Research

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.

Background: Dementia is associated with a greater burden of cardiovascular risk factors. There is a significant vascular contribution to dementia, and aspirin may play a role in targeting this vascular dysregulation via its anti-inflammatory and antiplatelet effects. We provide an overview of the effects of aspirin therapy on the prevention of dementia and cognitive decline in patients with or without dementia and/or cognitive impairment. Methods: We performed a search for studies enrolling adults with or without dementia or MCI and comparing aspirin with placebo, usual care, or active control with respect to cognitive outcomes. Results: We describe aspirin's effects on the primary prevention of cognitive impairment and various subtypes of dementia, as well as its role in cognitive decline in certain subsets of patients, including those with cerebral small vessel disease (CVSD), coronary heart disease (CHD), and gender differences. Overall, the benefits of aspirin in preventing dementia and cognitive decline remain inconclusive. The majority of cohort studies investigating aspirin's role in preventing cognitive decline or dementia looked promising, but this was not supported in most randomised controlled trials. However, aspirin may still be beneficial in certain subgroups of patients (such as CHD, VD, and CSVD) and warrants further investigation.

Background The role of bridging intravenous thrombolysis (IVT) before endovascular thrombectomy (EVT) in the treatment of acute ischemic stroke (AIS) remains debatable. Atrial fibrillation (AF) associated strokes may be associated with reduced treatment effect from IVT. This study compares the effect of bridging IVT in AF and non-AF patients. Methods This retrospective cohort study comprised anterior circulation large vessel occlusion (LVO) AIS patients receiving EVT alone or bridging IVT plus EVT within 6 hours of symptom onset. Primary outcome was good functional outcome defined as modified Rankin Scale (mRS) 0–2 at 90 days. Secondary outcomes were successful reperfusion defined as expanded Thrombolysis In Cerebral Infarction (eTICI) grading ≥2b flow, symptomatic intracerebral hemorrhage (sICH), and in-hospital mortality. Results We included 705 patients (314 AF and 391 non-AF patients). The mean age was 68.6 years and 53.9% were male. The odds of good functional outcomes with bridging IVT was higher in the non-AF (adjusted odds ratio (aOR) 2.28, 95% CI 1.06 to 4.91, P=0.035) compared with the AF subgroups (aOR 1.89, 95% CI 0.89 to 4.01, P=0.097). However, this did not constitute a significant effect modification by the presence of AF on bridging IVT (interaction aOR 0.12, 95% CI −1.94 to 2.18, P=0.455). The rate of successful reperfusion, sICH, and mortality were similar between bridging IVT and EVT for both AF and non-AF patients. Conclusion The presence of AF did not modify the treatment effect of bridging IVT. Further individual patient data meta-analysis of randomized trials may shed light on the comparative efficacy of bridging IVT in AF versus non-AF LVO strokes.

Background The optimal mechanical thrombectomy technique for acute ischaemic stroke (AIS) caused by distal, medium vessel occlusion (DMVO) is uncertain. We performed a systematic review and meta-analysis evaluating the efficacy and safety of first-line thrombectomy with combined techniques, which entail simultaneous use of a stent retriever and aspiration catheter, versus single-device techniques, whether stent retriever or direct aspiration alone, for DMVO-AIS patients. Methods We systematically searched the PubMed, Embase and Cochrane CENTRAL databases from inception until 2 September 2022 for studies comparing combined and single-device techniques in DMVO-AIS patients. We adopted the Distal Thrombectomy Summit Group’s definition of DMVO. Our outcomes were the modified first-pass effect (mFPE; modified Thrombolysis in Cerebral Infarction [mTICI] 2b-3 at first-pass), first-pass effect (FPE; mTICI 2c-3 at first-pass), successful and complete final reperfusion (mTICI 2b-3 and 2c-3 at end of all procedures, respectively), 90-day functional independence (modified Rankin scale 0-2), 90-day mortality, and symptomatic intracranial haemorrhage (sICH). Results Nine studies were included, with 477 patients receiving combined techniques, and 670 patients receiving single-device thrombectomy. Combined techniques achieved significantly higher odds of mFPE (odds ratio [OR], 2.12; 95% confidence interval [CI], 1.12-4.02; p=0.021) and FPE (OR, 3.55; 95% CI, 1.97-6.38; p<0.001), with lower odds of sICH (OR, 0.23; 95% CI, 0.06-0.93; p=0.040). There were no significant differences in final reperfusion, functional independence (OR, 1.19; 95% CI 0.87-1.63; p=0.658), or mortality (OR, 0.94; 95% CI, 0.50-1.76; p=0.850). Conclusions In DMVO-AIS patients, mechanical thrombectomy combining stent retrievers and aspiration catheters achieved higher odds of FPE and lower odds of sICH over single-device techniques. There were no differences in functional independence and mortality. Further trials are warranted to establish these findings.

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.

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.

This study sought to investigate the impact of pre-existing cognitive impairment on outcomes after transcatheter aortic valve implantation (TAVI). TAVI has been increasingly used in seniors, and evidence suggests better outcomes than surgical aortic valve replacement. Although frailty has been shown to be associated with poorer outcomes after TAVI, the effect of pre-existing cognitive impairment on patient outcomes after TAVI remains unclear. We searched the Medline, Embase, Scopus and Cochrane databases until May 14, 2022. The risk of bias was assessed using the Newcastle-Ottawa scale. The primary outcome was short-term (6 months to 1 year) mortality, and secondary outcomes included long-term (1 year to 3 years) mortality, in-hospital mortality, and postoperative delirium. A total of 14 studies with 32,746 patients (5,098 patients with cognitive impairment at baseline, 27,648 without) were included in our meta-analysis. Among studies that reported the raw proportion of patients with mortality of postoperative delirium, cognitive impairment significantly increased mortality (risk ratio 2.10, 95% confidence intervals [CIs] 1.43 to 3.08, p = 0.0002) and postoperative delirium (risk ratio 2.27, 95% CI 1.76 to 2.93, p <0.0001). Studies which reported the hazards for mortality (pooled hazards ratio 1.97, 95% CI 1.50 to 2.60, p <0.0001) and odds of postoperative delirium (pooled odds ratio 2.40, 95% CI: 1.51 to 3.80, p = 0.0002) yielded results consistent with the primary meta-analysis. In conclusion, pre-existing cognitive impairment is a significant risk factor for poorer outcomes after TAVI and should be carefully considered in this group of patients. Guidelines and future studies should take cognitive impairment into consideration for preoperative risk stratification.

Background Left ventricular thrombus (LVT) may develop in patients following myocardial infarction (MI), as well as in ischaemic and non-ischaemic cardiomyopathies, and may result in acute ischaemic stroke. Smaller studies comparing LVT associated with ischaemic and non-ischaemic aetiologies only reported 1-year outcomes or focused on specific subpopulations. We aimed to compare the clinical and echocardiographic characteristics and longer-term outcomes in a large population of patients with ischaemic versus non-ischaemic LVT. Methods This was a retrospective study of 552 consecutive patients with echocardiographically-identified LVT from March 2011 to January 2021 at a tertiary centre. Ischaemic LVT included LVT associated with MI and ischaemic cardiomyopathy. Non-ischaemic LVT included cases without evidence of ischaemia. Echocardiographic images were interpreted by trained cardiologists. We studied thrombus resolution as well as 5-year rates of ischaemic stroke and all-cause mortality. Results Of the 552 patients, mean age was 59.9 years and 84.4% were male. 492 patients had ischaemic LVT and 60 patients had non-ischaemic LVT. Ischaemic LVT was associated with older age (60.4 versus 55.3 years), male sex (86.8% versus 65.0%), smoking (49.2% versus 25.0%) and hyperlipidaemia (54.3% versus 28.3%). Left ventricular ejection fraction (LVEF) was lower in non-ischaemic LVT (28.9% versus 31.9%). LVEF ≤35% was associated with increased mortality in ischaemic LVT (HR 2.11, 95% CI 1.32–3.38). Rates of thrombus resolution, stroke and all-cause mortality were similar in the 2 groups. Anticoagulation was associated with a lower risk of stroke in ischaemic LVT (HR 0.32, 95% CI 0.16–0.66) and lower mortality in both ischaemic (HR 0.44, 95% CI 0.26–0.72) and non-ischaemic LVT (HR 0.14, 95% CI 0.03–0.61). Conclusion Patients with ischaemic LVT were more often older, male, smokers and had cardiovascular co-morbidities compared to those with non-ischaemic LVT. Thrombus resolution, stroke and all-cause mortality rates were similar in both groups. Anticoagulation was associated with lower mortality but this needs to be investigated in future prospective studies. Funding Acknowledgement Type of funding sources: Public Institution(s). Main funding source(s): CHS was supported by the National University of Singapore Yong Loo Lin School of Medicine's Junior Academic Faculty Scheme

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.

Acute ischemic strokes (AIS) are closely linked with air pollution, and there is some evidence that traditional cardiovascular risk factors may alter the relationship between air pollution and strokes. We investigated the effect of atrial fibrillation (AF) on the association of AIS with air pollutants. This was a nationwide, population-based, case-only study that included all AIS treated in public healthcare institutions in Singapore from 2009 to 2018. Using multivariable logistic regression, adjusted for time-varying meteorological effects, we examined how AF modified the association between AIS and air pollutant exposure. A total of 51,673 episodes of AIS were included, with 10,722 (20.7%) having AF. The odds of AIS in patients with AF is higher than those without AF for every 1 µg/m3 increase in O3 concentration (adjusted OR [aOR]: 1.005, 95% CI 1.003–1.007) and every 1 mg/m3 increase in CO concentration (aOR: 1.193, 95% CI 1.050–1.356). However, the odds of AIS in patients with AF is lower than those without AF for every 1 µg/m3 increase in SO2 concentration (aOR: 0.993, 95% CI 0.990–0.997). Higher odds of AIS among AF patients as O3− and CO concentrations increase are also observed in patients aged ≥65 years and non-smokers. The results suggest that AF plays an important role in exacerbating the risk of AIS as the levels of O3 and CO increase.

Background Mechanical thrombectomy (MT) is an effective treatment for patients with acute ischemic stroke (AIS) from basilar artery occlusion (BAO). Objective To compare the clinical outcomes of MT, with and without bridging intravenous thrombolysis (IVT), in acute BAO through a systematic review and meta-analysis of the current literature. Methods Systematic searches of Medline, EMBASE, and Cochrane Central were undertaken on August 1, 2022. Good functional outcome defined as 90-day modified Rankin Scale score 0–2 was the primary outcome measure. Secondary outcome measures were 90-day mortality, successful post-thrombectomy recanalization (modified Thrombolysis in Cerebral Infarction score ≥2b), symptomatic intracranial hemorrhage (sICH), and subarachnoid hemorrhage (SAH). Results Three studies reporting 1096 patients with BAO AIS were included in the meta-analysis. No significant differences in good functional outcome were detected between the two groups (RR=1.28 (95% CI 0.86 to 1.92); p=0.117). However, specifically patients with large artery atherosclerosis (LAA) benefited from bridging IVT (OR=2.52 (95% CI 1.51 to 4.22); p<0.001) with better functional outcomes. There was a significantly lower 90-day mortality rate for patients who underwent bridging IVT compared with MT alone (RR=0.70 (95% CI 0.62 to 0.80); p=0.008). No significant differences were detected in rates of post-treatment recanalization (RR=1.01 (95% CI 0.35 to 2.91); p=0.954), sICH (RR=0.96 (95% CI 0.66 to 1.42); p=0.724), and SAH (RR=0.93 (95% CI 0.31 to 2.83); p=0.563). Conclusions In patients with AIS due to BAO, bridging IVT was associated with lower mortality rates at 90 days, compared with direct MT. There were no improved functional outcomes or increased sICH or SAH between both arms, However, patients with LAA benefited from bridging IVT, with better functional outcomes.

We thank Dr Zhou Shunfeng for his kind comments on our study.¹ Our study synthesized data from case reports regarding cardio-cerebral infarctions (CCI), to determine the characteristics of the patients and the available treatment modalities. Given the high mortality rate of CCI, and consequently a low number of recorded cases in literature, no relevant large-scale studies surfaced during our search, which was also commented on by the author. We appreciate the author for highlighting this need, as further research is needed to determine the best treatment for these patients. Another suggestion was including patient characteristics such as body mass index, occupation and diet. We agree that the description of the above parameters would better characterize the population of patients that experience CCI. We are unfortunately limited in the collection of such data due to the nature of the studies available for use in our analysis. Future large-scale studies would benefit by including the above parameters in their data collection and reporting.

Background and aims Patients with Moyamoya disease (MMD) can present with ischaemic or haemorrhagic stroke. There is no good evidence for treatment strategies in MMD-associated acute ischaemic stroke (AIS), particularly for treatments like intravenous thrombolysis (IVT) and endovascular thrombectomy (ET). As the intracranial vessels are friable in MMD, and the risk of bleeding is high, the use of IVT and ET is controversial. To clarify the safety and efficacy of IVT/ET in the treatment of MMD-associated AIS, we performed a systematic review and meta-summary to examine this issue. Methods A systematic search was performed from four electronic databases: PubMed (MEDLINE), Cochrane Library, EMBASE and Scopus, profiling data from inception till 21 November 2021, as well as, manually on Google Scholar. Results Ten case reports detailing 10 MMD patients presenting with AIS and undergoing IVT or ET, or both, were included in the analysis. The median National Institute of Health Stroke Scale score at presentation was 10 (Interquartile Range [IQR] = 6.0–16.5). IVT alone was instituted in 6 patients, primary ET was attempted in 2, and 2 had received bridging IVT with ET. Of the 4 patients who underwent ET, 2 patients achieved successful reperfusion (modified Thrombolysis In Cerebral Infarction scale [mTICI] ≥ 2b). In terms of functional outcomes, One patient achieved complete recovery (modified Rankin Scale 0), 4 patients attained improvement in neurological status, and 4 had no improvement, whilst functional outcome was unreported in 1 patient. No patient experienced symptomatic intracranial haemorrhage. Conclusions In this systematic review and meta-summary, the utility of IVT and ET in MMD-associated AIS appears feasible in selected cases. Further larger cohort studies are required to evaluate these treatment approaches. Highlights · AIS in MMD was typically managed with bypass surgery but not via thrombolysis or thrombectomy. · In this meta-summary, all patients treated with thrombolysis and/or thrombectomy survived and some experienced symptomatic and/or functional improvement. · Further larger cohort studies are necessary for investigating the role of thrombolysis and/or thrombectomy as treatment of AIS in MMD.

Introduction: Heart failure (HF) is associated with ischaemic stroke (IS). However, there are limited studies on prevalence of IS, white matter hyperintensities (WMHs) and silent brain infarcts (SBIs). Furthermore, interaction with ejection fraction (EF) is unclear. Methods: We searched 3 databases (PubMed, Embase, Cochrane) for studies reporting incidence or prevalence of IS, WMH, SBIs in HF. Two authors independently selected studies for inclusion. We used random-effects models and heterogeneity was evaluated with I2. Results: 41 articles with 870,002 patients were retrieved from 15,267 records. Among HF patients, pooled proportion of IS was 4.06% (95% CI: 2.94–5.59), WMH and SBI were significantly higher at 15.67% (95% CI: 4.11-44.63) and 23.45% (95% CI: 14.53-35.58). Sub-group analysis of HFpEF and HFrEF revealed pooled prevalence of 2.97% (95% CI: 2.01–4.39) and 3.69% (95% CI: 2.34–5.77). Subgroup analysis of WMH with Fazekas Score 1, 2, 3 revealed a decreasing trend from 60.57 % (95% CI: 35.13-81.33) to 11.57% (95% CI: 10.40-12.85) to 3.07% (95% CI: 0.95-9.47). Relative risk and hazard ratio of HF patients developing IS were 2.29 (95% CI: 1.43-3.68) and 1.63 (95% CI: 1.22-2.18). Conclusion: We obtained estimates for prevalence of IS, WMH, SBI in HF from systematic review of literature.

Background and Aims: Symptomatic intracranial atherosclerotic disease (ICAD) and extracranial carotid atherosclerotic disease (ECAD) each carry a high risk of ischemic stroke recurrence. However, limited evidence exists about how the outcomes of these diseases differ, especially when they overlap. We aimed to directly compare the 90-day outcomes of patients with ICAD, ECAD, and ICAD with concomitant ECAD. Methods: From 2017 to 2021, ischemic stroke patients with significant ICAD and/or ECAD were prospectively enrolled. The cohort was divided into three groups: ICAD, ECAD, and ICAD with concomitant ECAD. The primary outcome assessed was 90-day ischemic stroke recurrence. Secondary outcomes included 90-day all-cause mortality, myocardial infarction (MI), and major adverse cardiovascular events (MACE, including death, MI, and/or ischemic stroke). Results: Of 371 patients included in the analysis, 240 (64.7%) patients had ICAD only, 93 (25.0%) patients had ECAD only, and 38 (10.3%) patients had ICAD with concomitant ECAD. On multivariate time-to-event analysis adjusting for potential confounders and with ICAD as the reference comparator, the risk of 90-day clinical outcomes was highest among patients with ICAD and concomitant ECAD, with adjusted hazard ratios of 9.32 (95% CI=1.58, 54.8; p=0.014), 4.54 (95% CI=1.45, 14.2; p=0.006), and 8.52 (95% CI=3.54, 20.5; p<0.001) for 90-day MI, ischemic stroke, and MACE, respectively. Conclusions: Patients with ICAD and concomitant ECAD have a poorer prognosis and are at significantly higher risk for 90-day MI, ischemic stroke, and MACE. Further evaluation of coronary atherosclerotic disease and more aggressive medical therapy may reduce the risk of ischemic events in this population.

Purpose Transcatheter aortic valve replacement (TAVR) is increasingly carried out in patients with aortic valvular conditions. Atrial fibrillation (AF) is a common comorbidity among patients undergoing TAVR. Despite this, there remains a paucity of data and established guidelines regarding anticoagulation use post-TAVR in patients with AF. Methods Four databases were searched from inception until 12 October 2021. A title and abstract sieve, full-text review and data extraction were conducted by independent authors, and articles including patients without AF were excluded. The Review Manager (Version 5.4) was utilised in data analysis. Results A total of 25,199 post-TAVR patients with AF were included from seven articles, with 9764 patients on non-vitamin K antagonist oral anticoagulants (NOAC) and 15,435 patients on vitamin K antagonists (VKA). In this analysis, there was a significantly lower risk of all-cause mortality at 1 year (RR: 0.75, CI: 0.58–0.97, p = 0.04, I² = 56%), and bleeding at 1 year (RR: 0.73, CI: 0.68–0.79, p = < 0.00001, I² = 0%), between patients on NOAC and VKA. There were no detectable differences between patients on NOAC and VKA for all-cause mortality at 2 years, stroke within 30 days, stroke within 1 year, ischaemic stroke at 1 year and life-threatening bleeding at 30 days. Conclusion While the results of this analysis reveal NOAC as a potential alternate treatment modality to VKA in post-TAVR patients with AF, further research is needed to determine the full safety and efficacy profile of NOAC (PROSPERO: CRD42021283548).

Background Right-sided cardiac thrombus is rare and may be caused by venous thromboembolism, in association with medical devices or stasis of blood in atrial fibrillation and cardiomyopathies. Complications include pulmonary embolism (PE) and paradoxical stroke. Current data are limited and mostly from case series and PE registries. We aimed to describe the clinical characteristics, echocardiographic features, treatment and outcomes of right-sided cardiac thrombus patients. Methods This was a retrospective observational study of 97 consecutive patients with right-sided cardiac thrombus detected on echocardiography. We studied co-morbidities, predisposing factors, thrombus characteristics and therapeutic interventions and assessed their associations with development of PE, paradoxical stroke, circulatory collapse and all-cause mortality. Results Mean age was 58.7 years and 55/97 (56.7%) were female. Ischaemic heart disease, heart failure, chronic kidney disease and malignancy were common co-morbidities. Right atrial thrombus was often associated with medical devices while right ventricular thrombus was more commonly associated with cardiomyopathy. Thrombus mobility did not affect embolic events but was associated with greater short-term mortality. On multivariable analysis, anticoagulation (HR 0.25, 95% CI 0.09–0.68) and thrombus resolution (HR 0.28, 95% CI 0.13–0.62) were associated with greater survival. Conclusions Right-sided cardiac thrombus is rare but may have potentially life-threatening complications such as PE and paradoxical stroke. Further research is needed to determine optimal therapeutic strategies in this poorly-studied population.

Background Patients with mitral stenosis (MS) may be predisposed to acute cerebrovascular events (ACE) and peripheral thromboembolic events (TEE). Concomitant atrial fibrillation (AF), mitral annular calcification (MAC) and rheumatic heart disease (RHD) are independent risk factors. Our aim was to evaluate the incidence of ACEs in MS patients and the implications of AF, MAC, and RHD on thromboembolic risks. Methods This systematic review was registered on PROSPERO (CRD42021291316). Six databases were searched from inception to 19th December 2021. The clinical outcomes were composite ACE, ischaemic stroke/transient ischaemic attack (TIA), and peripheral TEE. Results We included 16 and 9 papers, respectively, in our qualitative and quantitative analyses. The MS cohort with AF had the highest incidence of composite ACE (31.55%; 95%CI 3.60-85.03; I²=99%), followed by the MAC (14.85%; 95%CI 7.21-28.11; I²=98%), overall MS (8.30%; 95%CI 3.45-18.63; I²=96%) and rheumatic MS population (4.92%; 95%CI 3.53-6.83; I²=38%). Stroke/TIA were reported in 29.62% of the concomitant AF subgroup (95%CI 2.91-85.51; I²=99%) and in 7.11% of the overall MS patients (95%CI 1.91-23.16; I²=97%). However, the heterogeneity of the pooled incidence of clinical outcomes in all groups, except the rheumatic MS group, were substantial and significant. The logit-transformed proportion of composite ACE increased by 0.0141 (95% CI 0.0111-0.0171; p<0.01) per year of follow-up. Conclusion In the MS population, MAC and concomitant AF are risk factors for the development of ACE. The scarcity of data in our systematic review reflects the need for further studies to explore thromboembolic risks in all MS subtypes.

Objective To investigate the incidence, risk factors, and association with cardiovascular outcomes of patients who developed symptomatic intracerebral hemorrhage (ICH) after non-emergency percutaneous coronary intervention (PCI).Methods We conducted a single-institution retrospective study of patients who developed symptomatic ICH after non-emergency PCI. To identify associations between clinical variables and outcomes, Cox-proportional hazards regression models were constructed. Outcomes analyzed include (1) all-cause mortality, (2) acute ischemic stroke (AIS) or transient ischemic attack (TIA), and (3) major adverse cardiovascular events (MACE).ResultsA total of 1,732 patients were included in the analysis. The mean (±SD) age was 61.1 (±11.3) years, and 1,396 patients (80.6%) were male. The cumulative incidence of symptomatic ICH after non-emergency PCI was 1.3% (22 patients). Age, chronic kidney disease, and prior coronary artery bypass graft surgery were independently associated with a higher risk of ICH after PCI, while hyperlipidemia was independently associated with a lower risk of ICH after PCI. ICH after PCI was independently associated with a higher risk of all-cause mortality and AIS or TIA after PCI.Conclusion Patients who are older, who have chronic kidney disease, and who have had prior coronary artery bypass graft surgery should be monitored for symptomatic ICH after non-emergency PCI.

Background and Purpose: Symptomatic intracranial atherosclerotic disease (ICAD) and extracranial carotid atherosclerotic disease (ECAD) each carry a high risk of ischemic stroke recurrence. However, limited evidence exists about how the outcomes of these diseases differ, especially when they overlap. We aimed to directly compare the 90-day outcomes of patients with ICAD, ECAD, and ICAD with concomitant ECAD. Methods: From 2017 to 2021, ischemic stroke patients with significant ICAD and/or ECAD were prospectively enrolled. The cohort was divided into three groups: ICAD, ECAD, and ICAD with concomitant ECAD. The primary outcome assessed was 90-day ischemic stroke recurrence. Secondary outcomes included 90-day all-cause mortality, myocardial infarction (MI), and major adverse cardiovascular events (MACE, including death, MI, and/or ischemic stroke). Results: Of 371 patients included in the analysis, 240 (64.7%) patients had ICAD only, 93 (25.0%) patients had ECAD only, and 38 (10.3%) patients had ICAD with concomitant ECAD. On multivariate time-to-event analysis adjusting for potential confounders and with ICAD as the reference comparator, the risk of 90-day clinical outcomes was highest among patients with ICAD and concomitant ECAD, with adjusted hazard ratios of 9.32 (95% CI=1.58, 54.8; p=0.014), 4.54 (95% CI=1.45, 14.2; p=0.006), and 8.52 (95% CI=3.54, 20.5; p<0.001) for 90-day MI, ischemic stroke, and MACE, respectively. Conclusions: Patients with ICAD and concomitant ECAD have a poorer prognosis and are at significantly higher risk for 90-day MI, ischemic stroke, and MACE. Further evaluation of coronary atherosclerotic disease and more aggressive medical therapy may reduce the risk of ischemic events in this population.

INTRODUCTION The burden of cognitive impairment in HF patients is significant and leads to longer hospital stay, higher readmission rates, and increased mortality. This review seeks to synthesize the available studies to determine the prevalence and incidence of cognitive impairment and dementia in HF patients. METHODS PubMed, Embase, PsychoINFO and Cochrane databases were systematically searched from their inception through to 3 May 2021. Study and population characteristics, total patients with HF, prevalence of cognitive impairment and dementia in HF patients and cognitive assessment tool were abstracted by two reviewers. RESULTS In heart failure patients, overall prevalence for cognitive impairment and dementia was 41.42% (CI) and 19.79% (dementia) respectively. We performed a meta-regression analysis which demonstrated that the risk of cognitive impairment and dementia increased with age. DISCUSSION Further research should investigate whether HF accelerates the rate of cognitive decline and the progression of dementia.

Introduction White matter hyperintensities (WMHs) have been observed with greater frequency in patients with migraine and are thought to be associated with impaired cognition and function. The relationship between WMHs and right-to-left shunt (RLS) in migraine patients is unknown. We performed a systematic review to determine if there is an association between RLS and WMHs in patients with migraine. Methods A systematic search of the literature was performed in PubMed and Embase using a suitable keyword search strategy from inception up to 16th June 2021. All studies that included patients with migraine and studied RLS and WMHs were included. Results A total of 8 non-randomized observational studies comprising 1125 patients with migraine were included; 576 had an RLS, compared to 549 patients with no RLS. The mean age of the study populations ranged from 28.4–43 years, while the average duration from migraine diagnosis ranged from 5.1–19 years. The proportion of female to male patients was consistently higher in all studies (60.0%–94.4%). Amongst migraine patients with RLS, 338 patients (58.7%) had WMHs. In contrast, 256 (46.6%) of migraine patients without RLS had WMHs. RLS was significantly associated with the presence of WMHs in migraine patients (OR: 1.56, 95% CI: 1.05-2.34, p = 0.03). Conclusion In migraine patients, RLS was significantly associated with the presence of WMHs. Longitudinal studies are warranted to establish RLS as a risk factor for WMHs in patients with migraine, and to establish the significance of these changes.

Objective The primary objective is to evaluate the use of colchicine as an anti-inflammatory agent for stroke prevention in patients with coronary artery disease. Background There has been a rising number of randomized controlled trials conducted in patients with coronary artery disease on the use of colchicine in reducing cardiovascular complications. Recent publications suggest colchicine reduces the risk of stroke and other cardiovascular events. Methods We performed a systematic review of known trials in the current literature to characterize the clinical characteristics and outcomes of colchicine treatment in patients with coronary artery disease. A literature search was performed in PubMed, Embase and SCOPUS using a suitable keyword search strategy from inception to 4 June 2021. All studies evaluating cardiovascular outcomes of colchicine treatment in patients with coronary artery disease were included. Results The systemic review included 5 randomized controlled trials assessing a total of 11,790 patients. Majority of studies used a colchicine dosing regimen of 0.5 mg once daily, with the median follow-up duration ranging from 6 to 36 months. Meta-analytic estimates for stroke incidence highlighted a statistically significant benefit for patients that were administered colchicine compared to placebo (OR 0.47, 95% CI 0.27–0.81, p = 0.006), and a non-significant benefit for myocardial infarction. There was no significant association between colchicine treatment and the adverse effects of gastrointestinal symptoms and myopathy/myalgia. Conclusions The use of colchicine reduces the risk of stroke in patients with a history of coronary artery disease, without a significant increase in gastrointestinal and myopathy/myalgia adverse effects.

Introduction/Objectives 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 prognosis of patients with hypertrophic cardiomyopathy. Methods 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 their types were not specified in the studies. Meta-analysis was performed using StataSE 16 software, and heterogeneity was assessed using I² test. Results 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. • Download figure • Open in new tab • Download powerpoint Abstract 15 Figure 1 Flow Chart. *We excluded the patients who did not have any hospitalization events during the follow-up. • Download figure • Open in new tab • Download powerpoint Abstract 15 Figure 2 Kaplan-Meier Carve for 90-day readmission View this table: • View inline • View popup Abstract 15 Table 1 Clinical Characteristics at 1st admission View this table: • View inline • View popup Abstract 15 Table 2 Differences between patients with Epilepsy and those without Epilepsy at readmission Conclusions 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. Conflict of Interest None

Recent studies have shown that sodium/glucose cotransporter 2 (SGLT2) inhibitors might exert favourable changes on cardiac parameters as observed on cardiovascular imaging. We conducted a systematic review and meta-analysis to determine the effects of SGLT2 inhibitors on cardiac imaging parameters. Four electronic databases (PubMed, Embase, Cochrane, Scopus) were searched for studies in which the effects of SGLT2 inhibitors on cardiac imaging parameters were examined. Studies in which a population was administered SGLT2 inhibitors and analysed by echocardiography and/or cardiac magnetic resonance (CMR) imaging were included. Random-effects pair-wise meta-analysis models were utilized to summarize the studies. A total of 11 randomized controlled trials was included with a combined cohort of 910 patients. Comparing patients receiving SGLT2 inhibitors with subjects receiving placebo, the mean change in CMR-measured left ventricular mass (LVM) was −3.87 g (95% confidence interval [CI], −7.77 to 0.04), that in left ventricular end-systolic volume (LVESV) was −5.96 mL (95% CI, −10.52 to −1.41) for combined LVESV outcomes, that in left atrial volume index (LAVi) was −1.78 mL/m 2 (95% CI, −3.01 to −0.55) for combined LAVi outcomes, and that in echocardiography-measured E/e′ was −0.73 (95% CI, −1.43 to −0.03). Between-group differences were not observed in LVM and LVESV after indexation. The only between-group difference that persisted was for LAVi. Treatment with SGLT2 inhibitors resulted in reduction in LAVi and E/e′ on imaging, indicating they might have an effect on outcomes associated with LV diastolic function.

Background An increasing number of studies have shown an association between migraine and cardiovascular disease, in particular cardio- and cerebro-vascular events. Methods Three electronic databases (PubMed, Embase and Scopus) were searched from inception to May 22, 2021 for prospective cohort studies evaluating the risk of myocardial infarction, stroke and cardiovascular mortality in migraine patients. A random effects meta-analysis model was used to summarize the included studies. Results A total of 18 prospective cohort studies were included consisting of 370,050 migraine patients and 1,387,539 controls. Migraine was associated with myocardial infarction (hazard ratio, 1.36; 95% CI, 1.23–1.51; p = < 0.001), unspecified stroke (hazard ratio, 1.30; 95% CI, 1.07–1.60; p = 0.01), ischemic stroke (hazard ratio, 1.35; 95% CI, 1.03–1.78; p = 0.03) and hemorrhagic stroke (hazard ratio, 1.43; 95% CI, 1.07–1.92; p = 0.02). Subgroup analysis of migraine with aura found a further increase in risk of myocardial infarction and both ischemic and hemorrhagic stroke, as well as improved substantial statistical heterogeneity. Migraine with aura was also associated with an increased risk of cardiovascular mortality (hazard ratio, 1.27; 95% CI, 1.14–1.42; p = < 0.001). Conclusion Migraine, especially migraine with aura, is associated with myocardial infarction and stroke. Migraine with aura increases the risk of overall cardiovascular mortality.

Background Sodium-glucose cotransporter 2 inhibitors (SGLT2i) are a group of antidiabetic medications with a favourable cardiovascular, renal and overall safety profile. Given the limited treatment options available for neurological disorders, it is important to determine whether the pleiotropic effects of SGLT2i can be utilised in their prevention and management. Methods All articles published before 20 March 2021 were systematically searched in MEDLINE, EMBASE, Scopus, Web of Science, APA PsycINFO and ClinicalTrials.gov. Overall, 1395 titles were screened, ultimately resulting in 160 articles being included in the qualitative analysis. Screening and data extraction were conducted by two independent authors and studies were excluded if they were not an original research study. Findings Of the 160 studies, 134 addressed stroke, 19 cognitive impairment, 4 epilepsy and 4 movement disorders, encompassing a range from systematic reviews and randomised controlled trials to bioinformatic and animal studies. Most animal studies demonstrated significant improvements in behavioural and neurological deficits, which were reflected in beneficial changes in neurovascular units, synaptogenesis, neurotransmitter levels and target receptors’ docking energies. The evidence from the minority clinical literature was conflicting and many studies did not reach statistical significance. Interpretation SGLT2i may exert neurological benefits through three mechanisms: reduction in cardiovascular risk factors, augmentation of ketogenesis and anti-inflammatory pathways. Most clinical studies were observational, meaning that a causal relationship could not be established, while randomised controlled trials were heterogeneous and powered to detect cardiovascular or renal outcomes. We suggest that a longitudinal study should be conducted and specifically powered to detect neurological outcomes.

Background: frailty has been shown to be a better predictor of clinical outcomes than age alone across many diseases. Few studies have examined the relationship between frailty, stroke and stroke interventions such as endovascular thrombectomy (EVT). Objective: we aimed to investigate the impact of frailty measured by clinical frailty scale (CFS) on clinical outcomes after EVT for acute ischemic stroke (AIS) in older patients ≥70 years. Methods: in this retrospective cohort study, we included all consecutive AIS patients age ≥ 70 years receiving EVT at a single comprehensive stroke centre. Patients with CFS of 1-3 were defined as not frail, and CFS > 3 was defined as frail. The primary outcome was modified Rankin Score (mRS) at 90 days. The secondary outcomes included duration of hospitalisation, in-hospital mortality, carer requirement, successful reperfusion, symptomatic intracranial haemorrhage and haemorrhagic transformation. Results: a total of 198 patients were included. The mean age was 78.1 years and 52.0% were female. Frail patients were older, more likely to be female, had more co-morbidities. CFS was significantly associated with poor functional outcome after adjustment for age, NIHSS and time to intervention (adjusted odds ratio [aOR] 1.54, 95% confidence interval [CI] 1.04-2.28, P = 0.032). There was trend towards higher mortality rate in frail patients (frail: 18.3%; non-frail: 9.6%; P = 0.080). There were no significant differences in other secondary outcomes except increased carer requirement post discharge in frail patients (frail: 91.6%; non-frail: 72.8%; P = 0.002). Conclusions: Frailty was associated with poorer functional outcome at 90 days post-EVT in patients ≥ 70 years.

Introduction: Identifying differences in outcome of basilar artery occlusion (BAO) between males and females may be useful in aiding clinical management. Recent studies have demonstrated widespread underrepresentation of women in acute stroke clinical trials. This international multicentre study aimed to determine sex differences in outcome after mechanical thrombectomy (MT) for patients with acute BAO. Methods: We performed a retrospective analysis of consecutive patients with BAO who had undergone MT in seven stroke centres across five countries (Singapore, Taiwan, United Kingdom, Sweden, and Germany), between 2015 and 2020. Primary outcome was a favourable functional outcome measured by a modified Ranking Scale (mRS) of 0-3 at 90 days. Secondary outcomes were mRS 0-3 upon discharge, mortality, symptomatic intracranial haemorrhage (sICH) and subarachnoid haemorrhage (SAH). Results: Among the 322 patients who underwent MT, 206 (64.0%) patients were male and 116 (36.0%) were female. Females were older than males (mean ± SD 70.9 ± 14.3 years vs. 65.6 ± 133.6 years; p = 0.001) and had higher rates of atrial fibrillation (38.9% vs. 24.2%; p = 0.012). Time from groin puncture to reperfusion was shorter in females than males (mean ± SD 57.2 ± 37.2 min vs. 71.1 ± 50.9 min; p = 0.021). Despite these differences, primary and secondary outcome measures were similar in females and males, with comparable rates of favourable 90-day mRS scores (mean ± SD 46 ± 39.7 vs. 71 ± 34.5; OR = 1.20; 95% confidence interval [CI] = 0.59-2.43; p = 0.611), favourable discharge mRS scores (mean ± SD 39 ± 31.6 vs. 43 ± 25.9; OR = 1.38; 95% CI = 0.69-2.78; p = 0.368) and in-hospital mortality (mean ± SD 30 ± 25.9 vs. 47 ± 22.8; OR = 1.15; 95% CI = 0.55-2.43; p = 0.710. Rates of complications such as sICH (mean ± SD 5 ± 4.3 vs. 9 ± 4.4; OR = 0.46; 95% CI = 0.08-2.66; p = 0.385) and SAH (mean ± SD 4 ± 3.4 vs. 5 ± 2.4; OR = 0.29; 95% CI = 0.03-3.09; p = 0.303) comparably low in both groups. Conclusion: Females achieved comparable functional outcomes compared with males after undergoing MT for BAO acute ischemic stroke.

Introduction: Patients with migraines, particularly those with auras, may present with stroke. Atrial fibrillation is a known risk factor for stroke. With common pathophysiological factors between migraines and atrial fibrillation, we aimed to clarify the association between migraine and atrial fibrillation in this systematic review and meta-analysis. Materials and Methods: A literature search was conducted in EMBASE, PubMed, Scopus and Cochrane electronic bibliographic databases from inception to 14th June 2021 with the following inclusion criteria: (1) cohort or cross-sectional studies, (2) patients ≥ 18-years-old, (3) studies examining association between atrial fibrillation and migraines. Exclusion criteria were case-control studies, studies including patients with prior diagnosis of atrial fibrillation or non-migrainous headache. The Newcastle Ottawa Scale was used to assess the quality of studies. Results: 6 studies were included, demonstrating a 1.61% (95% CI 0.51, 3.29) pooled prevalence of atrial fibrillation in migraine with aura and 1.32% (95% CI 0.17, 3.41) in migraine without aura. The total prevalence of atrial fibrillation in migraine was 1.39% (95% CI 0.24, 3.46) overall. Conclusion: Overall, there was a higher prevalence of atrial fibrillation in migraine with aura compared to migraine without aura. Prevalence of atrial fibrillation in migraine patients was low.

Background Patients with atrial fibrillation (AF) require oral anticoagulation to prevent ischemic stroke. However, oral anticoagulation may cause bleeding, and patients with AF and a history of bleeding were excluded from pivotal trials comparing non-vitamin K antagonist oral anticoagulants (NOACs) and warfarin. We therefore aimed to assess the efficacy and safety of NOACs compared with warfarin in patients with AF and a history of bleeding. Methods We conducted a systematic review of retrospective studies and clinical trials using the PubMed, EMBASE, SCOPUS, Cochrane Library, and Web of Science databases to May 2021. Results Overall, 56,697 patients from six studies were included. NOACs significantly reduced the risk of ischemic stroke (hazard ratio [HR] 0.73, 95% confidence interval [CI] 0.59–0.91; p = 0.005), fatal ischemic stroke (HR 0.49, 95% CI 0.39–0.61; p < 0.001), all-cause mortality (HR 0.70, 95% CI 0.50–0.98; p = 0.04), major bleeding events (HR 0.75, 95% CI 0.67–0.84; p < 0.001), intracranial hemorrhage (ICH; HR 0.63, 95% CI 0.48–0.82; p < 0.001), fatal ICH (HR 0.33, 95% CI 0.20–0.56, p < 0.001), and gastrointestinal bleeding (HR 0.83, 95% CI 0.72–0.96; p = 0.01). Conclusions NOACs showed better efficacy and safety profile compared with warfarin in patients with AF and a history of bleeding. Randomized controlled trials are warranted to validate these findings.

Previous intracerebral hemorrhage (ICH) is labelled as a contraindication for the use of intravenous tissue plasminogen activator (IV-tPA) in acute ischemic stroke (AIS) based on expert opinion. However, there is a paucity of data available regarding the benefits and risks of IV-tPA in this population. Recent small retrospective cohort studies reporting its off-label use suggest it may be beneficial. This study aims to investigate the safety and efficacy of IV-tPA in AIS patients with previous ICH. We performed a systematic review and meta-analysis of studies reporting on IV-tPA use in AIS patients with and without previous ICH. We searched Embase, PubMed and Cochrane Library from inception to 20 April 2021. Outcomes measured included symptomatic ICH (sICH), 3-month modified Rankin Scale (mRS) score, and 3-month mortality. We included seven retrospective cohort studies comprising 5760 AIS patients who had received IV-tPA, of which 134 had previous ICH. There was no significant difference in the odds of sICH (OR 1.57, 95% CI 0.78-3.15, p = 0.21) and 3-month mRS (mRS 0-1: OR 0.78, 95% CI 0.37-1.65, p = 0.52; mRS 0-2: OR 1.07, 95% CI 0.36-3.15, p = 0.90) between patients with and without previous ICH. There was a trend towards higher 3-month mortality in patients with previous ICH (OR 1.69, 95% CI 0.98-2.91, p = 0.06), although this did not reach statistical significance. The use of IV-tPA in AIS patients with previous ICH was not associated with an increased risk of sICH or disability at 3 months. Further larger studies are needed to establish the safety and efficacy of IV-tPA use in this population.

Introduction: Hypertrophic cardiomyopathy (HCM) predisposes to adverse cerebrovascular events (ACEs) including ischaemic stroke, transient ischaemic attack (TIA), thromboembolic event (TEE) and peripheral embolism (PE). Concomitant atrial fibrillation (AF), which is more prevalent in the HCM population, confers even higher risk. Our aims are to report the prevalence of ACEs in HCM patients and to determine the additional clinical risks of AF on the prognosis of this population. Methods: A systematic literature search was performed on PubMed, Scopus, Embase/ Ovid and Cochrane library from inception to 20 th March 2021. No limitations on language or date of publication were applied. The primary outcome of this review was to examine and compare the prevalence of ischaemic stroke in the HCM population with or without AF. Secondary outcomes were to identify their risk of non-stroke clinical outcomes such as TIA, non-specified TEE and PE. Non-specified TEE in our paper only referred to thromboembolic events whereby their types were not specified in the included studies. Meta-analysis was performed using StataSE 16 software, and heterogeneity was assessed using I ² test. Results: A total of 713 studies were identified, and 35 articles with 42,570 patients were included. The pooled prevalence of stroke/ TIA was 7.45% (95% confidence interval [CI] 5.80 - 9.52, p = 0.000) across 24 studies in the overall HCM population of 37,643 patients. AF contributed to a significantly higher risk of non-specified TEE (Risk ratio [RR] 4.49, 95% CI 1.88 - 10.73, p = 0.0007, I ² = 87.0) and total stroke/ TIA (RR 3.26, 95% CI 1.75 - 6.08, p = 0.0002, I ² = 76.0) in our study population. Within the apical HCM (ApHCM) population, the prevalence of stroke/ TIA was 9.30% (95% CI 6.64 - 12.87, p = 0.316). Conclusion: Our study concludes that concomitant AF diagnosis increases the risk of developing thromboembolic events and the stroke-related mortality rate. Although the prevalence of stroke/ TIA in the ApHCM subtype was slightly higher than the overall HCM population, further studies investigating the clinical outcomes of HCM subtypes are warranted.

Introduction: Whilst surgical decompression in malignant middle cerebral artery infarction is well established, its role in malignant posterior circulation infarction (MPCI) is unclear. Recent small cohort studies suggest that neurosurgery in this group may be beneficial. This systematic review and meta-analysis aims to compare outcomes of MPCI patients undergoing surgical intervention versus medical therapy. Methods: Medline, Embase and Cochrane were searched from inception until 2 April 2021. Studies were included if they evaluated patients with posterior circulation stroke treated with neurosurgical intervention. Observational cohort studies and case series with death and functional outcome data were included. Death was defined as Glasgow Outcome Scale (GOS) 1 and modified Rankin scale (mRS) 6, or extracted from the text. Favourable functional outcome was defined as mRS 0-2, GOS 4-5, Barthel Index 91-100 or extracted from text at the latest follow-up period. 6673 studies were filtered, with 31 studies included for data extraction, of which 8 studies included both a surgical and medical therapy group. Random effects meta-analysis, analysis of proportions and meta-regression were performed. Results: The medical therapy cohort (n=235) had significantly better odds of good functional outcome (GFO) than the surgical cohort. There was no significant difference in odds of death between the two groups (Figure 1). Amongst surgical patients (n=184), 18% died and 55% had GFO. On meta-regression, the proportion of patients with atrial fibrillation and hydrocephalus was negatively associated with odds of death and GFO respectively (both p<0.05). Conclusion: In patients with MPCI, neurosurgery did not improve functional outcome or mortality in comparison with medical therapy. Larger cohort studies are warranted to resolve this clinical equipoise.

Introduction: It could be theorised that liver fibrosis and acute ischemic stroke (AIS) are related by inflammatory changes, but few studied this link, let alone in patients receiving intravenous thrombolysis (IVT). The Fibrosis (FIB)-4 index is an established rapid score to detect liver fibrosis. We aimed to understand the role of FIB-4 in predicting AIS subtype, severity and outcomes after IVT. Methods: AIS patients receiving IVT without severe liver derangement from 2006 to 2018 at a stroke centre were studied. Stroke subtype was defined using Trial of Org 10172 in Acute Stroke Treatment. Moderate and severe stroke was defined as National Institutes of Health Stroke Scale (NIHSS) ≥10. FIB-4 index was stratified into no advanced fibrosis (FIB-4 <1.45) and advanced fibrosis (FIB-4 >3.25). The primary outcome - functional outcome at 90-days using the modified Rankin Scale (mRS) - was analysed by ordinal shift analysis. Multivariable adjusted logistic regression evaluated associations of FIB-4 with stroke severity, functional independence (90-day mRS 0-2 vs 3-6), 90-day mortality, and symptomatic intracranial hemorrhage (SICH). Results: Among 900 patients, higher median FIB-4 was seen in cardioembolic stroke (CES) than non-CES (1.93 [IQR: 1.39-2.81] vs 1.27 [IQR: 0.92-1.90], p<0.001). On multivariate analysis, higher FIB-4 predicted moderate and severe stroke (OR: 1.33, 95% CI: 1.08-1.68, p=0.012). On ordinal shift analysis, advanced fibrosis was associated with an unfavourable shift in 90-day mRS compared to no advanced fibrosis (OR: 1.75, 95% CI: 1.06-2.89, p=0.028). Advanced fibrosis was also associated with increased mortality (OR: 3.07, 95% CI: 1.47-6.48, p=0.003) and SICH (OR: 3.65, 95% CI: 1.21-11.17, p=0.022), but not functional independence (OR: 0.80, 95% CI: 0.40-1.55, p=0.512). Conclusion: Liver fibrosis was associated with higher rates of CES, more severe AIS, and poorer outcomes after IVT. This is a novel marker that could prognosticate IVT use in AIS.

Background: Acute ischemic stroke (AIS) is significantly associated with gaseous pollutants. There is early evidence that susceptibility to air pollution interacts with traditional stroke cardiovascular risk factors, but data on AF is limited. We investigated the effect of AF on the association of AIS episodes with short-term exposure of air pollutants. Methods: In this nationwide, population-based case-only study, and all daily cases of AIS in Singapore from 2009 and 2018 were collected. We compared the outcome AF across different levels of air pollutants (PM 2.5 , PM 10 , O 3 , NO 2 , SO 2 and CO) in cases of AIS. Multivariable regression analysis adjusted for time varying meteorological effects. Prespecified subgroup analysis based on age (<65 years and ≥65 years), and smoking status were performed. Results: A total of 51,673 episodes of AIS were identified, and 10,722 (20.7%) had AF (Table 1). The risk of AIS was higher for patients with AF for every unit increase in CO (adjusted OR 1.193; 95% CI 1.050-1.356; p=0.007) and O 3 concentration (adjusted OR 1.005; 95% CI 1.003-1.007; p<0.001) than those without, but lower for every unit increase in SO 2 (aOR 0.993; 95% CI 0.990-0.997; p<0.001). AF had no significant interaction effect with PM 2.5 , PM 10 and NO 2 (Table 2). The risk of AIS associated with O 3 and CO concentration remained elevated in patients with AF for up to 5 days from exposure; O3 (OR 1.004; 95% CI 1.002-1.006; p<0.001) and CO (OR 1.206; 95% CI 1.064-1.367; p=0.003) respectively. Conclusion: AF increased the risk of AIS driven by air pollutants O 3 and CO but reduced the risk of AIS associated with SO 2 .

Background: Contradicting evidence exists regarding the role of lipids in intravenous (IV) thrombolysis with tissue plasminogen activator (tPA), with some studies suggesting low lipid levels are paradoxically associated with poorer post-thrombolysis outcomes. Methods: Restricted cubic spline regression, multivariable-adjusted logistic regression and risk score models evaluated associations of five lipid parameters with poor functional outcome (90-day modified Rankin Scale >2), symptomatic intracranial hemorrhage (SICH), and mortality among 1004 acute ischemic stroke (AIS) patients who received IV tPA in a comprehensive stroke center. Results: There was a U-shaped relationship of low-density lipoprotein cholesterol (LDL-C) and non-high-density lipoprotein cholesterol (non-HDL-C) with all three outcomes using spline regression. Quartile (Q) 2 and Q4 of non-HDL-C were associated with increased odds of SICH (OR 4.2, 95% CI 1.2-15.0, p=0.026 and OR 5.1, 95% CI 1.4-18.2, p=0.011) compared to Q3. Similar quartile associations were found for total cholesterol (TC), and for LDL-C/HDL-C ratio with poor functional outcome. Q1 and Q2 of HDL-C were associated with increased odds of poor functional outcome (OR 1.6, 95% CI 1.0-2.5, p=0.043 and OR 1.6, 95% CI 1.0-2.4, p=0.042) compared to Q4. Only Q3 of LDL-C/HDL-C ratio was associated with increased odds of large-artery atherosclerotic stroke (OR 1.9, 95% CI 1.0-3.7, p=0.039) compared to Q1. Conclusion: In AIS patients who received IV tPA, a U-shaped relationship was found between non-HDL-C and SICH. Low LDL-C was associated with increased odds of mortality, while HDL-C may be protective against poor functional outcome.

Intravenous tissue plasminogen activator (tPA) remains the cornerstone of recanalization therapy for acute ischemic stroke (AIS), albeit with varying degrees of response. The triglyceride-glucose (TyG) index is a novel marker of insulin resistance, but association with outcomes among AIS patients who have received tPA has not been well elucidated. We studied 698 patients with AIS who received tPA from 2006 to 2018 in a comprehensive stroke centre. TyG index was calculated using the formula: ln[fasting triglycerides (mg/dL) × fasting glucose (mg/dL)/2]. TyG index was significantly lower in patients that survived at 90-days than those who died (8.61 [Interquartile Range: 8.27–8.99] vs 8.76 [interquartile range: 8.39–9.40], p = 0.007). In multivariate analysis, TyG index was significantly associated with 90-day mortality (OR: 2.12, 95% CI: 1.39–3.23, p = 0.001), poor functional outcome (OR: 1.41 95% CI: 1.05–1.90, p = 0.022), and negatively associated with early neurological improvement (ENI) (OR: 0.68, 95% CI: 0.52–0.89, p = 0.004). There was no association between TyG index and symptomatic intracranial hemorrhage. ‘High TyG’ (defined by TyG index ≥ 9.15) was associated with mortality, poor functional outcomes and no ENI. In conclusion, the TyG index, a measure of insulin resistance, was significantly associated with poorer clinical outcomes in AIS patients who received tPA.

Background The use of a combination of balloon guide catheter (BGC), aspiration catheter, and stent retriever in acute ischemic stroke thrombectomy has not been shown to be better than a stent retriever and BGC alone, but this may be due to a lack of power in these studies. We therefore performed a meta-analysis on this subject. Methods A systematic literature search was performed on PubMed, Scopus, Embase/Ovid, and the Cochrane Library from inception to October 20, 2021. Our primary outcomes were the rate of successful final reperfusion (Treatment in Cerebral Ischemia (TICI) 2c–3) and first pass effect (FPE, defined as TICI 2c–3 in a single pass). Secondary outcomes were 3 month functional independence (modified Rankin Scale score of 0–2), mortality, procedural complications, embolic complications, and symptomatic intracranial hemorrhage (SICH). A meta-analysis was performed using RevMan 5,4, and heterogeneity was assessed using the I ² test. Results Of 1629 studies identified, five articles with 2091 patients were included. For the primary outcomes, FPE (44.9% vs 45.4%, OR 1.04 (95% CI 0.90 to 1.22), I ² =57%) or final successful reperfusion (64.5% vs 68.6%, OR 0.98 (95% CI 0.81% to 1.20%), I ² =85%) was similar between the combination technique and stent retriever only groups. However, the combination technique had significantly less rescue treatment (18.8% vs 26.9%; OR 0.70 (95% CI 0.54 to 0.91), I ² =0%). This did not translate into significant differences in secondary outcomes in functional outcomes, mortality, emboli, complications, or SICH. Conclusion There was no significant difference in successful reperfusion and FPE between the combined techniques and the stent retriever and BGC alone groups. Neither was there any difference in functional outcomes, complications, or mortality.

Cognitive impairment (CI) is common in heart failure (HF). Patients with HF demonstrate reduced global cognition as well as deficits in multiple cognitive domains compared to controls. Degree of CI may be related to HF severity. HF has also been associated with an increased risk of dementia. Anatomical brain changes have been observed in patients with HF, including grey matter atrophy and increased white matter lesions. Patients with HF and CI have poorer functional independence and self-care, more frequent rehospitalisations as well as increased mortality. Pathophysiological pathways linking HF and CI have been proposed, including cerebral hypoperfusion and impaired cerebrovascular autoregulation, systemic inflammation, proteotoxicity and thromboembolic disease. However, these mechanisms are poorly understood. We conducted a search on MEDLINE, Embase and Scopus for original research exploring the connection between HF and CI. We then reviewed the relevant literature and discuss the associations between HF and CI, the patterns of brain injury in HF and their potential mechanisms, as well as the recognition and management of CI in patients with HF.

Background and purpose: Mechanical thrombectomy (MT) is an effective treatment for patients with basilar artery occlusion (BAO) acute ischemic stroke. It remains unclear whether bridging intravenous thrombolysis (IVT) prior to MT confers any benefit. This study compared the outcomes of acute BAO patients who were treated with direct MT versus combined IVT plus MT. Methods: This multicenter retrospective cohort study included patients who were treated for acute BAO from eight comprehensive stroke centers between January 2015 and December 2019. Patients received direct MT or combined bridging IVT plus MT. Primary outcome was favorable functional outcome defined as modified Rankin Scale 0-3 measured at 90 days. Secondary outcome measures included mortality and symptomatic intracranial hemorrhage (sICH). Results: Among 322 patients, 127 (39.4%) patients underwent bridging IVT followed by MT and 195 (60.6%) underwent direct MT. The mean±standard deviation age was 67.5±14.1 years, 64.0% were male and median National Institutes of Health Stroke Scale was 16 (interquartile range, 8 to 25). At 90-day, the rate of favorable functional outcome was similar between the bridging IVT and direct MT groups (39.4% vs. 34.4%, P=0.361). On multivariable analyses, bridging IVT was not as Comorbidisociated with favorable functional outcome, mortality or sICH. In subgroup analyses, patients with underlying atherosclerosis treated with bridging IVT compared to direct MT had a higher rate of favorable functional outcome at 90 days (37.2% vs. 15.5%, P=0.013). Conclusions: Functional outcomes were similar in BAO patients treated with bridging IVT versus direct MT. In the subgroup of patients with underlying large-artery atherosclerosis stroke mechanism, bridging IVT may potentially confer benefit and this warrants further investigation.

PurposeConventional predictive models are based on a combination of clinical and neuroimaging parameters using traditional statistical approaches. Emerging studies have shown that the machine learning (ML) prediction models with multiple pretreatment clinical variables have the potential to accurately prognosticate the outcomes in acute ischemic stroke (AIS) patients undergoing thrombectomy, and hence identify patients suitable for thrombectomy. This article summarizes the published studies on ML models in large vessel occlusion AIS patients undergoing thrombectomy.Methods We searched electronic databases including PubMed from 1 January 2000 up to 14 October 2019 for studies that evaluated ML algorithms for the prediction of outcomes in stroke patients undergoing thrombectomy. We then used random-effects bivariate meta-analysis models to summarize the studies.ResultsWe retained a total of five studies that evaluated ML (4 support vector machine, 1 decision tree model) with a combined cohort of 802 patients. The prevalence of good functional outcome defined by 90-day mRS of 0–2 when available. Random effects model demonstrated that the AUC was 0.846 (95% confidence interval, CI 0.686–0.902). A pooled diagnostic odds ratio of 12.6 was computed. The pooled sensitivity and specificity were 0.795 (95% CI 0.651–0.889) and 0.780 (95% CI 0.634–0.879), respectively.ConclusionML may be useful as an adjunct to clinical assessment to predict functional outcomes in AIS patients undergoing thrombectomy, and hence identify suitable patients for treatment. Further studies validating ML models in large multicenter cohorts are necessary to explore this further.

Objectives Recent clinical trials have shown the potential of sodium glucose cotransporter (SGLT) 2 inhibitors to reduce the risk of atrial fibrillation but not stroke. We conducted a systematic review and meta-analysis to clarify if SGLT2 or combined SGLT1/2 inhibitors affect the risk of atrial fibrillation and stroke in patients regardless of diabetic status. Materials and methods Four electronic databases were searched on 21st November 2020 for studies evaluating outcomes of stroke and atrial fibrillation with SGLT2 or combined SGLT1/2 inhibitors in both diabetic and non-diabetic patients. Both random and fixed effect, pair-wise meta-analysis models were used to summarize the results of the studies. Results A total of 13 placebo-controlled, randomized-controlled trials were included. Eight trials comprising 35,702 patients were included in the analysis of atrial fibrillation outcomes and eight trials comprising 47,910 patients were included in the analysis of stroke outcomes. Patients on SGLT inhibitors, particularly SGLT2 inhibitors, had lower odds of atrial fibrillation (Peto odds ratio [95% confidence interval] = 0.76 [0.63–0.92]) compared to placebo. This effect remained significant with a follow-up duration longer than 1 year, in studies utilizing dapagliflozin, patients with type 2 diabetes mellitus, and patients with cardiovascular disease. No difference was observed in the odds of atrial fibrillation in patients with baseline heart failure. No effect was seen on the risk of stroke in patients taking SGLT inhibitors. Conclusions SGLT2 inhibitors significantly reduced the odds of atrial fibrillation in diabetic patients. However, SGLT inhibitors did not significantly affect the risk of stroke.

Left ventricular thrombus (LVT) is a common complication of acute myocardial infarction and is associated with morbidity from embolic complications. Predicting which patients will develop death or persistent LVT despite anticoagulation may help clinicians identify high-risk patients. We developed a random forest (RF) model that predicts death or persistent LVT and evaluated its performance. This was a single-center retrospective cohort study in an academic tertiary center. We included 244 patients with LVT in our study. Patients who did not receive anticoagulation (n = 8) or had unknown (n = 31) outcomes were excluded. The primary outcome was a composite outcome of death, recurrent LVT and persistent LVT. We selected a total of 31 predictors collected at the point of LVT diagnosis based on clinical relevance. We compared conventional regularized logistic regression with the RF algorithm. There were 156 patients who had resolution of LVT and 88 patients who experienced the composite outcome. The RF model achieved better performance and had an AUROC of 0.700 (95% CI 0.553–0.863) on a validation dataset. The most important predictors for the composite outcome were receiving a revascularization procedure, lower visual ejection fraction (EF), higher creatinine, global wall motion abnormality, higher prothrombin time, higher body mass index, higher activated partial thromboplastin time, older age, lower lymphocyte count and higher neutrophil count. The RF model accurately identified patients with post-AMI LVT who developed the composite outcome. Further studies are needed to validate its use in clinical practice.

Background Cardiocerebral infarction (CCI), which involves the simultaneous occurrence of acute ischemic stroke (AIS) and acute myocardial infarction (AMI), has a reported incidence of 0.0009%. Treatment of CCI presents a dilemma to physicians as both conditions are time critical. Despite the need for standardised treatment protocols, published data is sparse. Methods Four databases, Pubmed, Embase, Scopus and Google Scholar were searched until 25 August 2020. A title and abstract sieve, full-text review and extraction of data were conducted independently by three authors. Results 44 cases of CCI were identified from 37 case reports and series. 15 patients (34.1%) were treated using percutaneous coronary intervention (PCI) with stent, eight patients (18.2%) were treated with a PCI without stent, ten patients (22.7%) were treated via a cerebral vessel thrombectomy, eight patients (18.2%) were treated via a thrombectomy of a coronary vessel. For medications, 20 patients (45.5%) were treated with thrombolytics, ten patients (22.7%) were treated with anticoagulants, eight patients (18.2%) were treated with antiplatelets and 11 patients (25.0%) were treated with anticoagulants and antiplatelets. Of 44 patients, ten patients died, and nine of those were due to cardiac causes. Among the 44 patients, days to death was observed to be a median of 2.0 days (IQR: 1.5, 4.0). The modified Rankin Score (mRS) was measured in nine patients, with a median score of 2.0 (IQR: 1.0, 2.5) being reported. Conclusion The condition of CCI has substantial morbidity and mortality, and further studies are needed to examine the optimal diagnostic and treatment strategies of these patients.

Background Calcium deposits in the heart have been associated with cardiovascular events, mortality, stroke as well as atrial fibrillation (AF). However, there is no accepted standard method for scoring cardiac calcifications. Existing methods have also not been validated for assessment of patients with embolic strokes of undetermined source (ESUS). This study aims to evaluate the association of various cardiac calcification scores with new-onset AF and stroke recurrence in a cohort of patients with ESUS. Methods This study identified and evaluated 181 consecutive stroke patients diagnosed with ESUS. They were followed-up for new-onset AF and ischemic stroke recurrence for a median duration of 2.1 years. Various echocardiographic cardiac calcification scores were assessed on the transthoracic echocardiogram performed during the evaluation of ESUS and subsequently assessed for their relation to AF detection and recurrent stroke. The echocardiographic calcium scores assessed were the (a) Global Cardiac Calcium Score (GCCS), (b) Echocardiographic Calcium Score (eCS), (c) Echocardiographic calcification score (echo-CCS), (d) Echocardiographic Composite Cardiac Calcium Score (E-CCCS), and (e) Total Heart Calcification (THC) score. Only 2 out of 5 scoring schemes, namely GCCS and eCG, quantified the cardiac calcium burden. Results Higher calcium scores as measured by GCCS and eCS were found to be significantly associated with subsequent AF detection as well as recurrent ischemic stroke in ESUS patients. The association with recurrent stroke remained significant even after adjustment for comorbidities and AF. Conclusion Higher cardiac calcification scores measured using the GCCS and eCS are independently associated with AF detection and recurrent ischemic stroke in ESUS patients and can be useful markers for further risk stratification in ESUS patients.

Objectives Non-emergency percutaneous coronary intervention (PCI) has lower risk of stroke than emergency PCI. With increasing elective PCI and increasing risk of stroke after PCI, risk factors for stroke or transient ischaemic attack (TIA) in non-emergency PCI and long-term outcomes needs to be better characterised. We aim to identify risk factors for cerebrovascular accidents in patients undergoing non-emergency PCI and long-term outcomes after stroke or TIA. Materials and Methods A retrospective cohort study was performed on 1724 consecutive patients who underwent non-emergency PCI for non-ST-segment elevation myocardial infarction (NSTEMI), unstable and stable angina. The primary outcomes measured were stroke or TIA, myocardial infarction (MI) and all-cause death. Results Upon mean follow-up of 3.71 (SD 0.97) years, 70 (4.1%) had subsequent ischaemic stroke or TIA, and they were more likely to present with NSTEMI (50 [71.4%] vs 892 [54.0%], OR 2.13 [1.26–3.62], p = 0.004) and not stable angina (19 [27.1%] vs 648 [39.2%], OR 0.58 [0.34–0.99]). Femoral access was associated with subsequent stroke or TIA compared to radial access (OR 2.10 [1.30–3.39], p < 0.002). Previous stroke/TIA was associated with subsequent stroke/TIA (p < 0.001), death (p < 0.001) and MI (p = 0.002). Furthermore, subsequent stroke/TIA was significantly associated with subsequent MI (p = 0.006), congestive cardiac failure (CCF) (p = 0.008) and death (p < 0.001). Conclusions In patients undergoing non-emergency PCI, previous stroke/TIA predicted post-PCI ischaemic stroke/TIA, which was associated with death, MI, CCF.

Introduction: Concurrent cardiocerebral infarction (CCI), a rare condition defined as simultaneous occlusions in the cerebrovascular and coronary vessels, has high mortality but very limited literature on optimum treatment methods. A better understanding of the natural history and effect of treatment would improve patient outcomes. Methods: Using our prospective stroke database from 2014 to 2018, ten consecutive patients with CCI were identified (incidence = 0.29%). We recorded patient demographics, cardiovascular risk factors, cardiac and cerebral occlusions, circumstances of admission and management of each patient. Patient notes and imaging findings were reviewed to determine the underlying cause of CCI. Results: Median National Institute of Health Stroke Scale score was 15 (range 4-27). Mean patient age was 59 years and 90% were men. Two patients were treated with intravenous tissue plasminogen activator (IV tPA) only and three underwent endovascular treatment in both the cerebral and coronary vessels sequentially. One patient underwent percutaneous coronary intervention (PCI) only and two underwent PCI after IV tPA therapy. Two patients were conservatively treated due to poor premorbid status. At the three-month follow-up, five patients had excellent functional outcomes (modified Rankin Scale 0-1) while three died. Conclusion: CCI is a rare but devastating clinical scenario, with high incidence of morbidity and mortality. Treatment strategy can impact patient outcome, and further research is warranted on the ideal acute and post-reperfusion treatments for CCI. In this series, IV tPA at stroke doses appeared to be the preferred initial step for its treatment, with subsequent coronary or cerebral endovascular therapy, if necessary.

Background Patients with atrial fibrillation (AF) have a higher risk of developing thromboembolic events. Current guidelines recommend the use of oral anticoagulants for stroke prevention in these patients. Several clinical trials demonstrated that direct oral anticoagulants (DOACs) have similar efficacy and are safer alternatives to traditional oral anticoagulants. However, patients with concomitant liver cirrhosis were excluded from these trials.Objective We aimed to systematically identify and review published clinical studies on the use of DOACs in patients with AF and liver cirrhosis and assess the efficacy and safety of DOACs in these patients.MethodsA systematic review of clinical trials and retrospective studies was conducted by searching the PubMed, Cochrane Library, Embase, SCOPUS, and Web of Science databases up to September 2020.ResultsThree retrospective studies were included, involving 4011 patients with AF and liver cirrhosis. The use of DOACs was associated with a significant reduction in ischemic stroke (hazard ratio [HR] 0.62; 95% confidence interval [CI] 0.42–0.90; p = 0.01), major bleeding events (HR 0.64; 95% CI 0.57–0.72; p < 0.001), and intracranial hemorrhage (HR 0.49; 95% CI 0.40–0.59; p < 0.001).Conclusions Compared with warfarin in patients with AF and liver cirrhosis, DOACs appear to be associated with improved efficacy and safety outcomes. Randomized controlled trials are warranted to confirm these findings.

Introduction and hypothesis: In patients with acute ischemic stroke with large vessel occlusion (AIS-LVO), the role of intra-arterial adjunctive medications (IAM) like urokinase, tPA or glycoprotein IIb/IIIa inhibitors, during mechanical thrombectomy (MT) has not been clearly established. We hypothesize that AIS-LVO patients treated with both MT + IAM (rescue or concurrent) achieve better safety and efficacy outcomes than patients treated with MT alone and aim to determine the efficacy and safety of concomitant or rescue IAM for AIS-LVO patients undergoing MT. Methods: We searched Medline, Embase and Cochrane Stroke Group Trials Register databases from inception until 13th March 2020. We analysed all studies with patients diagnosed with AIS-LVO in the anterior or posterior circulation, that provided data for the two treatment arms: 1)MT+IAM and 2)MT-only, and also reported on at least one of the following outcomes: reperfusion, 90-days modified Rankin Scale (mRS), symptomatic intracranial hemorrhage (sICH) and 90-days mortality. Data were collated in accordance with the PRISMA guidelines. Results: Sixteen non-randomized observational studies with a total of 4581 patients were analysed. MT-only was performed in 3233 (70.6%) patients, while 1348 (29.4%) patients were treated with both MT+IAM. As compared to patients treated with MT alone, patients treated with combination therapy (MT +IAM) had a higher likelihood of achieving good functional outcome (risk ratio=1.13, 95% CI 1.03-1.24) and a lower risk of 90-day mortality (risk ratio=0.82, 95% CI 0.72-0.94). There was no significant difference in successful reperfusion (risk ratio=1.02, 95% CI 0.99-1.06) and sICH between the two groups (risk ratio = 1.13, 95% CI 0.87-1.46) (Figure 1). Conclusions: In AIS-LVO, use of IAM together with MT may achieve better functional outcomes and lower mortality rates. Randomized controlled trials are warranted to confirm the safety and efficacy of IAM as adjunctive treatment of MT.

Background: Acute ischemic stroke (AIS) is a life-threatening complication of coronavirus disease 2019 (COVID-19) infection. Increasing reports suggest an association between COVID-19 and AIS, although the underlying mechanism remains uncertain. Objectives: We performed a systematic review to characterize the clinical characteristics, neuroimaging findings, and outcomes of AIS in COVID-19 patients. Methods: A literature search was performed in PubMed and Embase using a suitable keyword search strategy from 1st December 2019 to 29th May 2020. All studies reporting AIS occurrence in COVID-19 patients were included. Results: A total of 39 studies comprising 135 patients were studied. The pooled incidence of AIS in COVID-19 patients from observational studies was 1.2% (54/4466) with a mean age of 63.4 ± 13.1 years. The mean duration of AIS from COVID-19 symptoms onset was 10 ± 8 days, and the mean NIHSS score was 19 ± 8. Laboratory investigations revealed an elevated mean D-dimer (9.2 ± 14.8 mg/L) and fibrinogen (5.8 ± 2.0 g/L). Antiphospholipid antibodies were detected in a significant number of cases. The majority of AIS neuroimaging patterns observed was large vessel thrombosis, embolism or stenosis (62.1%, 64/103), followed by multiple vascular territory (26.2%, 27/103). A high mortality rate was reported (38.0%, 49/129). Conclusion: We report the pooled incidence of AIS in COVID-19 patients to be 1.2%, with a high mortality rate. Elevated D-dimer, fibrinogen and the presence of antiphospholipid antibodies appear to be prominent in COVID-19 patients with concomitant AIS, but further mechanistic studies are required to elucidate their role in pathogenesis.

Introduction: Acute myocardial infarction (MI) and acute ischaemic stroke (AIS) are leading causes of morbidity and mortality. There is scarce data examining the interplay between post-MI left ventricular systolic dysfunction (LVSD), with or without atrial fibrillation (AF), and subsequent AIS, especially in patients with milder degrees of LVSD (ejection fraction 40-49%). Evidence of an association would be helpful in developing new strategies of reducing AIS after MI. As such, we sought to study this relationship in a real-world population-based registry. Methods: This study involved linking national-level data from the Singapore Myocardial Infarction Registry with the Singapore Stroke Registry from 1st January 2007 to 31st December 2018. Both data sets have similar definitions for patient demographics. The ejection fraction (EF) and AF status were recorded during the MI episode. The outcome studied was the first instance of AIS that developed after the MI episode. We also studied the relationship between EF, AF and the severity of AIS as measured by the NIH Stroke Scale (NIHSS). Results: There were 64,512 patients available for analysis. The median age was 65.7 (IQR 56.1-76.5) and 69.5% were male. The median duration post-MI to develop AIS was 16.9 (IQR 1.6-46.1) months. There was an independent association between LVSD and the outcome of AIS (adjusted HR 1.18, 95% CI 1.10-1.27); this was evident even in mild forms of LVSD (adjusted HR 1.16, 95% CI 1.06-1.27). AF was not a statistically significant predictor of AIS in post-MI patients with LVSD. Amongst patients without AF, post-MI LVSD was associated with a more severe stroke and higher NIHSS. Conclusion: Post-MI LVSD is associated with the occurrence of subsequent AIS. Although this relationship was independent of AF status, patients with LVSD but no AF had suffered a more severe AIS. These findings support the need to develop effectives therapies to prevent AIS post-MI, especially among those with LVSD.

Background and Purpose In patients with acute ischemic stroke with large vessel occlusion, the role of intra-arterial adjunctive medications (IAMs), such as urokinase, tPA (tissue-type plasminogen activator), or glycoprotein IIb/IIIa inhibitors, during mechanical thrombectomy (MT) has not been clearly established. We aim to evaluate the efficacy and safety of concomitant or rescue IAM for acute ischemic stroke with large vessel occlusion patients undergoing MT. Methods We searched Medline, Embase, and Cochrane Stroke Group Trials Register databases from inception until March 13, 2020. We analyzed all studies with patients diagnosed with acute ischemic stroke with large vessel occlusion in the anterior or posterior circulation that provided data for the two treatment arms, (1) MT+IAM and (2) MT only, and also reported on at least one of the following efficacy outcomes, recanalization and 90-day modified Rankin Scale, or safety outcomes, symptomatic intracranial hemorrhage and 90-day mortality. Data were collated in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. Results Sixteen nonrandomized observational studies with a total of 4581 patients were analyzed. MT only was performed in 3233 (70.6%) patients, while 1348 (29.4%) patients were treated with both MT and IAM. As compared with patients treated with MT alone, patients treated with combination therapy (MT+IAM) had a higher likelihood of achieving good functional outcome (risk ratio, 1.13 [95% CI, 1.03–1.24]) and a lower risk of 90-day mortality (risk ratio, 0.82 [95% CI, 0.72–0.94]). There was no significant difference in successful recanalization (risk ratio, 1.02 [95% CI, 0.99–1.06]) and symptomatic intracranial hemorrhage between the two groups (risk ratio, 1.13 [95% CI, 0.87–1.46]). Conclusions In acute ischemic stroke with large vessel occlusion, the use of IAM together with MT may achieve better functional outcomes and lower mortality rates. Randomized controlled trials are warranted to establish the safety and efficacy of IAM as adjunctive treatment to MT.

Background Recent studies have increasingly shown that sodium‐glucose cotransporter 2 (SGLT2) inhibitors may have beneficial cardiovascular and metabolic effects in patients without diabetes mellitus. Hence, we conducted a systematic review and meta‐analysis to determine the effect of SGLT2 inhibitors on cardiovascular and metabolic outcomes in patients without diabetes mellitus. Methods and Results Four electronic databases (PubMed, Embase, Cochrane, and SCOPUS) were searched on August 30, 2020 for articles published from January 1, 2000 to August 30, 2020, for studies that examined the effect of SGLT2 inhibitors on cardiovascular and metabolic outcomes in patients without diabetes mellitus. A random‐effects pairwise meta‐analysis model was used to summarize the studies. A total of 8 randomized‐controlled trials were included with a combined cohort of 5233 patients. In patients without diabetes mellitus, those with heart failure treated with SGLT2 inhibitors had a 20% relative risk reduction in cardiovascular deaths and heart failure hospitalizations, compared with those who were not treated (risk ratio, 0.78; P <0.001). We additionally found that treatment with SGLT2 inhibitors improved multiple metabolic indices. Patients on SGLT2 inhibitors had a reduction in body weight of −1.21 kg ( P <0.001), body mass index of −0.47 kg/m ² ( P <0.001), systolic blood pressure of −1.90 mm Hg ( P =0.04), and fasting plasma glucose of −0.38 mmol/L ( P =0.05), compared with those without. There were no between‐group differences in NT‐proBNP (N‐terminal pro‐B‐type natriuretic peptide) levels, waist circumference, diastolic blood pressure, glycated hemoglobin, low‐density lipoprotein cholesterol levels, and estimated glomerular filtration rates. Across our combined cohort of 5233 patients, hypoglycemia was reported in 22 patients. Conclusions SGLT2 inhibitors improve cardiovascular outcomes in patients without diabetes mellitus with heart failure. In patients without diabetes mellitus, SGLT2 inhibitors showed positive metabolic outcomes in weight and blood pressure control.

Background Stroke is one of the leading causes of death worldwide. Cilostazol, an antiplatelet and phosphodiesterase 3 inhibitor, has not been clearly established for ischaemic stroke use. We aim to determine the efficacy and safety of cilostazol for secondary stroke prevention. Methods MEDLINE, EMBASE, Cochrane Library, Web of Science and ClinicalTrials.gov were searched from inception to 25 September 2020, for randomised trials comparing the efficacy and safety of cilostazol monotherapy or dual therapy with another antiplatelet regimen or placebo, in patients with ischaemic stroke. Version 2 of the Cochrane risk-of-bias tool for randomised trials (RoB 2) was used to assess study quality. This meta-analysis was reported in line with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement. Results Eighteen randomised trials comprising 11 429 participants were included in this meta-analysis. Most trials possessed low risk of bias and were of low heterogeneity. Cilostazol significantly reduced the rate of ischaemic stroke recurrence (risk ratio, RR=0.69, 95% CI 0.58 to 0.81), any stroke recurrence (RR=0.64, 95% CI 0.54 to 0.74) and major adverse cardiovascular events (RR=0.67, 95% CI 0.56 to 0.81). Cilostazol did not significantly decrease mortality (RR=0.90, 95% CI 0.64 to 1.25) or increase the rate of good functional outcome (Modified Rankin Scale score of 0–1; RR=1.07, 95% CI 0.95 to 1.19). Cilostazol demonstrated favourable safety profile, significantly reducing the risk of intracranial haemorrhage (RR=0.46, 95% CI 0.31 to 0.68) and major haemorrhagic events (RR=0.49, 95% CI 0.34 to 0.70). Conclusions Cilostazol demonstrated superior efficacy and safety profiles compared with traditional antiplatelet regimens such as aspirin and clopidogrel for secondary stroke prevention but does not appear to affect functional outcomes. Future randomised trials can be conducted outside East Asia, or compare cilostazol with a wider range of antiplatelet agents.

Background Left ventricular thrombus (LVT) formation is a significant complication of acute myocardial infarction (AMI) due to its embolic potential. However, managing LVT requires balancing therapeutic benefits against bleeding risks. Our study provides a risk-benefit analysis of various antithrombotic regimens on long-term outcomes in treating post-AMI LVT patients. Methods We conducted a comprehensive literature search in Medline, Embase and SCOPUS up to 1 April 2020. All studies reporting outcomes of post-AMI LVT patients were included. Results 17 studies were included in total. Anticoagulation (47–100%) and triple therapy use (38–100%) varied largely across studies. On meta-analysis, administration of anticoagulation (OR 0.14, 95% CI 0.05–0.36, p < 0.001) and triple therapy (OR 0.22, 95% CI 0.07–0.66, p < 0.001) resulted in lower odds of mortality. Neither anticoagulation ( p = 0.24) nor triple therapy ( p = 0.73) was associated with bleeding. Triple therapy was associated with LVT resolution on meta-analysis (OR 2.53, 95% CI 1.53–4.19, p < 0.001) and regression analysis (OR 1.28, 95% CI 1.03–1.58, p = 0.03). Anticoagulation and triple therapy were independent predictors of systemic embolism ([OR 0.67, 95% CI 0.49–0.93, p = 0.02] and [OR 0.82, 95% CI 0.73–0.93, p = 0.001]) and stroke ([OR 0.62, 95% CI 0.41–0.94, p = 0.03] and [OR 0.73, 95% CI 0.55–0.96, p = 0.03]). Conclusions While there is clear therapeutic benefit in anticoagulation for post-AMI LVT, the extent of bleeding risk is uncertain. Future trials are necessary to determine the optimal antithrombotic strategy for post-AMI LVT management.

Background: Several P-wave indices are thought to represent underlying atrial remodeling and have been associated with ischaemic stroke even in the absence of atrial fibrillation (AF). However, the utility of these P-wave indices in predicting outcomes in patients with embolic stroke of undetermined source (ESUS) has not been studied. The aim of this study is to examine these different P-wave indices towards predicting new-onset AF and stroke recurrence in a cohort of patients with ESUS, thereby demonstrating the value of these electrocardiographic markers for stroke risk stratification. Methods: Between October 2014 and October 2017, consecutive patients diagnosed with ESUS were followed for new-onset AF and ischaemic stroke recurrence. The various P-wave indices, namely, the P-terminal force in the precordial lead V1 (PTFV1), P-wave duration, P-wave dispersion, interatrial blocks, and P-wave axis, were assessed on the initial electrocardiogram on presentation and studied for their relation to eventual AF detection and recurrent stroke. Results: 181 ischaemic stroke patients with ESUS were recruited and followed up for a median duration of 2.1 years. An abnormal PTFV1 was associated with occult AF detection but not with recurrent ischaemic strokes. No significant association was observed between the other P-wave indices with either occult AF or stroke recurrence. Conclusion: PTFV1 is associated with AF detection but not recurrent strokes in ESUS patients and can be a useful electrocardiographic marker for further risk stratification in ESUS patients.

A 32-year-old man presented with sudden loss of consciousness after passing urine with resultant trauma to the back of his neck. There were no palpitations prior. Examination revealed flaccid paralysis of all 4 limbs with priapism. Electrocardiogram demonstrated atrial fibrillation with rapid ventricular response. Laboratory showed normal potassium, magnesium, calcium, thyroid stimulating hormone and troponin I levels. Magnetic resonance imaging of the cervical spine demonstrated left C4 facet dislocation with grade 1 spondylolisthesis of C4 over C5, with moderate to severe narrowing of the spinal canal with cord compression and oedema. Transthoracic echocardiogram demonstrated an ejection fraction of 60% and no valvular abnormalities. Left atrium size was normal. The atrial fibrillation subsequently spontaneously reverted to sinus rhythm without treatment. Clinicians should be aware that atrial fibrillation can occur in the context of traumatic spinal cord injury due to disruption of the autonomic pathways in the cervical spine.

Background Valvular heart disease (VHD) may be an important comorbidity acute ischemic stroke (AIS), adversely affecting cerebral haemodynamics and consequently limiting functional recovery after endovascular thrombectomy (EVT). We examined the clinical profile and outcomes in patients with or without VHD who underwent EVT for AIS. Methods Consecutive patients (n=224) who underwent EVT for AIS were examined. All patients underwent transthoracic echocardiography within 6 months of AIS. The patients were divided into those with left-sided VHD (at least moderate severity of aortic valve or mitral valve stenosis or regurgitation) and those without. Univariate and multivariate analyses were employed to compare clinical profile and outcomes. Results There were 47 (20.9%) patients with VHD. Of these, 31 (66.0%) had mitral regurgitation, 15 (31.9%) had aortic stenosis, 8 (17.0%) had aortic regurgitation and 6 (12.8%) had mitral stenosis. VHD patients had a higher prevalence of atrial fibrillation (68.1% vs 43.5%, p=0.003) compared to those without, but stroke severity was similar. They had higher prevalence of pathological left ventricular (LV) remodelling, with larger end-diastolic volume index (77.9±34.5 vs 61.1±19.9ml/m2, p<0.001) and LV mass index (116.4±32.7 vs 99.8±32.2g/m2, p=0.002). Despite similar rates of recanalisation, VHD patients had poorer functional outcomes (mRS>2) at 3 months (68.1% vs 50.3%, p=0.029). On multivariable analyses, VHD remained independently associated with poor functional outcomes (adjusted OR 2.42, 95% CI 1.08–5.43), after adjusting for age, stroke severity and recanalisation rates. Conclusion VHD may be associated with poorer functional outcomes in patients with AIS undergoing EVT, despite similar rates of successful recanalisation. Ordinal shift analyses Funding Acknowledgement Type of funding source: None

Cerebral venous thrombosis (CVT) causes significant disability and mortality. Current guidelines for CVT management support the initial use of unfractionated heparin or low molecular weight heparin followed by longer-term oral vitamin K antagonist (VKA). There has been increasing, albeit limited, evidence for the use of direct oral anticoagulants (DOAC) as an alternative to VKA. We performed a systematic review and meta-analysis of studies that compared the safety and efficacy of DOACs to VKA in treating CVT. A comprehensive literature search was carried out in Medline, Embase and Cochrane Stroke Group Trials Register using a suitable keyword/MeSH term search strategy. All studies published in English comparing outcomes of patients with CVT treated with DOAC or VKA were included. In total, 6 studies (5 observational studies and 1 randomized clinical trial) comprising 412 patients (age range 16–83 years) were analyzed. DOAC was used in 151 patients, while 261 received VKA. The follow-up period was 3–11 months. The efficacy of DOACs was comparable with VKA in terms of partial or full thrombus recanalization (RR 1.02, 95% CI 0.89–1.16) and excellent functional recovery with modified Rankin scale < 2 (RR 1.02, 95% CI 0.93–1.13). Patients treated with DOAC developed lower major bleeding events when compared to VKA, although this did not reach statistical significance (RR 0.44, 95% CI 0.12–1.59). We provide preliminary evidence to support DOAC as effective and safe alternatives to VKA in CVT treatment. We await the results of upcoming randomized trials to further support our results and validate the use of DOAC.

Acute ischemic stroke (AIS) is a life-threatening complication of coronavirus disease 2019 (COVID-19) infection. Increasing reports suggest an association between COVID-19 and AIS, although the underlying mechanism remains uncertain. We performed a systematic review to characterize the clinical characteristics, neuroimaging findings, and outcomes of AIS in COVID-19 patients. A literature search was performed in PubMed and Embase using a suitable keyword search strategy from 1st December 2019 to 29th May 2020. All studies reporting AIS occurrence in COVID-19 patients were included. A total of 39 studies comprising 135 patients were studied. The pooled incidence of AIS in COVID-19 patients from observational studies was 1.2% (54/4466) with a mean age of 63.4 ± 13.1 years. The mean duration of AIS from COVID-19 symptoms onset was 10 ± 8 days, and the mean NIHSS score was 19 ± 8. Laboratory investigations revealed an elevated mean d-dimer (9.2 ± 14.8 mg/L) and fibrinogen (5.8 ± 2.0 g/L). Antiphospholipid antibodies were detected in a significant number of cases. The majority of AIS neuroimaging patterns observed was large vessel thrombosis, embolism or stenosis (62.1%, 64/103), followed by multiple vascular territory (26.2%, 27/103). A high mortality rate was reported (38.0%, 49/129). We report the pooled incidence of AIS in COVID-19 patients to be 1.2%, with a high mortality rate. Elevated d-dimer, fibrinogen and the presence of antiphospholipid antibodies appear to be prominent in COVID-19 patients with concomitant AIS, but further mechanistic studies are required to elucidate their role in pathogenesis.

Background: Endovascular thrombectomy (ET) has transformed acute ischemic stroke (AIS) therapy in patients with large vessel occlusion (LVO). Left ventricular systolic dysfunction (LVSD) decreases global cerebral blood flow and predisposes to hypoperfusion. We evaluated the relationship between LVSD, as measured by LV ejection fraction (LVEF), and clinical outcomes in patients with anterior cerebral circulation LVO who underwent ET. Methods: This multicenter retrospective cohort study examined anterior circulation LVO AIS patients from six international stroke centers. LVSD was measured by assessment of the echocardiographic LVEF using Simpson's biplane method of discs according to international guidelines. LVSD was defined as LVEF <50%. The primary outcome was defined as a good functional outcome using a modified Rankin Scale (mRS) of 0-2 at 3 months. Results: We included 440 AIS patients with LVO who underwent ET. On multivariate analyses, pre-existing diabetes mellitus (OR 2.05, 95% CI 1.24 to 3.39;p=0.005), unsuccessful reperfusion (Treatment in Cerebral Infarction (TICI) grade 0-2a) status (OR 4.21, 95% CI 2.04 to 8.66; p<0.001) and LVSD (OR 2.08, 95% CI 1.18 to 3.68; p=0.011) were independent predictors of poor functional outcomes at 3 months. On ordinal (shift) analyses, LVSD was associated with an unfavorable shift in the mRS outcomes (OR 2.32, 95% CI 1.52 to 3.53; p<0.001) after adjusting for age and ischemic heart disease. Conclusion: Anterior circulation LVO AIS patients with LVSD have poorer outcomes after ET, suggesting the need to consider cardiac factors for ET, the degree of monitoring and prognostication post-procedure.

Background Transient hyperglycaemia in the context of illness with or without known diabetes has been termed as ‘stress hyperglycaemia’. Stress hyperglycaemia can result in poor functional outcomes in patients with acute ischaemic stroke who underwent mechanical thrombectomy. We investigated the association between stress hyperglycaemia and clinical outcomes in acute ischaemic stroke patients undergoing intravenous thrombolysis (IVT). Methods We examined 666 consecutive patients with acute ischaemic stroke who underwent IVT from 2006-2018. All patients had a glycated haemoglobin level (HbA1c) and fasting venous blood glucose measured within 24 hours of admission. Stress hyperglycaemia ratio (SHR) was defined as the ratio of the fasting glucose to the HbA1c. Univariate and multivariate analyses were employed to identify predictors of poor functional outcomes (modified Rankin Scale 3-6 at 3 months) after IVT. Results Three-hundred and sixty-one patients (54.2%) had good functional outcomes. These patients tended to be younger (60.7±12.7 vs 70 ±14.4 years, p < 0.001), male (70.7% vs 51.5%, p < 0.001), had lower prevalence of atrial fibrillation (13.0% vs 20.7%, p = 0.008) and lower SHR (0.88±0.20 vs 0.99±26, p < 0.001). Patients with high SHR (≥0.97) were slightly older than those with low SHR (<0.97), and were more likely to have diabetes mellitus. On multivariate analysis, higher SHR was independently associated with poor functional outcomes (adjusted odds ratio 3.85, 95% CI 1.59 – 9.09, p = 0.003). Conclusions SHR appears to be an important predictor of functional outcomes in patients with AIS undergoing IVT. This may have important implications on the role of glycaemic control in the acute management of ischaemic stroke.

Introduction Bickerstaff’s brainstem encephalitis (BBE) is a neurological condition characterised by ataxia, opthalmoplegia and altered sensorium. Neurological diseases, such as Guillain-Barre syndrome, have previously been reported in association with Takotsubo cardiomyopathy. We describe a case of Takotsubo cardiomyopathy associated with BBE. Methods/Results A 62-year-old Chinese female with no significant medical history was admitted after a fall due to transient bilateral lower limb numbness. A day after her initial presentation, she developed altered sensorium and further deteriorated within hours - with bulbar weakness, increasing oxygen requirements requiring intubation and cardiogenic shock needing noradrenaline support. She also had rapid atrial fibrillation treated with amiodarone. Her cardiac enzymes were elevated (high sensitivity troponin I 2137pg/ml; upper limit 15.6pg/ml) and echocardiography demonstrated apical ballooning and dyskinesis with hypercontractility of the base in the left ventricle consistent with Takotsubo cardiomyopathy. Examination revealed bulbar weakness with poor gag and cough reflexes, ataxia and complex opthalmoplegia. Her reflexes were brisk and pupils mydriatic with sluggish pupillary response. Magnetic resonance imaging revealed a gadolinium-enhancing lesion in the brainstem on T1 sequence and anti-GQ1b antibody was positive. She was diagnosed with BBE and treated with intravenous immunoglobulin with good functional recovery. Repeat echocardiography demonstrated interval improvement in apical ballooning. Conclusion This is the first described case of Takotsubo cardiomyopathy associated with BBE. The pathogenesis of Takotsubo cardiomyopathy in relation to BBE is postulated to be related to dysautonomia with sympathetic overactivity and excessive catecholamine release. In cases of hemodynamic instability in BBE, Takotsubo cardiomyopathy should be considered.

Introduction: It is unclear which surrogate of atrial cardiopathy best predicts the risk of developing a recurrent ischemic stroke in embolic stroke of undetermined source (ESUS). Left atrial diameter (LAD) and LAD index (LADi) are often used as markers of left atrial enlargement in current ESUS research, but left atrial volume index (LAVi) has been found to be a better predictor of cardiovascular outcomes in other patient populations. Objective: We aim to compare the performance of LAVi, LAD, and LADi in predicting the development of new-onset atrial fibrillation (AF) and stroke recurrence in ESUS. Methods: Between October 2014 and October 2017, consecutive patients diagnosed with ESUS were followed for new-onset AF, ischemic stroke recurrence, and a composite outcome of occult AF and stroke recurrence. LAVi and LADi were measured by transthoracic echocardiogram; "high" LAVi was defined as ≥35 mL/m2 in accordance with American Society of Echocardiography guidelines. Results: 185 ischemic stroke patients with ESUS were recruited and followed for a median duration of 2.1 years. Increased LAVi was associated with new-onset AF detection (aOR 1.08; 95% CI 1.03-1.14; p = 0.003) and stroke recurrence (aOR 1.05; 95% CI 1.01-1.10; p = 0.026). Patients with "high" LAVi had a higher likelihood of developing a composite of AF detection and stroke recurrence (HR 3.45; 95% CI 1.55-7.67; p = 0.002). No significant association was observed between LADi and either occult AF or stroke recurrence. Conclusions: LAVi is associated with new-onset AF and stroke recurrence in ESUS patients and may be a better surrogate of atrial cardiopathy.

Background Left ventricular thrombosis (LVT) is a potentially devastating complication in post-acute myocardial infarction (AMI) patients. Previous studies have demonstrated that inflammation may contribute to thrombus formation, but its role on thrombus resolution is uncertain. The neutrophil-lymphocyte ratio (NLR) and platelet-lymphocyte ratio (PLR) are easily accessible haematological markers of inflammation. Objectives We aimed to identify differences between post-AMI LVT patients with and without LVT resolution, and to evaluate the utility of NLR and PLR in predicting LVT resolution. Methods We included 289 consecutive post-AMI patients with LVT. Acute LVT was diagnosed based on echocardiogram. Patients were stratified based on LVT resolution. Logistic regression was performed to evaluate for independent predictors of thrombus resolution. Results Compared to post-AMI patients with eventual LVT resolution, those with unresolved LVT had more co-morbidities such as hypertension (p = 0.003) and ischaemic heart disease (p < 0.001), fewer underwent percutaneous coronary intervention (PCI) (p < 0.001) or were treated with triple therapy (p < 0.001). NLR (p = 0.064) and PLR (p = 0.028) were higher in unresolved LVT patients. In non-PCI patients, NLR (OR 0.818, 95% CI 0.674–0.994, p = 0.043) and PLR (OR 0.989, 95% CI 0.979–0.999, p = 0.026) were independent predictors of thrombus resolution after adjustment for age and anticoagulation use. Conclusions Post-AMI patients not receiving PCI may have a greater inflammatory response and a higher NLR and PLR, which is associated with less LVT resolution despite anticoagulation. Further studies are required to study this association.

Background and aim Bi-directional feedback mechanisms exist between the heart and brain, which have been implicated in heart failure. We postulate that aortic stenosis may alter cerebral haemodynamics and influence functional outcomes after endovascular thrombectomy for acute ischaemic stroke. We compared clinical characteristics, echocardiographic profile and outcomes in patients with or without aortic stenosis that underwent endovascular thrombectomy for large vessel occlusion acute ischaemic stroke. Methods Consecutive acute ischaemic stroke patients with anterior and posterior circulation large vessel occlusion (internal carotid artery, middle cerebral artery and basilar artery) who underwent endovascular thrombectomy were studied. Patients were divided into those with significant aortic stenosis (aortic valve area <1.5 cm ² ) and without. Univariate and multivariate analyses were employed to compare and determine predictors of functional outcomes measured by modified Rankin scale at three months. Results We identified 26 (8.5%) patients with significant aortic stenosis. These patients were older (median age 76 (interquartile range 68–84) vs. 67 (interquartile range 56–75) years, p = 0.001), but similar in terms of medical comorbidities and echocardiographic profile. Rates of successful recanalisation (73.1% vs. 78.0%), symptomatic intracranial haemorrhage (7.7% and 7.9%) and mortality (11.5% vs. 12.6%) were similar. Significant aortic stenosis was independently associated with poorer functional outcome (modified Rankin scale >2) at three months (adjusted odds ratio 2.7, 95% confidence interval 1.1–7.5, p = 0.048), after adjusting for age, door-to-puncture times, stroke severity and rates of successful recanalisation. Conclusion In acute ischaemic stroke patients managed with endovascular thrombectomy, significant aortic stenosis is associated with poor functional outcome despite comparable recanalisation rates. Larger cohort studies are needed to explore this relationship further.

Background: Endovascular thrombectomy (ET) has transformed acute ischaemic stroke (AIS) therapy in patients with large vessel occlusion (LVO). Left ventricular systolic dysfunction (LVSD) decreases global cerebral blood flow and predisposes to hypoperfusion. We evaluated the relationship between LVSD as measured by LVEF, and clinical outcomes in patients with anterior cerebral circulation LVO who undergo ET. Methods: This retrospective study examined patients from our AIS endovascular thrombectomy registry from 2013-2018. We included all consecutive patients who had anterior circulation LVO (ICA, M1, M2) who underwent ET, and had transthoracic two-dimensional echocardiography. LVSD was measured by assessment of the LVEF using Simpson’s biplane method of discs according to American Society of Echocardiography guidelines. LVSD was defined as a reduced LVEF of <50%. Primary outcome was defined as good functional outcome using a modified Rankin Scale (mRS) of 0-2 at 3-months. Results: Of 254 AIS patients with anterior circulation LVO, we included 229 patients with complete echocardiography assessment. On multivariate analyses, older age, diabetes mellitus, lower ASPECTS, unsuccessful recanalization, smaller LV outflow tract diameter and LVSD were significantly associated with poor functional outcomes (Table 1). On ordinal (shift) analyses, LVSD was associated with an unfavourable shift in the mRS outcomes (OR 3.09, 95% CI 1.68 - 5.69, p < 0.001) after adjusting for age and ischemic heart disease (Figure). Conclusion: Anterior circulation LVO AIS patients with LVSD have poorer outcomes after ET, suggesting the need to tailor peri-procedural management strategies.

In ESUS, the relationship between atrial cardiopathy, occult AF and embolic stroke risk remains unclear. Studies suggest that left atrial volume index (LAVi) may be a better estimate of atrial cardiopathy than LA diameter. We explored LAVi as a marker of occult AF detection and ischemic stroke recurrence. Methods: From 2015-2017, consecutive ESUS patients diagnosed based on consensus criteria were studied. LAVi was measured using the Biplane Area-Length Method on TTE by trained cardiologists. Clinical outcomes measured were occult AF detection and ischemic stroke recurrence in a time-to-event analysis. Kaplan-Meier curves were constructed to compare outcomes in those with high versus low LAVi at optimized cut-off values. Results: 199 consecutive ESUS patients were followed up for 2.2±1.0 years. 9 patients were excluded due to technically inadequate views. Increased LAVi was associated with AF detection (36.63mL/m ² ± 12.2 vs 26.93mL/m ² ± 9.6) and stroke recurrence (32.13mL/m ² ± 9.3 vs 27.23mL/m ² ± 10.1). On multivariate regression adjusting for age, sex, hypertension and diabetes mellitus, LAVI was independently associated with AF detection (OR 1.08, CI 95% 1.03-1.14; p=0.003) and stroke recurrence (OR 1.05, CI 95% 1.01-1.10; p=0.026). Kaplan-Meier curves showed significant differences in occult AF (log-rank 8.67, p=0.003) and stroke recurrence (log-rank 5.31, p=0.021) between high (>27.7ml/m ² ) and low LAVi (≤27.7ml/m ² ) groups. Conclusion: Increased LAVi in ESUS patients was associated with AF detection and stroke recurrence, suggesting that this may be a useful echocardiographic marker to identify high-risk patients who may potentially benefit from anticoagulation.

Funding Acknowledgements None Background/Introduction Left ventricular (LV) thrombus is a widely recognized complication of acute myocardial infarction (AMI). Limited data are available from South East Asian patients with this post-infarction complication nor on whether patients with non-ST segment elevation myocardial infarction (NSTEMI) or STEMI with associated LV thrombosis exhibit differing clinical characteristics and/or outcomes. Left Ventricular Ejection Fraction (LVEF) ≤ 40% is a recognized predictor of LV thrombus formation, but there is limited data on LV thrombus patients with EF > 40% or in NSTEMI patients. Purpose This study aims to investigate and compare the clinical characteristics, treatment and outcomes of post-AMI patients with LV thrombus formation, with a particular emphasis on those with EF ≤ 40% and in NSTEMI patients. Methods Among 5829 consecutive echocardiogram results containing the keyword "thrombus" from August 2006 to September 2017, we identified 289 post-AMI patients with acute LV thrombus formation. Demographics, treatment and outcome measures were analysed. Results Cardiovascular risk factors such as dyslipidaemia (54.0%) and hypertension (50.5%) were commonly present in post-AMI patients with LV thrombus. Mean LVEF was 33.0 ± 10.4%. The majority (68.0%) of patients received triple therapy and 59.5% achieved thrombus resolution. NSTEMI patients had greater number of co-morbidities including heart failure (p < 0.01), documented history of ischaemic heart disease preceding the AMI leading to thrombus formation (p < 0.01) and lower LVEF (28.3 ± 9.3% vs. 34.8 ± 10.3% , p < 0.01) compared with STEMI cases. On multivariate analysis, having a lower EF was a significant independent predictor of stroke (HR 0.96, 95% CI 0.93-1.00, p = 0.03) and all-cause mortality (HR 0.95, 95% CI 0.92-0.99, p < 0.01). The categories of STEMI and NSTEMI did not predict thrombus resolution, stroke events or all-cause mortality after adjustment. Conclusion(s) Post-AMI LV thrombus patients with NSTEMI and STEMI differed in terms of their co-morbidities in their demographics and co-morbidities but it was a lower EF that was associated with an increased risk of stroke and all-cause mortality. Further studies on this topic are required.

Acute ischemic stroke (AIS) is a feared complication in post-acute myocardial infarction (AMI) patients who develop left ventricular (LV) thrombus. There is limited data available on the incidence of stroke in this population, and characterisation of stroke subtypes has not been previously reported. Our study aims to evaluate the incidence of AIS in post-AMI patients with LV thrombus and to characterise the pattern of stroke subtypes. We screened 5829 patients with echocardiogram reports containing the “thrombus” keyword from August 2006 to September 2017. AIS that occurred after LV thrombosis was captured and relevant clinical data was collected. We identified 289 post-AMI patients with acute LV thrombus formation. Mean age was 59.3 ± 13.4 years. AIS occurred in 34 patients (11.8%), median duration of 20.5 days (IQR = 5.5–671.8) after LV thrombosis. Despite initial thrombus resolution, nine (5.2%) encountered AIS subsequently. Cardioembolic stroke subtype was identified in 76.5% of AIS, whilst 14.7% was small vessel disease and 8.8% was of large artery atherosclerosis subtype. Presence of thrombus protrusion (HR 3.04, 95% CI 1.25–7.41, p = 0.01), failure of initial thrombus resolution (HR 3.03, 95% CI 1.23–7.45, p = 0.02) and thrombus recurrence (HR 4.20, 95% CI 1.46–12.11, p < 0.01) were significant independent predictors for stroke. Incidence of AIS in this Asian population of post-AMI patients with LV thrombus was 11.8%. Duration of anticoagulation may need to be individualised for patients with higher risk for stroke occurrence after LV thrombosis.

Background and aims: Increasingly, insertable cardiac monitors (ICM) have been used to detect Atrial Fibrillation (AF) in patients with cryptogenic stroke or embolic strokes of undetermined source (ESUS). We aim to examine the characteristics of these patients who were subsequently found to have AF. Methods: We studied 83 consecutive patients who were comprehensively evaluated using neuroimaging and vessel imaging (computed tomography angiography, magnetic resonance angiography, or transcranial and extracranial Doppler sonography) to have met the previously established ESUS criteria. All 83 patients had ICM implanted between 2015 and 2017. All patients were followed up for at least 1 year, with a median follow-up period of 1.5 ± .5 years. We compared the baseline clinical, laboratory, echocardiographic, neuro-imaging profiles, and clinical outcomes in terms of functional recovery, recurrent stroke, and mortality in patients with and without detected AF. Results: AF detection rate in this ESUS cohort was 12% over the study period. Patients with detected AF were associated with bilateral infarcts pattern at presentation (30% versus 5.5%, P = .035). Infarcts involving multiple vascular territories was not significantly associated with the detection of AF. There were no significant differences in the other clinical characteristics and outcomes between the AF group compared to the group without detected AF. Echocardiographic parameters including left ventricular ejection fraction and left atrial diameter were also not shown to be significantly different. Conclusion: Our study found that a neuroimaging profile of bilateral infarcts was associated with AF detection using insertable cardiac monitor in ESUS patients. Larger prospective studies are needed to validate our findings.

Introduction: Left ventricular (LV) thrombus is a complication of ST-segment elevation myocardial infarction (STEMI) that leads to a higher risk of stroke. Atrial fibrillation (AF) is another independent risk factor for stroke, however there is a dearth of studies examining the outcomes of patients with concomitant AF and LV thrombus. Hypothesis: This study aims to investigate the impact of the presence of concomitant AF in post-STEMI patients with an LV thrombus on stroke and mortality outcomes. Methods: We screened 6007 transthoracic echocardiogram reports containing the “thrombus” keyword from July 2006 to September 2017. Relevant clinical data was collected from 196 post-STEMI patients positive for an LV thrombus, stratified into non-AF and AF groups. Results: AF patients (69.6 ± 11.8 years) were significantly older (p < 0.01) than non-AF patients (55.5 ± 12.2 years) and more were found to have chronic kidney disease (p = 0.02), hypertension (p = 0.04) and dyslipidaemia (p = 0.03), with significantly higher baseline HAS-BLED score (p < 0.01) and CHA2DS2-VASc score (p < 0.01). Fewer AF patients were treated with triple therapy (p = 0.04). Despite this, there was no difference observed in resolution of the LV thrombus on repeat imaging (p = 0.30). However, Kaplan-Meier analysis showed a higher incidence of stroke (p = 0.02) and all-cause mortality (p < 0.01) in AF patients. Conclusion: Post-STEMI patients with LV thrombus formation and AF have significant differences from non-AF patients and are associated with poorer outcomes. These findings should be validated in larger cohorts.

We read with great interest the study by Ram et al. They concluded in their study that patients with left ventricular thrombus (LVT) post‐anterior ST‐segment elevation myocardial infarction (STEMI) was associated with increased in‐hospital thromboembolic events and length of hospital stay, but not in‐hospital mortality or bleeding risks compared to those without LVT formation [1].

Left ventricular (LV) thrombus is commonly seen in patients with extensive anterior ST-elevation myocardial infarction. The standard of care for LV thrombus is anticoagulation with warfarin. However, there has been an increasing trend of case reports using non-vitamin K antagonist oral anticoagulants (NOAC) for the treatment of LV thrombus. This study aimed to perform a meta-summary of the literature to characterise and evaluate the safety and feasibility of using NOAC in patients with LV thrombus. We searched for articles published in four electronic databases: PubMed, EMBASE, Scopus and Google Scholar using an appropriate keyword/MeSH term search strategy. Twenty-four studies comprising 36 patients were included in the analysis. Rivaroxaban was used in majority of patients (47.2%), whilst Apixaban and Dabigatran were prescribed in 25.0% and 27.8% of patients respectively. The most commonly associated risk factor found was post-acute myocardial infarction in 15 patients (41.7%). LV thrombus resolution was met by most patients (87.9%), and the median duration of treatment to resolution was 30.0 days (IQR = 22.5–47.0). One non-fatal bleeding event (3.0%) and no embolic events were reported. The use of NOAC may have a role in the treatment of LV thrombus in selected patients. Further randomized controlled trials are needed to evaluate this treatment strategy.

A cardiocerebral ischemic attack (CCI) or a concurrent acute ischemic stroke (AIS) and myocardial infarction (AMI) is a severe event with no clear recommendations for ideal management because of the rarity of the scenario. The narrow time window for treatment and complexity of the treatment decision puts immense pressure on the treating physician. We evaluated this challenging situation at our tertiary center. Using our prospective stroke database out of a total of 555 patients with acute ischemic stroke between 2009 and 2014, we identified five consecutive cases with CCI (incidence 0.009%). Demography, risk factor characteristics, vascular occlusions and treatment approach were recorded. Good functional outcome was defined by the modified Rankin scale (mRS) score of 0–2 points. Out of five patients, AIS was treated with endovascular treatment in three cases, while two were treated with intravenous thrombolysis only. One out of three patients had embolectomy of the brain performed prior to the coronary intervention, while the other two patients underwent coronary intervention first. One patient developed sudden cardiac arrest on day-2 and passed away. CCI is an uncommon and devastating clinical scenario, further research is needed for the ideal management strategy that provides the best outcomes. However, the rarity of the disease does not lend itself to the conduct of a trial easily. We have proposed a considered treatment algorithm based on the current literature and our experience.

Background and Purpose—We assessed the feasibility of obtaining diagnostic quality images of the heart and thoracic aorta by extending the z axis coverage of a non–ECG-gated computed tomographic angiogram performed in the primary evaluation of acute stroke without increasing the contrast dose. Methods—Twenty consecutive patients with acute ischemic stroke within the 4.5 hours of symptom onset were prospectively recruited. We increased the longitudinal coverage to the domes of the diaphragm to include the heart. Contrast administration (Omnipaque 350) remained unchanged (injected at 3–4 mL/s; total 60–80 mL, triggered by bolus tracking). Images of the heart and aorta, reconstructed at 5 mm slice thickness in 3 orthogonal planes, were read by a radiologist and cardiologist, findings conveyed to the treating neurologist, and correlated with the transthoracic or transesophageal echocardiogram performed within the next 24 hours. Results—Of 20 patients studied, 3 (15%) had abnormal findings: a left ventricular thrombus, a Stanford type A aortic dissection, and a thrombus of the left atrial appendage. Both thrombi were confirmed by transesophageal echocardiography, and anticoagulation was started urgently the following day. None of the patients developed contrast-induced nephropathy on follow-up. The radiation dose was slightly increased from a mean of 4.26 mSV (range, 3.88–4.70 mSV) to 5.17 (range, 3.95 to 6.25 mSV). Conclusions—Including the heart and ascending aorta in a routine non–ECG-gated computed tomographic angiogram enhances an existing imaging modality, with no increased incidence of contrast-induced nephropathy and minimal increase in radiation dose. This may help in the detection of high-risk cardiac and aortic sources of embolism in acute stroke patients. http://stroke.ahajournals.org/content/early/2017/04/06/STROKEAHA.117.016903