Stroke Risk Stratification Research Articles

Abstract 4137927: Physicians’ Misrecognition of Stroke Risk in Patients with Atrial Fibrillation

Background: Current clinical practice guidelines for atrial fibrillation (AF) recommend stroke risk stratification and the use of oral anticoagulants (OACs) for patients at risk. However, physicians’ recognition of patients’ stroke risk may differ from the calculated risk, and the effect of this discrepancy on subsequent care remains unknown. Aims: We aimed to document treating physicians’ estimations of individual patients' stroke risk and assess its association with OAC utilization. Methods: A multicenter, prospective cohort study was conducted in two outpatient practices in Tokyo, Japan, between 2018 to 2020. Participants included patients with newly diagnosed AF or those referred for initial treatment for AF. Treating physicians were asked to document the patient's estimated risk of stroke in numbers. The estimations were categorized as low risk (<1.0%/year), intermediate risk (1.0%≤ to <2.0%/ year), and high risk (2.0%≤/year). We then calculated patients’ baseline CHA 2 DS 2 -VASc scores and divided them into three risk groups: 0 or 1 point as low risk, 2 points as intermediate risk, and 3 or more points as high risk. Higher risk categorization by physicians was defined as "overestimation," while lower risk categorization was defined as "underestimation." The independent association of physician-patient risk concordance with OAC use was explored by multivariable Logistic regression models. Results: Among the 285 patients enrolled in this study (mean age 68±12 years, male 72.6%), the mean CHA 2 DS 2 -VASc score was 2.3±1.6. Physicians correctly estimated stroke risk in 147 patients (51.6%), underestimated it in 25 patients (8.8%) and overestimated it in 113 patients (39.6%). OACs were used in 89.8% of patients whose stroke risk was correctly estimated, 72.0% of those whose stroke risk was underestimated, and 84.1% of patients whose health status was overestimated. After multivariable adjustment, the underestimation of stroke risk was independently associated with less use of OACs (adjusted odds ratio 0.23, 95% CI 0.061-0.85, P=0.028). Conclusions: In this cohort study, physician underestimation of stroke risk was not rare and associated with less use of OACs.

Refining the CHA2DS2VASc risk stratification scheme: Shall we drop the Sex Category criterion?

The CHA2DS2VASc score is recommended for stroke risk stratification in patients with atrial fibrillation (AF). This score assigns one extra point to female sex based on evidence from the early 2000s suggesting higher thromboembolic risk in women. This incremental risk of thromboembolism in women has decreased over time between 2007 and 2018, becoming non-significant in recent years. To assess the impact of removing the sex category (Sc) from the CHA2DS2VASc score, thus validating a non-sex CHA2DS2VASc (i.e., CHA2DS2VA) score. We analysed UK primary and secondary care data comprising 195,719 patients with AF followed between 1998-2016 (mean age: 75.9±12.3 years; 49.2% women). Among 126,428 non-anticoagulated patients, we compared the CHA2DS2VASc vs. CHA2DS2VA scores every calendar year. Throughout 413,007 patient-years, a total of 8,742 events of ischaemic stroke or systemic embolism were recorded. Sex differences in thromboembolic risk were not observed in the lower-risk population, but higher stroke rates were consistently seen in female patients in the higher-risk category (i.e., CHA2DS2VA ≥2). C-statistics for both CHA2DS2VA and CHA2DS2VASc scores were similar over the years (ranging from 0.62 to 0.71). With CHA2DS2VA no relevant differences were observed in IDI, and NRI resulted in improved reclassification (11%) in lower thromboembolic risk groups. NRI suggested misclassification in higher thromboembolic risk patients (-7%), but this did not affect their indication for anticoagulation (i.e., patients retained their high-risk status). Removing Sc from the CHA2DS2VASc score does not affect its ability to discriminate thromboembolic events in the AF population. Use of CHA2DS2VA may simplify initial decision-making for thromboprophylaxis.

Performance of Atrial Fibrillation Burden Trends for Stroke Risk Stratification.

Atrial fibrillation (AF) is associated with an increased risk of stroke, yet the limitations of conventional monitoring have restricted our understanding of AF burden risk thresholds. Predictive algorithms incorporating continuous AF burden measures may be useful for predicting stroke. This study evaluated the performance of temporal AF burden trends as predictors of stroke from a large cohort with insertable cardiac monitors. Using deidentified data from Optum Clinformatics Data Mart (2007-2019) linked with the Medtronic CareLink insertable cardiac monitor database, we identified patients with an insertable cardiac monitor for AF management (n=1197), suspected AF (n=1611), and cryptogenic stroke (n=2205). Daily AF burden was transformed into simple moving averages, and temporal AF burden trends were defined as the comparison of unique simple moving average pairs. Classification trees were used to predict ischemic stroke, and AF burden significance was quantified using bootstrapped mean variable importance. Of 5013 patients (age, 69.2±11.7 years; 50% male; CHA2DS2-VASc, 3.7±1.9) who met inclusion criteria, 869 had an ischemic stroke over 2 409 437 days total follow-up. Prior stroke or transient ischemic attack (variable importance, 13.13) was the number 1 predictor of future stroke followed by no prior diagnosis of AF (7.35) and AF burden trends in follow-up (2.59). Temporal proximity of AF and risk of stroke differed by device indication (simple moving averages: AF management, <8 days and suspected AF and cryptogenic stroke, 8-21 days). Together, baseline characteristics and AF burden trends performed optimally for the area under the receiver operating characteristic curve (0.73), specificity (0.70), and relative risk (5.00). AF burden trends may provide incremental prognostic value as leading indicators of stroke risk compared with conventional schemes.

Duplex ultrasonography for screening and monitoring of carotid artery stenosis for risk stratification of ischemic stroke

Aim: To evaluate the efficiency of Duplex Ultrasonography (DUS) for monitoring and screening of Carotid Artery Stenosis (CAS).Methods: PubMed, Web of Science, Cochrane, and SCOPUS were searched for relevant articles. The quality assessment of the included studies was conducted according to the Cochrane Risk of Bias Tool.Results: Our meta-analysis included six articles. We found that carotid DUS could detect mild CAS in 25%, moderate CAS in 13%, severe CAS in 14.5% of the examined vessels, detection of carotid artery plaques in 36.5% of the examined vessels, and abnormal intima thickness in 21.5% of the examined vessels.Conclusion: DUS is an important exam in the identification of patients with symptomatic CAS. It can improve clinical practice and provide cost-effective management for CAS. Carotid DUS showed high specificity and sensitivity in the diagnosis of CAS, especially a severe degree of stenosis

Predictors of left atrial appendage emptying velocity: Derivation and validation of CHIRP3(M-1) score

BackgroundAtrial fibrillation (AF) leads to impaired left atrial appendage contractility, increasing the risk of thromboembolic stroke. The left atrial appendage emptying velocity (LAAev) measured on transesophageal echocardiogram (TEE) is a marker of increased thromboembolic risk. ObjectivesThe purpose of this study was to evaluate predictors of reduced LAAev for identifying individuals at increased risk for cardioembolic stroke. MethodsThis was a single-center retrospective review of TEEs and clinical charts. Predictors of LAAev <30 cm/s were identified using logistic regression. A risk prediction model was created using stepwise selection in a derivation set (n = 695) and separately tested in a validated set (n = 300). ResultsWe included TEEs on 995 patients (age 71.3±12.7 years; female 38.1%; history of AF 82.1%; in AF at evaluation 27.7%; CHA2DS2-VASc score 4.1 ± 1.9; LAAev 41.6 ± 21.0 cm/s). Significant multivariable predictors of LAAev <30 cm/s in derivation set were used to create the CHIRP3M-1 score containing 8 variables: Coronary artery disease (1), congestive Heart failure (1), Increased left atrial volume index ≥42 mL/m2 (1), current Rhythm AF (1), Paroxysmal AF (2), Persistent AF (3), longstanding Persistent/permanent AF (4), and greater than moderate Mitral regurgitation (-1). In the validation set, as compared to intermediate scores (3–4), those with low scores (≤2) and high scores (≥5) had odds ratios for LAAev <30 cm/s of 0.41 (0.21, 0.78, P = .007) and 2.58 (95% confidence interval 1.45–4.61, P = .001), respectively. ConclusionWe developed and validated a novel risk stratification system to predict reduced LAAev using clinical and echocardiographic variables. This may help refine the stratification of cardioembolic stroke risk.

A digital twin approach for stroke risk assessment in Atrial Fibrillation Patients

Atrial fibrillation (AF) is associated with a fivefold increased risk of cerebrovascular events, contributing to 15–18 % of all strokes. Stroke prevention in clinical practice is typically guided by the CHA2DS2-VASc score, which depends on general clinical risk factors but falls short in predicting risk at an individual patient level. In this study, we introduce a digital twin model of the left atrium (LA) combined with computational fluid dynamics (CFD) simulations to enhance personalized stroke risk assessment. Simulations were performed on patient-specific dynamic LA models in sinus rhythm (SR) across three patient groups: 10 controls (CTRL), 10 with paroxysmal AF (PAR-AF), and 10 with persistent AF (PER-AF). Blood flow velocity and areas susceptible to thrombogenesis, based on several factors including endothelial damage, were identified in the left atrial appendage (LAA). In general, control subjects exhibited higher average blood velocity in both the LAA and its ostium (0.11 ± 0.03 m/s and 0.28 ± 0.05 m/s, respectively) compared to those with AF. In the AF groups, the velocities were lower (LAA: PAR-AF 0.05 ± 0.02 m/s, PER-AF 0.04 ± 0.02 m/s; LAA ostium: PAR-AF 0.14 ± 0.03 m/s, PER-AF 0.11 ± 0.04 m/s). CFD analysis revealed that endothelial cell activation potential (ECAP) was significantly higher in AF patients (PAR-AF: 3.96 ± 3.28 Pa⁻1, PER-AF: 4.77 ± 2.08 Pa⁻1) compared to controls (0.93 ± 0.63 Pa⁻1). These findings suggest that AF patients experience slower and more oscillatory blood flow in the LAA, increasing their risk of thrombosis. Additionally, blood tends to stagnate within the LAA, further raising the likelihood of clot formation. This proposed method could be used to enhance stroke risk stratification in AF patients by incorporating an index that integrates blood velocity-derived parameters.

Using machine learning to predict carotid artery symptoms from CT angiography: A radiomics and deep learning approach

PurposeTo assess radiomics and deep learning (DL) methods in identifying symptomatic Carotid Artery Disease (CAD) from carotid CT angiography (CTA) images. We further compare the performance of these novel methods to the conventional calcium score. MethodsCarotid CT angiography (CTA) images from symptomatic patients (ischaemic stroke/transient ischaemic attack within the last 3 months) and asymptomatic patients were analysed. Carotid arteries were classified into culprit, non-culprit and asymptomatic. The calcium score was assessed using the Agatston method. 93 radiomic features were extracted from regions-of-interest drawn on 14 consecutive CTA slices. For DL, convolutional neural networks (CNNs) with and without transfer learning were trained directly on CTA slices. Predictive performance was assessed over 5-fold cross validated AUC scores. SHAP and GRAD-CAM algorithms were used for explainability. Results132 carotid arteries were analysed (41 culprit, 41 non-culprit, and 50 asymptomatic). For asymptomatic vs symptomatic arteries, radiomics attained a mean AUC of 0.96(± 0.02), followed by DL 0.86(± 0.06) and then calcium 0.79(± 0.08). For culprit vs non-culprit arteries, radiomics achieved a mean AUC of 0.75(± 0.09), followed by DL 0.67(± 0.10) and then calcium 0.60(± 0.02). For multi-class classification, the mean AUCs were 0.95(± 0.07), 0.79(± 0.05), and 0.71(± 0.07) for radiomics, DL and calcium, respectively. Explainability revealed consistent patterns in the most important radiomic features. ConclusionsOur study highlights the potential of novel image analysis techniques in extracting quantitative information beyond calcification in the identification of CAD. Though further work is required, the transition of these novel techniques into clinical practice may eventually facilitate better stroke risk stratification.

Associations of polygenic risk scores with risks of stroke and its subtypes in Chinese

Background and purposePrevious studies, mostly focusing on the European population, have reported polygenic risk scores (PRSs) might achieve risk stratification of stroke. We aimed to examine the association strengths of...

Pathological Intraplaque Hemorrhage as the Gold Standard to Assess the Efficacy of Ultrasound in Predicting Vulnerable Carotid Plaque Rupture.

To assess the clinical utility of ultrasound in predicting the risk of carotid vulnerable plaque rupture using pathological intraplaque hemorrhage as the gold standard. A total of 118 patients who underwent endarterectomy due to symptomatic carotid artery stenosis were enrolled. Conventional ultrasound assessed the plaque thickness, area stenosis rate, echo, and surface morphology. Neovascularization were assessed by contrast-enhanced ultrasound (CEUS) and tracing intraplaque nonenhanced areas. According to neovascularization grade (0-4), plaques were classified as low-, intermediate-, and high risk. Fresh intraplaque hemorrhage within the pathology was adopted as the gold standard for diagnosing plaque rupture risk. Thus, we divided patients into ruptured risk and nonruptured risk groups to assess the value of crucial factors for plaque rupture risk using ultrasound. Of the 118 patients, hypertension accounted for 71.2%, hyperlipidemia 68.6%, diabetes 52.5%, and statin history 64.4%. In the rupture risk group, diabetes, smoking, and stenosis rate were significantly higher than the nonrupture risk group (P < .001); plaque thickness ≥4 mm (P > .05); and mainly hypoechoic with irregular surface morphology (P < .001), nonenhanced areas in the plaques (P < .001), and neovascularization >grade 2 (P < .001). Compared with the low-risk group, plaque rupture risk was 7.219 times higher in the medium-risk group and 18.333 times higher in the high-risk group. The kappa value of the interobserver consistency of crucial ultrasound parameters was >0.75, and the intraclass correlation coefficient was 0.919 (P < .01). Both conventional ultrasound and CEUS have significant clinical importance in the prediction of rupture risk in vulnerable carotid plaques, thereby enabling stroke risk stratification and the assessment of plaque rupture risk.

Dual-trajectory of TyG levels and lifestyle scores and their associations with ischemic stroke in a non-diabetic population: a cohort study

BackgroundThe Triglyceride-glucose (TyG) index, a surrogate marker of insulin resistance, has been implicated in the risk of ischemic stroke. However, the interplay between TyG levels, lifestyle factors, and their collective impact on stroke risk in non-diabetic populations remains inadequately explored. This study aims to evaluate the association of ischemic stroke with the joint development of the TyG index and lifestyle in the non-diabetic population.MethodsIn this prospective cohort study, data was collected across three consecutive biennial surveys of the Kailuan Study from 2006 to 2011. The dual-trajectory model was used to determine the temporal development of TyG levels and lifestyle scores. Statistical analysis involved Cox regression models to evaluate the association between TyG-lifestyle trajectories and ischemic stroke risk, adjusting for potential confounders.ResultsA total of 44,403 participants were included, with five distinct TyG levels and lifestyle scores trajectory subtypes identified. In the multivariable-adjusted analyses, significant differences in ischemic stroke risk among the trajectory subtypes. Group 5, characterized by the highest TyG levels and moderate lifestyle scores, exhibited the greatest ischemic stroke risk (HR = 1.81, 95% CI: 1.51–2.18), while group 4, with moderate TyG levels and higher lifestyle scores, demonstrated the lowest risk (HR = 1.19, 95% CI: 1.04–1.37), compared with group 3. Participants with elevated TyG levels were at an increased risk of ischemic stroke in cases of pronounced insulin resistance, even with a healthy lifestyle.ConclusionsThis study reveals the significant associations between the identified TyG and lifestyle trajectories and the stratification of ischemic stroke risk among non-diabetics. The TyG index is a valuable indicator for assessing insulin resistance. However, the potential benefits of lifestyle changes for those with significantly high TyG levels need to be clarified by more research to develop more effective stroke prevention strategies.

Evaluation of CHA2DS2VASc scale as a tool of prognosis of death in transvenous lead extraction patients in long term follow-up

Abstract Background CHA2DS2VASc scale is commonly used to risk stratification of stroke in atrial fibrillation patients. With the exception of female gender, the remaining components of the scale are also risk factors for long-term prognosis. Aim Assessment of the usefulness of the CHA2DS2VASc scale for predicting the short and long term risk of death in the population of transvenous lead extraction (TLE) patients. Methods Retrospective analysis of data of 3822 consecutive patients underwent TLE followed by to 6239 days: median (Q1-Q3) 1846 (852 – 3146). Results The strong corelation between number of CHA2DS2VASc scale points and mortality was detected both in 30-days, 1-year, 3-year and all time of follow-up (Spearman r for all follow-up = 0.983, p&amp;lt;0.001). In all TLE population multivariable Cox regression shown that number of points of CHA2DS2VASc scale is independent predictor of death [HR=1.181; 95%CI (1.104-1.264), p&amp;lt;0.001], alongside Carlson index, atrial fibrillation, infective TLE indications and renal dysfunction. A scale value higher by 1 point is associated with an increase in the risk of death by 18.1%. In female group the risk increased by 37.5% [HR=1.375; 95%CI(1.193-1.584), p&amp;lt;0.001)] and in male group the risk increased by 22.00% [HR=1.220; 95%CI 1.110-1.342), p&amp;lt;0.001)]. Conclusion The commonly known stroke risk CHA2DS2VASc scale may be a useful tool for predicting the risk of death both in short and long-term observation in the group of patients after transvenous lead extraction.Table 1

Stroke risk assessment in different atrial fibrillation subtypes: CHA2DS2-VASc score and beyond

Abstract Background Patients with atrial fibrillation (AF) have been known to have an inhomogeneous risk of stroke, with several well-documented risk factors including hypertension, history of stroke, and diabetes mellitus that have been incorporated into the CHA2DS2–VASc score to stratify risk levels. Accumulating evidence has suggested that AF subtype, namely persistent AF and paroxysmal AF, also have an impact on stroke development. Purpose This study focused on the impact of AF subtype on stroke risk in a large, long-term follow-up cohort as to provide insight of the impact on ischemic stroke risks. Such findings may play a role in future ischemic stroke risk stratification in selected patients. Methods A total of 7346 AF patients were followed up for 10 years from January 2010 to December 2020 (mean follow-up time 2.74 years). Among these patients, 2460 (33.5%) had persistent or permanent AF (PerAF) and 4886 (66.5%) had paroxysmal AF (PAF). The study evaluated the risk of ischemic stroke between the two groups using Cox models adjusting for all components of the CHA2DS2–VASc score. Analyses were further stratified into the usage of oral anticoagulation (OAC) or no OAC. Results Comparing AF patients based on subtype, it was found that PerAF patients were older, had a higher prevalence of previous stroke, congestive heart failure, PAD, DM, and were more often prescribed anticoagulants. Univariate analysis found patients with PerAF at a higher risk for ischemic stroke (HR 1.262, p&amp;lt;0.001). The results remained significant after multivariate analysis with factors of the CHA2DS2–VASc score (HR 1.234, p&amp;lt;0.001). After stratifying patients according to anticoagulation prescription, PerAF and PAF patients were found to have similar rates of developing ischemic stroke in patients under DOAC. Conclusions Patients with PerAF have a higher risk of stroke during follow-up independent of components of the CHA2DS2VASc score. In patients with OAC use, there was no difference in stroke risk between AF subtypes.Stroke Risk in OAC-naive patientsStroke Risk in OAC-experienced patients

In Vivo Classification and Characterization of Carotid Atherosclerotic Lesions with Integrated 18F-FDG PET/MRI.

The aim of this study was to exploit integrated PET/MRI to simultaneously evaluate the morphological, component, and metabolic features of advanced atherosclerotic plaques and explore their incremental value. In this observational prospective cohort study, patients with advanced plaque in the carotid artery underwent 18F-FDG PET/MRI. Plaque morphological features were measured, and plaque component features were determined via MRI according to AHA lesion-types. Maximum standardized uptake values (SUVmax) and tissue to background ratio (TBR) on PET were calculated. Area under the receiver-operating characteristic curve (AUC) and net reclassification improvement (NRI) were used to compare the incremental contribution of FDG uptake when added to AHA lesion-types for symptomatic plaque classification. A total of 280 patients with advanced plaque in the carotid artery were recruited. A total of 402 plaques were confirmed, and 87 of 402 (21.6%) were symptomatic plaques. 18F-FDG PET/MRI was performed a mean of 38 days (range 1-90) after the symptom. Increased stenosis degree (61.5% vs. 50.0%, p < 0.001) and TBR (2.96 vs. 2.32, p < 0.001) were observed in symptomatic plaques compared with asymptomatic plaques. The performance of the combined model (AHA lesion type VI + stenosis degree + TBR) for predicting symptomatic plaques was the best among all models (AUC = 0.789). The improvement of the combined model (AHA lesion type VII + stenosis degree + TBR) over AHA lesion type VII model for predicting symptomatic plaques was the highest (AUC = 0.757/0.454, combined model/AHA lesion type VII model), and the NRI was 50.7%. Integrated PET/MRI could simultaneously evaluate the morphological component and inflammation features of advanced atherosclerotic plaques and provide supplementary optimization information over AHA lesion-types for identifying vulnerable plaques in atherosclerosis subjects to achieve further stratification of stroke risk.

CT texture analysis of vertebrobasilar artery calcification to identify culprit plaques.

The aim of this study was to extract radiomic features from vertebrobasilar artery calcification (VBAC) on head computed tomography (CT) images and investigate its diagnostic performance to identify culprit lesions responsible for acute cerebral infarctions. Patients with intracranial atherosclerotic disease who underwent vessel wall MRI (VW-MRI) and head CT examinations from a single center were retrospectively assessed for VBAC visual and textural analyses. Each calcified plaque was classified by the likelihood of having caused an acute cerebral infarction identified on VW-MRI as culprit or non-culprit. A predefined set of texture features extracted from VBAC segmentation was assessed using the minimum redundancy and maximum relevance method. Five key features were selected to integrate as a radiomic model using logistic regression by the Aikaike Information Criteria. The diagnostic value of the radiomic model was calculated for discriminating culprit lesions over VBAC visual assessments. A total of 1,218 radiomic features were extracted from 39 culprit and 50 non-culprit plaques, respectively. In the VBAC visual assessment, culprit plaques demonstrated more observed presence of multiple calcifications, spotty calcification, and intimal predominant calcification than non-culprit lesions (all p < 0.05). In the VBAC texture analysis, 55 (4.5%) of all extracted features were significantly different between culprit and non-culprit plaques (all p < 0.05). The radiomic model incorporating 5 selected features outperformed multiple calcifications [AUC = 0.81 with 95% confidence interval (CI) of 0.72, 0.90 vs. AUC = 0.61 with 95% CI of 0.49, 0.73; p = 0.001], intimal predominant calcification (AUC = 0.67 with 95% CI of 0.58, 0.76; p = 0.04) and spotty calcification (AUC = 0.62 with 95% CI of 0.52, 0.72; p = 0.005) in the identification of culprit lesions. Culprit plaques in the vertebrobasilar artery exhibit distinct calcification radiomic features compared to non-culprit plaques. CT texture analysis of VBAC has potential value in identifying lesions responsible for acute cerebral infarctions, which may be helpful for stroke risk stratification in clinical practice.

Sex differences in the correlation between white matter hyperintensity and 3-month outcome in acute stroke patients

BackgroundThe severity of white matter hyperintensities (WMH) has been shown to be an independent predictor of poor stroke outcome, but the effect of sex on this correlation has not been investigated further. Therefore, the purpose of our study was to assess whether there was a sex difference between the severity of WMH and poor stroke outcome. MethodsThis retrospective study included 449 patients with acute ischemic stroke (AIS) who received intravenous thrombolysis. WMH severity was graded based on the Fazekas scale. The association between WMH severity and stroke outcome was explored through multivariable regression analyses in men and women. ResultsAmong women, when dividing WMH severity into tertiles, T3 (Fazekas scale >3) had a 5.334 times higher risk for unfavorable outcomes than T1 (Fazekas scale <2) (p-trend = 0.026) in the adjusted model. In addition, moderate-severe WMH (Fazekas scale 3–6) had a 3.391 (1.151–9.991) times higher risk than none-mild WMH (Fazekas scale 0–2) (p = 0.027). ConclusionsThe risk of unfavorable outcomes increased proportionally with the enlargement of the WMH severity in females, suggesting the sex-specific value of the WMH severity in optimizing the risk stratification of stroke.

Circulating levels of potential markers of ischemic stroke in patients with the different forms of atrial fibrillation and chronic heart failure

Atrial fibrillation (AF) is the most common abnormal type of heart rhythm (cardiac arrhythmia), which is considered the leading cause of stroke. There have been limited studies on the prognostic markers for atrial disease and AF-associated ischemic stroke, despite the high demand for this procedure in daily clinical practice to monitor disease course and assess risk of stroke in patients with AF and chronic heart failure (CHF). Thus, the aim of the present study was to evaluate the levels of serum biomarkers related to ischemic stroke in CHF patients with the different forms of AF. Forty-six patients with various types of AF (paroxysmal, persistent and permanent) with or without ischemic stroke were enrolled in the study, 36 clinically healthy donors served as a control. The levels of inducible nitric oxide synthase (iNOS), vascular endothelial growth factor (VEGF) and angiostatins (AS) were evaluated by western blot analysis in the serum. The levels of active matrix metalloproteinases (MMPs) were analysed by gelatin zymography. Elevated levels of iNOS were shown in patients with all AF forms as compared with control, but iNOS levels in post-ischemic patients were significantly higher than that in paroxysmal AF individuals. However, the levels of VEGF and AS did not differ from the baseline value in patients with paroxysmal AF, while dramatic increase of their contents was shown in post-stroke patients with persistent and permanent types of AF. Elevated active MMP-9 levels were shown to be associated with the diagnosis of all AF forms, regardless of the occurrence of stroke. Taken together, our findings­ demonstrate that tested proteins can be considered as valuable biomarkers of AF forms transformation and potentially useful for ischemic stroke risk stratification in patients with AF and CHF. Observed changes in regulatory protein levels may expand our understanding of pathological roles of endothelial function dysregulation, disrupted angiogenesis balance and abnormal tissue remodeling in AF and associated ischemic events. Keywords: angiostatins, atrial fibrillation, biomarkers, iNOS, ischemic stroke, MMP-9, VEGF

Predicting stroke risk after sepsis hospitalization with new-onset atrial fibrillation.

New-onset atrial fibrillation (AF) during sepsis is common, but models designed to stratify stroke risk excluded patients with secondary AF. We assessed the predictive validity of CHA2DS2VASc scores among patients with new-onset AF during sepsisand developed a novel stroke prediction model incorporating presepsis and intrasepsis characteristics. We included patients ≥40 years old who survived hospitalizations with sepsis and new-onset AF across 21 Kaiser Permanente Northern California hospitals from January 1, 2011 to September 30, 2017. We calculated the area under the receiver operating curve (AUC) for CHA2DS2VASc scores to predict stroke or transient ischemic attack (TIA) within 1 year after a hospitalization with new-onset AF during sepsis using Fine-Gray models with death as competing risk. We similarly derived and validated a novel model using presepsis and intrasepsis characteristics associated with 1-year stroke/TIA risk. Among 82,748 adults hospitalized with sepsis, 3992 with new-onset AF (median age: 80 years, median CHA2DS2VASc of 4) survived to discharge, among whom 70 (2.1%) experienced stroke or TIA outcomeand 1393 (41.0%) died within 1 year of sepsis. The CHA2DS2VASc score was not predictive of stroke risk after sepsis (AUC: 0.50, 95% confidence interval [CI]: 0.48-0.52). A newly derived model among 2555 (64%) patients in the derivation set and 1437 (36%) in the validation set included 13 variables and produced an AUC of 0.61 (0.49-0.73) in derivation and 0.54 (0.43-0.65) in validation. Current models do not accurately stratify risk of stroke following new-onset AF secondary to sepsis. New tools are required to guide anticoagulation decisions following new-onset AF in sepsis.

Clinical decisions for appropriate management of patients with atrial fibrillation.

The management of patients with atrial fibrillation (AF) requires intricate clinical decision-making to optimize outcomes. In everyday clinical practice, physicians undergo difficult choices to better manage patients with AF. They need to balance thromboembolic and bleeding risk to focus on patients' symptoms and to manage a variety of multiple comorbidities. In this review, we aimed to explore the multifaceted dimensions of clinical decision-making in AF patients, encompassing the definition and diagnosis of clinical AF, stroke risk stratification, oral anticoagulant therapy selection, consideration of bleeding risk, and the ongoing debate between rhythm and rate control strategies. We will also focus on possible grey zones for the management of AF patients. In navigating this intricate landscape, clinicians must reconcile the dynamic interplay of patient-specific factors, evolving guidelines, and emerging therapies. The review underscores the need for personalized, evidence-based clinical decision-making to tailor interventions for optimal outcomes according to specific AF patient profiles.

Added Clinical Value of Intraplaque Neovascularization Detection to Color Doppler Ultrasound for Assessing Ischemic Stroke Risk.

Intraplaque neovascularization, assessed using contrast-enhanced ultrasound (CEUS), is associated with ischemic stroke. It remains unclear whether detection of intraplaque neovascularization combined with color Doppler ultrasound (CDUS) provides additional value compared with CDUS alone in assessing ischemic stroke risk. Therefore, we investigated the clinical value of combined CEUS, CDUS, and clinical features for ischemic stroke risk stratification. We recruited 360 patients with ≥50% carotid stenosis between January 2019 and September 2022. Patients were examined using CDUS and CEUS. Covariates associated with ischemic stroke were identified using multivariate logistic regression analysis. The discrimination and calibration were verified using the C-statistic and Hosmer-Lemeshow test. The incremental value of intraplaque neovascularization in the assessment of ischemic stroke was analyzed using the Delong test. We analyzed the data of 162 symptomatic and 159 asymptomatic patients who satisfied the inclusion and exclusion criteria, respectively. Based on multivariate logistic regression analysis, we constructed a nomogram using intraplaque neovascularization, degree of carotid stenosis, plaque hypoechoicity, and smoking status, with a C-statistic of 0.719 (95% confidence interval [CI]: 0.666-0.768) and a Hosmer-Lemeshow test p value of 0.261. The net reclassification index of the nomogram was 0.249 (95% CI: 0.138-0.359), and the integrated discrimination improvement was 0.053 (95% CI: 0.029-0.079). Adding intraplaque neovascularization to the combination of CDUS and clinical features (0.672; 95% CI: 0.617-0.723) increased the C-statistics (p=0.028). Further assessment of intraplaque neovascularization after CDUS may help more accurately identify patients at risk of ischemic stroke. Combining multiparametric carotid ultrasound and clinical features may help improve the risk stratification of patients with ischemic stroke with ≥50% carotid stenosis.

Cardiac imaging correlates and predictors of stroke in patients with atrial fibrillation: a meta-analysis.

New nonclinical parameters are needed to improve the current stroke risk stratification schemes for patients with atrial fibrillation. This study aimed to summarize data on potential cardiac imaging correlates and predictors of stroke or systemic embolism in patients with atrial fibrillation. MEDLINE, EMBASE, and Web of Science were searched to identify all published studies providing relevant data through 16 November 2022. Random effects meta-analysis method was used to pool estimates. We included 64 studies reporting data from a pooled population of 56 639 patients. Left atrial spontaneous echo-contrast [adjusted odds ratio (aOR) 3.32, 95% confidence interval (CI) 1.98-5.49], nonchicken wing left atrial appendage (LAA) morphology (aOR 2.15, 95% CI 1.11-4.18), left atrial enlargement (aOR 2.12, 95% CI 1.45-3.08), and higher LAA orifice diameter (aOR 1.56, 95% CI 1.18-2.05) were highly associated with stroke. Other parameters associated with stroke included higher left atrial sphericity (aOR 1.14, 95% CI 1.01-1.29), higher left atrial volume (aOR 1.03, 95% CI 1.01-1.04), higher left atrial volume index (aOR 1.014, 95% CI 1.004-1.023), lower left atrial reservoir strain [adjusted hazard ratio (aHR) 0.86, 95% CI 0.76-0.98], higher left ventricular mass index (aOR 1.010, 95% CI 1.005-1.015) and E / e' ratio (aOR 1.12, 95% CI 1.07-1.16). There was no association between LAA volume (aOR 1.37, 95% CI 0.85-2.21) and stroke. These cardiac imaging parameters identified as potential predictors of thromboembolism may improve the accuracy of stroke risk stratification schemes in patients with atrial fibrillation. Further studies should evaluate the performance of holistic risk scores including clinical factors, biomarkers, and cardiac imaging.