Project description:INTRODUCTION:Cryptogenic stroke accounts for approximately 30% of all ischemic strokes. Recently, atrial cardiopathy diagnosed by the presence of one of its serum, imaging, or electrocardiogram biomarkers has been shown to be associated with ischemic stroke, particularly of embolic subtypes. Areas covered: This paper aims to summarize data on occult atrial fibrillation and stroke, provide an overview on mechanisms, such as inflammation and fibrosis, of stroke in atrial cardiopathy, critically review data on biomarkers of atrial cardiopathy and their association with stroke, and suggest therapeutic implications, including directions for future research. Expert commentary: Atrial cardiopathy may constitute one of the mechanisms in cryptogenic stroke, and patients with evidence of atrial cardiopathy constitute a group of patients in whom clinical trials are warranted to test anticoagulation versus antiplatelet therapy to reduce stroke recurrence risk. In addition, more studies are needed to determine the degree of overlap between these atrial cardiopathy biomarkers and which one is more useful in predicting the risk of stroke and response to anticoagulation therapy.
Project description:ObjectiveCerebral microbleeds (CMB) are small accumulations of hemosiderin associated with cerebrovascular risk factors, but whether they are associated with atrial cardiopathy is not known. The goal of this study is to determine, among ischemic stroke patients, the association between study-defined atrial cardiopathy and CMB presence, location, and number.MethodsIschemic stroke patients admitted to Johns Hopkins (2015-2019) with transthoracic echocardiography and electrocardiography were included. Cerebral microbleeds were defined as small, round hypo-intensities on T2* susceptibility weighted imaging or gradient recalled echo magnetic resonance imaging sequences. Atrial cardiopathy was defined as the presence of ≥1: left atrium diameter >4.0 cm (males) or >3.8 cm (females), PR interval >200 ms, or N-terminal pro-B-type natriuretic peptide >250 pg/ml. Binary/Ordinal logistic regression models were used to determine the association between atrial cardiopathy, and cerebral microbleed presence, location (lobar/deep), or number, each, adjusted for potential confounders.ResultsPatients (N = 120) were mean age 60 years (range 22-98), 46% female, 62% black, and 39% were on anti-thrombotic medication at time of admission. 39 (32%) participants had ≥1 cerebral microbleeds. Forty-six (38%) patients had atrial cardiopathy. Atrial cardiopathy was associated with higher odds of having cerebral microbleeds (OR 2.50, 95% CI 1.02-6.15). Atrial cardiopathy was associated with lobar cerebral microbleeds (OR 2.33, 95% CI 1.01-5.37) in univariate analysis but not with deep cerebral microbleeds (OR 0.45, 95% CI 0.13-1.54), with neither association significant after adjustment. There was no difference in risk of having 1 vs. no cerebral microbleeds (RRR 2.51, 95% CI 0.75-8.37) and >1 cerebral microbleed vs none (RRR 2.57, 95% CI 0.87-7.60) among those with atrial cardiopathy.ConclusionsAtrial cardiopathy is associated with the presence, but not burden, of cerebral microbleeds in ischemic stroke patients. We cautiously suggest that atrial cardiopathy, either directly or through shared vascular risk, may contribute to the presence of CMB.
Project description:IntroductionWhether atrial cardiopathy is associated with stroke prognosis remains unclear. We evaluated the association between atrial cardiopathy markers and outcomes in patients with ischemic stroke using a nationwide prospective registry.Patients and methodsBased on the Third China National Stroke Registry, we evaluated different atrial cardiopathy markers including increased P-wave terminal force in V1 (PTFV1), advanced interatrial block (aIAB), prolonged P-wave duration, prolonged P-wave dispersion, paroxysmal supraventricular tachycardia, premature atrial contractions, prolonged PR interval, and severe left atrial enlargement in ischemic stroke patients. The outcomes were death and ischemic stroke recurrence at 1 year. The association between atrial cardiopathy markers and outcomes was analyzed using Cox regression models.ResultsAt 1-year follow-up, 486 (3.4%) patients had died and 1317 (9.3%) patients had experienced ischemic stroke recurrence. After adjustment for clinical risk factors including atrial fibrillation, PTFV1 > 5000 μV·ms (adjusted hazard ratio [HR] 1.70, 95% confidence interval [CI]: 1.18-2.45, p = 0.004) and aIAB (adjusted HR 1.47, 95% CI: 1.14-1.91, p = 0.003) were significantly associated with mortality. PTFV1 > 5000 μV·ms was significantly associated with ischemic stroke recurrence (adjusted HR 1.54, 95% CI: 1.22-1.96, p = 0.0004). This association was observed although we excluded patients diagnosed with atrial fibrillation.Discussion and conclusionAtrial cardiopathy markers, especially PTFV1 and aIAB, are significantly associated with a higher risk of poor prognosis in patients with ischemic stroke.
Project description:Background Atrial fibrillation (AF) is a major, often undetected, cardiac cause of stroke. Markers of atrial cardiopathy, including left atrial enlargement (LAE) or excessive atrial ectopy (EAE) increase the risk of AF and have shown associations with stroke. We sought to determine whether these markers improve stroke risk prediction beyond traditional vascular risk factors (eg CHA2DS2-VASc score). Methods and Results Retrospective longitudinal cohort of 32 454 consecutive community-dwelling adults aged ≥65 years referred for outpatient echocardiogram or Holter in Ontario, Canada (2010-2017). Moderate-severe LAE was defined as men >47 mm and women >43 mm, and EAE was defined as >30 APBs per hour. Cause-specific competing risks Cox proportional hazards used to estimate risk of ischemic stroke (primary), incident AF, and death (secondary). C-statistics, incremental discrimination improvement and net reclassification were used to compare CHA2DS2-VASc with LAE and EAE to CHA2DS2-VASc alone. Each 10 mm increase in left atrial diameter increased 2- and 5-year adjusted cause-specific stroke hazard almost 2-fold (LAE: 2-year hazard ratio (HR), 1.72; P=0.007; 5-year HR, 1.87; P<0.0001), while EAE showed no significant associations with stroke (2-year HR, 1.00; P=0.99; 5-year HR, 1.08, P=0.70), adjusting for incident AF. Stroke risk estimation improved significantly at 2 (C-statistics=0.68-0.75, P=0.008) and 5 years (C-statistics=0.70-0.76, P=0.003) with LAE and EAE. Conclusions LAE was independently associated with an increased risk of ischemic stroke in the absence of AF and both LAE and EAE improved stroke risk prediction. These findings have implications for stroke risk stratification, AF screening, and stroke prevention before the onset of AF.
Project description:Background: The left atrial appendage (LAA) is a major source of thrombus and non-chicken wing (CW). LAA morphology is a risk factor for embolic events in atrial fibrillation. However, the association of non-CW morphology with embolic stroke recurrence is unknown in patients with embolic stroke of undetermined source (ESUS) and atrial cardiopathy. Methods: We conducted retrospective analyses using a prospective institutional stroke registry (2013-2017). Patients with ESUS and atrial cardiopathy were enrolled. Atrial cardiopathy was diagnosed if an increased left atrial diameter (>40 mm, men; >38 mm, women), supraventricular tachycardia, or LAA filling defect on computed tomography (CT) were present. Patients admitted >24 h after onset were excluded. LAA morphology was evaluated using CT and categorized into CW vs. non-CW types. The primary outcome was embolic stroke recurrence. Multivariable Cox proportional hazards models were used to examine the independent association between LAA morphology and outcome. Results: Of 157 patients, 81 (51.6%) had CW LAA morphology. The median follow-up was 41.5 (interquartile range 12.3-58.5) months corresponding to 509.8 patient years. In total, 18 participants experienced embolic stroke recurrences (3.80 per 100 patient-years). Non-CW morphology was more associated with embolic stroke recurrence than CW morphology (hazard ratio (HR), 3.17; 95% confidence interval (CI), 1.13-8.91; p = 0.029). After adjusting for CHA2DS2-VASc score and number of potential embolic sources, non-CW morphology showed an independent association with outcome (adjusted HR, 2.90; 95% CI, 1.02-8.23; p = 0.045). Conclusions: The LAA morphology types may help identify high risk of embolic stroke recurrence in ESUS with atrial cardiopathy. LAA morphology in atrial cardiopathy may provide clues for developing therapies tailored to specific mechanisms.
Project description:Background and purposeEmerging evidence suggests that an underlying atrial cardiopathy may result in thromboembolism before atrial fibrillation (AF) develops. We examined the association between various markers of atrial cardiopathy and the risk of ischemic stroke.MethodsThe CHS (Cardiovascular Health Study) prospectively enrolled community-dwelling adults ≥65 years of age. For this study, we excluded participants diagnosed with stroke or AF before baseline. Exposures were several markers of atrial cardiopathy: baseline P-wave terminal force in ECG lead V1, left atrial dimension on echocardiogram, and N terminal pro B type natriuretic peptide (NT-proBNP), as well as incident AF. Incident AF was ascertained from 12-lead electrocardiograms at annual study visits for the first decade after study enrollment and from inpatient and outpatient Medicare data throughout follow-up. The primary outcome was incident ischemic stroke. We used Cox proportional hazards models that included all 4 atrial cardiopathy markers along with adjustment for demographic characteristics and established vascular risk factors.ResultsAmong 3723 participants who were free of stroke and AF at baseline and who had data on all atrial cardiopathy markers, 585 participants (15.7%) experienced an incident ischemic stroke during a median 12.9 years of follow-up. When all atrial cardiopathy markers were combined in 1 Cox model, we found significant associations with stroke for P-wave terminal force in ECG lead V1 (hazard ratio per 1000 μV*ms 1.04; 95% confidence interval, 1.001-1.08), log-transformed NT-proBNP (hazard ratio per doubling of NT-proBNP, 1.09; 95% confidence interval, 1.03-1.16), and incident AF (hazard ratio, 2.04; 95% confidence interval, 1.67-2.48) but not left atrial dimension (hazard ratio per cm, 0.96; 95% confidence interval, 0.84-1.10).ConclusionsIn addition to clinically apparent AF, other evidence of abnormal atrial substrate is associated with subsequent ischemic stroke. This finding is consistent with the hypothesis that thromboembolism from the left atrium may occur in the setting of several different manifestations of atrial disease.
Project description:Background and Purpose- Atrial cardiopathy and atherosclerotic plaque are two potential mechanisms underlying embolic strokes of undetermined source (ESUS). The relationship between these two mechanisms among ESUS patients remains unclear. A better understanding of their association may inform targeted secondary prevention strategies. Methods- We examined the association between atrial cardiopathy and atherosclerotic plaque in the NAVIGATE ESUS trial (New Approach Rivaroxaban Inhibition of Factor Xa in a Global Trial Versus ASA to Prevent Embolism in Embolic Stroke of Undetermined Source), which enrolled 7213 patients with recent ESUS during 2014 to 2017. For this analysis, we included patients with data on left atrial dimension, location of brain infarction, and cervical large artery plaque. The variables of primary interest were left atrial diameter and cervical plaque ipsilateral to brain infarction. Secondary markers of atrial cardiopathy were premature atrial contractions on Holter monitoring and newly diagnosed atrial fibrillation. For descriptive purposes, left atrial enlargement was defined as ≥4.7 cm. Multivariable logistic regression was used to examine the association between atrial cardiopathy markers and ipsilateral plaque after adjustment for age, sex, body mass index, hypertension, diabetes mellitus, current smoking, and hyperlipidemia. Results- Among 3983 eligible patients, 235 (5.9%) had left atrial enlargement, 939 (23.6%) had ipsilateral plaque, and 94 (2.4%) had both. Shared risk factors for left atrial enlargement and ipsilateral plaque were male sex, white race, hypertension, tobacco use, and coronary artery disease. Despite shared risk factors, increasing left atrial dimension was not associated with ipsilateral plaque after adjustment for covariates (odds ratio per cm, 1.1 [95% CI, 1.0-1.2]; P=0.08). We found no consistent associations between secondary markers of atrial cardiopathy and ipsilateral plaque. Conclusions- In a large population of patients with ESUS, we did not observe a notable association between atrial cardiopathy and atherosclerotic plaque, and few patients had both conditions. These findings suggest that atrial cardiopathy and atherosclerotic plaque may be distinct, nonoverlapping risk factors for stroke among ESUS patients.
Project description:BackgroundAtrial cardiopathy (AC) has emerged as a potential pathological thrombogenic atrial substract of embolic stroke of undetermined source (ESUS), even in the absence of atrial fibrillation. Left atrium (LA) myocardial deformation analysis may be of value as a subclinical marker of AC and a predictor of ESUS.AimsTo compare LA mechanical function between ESUS cases and age and sex-matched controls.MethodsA single-center analytical study with case-control design was performed. Case group was composed by young patients admitted in the Neurology department from January 2017 to June 2021. Control group was composed by age and sex matched controls recruited from the community. All participants performed echocardiogram and a smaller sample underwent cardiac magnetic resonance.ResultsWe recruited 31 ESUS patients aged between 18 and 65 years and 31 age and sex matched controls. ESUS patients had a significantly higher prevalence of cardiovascular risk factors and patent foramen ovale (PFO). The prevalence of AC was not different between groups. Echocardiogram parameters, including strain analysis, were similar between groups, except for LA appendage (LAA) ostium variation which was significantly lower in ESUS patients (absolute: 6.5vs8.7mm, p<0.001; relative: 44.5%vs53.4%, p=0.002). After exclusion of patients with PFO, all the results were statistically similar. Regarding cardiac magnetic resonance analysis, there were no statistically significant differences between groups.ConclusionThis study shows that in our population atria cardiopathy and atrial function was not associated with ESUS.LAA structural and functional abnormalities may play a major role. The role of LAA in ESUS warrants further studies.
Project description:ImportanceAtrial cardiopathy is associated with stroke in the absence of clinically apparent atrial fibrillation. It is unknown whether anticoagulation, which has proven benefit in atrial fibrillation, prevents stroke in patients with atrial cardiopathy and no atrial fibrillation.ObjectiveTo compare anticoagulation vs antiplatelet therapy for secondary stroke prevention in patients with cryptogenic stroke and evidence of atrial cardiopathy.Design, setting, and participantsMulticenter, double-blind, phase 3 randomized clinical trial of 1015 participants with cryptogenic stroke and evidence of atrial cardiopathy, defined as P-wave terminal force greater than 5000 μV × ms in electrocardiogram lead V1, serum N-terminal pro-B-type natriuretic peptide level greater than 250 pg/mL, or left atrial diameter index of 3 cm/m2 or greater on echocardiogram. Participants had no evidence of atrial fibrillation at the time of randomization. Enrollment and follow-up occurred from February 1, 2018, through February 28, 2023, at 185 sites in the National Institutes of Health StrokeNet and the Canadian Stroke Consortium.InterventionsApixaban, 5 mg or 2.5 mg, twice daily (n = 507) vs aspirin, 81 mg, once daily (n = 508).Main outcomes and measuresThe primary efficacy outcome in a time-to-event analysis was recurrent stroke. All participants, including those diagnosed with atrial fibrillation after randomization, were analyzed according to the groups to which they were randomized. The primary safety outcomes were symptomatic intracranial hemorrhage and other major hemorrhage.ResultsWith 1015 of the target 1100 participants enrolled and mean follow-up of 1.8 years, the trial was stopped for futility after a planned interim analysis. The mean (SD) age of participants was 68.0 (11.0) years, 54.3% were female, and 87.5% completed the full duration of follow-up. Recurrent stroke occurred in 40 patients in the apixaban group (annualized rate, 4.4%) and 40 patients in the aspirin group (annualized rate, 4.4%) (hazard ratio, 1.00 [95% CI, 0.64-1.55]). Symptomatic intracranial hemorrhage occurred in 0 patients taking apixaban and 7 patients taking aspirin (annualized rate, 1.1%). Other major hemorrhages occurred in 5 patients taking apixaban (annualized rate, 0.7%) and 5 patients taking aspirin (annualized rate, 0.8%) (hazard ratio, 1.02 [95% CI, 0.29-3.52]).Conclusions and relevanceIn patients with cryptogenic stroke and evidence of atrial cardiopathy without atrial fibrillation, apixaban did not significantly reduce recurrent stroke risk compared with aspirin.Trial registrationClinicalTrials.gov Identifier: NCT03192215.
Project description:Background The contribution of atrial cardiopathy to dementia risk is uncharacterized. We aimed to evaluate the association of atrial cardiopathy with incident dementia and potential mediation by atrial fibrillation (AF) and stroke. Methods and Results We conducted a prospective cohort analysis of participants in the ARIC (Atherosclerosis Risk in Communities) study attending visit 5 (2011-2013). We used Cox regression to determine the association between atrial cardiopathy and risk of dementia. Structural equation modeling methods were used to determine potential mediation by AF and/or stroke. Atrial cardiopathy was defined if ≥1 of the following at visit 5: P-wave terminal force >5000 mV·ms in ECG lead V1, NT-proBNP (N-terminal pro-brain natriuretic peptide) >250 pg/mL or left atrial volume index ≥34 mL/m2 by transthoracic echocardiography. We repeated our analysis necessitating ≥2 markers to define atrial cardiopathy. The prevalence of atrial cardiopathy was 34% in the 5078 participants (mean age 75 years, 59% female, 21% Black adults), with 763 participants developing dementia. Atrial cardiopathy was significantly associated with dementia (adjusted HR, 1.35 [95% CI, 1.16-1.58]), with strengthening of the effect estimate when necessitating ≥2 biomarkers (adjusted HR, 1.54 [95% CI, 1.25-1.89]). There was an increased risk of dementia among those with atrial cardiopathy when excluding those with AF (adjusted HR, 1.31 [95% CI, 1.12-1.55]) or stroke (adjusted HR, 1.28 [95% CI, 1.09-1.52]). The proportion of the effect mediated by AF was 4% (P=0.005), and 9% was mediated by stroke (P=0.048). Conclusions Atrial cardiopathy was significantly associated with an increased risk of dementia, with only a small percent mediation of the effect by AF or stroke.