Patent foramen ovale closure in ischemic stroke patients with and without thrombophilia: a systematic review and meta-analyses.

Ischemic stroke patients with thrombophilia and patient foramen ovale (PFO) may have an increased risk of recurrent stroke and transient ischemic attack (TIA), and may benefit from PFO closure. However, screening for thrombophilia is not routinely performed and the impact of thrombophilia on prognosis after PFO closure is uncertain. We aim to compare the risk of recurrent stroke and TIA after PFO closure in patients with thrombophilia versus those without. We performed a systematic review and meta-analyses of the literature, with a comprehensive literature search performed on 12 January 2023. Studies comparing the outcomes of patients with and without thrombophilia after PFO closure were included. The primary outcome evaluated was a recurrence of acute cerebrovascular event (ACE), a composite of recurrent ischemic stroke and recurrent TIA. The secondary outcomes included recurrent ischemic stroke only or TIA only. A total of 8 cohort studies were included, with a total of 3514 patients. There was an increased risk of stroke/TIA in patients with thrombophilia compared to those without thrombophilia after PFO (OR: 1.42, 95% CI: 1.01-1.99, I2 = 50%). The association between risk of TIA only (OR: 1.36, 95% CI: 0.77-2.41, I2 = 0%) and stroke only (OR: 1.09, 95% CI: 0.54-2.21, I2 = 0%) with thrombophilia did not reach statistical significance. There is an increased risk of recurrent cerebral ischemia event in patients with thrombophilia compared to those without thrombophilia after PFO closure. Future large prospective studies are necessary to characterise the risk and benefits of PFO closure, as well as the appropriate medical treatment to reduce the risk of recurrent stroke and TIA in this high-risk population.

Detection of Atrial Fibrillation After Ischemic Stroke with an Insertable Cardiac Monitor: A Systematic Review and Individual Patient Data Meta-Analysis of Randomised Clinical Trials.

OBJECTIVE: In ischemic stroke patients, we compared the use of insertable cardiac monitor (ICM) versus non-ICM methods of cardiac monitoring on the incidence of atrial fibrillation (AF) detection and other clinical outcomes. BACKGROUND: Current guidelines recommend the routine use of 12-lead electrocardiography or Holter monitoring for AF detection after ischemic stroke. Recent randomised controlled trials have investigated the impact of ICM versus non-ICM methods of cardiac monitoring for AF detection in this population. However, precise recommendations for monitoring post-stroke AF are lacking; including the optimal timing, duration, and method of electrocardiography monitoring. METHODS: A systematic search was conducted on Embase and PubMed from database inception until 27 October 2022 to include randomised controlled trials that compared ICM with non-ICM methods of cardiac monitoring for post-stroke AF detection. This yielded 3 randomised controlled trials with a combined cohort of 1231 patients with a recent ischemic stroke. Individual patient data (IPD) was then reconstructed from Kaplan-Meier curves and analysed using the shared-frailty Cox model. An aggregate data meta-analysis was conducted for 1231 patients across all 3 studies for outcomes that could not be reconstructed using IPD. RESULTS: One-stage meta-analysis demonstrated an increase in the hazard ratio (HR 6.01, 95% CI 3.40-10.60; p<0.001) of AF detection in patients undergoing monitoring via ICM compared to standard care. Aggregate data meta analysis revealed a significant increase in initiation of anticoagulation (OR 3.09, 95% CI 2.05 - 4.66; p<0.00001) in the ICM group. However, no significant differences in the incidence of recurrent ischemic stroke, transient ischemic attack or death were found. CONCLUSIONS: In this meta-analysis, we found that the use of ICM increased the detection rate of post-stroke AF and the rate of anticoagulation initiation. However, this did not translate into a reduced incidence of recurrent ischemic stroke.

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.

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

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

Association of Electrocardiographic P-Wave Markers and Atrial Fibrillation in Embolic Stroke of Undetermined Source.

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.

Long-Term Outcomes of Stroke or Transient Ischemic Attack after Non-Emergency Percutaneous Coronary Intervention.

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.

Cerebral Venous Thrombosis in Patients with COVID-19 Infection: a Case Series and Systematic Review.

BACKGROUND: There has been increasing reports associating the coronavirus disease 2019 (COVID-19) with thromboembolic phenomenon including ischemic strokes and venous thromboembolism. Cerebral venous thrombosis (CVT) is a rare neurovascular emergency that has been observed in some COVID-19 patients, yet much remains to be learnt of its underlying pathophysiology. OBJECTIVE: We present a case series of local patients with concomitant COVID-19 infection and CVT; and aim to perform a systematic review of known cases in the current literature. METHODS: We describe two patients with concomitant COVID-19 infection and CVT from a nationwide registry in Singapore. We then conducted a literature search in PubMed and Embase using a suitable keyword search strategy from 1st December 2019 to 11th June 2020. All studies reporting CVT in COVID-19 patients were included. RESULTS: Nine studies and 14 COVID-19 patients with CVT were studied. The median age was 43 years (IQR=36-58) and majority had no significant past medical conditions (60.0%). The time taken from onset of COVID-19 symptoms to CVT diagnosis was a median of 7 days (IQR=6-14). CVT was commonly seen in the transverse (75.0%) and sigmoid sinus (50.0%); 33.3% had involvement of the deep venous sinus system. A significant proportion of patients had raised D-dimer (75.0%) and CRP levels (50.0%). Two patients reported presence of antiphospholipid antibodies. Most patients received anticoagulation (91.7%) while overall mortality rate was 45.5%. CONCLUSIONS: The high mortality rate of CVT in COVID-19 infection warrants a high index of suspicion from physicians, and early treatment with anticoagulation should be initiated.

Intracranial Artery Calcium Burden Predicts Recurrent Cerebrovascular Events in Transient Ischaemic Attack Patients.

BACKGROUND: Patients with initial transient ischaemic attack (TIA) subsequently have a higher risk of recurrent TIA or acute ischemic stroke (AIS). The role of scoring intracranial arterial calcification (IAC) in predicting the prevalence of stroke remains unclear. We aim to evaluate if radiological CT calcium score measuring IAC burden could predict future ischemic events in a cohort of TIA patients. METHODS: We studied consecutive patients from July 2014 to December 2015 who presented with first episode of TIA. All patients had noncontrasted CT or CT-angiogram of the brain on admission. CT calcium score (cm3) was quantified by measuring calcium deposition in the bilateral internal carotid arteries, middle cerebral arteries, and vertebrobasilar system. Patients were followed up for 2 years and ischemic events for either recurrent TIA or AIS were recorded. We compared patients in terms of clinical profile at presentation and CT calcium score using appropriate univariate and multivariable analyses. RESULTS: Of 156 TIA patients studied, 22% (n = 35) had recurrent TIA or AIS within 2 years of follow-up. On univariate analyses, recurrent TIA/AIS was associated with gender (OR 0.61; 95%CI 0.40-0.95; P = .038), hypertension (mean difference 2.49; 95%CI 1.08-5.75; P = .030) and higher CT calcium score (mean difference 0.84 95%CI 0.16-1.52 P = .016). On multivariable logistic regression, a higher CT calcium score was significantly associated with recurrent TIA/AIS (adjusted OR 1.25 95%CI 1.01-1.55 P = .042). CONCLUSIONS: In TIA patients, higher IAC burden by measurement of a quantitative CT calcium score may be associated with recurrent ischemic events.

Use of wearable technology in cardiac monitoring after cryptogenic stroke or embolic stroke of undetermined source: a systematic review.

INTRODUCTION: Prolonged cardiac monitoring after cryptogenic stroke or embolic stroke of undetermined source (ESUS) is necessary to identify atrial fibrillation (AF) that requires anticoagulation. Wearable devices may improve AF detection compared to conventional management. We aimed to review the evidence for the use of wearable devices in post-cryptogenic stroke and post-ESUS monitoring. METHODS: We performed a systematic search of PubMed, EMBASE, Scopus and clinicaltrials.gov on 21 July 2022, identifying all studies that investigated the use of wearable devices in patients with cryptogenic stroke or ESUS. The outcomes of AF detection were analysed. Literature reports on electrocardiogram (ECG)-based (external wearable, handheld, patch, mobile cardiac telemetry [MCT], smartwatch) and photoplethysmography (PPG)-based (smartwatch, smartphone) devices were summarised. RESULTS: A total of 27 relevant studies were included (two randomised controlled trials, seven prospective trials, 10 cohort studies, six case series and two case reports). Only four studies compared wearable technology to Holter monitoring or implantable loop recorder, and these studies showed no significant differences on meta-analysis (odds ratio 2.35, 95% confidence interval [CI] 0.74-7.48, I 2 = 70%). External wearable devices detected AF in 20.7% (95% CI 14.9-27.2, I 2 = 76%) of patients and MCT detected new AF in 9.6% (95% CI 7.4%-11.9%, I 2 = 56%) of patients. Other devices investigated included patch sensors, handheld ECG recorders and PPG-based smartphone apps, which demonstrated feasibility in the post-cryptogenic stroke and post-ESUS setting. CONCLUSION: Wearable devices that are ECG or PPG based are effective for paroxysmal AF detection after cryptogenic stroke and ESUS, but further studies are needed to establish how they compare with Holter monitors and implantable loop recorder.

Machine Learning Modeling to Predict Atrial Fibrillation Detection in Embolic Stroke of Undetermined Source Patients.

BACKGROUND: In patients with embolic stroke of undetermined source (ESUS), occult atrial fibrillation (AF) has been implicated as a key source of cardioembolism. However, only a minority acquire implantable cardiac loop recorders (ILRs) to detect occult paroxysmal AF, partly due to financial cost and procedural inconvenience. Without the initiation of appropriate anticoagulation, these patients are at risk of increased ischemic stroke recurrence. Hence, cost-effective and accurate methods of predicting AF in ESUS patients are highly sought after. OBJECTIVE: We aimed to incorporate clinical and echocardiography data into machine learning (ML) algorithms for AF prediction on ILRs in ESUS. METHODS: This was a single-center cohort study that included 157 consecutive patients diagnosed with ESUS from October 2014 to October 2017 who had ILR evaluation. We developed four ML models, with hyperparameters tuned, to predict AF detection on an ILR. RESULTS: The median age of the cohort was 67 (IQR 59-74) years old and the median monitoring duration was 1051 (IQR 478-1287) days. Of the 157 patients, 32 (20.4%) had occult AF detected on the ILR. Support vector machine predicted for AF with a 95% confidence interval area under the receiver operating characteristic curve (AUC) of 0.736-0.737, multilayer perceptron with an AUC of 0.697-0.708, XGBoost with an AUC of 0.697-0.697, and random forest with an AUC of 0.663-0.674. ML feature importance found that age, HDL-C, and admitting heart rate were important non-echocardiography variables, while peak mitral A-wave velocity and left atrial volume were important echocardiography parameters aiding this prediction. CONCLUSION: Machine learning modeling incorporating clinical and echocardiographic variables predicted AF in ESUS patients with moderate accuracy.

First pass effect as an independent predictor of functional outcomes in medium vessel occlusions: An analysis of an international multicenter study.

INTRODUCTION: First pass effect (FPE), achievement of complete recanalization (mTICI 2c/3) with a single pass, is a significant predictor of favorable outcomes for endovascular treatment (EVT) in large vessel occlusion stroke (LVO). However, data concerning the impact on functional outcomes and predictors of FPE in medium vessel occlusions (MeVO) are scarce. PATIENTS AND METHODS: We conducted an international retrospective study on MeVO cases. Multivariable logistic modeling was used to establish independent predictors of FPE. Clinical and safety outcomes were compared between the two study groups (FPE vs non-FPE) using logistic regression models. Good outcome was defined as modified Rankin Scale 0-2 at 3 months. RESULTS: Eight hundred thirty-six patients with a final mTICI ⩾ 2b were included in this analysis. FPE was observed in 302 patients (36.1%). In multivariable analysis, hypertension (aOR 1.55, 95% CI 1.10-2.20) and lower baseline NIHSS score (aOR 0.95, 95% CI 0.93-0.97) were independently associated with an FPE. Good outcomes were more common in the FPE versus non-FPE group (72.8% vs 52.8%), and FPE was independently associated with favorable outcome (aOR 2.20, 95% CI 1.59-3.05). 90-day mortality and intracranial hemorrhage (ICH) were significantly lower in the FPE group, 0.43 (95% CI, 0.25-0.72) and 0.55 (95% CI, 0.39-0.77), respectively. CONCLUSION: Over 2/3 of patients with MeVOs and FPE in our cohort had a favorable outcome at 90 days. FPE is independently associated with favorable outcomes, it may reduce the risk of any intracranial hemorrhage, and 3-month mortality.

Symptomatic intracerebral hemorrhage in proximal and distal medium middle cerebral artery occlusion patients treated with mechanical thrombectomy.

BACKGROUND: Acute ischemic stroke (AIS) caused by distal medium vessel occlusions (DMVOs) represents a significant proportion of overall stroke cases. While intravenous thrombolysis (IVT) has been a primary treatment, advancements in endovascular procedures have led to increased use of mechanical thrombectomy (MT) in DMVO stroke patients. However, symptomatic intracerebral hemorrhage (sICH) remains a critical complication of AIS, particularly after undergoing intervention. This study aims to identify factors associated with sICH in DMVO stroke patients undergoing MT. METHODS: This retrospective analysis utilized data from the Multicenter Analysis of Distal Medium Vessel Occlusions: Effect of Mechanical Thrombectomy (MAD-MT) registry, involving 37 centers across North America, Asia, and Europe. Middle cerebral artery (MCA) DMVO stroke patients were included. The primary outcome measured was sICH, as defined per the Heidelberg Bleeding Classification. Univariable and multivariable logistic regression were used to identify factors independently associated with sICH. RESULTS: Among 1708 DMVO stroke patients, 148 (8.7%) developed sICH. Factors associated with sICH in DMVO patients treated with MT included older age (adjusted odds ratio (aOR) 1.01, 95% confidence interval (95% CI) 1.00 to 1.03, P=0.048), distal occlusion site (M3, M4) compared with medium occlusions (M2) (aOR 1.71, 95% CI 1.07 to 2.74, P=0.026), prior use of antiplatelet drugs (aOR 2.06, 95% CI 1.41 to 2.99, P<0.001), lower Alberta Stroke Program Early CT Scores (ASPECTS) (aOR 0.75, 95% CI 0.66 to 0.84, P<0.001), higher preoperative blood glucose level (aOR 1.00, 95% CI 1.00 to 1.01, P=0.012), number of passes (aOR 1.27, 95% CI 1.15 to 1.39, P<0.001), and successful recanalization (Thrombolysis In Cerebral Infarction (TICI) 2b-3) (aOR 0.43, 95% CI 0.28 to 0.66, P<0.001). CONCLUSION: This study provides novel insight into factors associated with sICH in patients undergoing MT for DMVO, emphasizing the importance of age, distal occlusion site, prior use of antiplatelet drugs, lower ASPECTS, higher preoperative blood glucose level, and procedural factors such as the number of passes and successful recanalization. Pending confirmation, consideration of these factors may improve personalized treatment strategies.

Incidence and clinical outcomes of perforations during mechanical thrombectomy for medium vessel occlusion in acute ischemic stroke: A retrospective, multicenter, and multinational study.

BACKGROUND: Mechanical thrombectomy (MT) has revolutionized the treatment of acute ischemic stroke (AIS) due to large vessel occlusion (LVO), but its efficacy and safety in medium vessel occlusion (MeVO) remain less explored. This multicenter, retrospective study aims to investigate the incidence and clinical outcomes of vessel perforations (confirmed by extravasation during an angiographic series) during MT for AIS caused by MeVO. METHODS: Data were collected from 37 academic centers across North America, Asia, and Europe between September 2017 and July 2021. A total of 1373 AIS patients with MeVO underwent MT. Baseline characteristics, procedural details, and clinical outcomes were analyzed. RESULTS: The incidence of vessel perforation was 4.8% (66/1373). Notably, our analysis indicates variations in perforation rates across different arterial segments: 8.9% in M3 segments, 4.3% in M2 segments, and 8.3% in A2 segments (p = 0.612). Patients with perforation had significantly worse outcomes, with lower rates of favorable angiographic outcomes (TICI 2c-3: 23% vs 58.9%, p < 0.001; TICI 2b-3: 56.5% vs 88.3%, p < 0.001). Functional outcomes were also worse in the perforation group (mRS 0-1 at 3 months: 22.7% vs 36.6%, p = 0.031; mRS 0-2 at 3 months: 28.8% vs 53.9%, p < 0.001). Mortality was higher in the perforation group (30.3% vs 16.8%, p = 0.008). CONCLUSION: This study reveals that while the occurrence of vessel perforation in MT for AIS due to MeVO is relatively rare, it is associated with poor functional outcomes and higher mortality. The findings highlight the need for increased caution and specialized training in performing MT for MeVO. Further prospective research is required for risk mitigation strategies.

Outcomes of mechanical thrombectomy in anticoagulated patients with acute distal and medium vessel stroke.

BACKGROUND: Stroke remains a major health concern globally, with oral anticoagulants widely prescribed for stroke prevention. The efficacy and safety of mechanical thrombectomy (MT) in anticoagulated patients with distal medium vessel occlusions (DMVO) are not well understood. METHODS: This retrospective analysis involved 1282 acute ischemic stroke (AIS) patients who underwent MT in 37 centers across North America, Asia, and Europe from September 2017 to July 2023. Data on demographics, clinical presentation, treatment specifics, and outcomes were collected. The primary outcomes were functional outcomes at 90 days post-MT, measured by modified Rankin Scale (mRS) scores. Secondary outcomes included reperfusion rates, mortality, and hemorrhagic complications. RESULTS: Of the patients, 223 (34%) were on anticoagulation therapy. Anticoagulated patients were older (median age 78 vs 74 years; p < 0.001) and had a higher prevalence of atrial fibrillation (77% vs 26%; p < 0.001). Their baseline National Institutes of Health Stroke Scale (NIHSS) scores were also higher (median 12 vs 9; p = 0.002). Before propensity score matching (PSM), anticoagulated patients had similar rates of favorable 90-day outcomes (mRS 0-1: 30% vs 37%, p = 0.1; mRS 0-2: 47% vs 50%, p = 0.41) but higher mortality (26% vs 17%, p = 0.008). After PSM, there were no significant differences in outcomes between the two groups. CONCLUSION: Anticoagulated patients undergoing MT for AIS due to DMVO did not show significant differences in 90-day mRS outcomes, reperfusion, or hemorrhage compared to non-anticoagulated patients after adjustment for covariates.

What's the optimal duration of anticoagulation in patients with left ventricular thrombus?

INTRODUCTION: Left ventricular thrombus (LVT) occurs in acute myocardial infarction and in ischemic and non-ischemic cardiomyopathies. LVT may result in embolic stroke. Currently, the duration of anticoagulation for LVT is unclear. This is an important clinical question as prolonged anticoagulation is associated with increased bleeding risks, while premature discontinuation may result in embolic complications. AREAS COVERED: There are no randomized trial data regarding anticoagulation duration for LVT. Guidelines and expert consensus recommend anticoagulation for 3-6 months with cessation of anticoagulation if interval imaging demonstrates thrombus resolution. Cardiac magnetic resonance imaging (CMR) is more sensitive and specific compared to echocardiography for LVT detection, and may be appropriate for high-risk patients. Prolonged anticoagulation may be considered in unresolved protuberant or mobile LVT, and in patients with resolved LVT but persistent depressed left ventricular ejection fraction and/or myocardial akinesia or dyskinesia. EXPERT OPINION: CMR will likely be increasingly used for LVT surveillance to guide anticoagulation duration. Further research is needed to determine which patients with persistent LVT on CMR benefit from prolonged anticoagulation.

Benefit and risk of intravenous alteplase in patients with acute large vessel occlusion stroke and low ASPECTS.

BACKGROUND: The benefit of best medical treatment including intravenous alteplase (IVT) before mechanical thrombectomy (MT) in patients with acute ischemic stroke and extensive early ischemic changes on baseline CT remains uncertain. The purpose of this study was to evaluate the benefit of IVT for patients with low ASPECTS (Alberta Stroke Programme Early CT Score) compared with patients with or without MT. METHODS: This multicenter study pooled consecutive patients with anterior circulation acute stroke and ASPECTS≤5 to analyze the impact of IVT on functional outcome, and to compare bridging IVT with direct MT. Functional endpoints were the rates of good (modified Rankin Scale (mRS) score ≤2) and very poor (mRS ≥5) outcome at day 90. Safety endpoint was the occurrence of symptomatic intracranial hemorrhage (sICH). RESULTS: 429 patients were included. 290 (68%) received IVT and 168 (39%) underwent MT. The rate of good functional outcome was 14.4% (95% CI 7.1% to 21.8%) for patients who received bridging IVT and 24.4% (95% CI 16.5% to 32.2%) for those who underwent direct MT. The rate of sICH was significantly higher in patients with bridging IVT compared with direct MT (17.8% vs 6.4%, p=0.004). In multivariable logistic regression analysis, IVT was significantly associated with very poor outcome (OR 2.22, 95% CI 1.05 to 4.73, p=0.04) and sICH (OR 3.44, 95% CI 1.18 to 10.07, p=0.02). Successful recanalization, age, and ASPECTS were associated with good functional outcome. CONCLUSIONS: Bridging IVT in patients with low ASPECTS was associated with very poor functional outcome and an increased risk of sICH. The benefit of this treatment should therefore be carefully weighed in such scenarios. Further randomized controlled trials are required to validate our findings.

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.

Incidence of acute cerebrovascular events in patients with rheumatic or calcific mitral stenosis: A systematic review and meta-analysis.

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, was 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.

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

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

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.