Altered left atrial metrics in patients with cryptogenic stroke: A systematic review and meta-analysis.

BACKGROUND: There is no defined cause for cryptogenic stroke/embolic stroke of undetermined source (CS-ESUS). As atrial fibrillation (AF) develops in a significant proportion of these patients, it has been suggested that left atrial (LA) myopathy may predispose to CS-ESUS. We investigated alterations in echocardiographic measures of LA size and function in patients with CS-ESUS. METHODS: A systematic literature review and meta-analysis was performed. PubMed, EMBASE, Cochrane Library, Web of Science and SCOPUS were searched for articles published between 1 January 1990 and 10 February 2023. All observational studies of adult CS-ESUS patients with LA volume or function measurements performed by transthoracic echocardiogram were included. Individual random effects meta-analyses were performed on LA measurements in the CS-ESUS patients using subgroup analysis of comparator groups. RESULTS: We included 29 articles with 3927 CS-ESUS patients. Analysis of weighted mean differences showed CS-ESUS patients had altered LA structure and function parameters, with a larger maximum indexed LA volume, reduced LA emptying fraction and/or LA reservoir strain, compared to healthy controls and noncardioembolic stroke patients. Conversely, CS-ESUS patients had a smaller left atrium with better function, compared to cardioembolic stroke patients and CS-ESUS patients who subsequently developed atrial fibrillation. CONCLUSIONS: LA volume and function are altered in CS-ESUS patients compared to healthy controls and other stroke aetiologies. An underlying atrial myopathy in a subset of CS-ESUS patients may be involved in both thrombogenesis and dysrhythmia (specifically AF). While LA functional assessment is not currently recommended following stroke, it may offer an opportunity for recurrent stroke risk stratification.

Association Between Oral Anticoagulants and Stroke Severity at Onset in Elderly Patients with Cardioembolic Stroke Due to Non-Valvular Atrial Fibrillation.

OBJECTIVES: This study aimed to determine whether oral anticoagulant therapy affects the severity of cerebral infarction at onset in elderly patients with non-valvular atrial fibrillation. MATERIALS AND METHODS: This retrospective study included 330 elderly patients (aged ≥75 years) who were hospitalized for cardioembolic stroke due to non-valvular atrial fibrillation. Patients' medical history, stroke severity at onset (National Institutes of Health Stroke Scale score), and the prevalence of large vessel occlusion were compared between patients who received oral anticoagulant therapy (n = 109) and those who did not receive oral anticoagulant therapy (n = 221). RESULTS: Stroke severity was significantly lower in patients who received anticoagulants than in those who did not receive anticoagulants (6 versus 12; P = 0.021). Patients who did not receive anticoagulants had a significantly higher prevalence of large vessel occlusion (52% versus 37%; P = 0.010). After resampling based on propensity score matching, both median stroke severity (7 versus 12; P = 0.046) and large vessel occlusion prevalence (36% versus 57%; P = 0.019) were significantly lower in patients who received anticoagulant therapy. CONCLUSIONS: The results of this study suggest that elderly patients with non-valvular atrial fibrillation who are administered oral anticoagulant therapy before the onset of cerebral infarction develop less severe stroke than those who are not receiving oral anticoagulant therapy. Thus, oral anticoagulant therapy should be actively considered in patients with non-valvular atrial fibrillation as it does not only prevents cerebral embolism, but also reduces the risk of severe sequelae.

Endovascular Treatment of Infective Endocarditis-Related Acute Large Vessel Occlusion Stroke.

OBJECTIVES: Embolic stroke is a frequent complication of infective endocarditis yet lacks acute treatment as intravenous thrombolysis should be avoided due to high risk of intracerebral hemorrhage. Mechanical thrombectomy for large vessel occlusion may be a promising treatment but there is limited data on safety outcomes in infective endocarditis. MATERIALS AND METHODS: In this multi-center retrospective case series, we reviewed data from patients with infective endocarditis-related large vessel occlusion who underwent mechanical thrombectomy in 9 US hospitals. RESULTS: We identified 15 patients at 9 hospitals. A minority presented with signs suggesting infection (2 patients (14%) had fever, 7 (47%) were tachycardic, 2 (13%) were hypotensive, and 8 (53%) had leukocytosis). The median National Institute of Health Stroke Score decreased from 19 (range 9-25) at presentation to 7 post-thrombectomy (range 0-22, median best score post-thrombectomy), and the median modified Rankin Scale on or after discharge for survivors was 3 (range 0-6). Approximately 57% of patients had a modified Rankin Scale between 0 and 3 on or after discharge. Hemorrhagic transformation was observed in 7/15 (47%). The mechanical thrombectomy group had 2/9 petechial hemorrhagic transformation (22%), compared to 4/6 parenchymal hematomas (67%) in the tissue plasminogen activator + mechanical thrombectomy group. CONCLUSIONS: Our findings suggest that patients with large vessel occlusion due to infective endocarditis may not present with overt signs of infection. Mechanical thrombectomy may be an effective treatment in this patient population for whom intravenous thrombolysis should be avoided.

Analyzing Cost-Effectiveness of Allocating Neurointerventionist for Drive and Retrieve System for Patients with Acute Ischemic Stroke.

OBJECTIVES: There are regional disparities in implementation rates of endovascular thrombectomy due to time and resource constraints such as endovascular thrombectomy specialists. In Hokkaido, Japan, Drive and Retrieve System (DRS), where endovascular thrombectomy specialists perform early endovascular thrombectomies by traveling from the facilities where they normally work to facilities closer to the patient. This study analyzed the cost-effectiveness of allocating a endovascular thrombectomy specialist for DRS to treat stroke patients. MATERIALS AND METHODS: he number of ischemic stroke patients expected to receive endovascular thrombectomy in Hokkaido in 2015 was estimated. It was assumed that an additional neutointerventionist was allocated for DRS. The analysis was performed from the government's perspective, which includes medical and nursing-care costs, and the personnel cost for endovascular thrombectomy specialist. The analysis was conducted comparing the current scenario, where patients received endovascular thrombectomy in facilities where endovascular thrombectomy specialists normally work, with the scenario with DRS within 60 min drive distance. Patient transport time was analyzed using geographic information system, and patient severity was estimated from the transport time. The primary outcome was incremental cost-effectiveness ratio (ICER) in each medical area which was calculated from the incremental costs and the incremental quality-adjusted life years (QALYs), estimated from patient severity using published literature. The entire process was repeated 100 times. RESULTS: DRS was most cost-effective in Kamikawachubu area, where the ICER was $14,173±16,802/QALY, significantly lower than the threshold that the Japanese guideline suggested. CONCLUSIONS: Since DRS was cost-effective in Kamikawachubu area, the area should be prioritized when a endovascular thrombectomy specialist for DRS is allocated as a policy.

ASPECTS-Region-Dependent Functional Outcomes after Endovascular Therapy in Patients with Cardioembolic Stroke.

OBJECTIVES: Cardioembolic stroke has a poor prognosis. We evaluated the region-dependent efficacy of endovascular therapy (EVT) based on diffusion-weighted imaging-Alberta Stroke Program Early CT Score (DWI-ASPECTS). METHODS: This post-hoc analysis of the RELAXED study, which investigated the optimal timing of rivaroxaban to prevent nonvalvular atrial fibrillation (NVAF) recurrence in patients with acute ischemic stroke (AIS), included NVAF patients admitted with AIS or transient ischemic attack in the middle cerebral artery (MCA), with internal carotid artery (ICA), M1, or M2-MCA occlusion. Relationships between DWI-ASPECTS region and functional outcome (modified Rankin Scale [mRS]), mortality, recurrence, and hemorrhagic stroke were compared between patients with and without EVT, and adjusted odds ratios for age, pre-stroke mRS, National Institutes of Health Stroke Scale (NIHSS), ICA occlusion, infarct size, recombinant tissue plasminogen activator (rt-PA) use, and onset-to-hospitalization time were estimated. RESULTS: EVT patients had significantly lower hemoglobin levels, higher median NIHSS scores, more lentiform nucleus infarcts, ICA or M1-MCA occlusions, treatment with rt-PA, and fewer M3, M5, or M6 infarcts and M2-MCA occlusions than no-EVT patients. EVT patients had shorter onset-to-hospitalization times and more frequent favorable functional outcomes (p=0.007). Mortality, recurrent ischemic stroke, and hemorrhagic infarction were similar in both groups. EVT was associated with significantly better functional outcomes among patients with insular ribbon (p=0.043) and M3 (p=0.0008) infarcts. M3 patients had significantly fewer rt-PA and EVT, and longer onset-to-hospitalization times. CONCLUSIONS: An occlusion in the insular ribbon or M3 region was associated with favorable functional outcomes in patients treated with EVT after cardioembolic stroke.

Endovascular Therapy for Acute Ischemic Stroke in Patients with Large-Vessel Occlusion due to Atherosclerotic Stenosis.

OBJECTIVES: Endovascular therapy (EVT) is safe and effective for acute ischemic stroke (AIS) due to large-vessel occlusion (LVO). However, the influence of the AIS subtype (large-artery atherosclerosis [LAA] or cardioembolism [CE]) on clinical outcome in patients treated with EVT remains unclear. This study aimed to evaluate the differences in clinical results between the two subtypes using data from a multicenter prospective registry (RESCUE-Japan Registry 2). MATERIALS AND METHODS: Among 2420 patients in RESCUE-Japan Registry, 682 patients who were diagnosed with LAA or CE were enrolled. The primary outcome was a modified Rankin Scale (mRS) score of 0-2 at 90 days. The secondary outcomes were 90-day mRS 0-1, 0-3, and 6. The relationship between time from onset and clinical outcome was also analyzed. RESULTS: Among the 682 patients, 124 were classified into the LAA group and 558 into the CE group. The baseline National Institutes of Health Stroke Scale score was significantly lower (median 15 vs. 18, p < 0.001). At 90 days, mRS 0-2 was observed in 54 of 124 patients (44%) in the LAA group and 232 of 558 patients (42%) in the CE group (p = 0.69). The proportion of patients with mRS 0-2 tended to decrease according to onset-to-puncture time in the CE group but not in the LAA group (ptrend=0.0007). CONCLUSIONS: The rate of good outcome was similar between LVO due to LAA and CE. However, the rate of favorable outcome did not decrease according to onset-to-puncture time in the LAA group.

Nonstenotic Carotid Plaque in Embolic Stroke of Undetermined Source: Interplay of Arterial and Atrial Disease.

BACKGROUND AND PURPOSE: Approximately one-sixth of all ischemic strokes are attributable to embolic stroke of undetermined source (ESUS). Recent analyses suggest that atrial cardiopathy and nonstenotic carotid plaque (nsCP) may represent 2 distinct underlying causes in patients with ESUS, although both diseases share common risk factors and are pathophysiologically intertwined. In this study, we, therefore, aimed to search for associations between nsCP and markers of atrial remodeling and function in patients with embolic stroke. METHODS: Sixty-eight patients with ESUS or atrial fibrillation (AF)-related stroke proven by imaging who underwent comprehensive echocardiographic studies, including measurements of left atrial function and remodeling, were considered. Patients with ESUS underwent a follow-up of at least 1 year after index stroke. For 20 patients with ESUS, NT-proBNP (N-terminal pro-B-type natriuretic peptide) values were available. Presence of nsCP was evaluated considering Duplex sonography and computed tomography angiography and was further categorized in possibly or probably symptomatic nsCP. RESULTS: ESUS patients with nsCP tended to have higher values of septal and lateral total atrial conduction times (P=0.071 and P=0.072, respectively), left atrial volume index (P=0.077), and revealed significantly higher strain rates during early diastole (P=0.013) as well as higher NT-proBNP values (P=0.010) than ESUS patients without nsCP. Moreover, septal total atrial conduction time was significantly longer in ESUS patients with possibly symptomatic nsCP compared with those without (P=0.015). Comparison of ESUS with AF patients revealed significantly higher proportions of nsCP (P=0.010), possibly symptomatic nsCP (P=0.037), and probably symptomatic nsCP (P=0.036) in patients with atrial fibrillation-related stroke. In the regression analysis adjusted for vascular risk factors probably symptomatic nsCP remained significantly associated with AF (P=0.048, odds ratio: 4.46 [95% CI, 1.02-19.56]). CONCLUSIONS: Presence of nsCP is associated with AF and markers of left atrial disease in patients with embolic stroke. Therefore, a thorough evaluation regarding atrial cardiopathy and AF in patients with ESUS should not be restricted if nsCP are found, even if high-risk plaque characteristics are evident.

Quantitative Morphology of Cerebral Thrombi Related to Intravital Contraction and Clinical Features of Ischemic Stroke.

BACKGROUND AND PURPOSE: The purpose was to assess quantitatively and qualitatively the composition and structure of cerebral thrombi and correlate them with the signs of intravital clot contraction (retraction), as well as with etiology, severity, duration, and outcomes of acute ischemic stroke. METHODS: We quantified high-resolution scanning electron micrographs of 41 cerebral thrombi for their detailed cellular and noncellular composition and analyzed histological images for the overall structure with the emphasis on red blood cell compression, fibrin age, and the signs of inflammation. RESULTS: Cerebral thrombi were quite compact and had extremely low porosity. The prevailing cell type was polyhedral compressed erythrocytes (polyhedrocytes) in the core, and fibrin-platelet aggregates were concentrated at the periphery; both findings are indicative of intravital contraction of the thrombi. The content of polyhedrocytes directly correlated with the stroke severity. The prevalence of fibrin bundles was typical for more severe cases, while the content of fibrin sponge prevailed in cases with a more favorable course. The overall platelet content in cerebral thrombi was surprisingly small, while the higher content of platelet aggregates was a marker of stroke severity. Fibrillar types of fibrin prevailed in atherothrombogenic thrombi. Older fibrin prevailed in thrombi from the patients who received thrombolytics, and younger fibrin dominated in cardioembolic thrombi. Alternating layers of erythrocytes and fibrin mixed with platelets were common for thrombi from the patients with more favorable outcomes. Thrombi with a higher number of leukocytes were associated with fatal cases. CONCLUSIONS: Most cerebral thrombi undergo intravital clot contraction (retraction) that may be of underestimated clinical importance. Despite the high variability of the composition and structure of cerebral thrombi, the content of certain types of blood cells and fibrin structures combined with the morphological signs of intravital contraction correlate with the clinical course and outcomes of acute ischemic stroke.

Prolonged ECG with a novel recorder utilizing electrode belt and mobile device in patients with recent embolic stroke of undetermined source: A pilot study.

BACKGROUND: Paroxysmal atrial fibrillation (pAF) is a major risk factor for ischemic stroke, but challenging to detect with routine short-term monitoring methods. In this pilot study, we present a novel method for prolonged ECG and screening for pAF in patients with a recent embolic stroke of unknown source (ESUS). METHODS: Fifteen patients aged ≥ 50 years with a recent ESUS were assigned to wear an external electrode belt-based 1-lead ECG device (Beat2Phone) continuously for 2 weeks (wear time). The device was operated via a mobile phone application in nonhospital conditions. The primary outcome was patient adherence to monitoring. Secondary outcomes were incidence of new pAF, quality-wise comparison to Holter, and usability of the novel ECG monitoring method with Systems Usability Scale (SUS). We also performed a 24- to 48-hr comparison between simultaneous Beat2Phone ECG and a standard Holter in 6 patients. RESULTS: Wear time of Beat2Phone device was over 80% in 5 (33.3%) patients, 50%-80% in 7 (46.6%) patients, and less than 50% in 3 (20%) patients. We detected pAF ≥ 30 s in 1 patient (6.7%). In the simultaneous monitoring with Beat2Phone and Holter, there were a total of 817 (out of 1979) analyzable periods of sinus rhythm or premature atrial or ventricular beats (Cohen's Kappa coefficient 0.92 ± 0.02 between Beat2Phone and Holter), and no pAF events. Beat2Phone ECG showed remarkable SUS scores in user evaluations (average score: 81.4 out of 100 on SUS). CONCLUSIONS: Beat2Phone device was easy to use among ESUS patients and in optimal conditions provided high-quality 1-lead ECG signal for diagnosing pAF. CLINICAL TRIAL REGISTRATION: The study was not registered, as it was a nonrandomized single-arm pilot study.

Carotid web leads to new thrombus formation: computational fluid dynamic analysis coupled with histological evidence.

Carotid web has been recognized as a rare cause of ischemic stroke with high recurrence rate. We describe a 48-year-old woman with carotid web who developed embolic stroke. We obtained a fresh thrombus from the internal carotid artery when carotid endarterectomy was performed. A preoperative computational fluid dynamics (CFD) study showed stagnation of blood around the web structure as well as the low wall shear stress. The rheological analysis newly disclosed mechanisms of thrombus formation related to the carotid web. CFD study in the carotid web may determine indication and timing of surgical interventions with further accumulation of clinical evidence.

Neuroinflammatory Mechanisms in Ischemic Stroke: Focus on Cardioembolic Stroke, Background, and Therapeutic Approaches.

One of the most important causes of neurological morbidity and mortality in the world is ischemic stroke. It can be a result of multiple events such as embolism with a cardiac origin, occlusion of small vessels in the brain, and atherosclerosis affecting the cerebral circulation. Increasing evidence shows the intricate function played by the immune system in the pathophysiological variations that take place after cerebral ischemic injury. Following the ischemic cerebral harm, we can observe consequent neuroinflammation that causes additional damage provoking the death of the cells; on the other hand, it also plays a beneficial role in stimulating remedial action. Immune mediators are the origin of signals with a proinflammatory position that can boost the cells in the brain and promote the penetration of numerous inflammatory cytotypes (various subtypes of T cells, monocytes/macrophages, neutrophils, and different inflammatory cells) within the area affected by ischemia; this process is responsible for further ischemic damage of the brain. This inflammatory process seems to involve both the cerebral tissue and the whole organism in cardioembolic stroke, the stroke subtype that is associated with more severe brain damage and a consequent worse outcome (more disability, higher mortality). In this review, the authors want to present an overview of the present learning of the mechanisms of inflammation that takes place in the cerebral tissue and the role of the immune system involved in ischemic stroke, focusing on cardioembolic stroke and its potential treatment strategies.

Statin treatment and outcomes after embolic stroke of undetermined source.

The association of low-density lipoprotein cholesterol lowering with outcomes in embolic stroke of undetermined source (ESUS) patients is unclear. In these patients we aimed to assess the effect of statin on stroke recurrence, major adverse cardiovascular events (MACE) and death rates. Consecutive ESUS patients in the Athens Stroke Registry were prospectively followed-up to 10 years for stroke recurrence, MACE, and death. The Nelson-Aalen estimator was used to estimate the cumulative probability by statin allocation at discharge and cox-regression analyses to investigate whether statin at discharge was a predictor of outcomes. Among 264 ESUS patients who were discharged and followed for 4 years, 89 (33.7%) were treated with statin at discharge. Patients who were discharged on statin had lower rates of stroke recurrence (3.58 vs. 7.23/100 patient-years, HR: 0.48; 95% CI 0.26-0.90), MACE (4.98 vs. 9.89/100 patient-years, HR: 0.49; 95% CI 0.29-0.85), and death (3.93 vs. 8.21/100 patient-years, HR: 0.50; 95% CI: 0.28-0.89). In the multivariate analysis, statin treatment at discharge was an independent predictor of stroke recurrence (adjusted HR: 0.48; 95% CI 0.26-0.91), MACE (adjusted HR: 0.48; 95% CI 0.28-0.82), and death (adjusted HR: 0.50; 95% CI 0.27-0.93). Patients with ESUS discharged on statins have lower rates of stroke recurrence, MACE, and death compared to those not receiving statin therapy.

Atrial Fibrillation After Ischemic Stroke Detected by Chest Strap-Style 7-Day Holter Monitoring and the Risk Predictors: EDUCATE-ESUS.

AIM: This study aimed to investigate the diagnostic yield of 7-day Holter monitoring for detecting covert atrial fibrillation (AF) in patients with recent embolic stroke of undetermined source (ESUS) and to identify the pre-entry screening biomarkers that had significant associations with later detection of AF (clinicaltrials.gov. NCT02801708). METHODS: A total of 206 patients who have recent ESUS without previously documented AF underwent Holter electrocardiography using a chest strap-style monitor. External validation of biomarkers predictive of AF was performed using 83 patients with ESUS who were implanted with insertable cardiac monitors. RESULTS: The 7-day Holter monitoring started at a median of 13 days after the onset of stroke. AF was detected in 14 patients, and three of these showed a single AF episode lasting ＜2 min. The median time delay to the first documented AF was 50 h. Each of serum brain natriuretic peptide ≥ 66.0 pg/mL (adjusted odds ratio 5.23), atrial premature contractions (APCs) ≥ 345 beats (3.80), and APC short runs ≥ 13 (5.74) on 24-h Holter prior to the 7-day Holter showed a significant association with detection of AF, independent of age and physiological findings in this derivation cohort, and all of these showed a significant association in the validation cohort (adjusted odds ratio 6.59, 7.87, and 6.16, respectively). CONCLUSIONS: In recent ESUS patients, the detection rate of AF using the 7-day Holter monitoring was 6.8% (95% CI 4.1%-11.1%). Brain natriuretic peptide, APC count, and APC short runs in the standard clinical workup seemed to be predictors of covert AF.

Ischemic Stroke.

This concise review of the epidemiology, pathophysiology, evaluation, acute management, and prevention of ischemic stroke targets internists, family practitioners, and emergency physicians who manage patient with stroke.

The Investigation of Left Atrial Structure and Stroke Etiology: The I-LASER Study.

Background Left atrial (LA) function is important in stroke, but often poorly characterized. We evaluated the association of 2-dimensional speckle tracking echocardiography LA variables with stroke subtype (cardioembolic stroke [CS] or cryptogenic stroke versus other). The hypothesis is worse LA active function is associated with CS, but not cryptogenic strokes. Methods and Results In this prospective cohort (2017-2019), left ventricular/LA structure and function were quantified by 2-dimensional and speckle tracking echocardiography in 151 patients with stroke. Strain/strain rate curves for the 3 components of the LA cycle, ie, (1) Reservoir (global longitudinal strain [Srmax]), (2) Conductive (early LA Sr [Sre]), and (3) Active (late LA strain [Sra]) were evaluated, masked to stroke subtype. Associations of cardiac features with stroke subtype were tested using multivariable logistic regressions. Odds of CS were increased in patients with a larger LA systolic diameter (odds ratio [OR], 2.96, 95% CI, 1.14-7.69) but reduced in patients with a higher Srmax (better reservoir) (OR, 0.80, 95% CI, 0.67-0.97). Lower Sra (worse function) was associated with an increased odds of CS (OR, 1.72, 95% CI, 1.07-2.76) but not independent of atrial fibrillation. Higher active LA emptying fraction (better active phase) was associated with reduced odds of CS (OR, 0.74, 95% CI, 0.57-0.95) or cryptogenic stroke (OR, 0.82, 95% CI, 0.68-0.98) versus other subtypes; other associations between cryptogenic stroke and speckle tracking echocardiography were not found. Conclusions Markers of LA structure and function were associated with CS. Similar associations were not found for cryptogenic stroke, which might suggest different underlying mechanisms, given study limitations. Further understanding could aid stroke diagnosis and secondary stroke prevention research.

Bovine Arch and Stroke Laterality.

Background Left-hemispheric strokes are more frequent and often have a worse outcome than their right-hemispheric counterparts. This study aimed to evaluate whether cardioembolic stroke laterality is affected by anatomical characteristics of the aortic arch. We hypothesized that laterality varies between patients with bovine versus standard arch. Methods and Results We retrospectively identified 1598 acute cardioembolic strokes in patients with atrial fibrillation from our institutional stroke database (2009-2017). Inclusion criteria were acute anterior circulation ischemic infarct and availability of both arch and brain imaging (magnetic resonance imaging or computed tomography). Alternative causes of stroke and anomalous arch were excluded. Imaging was reviewed for stroke characterization and laterality and arch branching pattern. Bovine arch denotes a common origin of the brachiocephalic trunk and left common carotid artery. Strokes were classified as bilateral (left or right). Univariate analysis was performed using chi-square tests. The final cohort comprised 615 patients, mean age 77 years (SD 11.8 years) with 376 women (61%) and 33% white, 30% black, and the remainder mixed/Hispanic. Standard arch (n=424) stroke distribution was left 43.6% (185), right 45.1% (191), and bilateral 11.3% (48). Bovine arch (n=191) stroke distribution was left 51.3% (98), right 35.6% (68), and bilateral 13.1% (25). Bovine arches were associated with more left-sided strokes compared with standard arches (P=0.018). There was an association between black race and bovine arch (P=0.0001). Conclusions Bovine aortic arch configuration is associated with left hemispheric laterality of cardioembolic stroke. This study enriches the understanding that arch anatomy influences stroke laterality and highlights the need for further research into the causative hemodynamic factors.

Left atrial cross-sectional area is a novel measure of atrial shape associated with cardioembolic strokes.

OBJECTIVE: Cardioembolic (CE) stroke carries significant morbidity and mortality. Left atrial (LA) size has been associated with CE risk. We hypothesised that differential LA remodelling impacts on pathophysiological mechanism of major CE strokes. METHODS: A cohort of consecutive patients hospitalised with ischaemic stroke, classified into CE versus non-CE strokes using the Causative Classification System for Ischaemic Stroke were enrolled. LA shape and remodelling was characterised by assessing differences in maximal LA cross-sectional area (LA-CSA) in a cohort of 40 prospectively recruited patients with ischaemic stroke using three-dimensional (3D) echocardiography. Flow velocity profiles were measured in spherical versus ellipsoidal in vitro models to determine if LA shape influences flow dynamics. Two-dimensional (2D) LA-CSA was subsequently derived from standard echocardiographic views and compared with 3D LA-CSA. RESULTS: A total of 1023 patients with ischaemic stroke were included, 230 (22.5%) of them were classified as major CE. The mean age was 68±16 years, and 464 (45%) were women. The 2D calculated LA-CSA correlated strongly with the LA-CSA measured by 3D in both end-systole and end-diastole. In vitro flow models showed shape-related differences in mid-level flow velocity profiles. Increased LA-CSA was associated with major CE stroke (adjusted relative risk 1.10, 95% CI 1.04 to 1.16; p<0.001), independent of age, gender, atrial fibrillation, left ventricular ejection fraction and CHA2DS2-VASc score. Specifically, the inclusion of LA-CSA in a model with traditional risk factors for CE stroke resulted in significant improvement in model performance with the net reclassification improvement of 0.346 (95% CI 0.189 to 0.501; p=0.00001) and the integrated discrimination improvement of 0.013 (95% CI 0.003 to 0.024; p=0.0119). CONCLUSIONS: LA-CSA is a marker of adverse LA shape associated with CE stroke, reflecting importance of differential LA remodelling, not simply LA size, in the mechanism of CE risk.

Intracardiac metastasis from head and neck squamous cell carcinoma.

Cardiac metastasis from head and neck cancer is an extremely rare and devastating condition with an abysmal prognosis. Most of our knowledge about this condition is from case reports and series. We present a case of squamous cell carcinoma of the tonsils that was complicated by embolic stroke and critical limb ischemia that were found to be secondary to intracardiac metastasis. We believe that this condition is under-reported; hence, we conducted a thorough review of the literature to highlight the characteristics and previous therapeutic experiences with various presentations of cardiac metastasis from head and neck carcinoma. Clinicians are encouraged to report their experience with evaluating and managing this type of metastasis.

Immune-Inflammatory, Metabolic, Oxidative, and Nitrosative Stress Biomarkers Predict Acute Ischemic Stroke and Short-Term Outcome.

Immune-inflammatory, metabolic, oxidative, and nitrosative stress (IMO&NS) pathways and, consequently, neurotoxicity are involved in acute ischemic stroke (IS). The simultaneous assessment of multiple IMO&NS biomarkers may be useful to predict IS and its prognosis. The aim of this study was to identify the IMO&NS biomarkers, which predict short-term IS outcome. The study included 176 IS patients and 176 healthy controls. Modified Rankin scale (mRS) was applied within 8 h after IS (baseline) and 3 months later (endpoint). Blood samples were obtained within 24 h after hospital admission. IS was associated with increased white blood cell (WBC) counts, high sensitivity C-reactive protein (hsCRP), interleukin (IL-6), lipid hydroperoxides (LOOHs), nitric oxide metabolites (NOx), homocysteine, ferritin, erythrocyte sedimentation rate (ESR), glucose, insulin, and lowered iron, 25-hydroxyvitamin D [25(OH)D], total cholesterol, and high-density lipoprotein (HDL) cholesterol. We found that 89.4% of the IS patients may be correctly classified using the cumulative effects of male sex, systolic blood pressure (SBP), glucose, NOx, LOOH, 25(OH)D, IL-6, and WBC with sensitivity of 86.2% and specificity of 93.0%. Moreover, increased baseline disability (mRS ≥ 3) was associated with increased ferritin, IL-6, hsCRP, WBC, ESR, and glucose. We found that 25.0% of the variance in the 3-month endpoint (mRS) was explained by the regression on glucose, ESR, age (all positively), and HDL-cholesterol, and 25(OH)D (both negatively). These results show that the cumulative effects of IMO&NS biomarkers are associated with IS and predict a poor outcome at 3-month follow-up.