Arterial Stiffness and Indices of Left Ventricular Diastolic Dysfunction in Patients with Embolic Stroke of Undetermined Etiology

Hindawi Disease Markers Volume 2019, Article ID 9636197, 10 pages https://doi.org/10.1155/2019/9636197 Research Article Arterial Stiffness and Indices of Left Ventricular Diastolic Dysfunction in Patients with Embolic Stroke of Undetermined Etiology Paulina Gąsiorek ,1 Agata Sakowicz ,2 Maciej Banach ,3,4 Stephan von Haehling,5,6 and Agata Bielecka-Dabrowa3,4 1 Department of Neurology and Ischemic Strokes, Medical University of Lodz, Zeromskiego 113, 90-549 Lodz, Poland Department of Medical Biotechnology, Medical University of Lodz, Poland 3 Department of Hypertension, Chair of Nephrology and Hypertension, Medical University of Lodz, Poland 4 Department of Cardiology and Congenital Diseases of Adults, Polish Mother’s Memorial Hospital Research Institute (PMMHRI), Rzgowska 281/289, 93-338 Lodz, Poland 5 Department of Cardiology and Pneumology, University of Göttingen Medical Center, Göttingen, Germany 6 German Center for Cardiovascular Research (DZHK), Partner Site Göttingen, Germany 2 Correspondence should be addressed to Paulina Gąsiorek; Received 15 April 2019; Revised 4 July 2019; Accepted 27 July 2019; Published 12 September 2019 Academic Editor: Alexandra Scholze Copyright © 2019 Paulina Gąsiorek et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. Purpose. The study is aimed at identifying echocardiographic and circulating biomarkers as well as hemodynamic indices of embolic stroke of undetermined etiology (ESUS) in patients aged <65. Methods. We prospectively investigated 520 patients with confirmed ischemic stroke and selected those 65 patients who were diagnosed with ESUS (age 54 (47-58) years, 42% male). An additional 36 without stroke but with a similar risk profile were included as a control group (age 53 (47-58) years, 61% male). All patients underwent echocardiography, noninvasive assessment of hemodynamic parameters using a SphygmoCor tonometer (AtCor Med., Australia), and measurements of selected biomarkers. Results. ESUS patients and controls were well matched for baseline characteristics including blood pressure and left ventricular ejection fraction (LVEF). Compared to controls, patients with ESUS had lower mean early diastolic (E ′ ) and systolic (S ′ ) mitral annular velocities and a higher ratio of the peak velocity of early diastolic transmitral flow to the peak velocity of early diastolic mitral annular motion (all p < 0 01). The peak velocity flow in the late diastole (A wave) value and LV mass indexed to the body surface area (LVMI) (g/m2) were higher in the ESUS group than in the control group (both p < 0 01). The isovolumetric relaxation time (IVRT) was longer and the mean left atrial volume index (LAVI) was higher in ESUS patients compared to the control group. Parameters of arterial stiffness such as augmentation pressure, augmentation index, and augmentation index adjusted to a heart rate of 75 bpm (AIx75) were higher in ESUS patients compared to controls (p < 0 05). Patients in the ESUS group had higher levels of asymmetric dimethylarginine, interleukin 6, and N-terminal probrain natriuretic peptide (NT-proBNP, all p < 0 05) than those in the control group. In multivariate analysis, the following factors were significantly associated with the presence of ESUS: AIx75 (odds ratio (OR) 1.095, 95% confidence interval (CI) 1.004-1.194; p = 0 04), IVRT (OR 1.045, 95% CI: 1.009-1.082; p = 0 014), LAVI (OR 1.3, 95% CI: 1.099-1.537; p = 0 002), and NT-proBNP (OR 1.003, 95% CI: 1.001-1.005; p = 0 005). Conclusions. Increased arterial stiffness and indices of diastolic dysfunction as well as a higher NT-proBNP level are significantly associated with ESUS. These parameters require further scrutiny over time to understand their impact on the development of symptomatic heart failure. The ClinicalTrials.gov identifier is NCT03377465. 2 1. Introduction More than one million inhabitants of Europe suffer from stroke yearly, and ischemic stroke accounts for approximately 80% of all cases. Despite the reduction in stroke mortality, the absolute number of people with stroke-related death has increased greatly in the past two decades [1, 2]. Identification of the etiology of stroke is necessary to prepare an adequate prevention strategy [3]. The term embolic stroke of undetermined etiology (ESUS) was introduced by the Cryptogenic Stroke (CS)/ESUS International Working Group in 2014 [4]. ESUS refers to a nonlacunar infarct, which means a subcortical infarct ≤ 1 5 cm on computed tomography or ≤2.0 cm on magnetic resonance imaging in the absence of the following: cardioembolic sources such as permanent or paroxysmal atrial fibrillation (AF) or atrial flutter, intracardiac thrombus or tumors, prosthetic cardiac valve, mitral stenosis, myocardial infarction within the past 4 weeks, left ventricular ejection fraction < 30%, valvular vegetations, or infective endocarditis as well as extracranial or intracranial atherosclerosis causing >50% luminal stenosis in the artery supplying the ischemic region and other specific causes of stroke (e.g., dissection, arteritis, migraine/vasospasm, and drug misuse) [4, 5]. Approximately one-fourth of all strokes are ESUS. Identification of the prognostic factors is necessary in order to optimize the preventive strategy [6]. The presence of ESUS strokes indicates that the conventional risk factors cannot fully account for the pathogenesis of stroke. The characteristics and predictors of ESUS stroke in patients with heart failure without significant LVEF reduction and without AF are unknown [7]. A growing number of studies have demonstrated the association between parameters of arterial stiffness and stroke [8]. Endothelial dysfunction assessed by an increased level of asymmetric dimethylarginine (ADMA) may affect the inflammatory state in patients with ESUS [9]. It is very important to detect useful biomarkers of the risk of ESUS for appropriate intervention. The aim of this study was to identify echocardiographic and circulating biomarkers as well as hemodynamic indices of embolic stroke of undetermined etiology (ESUS) in patients aged <65. 2. Methods 2.1. Study Population. We prospectively investigated 520 patients with confirmed ischemic stroke hospitalized in the Department of Neurology and Ischemic Strokes, Medical University of Lodz [10]. We enrolled patients (males, females; age median 54 (interquartile range, IQR 47-58) years) with ESUS and 36 to the control group (median 53 age 47-58 years, 61% male) from the Department of Hypertension, Medical University of Lodz. All patients underwent neuroimaging examination, arterial ultrasound examination, electrocardiogram (ECG) monitoring, echocardiography, and noninvasive assessment of hemodynamic parameters using a SphygmoCor tonometer [9, 11]. Other measurements obtained included the levels of selected biochemical biomarkers (...truncated)