Predictive Indicators in Peripheral Blood and Left Atrium Blood for Left Atrial Spontaneous Echo Contrast in Atrial Fibrillation Patients

Predictive Indicators in Peripheral Blood and Left Atrium Blood for Left Atrial Spontaneous Echo Contrast in Atrial Fibrillation Patients | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Advisory Board Help Center Sign In Submit a Preprint Cite Share Download PDF Research Article Predictive Indicators in Peripheral Blood and Left Atrium Blood for Left Atrial Spontaneous Echo Contrast in Atrial Fibrillation Patients Bing Ding, Jing Zhou, Yunlang Dai, Linyan He, Cao Zou This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-3865469/v1 This work is licensed under a CC BY 4.0 License Status: Published Journal Publication published 11 Sep, 2024 Read the published version in BMC Cardiovascular Disorders → Version 1 posted 16 You are reading this latest preprint version Abstract Objectives: The purpose of this study was to demonstrate the discriminating predictive indicators in peripheral blood and left atrium blood for predicting the risk of left atrial spontaneous echo contrast (LASEC) in atrial fibrillation patients underwent catheter ablation. Methods: A total of 108 consecutive AF patients treated with radiofrequency ablation between July 2022 and July 2023 were enrolled and divided into two groups based on preprocedural transesophageal echocardiography: the non LASEC group (n=71) and the LASEC group (n=37). Circulating platelet and endothelial- derived MPs (PMPs and EMPs) in peripheral blood and left atrial blood were detected. Plasma soluble P-selectin (sP-selectin) and von Willebrand factor (vWF) were observed. Diagnostic efficiency was measured using receiver operating characteristic (ROC) curve. Results: Peripheral sP-selectin, vWF and EMPs expressions elevated in all subjects when compared to those in left atrium blood. Levels of sP-selectin and vWF were significantly higher in peripheral blood of LASEC group than those of non LASEC group ( p=0.0018, p=0.0271 ). Significant accumulations of peripheral PMPs and EMPs were documented in LASEC group by comparison with non LASEC group ( p=0.0395, p=0.018 ). The area under curve(AUC) of combined PMPs and sP-selectin in predicting LASEC was 0.769 (95%CI: 0.678–0.845, sensitivity: 86.49%, specificity: 59.15%)，significantly larger than PMPs or sP-selectin alone. Conclusions: Expressionsof PMPs, sP-selectin, EMPs and vWF Increased in NVAF patients with LASEC and that might be potential biomarkers for LASEC prediction. Atrial fibrillation spontaneous echo contrast platelet derived microparticles endothelial derived microparticles P-selectin Figures Figure 1 Introduction Atrial fibrillation is the most common arrhythmia, occurring in 1–2% of the world's population [ 1 ] . Among them, non-valvular atrial fibrillation is the most common persistent arrhythmia. Radiofrequency ablation (RFCA), is an effective first-line treatment of paroxysmal atrial fibrillation. Although previous study proved RFCA can be operated safely in patients with left atrial sludge [ 2 ] , RFCA is a contraindication in patients have thrombosis in left atrial appendage (LAA) generally. As reported, AF increases the prevalence of ischemic strokes especially in the elderly [ 3 ] . CHA2DS2-VASc score was a commonly used scheme to evaluate the stroke risk. However, stroke still happens in the patients with low stroke risk (CHA2DS2-VASc score 0 or 1). Recent studies have reflected LASEC could be a surrogate indicator of stroke. According to meta-analysis data, about 10% of patients with NVAF developed left atrial thrombosis [ 4 ] . Esophageal echocardiography (TEE) can identify left atrial autography and thrombus, but TEE examinations are contraindicated in some patients that can not tolerate TEE procedure or that have esophageal lesions. Soluble P-selectin (platelet activation marker) and von Willebrand factor (vWF, endothelial activation marker) were reported to reflect the hemostatic environment. During cell activation, vascular damage, inflammation and apoptosis, a large number of vesicles or MPs (size 0.1-1 µm diameter) can form and shed from the surface of platelets, lymphocyte, monocyte, and vascular cells. Increasing studies have concentrated on the involvement of microparticles (MPs) in cardiocerebrovascular diseases [ 5 ] . Procoagulant MPs, mainly EMPs and PMPs, have been observed in various coagulative diseases, including venous thromboembolism, ischemic stroke, preeclampsia and atrial fibrillation [ 6 , 7 ] . Moreover, phosphatidylserine contained microparticles provide the activated membrane surface to facilitate enzymatic reactions necessary for hemostasis. LASEC presence indicated the LA thrombus, with a rate of stroke or other systemic embolic event reaching 9.5% every year [ 8 , 9 ] . An accurate model to predict LASEC becomes desirable due to the lacking of the studies on this issue. In this study, we aimed to identify the predicting role of PMPs, EMPs, s-P-selectin and vWF on LASEC detection in both peripheral blood and left atrial blood in patients with AF. Materials and Methods Study population We randomly enrolled 108 patients diagnosed with non-valvular atrial fibrillation (56 with paroxysmal AF, 52 with persistent AF) from July 2022 to July 2023 in the First Affiliated Hospital of Soochow University. All clinical, echocardiographic, laboratory data, CHA2DS2-VASc score and baseline characteristics were collected. The Ethics Committee of the First Affiliated Hospital of Soochow University approved the study. Written informed consent for the procedure was obtained from all patients. The inclusion criteria were as follows: aged > 18 years old; non-valvular AF; candidates for radiofrequency ablation. Type of AF was confirmed according to the European Society of Cardiology (ESC) guideline previously [ 10 ] .The exclusion criteria were valvular heart disease, hyperthyroidism, acute coronary syndrome, Liver and kidney dysfunction. Transesophageal echocardiography (TEE) examination All the patients underwent TEE examinations prior to RFCA. Ultrasound scanners (GE, Vivid E95, Horten, Norway) equipped with a 1.5–4.6 MHz transducer and a 3–8 MHz multiplane phase probe were used. TEE was performed within 24 h before the operation by two or three experienced echocardiographers. Left atrium and/or left atrium appendage (LAA) thrombus were detected in these patients. Flow velocity in the left atrial appendage was evaluated using pulsed wave Doppler interrogation on TEE in the view at 0 and 90 degrees. LASEC was defined as dynamic “smoke-like” echoes featured by a swirling motion and observed during the cardiac cycle using an optimal gain setting [ 11 ] . Blood sampling Peripheral femoral blood samples (4mL) were drawn in the morning before RFCA procedure. Left atrium blood samples were drawn through the atrial septal sheath during the RFCA procedure. Whole blood was anticoagulated with acid-citrate-dextrose (ACD,1/7 volume). The samples were gently inverted to ensure complete mixing with anticoagulants and performed flow cytometry assay within 2 hours. The serum was stored at -80 ℃ for further use. Platelet-rich plasma (PRP) was obtained by 200 g centrifugation for 10 minutes at room temperature. Preparation of plasma with MPs MPs were separated from whole blood by differential centrifugation. Whole blood was centrifuged at 11,000g for 2 minutes at 4 ℃ to obtain platelet-poor plasma (PPP). The PPP was then centrifuged at 13,000g for 45 minutes at 4 ℃ to isolate MPs. The isolated circulating MPs was resuspended in modified Tyrode buffer (0.4 mmol/L NaH2PO4, 5 mmol/L HEPES, 0.1% glucose and 0.35% bovine serum albumin, pH7.2) for Flow cytometry assay. The MPs was incubated with FITC-labeled AnnexinⅤ (Cat:640945, Biolegend, USA), PE-labeled anti-human CD41 (Cat:303706, Biolegend, USA) and Percp-labeled anti-human CD31 (Cat:FAB3567C, R&D Systems ,USA) or isotype as control for 45 minutes at room temperature. The PMPs were characterized as AnnexinⅤ+ CD41+/CD31- while the EMPS was defined as CD41-/CD31+. Gating strategy was set by forward (FSC) and side scatter (SSC). Labeled microparticle samples were assessed at a rate less than 10,000 events. The numberS of MPs were calculated by known concentration of 5µm and 10 µm size microbeads (Hugo,China) as previous [ 12 ] . The results were expressed as the number of MP/µl of plasma. Flow cytometry assay Activation status of platelets was measured by flow cytometry. PRP was stained with phycoerythrin (PE) anti-human CD41 (Cat:A07781, Beckman Coulter, USA) and platelet activation marker FITC-labeled anti-human CD62P (Cat:304904, BioLegend, San Diego, CA, USA) for 45 minutes at room temperature. Enzyme-linked immunosorbent assay (ELISA) ELISA detection of vWF and sP-selectin was assessed using anti-human Von Willebrand Factor ELISA and sP-selectin ELISA Kit (Cat: ELH-vWF-1; ELH-PSeletin-1, Raybiotech, USA). All experiments were conducted in duplicate. Quantification of concentration was obtained by the optical density (OD) value of 450 nm in MULTISKAN FC microplate reader (Thermo, MA, USA). Statistical analyses All continuous data are expressed as mean ± standard deviation or median (P 25 ,P 75 ). Categorical data are presented as counts and percentages. Values were analyzed by STATA 15.0 and MedCalc software. A t-test was conducted to compare variables that followed a normal distribution, while the Wilcoxon test was employed for variables with a biased distribution. Chi-square tests or Fisher exact Chi-square tests were used to assess the ratio across groups. Receiver operating characteristic (ROC) curve analysis was conducted in order to ascertain the optimal threshold, sensitivity, and specificity of the variables. The assessment of the cut-off value was carried out utilizing the Youden index. The Z-test was utilized to conduct the comparison of AUC.DeLong’s test was conducted to analyze the diagnostic value. Values of p < 0.05 were considered statistically significant. Results Baseline Characteristics Demographic details of subjects was depicted in Table 1 . The study population was comprised of 108 AF patients (paroxysmal, n = 56 [51.9%]; persistent, n = 52 [48.1%]). Most of the patients were at the high stroke risk (n = 74 [68.5%]). Twelve patients had a low risk of stroke (n = 14 [11.1%]). For all the patients, platelet counts (non LASEC group: [184.7 ± 51.8]×10 9 /µl, LASEC group: [183.9 ± 67.3]×10 9 /µl) were within the normal range. There were no difference in age, BMI, smoking, hypertension, diabetes mellitus, coronary artery disease, cerebral infarction, Hs-CRP, D-dimer, LVDD and LVSD between two groups. More patients in the non LASEC group were receiving β-blocker, cordarone and ACEI/ARB/ARNI ( p = 0.023, p = 0.033, p = 0.006 ). Significant differences were found in patient characteristics including gender, History of heart failure, NT-proBNP, left atrial size and ejection fraction (p = 0.007, p = 0.030, p = 0.000,p = 0.003, p = 0.0002). Table 1 Baseline Characteristics in patients with AF Variable non LASEC group (n = 71) LASEC group (n = 37) p Value Male [n(%)] 46 (64.8) 14 (37.8) 0.007 Age (year) 67 (58–72) 69 (60–74) 0.119 BMI (kg/m 2 ) 25.10 (22.49–27.18) 25.18 (23.18–26.67) 0.793 Smoking 13 (18.3) 5 (13.5) 0.526 Hypertension 39 (54.9) 26 (70.3) 0.122 Diabetes mellitus 8 (11.3) 7 (18.9) 0.275 Coronary artery disease 9 (12.7) 2 (5.4) 0.236 Cerebral infarction 8 (11.3) 3 (8.1) 0.606 Heart failure 9 (12.7) 11 (29.7) 0.030 CHA2DS2-VASc 2.3 ± 1.7 3.0 ± 1.5 0.035 0 11 (15.5) 1 (2.7) 1 16 (22.5) 6 (16.2) ≥ 2 44 (62.0) 30 (81.1) AF type (n,%) 0.000 Paroxysmal 48 (67.6) 8 (21.6) Persistent 23 (32.4) 29 (78.4) Medications (n,%) Pradaxa 1 (1.4) 0 (0) Rivaroxaban 64 (90.1) 36 (97.3) Edoxaban 6 (8.45) 1 (2.7) β-blocker 26 (36.6) 22 (59.5) 0.023 Cordarone 41 (57.8) 29 (78.4) 0.033 Propafenone 9 (12.7) 5 (13.5) 0.902 Dronedarone 1(1.4) 1(2.7) 0.636 ACEI/ARB/ARNI 32 (45.1) 27 (73.0) 0.006 CCB 24 (33.8) 13 (35.1) 0.890 Laboratory parameters Platelets(10 9 /µl) 184.7 ± 51.8 183.9 ± 67.3 0.944 Hs-CRP(mg/L) 0.91 (0.56–2.93) 1.37 (0.58–4.45) 0.155 NT-proBNP(pg/mL) 206.2 (106.1-561.2) 1403 (591–2147) 0.000 D-dimer(mg/L) 0.17 (0.10–0.32) 0.25 (0.1–0.48) 0.185 Echocardiography Left atrial size (mm) 42.6 ± 5.4 45.9 ± 5.0 0.003 LVDD (mm) 49.3 ± 3.5 48.6 ± 4.8 0.404 LVSD (mm) 33 (31–35) 34 (32–37) 0.113 Ejection fraction (%) 60 (57–63) 55 (50–60) 0.0002 Values are presented as n (%), mean ± SD, or median (IQR). ARB: angiotensin Ⅱ receptor blocker; ARNI: Angiotensin receptor enkephalase inhibitors; ACEI: angiotensin-converting enzyme inhibitor; BMI: body mass index; CCB: calcium channel blocker; Hs-CRP; high sensitive C-reactive protein; LVDD: left ventricular end diastolic dimension; LVSD:Left Ventricular End Systolic Diameter. Levels of sP-selectin and vWF in femoral vein blood and left atrial blood As seen in Table 2 , when compared to non LASEC group, a significant increase of preintervention sP-selectin levels in femoral blood of LASEC group was observed ( p = 0.0018 ). Similarly, an elevated expression of preintervention vWF was found in femoral blood ( p = 0.0271 ). In patients with LASEC, levels of peripheral sP-selectin and vWF were higher than those in left atrial blood ( p = 0.0011, p = 0.0102). Nevertheless, there were no significant differences in levels of sP-selectin and vWF in left atrial blood between non LASEC group and LASEC group ( p = 0.5372, p = 0.1698 ). Table 2 Soluble P-selectin and vWF concentration in the study population Parameters non LASEC group (n = 71) LASEC group (n = 37) p Value Peripheral blood sP-selectin (ng/mL) 36.40 ± 10.83 44.08 ± 13.47 0.0018 vWF (µg/mL) 14.54 ± 6.49 17.45 ± 6.22 0.0271 Left atrial blood sP-selectin (ng/mL) 34.00 ± 11.34 35.36 ± 9.75 0.5372 vWF (µg/mL) 12.36 ± 5.92 14.04 ± 6.14 0.1698 Levels of circulating microparticles in femoral blood and left atrial blood Concentrations of MPs in peripheral femoral blood and left atrial blood were shown in Table 3 . When compared to non LASEC group, significant accumulations of PMPs and EMPs were found in peripheral femoral blood of LASEC group ( p = 0.0395, p = 0.018 ) while no significant differences in left atrial blood ( p = 0.5322, p = 0.8816 ). In patients with LASEC, concentrations of peripheral PMPs and EMPs were significantly higher than those in the left atrial blood ( p = 0.0364, p = 0.0278). The comparison of peripheral venous and left atrial blood parameters in all patients showed sP-selectin, vWF and EMPs levels in the peripheral blood were significantly higher than those in left atrial blood (Table 4 ). No regional difference of PMPs concentration was found in all patients ( p = 0.2649). Table 3 Numbers of PMPs and EMPs in the study population Parameters (×10 3 /µL) non LASEC group (n = 71) LASEC group (n = 37) p Value Peripheral blood PMPs 1.83 (0.51–8.98) 4.38 (1.20-14.99) 0.0395 EMPs 1.71 (0.76–4.73) 4.74 (1.49–12.65) 0.0180 Left atrial blood PMPs 2.01 (0.49–6.70) 1.25 (0.41–5.27) 0.5322 EMPs 1.22 (0.35–5.87) 1.01 (0.30–8.40) 0.8816 Table 4 Parameters between peripheral blood and left atrial blood Parameters Peripheral blood (n = 108) Left atrial blood (n = 108) p Value sP-selectin (ng/mL) 39.03 ± 12.29 34.46 ± 10.80 0.0041 vWF (µg/mL) 15534.78 ± 6522.63 12932.81 ± 6018.10 0.0026 PMPs (×10 3 /µL) 2.27 (0.59–9.86) 1.47 (0.46–6.49) 0.2649 EMPs (×10 3 /µL) 2.05 (0.80–8.25) 1.19 (0.35–5.96) 0.0120 ROC Curve Analysis After constructing the ROC curves for biomarkers, the results showed that area under curve of PMPs and sP-selectin was 0.621 (95%CI: 0.522–0.712, sensitivity: 48.65%,specificity: 71.83%) and 0.669 (95%CI: 0.572–0.757, sensitivity:59.46%, specificity: 74.65%), respectively. The AUC of EMPs was 0.639 (95%CI: 0.541–0.729, sensitivity: 64.86%, specificity: 66.20%). The AUC of vWF was 0.624 (95%CI: 0.526–0.716, sensitivity: 86.49%, specificity: 40.85%). Moreover, the AUC of combined PMPs and sP-selectin was 0.769 (95%CI: 0.678–0.845, sensitivity: 86.49%, specificity: 59.15%, Fig. 1 ), presenting the superior predictive value than PMPs or sP-selectin alone ( Z = 2.363, p = 0.0181; Z = 1.961, p = 0.0499). The AUC of combined EMPs and vWF was 0.672 (95%CI: 0.575–0.760, sensitivity: 37.84%, specificity: 90.14%). When the combination model of PMPs, sP-selectin, EMPs and vWF was used, the predictive value improved to an AUC of 0.767 (95%CI: 0.676–0.843, sensitivity: 83.78%, specificity: 61.97%). A combination of four markers showed a more useful screening test than combination of EMPs and vWF markers( Z = 2.000, p = 0.0455) but not combination of PMPs and sP-selectin ( Z = 0.194, p = 0.0863). Discussion Accumulating studies have documented the vital role of LASEC in predicting cardiovascular events [ 13 , 14 ] . In the present study, approximately 34.26% (37/108) of the NVAF patients had LASEC, which is in line with previous data [ 15 ] . To gain better understanding of discriminating predictive indicators in LASEC, changes of local vascular biomarkers in the left atrium and peripheral femoral blood were investigated. Our data showed elevated local and peripheral blood levels of sP-selectin and vWF in NVAF patients with LASEC, suggesting the endothelial dysfunction and abnormal platelet activation in patients had LASEC. Increased sP-selectin and vWF are linked with high risk of stroke and adverse outcomes. Also, this study found the levels of sP-selectin and vWF concerning the LASEC group in peripheral blood were higher than those in left atrial blood, which controverts with previous studies [ 16 , 17 ] . A possible explanation is that vascular dysfunction and platelet activation also occurred in other sites, and the mean CHA 2 DS 2 -VASc scores were 2.5 ± 1.6 in this study, which means most patients had higher thromboembolism risk than previous studies. In a pile of papers, it was demonstrated that thrombi were not rare in the right atrium [ 18 , 19 , 20 ] .Hence sP-selectin and vWF levels in peripheral vessels maybe more accurate and comprehensive, instead of those in left atrium blood. Platelet- and endothelial-derived microparticles are closely related to hemostasis and thrombosis [ 21 , 22 ] . Endothelial injury activates platelets and releases MPs which are abundant of micro-RNA and cytokines, resulting in activating relevant signaling and thrombosis formation. Sample collection, processing, MPs isolation and related technology was challenging as MPs are easily to degrade or elevate [ 23 , 24 ] . In this study, fresh whole blood samples were used and freezing was avoided to obtained precise quantification. Similarly, we found significantly enhanced peripheral PMPs and EMPs but not local PMPs and EMPs in LASEC group comparing non LASEC group. To examine the predictive role of peripheral serological indicator, we conducted the ROC analyses of sP-selectin, vWF, PMPs and EMPs. Despite the sP-selectin exclusively derives from platelets, it could be partially released on endothelial cells [ 25 , 26 ] . VWF is a multimeric glycoprotein synthesized and secreted by injured vascular endothelium [ 27 ] . At a cutoff value of 42.23 ng/mL, sP-selectin presented sensitivity of 59.46% and specificity of 74.65%. The cutoff of vWF was 11.64 µg/mL, with a sensitivity of 86.49% and specificity of 40.85%. There are limited studies on MPs numbers of NVAF patients during anticoagulation. Here we identified at a cutoff of 5.59×10 3 /µL, PMPs had sensitivity of 48.65% and specificity of 71.83%. And at a cutoff of 2.52×10 3 /µL, EMPs had sensitivity of 64.86% and specificity of 66.20%. We found the combination of four markers were prior to PMPs, sP-selectin, EMPs and vWF alone. Of course there are some limitations in our study. Firstly, the study was based on a single-center. More cases need to be enrolled to verify whether the severity of LASEC would influence the expressions of sP-selectin, vWF and microparticles. Secondly, atrial inflammation and irregular blood flow induced by AF may cause endothelial dysfunction, but the impaired endothelial function of AF patients would improve after catheter ablation regardless of the type of AF [ 28 ] . Further studies concerning the variations of biomarkers over time are still in need. To summarize, spontaneous echo contrast was commonly seen in left atrium of patients with non-valvular atrial fibrillation. Our data demonstrated the elevated expressions of sP-selectin, vWF, PMPs and EMPs in NVAF patients with LASEC. We provided useful indicators and related thresholds regarding the existence of LASEC in atrial fibrillation. Declarations Ethics approval and consent to participate This study involving experiments on humans and the use of human blood samples was conducted in accordance with ethical standards, and all experimental protocols were approved by the First Affiliated Hospital of Soochow University of Ethics Committee (Approval No: 277]. Informed consent was obtained from all human subjects involved in the study. The consent process was conducted in accordance with the First Affiliated Hospital of Soochow University of Ethics Committee. Each participant was provided with detailed information about the study objectives, procedures, potential risks, and benefits, and written consent was obtained before their participation. Consent for publication Not applicable, as our study does not involve the collection or publication of any revealing information about individual participants. Availability of data and materials Data is provided within the manuscript or supplementary information files Competing interests The authors declare that they have no competing interests. Funding This research was funded by the Jiangsu Provincial Key Medical Center and the Priority Academic Program Development of Jiangsu Higher Education Institutions (PAPD) under grant number (YXZXA2016002). Authors' contributions B.D. and J.Z. collected and analyzed data; L.Y.H. wrote the main manuscript text; L.Y.H. J.Z. and B.D. performed experiments; B.D. and Y.L.D. prepared figures and tables; C.Z. initiated and supervised the project, analyzed and interpreted results. All authors reviewed the manuscript. References Zimetbaum P.Atrial Fibrillation[J].Ann Intern Med,2017,166(5):ITC33-ITC48. Hajjiri M, Bernstein S, Saric M, et al . Atrial fibrillation ablation in patients with known sludge in the left atrial appendage [J]. J Interv Card Electrophysiol. 2014;40(2):147-151. 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Supplementary Files BaselineCharacteristicsinpatientswithAF.xlsx LevelsofcirculatingmicroparticlessPselectinandvWFinfemoralbloodandleftatrialblood.xlsx Cite Share Download PDF Status: Published Journal Publication published 11 Sep, 2024 Read the published version in BMC Cardiovascular Disorders → Version 1 posted Editorial decision: Revision requested 14 Aug, 2024 Reviews received at journal 07 Aug, 2024 Reviewers agreed at journal 06 Aug, 2024 Reviews received at journal 03 Aug, 2024 Reviews received at journal 01 Aug, 2024 Reviewers agreed at journal 01 Aug, 2024 Reviewers agreed at journal 29 Jul, 2024 Reviewers agreed at journal 06 Jul, 2024 Reviews received at journal 20 Jun, 2024 Reviewers agreed at journal 16 Jun, 2024 Reviewers agreed at journal 13 Jun, 2024 Reviewers invited by journal 15 May, 2024 Editor assigned by journal 15 May, 2024 Editor invited by journal 24 Jan, 2024 Submission checks completed at journal 24 Jan, 2024 First submitted to journal 15 Jan, 2024 You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. 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Also discoverable on Platform About Our Team In Review Editorial Policies Advisory Board Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {"props":{"pageProps":{"initialData":{"identity":"rs-3865469","acceptedTermsAndConditions":true,"allowDirectSubmit":false,"archivedVersions":[],"articleType":"Research Article","associatedPublications":[],"authors":[{"id":269663459,"identity":"6fc1cfd8-65ec-41d8-975c-140431e7b3c6","order_by":0,"name":"Bing Ding","email":"","orcid":"","institution":"The First Affiliated Hospital of Soochow University","correspondingAuthor":false,"prefix":"","firstName":"Bing","middleName":"","lastName":"Ding","suffix":""},{"id":269663460,"identity":"239ebabf-d21d-47ab-8d22-8d70162594e0","order_by":1,"name":"Jing Zhou","email":"","orcid":"","institution":"The First Affiliated Hospital of Soochow University","correspondingAuthor":false,"prefix":"","firstName":"Jing","middleName":"","lastName":"Zhou","suffix":""},{"id":269663461,"identity":"325f7fed-8171-4e1d-8b92-9675782b017d","order_by":2,"name":"Yunlang Dai","email":"","orcid":"","institution":"The First Affiliated Hospital of Soochow University","correspondingAuthor":false,"prefix":"","firstName":"Yunlang","middleName":"","lastName":"Dai","suffix":""},{"id":269663462,"identity":"46e20b62-4dd0-494e-b9b5-86483d699327","order_by":3,"name":"Linyan He","email":"","orcid":"","institution":"National Clinical Research Center for Hematologic Diseases, The First Affiliated Hospital of Soochow University","correspondingAuthor":false,"prefix":"","firstName":"Linyan","middleName":"","lastName":"He","suffix":""},{"id":269663463,"identity":"00ba9969-84ed-494f-b101-40a443860b29","order_by":4,"name":"Cao Zou","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAAAzUlEQVRIiWNgGAWjYDACHgYG5r9/bICsBCBmI1ILA29DGulaDpOgxZzn+MMPkjvO2xscT37A8KHsMAP/7Ab8Wix7G5IlDM/cTtxw5pkB44xzhxkk7hzAr8XgPMMxhgS22wkGNxIMmHnbDjMYSCQQ0sLYxnCA7Zy9wY30D8x/idJytpmNsbHtAOOGGzkGzIxEaTlzjFma4Uxy4swzbwoO9pxL55G4QVBL+sPPDBV29nzH0zc++FFmLcc/g4AWFHCAARJPo2AUjIJRMAooBQA1uUY1tuyvCwAAAABJRU5ErkJggg==","orcid":"","institution":"The First Affiliated Hospital of Soochow University","correspondingAuthor":true,"prefix":"","firstName":"Cao","middleName":"","lastName":"Zou","suffix":""}],"badges":[],"createdAt":"2024-01-15 05:14:12","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-3865469/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-3865469/v1","draftVersion":[],"editorialEvents":[{"content":"https://doi.org/10.1186/s12872-024-04162-w","type":"published","date":"2024-09-11T15:58:11+00:00"}],"editorialNote":"","failedWorkflow":false,"files":[{"id":50328073,"identity":"aa65938a-ffbe-4d0d-95e4-70f91cc21a5c","added_by":"auto","created_at":"2024-01-29 20:44:56","extension":"jpg","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":615378,"visible":true,"origin":"","legend":"\u003cp\u003eROC curves of predictive scores. \u003cstrong\u003eA\u003c/strong\u003e. ROC analysis of PMPs and sP-selectin in peripheral femoral blood for LASEC diagnosis. \u003cstrong\u003eB\u003c/strong\u003e. ROC analysis of four biomarkers in peripheral femoral blood for LASEC presence.\u003c/p\u003e","description":"","filename":"Figure1.jpg","url":"https://assets-eu.researchsquare.com/files/rs-3865469/v1/feadf11ae1e01e37bf3586d9.jpg"},{"id":64619295,"identity":"402fa514-6f45-4ac0-b73d-4d7d443da17f","added_by":"auto","created_at":"2024-09-16 16:13:52","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":1304458,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-3865469/v1/329faeb3-e2ff-4f97-afcc-3b4987c86856.pdf"},{"id":50328520,"identity":"cf3f5041-d4c2-47d8-ba73-bb62d941f1af","added_by":"auto","created_at":"2024-01-29 20:52:56","extension":"xlsx","order_by":7,"title":"","display":"","copyAsset":false,"role":"supplement","size":36742,"visible":true,"origin":"","legend":"","description":"","filename":"BaselineCharacteristicsinpatientswithAF.xlsx","url":"https://assets-eu.researchsquare.com/files/rs-3865469/v1/5be5b2ad9b782b48623212a0.xlsx"},{"id":50328074,"identity":"556bb6c4-a344-4b4a-b2e3-2844d78890b3","added_by":"auto","created_at":"2024-01-29 20:44:56","extension":"xlsx","order_by":8,"title":"","display":"","copyAsset":false,"role":"supplement","size":20192,"visible":true,"origin":"","legend":"","description":"","filename":"LevelsofcirculatingmicroparticlessPselectinandvWFinfemoralbloodandleftatrialblood.xlsx","url":"https://assets-eu.researchsquare.com/files/rs-3865469/v1/5708d011c58d10d41d1c4c20.xlsx"}],"financialInterests":"No competing interests reported.","formattedTitle":"Predictive Indicators in Peripheral Blood and Left Atrium Blood for Left Atrial Spontaneous Echo Contrast in Atrial Fibrillation Patients","fulltext":[{"header":"Introduction","content":"\u003cp\u003eAtrial fibrillation is the most common arrhythmia, occurring in 1\u0026ndash;2% of the world's population\u003csup\u003e[\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e]\u003c/sup\u003e. Among them, non-valvular atrial fibrillation is the most common persistent arrhythmia. Radiofrequency ablation (RFCA), is an effective first-line treatment of paroxysmal atrial fibrillation. Although previous study proved RFCA can be operated safely in patients with left atrial sludge\u003csup\u003e[\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e]\u003c/sup\u003e, RFCA is a contraindication in patients have thrombosis in left atrial appendage (LAA) generally. As reported, AF increases the prevalence of ischemic strokes especially in the elderly\u003csup\u003e[\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e]\u003c/sup\u003e. CHA2DS2-VASc score was a commonly used scheme to evaluate the stroke risk. However, stroke still happens in the patients with low stroke risk (CHA2DS2-VASc score 0 or 1). Recent studies have reflected LASEC could be a surrogate indicator of stroke. According to meta-analysis data, about 10% of patients with NVAF developed left atrial thrombosis\u003csup\u003e[\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e]\u003c/sup\u003e. Esophageal echocardiography (TEE) can identify left atrial autography and thrombus, but TEE examinations are contraindicated in some patients that can not tolerate TEE procedure or that have esophageal lesions.\u003c/p\u003e \u003cp\u003eSoluble P-selectin (platelet activation marker) and von Willebrand factor (vWF, endothelial activation marker) were reported to reflect the hemostatic environment. During cell activation, vascular damage, inflammation and apoptosis, a large number of vesicles or MPs (size 0.1-1 \u0026micro;m diameter) can form and shed from the surface of platelets, lymphocyte, monocyte, and vascular cells. Increasing studies have concentrated on the involvement of microparticles (MPs) in cardiocerebrovascular diseases\u003csup\u003e[\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e]\u003c/sup\u003e. Procoagulant MPs, mainly EMPs and PMPs, have been observed in various coagulative diseases, including venous thromboembolism, ischemic stroke, preeclampsia and atrial fibrillation\u003csup\u003e[\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e, \u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e]\u003c/sup\u003e. Moreover, phosphatidylserine contained microparticles provide the activated membrane surface to facilitate enzymatic reactions necessary for hemostasis.\u003c/p\u003e \u003cp\u003eLASEC presence indicated the LA thrombus, with a rate of stroke or other systemic embolic event reaching 9.5% every year\u003csup\u003e[\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e, \u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e]\u003c/sup\u003e. An accurate model to predict LASEC becomes desirable due to the lacking of the studies on this issue. In this study, we aimed to identify the predicting role of PMPs, EMPs, s-P-selectin and vWF on LASEC detection in both peripheral blood and left atrial blood in patients with AF.\u003c/p\u003e"},{"header":"Materials and Methods","content":"\u003cdiv id=\"Sec3\" class=\"Section2\"\u003e \u003ch2\u003eStudy population\u003c/h2\u003e \u003cp\u003eWe randomly enrolled 108 patients diagnosed with non-valvular atrial fibrillation (56 with paroxysmal AF, 52 with persistent AF) from July 2022 to July 2023 in the First Affiliated Hospital of Soochow University. All clinical, echocardiographic, laboratory data, CHA2DS2-VASc score and baseline characteristics were collected. The Ethics Committee of the First Affiliated Hospital of Soochow University approved the study. Written informed consent for the procedure was obtained from all patients. The inclusion criteria were as follows: aged\u0026thinsp;\u0026gt;\u0026thinsp;18 years old; non-valvular AF; candidates for radiofrequency ablation. Type of AF was confirmed according to the European Society of Cardiology (ESC) guideline previously\u003csup\u003e[\u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e]\u003c/sup\u003e.The exclusion criteria were valvular heart disease, hyperthyroidism, acute coronary syndrome, Liver and kidney dysfunction.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec4\" class=\"Section2\"\u003e \u003ch2\u003eTransesophageal echocardiography (TEE) examination\u003c/h2\u003e \u003cp\u003eAll the patients underwent TEE examinations prior to RFCA. Ultrasound scanners (GE, Vivid E95, Horten, Norway) equipped with a 1.5\u0026ndash;4.6 MHz transducer and a 3\u0026ndash;8 MHz multiplane phase probe were used. TEE was performed within 24 h before the operation by two or three experienced echocardiographers. Left atrium and/or left atrium appendage (LAA) thrombus were detected in these patients. Flow velocity in the left atrial appendage was evaluated using pulsed wave Doppler interrogation on TEE in the view at 0 and 90 degrees. LASEC was defined as dynamic \u0026ldquo;smoke-like\u0026rdquo; echoes featured by a swirling motion and observed during the cardiac cycle using an optimal gain setting\u003csup\u003e[\u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e]\u003c/sup\u003e.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec5\" class=\"Section2\"\u003e \u003ch2\u003eBlood sampling\u003c/h2\u003e \u003cp\u003ePeripheral femoral blood samples (4mL) were drawn in the morning before RFCA procedure. Left atrium blood samples were drawn through the atrial septal sheath during the RFCA procedure. Whole blood was anticoagulated with acid-citrate-dextrose (ACD,1/7 volume). The samples were gently inverted to ensure complete mixing with anticoagulants and performed flow cytometry assay within 2 hours. The serum was stored at -80 ℃ for further use. Platelet-rich plasma (PRP) was obtained by 200 g centrifugation for 10 minutes at room temperature.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec6\" class=\"Section2\"\u003e \u003ch2\u003ePreparation of plasma with MPs\u003c/h2\u003e \u003cp\u003eMPs were separated from whole blood by differential centrifugation. Whole blood was centrifuged at 11,000g for 2 minutes at 4 ℃ to obtain platelet-poor plasma (PPP). The PPP was then centrifuged at 13,000g for 45 minutes at 4 ℃ to isolate MPs. The isolated circulating MPs was resuspended in modified Tyrode buffer (0.4 mmol/L NaH2PO4, 5 mmol/L HEPES, 0.1% glucose and 0.35% bovine serum albumin, pH7.2) for Flow cytometry assay. The MPs was incubated with FITC-labeled AnnexinⅤ (Cat:640945, Biolegend, USA), PE-labeled anti-human CD41 (Cat:303706, Biolegend, USA) and Percp-labeled anti-human CD31 (Cat:FAB3567C, R\u0026amp;D Systems ,USA) or isotype as control for 45 minutes at room temperature. The PMPs were characterized as AnnexinⅤ+ CD41+/CD31- while the EMPS was defined as CD41-/CD31+. Gating strategy was set by forward (FSC) and side scatter (SSC). Labeled microparticle samples were assessed at a rate less than 10,000 events. The numberS of MPs were calculated by known concentration of 5\u0026micro;m and 10 \u0026micro;m size microbeads (Hugo,China) as previous\u003csup\u003e[\u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e]\u003c/sup\u003e. The results were expressed as the number of MP/\u0026micro;l of plasma.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec7\" class=\"Section2\"\u003e \u003ch2\u003eFlow cytometry assay\u003c/h2\u003e \u003cp\u003eActivation status of platelets was measured by flow cytometry. PRP was stained with phycoerythrin (PE) anti-human CD41 (Cat:A07781, Beckman Coulter, USA) and platelet activation marker FITC-labeled anti-human CD62P (Cat:304904, BioLegend, San Diego, CA, USA) for 45 minutes at room temperature.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec8\" class=\"Section2\"\u003e \u003ch2\u003eEnzyme-linked immunosorbent assay (ELISA)\u003c/h2\u003e \u003cp\u003eELISA detection of vWF and sP-selectin was assessed using anti-human Von Willebrand Factor ELISA and sP-selectin ELISA Kit (Cat: ELH-vWF-1; ELH-PSeletin-1, Raybiotech, USA). All experiments were conducted in duplicate. Quantification of concentration was obtained by the optical density (OD) value of 450 nm in MULTISKAN FC microplate reader (Thermo, MA, USA).\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec9\" class=\"Section2\"\u003e \u003ch2\u003eStatistical analyses\u003c/h2\u003e \u003cp\u003eAll continuous data are expressed as mean\u0026thinsp;\u0026plusmn;\u0026thinsp;standard deviation or median (P\u003csub\u003e25\u003c/sub\u003e,P\u003csub\u003e75\u003c/sub\u003e). Categorical data are presented as counts and percentages. Values were analyzed by STATA 15.0 and MedCalc software. A t-test was conducted to compare variables that followed a normal distribution, while the Wilcoxon test was employed for variables with a biased distribution. Chi-square tests or Fisher exact Chi-square tests were used to assess the ratio across groups. Receiver operating characteristic (ROC) curve analysis was conducted in order to ascertain the optimal threshold, sensitivity, and specificity of the variables. The assessment of the cut-off value was carried out utilizing the Youden index. The Z-test was utilized to conduct the comparison of AUC.DeLong\u0026rsquo;s test was conducted to analyze the diagnostic value. Values of p\u0026thinsp;\u0026lt;\u0026thinsp;0.05 were considered statistically significant.\u003c/p\u003e \u003c/div\u003e"},{"header":"Results","content":"\u003cdiv id=\"Sec11\" class=\"Section2\"\u003e \u003ch2\u003eBaseline Characteristics\u003c/h2\u003e \u003cp\u003eDemographic details of subjects was depicted in Table\u0026nbsp;\u003cspan refid=\"Tab1\" class=\"InternalRef\"\u003e1\u003c/span\u003e. The study population was comprised of 108 AF patients (paroxysmal, n\u0026thinsp;=\u0026thinsp;56 [51.9%]; persistent, n\u0026thinsp;=\u0026thinsp;52 [48.1%]). Most of the patients were at the high stroke risk (n\u0026thinsp;=\u0026thinsp;74 [68.5%]). Twelve patients had a low risk of stroke (n\u0026thinsp;=\u0026thinsp;14 [11.1%]). For all the patients, platelet counts (non LASEC group: [184.7\u0026thinsp;\u0026plusmn;\u0026thinsp;51.8]\u0026times;10\u003csup\u003e9\u003c/sup\u003e/\u0026micro;l, LASEC group: [183.9\u0026thinsp;\u0026plusmn;\u0026thinsp;67.3]\u0026times;10\u003csup\u003e9\u003c/sup\u003e/\u0026micro;l) were within the normal range. There were no difference in age, BMI, smoking, hypertension, diabetes mellitus, coronary artery disease, cerebral infarction, Hs-CRP, D-dimer, LVDD and LVSD between two groups. More patients in the non LASEC group were receiving β-blocker, cordarone and ACEI/ARB/ARNI (\u003cem\u003ep\u0026thinsp;=\u0026thinsp;0.023, p\u0026thinsp;=\u0026thinsp;0.033, p\u0026thinsp;=\u0026thinsp;0.006\u003c/em\u003e). Significant differences were found in patient characteristics including gender, History of heart failure, NT-proBNP, left atrial size and ejection fraction (p\u0026thinsp;=\u0026thinsp;0.007, p\u0026thinsp;=\u0026thinsp;0.030, p\u0026thinsp;=\u0026thinsp;0.000,p\u0026thinsp;=\u0026thinsp;0.003, p\u0026thinsp;=\u0026thinsp;0.0002).\u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab1\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 1\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eBaseline Characteristics in patients with AF\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"4\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e \u003cp\u003eVariable\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003enon LASEC group (n\u0026thinsp;=\u0026thinsp;71)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003eLASEC group (n\u0026thinsp;=\u0026thinsp;37)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c4\"\u003e \u003cp\u003e\u003cem\u003ep\u003c/em\u003e Value\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eMale [n(%)]\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e46 (64.8)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e14 (37.8)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e\u003cb\u003e0.007\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eAge (year)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e67 (58\u0026ndash;72)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e69 (60\u0026ndash;74)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.119\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eBMI (kg/m\u003csup\u003e2\u003c/sup\u003e)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e25.10 (22.49\u0026ndash;27.18)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e25.18 (23.18\u0026ndash;26.67)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.793\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eSmoking\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e13 (18.3)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e5 (13.5)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.526\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eHypertension\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e39 (54.9)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e26 (70.3)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.122\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eDiabetes mellitus\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e8 (11.3)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e7 (18.9)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.275\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eCoronary artery disease\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e9 (12.7)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e2 (5.4)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.236\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eCerebral infarction\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e8 (11.3)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e3 (8.1)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.606\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eHeart failure\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e9 (12.7)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e11 (29.7)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e\u003cb\u003e0.030\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eCHA2DS2-VASc\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e2.3\u0026thinsp;\u0026plusmn;\u0026thinsp;1.7\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e3.0\u0026thinsp;\u0026plusmn;\u0026thinsp;1.5\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e\u003cb\u003e0.035\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e11 (15.5)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e1 (2.7)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e16 (22.5)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e6 (16.2)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u0026ge;\u0026thinsp;2\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e44 (62.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e30 (81.1)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eAF type (n,%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e\u003cb\u003e0.000\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eParoxysmal\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e48 (67.6)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e8 (21.6)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePersistent\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e23 (32.4)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e29 (78.4)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eMedications (n,%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePradaxa\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e1 (1.4)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0 (0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eRivaroxaban\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e64 (90.1)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e36 (97.3)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eEdoxaban\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e6 (8.45)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e1 (2.7)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eβ-blocker\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e26 (36.6)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e22 (59.5)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e\u003cb\u003e0.023\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eCordarone\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e41 (57.8)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e29 (78.4)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e\u003cb\u003e0.033\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePropafenone\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e9 (12.7)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e5 (13.5)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.902\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eDronedarone\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e1(1.4)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e1(2.7)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.636\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eACEI/ARB/ARNI\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e32 (45.1)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e27 (73.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e\u003cb\u003e0.006\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eCCB\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e24 (33.8)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e13 (35.1)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.890\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eLaboratory parameters\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePlatelets(10\u003csup\u003e9\u003c/sup\u003e/\u0026micro;l)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e184.7\u0026thinsp;\u0026plusmn;\u0026thinsp;51.8\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e183.9\u0026thinsp;\u0026plusmn;\u0026thinsp;67.3\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.944\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eHs-CRP(mg/L)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e0.91 (0.56\u0026ndash;2.93)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e1.37 (0.58\u0026ndash;4.45)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.155\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eNT-proBNP(pg/mL)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e206.2 (106.1-561.2)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e1403 (591\u0026ndash;2147)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e\u003cb\u003e0.000\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eD-dimer(mg/L)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e0.17 (0.10\u0026ndash;0.32)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0.25 (0.1\u0026ndash;0.48)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.185\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eEchocardiography\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eLeft atrial size (mm)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e42.6\u0026thinsp;\u0026plusmn;\u0026thinsp;5.4\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e45.9\u0026thinsp;\u0026plusmn;\u0026thinsp;5.0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e\u003cb\u003e0.003\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eLVDD (mm)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e49.3\u0026thinsp;\u0026plusmn;\u0026thinsp;3.5\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e48.6\u0026thinsp;\u0026plusmn;\u0026thinsp;4.8\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.404\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eLVSD (mm)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e33 (31\u0026ndash;35)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e34 (32\u0026ndash;37)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.113\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eEjection fraction (%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e60 (57\u0026ndash;63)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e55 (50\u0026ndash;60)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e\u003cb\u003e0.0002\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003cp\u003eValues are presented as n (%), mean\u0026thinsp;\u0026plusmn;\u0026thinsp;SD, or median (IQR). ARB: angiotensin Ⅱ receptor blocker; ARNI: Angiotensin receptor enkephalase inhibitors; ACEI: angiotensin-converting enzyme inhibitor; BMI: body mass index; CCB: calcium channel blocker; Hs-CRP; high sensitive C-reactive protein; LVDD: left ventricular end diastolic dimension; LVSD:Left Ventricular End Systolic Diameter.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec12\" class=\"Section2\"\u003e \u003ch2\u003eLevels of sP-selectin and vWF in femoral vein blood and left atrial blood\u003c/h2\u003e \u003cp\u003eAs seen in Table\u0026nbsp;\u003cspan refid=\"Tab2\" class=\"InternalRef\"\u003e2\u003c/span\u003e, when compared to non LASEC group, a significant increase of preintervention sP-selectin levels in femoral blood of LASEC group was observed (\u003cem\u003ep\u0026thinsp;=\u0026thinsp;0.0018\u003c/em\u003e). Similarly, an elevated expression of preintervention vWF was found in femoral blood (\u003cem\u003ep\u0026thinsp;=\u0026thinsp;0.0271\u003c/em\u003e). In patients with LASEC, levels of peripheral sP-selectin and vWF were higher than those in left atrial blood (\u003cem\u003ep\u0026thinsp;=\u003c/em\u003e\u0026thinsp;0.0011, \u003cem\u003ep\u0026thinsp;=\u003c/em\u003e\u0026thinsp;0.0102). Nevertheless, there were no significant differences in levels of sP-selectin and vWF in left atrial blood between non LASEC group and LASEC group (\u003cem\u003ep\u0026thinsp;=\u0026thinsp;0.5372, p\u0026thinsp;=\u0026thinsp;0.1698\u003c/em\u003e).\u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab2\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 2\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eSoluble P-selectin and vWF concentration in the study population\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"4\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\"\u0026plusmn;\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\"\u0026plusmn;\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e \u003cp\u003eParameters\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003enon LASEC group (n\u0026thinsp;=\u0026thinsp;71)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003eLASEC group (n\u0026thinsp;=\u0026thinsp;37)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c4\"\u003e \u003cp\u003e\u003cem\u003ep\u003c/em\u003e Value\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePeripheral blood\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003esP-selectin (ng/mL)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c2\"\u003e \u003cp\u003e36.40\u0026thinsp;\u0026plusmn;\u0026thinsp;10.83\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c3\"\u003e \u003cp\u003e44.08\u0026thinsp;\u0026plusmn;\u0026thinsp;13.47\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e\u003cb\u003e0.0018\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003evWF (\u0026micro;g/mL)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c2\"\u003e \u003cp\u003e14.54\u0026thinsp;\u0026plusmn;\u0026thinsp;6.49\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c3\"\u003e \u003cp\u003e17.45\u0026thinsp;\u0026plusmn;\u0026thinsp;6.22\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e\u003cb\u003e0.0271\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eLeft atrial blood\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003esP-selectin (ng/mL)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c2\"\u003e \u003cp\u003e34.00\u0026thinsp;\u0026plusmn;\u0026thinsp;11.34\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c3\"\u003e \u003cp\u003e35.36\u0026thinsp;\u0026plusmn;\u0026thinsp;9.75\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.5372\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003evWF (\u0026micro;g/mL)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c2\"\u003e \u003cp\u003e12.36\u0026thinsp;\u0026plusmn;\u0026thinsp;5.92\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c3\"\u003e \u003cp\u003e14.04\u0026thinsp;\u0026plusmn;\u0026thinsp;6.14\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.1698\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec13\" class=\"Section2\"\u003e \u003ch2\u003eLevels of circulating microparticles in femoral blood and left atrial blood\u003c/h2\u003e \u003cp\u003eConcentrations of MPs in peripheral femoral blood and left atrial blood were shown in Table\u0026nbsp;\u003cspan refid=\"Tab3\" class=\"InternalRef\"\u003e3\u003c/span\u003e. When compared to non LASEC group, significant accumulations of PMPs and EMPs were found in peripheral femoral blood of LASEC group (\u003cem\u003ep\u0026thinsp;=\u0026thinsp;0.0395, p\u0026thinsp;=\u0026thinsp;0.018\u003c/em\u003e) while no significant differences in left atrial blood (\u003cem\u003ep\u0026thinsp;=\u0026thinsp;0.5322, p\u0026thinsp;=\u0026thinsp;0.8816\u003c/em\u003e). In patients with LASEC, concentrations of peripheral PMPs and EMPs were significantly higher than those in the left atrial blood (\u003cem\u003ep\u0026thinsp;=\u003c/em\u003e\u0026thinsp;0.0364, \u003cem\u003ep\u0026thinsp;=\u003c/em\u003e\u0026thinsp;0.0278). The comparison of peripheral venous and left atrial blood parameters in all patients showed sP-selectin, vWF and EMPs levels in the peripheral blood were significantly higher than those in left atrial blood (Table\u0026nbsp;\u003cspan refid=\"Tab4\" class=\"InternalRef\"\u003e4\u003c/span\u003e). No regional difference of PMPs concentration was found in all patients (\u003cem\u003ep\u0026thinsp;=\u003c/em\u003e\u0026thinsp;0.2649).\u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab3\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 3\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eNumbers of PMPs and EMPs in the study population\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"4\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e \u003cp\u003eParameters (\u0026times;10\u003csup\u003e3\u003c/sup\u003e/\u0026micro;L)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003enon LASEC group (n\u0026thinsp;=\u0026thinsp;71)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003eLASEC group (n\u0026thinsp;=\u0026thinsp;37)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c4\"\u003e \u003cp\u003e\u003cem\u003ep\u003c/em\u003e Value\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePeripheral blood\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePMPs\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e1.83 (0.51\u0026ndash;8.98)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e4.38 (1.20-14.99)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e\u003cb\u003e0.0395\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eEMPs\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e1.71 (0.76\u0026ndash;4.73)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e4.74 (1.49\u0026ndash;12.65)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e\u003cb\u003e0.0180\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eLeft atrial blood\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePMPs\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e2.01 (0.49\u0026ndash;6.70)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e1.25 (0.41\u0026ndash;5.27)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.5322\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eEMPs\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e1.22 (0.35\u0026ndash;5.87)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e1.01 (0.30\u0026ndash;8.40)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.8816\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab4\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 4\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eParameters between peripheral blood and left atrial blood\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"4\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e \u003cp\u003eParameters\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003ePeripheral blood (n\u0026thinsp;=\u0026thinsp;108)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003eLeft atrial blood (n\u0026thinsp;=\u0026thinsp;108)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c4\"\u003e \u003cp\u003e\u003cem\u003ep\u003c/em\u003e Value\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003esP-selectin (ng/mL)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e39.03\u0026thinsp;\u0026plusmn;\u0026thinsp;12.29\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e34.46\u0026thinsp;\u0026plusmn;\u0026thinsp;10.80\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e\u003cb\u003e0.0041\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003evWF (\u0026micro;g/mL)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e15534.78\u0026thinsp;\u0026plusmn;\u0026thinsp;6522.63\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e12932.81\u0026thinsp;\u0026plusmn;\u0026thinsp;6018.10\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e\u003cb\u003e0.0026\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePMPs (\u0026times;10\u003csup\u003e3\u003c/sup\u003e/\u0026micro;L)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e2.27 (0.59\u0026ndash;9.86)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e1.47 (0.46\u0026ndash;6.49)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.2649\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eEMPs (\u0026times;10\u003csup\u003e3\u003c/sup\u003e/\u0026micro;L)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e2.05 (0.80\u0026ndash;8.25)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e1.19 (0.35\u0026ndash;5.96)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e\u003cb\u003e0.0120\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec14\" class=\"Section2\"\u003e \u003ch2\u003eROC Curve Analysis\u003c/h2\u003e \u003cp\u003eAfter constructing the ROC curves for biomarkers, the results showed that area under curve of PMPs and sP-selectin was 0.621 (95%CI: 0.522\u0026ndash;0.712, sensitivity: 48.65%,specificity: 71.83%) and 0.669 (95%CI: 0.572\u0026ndash;0.757, sensitivity:59.46%, specificity: 74.65%), respectively. The AUC of EMPs was 0.639 (95%CI: 0.541\u0026ndash;0.729, sensitivity: 64.86%, specificity: 66.20%). The AUC of vWF was 0.624 (95%CI: 0.526\u0026ndash;0.716, sensitivity: 86.49%, specificity: 40.85%).\u003c/p\u003e \u003cp\u003eMoreover, the AUC of combined PMPs and sP-selectin was 0.769 (95%CI: 0.678\u0026ndash;0.845, sensitivity: 86.49%, specificity: 59.15%, Fig.\u0026nbsp;\u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e1\u003c/span\u003e), presenting the superior predictive value than PMPs or sP-selectin alone (\u003cem\u003eZ\u003c/em\u003e\u0026thinsp;=\u0026thinsp;2.363, \u003cem\u003ep\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.0181; \u003cem\u003eZ\u003c/em\u003e\u0026thinsp;=\u0026thinsp;1.961, \u003cem\u003ep\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.0499). The AUC of combined EMPs and vWF was 0.672 (95%CI: 0.575\u0026ndash;0.760, sensitivity: 37.84%, specificity: 90.14%).\u003c/p\u003e \u003cp\u003eWhen the combination model of PMPs, sP-selectin, EMPs and vWF was used, the predictive value improved to an AUC of 0.767 (95%CI: 0.676\u0026ndash;0.843, sensitivity: 83.78%, specificity: 61.97%). A combination of four markers showed a more useful screening test than combination of EMPs and vWF markers(\u003cem\u003eZ\u003c/em\u003e\u0026thinsp;=\u0026thinsp;2.000, \u003cem\u003ep\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.0455) but not combination of PMPs and sP-selectin (\u003cem\u003eZ\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.194, \u003cem\u003ep\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.0863).\u003c/p\u003e \u003c/div\u003e"},{"header":"Discussion","content":"\u003cp\u003eAccumulating studies have documented the vital role of LASEC in predicting cardiovascular events\u003csup\u003e[\u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e, \u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e]\u003c/sup\u003e. In the present study, approximately 34.26% (37/108) of the NVAF patients had LASEC, which is in line with previous data\u003csup\u003e[\u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e]\u003c/sup\u003e.\u003c/p\u003e \u003cp\u003eTo gain better understanding of discriminating predictive indicators in LASEC, changes of local vascular biomarkers in the left atrium and peripheral femoral blood were investigated. Our data showed elevated local and peripheral blood levels of sP-selectin and vWF in NVAF patients with LASEC, suggesting the endothelial dysfunction and abnormal platelet activation in patients had LASEC. Increased sP-selectin and vWF are linked with high risk of stroke and adverse outcomes. Also, this study found the levels of sP-selectin and vWF concerning the LASEC group in peripheral blood were higher than those in left atrial blood, which controverts with previous studies\u003csup\u003e[\u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e, \u003cspan citationid=\"CR17\" class=\"CitationRef\"\u003e17\u003c/span\u003e]\u003c/sup\u003e. A possible explanation is that vascular dysfunction and platelet activation also occurred in other sites, and the mean CHA\u003csub\u003e2\u003c/sub\u003eDS\u003csub\u003e2\u003c/sub\u003e-VASc scores were 2.5\u0026thinsp;\u0026plusmn;\u0026thinsp;1.6 in this study, which means most patients had higher thromboembolism risk than previous studies. In a pile of papers, it was demonstrated that thrombi were not rare in the right atrium\u003csup\u003e[\u003cspan citationid=\"CR18\" class=\"CitationRef\"\u003e18\u003c/span\u003e, \u003cspan citationid=\"CR19\" class=\"CitationRef\"\u003e19\u003c/span\u003e, \u003cspan citationid=\"CR20\" class=\"CitationRef\"\u003e20\u003c/span\u003e]\u003c/sup\u003e .Hence sP-selectin and vWF levels in peripheral vessels maybe more accurate and comprehensive, instead of those in left atrium blood.\u003c/p\u003e \u003cp\u003ePlatelet- and endothelial-derived microparticles are closely related to hemostasis and thrombosis\u003csup\u003e[\u003cspan citationid=\"CR21\" class=\"CitationRef\"\u003e21\u003c/span\u003e, \u003cspan citationid=\"CR22\" class=\"CitationRef\"\u003e22\u003c/span\u003e]\u003c/sup\u003e. Endothelial injury activates platelets and releases MPs which are abundant of micro-RNA and cytokines, resulting in activating relevant signaling and thrombosis formation. Sample collection, processing, MPs isolation and related technology was challenging as MPs are easily to degrade or elevate\u003csup\u003e[\u003cspan citationid=\"CR23\" class=\"CitationRef\"\u003e23\u003c/span\u003e, \u003cspan citationid=\"CR24\" class=\"CitationRef\"\u003e24\u003c/span\u003e]\u003c/sup\u003e. In this study, fresh whole blood samples were used and freezing was avoided to obtained precise quantification. Similarly, we found significantly enhanced peripheral PMPs and EMPs but not local PMPs and EMPs in LASEC group comparing non LASEC group.\u003c/p\u003e \u003cp\u003eTo examine the predictive role of peripheral serological indicator, we conducted the ROC analyses of sP-selectin, vWF, PMPs and EMPs. Despite the sP-selectin exclusively derives from platelets, it could be partially released on endothelial cells\u003csup\u003e[\u003cspan citationid=\"CR25\" class=\"CitationRef\"\u003e25\u003c/span\u003e, \u003cspan citationid=\"CR26\" class=\"CitationRef\"\u003e26\u003c/span\u003e]\u003c/sup\u003e. VWF is a multimeric glycoprotein synthesized and secreted by injured vascular endothelium\u003csup\u003e[\u003cspan citationid=\"CR27\" class=\"CitationRef\"\u003e27\u003c/span\u003e]\u003c/sup\u003e. At a cutoff value of 42.23 ng/mL, sP-selectin presented sensitivity of 59.46% and specificity of 74.65%. The cutoff of vWF was 11.64 \u0026micro;g/mL, with a sensitivity of 86.49% and specificity of 40.85%. There are limited studies on MPs numbers of NVAF patients during anticoagulation. Here we identified at a cutoff of 5.59\u0026times;10\u003csup\u003e3\u003c/sup\u003e/\u0026micro;L, PMPs had sensitivity of 48.65% and specificity of 71.83%. And at a cutoff of 2.52\u0026times;10\u003csup\u003e3\u003c/sup\u003e/\u0026micro;L, EMPs had sensitivity of 64.86% and specificity of 66.20%. We found the combination of four markers were prior to PMPs, sP-selectin, EMPs and vWF alone.\u003c/p\u003e \u003cp\u003eOf course there are some limitations in our study. Firstly, the study was based on a single-center. More cases need to be enrolled to verify whether the severity of LASEC would influence the expressions of sP-selectin, vWF and microparticles. Secondly, atrial inflammation and irregular blood flow induced by AF may cause endothelial dysfunction, but the impaired endothelial function of AF patients would improve after catheter ablation regardless of the type of AF\u003csup\u003e[\u003cspan citationid=\"CR28\" class=\"CitationRef\"\u003e28\u003c/span\u003e]\u003c/sup\u003e. Further studies concerning the variations of biomarkers over time are still in need.\u003c/p\u003e \u003cp\u003eTo summarize, spontaneous echo contrast was commonly seen in left atrium of patients with non-valvular atrial fibrillation. Our data demonstrated the elevated expressions of sP-selectin, vWF, PMPs and EMPs in NVAF patients with LASEC. We provided useful indicators and related thresholds regarding the existence of LASEC in atrial fibrillation.\u003c/p\u003e"},{"header":"Declarations","content":"\u003cp\u003e\u003cstrong\u003eEthics approval and consent to participate\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThis study involving experiments on humans and the use of human blood samples was conducted in accordance with ethical standards, and all experimental protocols were approved by the First Affiliated Hospital of Soochow University of Ethics Committee (Approval No: 277].\u003c/p\u003e\n\u003cp\u003eInformed consent was obtained from all human subjects involved in the study. The consent process was conducted in accordance with the First Affiliated Hospital of Soochow University of Ethics Committee. Each participant was provided with detailed information about the study objectives, procedures, potential risks, and benefits, and written consent was obtained before their participation.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConsent for publication\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eNot applicable, as our study does not involve the collection or publication of any revealing information about individual participants.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAvailability of data and materials\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eData is provided within the manuscript or supplementary information files\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eCompeting interests\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe authors declare that they have no competing interests.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eFunding\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThis research was funded by the Jiangsu Provincial Key Medical Center and the Priority Academic Program Development of Jiangsu Higher Education Institutions (PAPD) under grant number (YXZXA2016002).\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAuthors\u0026apos; contributions\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eB.D. and J.Z. collected and analyzed data; L.Y.H. wrote the main manuscript text; L.Y.H. J.Z. and B.D. performed experiments; B.D. and Y.L.D. prepared figures and tables; C.Z. initiated and supervised the project, analyzed and interpreted results. All authors reviewed the manuscript.\u003c/p\u003e"},{"header":"References","content":"\u003col class=\"decimal_type\"\u003e\n\u003cli\u003eZimetbaum P.Atrial Fibrillation[J].Ann Intern Med,2017,166(5):ITC33-ITC48. \u003c/li\u003e\n\u003cli\u003eHajjiri M, Bernstein S, Saric M, \u003cem\u003eet al\u003c/em\u003e. Atrial fibrillation ablation in patients with known sludge in the left atrial appendage [J]. J Interv Card Electrophysiol. 2014;40(2):147-151. \u003c/li\u003e\n\u003cli\u003eLubitz SA, Parsons OE, Anderson CD, \u003cem\u003eet al\u003c/em\u003e. Atrial fibrillation genetic risk and ischemic stroke mechanisms [J]. 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Correlation between left atrial spontaneous echocardiographic contrast and 5-year stroke/death in patients with non-valvular atrial fibrillation![J]. Arch Cardiovasc Dis. 2020;113(8-9):525-533.\u003c/li\u003e\n\u003cli\u003eLi Z, Liu Q, Liu F,\u003cem\u003e et al\u003c/em\u003e. Nomogram to predict left atrial thrombus or spontaneous echo contrast in patients with non-valvular atrial fibrillation[J]. Front Cardiovasc Med. 2021;8:737551. \u003c/li\u003e\n\u003cli\u003eHindricks G, Potpara T, Dagres N, \u003cem\u003eet al\u003c/em\u003e. 2020 ESC Guidelines for the diagnosis and management of atrial fibrillation developed in collaboration with the European Association for Cardio-Thoracic Surgery (EACTS): The Task Force for the diagnosis and management of atrial fibrillation of the European Society of Cardiology (ESC) Developed with the special contribution of the European Heart Rhythm Association (EHRA) of the ESC [published correction appears in Eur Heart J. 2021 Feb 1;42(5):507] [published correction appears in Eur Heart J. 2021 Feb 1;42(5):546-547] [published correction appears in Eur Heart J. 2021;42(40):4194]. \u003cem\u003eEur Heart J\u003c/em\u003e. 2021;42(5):373-498. \u003c/li\u003e\n\u003cli\u003eGage BF, Waterman AD, Shannon W,\u003cem\u003eet al\u003c/em\u003e. Validation of clinical classification schemes for predicting stroke: results from the National Registry of Atrial Fibrillation. JAMA. 2001;285(22):2864-2870.\u003c/li\u003e\n\u003cli\u003eChiva-Blanch G, Laake K, Myhre P, \u003cem\u003eet al\u003c/em\u003e. Platelet-, monocyte-derived and tissue factor-carrying circulating microparticles are related to acute myocardial infarction severity[J]. PLoS One, 2017;12(2):e0172558.\u003c/li\u003e\n\u003cli\u003eKhumri TM, Idupulapati M, Rader VJ,\u003cem\u003eet al\u003c/em\u003e. Clinical and echocardiographic markers of mortality risk in patients with atrial fibrillation[J]. Am J Cardiol. 2007;99(12):1733-1736.\u003c/li\u003e\n\u003cli\u003eSoulat-Dufour L, Lang S, Etienney A, \u003cem\u003eet al\u003c/em\u003e. Correlation between left atrial spontaneous echocardiographic contrast and 5-year stroke/death in patients with non-valvular atrial fibrillation[J]. Arch Cardiovasc Dis. 2020;113(8-9):525-533.\u003c/li\u003e\n\u003cli\u003eBackhaus JF, Pflaumbaum A, Krogias C, \u003cem\u003eet al\u003c/em\u003e. Short- and long-term outcome of patients with spontaneous echo contrast or thrombus in the left atrial appendage in the era of the direct acting anticoagulants[J]. Clin Res Cardiol. 2021;110(11):1811\u0026ndash;21.\u003c/li\u003e\n\u003cli\u003eKornej J, Dinov B, Blann AD, \u003cem\u003eet al\u003c/em\u003e. Effects of radiofrequency catheter ablation of atrial fibrillation on soluble P-selectin, von Willebrand factor and IL-6 in the peripheral and cardiac circulation. PLoS One. 2014;9(11):e111760.\u003c/li\u003e\n\u003cli\u003eLuo ZQ, Hao XH, Li JH, \u003cem\u003eet al\u003c/em\u003e. Left atrial endocardial dysfunction and platelet activation in patients with atrial fibrillation and mitral stenosis. J Thorac Cardiovasc Surg. 2014;148(5):1970-1976.\u003c/li\u003e\n\u003cli\u003eAnfinogenova ND, Vasiltseva OY, Vrublevsky AV, \u003cem\u003eet al\u003c/em\u003e. Right Atrial Thrombosis and Pulmonary Embolism: A Narrative Review[J]. Semin Thromb Hemost. 2020;46(8):895-907.\u003c/li\u003e\n\u003cli\u003eDegiovanni A, Carassia C, De Vecchi S, \u003cem\u003eet al\u003c/em\u003e.. Atrial thrombosis: Not only left, think also about right![J]. J Clin Ultrasound. 2022;50(8):1194-1201.\u003c/li\u003e\n\u003cli\u003eDi Biase L, Santangeli P, Anselmino M, et al. Does the left atrial appendage morphology correlate with the risk of stroke in patients with atrial fibrillation? Results from a multicenter study[J]. J Am Coll Cardiol 2012;60:531\u0026ndash;8.\u003c/li\u003e\n\u003cli\u003ePapapanagiotou A, Daskalakis G, Siasos G, \u003cem\u003eet al\u003c/em\u003e. The Role of Platelets in Cardiovascular Disease: Molecular Mechanisms[J]. Curr Pharm Des, 2016;22(29):4493-4505. \u003c/li\u003e\n\u003cli\u003eJeske WP, Walenga JM, Menapace B, \u003cem\u003eet al\u003c/em\u003e. Blood cell microparticles as biomarkers of hemostatic abnormalities in patients with implanted cardiac assist devices[J]. Biomark Med, 2016;10(10):1095‐1104.\u003c/li\u003e\n\u003cli\u003eBurger D, Oleynik P. Isolation and Characterization of Circulating Microparticles by Flow Cytometry[J]. Methods Mol Biol, 2017;1527:271‐281.\u003c/li\u003e\n\u003cli\u003eKailashiya J. Platelet-derived microparticles analysis: Techniques, challenges and recommendations[J]. Anal Biochem, 2018;546:78‐85.\u003c/li\u003e\n\u003cli\u003eJurk K, Kehrel BE. Platelets: physiology and biochemistry[J]. Semin Thromb Hemost. 2005;31(4):381-392.\u003c/li\u003e\n\u003cli\u003eAndr\u0026eacute; P. P-selectin in haemostasis[J]. Br J Haematol. 2004;126(3):298-306.\u003c/li\u003e\n\u003cli\u003eXiang Y, Hwa J. Regulation of VWF expression, and secretion in health and disease[J]. Curr Opin Hematol. 2016;23(3):288-293.\u003c/li\u003e\n\u003cli\u003eShin SY, Na JO, Lim HE, et al. Improved endothelial function in patients with atrial fibrillation through maintenance of sinus rhythm by successful catheter ablation[J]. J Cardiovasc Electrophysiol, 2011;22(4):376‐382.\u003c/li\u003e\n\u003c/ol\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":false,"highlight":"","institution":"","isAcceptedByJournal":true,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"bmc-cardiovascular-disorders","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"bcar","sideBox":"Learn more about [BMC Cardiovascular Disorders](http://bmccardiovascdisord.biomedcentral.com/)","snPcode":"","submissionUrl":"https://www.editorialmanager.com/bcar/default.aspx","title":"BMC Cardiovascular Disorders","twitterHandle":"BMC_series","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"em","reportingPortfolio":"BMC Series","inReviewEnabled":true,"inReviewRevisionsEnabled":true},"keywords":"Atrial fibrillation, spontaneous echo contrast, platelet derived microparticles, endothelial derived microparticles, P-selectin","lastPublishedDoi":"10.21203/rs.3.rs-3865469/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-3865469/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003cp\u003e\u003cstrong\u003eObjectives:\u003c/strong\u003e The purpose of this study was to demonstrate the discriminating predictive indicators in peripheral blood and left atrium blood for predicting the risk of left atrial spontaneous echo contrast (LASEC) in atrial fibrillation patients underwent catheter ablation.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eMethods:\u003c/strong\u003e A total of 108 consecutive AF patients treated with radiofrequency ablation between July 2022 and July 2023 were enrolled and divided into two groups based on preprocedural transesophageal echocardiography: the non LASEC group (n=71) and the LASEC group (n=37). Circulating platelet and endothelial- derived MPs (PMPs and EMPs) in peripheral blood and left atrial blood were detected. Plasma soluble P-selectin (sP-selectin) and von Willebrand factor (vWF) were observed. Diagnostic efficiency was measured using receiver operating characteristic (ROC) curve.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eResults:\u003c/strong\u003e Peripheral sP-selectin, vWF and EMPs expressions elevated in all subjects when compared to those in left atrium blood. Levels of sP-selectin and vWF were significantly higher in peripheral blood of LASEC group than those of non LASEC group (\u003cem\u003ep=0.0018, p=0.0271\u003c/em\u003e). Significant accumulations of peripheral PMPs and EMPs were documented in LASEC group by comparison with non LASEC group (\u003cem\u003ep=0.0395, p=0.018\u003c/em\u003e). The area under curve(AUC) of combined PMPs and sP-selectin in predicting LASEC was 0.769 (95%CI: 0.678–0.845, sensitivity: 86.49%, specificity: 59.15%)，significantly larger than PMPs or sP-selectin alone.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConclusions:\u003c/strong\u003e Expressionsof PMPs, sP-selectin, EMPs and vWF Increased in NVAF patients with LASEC and that might be potential biomarkers for LASEC prediction.\u003c/p\u003e","manuscriptTitle":"Predictive Indicators in Peripheral Blood and Left Atrium Blood for Left Atrial Spontaneous Echo Contrast in Atrial Fibrillation Patients","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2024-01-29 20:44:51","doi":"10.21203/rs.3.rs-3865469/v1","editorialEvents":[{"type":"communityComments","content":0},{"type":"decision","content":"Revision requested","date":"2024-08-14T09:19:08+00:00","index":"","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2024-08-07T06:33:51+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"190079210549153555021944432099454936762","date":"2024-08-06T23:03:40+00:00","index":"hide","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2024-08-04T02:05:48+00:00","index":"hide","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2024-08-01T09:11:18+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"235502150973644440365425464805960521178","date":"2024-08-01T08:02:43+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"81363083936460405987853919893415990033","date":"2024-07-29T14:14:58+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"138749705714493856679450231931489509387","date":"2024-07-06T07:11:37+00:00","index":"hide","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2024-06-20T08:02:17+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"29610219325548194754410787993426623968","date":"2024-06-16T09:31:15+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"263955353119157367806722163099566161291","date":"2024-06-13T07:16:58+00:00","index":"hide","fulltext":""},{"type":"reviewersInvited","content":"","date":"2024-05-15T08:38:38+00:00","index":"","fulltext":""},{"type":"editorAssigned","content":"","date":"2024-05-15T05:10:31+00:00","index":"","fulltext":""},{"type":"editorInvited","content":"","date":"2024-01-25T04:35:58+00:00","index":"","fulltext":""},{"type":"checksComplete","content":"","date":"2024-01-25T04:34:52+00:00","index":"","fulltext":""},{"type":"submitted","content":"BMC Cardiovascular Disorders","date":"2024-01-15T05:08:05+00:00","index":"","fulltext":""}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"bmc-cardiovascular-disorders","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"bcar","sideBox":"Learn more about [BMC Cardiovascular Disorders](http://bmccardiovascdisord.biomedcentral.com/)","snPcode":"","submissionUrl":"https://www.editorialmanager.com/bcar/default.aspx","title":"BMC Cardiovascular Disorders","twitterHandle":"BMC_series","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"em","reportingPortfolio":"BMC Series","inReviewEnabled":true,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"6f1d0b7f-66e8-4eb1-90bf-7d7e2e203735","owner":[],"postedDate":"January 29th, 2024","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"published-in-journal","subjectAreas":[],"tags":[],"updatedAt":"2024-09-16T16:05:33+00:00","versionOfRecord":{"articleIdentity":"rs-3865469","link":"https://doi.org/10.1186/s12872-024-04162-w","journal":{"identity":"bmc-cardiovascular-disorders","isVorOnly":false,"title":"BMC Cardiovascular Disorders"},"publishedOn":"2024-09-11 15:58:11","publishedOnDateReadable":"September 11th, 2024"},"versionCreatedAt":"2024-01-29 20:44:51","video":"","vorDoi":"10.1186/s12872-024-04162-w","vorDoiUrl":"https://doi.org/10.1186/s12872-024-04162-w","workflowStages":[]},"version":"v1","identity":"rs-3865469","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-3865469","identity":"rs-3865469","version":["v1"]},"buildId":"qtupq5eGEP_6zYnWcrvyt","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}