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Markers of endothelial pathology to support detection of atrial fibrillation in embolic stroke of undetermined source.

ABSTRACT: A relevant part of embolic strokes of undetermined source (ESUS) is assumed to be cardiogenic. As shown previously, certain biomarkers of endothelial pathology are related to atrial fibrillation (AF). In this long-term follow-up study, we aimed to investigate whether these biomarkers are associated with subsequently diagnosed AF and with atrial cardiopathy. In 98 patients who suffered ischemic stroke of known and unknown origin L-arginine, Asymmetric (ADMA) and Symmetric Dimethylarginine (SDMA) have been measured on follow-up at least one year after index stroke. Stroke-diagnostics were available for all patients, including carotid Intima-Media-Thickness (CIMT) and comprehensive echocardiography studies. CIMT was larger in AF- compared with ESUS-patients (P?2DS₂VASC in the regression analysis (P?=?0.004). SDMA-values were stable over time (P?2DS₂VASC and renal function in the regression analysis (P?=?0.02 and P?=?0.005, respectively). In conclusion, these results highlight SDMA and CIMT as potential markers of atrial cardiopathy and AF in ESUS-patients.

SUBMITTER: Ziegler NL

PROVIDER: S-EPMC6923420 | biostudies-literature | 2019 Dec

REPOSITORIES: biostudies-literature

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Markers of endothelial pathology to support detection of atrial fibrillation in embolic stroke of undetermined source.

Ziegler Nora L NL Sieweke Jan-Thorben JT Biber Saskia S Gabriel Maria M MM Schuppner Ramona R Worthmann Hans H Martens-Lobenhoffer Jens J Lichtinghagen Ralf R Bode-Böger Stefanie M SM Bavendiek Udo U Weissenborn Karin K Grosse Gerrit M GM

Scientific reports 20191219 1

A relevant part of embolic strokes of undetermined source (ESUS) is assumed to be cardiogenic. As shown previously, certain biomarkers of endothelial pathology are related to atrial fibrillation (AF). In this long-term follow-up study, we aimed to investigate whether these biomarkers are associated with subsequently diagnosed AF and with atrial cardiopathy. In 98 patients who suffered ischemic stroke of known and unknown origin L-arginine, Asymmetric (ADMA) and Symmetric Dimethylarginine (SDMA) ...[more]

PMID: 31857660

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Project description:ObjectivePrevention of recurrent stroke in patients with embolic stroke of undetermined source (ESUS) is challenging. The advent of safer anticoagulation in the form of direct oral anticoagulants (DOACs) has prompted exploration of prophylactic anticoagulation for all ESUS patients, rather than anticoagulating just those with documented atrial fibrillation (AF). However, recent trials have failed to demonstrate a clinical benefit, while observing increased bleeding. We modeled the economic impact of anticoagulating ESUS patients without documented AF across multiple geographies.MethodsCRYSTAL-AF trial data were used to assess ischaemic stroke event rates in ESUS patients confirmed AF-free after long-term monitoring. Anticipated bleeding event rates (including both minor and major bleeds) with aspirin, dabigatran 150 mg, and rivaroxaban 20 mg were sourced from published meta-analyses, whilst a 30% ischaemic stroke reduction for both DOACs was assumed. Cost data for clinical events and pharmaceuticals were collected from the local payer perspective.ResultsCompared with aspirin, dabigatran and rivaroxaban resulted in 17.9 and 29.9 additional bleeding events per 100 patients over a patient's lifetime, respectively. Despite incorporating into our model the proposed 30% reduction in ischaemic stroke risk, both DOACs were cost-additive over patient lifetime, as the costs of bleeding events and pharmaceuticals outweighed cost savings associated with the reduction in ischaemic strokes. DOACs added £5953-£7018 per patient (UK), €6683-€7368 (Netherlands), €4933-€9378 (Spain), AUD$5353-6539 (Australia) and $26,768-$32,259 (US) of payer cost depending on the agent prescribed. Additionally, in the U.S. patient pharmacy co-payments ranged from $2468-$12,844 depending on agent and patient plan. In all settings, cost-savings could not be demonstrated even when the modelling assumed 100% protection from recurrent ischaemic strokes, due to the very low underlying risk of recurrent ischaemic stroke in this population (1.27 per 100 patient-years).ConclusionsAnticoagulation of non-AF patients may cause excess bleeds and add substantial costs for uncertain benefits, suggesting a personalised approach to anticoagulation in ESUS patients.

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:AimsStroke is the most debilitating outcome of atrial fibrillation (AF). The use of implantable loop recorders increases the detection of AF episodes among patients with embolic stroke of undetermined source. The significance of device-detected AF, or subclinical AF, is unknown. This study aimed to compare the incidence of AF detected by implantable loop recorder in patients with and without embolic stroke of undetermined source.Methods and resultsWe retrospectively studied all patients without known AF who were referred to our institution for implantable loop recorder implantation following embolic stroke of undetermined source, syncope, or palpitations from March 2009 to November 2019. The primary endpoint was any detection of AF or atrial flutter by implantable loop recorder. Seven hundred and fifty patients were included and followed up for a mean duration of 731 days (SD 443). An implantable loop recorder was implanted following embolic stroke of undetermined source in 323 and for assessment of syncope, palpitations, or another reason in 427 patients. The incidence of AF was significantly (P < 0.001) higher among patients with embolic stroke of undetermined source compared with the non-embolic stroke of undetermined source group; 48.6% vs. 13.8% (for any duration of AF) and 32.2% vs. 12.4% (for AF lasting ≥30 s) both P < 0.001. Kaplan-Meier analysis showed significantly higher incidence of AF for incremental durations of AF up to >5.5 h, but not >24 h. This was driven by longest AF durations of <6 min and between 5.5 h and 24 h, suggesting a bimodal distribution. In a multivariable Cox regression analysis, embolic stroke of undetermined source independently conferred an almost 5-fold increase in the hazard for any duration of AF.ConclusionThe incidence of AF is significantly higher amongst embolic stroke of undetermined source vs. non-embolic stroke of undetermined source patients monitored constantly by an implantable loop recorder. A high number of embolic stroke of undetermined source survivors have short-duration AF episodes. Further work is needed to determine the optimal treatment strategy of these AF episodes in embolic stroke of undetermined source.

Dataset Information

Markers of endothelial pathology to support detection of atrial fibrillation in embolic stroke of undetermined source.

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Markers of endothelial pathology to support detection of atrial fibrillation in embolic stroke of undetermined source.

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