves recanalization without significantly increasing the risk of symptomatic intracranial hemorrhage. Despite this, functional independence was not increased in clinical trials, nor was a benefit shown with the adjunctive use of microbubbles or microspheres. Nonetheless, newer technologies such as endovascular ultrasound, endovascular delivery of microbubbles, and thrombolytic-filled microbubbles await clinical trials. More evidence is needed before sonothrombolysis can be routinely used in the hyperacute management of ischemic stroke.

Left Ventricular Diastolic Dysfunction Is Associated with Poor Functional Outcomes after Endovascular Thrombectomy.

INTRODUCTION: With the advent of endovascular thrombectomy (ET), patients with acute ischaemic strokes (AIS) with large vessel occlusion (LVO) have seen vast improvements in treatment outcomes. Left ventricular diastolic dysfunction (LVDD) has been shown to herald poorer prognosis in conditions such as myocardial infarction. However, whether LVDD is related to functional recovery and outcomes in ischaemic stroke remains unclear. We studied LVDD for possible relation with clinical outcomes in patients with LVO AIS who underwent ET. METHODS: We studied a retrospective cohort of 261 LVO AIS patients who had undergone ET at a single comprehensive stroke centre and correlated LVDD to short-term mortality (in-hospital death) as well as good functional recovery defined as modified Rankin Scale of 0-2 at 3 months. RESULTS: The study population had a mean age of 65-years-old and were predominantly male (54.8%). All of the patients underwent ET with 206 (78.9%) achieving successful reperfusion. Despite this, 25 (9.6%) patients demised during the hospital admission and 149 (57.1%) did not have good function recovery at 3 months. LVDD was present in 82 (31.4%) patients and this finding indicated poorer outcomes in terms of functional recovery at 3 months (OR 2.18, 95% CI 1.04-4.54, p = 0.038) but was not associated with increased in-hospital mortality (OR 2.18, 95% CI 0.60-7.99, p = 0.240) after adjusting for various confounders. CONCLUSION: In addition to conventional echocardiographic indices such as left ventricular ejection fraction, LVDD may portend poorer outcomes after ET, and this relationship should be investigated further.

Dual Antiplatelet Therapy for the Acute Management and Long-term Secondary Prevention of Ischemic Stroke and Transient Ischemic Attack, An Updated Review.

To improve the efficacy over antiplatelet monotherapy, dual antiplatelet therapy (DAPT) has been increasingly adopted in the management of non-cardioembolic stroke. For minor ischemic stroke and high-risk transient ischemic attack, the aspirin-clopidogrel combination is now recommended for acute short-term treatment, whereas aspirin-ticagrelor combination may be considered in selected patients, especially those with resistance to clopidogrel. For long-term stroke prevention, aspirin-dipyridamole combination has been used as an alternative to antiplatelet monotherapy, and aspirin or clopidogrel combined with cilostazole may be prescribed for added protection in high-risk patients. In this paper, we review the development of DAPT from a historical perspective and describe the findings from major clinical trials published up until the end of 2023. Using the 2021 American Heart Association guideline for secondary stroke prevention as a basis for our recommendations, we further discuss areas of controversy and more recent developments to provide an updated review for clinicians to consider in their daily practice.

Prevalence and Associations of Cognitive Impairment in Adult Patients with Moyamoya Disease: A Systematic Review and Meta-Analysis.

BACKGROUND: Cognitive impairment, and in the long term Alzheimer's disease, vascular, or mixed dementia, are potential complications of moyamoya disease (MMD), of which the prevalence and associations are not well established. OBJECTIVE: We performed a systematic review and meta-analysis to investigate the prevalence of cognitive impairment in adult patients with MMD as well as its clinical and demographic correlates. METHODS: We performed a systematic search of four electronic databases: PubMed (MEDLINE), EMBASE, Scopus, and Cochrane Library, profiling studies from inception until 7 May 2023. Clinical data consisting of population characteristics, comorbidities, cognitive assessment tools used, and prevalence of cognitive impairment was extracted. RESULTS: Seventeen studies were included in the meta-analysis, with a total study population of 1,190 patients. All studies assessed cognition, and the overall prevalence of cognitive impairment in MMD patients was 54.59%. A subgroup analysis identified that the prevalence of executive dysfunction in MMD patients was 31.55%. We performed a meta-regression analysis which identified that cognitive impairment was not associated with age, education level, or a history of ischemic or hemorrhagic stroke. CONCLUSIONS: A substantial proportion of MMD patients have cognitive impairment, and cognitive impairment was found to have no association with a history of stroke. Further research is necessary to investigate the longitudinal relationship of MMD and cognitive impairment, and the impact of bypass surgery on cognitive impairment.

Platform for the interdisciplinary study of cardiovascular, metabolic and neurovascular diseases (PICMAN) protocol.

Through extensive multisystem phenotyping, the central aim of Project PICMAN is to correlate metabolic flexibility to measures of cardiometabolic health, including myocardial diastolic dysfunction, coronary and cerebral atherosclerosis, body fat distribution and severity of non-alcoholic fatty liver disease. This cohort will form the basis of larger interventional trials targeting metabolic inflexibility in the prevention of cardiovascular disease. Participants aged 21-72 years with no prior manifest atherosclerotic cardiovascular disease (ASCVD) are being recruited from a preventive cardiology clinic and an existing cohort of non-alcoholic fatty liver disease (NAFLD) in an academic medical centre. A total of 120 patients will be recruited in the pilot phase of this study and followed up for 5 years. Those with 10-year ASCVD risk ≥ 5% as per the QRISK3 calculator are eligible. Those with established diabetes mellitus are excluded. Participants recruited undergo a detailed assessment of health behaviours and physical measurements. Participants also undergo a series of multimodality clinical phenotyping comprising cardiac tests, vascular assessments, metabolic tests, liver and neurovascular testing. Blood samples are also being collected and banked for plasma biomarkers, 'multi-omics analyses' and for generation of induced pluripotent stem cells (iPSC). Extensive evidence points to metabolic dysregulation as an early precursor of cardiovascular disease, particularly in Asia. We hypothesise that quantifiable metabolic inflexibility may be representative of an individual in his/her silent, but high-risk progression towards insulin resistance, diabetes and cardiovascular disease. The platform for interdisciplinary cardiovascular-metabolic-neurovascular diseases (PICMAN) is a pilot, prospective, multi-ethnic cohort study.

Association Between Calcium Supplementation and the Risk of Cardiovascular Disease and Stroke: A Systematic Review and Meta-Analysis.

BACKGROUND: Some observational studies and randomised controlled trials (RCTs) have reported an association between calcium supplementation and increased risk of cardiovascular disease. Previous meta-analyses on the topic, based on data from RCTs and observational studies, have contradictory findings. This meta-analysis was conducted to determine the difference in associated risks of calcium supplementation with cardiovascular disease and stroke in RCTs. METHODS: Relevant studies published from database inception to 6 August 2021 were sourced from PubMed, Embase, Scopus, and the Cochrane Central Register of Controlled Trials. Any RCTs focusing on the relationship between calcium supplementation and incidence of cardiovascular disease or stroke were included. Articles were screened independently by two authors, according to the PICO criteria, with disagreements resolved by a third author. RESULTS: Twelve RCTs were included in the meta-analysis. Calcium supplementation was not associated with myocardial infarction, total stroke, heart failure admission, and all-cause/cardiovascular mortality. Subgroup analysis focusing on calcium monotherapy/calcium co-therapy with vitamin D, female sex, follow-up duration, and geographical region did not affect the findings. CONCLUSION: Calcium supplementation was not associated with myocardial infarction, total stroke, heart failure admission, and cardiovascular/all-cause mortality. Further studies are required to examine and understand these associations.

Antiplatelet therapy in aneurysmal subarachnoid hemorrhage: an updated meta-analysis.

Antiplatelet therapy (AT) may serve to reduce the effects of aneurysmal subarachnoid hemorrhage (aSAH)-induced pro-coagulant state in the cerebral circulation. Several studies, however, have delivered conflicting conclusions on the efficacy of AT post aSAH. Systematic searches of Medline, Embase, and Cochrane Central were undertaken on 27th March 2023. The primary outcome was delayed cerebral ischaemia (DCI). Secondary outcomes were symptomatic and angiographic vasospasm, good functional outcome (modified Rankin Scale [mRS] with scores 0-2), hemorrhagic events, and in-hospital mortality. Twenty-two studies reporting 4378 patients with aSAH were included in the meta-analysis. AT was associated with lower rates of DCI (RR=0.62, 95% CI: 0.43; 0.89), symptomatic vasospasm (RR=0.63, 95% CI: 0.46; 0.86), and moderate/severe angiographic vasospasm (RR=0.74, 95% CI: 0.65; 0.84), with no effect on hemorrhagic complications (RR=1.36, 95% CI: 0.77; 2.41). When analyzing only post-ictal use of AT, AT additionally favored rates of good functional outcomes (RR=1.18, 95% CI: 1.10; 1.26) and in-hospital mortality (RR=0.56, 95% CI: 0.39; 0.80). In the subgroup treated with cilostazol, AT was associated with lower rates of DCI (RR=0.40, 95% CI: 0.32), symptomatic vasospasm (RR=0.47, 95% CI: 0.33; 0.65), moderate/severe angiographic vasospasm (RR=0.75, 95% CI: 0.57; 0.98) and good functional outcome (RR=1.24, 95% CI: 1.08; 1.43). In the surgically treated aSAH subgroup, AT favored rates of symptomatic vasospasm (RR=0.55, 95% CI: 0.30; 0.98), moderate/severe angiographic vasospasm (RR=0.70, 95% CI: 0.54; 0.90) and good functional outcome (RR=1.23, 95% CI: 1.09; 1.41). In the endovascularly treated aSAH subgroup, AT was associated with lower rates of in-hospital mortality (RR=0.60, 95% CI: 0.41; 0.88). In aSAH patients, post-ictal AT is associated with benefits in terms of rates of DCI, vasospasm, good functional outcomes, and in-hospital mortality without an increased risk of hemorrhagic events.

Acute Myocardial Infarction and Risk of Cognitive Impairment and Dementia: A Review.

Cognitive impairment (CI) shares common cardiovascular risk factors with acute myocardial infarction (AMI), and is increasingly prevalent in our ageing population. Whilst AMI is associated with increased rates of CI, CI remains underreported and infrequently identified in patients with AMI. In this review, we discuss the evidence surrounding AMI and its links to dementia and CI, including pathophysiology, risk factors, management and interventions. Vascular dysregulation plays a major role in CI, with atherosclerosis, platelet activation, microinfarcts and perivascular inflammation resulting in neurovascular unit dysfunction, disordered homeostasis and a dysfunctional neurohormonal response. This subsequently affects perfusion pressure, resulting in enlarged periventricular spaces and hippocampal sclerosis. The increased platelet activation seen in coronary artery disease (CAD) can also result in inflammation and amyloid-ß protein deposition which is associated with Alzheimer's Dementia. Post-AMI, reduced blood pressure and reduced left ventricular ejection fraction can cause chronic cerebral hypoperfusion, cerebral infarction and failure of normal circulatory autoregulatory mechanisms. Patients who undergo coronary revascularization (percutaneous coronary intervention or bypass surgery) are at increased risk for post-procedure cognitive impairment, though whether this is related to the intervention itself or underlying cardiovascular risk factors is debated. Mortality rates are higher in dementia patients with AMI, and post-AMI CI is more prevalent in the elderly and in patients with post-AMI heart failure. Medical management (antiplatelet, statin, renin-angiotensin system inhibitors, cardiac rehabilitation) can reduce the risk of post-AMI CI; however, beta-blockers may be associated with functional decline in patients with existing CI. The early identification of those with dementia or CI who present with AMI is important, as subsequent tailoring of management strategies can potentially improve outcomes as well as guide prognosis.

Association Between Breast Arterial Calcifications and Cardiovascular Disease: A Systematic Review and Meta-analysis.

BACKGROUND: Recent studies have shown that breast arterial calcification (BAC) detected on screening mammography is linked to cardiovascular diseases via medial calcification. However, its effect on cardiovascular outcomes remains unclear. Therefore, we conducted a meta-analysis to determine the effect of BAC on cardiovascular outcomes in patients. METHODS: Three electronic databases (Pubmed, Embase, and Scopus) were searched on May 1, 2022, for studies examining the relationship between BAC and cardiovascular outcomes including cardiac death, acute myocardial infarction, ischemic heart disease, stroke, peripheral artery disease, and heart failure. A random-effects meta-analysis model was used to summarise the studies. RESULTS: A total of 5 longitudinal studies were included with a combined cohort of 87,865 patients. Significantly, the pooled risk ratio (RR) of the association between BAC and cardiac death was 2.06 (P < 0.00001). BAC was associated with a significantly increased risk of developing other cardiovascular diseases, such as ischemic/hemorrhagic stroke (RR 1.51; P = 0.003), ischemic stroke (RR 1.82; P < 0.00001), peripheral vascular disease (RR 1.24; P = 0.003), and heart failure (RR 1.84; P < 0.00001). There was no significant relationship for developing myocardial infarction or for total cardiovascular diseases. CONCLUSIONS: Our findings suggest that BAC was associated with an increased risk of cardiovascular mortality, and certain cardiovascular outcomes. There is thus a potential to use BAC as a sex-specific cardiovascular risk assessment tool. Furthermore, there is a need for more widespread reporting of BAC to better understand the pathophysiologic mechanisms behind its correlation with cardiovascular disease and to apply it in clinical practice.

Left Ventricular Ejection Fraction Association with Acute Ischemic Stroke Outcomes in Patients Undergoing Thrombolysis.

(1) Background: Little is known about how left ventricular systolic dysfunction (LVSD) affects functional and clinical outcomes in acute ischemic stroke (AIS) patients undergoing thrombolysis; (2) Methods: A retrospective observational study conducted between 2006 and 2018 included 937 consecutive AIS patients undergoing thrombolysis. LVSD was defined as left ventricular ejection fraction (LVEF) < 50%. Univariate and multivariate binary logistic regression analysis was performed for demographic characteristics. Ordinal shift regression was used for functional modified Rankin Scale (mRS) outcome at 3 months. Survival analysis of mortality, heart failure (HF) admission, myocardial infarction (MI) and stroke/transient ischemic attack (TIA) was evaluated with a Cox-proportional hazards model; (3) Results: LVSD patients in comparison with LVEF ≥ 50% patients accounted for 190 and 747 patients, respectively. LVSD patients had more comorbidities including diabetes mellitus (100 (52.6%) vs. 280 (37.5%), p < 0.001), atrial fibrillation (69 (36.3%) vs. 212 (28.4%), p = 0.033), ischemic heart disease (130 (68.4%) vs. 145 (19.4%), p < 0.001) and HF (150 (78.9%) vs. 46 (6.2%), p < 0.001). LVSD was associated with worse functional mRS outcomes at 3 months (adjusted OR 1.41, 95% CI 1.03-1.92, p = 0.030). Survival analysis identified LVSD to significantly predict all-cause mortality (adjusted HR [aHR] 3.38, 95% CI 1.74-6.54, p < 0.001), subsequent HF admission (aHR 4.23, 95% CI 2.17-8.26, p < 0.001) and MI (aHR 2.49, 95% CI 1.44-4.32, p = 0.001). LVSD did not predict recurrent stroke/TIA (aHR 1.15, 95% CI 0.77-1.72, p = 0.496); (4) Conclusions: LVSD in AIS patients undergoing thrombolysis was associated with increased all-cause mortality, subsequent HF admission, subsequent MI and poorer functional outcomes, highlighting a need to optimize LVEF.

Enhanced external counter pulsation therapy in patients with symptomatic and severe intracranial steno-occlusive disease: a randomized clinical trial protocol.

Intracranial stenosis is prevalent among Asians and constitutes a common cause of cerebral ischemia. While the best medical therapy carries stroke recurrence rates in excess of 10% per year, trials with intracranial stenting have been associated with unacceptable peri-procedural ischemic events. Cerebral ischemic events are strongly related to the severity of intracranial stenosis, which is high in patients with severe intracranial stenosis with poor vasodilatory reserve. Enhanced External Counter Pulsation (EECP) therapy is known to improve myocardial perfusion by facilitating the development of collateral blood vessels in the heart. In this randomized clinical trial, we evaluate whether EECP therapy may be useful in patients with severe stenosis of intracranial internal carotid (ICA) or middle cerebral artery (MCA). The review of literature, methods of evaluation, status of currently used therapeutic approaches, and trial protocol have been presented. Clinical trial registration: ClinicalTrials.gov, Identifier: NCT03921827.

Distal medium vessel occlusions in acute ischaemic stroke - Stent retriever versus direct aspiration: A systematic review and meta-analysis.

BACKGROUND: Acute ischaemic stroke due to distal medium vessel occlusion (AIS-DMVO) causes significant morbidity. Endovascular thrombectomy advancement has made treating AIS-DMVO with stent retrievers (SR) and aspiration catheters (AC) possible, however the optimal technique remains unknown. We performed a systematic review and meta-analysis to investigate the efficacy and safety of SR use compared to purely AC use in patients with AIS-DMVO. METHODS: We systematically searched PubMed, Cochrane Library and EMBASE, from inception to 2nd September 2022, for studies comparing SR or primary combined (SR/PC) against AC in AIS-DMVO. We adopted the Distal Thrombectomy Summit Group's definition of DMVO. Efficacy outcomes were functional independence (modified Rankin Scale (mRS) 0-2 at 90 days), first pass effect (modified Thrombolysis in Cerebral Infarction scale (mTICI) 2c-3 or expanded Thrombolysis in Cerebral Infarction scale (eTICI) 2c-3 at first pass), successful final recanalisation (mTICI or eTICI 2b-3), and excellent final recanalisation (mTICI or eTICI 2c-3). Safety outcomes were symptomatic intracranial haemorrhage (sICH) and 90-day mortality. RESULTS: 12 cohort studies and 1 randomised-controlled trial were included, involving 1881 patients with 1274 receiving SR/PC and 607 receiving AC only. SR/PC achieved higher odds of functional independence (odds ratio (OR) 1.33, 95% confidence interval (CI) 1.06-1.67) and lower odds of mortality (OR 0.69, 95% CI 0.50-0.94) than AC. Odds of successful/excellent recanalisation and sICH were similar between both groups. Stratified to compare only SR and only AC, the use of only SR, achieved significantly higher odds of successful recanalisation as compared to only AC (OR 1.80, 95% CI 1.17-2.78). CONCLUSION: There is potential for efficacy and safety benefits in SR/PC use as compared to AC only in AIS-DMVO. Further trials are necessary to validate the efficacy and safety of SR use in AIS-DMVO.

Functional and Mortality Outcomes with Medical and Surgical Therapy in Malignant Posterior Circulation Infarcts: A Systematic Review.

BACKGROUND: There remains uncertainty regarding optimal definitive management for malignant posterior circulation infarcts (MPCI). While guidelines recommend neurosurgery for malignant cerebellar infarcts that are refractory to medical therapy, concerns exist about the functional outcome and quality of life after decompressive surgery. OBJECTIVE: This study aims to evaluate the outcomes of surgical intervention compared to medical therapy in MPCI. METHODS: In this systematic review, MEDLINE, Embase and Cochrane databases were searched from inception until 2 April 2021. Studies were included if they involved posterior circulation strokes treated with neurosurgical intervention and reported mortality and functional outcome data. Data were collected according to PRISMA guidelines. RESULTS: The search yielded 6677 studies, of which 31 studies (comprising 723 patients) were included for analysis. From the included studies, we found that surgical therapy led to significant differences in mortality and functional outcomes in patients with severe disease. Neurological decline and radiological criteria were often used to decide the timing for surgical intervention, as there is currently limited evidence for preventative neurosurgery. There is also limited evidence for the superiority of one surgical modality over another. CONCLUSION: For patients with MPCI who are clinically stable at the time of presentation, in terms of mortality and functional outcome, surgical therapy appears to be equivocal to medical therapy. Reliable evidence is lacking, and further prospective studies are rendered.

Association of Shunt Size and Long-Term Clinical Outcomes in Patients with Cryptogenic Ischemic Stroke and Patent Foramen Ovale on Medical Management.

INTRODUCTION: Patent foramen ovale (PFO) is a potential source of cardiac embolism in cryptogenic ischemic stroke, but it may also be incidental. Right-to-left shunt (RLS) size may predict PFO-related stroke, but results have been controversial. In this cohort study of medically-managed PFO patients with cryptogenic stroke, we aimed to investigate the association of shunt size with recurrent stroke, mortality, newly detected atrial fibrillation (AF), and to identify predictors of recurrent stroke. METHODS: Patients with cryptogenic stroke who screened positive for a RLS using a transcranial Doppler bubble study were included. Patients who underwent PFO closure were excluded. Subjects were divided into two groups: small (Spencer Grade 1, 2, or 3; n = 135) and large (Spencer Grade 4 or 5; n = 99) shunts. The primary outcome was risk of recurrent stroke, and the secondary outcomes were all-cause mortality and newly detected AF. RESULTS: The study cohort included 234 cryptogenic stroke patients with medically-managed PFO. The mean age was 50.5 years, and 31.2% were female. The median period of follow-up was 348 (IQR 147-1096) days. The rate of recurrent ischemic stroke was higher in patients with large shunts than in those with small shunts (8.1% vs. 2.2%, p = 0.036). Multivariate analyses revealed that a large shunt was significantly associated with an increased risk of recurrent ischemic stroke [aOR 4.09 (95% CI 1.04-16.0), p = 0.043]. CONCLUSIONS: In our cohort of cryptogenic stroke patients with medically managed PFOs, those with large shunts were at a higher risk of recurrent stroke events, independently of RoPE score and left atrium diameter.

Co-prevalence and incidence of myocardial infarction and/or stroke in patients with depression and/or anxiety: A systematic review and meta-analysis.

OBJECTIVE: Co-prevalence and incidence of depression and/or anxiety with stroke and myocardial infarction are currently unclear. This paper explores the relationships, as these are important comorbidities affecting patient outcomes. METHODS: A systematic search across five databases (PubMed, Scopus, PsycINFO, Embase, Cochrane) was conducted for observational studies reporting co-prevalence of depression or anxiety with stroke or myocardial infarction. We used random-effects models in all meta-analyses and evaluated heterogeneity using I2. RESULTS: This analysis included 48 studies with a total of 57,342 patients. In patients with depression, the pooled prevalence of stroke was 5.9% (95% CI = 5.53-6.37). In patients with myocardial infarction, the pooled prevalence of anxiety and depression was 9.1% (95% CI = 7.07-11.40, I2 = 85.6%) and 25.9% (95% CI = 18.46-34.12, I2 = 99.1%), respectively, and the pooled cumulative incidence of depression at one year was 20.5% (95% CI = 18.36-22.79). The pooled prevalence of anxiety and depression in patients with stroke was 13.5% (95% CI = 7.67-22.66, I2 = 96.9%) and 23.0% (95% CI = 17.93-28.99, I2 = 96.7%), respectively. The pooled cumulative incidences of depression at two weeks, three months, six months, and one year, were 29.1% (95% CI = 26.60-31.81), 17.0% (95% CI = 10.74-25.92, I2 = 98.0%), 7.4% (95% CI = 6.52-8.49), and 9.1% (95% CI = 3.71-20.79, I2 = 99.8%), respectively. CONCLUSIONS: This meta-analysis outlines the co-morbid burden between depression/anxiety and stroke/myocardial infarction. Future research should be done to evaluate the effectiveness of screening anxiety/depression in myocardial infarction/stroke.

Risk of Liver Fibrosis Is Associated with More Severe Strokes, Increased Complications with Thrombolysis, and Mortality.

The Fibrosis (FIB)-4 index is an established non-invasive test to detect liver fibrosis. Liver fibrosis is postulated to be one of the predictors of the risk of symptomatic Intracranial Haemorrhage (SICH) after intravenous tissue plasminogen activator (IV tPA) therapy, the mainstay of treatment following acute ischemic stroke (AIS). However, SICH is a feared complication of thrombolytic therapy. We aimed to evaluate the association of FIB-4 with outcomes of AIS after IV tPA. Consecutive AIS patients receiving IV tPA from 2006 to 2018 at a single stroke centre were studied in a retrospective cohort study. Multivariable adjusted logistic regression was performed to assess associations of FIB-4 with outcomes. The primary outcome was SICH, and secondary outcomes included functional independence (mRS of 0−2) and mortality measured at 90 days. Among 887 patients (median age: 67 (IQR: 57−77)), 342 had FIB-4 < 1.3 and 161 had FIB-4 > 2.67. A greater proportion of moderate to severe strokes (NIHSS ≥10) occurred in the FIB-4 > 2.67 group (n = 142, 88.8%) compared to the FIB-4 < 1.3 group (n = 208, 61.2%). Amongst the different stroke subtypes, median FIB-4 was highest in cardioembolic stroke (CES) compared to the 3 other non-CES stroke subtypes (1.90 (IQR: 1.41−2.69)). Following IV tPA, having FIB-4 > 2.67 was associated with an increased rate of SICH (adjusted OR: 4.09, 95% CI: 1.04−16.16, p = 0.045) and increased mortality (adjusted OR 3.05, 95% CI: 1.28−7.26, p = 0.012). Advanced liver fibrosis was associated with an increased rate of SICH and increased 90-day mortality after IV tPA. The FIB-4 score may be useful for prognostication after IV tPA.

Potential Embolic Sources in Embolic Stroke of Undetermined Source Patients with Patent Foramen Ovale.

INTRODUCTION: A patent foramen ovale (PFO) may coexist with other potential embolic sources (PESs) in patients with embolic stroke of undetermined source (ESUS), leading to difficulty in attributing the stroke to either the PFO or other PESs. We aimed to investigate the prevalence and predictors of concomitant PESs in ESUS patients with PFOs. METHODS: A retrospective cohort study was conducted in a tertiary stroke centre. Consecutive patients with ESUS and a concomitant PFO admitted between 2012 and 2021 were included in the study. Baseline characteristics and investigations as a part of stroke workup including echocardiographic and neuroimaging data were collected. PESs were adjudicated by 2 independent neurologists after reviewing the relevant workup. RESULTS: Out of 1,487 ESUS patients, a total of 309 patients who had a concomitant PFO with mean age of 48.8 ± 13.2 years were identified during the study period. The median Risk of Paradoxical Embolism (RoPE) score for the study cohort was 6 (IQR 5-7.5). Of the 309 patients, 154 (49.8%) only had PFO, 105 (34.0%) patients had 1 other PES, 34 (11.0%) had 2 PES, and 16 (5.2%) had 3 or more PES. The most common PESs were atrial cardiopathy (23.9%), left ventricular dysfunction (22.0%), and cardiac valve disease (12.9%). The presence of additional PESs was associated with age ≥60 years (p < 0.001), RoPE score ≤6 (p ≤0.001), and the presence of comorbidities including diabetes mellitus (p = 0.004), hypertension (p≤ 0.001), and ischaemic heart disease (p = 0.011). CONCLUSION: A large proportion of ESUS patients with PFOs had concomitant PESs. The presence of concomitant PESs was associated with older age and a lower RoPE score. Further, large cohort studies are warranted to investigate the significance of the PES and their overlap with PFOs in ESUS.

Ischaemic events in hypertrophic cardiomyopathy patients with and without atrial fibrillation: a systematic review and meta-analysis.

Hypertrophic cardiomyopathy predisposes to acute cerebrovascular events including ischaemic stroke, transient ischaemic attack and systemic thromboembolism. Atrial fibrillation confers even higher risk. We aim to report the incidence of these complications and to investigate the impact of atrial fibrillation on the ischaemic risk in patients with hypertrophic cardiomyopathy. A literature search was performed on PubMed, Scopus, Embase/Ovid and Cochrane library from inception to 20th March 2021. We compared the incidence of ischaemic strokes, transient ischaemic attack, non-specified thromboembolism events and systemic thromboembolism in hypertrophic cardiomyopathy patients with or without atrial fibrillation. Non-specified thromboembolism events in our paper referred to thromboembolic events whereby types were not specified in the studies. Meta-analysis was performed using StataSE 16 software, and heterogeneity was assessed using I2 test. A total of 713 studies were identified. Thirty-five articles with 42,570 patients were included. The pooled incidence of stroke/ transient ischaemic attack was 7.45% (95% confidence interval [CI] 5.80-9.52, p < 0.001) across 24 studies with a total of 37,643 hypertrophic cardiomyopathy patients. Atrial fibrillation significantly increased the risk of total stroke/ transient ischaemic attack (Risk Ratio 3.26, 95% CI 1.75-6.08, p < 0.001, I2 = 76.0). The incidence of stroke/ transient ischaemic attack was 9.30% (95% CI 6.64-12.87, p = 0.316) in the apical hypertrophic cardiomyopathy subgroup. Concomitant atrial fibrillation in hypertrophic cardiomyopathy increases the risk of thromboembolic events including ischaemic stroke and transient ischaemic attack. The apical subgroup shows a similar risk of acute cerebrovascular events as the overall hypertrophic cardiomyopathy population.

Impact of Traditional and Non-Traditional Lipid Parameters on Outcomes after Intravenous Thrombolysis in Acute Ischemic Stroke.

Contradicting evidence exists regarding the role of lipids in outcomes following intravenous (IV) thrombolysis with tissue plasminogen activator (tPA). Restricted cubic spline curves and adjusted logistic regression were used to evaluate associations of low-density lipoprotein cholesterol (LDL-C), non-high-density lipoprotein cholesterol (non-HDL-C), total cholesterol (TC), high-density lipoprotein cholesterol (HDL-C) and LDL-C/HDL-C ratio with poor functional outcome, symptomatic intracranial hemorrhage (SICH) and 90-day mortality, among 1004 acute ischemic stroke (AIS) patients who received IV tPA in a comprehensive stroke center. Quartile (Q) 1, Q2 and Q3 of HDL-C were associated with increased odds of poor functional outcome (adjusted odds ratio (adjOR) 1.66, 95% CI 1.06-2.60, p = 0.028, adjOR 1.63, 95% CI 1.05-2.53, p = 0.027, adjOR 1.56, 95% CI 1.01-2.44, p = 0.048) compared to Q4. Q2 and Q4 of non-HDL-C were associated with increased odds of SICH (adjOR 4.28, 95% CI 1.36-18.90, p = 0.025, adjOR 5.17, 95% CI 1.64-22.81, p = 0.011) compared to Q3. Q1 and Q2 of LDL-C was associated with increased odds of mortality (adjOR 2.57, 95% CI 1.27-5.57, p = 0.011 and adjOR 2.28, 95% CI 1.10-5.02, p = 0.032) compared to Q3. In AIS patients who received IV tPA, low LDL-C was associated with increased odds of mortality while HDL-C may be protective against poor functional outcome.