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

Abstract

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.

Tocilizumab improves oxidative stress and endothelial glycocalyx: A mechanism that may explain the effects of biological treatment on COVID-19

“…Glycocalyx damage may be an early manifestation of endothelial dysfunction in atherosclerosis, such that measuring glycocalyx thickness in these patients may help to stratify their future cardiovascular risk. The assessment of glycocalyx thickness using SDF imaging lasts 3 min, provides recording and automated analysis of >3000 microvessel segments of sublingual microcirculation and has satisfactory reproducibility ( Ikonomidis et al, 2019c ). Hence, this technique was proposed as a valid method to assess endothelial function by the European Society of Cardiology Working Group on Peripheral Circulation ( Lekakis et al, 2011 ).…”

“…In all patients we measured global LV longitudinal systolic strain (GLS-%) and peak diastolic strain rate (GLSR E-1/s) from standard two-dimensional (2D) echocardiography images obtained with a frame rate of 70–80/s, from the apical 4, 2, and 3 chamber views using 17 LV segment model and utilizing a dedicated software (EchoPac PC 203, GE Healthcare, Horten, Norway), as previously published ( Ikonomidis et al, 2019c , 2015 ). The normal value for GLS is considered to be −22.5 ± 2.7% ( Sugimoto et al, 2017 ; Ikonomidis et al, 2014 ).…”

Implantable Cardiac Monitoring in the Secondary Prevention of Cryptogenic Stroke

“…Cryptogenic stroke was defined using the Trial of Org 10172 in Acute Stroke Treatment (TOAST) criteria, 8 and after excluding patients with incomplete evaluation, as previously described. [9][10][11][12][13] All patients underwent investigations with transthoracic and transesophageal echocardiogram where indicated. [9][10][11][12][13] The presence of left atrial enlargement was diagnosed according to the guidelines of the American Society of Echocardiography.…”

“…[9][10][11][12][13] All patients underwent investigations with transthoracic and transesophageal echocardiogram where indicated. [9][10][11][12][13] The presence of left atrial enlargement was diagnosed according to the guidelines of the American Society of Echocardiography. 14 All patients received neuroimaging with brain computed tomography (CT) and / or magnetic resonance imaging (MRI) and vascular imaging with the modality left at the discretion of the treating physician (cervical duplex ultrasound, transcranial Doppler, CT angiography and / or magnetic resonance [MR] angiography).…”

“…[9][10][11][12][13] Stroke severity on admission was assessed with the use of the National Institute of Health Stroke Scale (NIHSS) score by certified neurologists. [9][10][11][12][13] Strategies of Heart Rhythm Monitoring All patients recruited during the 8-year period underwent 24-hour Holter echocardiogram (ECG; H12+ digital Holter recorder; Mortara Instrument) during hospitalization as standard of care. In the years 2013 to 2017 patients with a negative 24-hour Holter-ECG investigation during their hospitalization were followed in our outpatient clinic with repeat 24-hour Holter-ECGs at the discretion of treating stroke physicians.…”