Patients With Undetermined Stroke Have Increased Atrial Fibrosis

Fonseca, Ana Catarina; Alves, Pedro Nascimento; Inácio, Nuno; Marto, João Pedro; Viana-Baptista, Miguel; Pinho‐e‐Melo, Teresa; Ferro, José M.; Almeida, Ana G.

doi:10.1161/strokeaha.117.019641

Cited by 74 publications

(49 citation statements)

References 9 publications

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“…This result suggests that the undetermined stroke group may harbor a great proportion of nonrecognized cardioembolic strokes, which is in line with current knowledge in the clinical setting. In fact, it has been described that some patients with stroke of undetermined etiology may have atrial structural or functional changes thus increasing the risk of cardioembolism [34].…”

Section: Discussionmentioning

confidence: 99%

Circular RNA expression profile in blood according to ischemic stroke etiology

et al. 2020

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Background: The discovery of novel biomarkers of stroke etiology would be most helpful in management of acute ischemic stroke patients. Recently, circular RNAs (circRNAs) have been proposed as candidate biomarkers of neurological conditions due to its high stability. circRNAs function as sponges, sequestering miRNAs and are involved in most relevant biological functions. Our aim was to identify differentially expressed circRNAs in acute ischemic stroke patients according to stroke etiology. Methods: A comprehensive expression profile of blood circRNAs was conducted by Arraystar Human circRNA arrays (13,617 probes) on a discovery cohort of 30 stroke patients with different stroke etiologies by TOAST classification. Real-time quantitative PCR (RT-qPCR) was used to validate array results in a cohort of 50 stroke patients. Functional in silico analysis was performed to identify potential interactions with microRNAs (miRNAs) and pathways underlying deregulated circRNAs. Results: A set of 60 circRNAs were found to be upregulated in atherotrombotic versus cardioembolic strokes (foldchange > = 1.5 and p-value ≤ 0.05). Differential expression of hsa_circRNA_102488, originated from UBA52 gene, was replicated in the validation cohort. RNA-binding proteins (RBPs) sites of hsa_circRNA_102488 clustered around AGO2 and FUS proteins. Further functional analysis revealed interactions between deregulated circRNAs and a set of miRNAs involved in stroke-related pathways, such as fatty acid biogenesis or lysine degradation. Conclusion: Different stroke subtypes show specific profiles of circRNAs expression. circRNAs may serve as a new source of biomarkers of stroke etiology in acute ischemic stroke patients.

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Section: Discussionmentioning

confidence: 99%

Circular RNA expression profile in blood according to ischemic stroke etiology

et al. 2020

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“…Clinical studies are needed to confirm its utility and applicability as a protective agent in AIS. A recent study revealed that patients with atrial fibrillation of undetermined cause develop atrial fibrosis more frequently than those whose atrial fibrillation has a recognized cause, supporting the theory that chronic atrial remodeling could be associated with AIS [58]. Takotsubo cardiomyopathy is an example of left ventricular dysfunction that involves the apex and is associated with changes in cardiac biomarkers and electrocardiographic tracing.…”

Section: Left Ventricular Systolic and Diastolic Dysfunctionsmentioning

confidence: 93%

Brain–heart interaction after acute ischemic stroke

et al. 2020

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Early detection of cardiovascular dysfunctions directly caused by acute ischemic stroke (AIS) has become paramount. Researchers now generally agree on the existence of a bidirectional interaction between the brain and the heart. In support of this theory, AIS patients are extremely vulnerable to severe cardiac complications. Sympathetic hyperactivity, hypothalamic-pituitary-adrenal axis, the immune and inflammatory responses, and gut dysbiosis have been identified as the main pathological mechanisms involved in brain-heart axis dysregulation after AIS. Moreover, evidence has confirmed that the main causes of mortality after AIS include heart attack, congestive heart failure, hemodynamic instability, left ventricular systolic dysfunction, diastolic dysfunction, arrhythmias, electrocardiographic anomalies, and cardiac arrest, all of which are more or less associated with poor outcomes and death. Therefore, intensive care unit admission with continuous hemodynamic monitoring has been proposed as the standard of care for AIS patients at high risk for developing cardiovascular complications. Recent trials have also investigated possible therapies to prevent secondary cardiovascular accidents after AIS. Labetalol, nicardipine, and nitroprusside have been recommended for the control of hypertension during AIS, while beta blockers have been suggested both for preventing chronic remodeling and for treating arrhythmias. Additionally, electrolytic imbalances should be considered, and abnormal rhythms must be treated. Nevertheless, therapeutic targets remain challenging, and further investigations might be essential to complete this complex multi-disciplinary puzzle. This review aims to highlight the pathophysiological mechanisms implicated in the interaction between the brain and the heart and their clinical consequences in AIS patients, as well as to provide specific recommendations for cardiovascular management after AIS.

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“…It might explain the reason why neither total EAT or BMI was not associated with the ES in the present study. Of note, LA fibrosis has been associated with a higher incidence of stroke or TIA in patients with AF regardless of CA . The mechanism of correlation between EAT and ES might be explained by EAT‐mediated atrial cardiomyopathy, which features LA enlargement, increased wall stiffness, hypercontractility, endothelial dysfunction, or impaired reservoir function, and contributes to atrial prothrombotic milieu …”

Section: Discussionmentioning

confidence: 99%

Association between epicardial adipose tissue and embolic stroke after catheter ablation of atrial fibrillation

Ahn

Shin

Shim

et al. 2019

Cardiovasc electrophysiol

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Introduction Risk factors of embolic stroke (ES) after atrial fibrillation (AF) ablation have not been fully elucidated especially among the Asian subjects, particularly regarding epicardial adipose tissue (EAT) in cardiac imaging. We aimed to assess the incidence of ES during a long‐term follow‐up period after AF ablation and to identify the risk factors associated with postablation ES, specifically focusing on EAT. Methods and Results We enrolled patients who experienced postablation ES and control subjects from a consortium of AF ablation registries from three institutes in Korea. EAT was assessed using multislice computed tomography before AF ablation. A total of 3464 patients who underwent AF ablation were recruited and followed‐up. During a follow‐up of 47.2 ± 36.4 months, ES occurred in 47 patients (1.36%) with a CHA2DS2‐VASc score of 1.48 ± 1.39 and the overall annual incidence of ES was 0.34%. Compared with the control group (n = 190), the ES group showed significantly higher prior thromboembolism (TE) and AF recurrence rates, larger left atrium size, lower creatinine clearance rate (CCr), and greater total and peri‐atrial EAT volume. Multivariate regression analysis demonstrated larger peri‐atrial EAT volume (hazards ratio, 1.065; 95% confidence interval, 1.005‐1.128), in addition to a prior history of TE and lower CCr, was independently associated with postablation ES. When a cut‐off value of peri‐atrial EAT volume of ≥20.15 mL was applied, patients with smaller peri‐atrial EAT volume showed significantly higher ES‐free survival. Conclusion Larger peri‐atrial EAT volume, in addition to prior TE and lower CCr, was independently associated with postablation ES regardless of AF recurrence and CHA2DS2‐VASc score. (ClinicalTrials.gov number, NCT03479073).

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Patients With Undetermined Stroke Have Increased Atrial Fibrosis

Abstract: The LA phenotype that was found in patients with undetermined cause supports the hypothesis that an atrial disease may be associated with stroke.

Cited by 74 publications

References 9 publications

Circular RNA expression profile in blood according to ischemic stroke etiology

Circular RNA expression profile in blood according to ischemic stroke etiology

Brain–heart interaction after acute ischemic stroke

Association between epicardial adipose tissue and embolic stroke after catheter ablation of atrial fibrillation

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