Atrial cardiopathy in patients with embolic strokes of unknown source and other stroke etiologies

Jalini, Shirin; Rajalingam, Rajasumi; Nisenbaum, Rosane; Javier, Angelo Dave; Woo, Anna; Pikula, Aleksandra

doi:10.1212/wnl.0000000000006748

Cited by 57 publications

(45 citation statements)

References 31 publications

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“…These prior studies did not use the ESUS definition, which ensures uniform evaluation of potential etiologies, and did not include continuous heart‐rhythm monitoring to rule out underlying AF, which may be involved in the relationship between left atrial size and stroke. A recent study found no significant difference in left atrial enlargement in ESUS patients versus non‐cardioembolic stroke patients, but this study was likely underpowered based on its reported confidence intervals . In this context, our study provides novel information about the relationship between left atrial size and ischemic stroke risk, suggesting that left atrial structural derangements may play a pathogenic role in strokes that are currently labeled as being of undetermined source.…”

Section: Discussionmentioning

confidence: 75%

“…Several markers of abnormal atrial anatomy and function have been associated with ischemic stroke independently of AF . Left atrial volume is a core feature of atrial cardiopathy but the relationship between left atrial volume and ESUS remains unclear given conflicting results from prior studies . If atrial cardiopathy is an under‐recognized risk factor for ESUS, it should be more prevalent among ESUS cases than strokes of known non‐cardioembolic etiology.…”

Section: Introductionmentioning

confidence: 99%

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Relationship between left atrial volume and ischemic stroke subtype

Kamel

Okin

Merkler

et al. 2019

Ann Clin Transl Neurol

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Objective Atrial cardiopathy without atrial fibrillation (AF) may be a potential cardiac source of embolic strokes of undetermined source (ESUS). Atrial volume is a feature of atrial cardiopathy, but the relationship between atrial volume and ESUS remains unclear. Methods We compared left atrial volume among ischemic stroke subtypes in the Cornell Acute Stroke Academic Registry (CAESAR), which includes all patients with acute ischemic stroke at our hospital since 2011. Stroke subtype was determined by neurologists per the TOAST classification and consensus ESUS definition. Left atrial volume index (LAVI) was obtained directly from our echocardiography image system (Xcelera, Philips Healthcare). We used t‐tests and analysis of variance for unadjusted comparisons and targeted minimum loss‐based estimation for comparisons adjusted for demographics and comorbidities. Results Among 2116 patients in CAESAR from 2011 to 2016, 1293 had LAVI measurements. LAVI varied across subtypes (P < 0.001) from 48.8 (±30.0) mL/m2 in cardioembolic strokes to 30.3 (±10.5) mL/m2 in small‐vessel strokes. LAVI was larger in ESUS (33.3 ± 13.6 mL/m2) than in small‐ or large‐vessel stroke (30.9 ± 10.7 mL/m2) (P = 0.01). The association between LAVI and ESUS persisted after the adjustment for demographics and comorbidities: a 10 mL/m2 increase in LAVI was associated with a 4.4% increase in ESUS probability (95% CI, 2.3%–6.4%). Results were similar after excluding patients with AF during post‐discharge heart‐rhythm monitoring. Interpretation We found larger left atria among patients with ESUS versus non‐cardioembolic stroke. There was significant overlap in left atrial size between ESUS and non‐cardioembolic stroke, highlighting that many ESUS cases are not cardioembolic.

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Section: Discussionmentioning

confidence: 75%

Section: Introductionmentioning

confidence: 99%

Relationship between left atrial volume and ischemic stroke subtype

Kamel

Okin

Merkler

et al. 2019

Ann Clin Transl Neurol

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“…Diverse current publications point to the notion that at least a proportion of ESUS patients display similarities with patients with cardioembolism, e.g., in regard to risk for stroke recurrence or thrombus histology [22,40,41]. Hypothetically, a part of ESUS may be due to embolism based on atrial cardiopathy even beyond AF, which may basically be interpreted as a symptom at the end stage of this pathology [42,43]. Thus, further research to elucidate the mechanisms behind ESUS and its linkage to atrial cardiopathy is highly warranted.…”

Section: Discussionmentioning

confidence: 99%

Plasma Dimethylarginine Levels and Carotid Intima–Media Thickness are related to Atrial Fibrillation in Patients with Embolic Stroke

Große

Biber

Sieweke

et al. 2019

IJMS

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A relevant part of embolic strokes of undetermined source (ESUS) is assumed to be due to non-detected atrial fibrillation (AF). In this study, we aimed to investigate if markers of endothelial dysfunction and damage may indicate AF risk in embolic stroke. Eighty-eight patients with ischemic stroke confirmed by imaging were assigned to one of three groups: ESUS, AF, or micro-/macroangiopathy. ESUS patients underwent prolonged Holter electrocardiography scheduled for three days. The National Institutes of Health Stroke Scale (NIHSS), the CHA2DS2VASC score, and the carotid intima–media thickness (CIMT) were obtained. Markers of endothelial (dys)function (L-arginine, asymmetric dimethylarginine (ADMA), symmetric dimethylarginine (SDMA)) were measured at day seven after stroke. ESUS patients were younger and had fewer cardiovascular risk factors than patients with determined stroke etiology. Compared with AF patients, ESUS patients showed significantly lower values of SDMA (p = 0.004) and higher values of L-arginine (p = 0.031), L-arginine/ADMA ratio (p = 0.006), L-arginine/SDMA ratio (p = 0.002), and ADMA/SDMA ratio (p = 0.013). Concordant differences could be observed comparing ESUS patients with those with newly diagnosed AF (p = 0.026; p = 0.03; p = 0.009; p = 0.004; and p = 0.046, respectively). CIMT was significantly larger in AF than in ESUS patients (p < 0.001), and was identified as an AF risk factor independent from CHA2DS2VASC in the regression analysis (p = 0.014). These findings may support future stratification for AF risk in patients who have suffered embolic stroke.

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“…In support of this mechanism, a recent study demonstrated that the prevalence of atrial cardiopathy, as assessed by ECG markers and LA dilation, was higher in ESUS patients compared with noncardioembolic stroke patients (26.6% in ESUS vs. 12.1% in LAA vs. 16.9% in SVD). 38 Certain limitations of the present report need to be acknowledged. First, the case-control design does not allow us to confirm causative associations between the measured markers.…”

Section: Arterial Stiffness and Left Atrial Function In Esusmentioning

confidence: 82%

Impaired Arterial Elastic Properties and Endothelial Glycocalyx in Patients with Embolic Stroke of Undetermined Source

et al. 2019

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Background and Purpose Cardioembolism is a postulated mechanism of embolic stroke of undetermined source (ESUS). We investigated endothelial glycocalyx, aortic elastic properties, oxidative stress, and their association with left atrial (LA) function in ESUS and healthy individuals. Methods In 90 ESUS patients (age 50.4 ± 13.2) and 90 controls with similar risk factors, we measured: (1) perfused boundary region (PBR) of the sublingual arterial microvessels (range 5–25 µm), a marker inversely related with glycocalyx thickness, (2) pulse wave velocity (PWV), central systolic blood pressure (cSBP), and augmentation index (AIx), (3) LA volume and strain using speckle-tracking imaging, and (4) malondialdehyde (MDA) and protein carbonyls (PCs), as oxidative stress markers. Results Compared with controls, ESUS had higher PWV, PBR, MDA, and PC levels as well as higher LA volume and reduced reservoir LA strain (p < 0.05). PBR > 1.2 μm of microvessel ranging from 5 to 9 μm and PWV > 10.2 m/s were associated with ESUS on multivariable analysis (odds ratio: 2.374 and 5.429, p < 0.05, respectively) and increased the c-statistic of the initial model from 0.54 to 0.71. In ESUS, glycocalyx damage (increased PBR) was related with increased PWV (p < 0.01) which was linked with LA reservoir strain after controlling for age, sex, and risk factors (p = 0.03). Increased MDA and PC were related with glycocalyx damage, increased PWV (r = 0.67 and r = 0.52), AIx, cSBP, and aortic atheroma (p < 0.01). Conclusion Arterial function and endothelial glycocalyx are severely impaired in ESUS and are linked to LA dysfunction suggesting their contribution to ESUS pathogenesis. Clinical Trial Registration URL-http://www.clinicaltrials.gov. Unique identifier: NCT03609437.

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Atrial cardiopathy in patients with embolic strokes of unknown source and other stroke etiologies

Cited by 57 publications

References 31 publications

Relationship between left atrial volume and ischemic stroke subtype

Relationship between left atrial volume and ischemic stroke subtype

Plasma Dimethylarginine Levels and Carotid Intima–Media Thickness are related to Atrial Fibrillation in Patients with Embolic Stroke

Impaired Arterial Elastic Properties and Endothelial Glycocalyx in Patients with Embolic Stroke of Undetermined Source

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