Detection and management of atrial fibrillation after cryptogenic stroke or embolic stroke of undetermined source.
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ABSTRACT:
SUBMITTER: Sanna T
PROVIDER: S-EPMC6490022 | biostudies-literature | 2018 Mar
REPOSITORIES: biostudies-literature
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Detection and management of atrial fibrillation after cryptogenic stroke or embolic stroke of undetermined source.
Sanna Tommaso T Ziegler Paul D PD Crea Filippo F
Clinical cardiology 20180322 3
Cryptogenic stroke (CS) and embolic stroke of unknown source (ESUS) represent a major challenge to healthcare systems worldwide. Atrial fibrillation (AF) is commonly found after CS or ESUS. Independent of the mechanism of the index CS or ESUS, detection of AF in these patients offers the opportunity to reduce the risk of stroke recurrence by prescribing an anticoagulant instead of aspirin. The detection of AF may be pursued with different monitoring strategies. Comparison of monitoring strategie ...[more]
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Project description: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?<?0.001), independently from CHA2DS2VASC in the regression analysis (P?=?0.004). SDMA-values were stable over time (P?<?0.001; r?=?0.788), whereas for ADMA moderate correlation with the initial values could be found (P?=?0.007; r?=?0.356). According to Kaplan-Meier-analyses, AF-detection rates were associated with CIMT (P?=?0.003) and SDMA (P?<?0.001). SDMA correlated with left atrial volume-index within the whole collective (P?=?0.003, r?=?0.322) and within the ESUS-subgroup (P?=?0.003; r?=?0.446). These associations were independent from CHA2DS2VASC 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.
| S-EPMC6923420 | biostudies-literature
Project description:BackgroundCovert atrial fibrillation (AF) is a predominant aetiology of embolic stroke of undetermined source (ESUS). Evidence suggested that AF is more frequently detected by implantable loop recorder (ILR) than by conventional monitoring. However, the predictive factors associated with occult AF detected using ILRs are not well established yet. In this study we aim to investigate the predictors of AF detection in patients with ESUS undergoing an ILR.MethodsThis observational multi-centre study included consecutive ESUS patients who underwent ILR implantation. The infarcts were divided in deep, cortical infarcts or both. The infarction sites were categorized as anterior and middle cerebral artery, posterior cerebral artery with and without brainstem/cerebellum involvement. Multivariable logistic regression analysis was performed to investigate variables associated with AF detection.ResultsOverall, 3,000 patients were initially identified. However, in total, 127 patients who consecutively underwent ILR implantation were included in our analysis. AF was detected in 33 (26%) out of 127 patients. The median follow-up was 411 days. There were no significant differences in clinical characteristics and comorbidities between patients with and without AF detected. AF was detected more often after posterior cerebral artery infarct with brainstem/cerebellum involvement (p < 0.001) whereas less often after infarction in the anterior and middle cerebral artery (p = 0.021). Multivariable regression analysis demonstrated that posterior cerebral artery infarct with brainstem/cerebellum involvement was an independent predictor of AF detection.ConclusionOur study showed that posterior circulation infarcts with brainstem/cerebellum involvement are associated with AF detection in ESUS patients undergoing ILR. Larger prospective studies are needed to validate our findings.
| S-EPMC10944994 | biostudies-literature
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.
| S-EPMC8015049 | biostudies-literature
Project description:BackgroundDetection of atrial fibrillation (AF) in patients with embolic stroke of undetermined source (ESUS) is challenging due to its paroxysmal nature. We sought to assess AF detection with an insertable cardiac monitor (ICM) and to perform cost analysis for various AF monitoring strategies post-ESUS We applied this cost analysis modeling to recently published Stroke AF and Per Diem trials.MethodsRetrospective chart review was performed in consecutive hospitalized patients with ESUS who had ICM placed prior to discharge. Utilizing rate of ICM-detected AF and Medicare average payments, we modeled 30-day per-patient diagnostic costs of Immediate ICM insertion prior to discharge versus using a wearable monitor followed by ICM in patients with ESUS, from Medicare and patient out-of-pocket perspectives. Similar modeling strategy and cost analysis was applied to the Stroke AF and Per Diem trials.ResultsIn 192 ESUS patients, AF detection increased with length of monitoring: 7.3 % at 14 days, 9.4 % at 30 days, and 17.2 % after a median ~ 6 months (189 days). Cost modeling predicted that immediate ICM leads to $3683-$4070 lower Medicare payments per-patient and $1425-$1503 lower patient out-of-pocket costs compared to Wearable-to-ICM strategies. Using similar modeling in the PER DIEM and STROKE AF trials, the additive costs of the 30-day ELR to ICM strategy ranged from $3786-$3946 from a payer perspective and $1472-$1503 from a patient out-of-pocket perspective.ConclusionsUse of ICM immediately after ESUS is cost-saving compared to Wearable-to-ICM strategies, due to the cost and low diagnostic yield of short-term wearable cardiac monitoring.
| S-EPMC10978394 | biostudies-literature
Project description:One-quarter to one-third of ischemic strokes have no established mechanism after standard diagnostic evaluation and are classified as embolic stroke of undetermined source (ESUS). Failure of randomized trials to demonstrate a benefit of direct oral anticoagulants over aspirin for the treatment of ESUS as a single homogeneous entity has led to renewed interest by stroke experts to divide ESUS into subgroups. Emerging data suggest that active cancer, which is present in 5% to 10% of patients with ESUS, is a distinct and important subgroup of ESUS with unique clinical characteristics, underlying pathophysiologies, and treatment and prognostic considerations. Furthermore, the prevalence of cancer-related ESUS is expected to increase as patients with cancer, even those with distant metastases, survive longer due to improvements in cancer treatments. In this topical review, we examine the epidemiological link between ESUS and cancer, the clinical features and potential mechanistic underpinnings of ESUS with cancer (with a focus on novel biomarkers and their relationship to recurrent stroke and other thromboembolic events), and the potential treatment strategies for cancer-related ESUS. We include a critical appraisal of existing data and ongoing or planned clinical trials of different antithrombotic approaches. As cancer-related ESUS is a dynamic disease with variable course, we recommend close collaboration between neurologists and oncologists to develop individualized management plans.
| S-EPMC7902455 | biostudies-literature
Project description:IntroductionProlonged cardiac monitoring after cryptogenic stroke or embolic stroke of undetermined source (ESUS) is necessary to identify atrial fibrillation (AF) that requires anticoagulation. Wearable devices may improve AF detection compared to conventional management. We aimed to review the evidence for the use of wearable devices in post-cryptogenic stroke and post-ESUS monitoring.MethodsWe performed a systematic search of PubMed, EMBASE, Scopus and clinicaltrials.gov on 21 July 2022, identifying all studies that investigated the use of wearable devices in patients with cryptogenic stroke or ESUS. The outcomes of AF detection were analysed. Literature reports on electrocardiogram (ECG)-based (external wearable, handheld, patch, mobile cardiac telemetry [MCT], smartwatch) and photoplethysmography (PPG)-based (smartwatch, smartphone) devices were summarised.ResultsA total of 27 relevant studies were included (two randomised controlled trials, seven prospective trials, 10 cohort studies, six case series and two case reports). Only four studies compared wearable technology to Holter monitoring or implantable loop recorder, and these studies showed no significant differences on meta-analysis (odds ratio 2.35, 95% confidence interval [CI] 0.74-7.48, I 2 = 70%). External wearable devices detected AF in 20.7% (95% CI 14.9-27.2, I 2 = 76%) of patients and MCT detected new AF in 9.6% (95% CI 7.4%-11.9%, I 2 = 56%) of patients. Other devices investigated included patch sensors, handheld ECG recorders and PPG-based smartphone apps, which demonstrated feasibility in the post-cryptogenic stroke and post-ESUS setting.ConclusionWearable devices that are ECG or PPG based are effective for paroxysmal AF detection after cryptogenic stroke and ESUS, but further studies are needed to establish how they compare with Holter monitors and implantable loop recorder.
| S-EPMC11321540 | biostudies-literature
Project description:BackgroundThe term embolic stroke of undetermined source (ESUS) has been defined for patients with ischemic strokes, where neither a cardioembolic nor a non-cardiac source can be detected. These patients may have asymptomatic episodes of atrial fibrillation (AF). Prolonged monitoring with implantable loop recorder (ILR) and daily remote interrogation in patients after an ESUS has shown an incidence of AF of about 25%.AimsThe main objective of this study was to analyze the incidence and predictive factors of atrial fibrillation in patients with ESUS who underwent an ILR implantation.MethodsIt was a single center study. From June 2013 to January 2017 all consecutive patients with an ESUS, who underwent an ILR implantation searching for hidden AF, were included. Possible predictive factors of AF were also analyzed.Results65 patients were included (mean age 65.4±13.8 years, 55.4% males, mean CHA2DS2VASc score 2.3± 1.5). After a median follow-up of 17.1±10.7 months, AF was detected in 19 (29.2%) of patients. Variables associated with AF were: age > 65 years (HR 9.45 (CI 95% 1.25-71.34); p= 0.02), CHA2DS2VASC score≥2 (HR 4.09 (CI 95% 0.93-17.87); p=0,06), left atrial enlargement (HR 2.29 (CI 95% 0.89-5.91); p=0.08) and presence of Supraventricular premature complex(SVC) on 24-hour Holter (HR 4.05 (CI 95% 1.55-10.57); p = 0.004) A cut-point of 0.15% for SVC was identified to predict AF with a sensitivity and specificity of 88.9 and 90%, respectively. A CHA2DS2VASc score<2 and age<65 years showed a negative predictive value to exclude AF of 91.3% and 96%, respectively.ConclusionA high incidence of AF was detected in this population. Age >65 years, LA enlargement, CHA2DS2VASC score≥2 and presence of SVC on 24-hour Holter are predictive factors of AF in patients with ESUS.
| S-EPMC6533811 | biostudies-literature
Project description:IntroductionUpon completion of the workup for stroke, etiology cannot be identified in approximately one-third of the patients, with an embolic stroke of undetermined source (ESUS) accounting for around 50% of these cryptogenic etiologies. Whether management of complex long-term monitoring in order to detect suspected atrial fibrillation (AFib) could be initiated and managed through a neurologist is not sufficiently investigated.Patients and methodsWe recruited all consecutive patients with ESUS who received implantation after neurological adjudication of Reveal LINQ® loop recorder between January 2016 and July 2020. We collected demographic, clinical, heart- and neuroimaging, laboratory, and electrocardiographic data assessed on prolonged baseline ECG monitoring, number of supraventricular (SVEs) and ventricular (VEs) extrasystolic complexes, and from preimplantation ECG-PQ interval. AFib detection was manually supervised and determined positive when the duration was over 120 s.ResultsWe followed a total of 131 patients for a median of 504 days. There were 45 (34%) manually verified AFib diagnoses. In univariate analysis, earlier implantation after ESUS was associated with AFib detection (13 vs. 31 days, p = 0.011). In multivariate analysis, increased rate of AFib was associated with a more prolonged PQ interval (per 50-ms increase) (HR 1.99, 95% CI 1.39-2.85) and number of SVEs (HR 1.29, 95% CI 1.05-1.57) measured on pre-implantation ECG.ConclusionWe observed similar predictors for Afib after ESUS, albeit with higher frequency than previously reported. This study suggests that the neurologist-led decision, management, and evaluation of ILR after ESUS is feasible.
| S-EPMC8831881 | biostudies-literature
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.
| S-EPMC8258144 | biostudies-literature
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.
| S-EPMC7042078 | biostudies-literature