Risk Of Cardioembolic Stroke Research Articles

The impact of atrial fibrillation and stroke risk factors on left atrial blood flow characteristics.

Aims Altered left atrial (LA) blood flow characteristics account for an increase in cardioembolic stroke risk in atrial fibrillation (AF). Here, we aimed to assess whether exposure to stroke risk factors is sufficient to alter LA blood flow even in the presence of sinus rhythm (SR).Methods and results We investigated 95 individuals: 37 patients with persistent AF, who were studied before and after cardioversion [Group 1; median CHA2DS2-VASc = 2.0 (1.5–3.5)]; 35 individuals with no history of AF but similar stroke risk to Group 1 [Group 2; median CHA2DS2-VASc = 3.0 (2.0–4.0)]; and 23 low-risk individuals in SR [Group 3; median CHA2DS2-VASc = 0.0 (0.0–0.0)]. Cardiac function and LA flow characteristics were evaluated using cardiac magnetic resonance. Before cardioversion, Group 1 displayed impaired left ventricular (LV) and LA function, reduced LA flow velocities and vorticity, and a higher normalized vortex volume (all P < 0.001 vs. Groups 2 and 3). After restoration of SR at ≥4-week post-cardioversion, LV systolic function and LA flow parameters improved significantly (all P < 0.001 vs. pre-cardioversion) and were no longer different from those in Group 2. However, in the presence of SR, LA flow peak and mean velocity, and vorticity were lower in Groups 1 and 2 vs. Group 3 (all P < 0.01), and were associated with impaired LA emptying fraction (LAEF) and LV diastolic dysfunction.Conclusion Patients at moderate-to-high stroke risk display altered LA flow characteristics in SR in association with an LA myopathic phenotype and LV diastolic dysfunction, regardless of a history of AF.

The impact of plasma vitamin C levels on the risk of cardiovascular diseases and Alzheimer's disease: A Mendelian randomization study

Previous observational studies have reported associations between plasma vitamin C levels, and cardiovascular diseases (CVDs) and Alzheimer's disease (AD); however, no conclusive results have been obtained. We conducted a Mendelian randomization (MR) study to investigate the causality of vitamin C on the risk of nine CVDs [including coronary artery disease (CAD), myocardial infarction (MI), atrial fibrillation (AF), heart failure (HF), stroke, ischemic stroke (IS), and IS subtypes] and Alzheimer's disease. Eleven single-nucleotide polymorphisms (SNPs) identified in a recent genome-wide meta-analysis (N=52,018) were used as the instrumental variables for plasma vitamin C levels. The summary-level data for CVDs and AD were extracted from consortia and genome-wide association studies (GWAS). We performed MR analyses using the fixed-effects inverse-variance-weighted (IVW) method, weighted median, and MR-Egger approaches. This MR study found suggestive evidence that genetic liability to higher vitamin C levels was associated with a lower risk of cardioembolic stroke [odds ratio (OR, presented per 1 standard deviation increase in plasma vitamin C levels)=0.773; 95% confidence interval (CI), 0.623-0.959; P=0.020] and AD (OR=0.968; 95% CI, 0.946-0.991; P=0.007) using the fixed-effects IVW method. Sensitivity analysis yielded directionally similar results. A null-association was observed between vitamin C and the other CVDs. Our MR study provided suggestive evidence that higher vitamin C levels were casually associated with a decreased risk of cardioembolic stroke and AD. No evidence was observed to suggest that vitamin C affected the risk of CAD, MI, AF, HF, stroke, IS, large artery stroke, or small vessel stroke. However, well-designed studies are warranted to confirm these results and determine the underlying mechanisms of the causal links.

Altered left atrial appendage function associated with cardioembolic stroke in patients with rheumatic heart disease

Background: Left atrial appendage (LAA) is usually the first site for thrombus formation in rheumatic heart disease (RHD). LAA function is altered in RHD which may predispose it to thrombus formation. The aim of this study was to determine an association between function of LAA and cardioembolic stroke.Methods:Total 132 patients with RHD were studied by means of transthoracic echocardiography and/or transesophageal echocardiography and left atrial (LA) size, LAA ejection fraction (EF) and peak flow velocities were measured. These patients were followed up for 18 months with reference to development of cardioembolic stroke.Results: Seventy nine patients had atrial fibrillation (AF), of which 34 had thrombus in LAA. Out of 53 patients with sinus rhythm, 5 had LAA thrombus. Mean LAA EF was significantly lower in patients with thrombus in LAA, so was the peak flow velocity (both variables p&lt;0.0001). Saw tooth LAA outflow velocity pattern was visible in 30 (80%) patients with LAA thrombus versus 20 (28%) patients without LAA thrombus. Total 14 patients experienced cardioembolic stroke. Patients with cardioembolic stroke had lower mean LAA EF and peak flow velocity as compared to patients without cardioembolic stroke.Conclusions:Increased LAA size, reduced LAA EF and reduced peak flow velocity are associated with increased risk of cardioembolic stroke. LAA evaluation should be mandatory in deciding treatment strategies in patients with RHD and AF.

Genetically predicted circulating vitamin C in relation to cardiovascular disease.

We conducted a two-sample Mendelian randomization (MR) study to assess the associations of genetically predicted circulating vitamin C levels with cardiovascular diseases (CVDs). Ten lead single-nucleotide polymorphisms associated with plasma vitamin C levels at the genome-wide significance level were used as instrumental variables. Summary-level data for 15 CVDs were obtained from corresponding genetic consortia, the UK Biobank study, and the FinnGen consortium. The inverse-variance-weighted method was the primary analysis method, supplemented by the weighted median and MR-Egger methods. Estimates for each CVD from different sources were combined. Genetically predicted vitamin C levels were not associated with any CVD after accounting for multiple testing. However, there were suggestive associations of higher genetically predicted vitamin C levels (per 1 standard deviation increase) with lower risk of cardioembolic stroke [odds ratio, 0.79; 95% confidence interval (CI), 0.64, 0.99; P = 0.038] and higher risk of atrial fibrillation (odds ratio, 1.09; 95% CI, 1.00, 1.18; P = 0.049) in the inverse-variance-weighted method and with lower risk of peripheral artery disease (odds ratio, 0.76, 95% CI, 0.62, 0.93; P = 0.009) in the weighted median method. We found limited evidence with MR techniques for an overall protective role of vitamin C in the primary prevention of CVD. The associations of vitamin C levels with cardioembolic stroke, atrial fibrillation, and peripheral artery disease need further study.

Time in therapeutic range is lower in women than in men and is not explained by differences in age or comorbidity

BackgroundTime in therapeutic range (TTR) measures the stability of the international normalized ratio in patients on vitamin K antagonists (VKA). Low values are associated with poor outcomes. Women were shown to have lower TTR than men, but the causes are poorly defined. It was suggested that women on VKA are older and more morbid than men, and this could affect the stability of anticoagulation. We aimed to identify variables that affect TTR differently in women and men. Materials and methodsThis is a retrospective study in patients referred to a University hospital anticoagulant clinic. Age, sex, comorbidities, number of daily medications, indication and type of anticoagulant, weekly dosage and distribution, were derived from electronic records. Differences by sex and regression analysis to identify significant modulators of TTR were computed. Results1182 women and 1281 men on VKA were studied. Women were older than men (81.5 yrs. ± 11.2 vs 78.4 yrs. ± 12.2), and had lower TTR (65% ± 20.3 vs 69% ± 19.8). Comorbidity was similar between sexes and negatively affected TTR in both. Mechanical valves as an indication to anticoagulation and acenocoumarol as an anticoagulant as opposed to warfarin had a strong negative influence on TTR, while age increased TTR. Being a man rather than a woman afforded more than three TTR points. Number of medications and average anticoagulant dose were equal between sexes. DiscussionWomen have a lower TTR than men, on average below the safety threshold. They were indeed older, but age positively influenced TTR. Since women and men were equally comorbid, neither age nor disease explains differences in TTR. None of the other variables included in the study could explain the gender gap in TTR. Since women are at increased risk of cardioembolic stroke in atrial fibrillation, an effort at defining other causes for the observed differences, closer monitoring and switching to direct anticoagulants whenever possible is warranted.

BNP combined with echocardiographic parameters to predict the risk of cardioembolic stroke

BackgroundPrevious studies have found that BNP and some indicators of cardiac structure and function are closely associated with atrial fibrillation, so we aim to investigate the potential role of BNP and echocardiographic parameters to identify the acute ischemic stroke with atrial fibrillation patients who have high risks of cardioembolic stroke based on it. Methods436 AIS patients were divided into an AF group and non-AF group on the basis of the electrocardiogram and Holter results. Then we compared vascular risk factors, laboratory test indicators, and echocardiographic parameters among different groups. ResultsAIS with AF group had significantly higher age, CHD, previous medication, creatinine, d-dimer, fibrinogen, CRP, BNP, LAD, LVDd, LVDs and lower cholesterol, triglyceride, LDL and ejection fraction than the non-AF group (P < 0.05). Increased BNP, LAD, LVDd, LVDs and ejection fraction reduction were independent risk factors to predict cardioembolic stroke. BNP and LAD could be the two most effective indicators of the high risk of cardioembolic stroke. The area under the curve (AUC) of BNP and LAD were 0.791 [95%CI (0.743–0.838), p < 0.001), 0.786 [95%CI (0.739–0.833), p < 0.001]. The combined score we designed improved the prediction effect of single-indicator. The AUC of it was 0.822 with a sensitivity of 69.5% and specificity of 83.9%.There was an apparent positive correlation between BNP and LAD in AIS patients (r = 0.327, P < 0.001). ConclusionBNP combined with echocardiographic parameters has outstanding value to predict the risk of cardioembolic stroke, especially for BNP and LAD.

Genome-wide analysis suggests the importance of vascular processes and neuroinflammation in late-life antidepressant response

Antidepressant outcomes in older adults with depression is poor, possibly because of comorbidities such as cerebrovascular disease. Therefore, we leveraged multiple genome-wide approaches to understand the genetic architecture of antidepressant response. Our sample included 307 older adults (≥60 years) with current major depression, treated with venlafaxine extended-release for 12 weeks. A standard genome-wide association study (GWAS) was conducted for post-treatment remission status, followed by in silico biological characterization of associated genes, as well as polygenic risk scoring for depression, neurodegenerative and cerebrovascular disease. The top-associated variants for remission status and percentage symptom improvement were PIEZO1 rs12597726 (OR = 0.33 [0.21, 0.51], p = 1.42 × 10−6) and intergenic rs6916777 (Beta = 14.03 [8.47, 19.59], p = 1.25 × 10−6), respectively. Pathway analysis revealed significant contributions from genes involved in the ubiquitin-proteasome system, which regulates intracellular protein degradation with has implications for inflammation, as well as atherosclerotic cardiovascular disease (n = 25 of 190 genes, p = 8.03 × 10−6, FDR-corrected p = 0.01). Given the polygenicity of complex outcomes such as antidepressant response, we also explored 11 polygenic risk scores associated with risk for Alzheimer’s disease and stroke. Of the 11 scores, risk for cardioembolic stroke was the second-best predictor of non-remission, after being male (Accuracy = 0.70 [0.59, 0.79], Sensitivity = 0.72, Specificity = 0.67; p = 2.45 × 10−4). Although our findings did not reach genome-wide significance, they point to previously-implicated mechanisms and provide support for the roles of vascular and inflammatory pathways in LLD. Overall, significant enrichment of genes involved in protein degradation pathways that may be impaired, as well as the predictive capacity of risk for cardioembolic stroke, support a link between late-life depression remission and risk for vascular dysfunction.

Evaluating the use of a mobile device for detection of atrial fibrillation in primary care.

A trial fibrillation (AF) increases cardio-embolic stroke risk, yet AF diagnosis and subsequent prophylactic anticoagulant prescription rates are suboptimal globally. This project aimed to increase AF diagnosis and subsequent anticoagulation prescription rates in East Midlands Clinical Commissioning Groups (CCGs). This service improvement evaluation of the East Midlands AF Advance programme investigated the implementation of mobile AF detection devices (Kardia, AliveCor) into primary-care practices within East Midlands CCGs, along with audit tools and clinician upskilling workshops designed to increase AF diagnosis and anticoagulation prescription rates. AF prevalence and prescription data were collected quarterly from July to September (Q3) 2017/18 to April to June/July to September (Q2/3) 2018/19. AF prevalence increased from 1.9% (22,975 diagnoses) in Q3 2017/18 to 2.4% (24,246 diagnoses) in Q2 2018/19 (p=0.026), while the percentage of high-risk AF patients receiving anticoagulants increased from 80.5% in Q3 2017/18 to 86.9% in Q3 2018/19 (p=0.57), surpassing the Public Health England 2019 target of 85%. The East Midlands AF Advance programme increased AF diagnosis and anticoagulation rates, which is expected to be of significant clinical benefit. The mobile AF detection devices provide a more practical alternative to traditional 12-lead electrocardiograms (ECGs) and should be incorporated into routine clinical practice for opportunistic AF detection, in combination with medication reviews to increase anticoagulant prescription.

Height and risk of ischaemic stroke subtypes: a Mendelian randomisation study

Abstract Background Taller adult height is associated with lower risks of ischaemic heart disease in both conventional and Mendelian randomisation studies, providing support for a causal association, but the associations of height with ischaemic stroke and ischaemic stroke subtypes are uncertain. Purpose To examine the causal relevance of height for ischaemic stroke and ischaemic stroke subtypes. Methods Two-sample Mendelian randomisation analyses were used to examine the associations of height with: (i) ischaemic stroke and ischaemic stroke subtypes in MEGASTROKE (using summary data from 34 217 ischaemic stroke cases), and with (ii) established cardiovascular and other risk factors using individual data from 336 433 participants in UK Biobank and 57 785 in the China Kadoorie Biobank. Instruments for Mendelian randomisation were constructed from up to 3280 height-associated genetic variants, previously identified as having genome-wide significant effects on height. Results Genetically-determined taller height was inversely associated with ischaemic stroke (3% [95% CI: 1–6] lower risk per 1 standard deviation taller height) in MEGASTROKE but this masked much stronger opposing associations on risks of different ischaemic stroke subtypes: 15% (95% CI: 9–21) higher risk of cardioembolic stroke, 10% (4–15) lower risk of large-artery atherosclerotic stroke, and 15% (10–20) lower risk of small-vessel stroke (Figure). Genetically-determined taller height was strongly associated with atrial fibrillation and higher lean body mass and lung function but more weakly associated with lower levels of LDL cholesterol and blood pressure. Conclusions The findings support a causal association between taller adult height and risk of atrial fibrillation and cardioembolic stroke. The opposing associations of height with other ischaemic stroke subtypes provide further support for considering ischaemic stroke subtypes as distinct diseases in both research and clinical practice. Funding Acknowledgement Type of funding source: Foundation. Main funding source(s): Medical Research Council, British Heart Foundation

The impact of growth differentiation factor 15 on the risk of cardiovascular diseases: two-sample Mendelian randomization study

BackgroundGrowth differentiation factor 15 (GDF-15), a stress responsive cytokine, belongs to transforming growth factor β cytokine superfamily. Some evidence support that it’s involved in inflammation, coagulation, oxidative stress, endothelial dysfunction, and hemostasis. However, it’s still controversial whether GDF-15 directly contributes to the morbidity and mortality of patients suffered with cardiovascular disease (CVD). Besides prospective cohort study and randomized controlled trial, Mendelian randomization (MR) is a genetic epidemiological method that exploits genetic variants as unbiased proxies for modifiable to determine the causal relationships between exposures and health outcomes. Herein, we introduced a two-sample MR approach to evaluate the causal relationships of circulating GDF-15 levels with major CVDs incidence.MethodsGenetic instruments and summary statistics for two-sample MR analysis were obtained from 5 independent large genome-wide association studies (GWAS) to investigate the causal correlation between circulating GDF-15 levels and 9 CVDs, respectively. Conventional inverse variance weighted method was adopted to evaluate the causality of GDF-15 with different outcomes; weighted median and MR egger were used for sensitivity analyses.ResultsAmong 9 SNPs identified from 5 GWASs in 2.6 million individuals, 5 SNPs (rs1227731, rs3195944, rs17725099, rs888663, rs749451) coming from chromosome 19 and containing the PGPEP1 and GDF-15 genes were employed. Based on the instruments, circulating GDF-15 levels significantly linked to the increased risk of cardioembolic stroke, atrial fibrillation, coronary artery disease and myocardial infarction. However, no significant causal association was observed for circulating GDF-15 levels with the incidence of any ischemic stroke, large-artery atherosclerotic stroke, small vessel stroke, heart failure and nonischemic cardiomyopathy.ConclusionsThe MR study provides with genetic evidence for the causal relationship of circulating GDF-15 levels with the increased risk of cardioembolic stroke, atrial fibrillation, coronary artery disease and myocardial infarction, but not any ischemic stroke, large-artery atherosclerotic stroke, small vessel stroke, heart failure and nonischemic cardiomyopathy. It indicates that GDF-15 might be a promising biomarker or potential therapeutic target for some CVDs.

Techniques of left atrial appendage tomography for planning intervention treatment of atrial fibrillation

Due to intracardiac circulatory changes atrial fibrillation creates conditions for thrombus formation in the left atrial appendage (LAA). The presence of thrombus in LAA is poor prognostic factor of subsequent cardiovascular events. It is the source of up to 64% of ischemic stroke cases, and concomitant anticoagulant therapy leads to a high frequency of hemorrhagic conversion. For patient with symptomatic and drug-refractory arrhythmia is recommended surgical rhythm correction or electrical cardioversion. There is a high risk of cardioembolic stroke during the intervention, so it is necessary to exclude LAA thrombosis at pre-operation stage. The main method of LAA visualization is transesophageal echocardiography, but today computed tomography and, less, magnetic resonance tomography become important. The purpose of this review is to analyze the possibilities of each visualisation technique and their role in the diagnostic algorithm when examining patients before catheter ablation of atrial fibrillation sources.

Sleep Duration and Stroke: A Mendelian Randomization Study.

Study Objectives: To clarify the effects of sleep duration on stroke and stroke subtypes, we adopted a Mendelian randomization (MR) approach to evaluate their causal relationship.Methods: A genome-wide association study including 446,118 participants from UK biobank was used to identify instruments for short sleep, long sleep and sleep duration. Summary-level data for all stroke, ischemic stroke, intracerebral hemorrhage, and their subtypes were obtained from meta-analyses conducted by the MEGASTROKE consortium. MR analyses were performed using the inverse-variance-weighted method, weighted median estimator, MR pleiotropy residual sum and outlier (MR-PRESSO) test, and MR-Egger regression. Sensitivity analyses were further performed using leave-one-out analysis, MR-PRESSO global test and Cochran's Q test to verify the robustness of our findings.Results: By two-sample MR, we didn't find causal associations between sleep duration and risk of stroke. However, in the subgroup analysis, we found weak evidence for short sleep in increasing risk of cardio-embolic stroke (odds ratio [OR], 1.33; 95% confidence interval [CI], 1.11–1.60; P = 0.02) and long sleep in increasing risk of large artery stroke [OR, 1.41; 95% CI, 1.02–1.95; P = 0.04]. But the associations were not significant after Bonferroni correction for multiple comparisons.Conclusions: Our study suggests that sleep duration is not causally associated with risk of stroke and its subtypes.

1138 OSA In A Patient With PFO, Is It The “Perfect Storm” For A Stroke? A Case Series Of 3 Patients With Stroke At Young Age, Due To PFO And Comorbid OSA

Abstract Introduction Approximately 25% of all strokes are cryptogenic in nature, and about 50% of all young patients with cryptogenic stroke are found to have patent foramen ovale (PFO), which is known to be the most common cause of right-to-left shunting (RTLS). Studies have shown a 2.2-fold increase in right-to-left shunt in patients with OSA and PFO, compared to patients with PFO alone. Hence, increasing the risk of cardio-embolic stroke in such patients. We present a case series of 3 patients with PFO that had embolic stroke at a young age and were found to have comorbid OSA, the likely exacerbating factor of a RTLS. Methods A 38-year old female, a 59-year old male, and a 27-year old female presented with stroke-like symptoms without clear vascular pathology. Upon further work-up, all were found to have PFO with RTLS. Subsequently, these patients were referred for sleep evaluation, and each one was found to severe REM-related OSA with prominent oxygen desaturations. All three patients were started on PAP therapy for control of their OSA. Two out of the 3 patients opted for PFO closure, and the 3rd patient opted for anti-platelet therapy alone. He has had no recurrence of TIA/stroke after 12 years so far. Results These cases illustrate a correlation between right-to-left shunting and severe REM-related OSA, through possible elevation of right-sided pressure due to nocturnal desaturations/hypoxemia. Hence, it is worth consideration that the increased right-sided pressure induced by apneic events in sleep may be a potential exacerbating factor in producing stroke-like symptoms sooner in patients with PFO than in patients with PFO who are without OSA. Conclusion It may be beneficial to assess young patients with stroke due to PFO, for comorbid OSA as a cause of the RTLS. This would help to prevent recurrent stroke in such patients and improve quality of life. Support No financial support.

Use of Cerebral Embolic Protection in High-Risk Patients Undergoing Left Atrial Appendage Occlusion

Atrial fibrillation (AF) is the most common cardiac arrhythmia affecting more than 33 million people worldwide. Patients with AF are at an increased risk of cardioembolic stroke, making oral antico...

The Atrium and Embolic Stroke: Myopathy Not Atrial Fibrillation as the Requisite Determinant?

Atrial fibrillation (AF) is well-recognized in the pathophysiology of left atrial thrombogenesis and resultant cardioembolic stroke. Subclinical AF is believed to account for a significant proportion of embolic stroke. However, recent randomized control trials failed to demonstrate a significant benefit for oral anticoagulation, in an unselected population with embolic stroke of undetermined source. This has reinvigorated the focus on finding robust markers to identify patients at risk of cardioembolic stroke. Several nonfibrillatory atrial electrical markers, along with structural and biochemical abnormalities, have been associated with ischemic stroke, independently of AF. An increasingly complex relationship exists among vascular risk factors, atrial remodeling, and thrombogenesis. Identifying robust markers of an underlying atrial myopathy may allow for early identification of patients at risk for cardioembolic stroke. This review outlines the inconsistencies in the evidence for AF as the prerequisite for left atrial thrombogenesis and embolic stroke. It will highlight the current evidence and controversies for adverse atrial remodeling, independent from rhythm, as a plausible mechanism for left atrial thrombogenesis and ischemic stroke.

Abstract WMP70: Increased Left Atrial Appendage Density on Computerized Tomography is Associated With Cardioembolic Stroke

Background and Purpose: While studies have stratified cardioembolic (CE) stroke risk by qualitative left atrial appendage (LAA) morphology and biomarkers of atrial dysfunction, the quantitative properties that underlie these observations are not well established. Accordingly, we hypothesized that LAA volume and contrast density (attenuation) on computerized tomography (CT) may capture the structural and hemodynamic processes that underlie CE stroke risk. Methods: Data were collected from a single center prospective ischemic stroke database over 18 months and included all patients with ischemic stroke who previously underwent routine, non-gated, contrast enhanced thin-slice (≤2.5 mm) chest CT. Stroke subtype was determined based on the inpatient diagnostic evaluation. LAA volume and attenuation were determined from CT studies performed for various clinically appropriate indications. Univariate and multivariable analyses were performed to determine factors associated with ischemic stroke subtype, including known risk factors and biomarkers, as well as LAA density and morphologic measures. Results: We identified 311 patients with a qualifying chest CT (119 CE subtype, 109 ESUS, and 83 non-CE). In unadjusted models, there was an association between CE (vs. non-CE) stroke subtype and LAA volume (OR per mL increase 1.15, 95% CI 1.07-1.24, p&lt;0.001) and LAA density (4 th quartile vs. 1 st quartile; OR 2.95, 95% CI 1.28-6.80, p=0.011), but not with ESUS (vs. non-CE) subtype. In adjusted models, only the association between LAA density and CE stroke subtype persisted (adjusted OR 3.71, 95% CI 1.37-10.08, p=0.010). Conclusion: The LAA volume and density values on chest CT are associated with CE stroke subtype but not ESUS subtype. Patients with ESUS and increased LAA volume or attenuation may be a subgroup where the mechanism is cardioembolic and anticoagulation can be tested for secondary stroke prevention.

P921 Left atrial appendage flow velocity (LAAV) and n-terminal pro brain natriuretic peptide (NT-proBNP) as strong predictors of high thromboembolic events in patients with nonvalvular atrial fibrillatio

Abstract Background Many studies demonstrated that the presence of non valcular atrial fibrillation (NVAF) increased the risk of cardioembolic stroke from fivefold to sixfold. Cardioembolic stroke is commonly sourced by thrombi in Left Atrial Appendage (LAA) and since this is a treatable condition, early detection would be highly beneficial for a better prognosis. Aim : The aim of this study was to investigate the change of LAA flow felocity (LAAV) and its correlation with NT-proBNP plasma levels, Left atrial spontaneous echo contrast (LASEC) and CHA2DS2-Vasc score, as well as evaluating the prognostic value of these parameters in detecting thromboembolic events in patients with NVAF. Methods A non-interventional, cross-sectional observational study of 31 people with NVAF. Baseline patient characteristics, CHA2DS2-Vasc score, the five-grades of LASEC, NT-proBNP plasma levels were measured and LAAV visualized by transesophageal echocardiography (TEE) were performed. Results : LAAV were correlated with NT-proBNP (r = -0,511 , p = 0,003), high degree of SEC (r= -0,866 , p &amp;lt; 0,0001) and high CHA2DS2-VASc Score (p = 0.004). In addition, the receiver operating characteristic analysis revealed that the best cut-off value of NT-proBNP to predict higher risk of thromboembolic evants in patientswas 1052pg/mL with 76% sensitivity and 83.3% specificity (area under the curve: X2 = 7,441, p = 0.003). In the subgroup analysis based on different CHA2DS2-VASc scores, the predictive value of NT-proBNP remained significant in patients with a CHA2DS2-VASc score of ≥ 2. Conclusion LAAV were significanty correlated positively with NT-proBNP levels, degrees of SEC and CHA2DS2-VASc score. Plasma NT-proBNP along with CHA2DS2-VASc score were strong predictors of thromboembolic events in patients with NVAF

Impairment of left atrial function and cryptogenic stroke: Potential insights in the pathophysiology of stroke in the young

BackgroundStroke is one of the leading causes of morbidity and mortality with a significant percentage classified as cryptogenic. Left atrial (LA) remodelling, a substrate for atrial fibrillation (AF) and stroke development, may play a role in identification of the aetiology of cryptogenic stroke. We aimed to examine LA function to gain mechanistic insights into the pathophysiology of cryptogenic stroke in young patients otherwise at low risk for cardiovascular disease. MethodsPatients aged <60 years without traditional cardiovascular risk factors and who were diagnosed with ischaemic cryptogenic stroke or TIA were evaluated and compared to healthy controls and patients with paroxysmal AF with a CHA2DS2-VA score of 0. Conventional and novel left ventricular (LV) and LA echocardiographic parameters between the three groups were assessed. ResultsEach group consisted of thirty patients. There were no significant differences in LV parameters (LVEF, LV endoGLS) between groups. LA strain in stroke patients was significantly lower compared to the controls (median 33%; interquartile range (IQ) [32/39] vs 31 [27/34]; p = 0.008). LA strain was significantly lower in AF patients compared to stroke patients (median 21% [19/22] vs 31% [27/34]; p < 0.0001). ConclusionA stepwise reduction in measures of LA function was appreciated between controls, young stroke and paroxysmal AF groups. This may indicate dynamic LA remodelling occurring in the young stroke population and suggest a shared causal mechanism for stroke development in this group. LA strain may further refine the risk for cardioembolic stroke.

Mitral annular calcification and its severity predict high risk for cardio-embolic stroke in elderly patients with first diagnosed atrial fibrillation

Background Atrial fibrillation (AF) is the most common arrhythmia worldwide and a large proportion of patients with AF are older than 75 years of age. Mitral annular calcification (MAC), which is usually observed in advanced age, is associated with increased risk of AF and cardio-embolic stroke in the general population. Objectives This study was performed to assess whether presence of MAC and its severity predict cardio-embolic stroke in elderly patients with first diagnosed AF. Methods In this cross-sectional study, 72 elderly patients suffering from acute cardio-embolic stroke with first diagnosed AF and 79 elderly control group patients with first diagnosed AF and without stroke were investigated. A parasternal short-axis view at the level of the mitral annulus was used for MAC measurements. The severity of MAC was measured from the anterior to posterior edge at its greatest width. Results MAC thicknesses were significantly higher in the stroke group. ROC curve analysis showed that a cut point of 2.5 mm for the value of MAC thickness exhibited 68.1% sensitivity and 77.2% specificity for detecting cardio-embolic stroke in elderly patients with AF. In multivariate logistic regression analysis, MAC thickness (OR = 1.173, 95% CI 1.083–1.270; p < 0.001) was found to be independent predictor of cardio-embolic stroke in elderly patients with AF. Conclusion MAC thickness may provide useful information for the relevant risk evaluation of elderly patients with AF. Pre-stroke MAC presence and its severity appear to have better clinical value for predicting cardio-embolic stroke in elderly patients with AF, independent from traditional risk factors for stroke.

P3706Atrial fibrillation with CHA2DS2-VASC =0. Really no need for anticoagulation?

Abstract Background Based on the ESC guidelines on Atrial Fibrillation, oral anticoagulation is recommended in male patients with CHA2DS2-VASC score ≥1, in females if CHA2DS2-VASC is ≥2. In our research, we evaluated if there are patients at risk of significant thromboembolic events among those whose CHA2DS2-VASC score is apparently = 0, that could benefit of anticoagulant therapy. Methods Over the last 12 years, 20,154 outpatients were evaluated in our clinics. We found the presence of non valvular atrial fibrillation in 3.043 (15.1%) patients. In 176 (5.7%) of them the CHA2DS2-VASC was = 0. None of them, as suggested in the guidelines, received oral anticoagulants or antiplatelet drugs. In these patients, we evaluated the presence of other two important cardiovascular risk factors, not included in CHA2DS2-VASC score: cigarette smoking and hypercholesterolemia. Results Smoking patients were 70, of whom heavy smokers (≥20 cigarettes/day) were 32. Patients with LDL cholesterol&gt;115 mg/dl were 55. During one year follow-up, 3 of 176 patients (1.7%) with CHA2DS2-VASC score = 0 had a stroke. These patients were all heavy smokers and one of them also had high LDL values; they didn't show significant carotid stenosis or carotid dissection. None of the patients was found to have thrombophilic disorders. Transthoracic echocardiogram was performed, resulting negative for patent foramen ovale, ventricular dysfunction, or masses. All patients underwent 24 hours blood pressure monitoring, and it was found that all of them had masked hypertension; lower extremity arterial evaluation revealed mild, asymptomatic peripheral arterial disease, with ABI &lt;0.9. No events occurred in patients with elevated LDL, not heavy smokers. The risk of stroke in the population of heavy smokers, even if CHA2DS2-VASC score was apparently = 0, was 9.3%, with a clear indication for anticoagulation. Conclusions In heavy smokers patients with atrial fibrillation, CHA2DS2-VASC score could apparently be =0, when they are only clinically evaluated. In fact, these patients often have asymptomatic peripheral arterial disease of the lower limbs and masked hypertension. Our research highlights how in some subgroups of patients there could be some “hidden” risk factors, that we should keep in mind and closely search for when evaluating the risk of cardioembolic stroke, that remains high.