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Objective: Clinical predictors of ischemic stroke in the setting of atrial fibrillation (AF) have been identified, but there is limited data on predictors in the context of abnormal flow originating from the left atrial appendage. We hypothesize that reduced LAA flow velocity is associated with cerebrovascular ischemic events in patients with AF. Methods: We investigated consecutive patients with AF evaluated for ablation. Peak flow velocities at the orifice of the left atrial appendage (LAA) were obtained by transeosphageal echocardiography (TEE) studies, and elevated velocities were defined as greater than 40 cm/sec, in line with prior studies. The primary outcome was defined as the presence of any of the following: history of stroke/transient ischemic event, or non-lacunar brain infarct on brain imaging performed before the TEE. Univariate and multivariable analyses were performed to determine the association between LAA peak flow and the primary outcome, adjusting for CHADS2Vasc score. Results: We identified 322 patients with TEE performed. The mean age was 62.1 years and 24.5% men. Patients with LAA-flow velocity < 40 cm/sec were more likely to have the primary outcome (10.7% vs 4.3%, p=0.023). This association persisted after adjusting for CHADS2VASc (OR, 2.62; 95% CI, 1.09-6.33, p = 0.032). Conclusion: Low velocity in the LAA is associated with cerebrovascular ischemic events in patients with AF. More studies are needed to deterine whether LAA flow velocity can help risk stratify “low risk” patients with AF.

Background and Purpose: While studies have stratified cardioembolic (CE) stroke risk by qualitative left atrial appendage (LAA) morphology and biomarkers of atrial dysfunction, the quantitative properties that underlie these observations are not well established. Accordingly, we hypothesized that LAA volume and contrast density (attenuation) on computerized tomography (CT) may capture the structural and hemodynamic processes that underlie CE stroke risk. Methods: Data were collected from a single center prospective ischemic stroke database over 18 months and included all patients with ischemic stroke who previously underwent routine, non-gated, contrast enhanced thin-slice (≤2.5 mm) chest CT. Stroke subtype was determined based on the inpatient diagnostic evaluation. LAA volume and attenuation were determined from CT studies performed for various clinically appropriate indications. Univariate and multivariable analyses were performed to determine factors associated with ischemic stroke subtype, including known risk factors and biomarkers, as well as LAA density and morphologic measures. Results: We identified 311 patients with a qualifying chest CT (119 CE subtype, 109 ESUS, and 83 non-CE). In unadjusted models, there was an association between CE (vs. non-CE) stroke subtype and LAA volume (OR per mL increase 1.15, 95% CI 1.07-1.24, pth quartile vs. 1 st quartile; OR 2.95, 95% CI 1.28-6.80, p=0.011), but not with ESUS (vs. non-CE) subtype. In adjusted models, only the association between LAA density and CE stroke subtype persisted (adjusted OR 3.71, 95% CI 1.37-10.08, p=0.010). Conclusion: The LAA volume and density values on chest CT are associated with CE stroke subtype but not ESUS subtype. Patients with ESUS and increased LAA volume or attenuation may be a subgroup where the mechanism is cardioembolic and anticoagulation can be tested for secondary stroke prevention.

Background and Purpose— Left atrial enlargement has been shown to be associated with ischemic stroke, but the association with embolic stroke mechanisms remains unknown. We aim to study the associations between left atrial volume index (LAVI) and embolic stroke subtypes and atrial fibrillation (AF) detection on cardiac event monitoring in patients with embolic stroke of unknown source. Methods— Data were collected from a prospective cohort of consecutive patients with ischemic stroke admitted to a comprehensive stroke center over 18 months. Stroke subtype was classified into cardioembolic stroke, noncardioembolic stroke of determined mechanism (NCE), or embolic stroke of undetermined source (ESUS). Univariate and prespecified multivariable analyses were performed to assess associations between LAVI and stroke subtype and AF detection in patients with ESUS. Results— Of 1224 consecutive patients identified during the study period, 1020 (82.6%) underwent transthoracic echocardiography and had LAVI measurements. LAVI was greater in patients with cardioembolic stroke than NCE (41.4 mL/m 2 ±18.0 versus 28.6 mL/m 2 ±12.2; P 2 ±12.6 versus 28.6 mL/m 2 ±12.2; P =0.61). In multivariable logistic regression models, LAVI was greater in cardioembolic stroke versus NCE (adjusted odds ratio per mL/m 2 , 1.07; 95% CI, 1.05–1.09; P 2 , 1.00; 95% CI, 0.99–1.02; P =0.720). Among 99 patients with ESUS who underwent cardiac monitoring, 18.2% had AF detected; LAVI was independently associated with AF detection in ESUS (adjusted odds ratio per mL/m 2 , 1.09; 95% CI, 1.02–1.15; P =0.007). Conclusions— LAVI is associated with cardioembolic stroke as well as AF detection in patients with ESUS, 2 subsets of ischemic stroke that benefit from anticoagulation therapy. Patients with increased LAVI may be a subgroup where anticoagulation may be tested for stroke prevention.

Background: The left atrial appendage (LAA) is the main source of thrombus in atrial fibrillation (AF); biomarkers of LAA dysfunction are associated with ischemic stroke (IS) risk in patients with AF. We hypothesized that high risk LAA features [High risk morphology (LAA-H), LAA volume (LAAV), and LAA orifice surface area (LAAOSA)] would be more prevalent among patients with cardioembolic (CE) stroke and embolic stroke of undetermined source (ESUS) than among those with non-cardioembolic stroke (NCS). Methods: Consecutive patients with IS from a prospective comprehensive stroke center registry who previously underwent a clinically-indicated qualifying chest CT were included. Patients underwent inpatient diagnostic evaluation for ischemic stroke, and stroke subtype was determined based on ESUS criteria. LAA morphology [Low risk morphology was defined as two lobes with an acute angle between them or chicken wing morphology and LAA-H defined as all others], LAAOSA (measured in a plane parallel to the left atrium), and LAAV (measured using a volumetric analysis software) were determined using contrast enhanced thin-slice chest CT (≤2.5 mm thickness) by investigators blinded to stroke subtype. Results: Of 1234 patients with ischemic stroke, 329 (26.7%) patients had a qualifying chest CT performed (126 CE, 116 ESUS, and 87 NCS). The baseline characteristics of patients with and without chest CT were similar. When compared to NCS, LAA-H was more prevalent in ESUS (86.4% vs. 70.1%, p=0.018) and CE stroke (82.5% vs. 70.1%, p=0.042). The LAAOSA and volume did not significantly differ between the 3 groups (Table). Conclusion: LAA characteristics associated with cardioembolic stroke are also more prevalent in patients with ESUS. Larger studies are needed to confirm that LAA features are a risk factor for stroke among patients without AF, and whether anticoagulation is effective in patients with high-risk LAA features.

Background and Purpose— The presence of white matter hyperintensities on brain MRI is common among elderly individuals. Previous research suggests that cardiovascular risk factors are associated with increased white matter hyperintensities. Examining the role of direct physiological measures of vascular function will help to clarify the vascular mechanisms related to white matter hyperintensities. The aim of the present study was to examine the association between endothelial-dependent and endothelial-independent vasodilatation and white matter hyperintensity volume. Methods— Twenty-five older adults with a range of cardiovascular diseases underwent brain MRI and completed assessments of blood vessel integrity using endothelial-dependent and independent flow-mediated dilation of the brachial artery. A semi-automated pixel-based method was used to quantify total brain volume and white matter hyperintensity volume, with white matter hyperintensity volume corrected for total brain volume. The association between measures of flow-mediated dilation and log-transformed white matter hyperintensities was examined. Results— Correlation analysis revealed that endothelial-dependent vasodilatation was significantly and inversely associated with white matter hyperintensity volume. In contrast, endothelial-independent vasodilatation was not associated with white matter hyperintensities. Neither endothelial-dependent nor endothelial-independent vasodilatation was associated with total brain volume. Conclusions— These data provide preliminary evidence that the integrity of the vascular endothelium is associated with white matter hyperintensities in older adults with cardiovascular disease. Impaired vascular function may be one mechanism that contributes to the development of white matter hyperintensities in the brain. Additional longitudinal research combining measures of vessel function, neuroimaging and cognition will be helpful in clarifying this potential mechanism.