A Systematic Review of Delayed High-Grade Atrioventricular Block After Transcatheter Aortic Valve Implantation.

Background: High-grade atrioventricular block (HGAVB) is common after transcatheter aortic valve implantation (TAVI), often necessitating permanent pacemaker (PPM) implantation. Delayed HGAVB has varying definitions but typically refers to onset 48 hours after TAVI or following discharge and may cause syncope and sudden cardiac death. This review estimates the incidence of delayed HGAVB and identifies limitations of current literature. Methods: A systematic review was performed of the following online databases: Medline, Cochrane, Web of Science, and Scopus. Studies that labelled the outcome of "delayed" or "late" atrioventricular block after TAVI were included; patients with previous PPM or aortic valve surgery were excluded. Initial search yielded 775 studies, which, after screening, was narrowed to 19 studies. Results: Nineteen studies with 14,898 patients were included. Mean age was 81.7 years, and 46.3% were male. Mean Society of Thoracic Surgeons (STS) score was 5.6%, and 31.3% of patients had known atrial fibrillation. The most common access site was transfemoral (84.8%), whereas balloon-expandable valves were used in 62.1%, self-expanding valves in 34.0%, and mechanically expanding valves in 3.9% of cases. The incidence of delayed HGAVB ranged from 1.7% to 14.6%, with significant methodologic heterogeneity noted among the included studies. Conclusions: Delayed HGAVB is a common and potentially serious complication of TAVI, with similar risk factors to acute HGAVB. With a move toward an early discharge strategy post-TAVI, further prospective study of delayed HGAVB is warranted to improve understanding of predisposing factors, incidence, timing, and implications.

Contexte: L'apparition d'un bloc atrioventriculaire de haut degré (BAVHD) est fréquente après l'implantation valvulaire aortique par cathéter (IVAC), ce qui nécessite souvent l'implantation d'un stimulateur cardiaque permanent. Les définitions d'un BAVHD tardif varient, mais elles font habituellement référence à l'apparition du bloc 48 heures après l'IVAC ou après le congé de l'hôpital. Le bloc peut alors provoquer une syncope et une mort subite d'origine cardiaque. Cette analyse vise à estimer l'incidence de la formation d'un BAVHD tardif et à définir les lacunes dans les publications actuelles. Méthodologie: Une analyse des études publiées dans les bases de données en ligne suivantes a été menée : Medline, Cochrane, Web of Science et Scopus. Les études dont le libellé comprenait l'issue du bloc atrioventriculaire tardif ou éloigné (« delayed ¼ ou « late ¼) ont été retenues. Les patients qui avaient antérieurement reçu un stimulateur cardiaque permanent ou subi une intervention chirurgicale de la valve aortique ont été exclus. La recherche initiale a permis de recenser 775 études, nombre qui a été réduit à 19 après l'application des critères de sélection. Résultats: Dix-neuf études totalisant 14 898 patients ont été retenues. L'âge moyen était 81,7 ans, et 46,3 % des patients étaient des hommes. Le score STS (Society of Thoracic Surgeons) moyen était de 5,6 %, et 31,3 % des patients avaient une fibrillation auriculaire. Le point d'accès le plus fréquent était par l'artère fémorale (84,8 %). Des valves expansibles par ballonnet ont été utilisées dans 62,1 % des cas, des valves auto-expansibles dans 34,0 % des cas et des valves expansibles mécaniquement dans 3,9 % des cas. L'incidence du BAVHD tardif variait de 1,7 % à 14,6 %, mais la méthodologie était très hétérogène d'une étude à l'autre. Conclusions: Le BAVHD tardif est une complication fréquente et potentiellement grave de l'IVAC, et ses facteurs de risque sont comparables à ceux du BAVHD aigu. Étant donné la volonté d'adopter une stratégie de congé précoce après une IVAC, une autre étude prospective sur le BAVHD tardif s'impose pour mieux comprendre les facteurs prédisposants, l'incidence, la chronologie et les implications.

Sonothrombolysis for Ischemic Stroke.

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

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

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

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

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

Outcomes after surgical revascularization for adult Moyamoya disease: A Southeast Asian tertiary centre experience.

There are numerous studies on the natural history and outcomes of adult Moyamoya disease (MMD) in the literature, but limited data from Southeast Asian cohorts. Hence, we aimed to retrospectively review the clinical characteristics and outcomes after surgical revascularization for adult MMD in our Southeast Asian cohort. Patients were included if they were above 18 years old at the first surgical revascularization for MMD, and underwent surgery between 2012 and 2022 at the National University Hospital, Singapore. The outcomes were transient ischemic attack (TIA), ischemic stroke, intracerebral hemorrhage, and all-cause mortality during the postoperative follow-up period. In total, 26 patients who underwent 27 revascularization procedures were included. Most patients were of Chinese ethnicity, and the mean (SD) age at the time of surgery was 47.7 (12.6) years. The commonest clinical presentation was intracerebral hemorrhage, followed by TIA and ischemic stroke. Direct revascularization with superficial temporal artery-middle cerebral artery (STA-MCA) bypass was the most common procedure (24/27 surgeries, 88.9 %). The mean (SD) follow-up duration was 4.2 (2.5) years, during which the overall incidence of postoperative TIA/stroke was 25.9 % (7/27 surgeries), with most cases occurring within 7 days postoperatively. There were no mortalities during the postoperative follow-up period. Risk factors for 30-day postoperative TIA/stroke included a higher number of TIAs/strokes preoperatively (p = 0.044) and indirect revascularization (p = 0.028). Diabetes mellitus demonstrated a trend towards an increased risk of 30-day postoperative TIA/stroke, but this was not statistically significant (p = 0.056). These high-risk patients may benefit from more aggressive perioperative antithrombotic and hydration regimens.

Revolutionizing the Management of Large-Core Ischaemic Strokes: Decoding the Success of Endovascular Therapy in the Recent Stroke Trials.

Endovascular therapy (EVT) has revolutionized the management of acute ischaemic strokes with large vessel occlusion, with emerging evidence suggesting its benefit also in large infarct core volume strokes. In the last two years, four randomised controlled trials have been published on this topic-RESCUE-Japan LIMIT, ANGEL-ASPECT, SELECT2 and TENSION, with overall results showing that EVT improves functional and neurological outcomes compared to medical management alone. This review aims to summarise the recent evidence presented by these four trials and highlight some of the limitations in our current understanding of this topic.

Comparison of short-term outcomes between patients with extracranial carotid and/or intracranial atherosclerotic disease.

OBJECTIVE: To directly compare the 90-day outcomes of patients with symptomatic intracranial atherosclerotic disease (ICAD), extracranial carotid atherosclerotic disease (ECAD), and ICAD with concomitant ECAD. METHODS: From 2017-2021, patients who had (1) a transient ischemic attack or ischemic stroke within 30 days of admission as evaluated by a stroke neurologist and (2) ipsilateral 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 myocardial infarction (MI), all-cause mortality, and major adverse cardiovascular events (MACE, including cardiovascular death, nonfatal MI, and/or nonfatal 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 4.54 (95% CI=1.45, 14.2; p = 0.006), 9.32 (95% CI=1.58, 54.8; p = 0.014), and 8.52 (95% CI=3.54, 20.5; p < 0.001) for 90-day ischemic stroke, MI, and MACE, respectively. CONCLUSIONS: Patients with ICAD and concomitant ECAD have a poorer prognosis and are at significantly higher risk for 90-day ischemic stroke, MI, and MACE. Further research should focus on the evaluation of coronary atherosclerotic disease and more intensive medical therapy in this population.

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

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

Safety and clinical outcomes in endovascular treatment for symptomatic cerebral venous thrombosis: a single-center experience with meta-analysis.

The role of mechanical thrombectomy (MT) in cerebral venous sinus thrombosis (CVT) is ambiguous. This study aims to share our experience with MT in CVT, supplemented by a meta-analysis on this treatment. All patients who had MT for CVT at our institution, between 2016 and 2021, were retrospectively reviewed for treatment indications, the technique used, success and complication rates, and clinical outcomes. A meta-analysis was performed for clinical and safety outcomes from published literature with > 10 patients. A total of 15 patients were included in this study. All had a venous hemorrhage or deteriorating despite anticoagulation. MT was performed using aspiration (with wide bore catheters) in 7 patients: aspiration with stent retriever in 5 and transjugular Fogarty-balloon thrombectomy in 3 patients. Adjunctive intra-sinus thrombolysis (IST) was used in 4 cases and venoplasty in 3. Technical success (restoring antegrade venous flow on arterial injection) was 100% with no procedure-related major complication. The direct transjugular approach was cheaper and faster. At 3-month follow-up, 86% of patients had good outcomes (MRS < 2). Meta-analysis of clinical and safety outcomes from 22 and 20 studies, respectively, demonstrated a positive association between MT and good outcomes as well as no significant association with hazardous periprocedural events. EVT via mechanical means for CVT is feasible in our series and meta-analysis. From our experience, trans-jugular Fogarty balloon embolectomy seems to be a potential cost-saving option, at least in a certain part of the world.

Etiologies, mechanisms, and risk factors of ischemic stroke in a young Asian adult cohort.

OBJECTIVES: Risk factors and causes of acute ischemic stroke (AIS) are more diverse in young adults, and traditional stroke classifications may be inadequate. Precise characterisation of AIS is important for guiding management and prognostication. We describe stroke subtypes, risk factors and etiologies for AIS in a young Asian adult population. MATERIALS AND METHODS: Young AIS patients aged 18-50 years admitted to two comprehensive stroke centres from 2020-2022 were included. Stroke etiologies and risk factors were adjudicated using Trial of Org 10172 in Acute Stroke Treatment (TOAST) and International Pediatric Stroke Study (IPSS) risk factors. Potential embolic sources (PES) were identified in a subgroup with embolic stroke of undetermined source (ESUS). These were compared across sex, ethnicities and age groups (18-39 years versus 40-50 years). RESULTS: A total of 276 AIS patients were included, with mean age 43±5.7 years and 70.3% male. Median duration of follow-up was 5 months (IQR: 3-10). The most common TOAST subtypes were small-vessel disease (32.6%) and undetermined etiology (24.6%). IPSS risk factors were identified in 95% of all patients and 90% with undetermined etiology. IPSS risk factors included atherosclerosis (59.5%), cardiac disorders (18.7%), prothrombotic states (12.4%) and arteriopathy (7.7%). In this cohort, 20.3% had ESUS, of which 73.2% had at least one PES, which increased to 84.2% in those <40 years old. CONCLUSIONS: Young adults have diverse risk factors and causes of AIS. IPSS risk factors and ESUS-PES construct are comprehensive classification systems that may better reflect heterogeneous risk factors and etiologies in young stroke patients.

Prospective observational study on the accuracy of predictors of high-grade atrioventricular conduction block after transcatheter aortic valve implantation (CONDUCT-TAVI): study protocol, background and significance.

INTRODUCTION: Aortic stenosis is the most common cardiac valve pathology worldwide and has a mortality rate of over 50% at 5 years if left untreated. Transcatheter aortic valve implantation (TAVI) is a minimally invasive and highly effective alternative treatment option to open-heart surgery. High-grade atrioventricular conduction block (HGAVB) is one of the most common complications after TAVI and requires a permanent pacemaker. Due to this, patients are typically monitored for 48 hours post TAVI, however up to 40% of HGAVB may delayed, and occur after discharge. Delayed HGAVB can cause syncope or sudden unexplained cardiac death in a vulnerable population, and no accurate methods currently exist to identify patients at risk. METHODS AND ANALYSIS: The prospective observational study on the accuracy of predictors of high-grade atrioventricular conduction block after transcatheter aortic valve implantation (CONDUCT-TAVI) trial is an Australian-led, multicentre, prospective observational study, aiming to improve the prediction of HGAVB, after TAVI. The primary objective of the trial is to assess whether published and novel invasive electrophysiology predictors performed immediately before and after TAVI can help predict HGAVB after TAVI. The secondary objective aims to further evaluate the accuracy of previously published predictors of HGAVB after TAVI, including CT measurements, 12-lead ECG, valve characteristics, percentage oversizing and implantation depth. Follow-up will be for 2 years, and detailed continuous heart rhythm monitoring will be obtained by inserting an implantable loop recorder in all participants. ETHICS AND DISSEMINATION: Ethics approval has been obtained for the two participating centres. Results of the study will be submitted for publication in a peer-reviewed journal. TRIAL REGISTRATION NUMBER: ACTRN12621001700820.

Role of plaque inflammation in symptomatic carotid stenosis.

Objective: Prior studies have shown that plaque inflammation on FDG-PET and the symptomatic carotid atheroma inflammation lumen-stenosis (SCAIL) score were associated with recurrent ischemic events, but the findings have thus far not been widely validated. Therefore, we aimed to validate the findings of prior studies. Methods: A single-center prospective cohort study that recruited patients with (1) recent TIA or ischemic stroke within the past 30 days, (2) ipsilateral carotid artery stenosis of ≥50%, and (3) were not considered for early carotid revascularization. The (1) maximum standardized uptake value (SUVmax) of the symptomatic carotid plaque, (2) the SCAIL score, and (3) stenosis severity of the symptomatic carotid artery were measured for all patients. The outcomes were (1) a 90-day ipsilateral ischemic stroke and (2) a 90-day ipsilateral symptomatic TIA or major adverse cardiovascular event (MACE). Results: Among the 131 patients included in the study, the commonest cardiovascular risk factor was hypertension (95 patients, 72.5%), followed by diabetes mellitus (77 patients, 58.8%) and being a current smoker (64 patients, 48.9%). The median (IQR) duration between the index cerebral ischemic event and recruitment to the study was 1 (0, 2.5) days. The median (IQR) duration between the index cerebral ischemic event and FDG-PET was 5 (4, 7) days. A total of 14 (10.7%) patients had a 90-day stroke, and 41 (31.3%) patients had a 90-day TIA or MACE. On comparison of the predictive performances of the SCAIL score and SUVmax, SUVmax was found to be superior to the SCAIL score for predicting both 90-day ipsilateral ischemic stroke (AUC: SCAIL = 0.79, SUVmax = 0.92; p < 0.001; 95% CI = 0.072, 0.229) and 90-day TIA or MACE (AUC: SCAIL = 0.76, SUVmax = 0.84; p = 0.009; 95% CI = 0.020, 0.143). Conclusion: Plaque inflammation as quantified on FDG-PET may serve as a reliable biomarker for risk stratification among patients with ECAD and recent TIA or ischemic stroke. Future studies should evaluate whether patients with significant plaque inflammation as quantified on FDG-PET benefit from carotid revascularization and/or anti-inflammatory therapy.

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

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

Impact of atrial fibrillation on the treatment effect of bridging thrombolysis in ischemic stroke patients undergoing endovascular thrombectomy: a multicenter international cohort study.

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.

Extrapulmonary manifestations and complications of severe acute respiratory syndrome coronavirus-2 infection: a systematic review.

Introduction: We aimed to describe the extrapulmonary manifestations of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection, including their frequency, onset with respect to respiratory symptoms, pathogenesis and association with disease severity. Methods: We searched the MEDLINE and Embase databases for SARS-CoV-2-related studies. Meta-analysis, observational studies, case series and case reports published in English or Chinese between 1 January 2020 and 1 May 2020 were included. Reports with only paediatric or obstetric cases were excluded. Results: 169 articles were included. Early manifestations (preceding respiratory symptoms until Day 6 of onset) included olfactory and gustatory disturbance (self-reported in up to 68% and 85% of cases, respectively), gastrointestinal symptoms (up to 65.9%) and rash (up to 20.4%). From Day 7 onwards, hypercytokinaemia, paralleled multi-organ complications including acute cardiac injury (pooled incidence of 17.7% in 1,412 patients, mostly with severe disease and 17.4% mortality), kidney and liver injury (up to 17% and 33%, respectively) and thrombocytopenia (up to 30%). Hypercoagulability resulted in venous thromboembolic events in up to 31% of all patients. Uncommon disease presentation and complications comprised Guillain-Barré syndrome, rhabdomyolysis, otitis media, meningoencephalitis and spontaneous pneumomediastinum. Conclusion: Although the systemic manifestations of SARS-CoV-2 infection are variegated, they are deeply interwoven by shared mechanisms. Two phases of extrapulmonary disease were identified: (a) an early phase with possible gastrointestinal, ocular and cutaneous involvement; and (b) a late phase characterised by multiorgan dysfunction and clinical deterioration. A clear, multidisciplinary consensus to define and approach thromboinflammation and cytokine release syndrome in SARS-CoV-2 is needed.

Combined balloon guide catheter, aspiration catheter, and stent retriever technique versus balloon guide catheter and stent retriever alone technique: a systematic review and meta-analysis.

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 I2 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), I2=57%) or final successful reperfusion (64.5% vs 68.6%, OR 0.98 (95% CI 0.81% to 1.20%), I2=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), I2=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.

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

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

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

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