C1QC, VSIG4, and CFD as Potential Peripheral Blood Biomarkers in Atrial Fibrillation-Related Cardioembolic Stroke.

Atrial fibrillation (AF) is a major risk factor for ischemic stroke. We aimed to identify novel potential biomarkers with diagnostic value in patients with atrial fibrillation-related cardioembolic stroke (AF-CE).Publicly available gene expression profiles related to AF, cardioembolic stroke (CE), and large artery atherosclerosis (LAA) were downloaded from the Gene Expression Omnibus (GEO). Differentially expressed genes (DEGs) were identified and then functionally annotated. The support vector machine recursive feature elimination (SVM-RFE) and least absolute shrinkage and selection operator (LASSO) regression analysis were conducted to identify potential diagnostic AF-CE biomarkers. Furthermore, the results were validated by using external data sets, and discriminability was measured by the area under the ROC curve (AUC). In order to verify the predictive results, the blood samples of 13 healthy controls, 20 patients with CE, and 20 patients with LAA stroke were acquired for RT-qPCR, and the correlation between biomarkers and clinical features was further explored. Lastly, a nomogram and the companion website were developed to predict the CE-risk rate. Three feature genes (C1QC, VSIG4, and CFD) were selected and validated in the training and the external datasets. The qRT-PCR evaluation showed that the levels of blood biomarkers (C1QC, VSIG4, and CFD) in patients with AF-CE can be used to differentiate patients with AF-CE from normal controls (P < 0.05) and can effectively discriminate AF-CE from LAA stroke (P < 0.05). Immune cell infiltration analysis revealed that three feature genes were correlated with immune system such as neutrophils. Clinical impact curve, calibration curves, ROC, and DCAs of the nomogram indicate that the nomogram had good performance. Our findings showed that C1QC, VSIG4, and CFD can potentially serve as diagnostic blood biomarkers of AF-CE; novel nomogram and the companion website can help clinicians to identify high-risk individuals, thus helping to guide treatment decisions for stroke patients.

Change of Heart: The Underexplored Role of Plaque Hemorrhage in the Evaluation of Stroke of Undetermined Etiology.

In the evaluation of embolic strokes of undetermined source, great emphasis is often placed on cardiovascular disease, namely on atrial fibrillation. Other pathophysiologic mechanisms, however, may also be involved. Carotid artery intraplaque hemorrhage (IPH)-the presence of blood components within an atheromatous plaque-has become increasingly recognized as a possible etiologic mechanism in some cryptogenic strokes. IPH is a marker of plaque instability and is associated with ipsilateral neurologic ischemic events, even in nonstenotic carotid plaques. As recognition of carotid IPH as an etiology of embolic strokes has grown, so too has the complexity with which such patients are evaluated and treated, particularly because overlaps exist in the risk factors for atrial fibrillation and IPH. In this article, we review what is currently known about carotid IPH and how this clinical entity should be approached in the context of the evaluation of embolic strokes of undetermined source.

Cryptogenic Stroke and Embolic Stroke of Undetermined Source: Risk Factors and Approaches for Detection of Atrial Fibrillation.

BACKGROUND: Stroke is a problem worldwide because of its high mortality and disability rates. Almost 90% of strokes are ischemic, and more than half of the deaths are caused by an ischemic stroke. Most risk factors for stroke are manageable so that it can be avoided with proper prevention. Despite the success in determining the causes of stroke in recent years, selectively, the "culprit" causing stroke remains unsolved. In such cases, a diagnosis of undetermined etiology (cryptogenic stroke) or embolic stroke of undetermined source (ESUS) is generated, resulting the prevention of a recurrent cerebrovascular occurrence impossible. Atrial fibrillation (AF) can be a cause of stroke by causing blood clots in the chambers of the heart. PURPOSE: The aim was to determine the optimal method of heart rate monitoring in patients with ischemic stroke, as methods and approaches for detecting AF are very diverse, but there is still no single opinion, which would be universal. PROCEDURES: In our review, we consider epidemiology, risk factors for the stroke of undetermined etiology, as well as analytical methods for detecting heart rhythm disturbances in this category of patients. FINDINGS: Atrial fibrillation (AF) is detected by thorough monitoring of heart rate of patients with cryptogenic stroke and ESUS can be diagnosed in up to 46% of patients. . CONCLUSION: After AF detection, consideration should be given to prescribing anticoagulants, instead of antiplatelet agents, for the secondary prevention of stroke.

Assessment of patients with a suspected cardioembolic ischemic stroke. A national consensus statement.

OBJECTIVES: Several cardiovascular, structural, and functional abnormalities have been considered as potential causes of cardioembolic ischemic strokes. Beyond atrial fibrillation, other sources of embolism clearly exist and may warrant urgent action, but they are only a minor part of the many stroke mechanisms and strokes that seem to be of embolic origin remain without a determined source. The associations between stroke and findings like atrial fibrillation, valve calcification, or heart failure are confounded by co-existing risk factors for atherosclerosis and vascular disease. In addition, a patent foramen ovale which is a common abnormality in the general population is mostly an innocent bystander in patients with ischemic stroke. For these reasons, experts from the national Danish societies of cardiology, neurology, stroke, and neuroradiology sought to develop a consensus document to provide national recommendations on how to manage patients with a suspected cardioembolic stroke. Design: Comprehensive literature search and analyses were done by a panel of experts and presented at a consensus meeting. Evidence supporting each subject was vetted by open discussion and statements were adjusted thereafter. Results: The most common sources of embolic stroke were identified, and the statement provides advise on how neurologist can identify cases that need referral, and what is expected by the cardiologist. Conclusions: A primary neurological and neuroradiological assessment is mandatory and neurovascular specialists should manage the initiation of secondary prophylactic treatment. If a cardioembolic stroke is suspected, a dedicated cardiologist experienced in the management of cardioembolism should provide a tailored clinical and echocardiographic assessment.

Artificial Inteligence-Based Decision for the Prediction of Cardioembolism in Patients with Chagas Disease and Ischemic Stroke.

BACKGROUND: Chagas disease (CD) and ischemic stroke (IS) have a close, but poorly understood, association. There is paucity of evidence on the ideal secondary prophylaxis and etiological determination, with few cardioembolic patients being identified. AIMS: This study aimed to describe a multicenter cohort of patients with concomitant CD and IS admitted in tertiary centers and to create a predictive model for cardioembolic embolism in CD and IS. MATERIALS AND METHODS: We retrospectively studied data obtained from electronic medical and regular medical records of patients with CD and IS in several academic, hospital-based, and university hospitals across Brazil. Descriptive analyses of cardioembolic and non-cardioembolic patients were performed. A prediction model for cardioembolism was proposed with 70% of the sample as the derivation sample, and the model was validated in 30% of the sample. RESULTS: A total of 499 patients were analyzed. The median age was similar in both groups; however, patients with cardioembolic embolism were younger and tended to have higher alcoholism, smoking, and death rates. The predictive model for the etiological classification showed close relation with the number of abnormalities detected on echocardiography and electrocardiography as well as with vascular risk factors. CONCLUSIONS: Our results replicate in part those previously published, with a higher prevalence of vascular risk factors and lower median age in patients with cardioembolic etiology. Our new model for predicting cardioembolic etiology can help identify patients with higher recurrence rate and therefore allow an optimized strategy for secondary prophylaxis.

Secondary Stroke Prevention Following Embolic Stroke of Unknown Source in the Absence of Documented Atrial Fibrillation: A Clinical Review.

Approximately one-third of ischemic strokes are classified as cryptogenic strokes. The risk of stroke recurrence in these patients is significantly elevated with up to one-third of patients with cryptogenic stroke experiencing a further stroke within 10 years. While anticoagulation is the mainstay of treatment for secondary stroke prevention in the context of documented atrial fibrillation (AF), it is estimated that up to 25% of patients with cryptogenic stroke have undiagnosed AF. Furthermore, the historical acceptance of a causal relationship between AF and stroke has recently come under scrutiny, with evidence to suggest that embolic stroke risk may be elevated even in the absence of documented atrial fibrillation attributable to the presence of electrical and structural changes constituting an atrial cardiomyopathy. More recently, the term embolic stroke of unknown source has garnered increasing interest as a subset of patients with cryptogenic stroke in whom a minimum set of diagnostic investigations has been performed, and a nonlacunar infarct highly suspicious of embolic etiology is suspected but in the absence of an identifiable secondary cause of stroke. The ongoing ARCADIA (Atrial Cardiopathy and Antithrombotic Drugs in Prevention After Cryptogenic Stroke) randomized trial and ATTICUS (Apixiban for Treatment of Embolic Stroke of Undetermined Source) study seek to further define this novel term. This review summarizes the relationship between AF, embolic stroke, and atrial cardiomyopathy and provides an overview of the clinical relevance of cardiac imaging, electrocardiographic, and serum biomarkers in the assessment of AF and secondary stroke risk. The implications of these findings on therapeutic considerations is considered and gaps in the literature identified as areas for future study in risk stratifying this cohort of patients.

Trends, Predictors and Outcomes of Ischemic Stroke Among Patients Hospitalized with Takotsubo Cardiomyopathy.

OBJECTIVES: This study assessed the temporal trends in the incidence of ischemic stroke among patients hospitalized with takotsubo cardiomyopathy (TCM) stratified by the subtypes of ischemic stroke (cardioembolic versus thrombotic). Predictors of each stroke subtype, the association with atrial fibrillation (AF), the occurrence of ventricular fibrillation/ventricular tachycardia (VF/VT), cardiogenic shock (CS), in-hospital mortality, length of stay (LOS), and total healthcare cost were also assessed. BACKGROUND: Ischemic stroke in TCM is thought to be primarily cardioembolic from left ventricular mural thromboembolism. Limited data are available on the incidence of thrombotic ischemic stroke in TCM. MATERIALS AND METHODS: We identified 27,970 patients hospitalized with the primary diagnosis of TCM from the 2008 to 2017 National Inpatient Sample, of which 751 (3%) developed ischemic stroke. Of those with ischemic stroke, 571 (76%) had thrombotic stroke while 180 (24%) had cardioembolic stroke. Cochrane armitage test was used to assess the incidence of thrombotic and cardioembolic strokes and multivariate regression was used to identify risk factors associated with each stroke subtype. We compared the incidence of AF, VF/VT, CS, LOS, in-hospital mortality and total cost between hospitalized patients with TCM alone to those with cardioembolic and thrombotic strokes. RESULTS: From 2008 - 2017, the incidence of thrombotic stroke (4.7%-9.5% (p< 0.0001) increased while it was unchanged for cardioembolic stroke (0.5%-0.7% P=0.5). In the multivariate regression, peripheral artery disease, prior history of stroke, and hyperlipidemia were significantly associated with thrombotic stroke, while CS, AF, and Asian race (compared to White race) were associated with cardioembolic stroke. Both cardioembolic and thrombotic strokes were associated with higher odds of IHM, AF, CS, longer LOS and increased cost. Trends in in-hospital mortality and the utilization of thrombolysis, cerebral angiography, and mechanical thrombectomy among patients with TCM and ischemic stroke were unchanged from 2008 to 2017. CONCLUSION: Among patients with TCM and ischemic stroke, thrombotic stroke was more common compared to cardioembolic stroke. Ischemic stroke was associated with poorer outcomes, including higher in-hospital mortality and increased healthcare resource utilization in TCM.

Recurrent Ischemic Stroke - A Systematic Review and Meta-Analysis.

OBJECTIVES: Recurrent stroke remains a challenge though secondary prevention is initiated immediately post-stroke. Stroke subtype may determine the risk of recurrent stroke and require specific preventive measures. We aimed to identify subtype-specific stroke recurrence and associated risk factors over time. METHODS AND MATERIALS: A systematic review was performed using PubMed and Embase for studies including adults >18 years, first-ever ischemic stroke in population-based observational studies or registries, documented TOAST-criteria and minimum 1-year follow-up. Meta-analysis on stroke recurrence rate was performed. Final search: November 2019. RESULTS: The search retrieved 26 studies (between 1997 and 2019). Stroke recurrence rate ranged from 5.7% to 51.3%. Recurrent stroke was most frequent in large artery atherosclerosis (LAA) and cardioembolic (CE) stroke with recurrent stroke similar to index stroke subtype. We identified a lower recurrence rate for small vessel occlusion (SVO) stroke with recurrence frequently of another stroke subtype. Based on a meta-analysis the summary proportion recurrence rate of recurrent stroke in studies using TOAST-criteria = 0.12 and = 0.14 in studies using TOAST-like criteria. Hypertension, diabetes mellitus, atrial fibrillation previous transient ischemic attack, and high stroke severity were independent risk factors for recurrence. CONCLUSION: Stroke recurrence rates seem unchanged over time despite the use of secondary prevention. The highest recurrence rate is in LAA and CE stroke eliciting same subtype recurrent stroke. A lower recurrence rate is seen with SVO stroke with a more diverse recurrence pattern. Extensive workup is important in all stroke subtypes - including SVO stroke. Future research needs to identify better preventive treatment and improve compliance to risk factor prevention to reduce stroke recurrence.

Computational modeling identifies embolic stroke of undetermined source patients with potential arrhythmic substrate.

Cardiac magnetic resonance imaging (MRI) has revealed fibrosis in embolic stroke of undetermined source (ESUS) patients comparable to levels seen in atrial fibrillation (AFib). We used computational modeling to understand the absence of arrhythmia in ESUS despite the presence of putatively pro-arrhythmic fibrosis. MRI-based atrial models were reconstructed for 45 ESUS and 45 AFib patients. The fibrotic substrate's arrhythmogenic capacity in each patient was assessed computationally. Reentrant drivers were induced in 24/45 (53%) ESUS and 22/45 (49%) AFib models. Inducible models had more fibrosis (16.7 ± 5.45%) than non-inducible models (11.07 ± 3.61%; p<0.0001); however, inducible subsets of ESUS and AFib models had similar fibrosis levels (p=0.90), meaning that the intrinsic pro-arrhythmic substrate properties of fibrosis in ESUS and AFib are indistinguishable. This suggests that some ESUS patients have latent pre-clinical fibrotic substrate that could be a future source of arrhythmogenicity. Thus, our work prompts the hypothesis that ESUS patients with fibrotic atria are spared from AFib due to an absence of arrhythmia triggers.

The heart usually beats with a regular rhythm to pump the blood that carries oxygen and nutrients to different organs. Sometimes, alterations in the heart's rhythm known as arrhythmias can occur. Atrial fibrillation, also called AFib, is a type of arrhythmia in which the heart beats rapidly and irregularly, causing abnormal blood-flow that can lead to the formation of blood clots. If one of these blood clots travels to the brain, it can block a blood vessel, causing a stroke. However, many strokes occur without any evidence of AFib. One subset of strokes that are not associated with AFib are embolic strokes of undetermined source (ESUS), which account for 25% of all strokes. By definition ESUS and AFib do not occur together, but both are associated with similar elevated levels of disease-related remodeling (i.e., fibrosis) in the heart tissue, which appears when the heart is injured. Fibrosis impairs the heart's normal electrical activity. Bifulco et al. wanted to determine whether there is some fundamental difference in fibrosis between people with AFib and those who have had an ESUS event. To do this, they used a computational approach to model the geometries and patterns of fibrosis of the hearts of 45 ESUS patients and 45 patients with AFib, essentially producing a virtual version of each patient's heart. Bifulco et al. then applied a virtual pace-maker (working in overdrive mode) to each heart model to determine whether electrical inputs that can lead to AFib had different effects on ESUS and AFib patients. The results showed that the electrical inputs had similar effects in all of the heart models. This led Bifulco et al. to conclude that ESUS and AFib patients have indistinguishable patterns of fibrosis. The key difference is that ESUS patients are missing the trigger to initiate the fibrillation process ­ if atrial fibrosis is the proverbial tinderbox, these triggers are the spark needed to ignite a fire. Further research, including confirmation of Bifulco et al.'s findings in live patients, will be needed to confirm the hypothesis that ESUS patients lack AFib primarily due to an absence of triggers. If this is indeed the case, these findings may make it easier to identify ESUS patients at higher risk for AFib or further strokes. Additionally, a better understanding of fibrosis as a link between stroke and AFib will help clinicians provide better, more personalized treatments, for example guiding whether a patient should take blood thinners or undergo more rigorous cardiac monitoring.

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

BACKGROUND: Previous 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. METHODS: 436 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. RESULTS: AIS 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). CONCLUSION: BNP combined with echocardiographic parameters has outstanding value to predict the risk of cardioembolic stroke, especially for BNP and LAD.

Analyzing Cost-Effectiveness of Allocating Neurointerventionist for Drive and Retrieve System for Patients with Acute Ischemic Stroke.

OBJECTIVES: There are regional disparities in implementation rates of endovascular thrombectomy due to time and resource constraints such as endovascular thrombectomy specialists. In Hokkaido, Japan, Drive and Retrieve System (DRS), where endovascular thrombectomy specialists perform early endovascular thrombectomies by traveling from the facilities where they normally work to facilities closer to the patient. This study analyzed the cost-effectiveness of allocating a endovascular thrombectomy specialist for DRS to treat stroke patients. MATERIALS AND METHODS: he number of ischemic stroke patients expected to receive endovascular thrombectomy in Hokkaido in 2015 was estimated. It was assumed that an additional neutointerventionist was allocated for DRS. The analysis was performed from the government's perspective, which includes medical and nursing-care costs, and the personnel cost for endovascular thrombectomy specialist. The analysis was conducted comparing the current scenario, where patients received endovascular thrombectomy in facilities where endovascular thrombectomy specialists normally work, with the scenario with DRS within 60 min drive distance. Patient transport time was analyzed using geographic information system, and patient severity was estimated from the transport time. The primary outcome was incremental cost-effectiveness ratio (ICER) in each medical area which was calculated from the incremental costs and the incremental quality-adjusted life years (QALYs), estimated from patient severity using published literature. The entire process was repeated 100 times. RESULTS: DRS was most cost-effective in Kamikawachubu area, where the ICER was $14,173±16,802/QALY, significantly lower than the threshold that the Japanese guideline suggested. CONCLUSIONS: Since DRS was cost-effective in Kamikawachubu area, the area should be prioritized when a endovascular thrombectomy specialist for DRS is allocated as a policy.

First approach to distinguish between cardiac and arteriosclerotic emboli of individual stroke patients applying the histological THROMBEX-classification rule.

Endovascular treatment of strokes caused by large vessel occlusion enables the histopathological investigation of the retrieved embolus, possibly providing a novel opportunity to contribute to the diagnostic workup of etiology and to define secondary prevention measures in strokes with uncertain genesis. We aimed to develop a classification rule based on pathophysiological considerations and adjustment to reference thrombi for distinction between cardiac and arteriosclerotic emboli and to validate this classification rule on a patient cohort. From 125 patients with stroke due to large vessel occlusion and thrombectomy, 82 patients with known etiology (55 cardioembolic and 27 arterioembolic strokes) were included. The corresponding emboli were histologically evaluated by two raters blinded to the etiology of stroke by means of a novel classification rule. Presumed etiology and classification results were compared. Agreement concerning cardiac emboli was 72.2% (95% CI: 58.4-83.5) for rater I and 78.2% (95% CI: 65.0-88.2) for rater II. Agreement concerning arteriosclerotic emboli was 70.4% (95% CI: 49.8-86.3) for rater I and 74.1% (95% CI: 53.7-88.9) for rater II. Overall agreement reached 71.6% (95% CI: 60.5-81.1) for rater I and 76.8% (95% CI: 66.2-85.4) for rater II. Within the limits of generally restricted accuracy of histological evaluations, the classification rule differentiates between cardiac and arteriosclerotic emboli of acute ischemic stroke patients. Further improvement is needed to provide valuable complementary data for stroke etiology workup.

Endovascular Treatment of Infective Endocarditis-Related Acute Large Vessel Occlusion Stroke.

OBJECTIVES: Embolic stroke is a frequent complication of infective endocarditis yet lacks acute treatment as intravenous thrombolysis should be avoided due to high risk of intracerebral hemorrhage. Mechanical thrombectomy for large vessel occlusion may be a promising treatment but there is limited data on safety outcomes in infective endocarditis. MATERIALS AND METHODS: In this multi-center retrospective case series, we reviewed data from patients with infective endocarditis-related large vessel occlusion who underwent mechanical thrombectomy in 9 US hospitals. RESULTS: We identified 15 patients at 9 hospitals. A minority presented with signs suggesting infection (2 patients (14%) had fever, 7 (47%) were tachycardic, 2 (13%) were hypotensive, and 8 (53%) had leukocytosis). The median National Institute of Health Stroke Score decreased from 19 (range 9-25) at presentation to 7 post-thrombectomy (range 0-22, median best score post-thrombectomy), and the median modified Rankin Scale on or after discharge for survivors was 3 (range 0-6). Approximately 57% of patients had a modified Rankin Scale between 0 and 3 on or after discharge. Hemorrhagic transformation was observed in 7/15 (47%). The mechanical thrombectomy group had 2/9 petechial hemorrhagic transformation (22%), compared to 4/6 parenchymal hematomas (67%) in the tissue plasminogen activator + mechanical thrombectomy group. CONCLUSIONS: Our findings suggest that patients with large vessel occlusion due to infective endocarditis may not present with overt signs of infection. Mechanical thrombectomy may be an effective treatment in this patient population for whom intravenous thrombolysis should be avoided.

[Embolic stroke of undetermined source (ESUS) - Classification of a new stroke entity]. / Embolischer Schlaganfall mit ungeklärter Emboliequelle (ESUS) ­ Klassifikation einer neuen Schlaganfallentität.

Embolic stroke of undetermined source (ESUS) represents a subpopulation of cryptogenic strokes defined by its embolic stroke pattern on imaging and if after a carefully performed diagnostic evaluation, a specific, well recognized cause of stroke has not been identified. This review article analyses the basics of the ESUS concept and provides an overview of the evidence from recent cohort studies. The definition, aetiology and diagnosis of ESUS are reassessed. Targeted diagnostics in ESUS patients can reduce the number of cryptogenic strokes by making a specific diagnosis.

Sex Differences in Management and Outcomes of Cardioembolic Stroke: Post HOC Analyses of the RELAXED Study.

INTRODUCTION: Experimental models have clearly demonstrated sex differences in the pathophysiology of stroke and prognosis, however clinical evidence remains elusive. In this study, we examined sex differences as a post hoc analysis of RELAXED (Recurrent Embolism Lessened by rivaroxaban, an anti-X agent, of Early Dosing for acute IS and TIA with atrial fibrillation) Study. METHODS: We stratified study participants by sex and compared baseline and clinical characteristics as well as clinical outcomes. The primary outcome measure was a good outcome defined as a modified Rankin Scale score of 0-2 at 90 days after stroke. Secondary outcomes were mortality at 90 days, intracranial hemorrhage within 90 days, and recurrence of stroke or transient ischemic attack within 90 days. We constructed a logistic regression model to estimate the adjusted odds ratio of female patients compared with male patients for the primary and secondary outcomes. RESULTS: Of 1303 patients, most were male (57.7%) with a mean age of 74.5 years. Female patients were older with a mean age of 80.6 ± 8.9 years and had significantly less frequent anticoagulation therapy before onset of stroke and more severe NIHSS scores. Good outcome was observed in 51.2% and 63.3% of the females and males (p < 0.0001). The adjusted odds ratio of a good outcome in females was 1.12 (95% confidence interval, 0.44-2.87) (p = 0.81). There were no sex differences in secondary outcomes. CONCLUSION: Adjusted regression analysis found no sex difference in the treatment outcomes at 90 days after stroke with non-valvular atrial fibrillation.

Association of ACE2 variant rs4646188 with the risks of atrial fibrillation and cardioembolic stroke in Uygur patients with type 2 diabetes.

BACKGROUND: Atrial fibrillation (AF) is the most common cardiac arrhythmia. Type 2 diabetes (T2D) is an independent risk factor for AF. The cardioembolic stroke (CS) risk is increased when both conditions coexist. Whether angiotensin-converting enzyme 2 (ACE2) genetic variants predict increased risks AF and CS in Uygur patients with T2D remain elusive. METHODS: A total of 547 Uygur subjects (272 controls and 275 T2D patients) were recruited to the study from south Xinjiang. Eight ACE2 variants were identified by MassARRAY system. RESULTS: ACE2 rs2074192 (CC, adjusted RR = 2.55, 95% CI 1.35-4.80, P = 0.004), rs4240157 (CC + CT, adjusted RR = 2.26, 95% CI 1.27-4.04, P = 0.006) and rs4646188 (TT, adjusted RR = 2.37, 95% CI 1.16-4.86, P = 0.018) were associated with higher AF risk. ACE2 rs4240157 (CC + CT, adjusted RR = 2.68, 95% CI 1.36-5.27, P = 0.004) and rs4646188 (TT, adjusted RR = 2.56, 95% CI 1.06-6.20, P = 0.037) were further associated with higher CS risk. The 3 ACE2 variants were related to larger left atrial end-systolic diameter (LAD) (all P < 0.05), but not all of the 3 ACE2 variants were related to increased levels of serum sodium (rs4240157 and rs4646188, all P < 0.05), HsCRP (rs4240157 and rs4646188, all P < 0.05) as well as decreased serum potassium levels (rs2074192 and rs4646188, all P < 0.05). The 3 ACE2 variants exhibited heterogeneity on circulating RAAS activation. In particular, ACE2 rs4646188 was associated with higher levels of ACE (P = 0.017 and 0.037), Ang I (P = 0.002 and 0.001), Ang II (both P < 0.001) and ALD (P = 0.005 and 0.011). CONCLUSION: These results indicated ACE2 rs4646188 was associated with increased risk of AF and CS among diabetic patients in Uygurs, which could be a promising genetic predisposition marker for early and personalized prevention strategies for the aforementioned clinical pathologies.

Cardioembolic stroke: risk factors, clinical features, and early outcome in 956 consecutive patients

ABSTRACT Background: There is little information about the early clinical features of cardioembolic stroke before complementary examinations. Objective: The aim of this study was to identify risk factors, clinical features, and early outcomes of cardioembolic stroke. Methods: Retrospective study based on prospectively collected data available from a university medical center hospital-based stroke registry. Consecutive patients diagnosed with cardioembolic infarction were selected and compared to those diagnosed with an atherothrombotic stroke. Predictors of cardioembolic infarction were assessed by multivariate analysis. Results: From a cohort of 4597 consecutive patients, we studied 956 patients diagnosed with cardioembolic infarction (80 years [standard deviation (SD) 9.14]; 63% women) and 945 with atherothrombotic infarction (77.01 years [SD 9.75]; 49.8% women). The univariate comparative analysis reported that advanced age (≥ 85 years), female gender, atrial fibrillation (AF), ischemic heart disease, and congestive heart failure were significantly more frequent in the cardioembolic group, whereas hypertension, diabetes, peripheral vascular disease, heavy smoking, hyperlipidemia, and previous transient ischemic attack were significant in the atherothrombotic group. In the logistic regression model, AF (odds ratio [OR] 15.75, 95% confidence interval [CI]: 12.14-20.42), ischemic heart disease (OR 3.12, 95% CI: 2.16-4.5), female gender (OR 1.56, 95% CI: 1.22-2.00), and sudden-onset (OR 1.97, 95% CI: 1.54-2.51), were independent significant predictors of cardioembolic stroke. Conclusions: Potential cardioembolic stroke requires a comprehensive evaluation, since early classification and identification through predictors would improve effective management. (REV INVEST CLIN. 2021;73(1):23-30)

The Investigation of Left Atrial Structure and Stroke Etiology: The I-LASER Study.

Background Left atrial (LA) function is important in stroke, but often poorly characterized. We evaluated the association of 2-dimensional speckle tracking echocardiography LA variables with stroke subtype (cardioembolic stroke [CS] or cryptogenic stroke versus other). The hypothesis is worse LA active function is associated with CS, but not cryptogenic strokes. Methods and Results In this prospective cohort (2017-2019), left ventricular/LA structure and function were quantified by 2-dimensional and speckle tracking echocardiography in 151 patients with stroke. Strain/strain rate curves for the 3 components of the LA cycle, ie, (1) Reservoir (global longitudinal strain [Srmax]), (2) Conductive (early LA Sr [Sre]), and (3) Active (late LA strain [Sra]) were evaluated, masked to stroke subtype. Associations of cardiac features with stroke subtype were tested using multivariable logistic regressions. Odds of CS were increased in patients with a larger LA systolic diameter (odds ratio [OR], 2.96, 95% CI, 1.14-7.69) but reduced in patients with a higher Srmax (better reservoir) (OR, 0.80, 95% CI, 0.67-0.97). Lower Sra (worse function) was associated with an increased odds of CS (OR, 1.72, 95% CI, 1.07-2.76) but not independent of atrial fibrillation. Higher active LA emptying fraction (better active phase) was associated with reduced odds of CS (OR, 0.74, 95% CI, 0.57-0.95) or cryptogenic stroke (OR, 0.82, 95% CI, 0.68-0.98) versus other subtypes; other associations between cryptogenic stroke and speckle tracking echocardiography were not found. Conclusions Markers of LA structure and function were associated with CS. Similar associations were not found for cryptogenic stroke, which might suggest different underlying mechanisms, given study limitations. Further understanding could aid stroke diagnosis and secondary stroke prevention research.