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1
Baule, Antonio. "About ESUS…" AboutOpen 4, no. 1 (October 26, 2018): 179–84. http://dx.doi.org/10.19156/abtpn.2018.0070.
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Five subtypes of Ischemic stroke are classified based on therir causes. ESUS (Embolic Stroke of Undetermined Source) stands for a non-lacunar cerebral infarct, in the absence of stenosis of large arteries or causes of cardioembolic stroke. It is estimated that ESUS accounts for about 25% of all ischemic strokes. A multidisciplinary, multistep diagnostic investigation is needed for a correct diagnosis, in order to exclude other possible causes of stroke. At present there are limited indications on how to plan secondary prevention of ischemic stroke in patients with ESUS. In the patient described, cortical ischemia, probably arising following an arterial embolization, represents an index event that could be classified as ESUS: in this case dabigatran was administered off-label, althoughin this type of patient this could be soon supported by the results of the RESPECT-ESUS study, a randomized trial comparing dabigatran and ASA in patients with recent ESUS, to test whether anticoagulant therapy can improve the outcome of patients in this clinical condition (Cardiology).
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Donnan, Geoffrey A. "ESUS and INTERACT." International Journal of Stroke 11, no. 5 (May 26, 2016): 499. http://dx.doi.org/10.1177/1747493016647234.
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Leventis, Ioannis, Kalliopi Perlepe, Dimitrios Sagris, Gaia Sirimarco, Davide Strambo, Georgios Georgiopoulos, Ashraf Eskandari, et al. "Characteristics and outcomes of Embolic Stroke of Undetermined Source according to stroke severity." International Journal of Stroke 15, no. 8 (March 2, 2020): 866–71. http://dx.doi.org/10.1177/1747493020909546.
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Background and aims Patients with embolic strokes of undetermined source (ESUS) usually present with mild symptoms. We aimed to compare the baseline characteristics between mild and severe ESUS, identify predictors for severe ESUS, and assess outcomes of patients with severe ESUS. Methods In the AF-ESUS (AF-ESUS) dataset, we stratified ESUS severity using the median National Institutes of Health Stroke Scale (NIHSS) score on admission as cut-off. We performed multivariable stepwise regression analyses to identify independent predictors of severe ESUS and to assess the association between ESUS severity and stroke recurrence, death, and new incident atrial fibrillation (AF) on follow-up. The 10-year cumulative probabilities of outcome incidence were estimated by the Kaplan–Meier product limit method. Results In 772 patients (median NIHSS: 6 (interquartile range: 3–12)), 414 (53.6%) patients had severe ESUS (i.e. NIHSS ≥6). Female sex was the only independent predictor for severe ESUS (odds ratio: 1.72 (1.27–2.33)). The rates of recurrence (3.3%/year vs. 3.4%/year, adjusted-hazard ratio: 1.09 (0.73–1.62)) and new incident AF (13.5% vs. 17.0%, adjusted odds ratio: 0.67 (0.44–1.03)) were similar between severe and mild ESUS, but mortality was higher (5.4%/year vs. 3.7%/year, adjusted-hazard ratio: 1.51 (1.05–2.16)) in severe ESUS. The 10-year cumulative probability for stroke recurrence was similar between severe and mild ESUS (38.1% (29.2–48.6) vs. 36.6% (27.8–47.0), log-rank test: 0.01, p = 0.920). The 10-year cumulative probability of death was higher in patients with severe ESUS compared with mild ESUS (40.5% (32.5–50.0) vs. 34.0% (26.0–43.6) respectively; log-rank test: 4.54, p = 0.033). Conclusions Women have more severe ESUS compared with men. Patients with severe ESUS have similar rates of stroke recurrence and new incident AF, but higher mortality compared with mild ESUS.
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Perera, Kanjana S., Thomas Vanassche, Jackie Bosch, Mohana Giruparajah, Balakumar Swaminathan, Katie R. Mattina, Scott D. Berkowitz, et al. "Embolic strokes of undetermined source: Prevalence and patient features in the ESUS Global Registry." International Journal of Stroke 11, no. 5 (April 11, 2016): 526–33. http://dx.doi.org/10.1177/1747493016641967.
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Background Recent evidence supports that most non-lacunar cryptogenic strokes are embolic. Accordingly, these strokes have been designated as embolic strokes of undetermined source (ESUS). Aims We undertook an international survey to characterize the frequency and clinical features of ESUS patients across global regions. Methods Consecutive patients hospitalized for ischemic stroke were retrospectively surveyed from 19 stroke research centers in 19 different countries to collect patients meeting criteria for ESUS. Results Of 2144 patients with recent ischemic stroke, 351 (16%, 95% CI 15% to 18%) met ESUS criteria, similar across global regions (range 16% to 21%), and an additional 308 (14%) patients had incomplete evaluation required for ESUS diagnosis. The mean age of ESUS patients (62 years; SD = 15) was significantly lower than the 1793 non-ESUS ischemic stroke patients (68 years, p ≤ 0.001). Excluding patients with atrial fibrillation ( n = 590, mean age = 75 years), the mean age of the remaining 1203 non-ESUS ischemic stroke patients was 64 years ( p = 0.02 vs. ESUS patients). Among ESUS patients, hypertension, diabetes, and prior stroke were present in 64%, 25%, and 17%, respectively. Median NIHSS score was 4 (interquartile range 2–8). At discharge, 90% of ESUS patients received antiplatelet therapy and 7% received anticoagulation. Conclusions This cross-sectional global sample of patients with recent ischemic stroke shows that one-sixth met criteria for ESUS, with additional ESUS patients likely among those with incomplete diagnostic investigation. ESUS patients were relatively young with mild strokes. Antiplatelet therapy was the standard antithrombotic therapy for secondary stroke prevention in all global regions.
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Hawkes, Maximiliano A., Mauricio F. Farez, Lucia Pertierra, Maia M. Gomez-Schneider, José M. Pastor-Rueda, and Sebastián F. Ameriso. "Differential characteristics, stroke recurrence, and predictors of covert atrial fibrillation of embolic strokes of undetermined source." International Journal of Stroke 13, no. 2 (July 31, 2017): 190–94. http://dx.doi.org/10.1177/1747493017724624.
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Background and purpose Identifying embolic strokes of undetermined source (ESUS) patients likely to harbor atrial fibrillation may have diagnostic and therapeutic implications. Our aim was to examine differences between ESUS and cardioembolic strokes, to evaluate stroke recurrence rate among ESUS and to identify baseline characteristics of ESUS patients who were later diagnosed with atrial fibrillation. Materials and methods We assessed all ischemic stroke patients admitted between June 2012 and November 2013. ESUS were compared to cardioembolic strokes at discharge. After at least 12-month follow-up, ESUS patients diagnosed with atrial fibrillation were compared to those who remained as ESUS. Results There were 236 ischemic strokes, 32.6% were ESUS. Compared to cardioembolic strokes, ESUS were younger (p < 0.0001), had milder strokes (p < 0.05), less prevalence of hypertension (p < 0.05), peripheral vascular disease (p < 0.05), and previous ischemic stroke (p < 0.05). After follow-up, 15% of ESUS patients had stroke recurrences and 12% evidenced paroxysmal atrial fibrillation. ESUS patients diagnosed with atrial fibrillation in the follow-up were older (p < 0.0001), had higher erythrocyte sedimentation rate (p < 0.05), and were more likely to have ≥2 infarcts in the same arterial territory in the initial magnetic resonance imaging (p < 0.05). Conclusions Older age, small-scattered infarcts on initial magnetic resonance imaging and high erythrocyte sedimentation rate levels appear to identify ESUS patients more likely to be diagnosed of atrial fibrillation during follow-up.
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Ziemann, Ulf. "Embolischer Schlaganfall unbekannter Quelle (ESUS)." Der Klinikarzt 48, no. 03 (March 2019): 78–81. http://dx.doi.org/10.1055/a-0861-8564.
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ZUSAMMENFASSUNGESUS (embolischer Schlaganfall unbekannter Quelle) wurde als pathogenetisches Konzept mit der Erwartung entwickelt, dass eine orale Antikoagulation wirksamer als eine Thrombozytenfunktionshemmung einen erneuten Schlaganfall verhindern kann. Zwei pivotale Phase-III-Studien (NAVIGATE ESUS, RE-SPECT ESUS) haben diese Erwartung nicht bestätigt. ESUS ist keine singuläre pathogenetische Entität. Zukünftige Konzepte müssen das berücksichtigen, um einer personalisierten Therapie den Weg zu ebnen.
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Masina, Marco, Annalena Cicognani, Carla Lofiego, Simona Malservisi, Riccardo Parlangeli, and Alessandro Lombardi. "Embolic stroke of undetermined source: a retrospective analysis from an Italian Stroke Unit." Italian Journal of Medicine 10, no. 3 (September 30, 2016): 202. http://dx.doi.org/10.4081/itjm.2016.690.
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The new clinical construct of embolic stroke of undetermined source (ESUS) suggests that many cryptogenic strokes are related to minor-risk covert embolic cardiac sources or to embolus from non-occlusive plaques in the aortic arch or in the cerebral arteries. The authors analyzed the prevalence of ESUS in a real-life condition in Italy and compared the recurrence rates in cryptogenic strokes, cardioembolic strokes, and ESUS. The authors retrospectively reassessed according to ESUS criteria 391 consecutive admissions in a stroke unit where extensive diagnostic search was routinely performed. Recurrences in each stroke type within a 3-year follow-up period (mean time: 25.44 months - standard deviation: 9.42) were also compared. The prevalence of ESUS in the aforementioned cohort was 10.5%. All ESUS patients received antiplatelet agents. Warfarin was prescribed in 56.9% of cardioembolic strokes. The recurrence rate in ESUS patients was 4.4% per year, slightly higher than in cardioembolic strokes (3.5%) and significantly higher than in cryptogenic non-ESUS (1.2%) (P<0.0001). This is the first description of a cohort of ESUS patients in an Italian stroke unit. Patients with ESUS have a significantly higher risk of recurrence than in those with non-ESUS cryptogenic strokes, and slightly higher than in those with cardioembolic strokes. Results support the hypothesis of a more extensive diagnostic evaluation in cryptogenic strokes and the feasibility of such approach.
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Al Khathaami, Ali M., Bayan Al Bdah, Abdulmjeed Alnosair, Abdulkarim Alturki, Rayan Alrebdi, Shorug Alwayili, Sulaiman Alhamzah, Fahad A. M. AlKhathaami, and Nasser Alotaibi. "Characteristics and Outcomes of Younger Adults with Embolic Stroke of Undetermined Source (ESUS): A Retrospective Study." Stroke Research and Treatment 2019 (December 3, 2019): 1–6. http://dx.doi.org/10.1155/2019/4360787.
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Introduction. Embolic stroke of undetermined source (ESUS) in younger adults may have different risk factors compared with ESUS in elderly, and the approach to ESUS in young adults may require new therapies. We aimed to investigate the characteristics and outcomes in younger adults with ESUS at a single centre in Saudi Arabia. Patients and Methods. A retrospective study was conducted using the medical records of younger adults with ESUS according to the criteria of the Cryptogenic Stroke/ESUS International Working Group. Younger adults (aged ≤50 years) with ESUS were compared with older patients, on admission and discharge from hospital, using the modified Rankin scale (mRS) and the National Institute of Health Stroke Scale (NIHSS). Results. Among 147 patients with ESUS, 39 (26.5%) were younger adults. Younger adults compared with older adults with ESUS had fewer vascular risk factors, including lower rates of hypertension (43.6% vs. 70.3%; P=0.004), diabetes (35.9% vs. 57.4%; P=0.03), and dyslipidaemia (12.8% vs. 28.7%; P=0.05). There was no significant difference in poor outcome at discharge (defined as mRS > 2), which was observed in 17.9% of younger adults and 28.7% of older adults. Further, there were no significant differences in stroke severity at discharge (NIHSS score ≤5) or median length of stay. Discussion. Although the outcomes of ESUS do not differ between younger and older patients, younger patients have fewer identified risk factors. Conclusion. This study showed that 26.5% of patients with ESUS were aged ≤50 years. Although younger adults with ESUS had fewer risk factors, there were no significant differences in neurologic disability or mortality at discharge, stroke severity, or median length of stay.
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Navi, Babak B., Scott E. Kasner, Mitchell S. V. Elkind, Mary Cushman, Oh Young Bang, and Lisa M. DeAngelis. "Cancer and Embolic Stroke of Undetermined Source." Stroke 52, no. 3 (March 2021): 1121–30. http://dx.doi.org/10.1161/strokeaha.120.032002.
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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.
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Jalini, Shirin, Rajasumi Rajalingam, Rosane Nisenbaum, Angelo Dave Javier, Anna Woo, and Aleksandra Pikula. "Atrial cardiopathy in patients with embolic strokes of unknown source and other stroke etiologies." Neurology 92, no. 4 (December 5, 2018): e288-e294. http://dx.doi.org/10.1212/wnl.0000000000006748.
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ObjectiveTo investigate the prevalence and clinical determinants of atrial cardiopathy in patients with embolic stroke of unknown source (ESUS) and compare with other established stroke etiologies.MethodsIn a cross-sectional study of 846 consecutive patients with ischemic stroke, we compared the prevalence of atrial cardiopathy (defined by p-wave terminal force in V1 >5,000 µV·ms or severe left atrial enlargement) between ESUS patients and patients with large artery atherosclerosis (LAA) and small vessel disease (SVD) strokes. Baseline characteristics were also compared between ESUS and cardioembolic (CE) patients.ResultsOf all, 158 (19%) patients met ESUS diagnostic criteria, while others were classified into LAA (n = 224, 26%), SVD (n = 154, 18%), and CE (n = 310, 37%). The prevalence of atrial cardiopathy was higher in ESUS patients compared to noncardioembolic stroke patients (26.6% vs 12.1% in LAA vs 16.9% in SVD; p = 0.001). ESUS patients were younger, were less hypertensive, and had higher cholesterol and low-density lipoprotein levels, but also had less left ventricular or atrial abnormalities when compared to CE patients.ConclusionThe prevalence of atrial cardiopathy was high in ESUS patients compared with patients with nonembolic strokes. Interestingly, ESUS patients were also clinically different from CE patients. While the presence of atrial cardiopathy may reflect a unique mechanism of thromboembolism in ESUS patients, it is still unclear if they may benefit from anticoagulation, or if the presence of atrial cardiopathy in this population could serve as a risk-stratifying marker for stroke recurrence. Further efforts are necessary to provide better characterization of the ESUS population in order to develop better stroke preventive strategies.
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Häckel, Andreas. "ESUS-Patienten brauchen besonderen Schutz." MMW - Fortschritte der Medizin 158, no. 19 (October 29, 2016): 79. http://dx.doi.org/10.1007/s15006-016-8916-3.
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Tsivgoulis, Georgios, Aristeidis H. Katsanos, Martin Köhrmann, Valeria Caso, Robin Lemmens, Konstantinos Tsioufis, George P. Paraskevas, et al. "Embolic strokes of undetermined source: theoretical construct or useful clinical tool?" Therapeutic Advances in Neurological Disorders 12 (January 2019): 175628641985138. http://dx.doi.org/10.1177/1756286419851381.
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In 2014, the definition of embolic strokes of undetermined source (ESUS) emerged as a new clinical construct to characterize cryptogenic stroke (CS) patients with complete vascular workup to determine nonlacunar, nonatherosclerotic strokes of presumable embolic origin. NAVIGATE ESUS, the first phase III randomized-controlled, clinical trial (RCT) comparing rivaroxaban (15 mg daily) with aspirin (100 mg daily), was prematurely terminated for lack of efficacy after enrollment of 7213 patients. Except for the lack of efficacy in the primary outcome, rivaroxaban was associated with increased risk of major bleeding and hemorrhagic stroke compared with aspirin. RE-SPECT ESUS was the second phase III RCT that compared the efficacy and safety of dabigatran (110 or 150 mg, twice daily) to aspirin (100 mg daily). The results of this trial have been recently presented and showed similar efficacy and safety outcomes between dabigatran and aspirin. Indirect analyses of these trials suggest similar efficacy on the risk of ischemic stroke (IS) prevention, but higher intracranial hemorrhage risk in ESUS patients receiving rivaroxaban compared to those receiving dabigatran (indirect HR = 6.63, 95% CI: 1.38–31.76). ESUS constitute a heterogeneous group of patients with embolic cerebral infarction. Occult AF represents the underlying mechanism of cerebral ischemia in the minority of ESUS patients. Other embolic mechanisms (paradoxical embolism via patent foramen ovale, aortic plaque, nonstenosing unstable carotid plaque, etc.) may represent alternative mechanisms of cerebral embolism in ESUS, and may mandate different management than oral anticoagulation. The potential clinical utility of ESUS may be challenged since the concept failed to identify patients who would benefit from anticoagulation therapy. Compared with the former diagnosis of CS, ESUS patients required thorough investigations; more comprehensive diagnostic work-up than is requested in current ESUS diagnostic criteria may assist clinicians in uncovering the source of brain embolism in CS patients and individualize treatment approaches.
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Feil, Katharina, Johanna Heinrich, Aenne S. von Falkenhausen, Regina Becker, Clemens Küpper, Katharina Müller, Dennis C. Thunstedt, Moritz F. Sinner, Stefan Kääb, and Lars Kellert. "Recurrent Stroke in a Young Patient with Embolic Stroke of Undetermined Source and Patent Foramen Ovale: Quo Vadis?" Case Reports in Neurology 12, no. 1 (January 29, 2020): 45–49. http://dx.doi.org/10.1159/000505180.
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So far, there has been no generally accepted diagnostic and therapeutic algorithm for patients with embolic stroke of undetermined source (ESUS). As recent clinical trials on secondary stroke prevention in ESUS did not support the use of oral anticoagulation and the concept of ESUS comprises heterogeneous subgroups of patients, including a wide age range, concomitant patent foramen ovale (PFO), variable cardiovascular risk factors as well as a variable probability for atrial fibrillation (AF), an individualized clinical approach is needed. In this context, we here present a case of recurrent stroke in a young patient with ESUS and PFO. During treatment according to our Catch-up-ESUS registry study, prolonged cardiac monitoring diagnosed AF, and PFO closure was omitted.
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Kitsiou, Alkisti, Frédéric Zuhorn, Rolf Wachter, Carsten Walter Israel, Wolf-Rüdiger Schäbitz, and Andreas Rogalewski. "Embolischer Schlaganfall mit ungeklärter Emboliequelle (ESUS) – Klassifikation einer neuen Schlaganfallentität." DMW - Deutsche Medizinische Wochenschrift 146, no. 06 (March 2021): 403–9. http://dx.doi.org/10.1055/a-1309-8701.
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ZusammenfassungAls embolischer Schlaganfall mit ungeklärter Emboliequelle (ESUS) wird eine Subgruppe kryptogener Schlaganfälle bezeichnet, welche durch ein embolisches Infarktmuster definiert werden, wenn gleichzeitig trotz einer sorgfältig durchgeführten Diagnostik keine eindeutige und spezifische Emboliequelle identifiziert werden kann. In diesem Übersichtsartikel werden die Grundlagen des ESUS-Konzepts analysiert und ein Überblick über die Evidenz jüngster Kohortenstudien gegeben. Es werden die Definition, Ätiologie und die Diagnostik eines ESUS neu bewertet. Durch eine gezielte Diagnostik bei ESUS-Patienten kann die Anzahl kryptogener Schlaganfälle durch Stellen einer spezifischen Diagnose reduziert werden.
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Tandon, Karman, David Tirschwell, W. T. Longstreth, Bryn Smith, and Nazem Akoum. "Embolic stroke of undetermined source correlates to atrial fibrosis without atrial fibrillation." Neurology 93, no. 4 (June 25, 2019): e381-e387. http://dx.doi.org/10.1212/wnl.0000000000007827.
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ObjectiveTo examine the hypothesis that atrial fibrosis and associated atrial cardiopathy may be in the causal pathway of cardioembolic stroke independently of atrial fibrillation (AF) by comparing atrial fibrosis burden between patients with embolic stroke of undetermined source (ESUS), patients with AF, and healthy controls.MethodsWe used late-gadolinium-enhancement MRI to compare atrial fibrosis in 10 patients with ESUS against 10 controls (no stroke, no AF) and 10 patients with AF. Fibrosis was compared between groups, controlling for stroke risk factors.ResultsMean age was 51 ± 15 years, and 43% of participants were female. Patients with ESUS had more atrial fibrosis than controls (16.8 ± 5.7% vs 10.6 ± 5.7%, p = 0.019) and similar fibrosis compared to patients with AF (17.8 ± 4.8%, p = 0.65). Odds ratios of ESUS per quartile of fibrosis were 3.22 (95% CI [CI] 1.11–9.32, p = 0.031, unadjusted) and 3.17 (95% CI 1.05–9.52, p = 0.041, CHA2DVASc score adjusted). Patients with >12% fibrosis had a higher percentage of ESUS (77.8% vs 27.3%, p = 0.02), and patients with >20% fibrosis had the highest proportion of ESUS (4 of 5).ConclusionsPatients with ESUS exhibit similar atrial fibrosis compared to patients with AF and more fibrosis than healthy controls. Fibrosis is associated with ESUS after controlling for stroke risk factors, supporting the hypothesis that fibrosis is in the causal pathway of cardioembolic stroke independently of AF. Prospective studies are needed to assess the role of anticoagulation in primary and secondary stroke prevention in patients with high atrial fibrosis.
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Grosse, Gerrit M., Jan-Thorben Sieweke, Saskia Biber, Nora L. Ziegler, Maria M. Gabriel, Ramona Schuppner, Hans Worthmann, Udo Bavendiek, and Karin Weissenborn. "Nonstenotic Carotid Plaque in Embolic Stroke of Undetermined Source." Stroke 51, no. 12 (December 2020): 3737–41. http://dx.doi.org/10.1161/strokeaha.120.030537.
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Background and Purpose: Approximately one-sixth of all ischemic strokes are attributable to embolic stroke of undetermined source (ESUS). Recent analyses suggest that atrial cardiopathy and nonstenotic carotid plaque (nsCP) may represent 2 distinct underlying causes in patients with ESUS, although both diseases share common risk factors and are pathophysiologically intertwined. In this study, we, therefore, aimed to search for associations between nsCP and markers of atrial remodeling and function in patients with embolic stroke. Methods: Sixty-eight patients with ESUS or atrial fibrillation (AF)-related stroke proven by imaging who underwent comprehensive echocardiographic studies, including measurements of left atrial function and remodeling, were considered. Patients with ESUS underwent a follow-up of at least 1 year after index stroke. For 20 patients with ESUS, NT-proBNP (N-terminal pro-B-type natriuretic peptide) values were available. Presence of nsCP was evaluated considering Duplex sonography and computed tomography angiography and was further categorized in possibly or probably symptomatic nsCP. Results: ESUS patients with nsCP tended to have higher values of septal and lateral total atrial conduction times ( P =0.071 and P =0.072, respectively), left atrial volume index ( P =0.077), and revealed significantly higher strain rates during early diastole ( P =0.013) as well as higher NT-proBNP values ( P =0.010) than ESUS patients without nsCP. Moreover, septal total atrial conduction time was significantly longer in ESUS patients with possibly symptomatic nsCP compared with those without ( P =0.015). Comparison of ESUS with AF patients revealed significantly higher proportions of nsCP ( P =0.010), possibly symptomatic nsCP ( P =0.037), and probably symptomatic nsCP ( P =0.036) in patients with atrial fibrillation-related stroke. In the regression analysis adjusted for vascular risk factors probably symptomatic nsCP remained significantly associated with AF ( P =0.048, odds ratio: 4.46 [95% CI, 1.02–19.56]). Conclusions: Presence of nsCP is associated with AF and markers of left atrial disease in patients with embolic stroke. Therefore, a thorough evaluation regarding atrial cardiopathy and AF in patients with ESUS should not be restricted if nsCP are found, even if high-risk plaque characteristics are evident.
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Ospel, Johanna M., Nishita Singh, Martha Marko, Mohammed Almekhlafi, Dar Dowlatshahi, Josep Puig, Andrew Demchuk, et al. "Prevalence of Ipsilateral Nonstenotic Carotid Plaques on Computed Tomography Angiography in Embolic Stroke of Undetermined Source." Stroke 51, no. 6 (June 2020): 1743–49. http://dx.doi.org/10.1161/strokeaha.120.029404.
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Background and Purpose— Embolic stroke of undetermined source (ESUS) constitutes a large proportion of acute ischemic stroke. It is crucial to identify possible stroke etiologies in this patient subgroup to individually tailor secondary stroke prevention strategies. This study aimed to assess the prevalence of carotid plaques causing <50% stenosis in ESUS patients on computed tomography angiography and the association of these plaques with ipsilateral strokes. Methods— Patients from INTERRSeCT—a multicenter prospective study of patients with acute ischemic stroke—were included in this study if their stroke etiology was not large artery atherosclerosis (>50% stenosis), and neck computed tomography angiography was obtained. Degree of stenosis (<30% versus 30%–50%), maximum plaque thickness, degree of plaque calcification (<50% versus ≥50%), plaque irregularity, ulceration, hypodensity, carotid web, and focal vessel outpouching were assessed for both carotid arteries on computed tomography angiography. Prevalence of carotid plaques with <50% stenosis (nonstenotic plaques), ipsilateral and contralateral to the stroke, in ESUS patients was determined and compared with non-ESUS patients. Features of these plaques with versus without ipsilateral stroke in ESUS patients were compared. Uni- and multivariable logistic regression was performed to determine associations between nonstenotic carotid plaque, plaque characteristics, and ipsilateral stroke in ESUS patients. Results— Four hundred forty-six patients were included in the study (median age, 73 years; 218 men), 138 of which were ESUS patients (median age, 70 years; 61 men). Nonstenotic carotid plaques (with <50% stenosis) were present in 54 of 138 (39.1%) ESUS patients. Twelve (8.7%) patients had bilateral carotid plaques. Forty (60.6%) of these plaques were ipsilateral and 26 (39.4%) contralateral to the side of the stroke ( P =0.004). Nonstenotic carotid plaques were significantly associated with ipsilateral strokes (adjusted odds ratio, 1.83 [95% CI, 1.05–3.18]). Conclusions— In patients with ESUS, nonstenotic carotid plaques were significantly more common on the side of the ischemic stroke, suggesting that these plaques could be a potential stroke etiology in patients in whom the ischemic stroke is classified currently as ESUS.
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Higuchi, Eiko, Sono Toi, Yuka Shirai, Takao Hoshino, Kentaro Ishizuka, Satoru Shimizu, Yukiko Tsutsumi, and Kazuo Kitagawa. "Prevalence of Microembolic Signals in Embolic Stroke of Undetermined Source and Other Subtypes of Ischemic Stroke." Stroke 51, no. 2 (February 2020): 655–58. http://dx.doi.org/10.1161/strokeaha.119.027008.
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Background and Purpose— Embolic stroke of undetermined source (ESUS) has been proposed to cause thromboembolic infarction from unknown but potential embolic sources. However, an embolus remains undetected in ESUS. The goal of this study was to characterize the prevalence and risk factors of microembolic signals (MESs) in ESUS. Methods— We examined 108 patients with acute ischemic stroke in the internal carotid artery territory or transient ischemic attack within 14 days of symptom onset and who were admitted to our hospital between April 2017 and March 2019. MESs were monitored in the middle cerebral artery on transcranial Doppler for 60 minutes. We examined the prevalence and number of MES in ESUS and other stroke subtypes, such as cardioembolism, large artery atherosclerosis, cerebral small vessel disease, and transient ischemic attack. The present study was registered in University Hospital Medical Information Network Clinical Trials Registry (UMIN000031913). Results— MESs were detected in 33 (31%) of 108 patients. ESUS showed the highest proportion (12/24 [50%]), followed by large artery atherosclerosis (8/20 [40%]), cardioembolism (6/18 [33%]), transient ischemic attack (4/24 [17%]), and cerebral small vessel disease (3/21 [14%]). Univariate analysis showed that higher systolic blood pressure, body mass index, hemoglobin A1c, and ESUS were significantly associated with MES. In multiple logistic regression analysis, ESUS remained significantly associated with MES after adjustment for described covariates from univariate analysis (odds ratio, 2.86 [95% CI, 1.01–8.08]). Conclusions— This study demonstrated significant association of ESUS with MES, supporting the embolic nature of this stroke subtype. Registration— URL: https://upload.umin.ac.jp . Unique identifier: UMIN000031913.
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Ikonomidis, Ignatios, Alexandra Frogoudaki, Agathi-Rosa Vrettou, Ioannis Andreou, Lina Palaiodimou, Konstantinos Katogiannis, Chryssa Liantinioti, et al. "Impaired Arterial Elastic Properties and Endothelial Glycocalyx in Patients with Embolic Stroke of Undetermined Source." Thrombosis and Haemostasis 119, no. 11 (August 17, 2019): 1860–68. http://dx.doi.org/10.1055/s-0039-1694752.
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Background and Purpose Cardioembolism is a postulated mechanism of embolic stroke of undetermined source (ESUS). We investigated endothelial glycocalyx, aortic elastic properties, oxidative stress, and their association with left atrial (LA) function in ESUS and healthy individuals. Methods In 90 ESUS patients (age 50.4 ± 13.2) and 90 controls with similar risk factors, we measured: (1) perfused boundary region (PBR) of the sublingual arterial microvessels (range 5–25 µm), a marker inversely related with glycocalyx thickness, (2) pulse wave velocity (PWV), central systolic blood pressure (cSBP), and augmentation index (AIx), (3) LA volume and strain using speckle-tracking imaging, and (4) malondialdehyde (MDA) and protein carbonyls (PCs), as oxidative stress markers. Results Compared with controls, ESUS had higher PWV, PBR, MDA, and PC levels as well as higher LA volume and reduced reservoir LA strain (p < 0.05). PBR > 1.2 μm of microvessel ranging from 5 to 9 μm and PWV > 10.2 m/s were associated with ESUS on multivariable analysis (odds ratio: 2.374 and 5.429, p < 0.05, respectively) and increased the c-statistic of the initial model from 0.54 to 0.71. In ESUS, glycocalyx damage (increased PBR) was related with increased PWV (p < 0.01) which was linked with LA reservoir strain after controlling for age, sex, and risk factors (p = 0.03). Increased MDA and PC were related with glycocalyx damage, increased PWV (r = 0.67 and r = 0.52), AIx, cSBP, and aortic atheroma (p < 0.01). Conclusion Arterial function and endothelial glycocalyx are severely impaired in ESUS and are linked to LA dysfunction suggesting their contribution to ESUS pathogenesis. Clinical Trial Registration URL-http://www.clinicaltrials.gov. Unique identifier: NCT03609437.
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Grosse, Gerrit, Saskia Biber, Jan-Thorben Sieweke, Jens Martens-Lobenhoffer, Maria Gabriel, Anne-Sophie Putzer, Isabel Hasse, et al. "Plasma Dimethylarginine Levels and Carotid Intima–Media Thickness are related to Atrial Fibrillation in Patients with Embolic Stroke." International Journal of Molecular Sciences 20, no. 3 (February 9, 2019): 730. http://dx.doi.org/10.3390/ijms20030730.
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A relevant part of embolic strokes of undetermined source (ESUS) is assumed to be due to non-detected atrial fibrillation (AF). In this study, we aimed to investigate if markers of endothelial dysfunction and damage may indicate AF risk in embolic stroke. Eighty-eight patients with ischemic stroke confirmed by imaging were assigned to one of three groups: ESUS, AF, or micro-/macroangiopathy. ESUS patients underwent prolonged Holter electrocardiography scheduled for three days. The National Institutes of Health Stroke Scale (NIHSS), the CHA2DS2VASC score, and the carotid intima–media thickness (CIMT) were obtained. Markers of endothelial (dys)function (L-arginine, asymmetric dimethylarginine (ADMA), symmetric dimethylarginine (SDMA)) were measured at day seven after stroke. ESUS patients were younger and had fewer cardiovascular risk factors than patients with determined stroke etiology. Compared with AF patients, ESUS patients showed significantly lower values of SDMA (p = 0.004) and higher values of L-arginine (p = 0.031), L-arginine/ADMA ratio (p = 0.006), L-arginine/SDMA ratio (p = 0.002), and ADMA/SDMA ratio (p = 0.013). Concordant differences could be observed comparing ESUS patients with those with newly diagnosed AF (p = 0.026; p = 0.03; p = 0.009; p = 0.004; and p = 0.046, respectively). CIMT was significantly larger in AF than in ESUS patients (p < 0.001), and was identified as an AF risk factor independent from CHA2DS2VASC in the regression analysis (p = 0.014). These findings may support future stratification for AF risk in patients who have suffered embolic stroke.
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Katano, Takehiro, Takao Kanzawa, Ban Mihara, and Kazumi Kimura. "Embolic stroke of undetermined source (ESUS)." Nosotchu 39, no. 6 (2017): 470–75. http://dx.doi.org/10.3995/jstroke.10501.
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Diener, Hans-Christoph, and Matthias Endres. "Vergangenheit und Zukunft des ESUS-Konzepts." Der Nervenarzt 91, no. 6 (March 27, 2020): 511–17. http://dx.doi.org/10.1007/s00115-020-00893-1.
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Stegmann, T., R. Wachter, and W. ‑R Schäbitz. "ESUS („embolic stroke of undetermined source“)." Herz 44, no. 4 (May 6, 2019): 289–95. http://dx.doi.org/10.1007/s00059-019-4805-8.
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Gąsiorek, Paulina, Agata Sakowicz, Maciej Banach, Stephan von Haehling, and Agata Bielecka-Dabrowa. "Arterial Stiffness and Indices of Left Ventricular Diastolic Dysfunction in Patients with Embolic Stroke of Undetermined Etiology." Disease Markers 2019 (September 12, 2019): 1–10. http://dx.doi.org/10.1155/2019/9636197.
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Purpose. The study is aimed at identifying echocardiographic and circulating biomarkers as well as hemodynamic indices of embolic stroke of undetermined etiology (ESUS) in patients aged <65. Methods. We prospectively investigated 520 patients with confirmed ischemic stroke and selected those 65 patients who were diagnosed with ESUS (age 54 (47-58) years, 42% male). An additional 36 without stroke but with a similar risk profile were included as a control group (age 53 (47-58) years, 61% male). All patients underwent echocardiography, noninvasive assessment of hemodynamic parameters using a SphygmoCor tonometer (AtCor Med., Australia), and measurements of selected biomarkers. Results. ESUS patients and controls were well matched for baseline characteristics including blood pressure and left ventricular ejection fraction (LVEF). Compared to controls, patients with ESUS had lower mean early diastolic (E′) and systolic (S′) mitral annular velocities and a higher ratio of the peak velocity of early diastolic transmitral flow to the peak velocity of early diastolic mitral annular motion (all p<0.01). The peak velocity flow in the late diastole (A wave) value and LV mass indexed to the body surface area (LVMI) (g/m2) were higher in the ESUS group than in the control group (both p<0.01). The isovolumetric relaxation time (IVRT) was longer and the mean left atrial volume index (LAVI) was higher in ESUS patients compared to the control group. Parameters of arterial stiffness such as augmentation pressure, augmentation index, and augmentation index adjusted to a heart rate of 75 bpm (AIx75) were higher in ESUS patients compared to controls (p<0.05). Patients in the ESUS group had higher levels of asymmetric dimethylarginine, interleukin 6, and N-terminal probrain natriuretic peptide (NT-proBNP, all p<0.05) than those in the control group. In multivariate analysis, the following factors were significantly associated with the presence of ESUS: AIx75 (odds ratio (OR) 1.095, 95% confidence interval (CI) 1.004-1.194; p=0.04), IVRT (OR 1.045, 95% CI: 1.009-1.082; p=0.014), LAVI (OR 1.3, 95% CI: 1.099-1.537; p=0.002), and NT-proBNP (OR 1.003, 95% CI: 1.001-1.005; p=0.005). Conclusions. Increased arterial stiffness and indices of diastolic dysfunction as well as a higher NT-proBNP level are significantly associated with ESUS. These parameters require further scrutiny over time to understand their impact on the development of symptomatic heart failure. The ClinicalTrials.gov identifier is NCT03377465.
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Feil, Katharina, Johanna Heinrich, Clemens Küpper, Katharina Müller, Christoph Laub, Aenne S. von Falkenhausen, Regina Becker, et al. "Catch-up-ESUS - follow-up in embolic stroke of undetermined source (ESUS) in a prospective, open-label, observational study: study protocol and initial baseline data." BMJ Open 9, no. 12 (December 2019): e031716. http://dx.doi.org/10.1136/bmjopen-2019-031716.
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IntroductionSo far there is no uniform, commonly accepted diagnostic and therapeutic algorithm for patients with embolic stroke of undetermined source (ESUS). Recent clinical trials on secondary stroke prevention in ESUS did not support the use of oral anticoagulation. As ESUS comprises heterogeneous subgroups including a wide age-range, concomitant patent foramen ovale (PFO), and variable probability for atrial fibrillation (AF), an individualised approach is urgently needed. This prospective registry study aims to provide initial data towards an individual, structured diagnostic and therapeutic approach in ESUS patients.Methods and analysisThe open-label, investigator-initiated, prospective, single-centre, observational registry study (Catch-up-ESUS) started in 01/2018. Consecutive ESUS patients ≥18 years who give informed consent are included and will be followed up for 3 years. Stratified by age <60 or ≥60 years, the patients are processed following a standardised diagnostic and treatment algorithm with an interdisciplinary design involving neurologists and cardiologists. Depending on the strata, patients receive a transesophageal echocardiogram; all patients receive an implantable cardiac monitor. Patients <60 years with PFO and without evidence of concomitant AF are planned for PFO closure within 6 months after stroke. The current diagnostic and therapeutic workup of ESUS patients requires improvement by both standardisation and a more individualised approach. Catch-up-ESUS will provide important data with respect to AF detection and PFO closure and will estimate stratified stroke recurrence rates after ESUS.Ethics and disseminationThe study has been approved by the responsible ethics committee at the Ludwig Maximilian University, Munich, Germany (project number 17–685). Catch-Up-ESUS is conducted in accordance with the Declaration of Helsinki. All patients will have to give written informed consent or, if unable to give consent themselves, their legal guardian will have to provide written informed consent for their participation. The first observation period of the registry study is 1 year, followed by the first publication of the results including follow-up of the patients. Further publications will be considered according the predefined individual follow-up dates of the stroke patients up to 36 months.Trial registration numberClinicaltrialsregister.gov registry (NCT03820375).
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Maier, Ilko L., Katharina Schregel, André Karch, Mark Weber-Krueger, Rafael T. Mikolajczyk, Raoul Stahrenberg, Klaus Gröschel, et al. "Association between Embolic Stroke Patterns, ESUS Etiology, and New Diagnosis of Atrial Fibrillation: A Secondary Data Analysis of the Find-AF Trial." Stroke Research and Treatment 2017 (2017): 1–6. http://dx.doi.org/10.1155/2017/1391843.
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Background. Atrial fibrillation (AF) is an important cause of embolic stroke of undetermined source (ESUS). Imaging-patterns like multiple infarcts, simultaneous involvement of different circulations, infarcts of different ages, and isolated cortical infarcts are likely to indicate cardioembolic stroke. The aim of our study was to evaluate the association between embolic stroke patterns, ESUS, and the new diagnosis of AF. Methods. Stroke etiology and imaging characteristics from patients included in the Find-AF study were obtained. Embolic stroke patterns in CT- or MR-imaging were correlated with the diagnosis of ESUS as well as the short- (on baseline ECG and during 7-day Holter) and long-term (12-month follow-up) diagnosis of AF. Results. From 281 patients included in the Find-AF study, 127 (45.2%) patients with ischemic lesions detected in CT or MRI were included. 26 (20.5%) of these patients had ESUS. At least one embolic stroke pattern was detected in 67 (52.7%) patients. Embolic stroke patterns were not associated with ESUS (OR 1.57, 0.65–3.79, p=0.317), the short-term (OR 0.64, 0.26–1.58, p=0.327) or long-term diagnosis of AF (OR 0.72, 0.31–1.68, p=0.448). Conclusions. This secondary data analysis of the Find-AF study could not provide evidence for an association between embolic stroke patterns, ESUS, and the new diagnosis of AF.
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Albers, Gregory W., Richard Bernstein, Johannes Brachmann, A. John Camm, Peter Fromm, Shinya Goto, Christopher B. Granger, et al. "Reexamination of the Embolic Stroke of Undetermined Source Concept." Stroke 52, no. 8 (August 2021): 2715–22. http://dx.doi.org/10.1161/strokeaha.121.035208.
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Occult atrial fibrillation (AF) is a leading cause of stroke of unclear cause. The optimal approach to secondary stroke prevention for these patients remains elusive. The term embolic stroke of undetermined source (ESUS) was coined to describe ischemic strokes in which the radiographic features demonstrate territorial infarcts resembling those seen in patients with confirmed sources of embolism but without a clear source of embolism detected. It was assumed that patients with ESUS had a high rate of occult AF and would benefit from treatment with direct oral anticoagulants, which are at least as effective as vitamin K antagonists for secondary stroke prevention in patients with AF, but with a much lower risk of intracerebral hemorrhage. Two recent large randomized trials failed to show superiority of direct oral anticoagulants over aspirin in ESUS patients. These findings prompt a reexamination of the ESUS concept, with the goal of improving specificity for detecting patients with a cardioembolic cause. Based on the negative trial results, there is renewed interest in the role of long-term cardiac monitoring for AF in patients who fit the current ESUS definition, as well as the clinical implication of detecting AF. Ongoing trials are exploring these questions. Current ESUS definitions do not accurately detect the patients who should be prescribed direct oral anticoagulants, potentially because occult AF is less common than expected in these patients and/or anticoagulants may be less beneficial in patients with ESUS but no AF than they are for patients with stroke with established AF. More specific criteria to identify patients who may be at higher risk for occult AF and reduce their risk of subsequent stroke have been developed and are being tested in ongoing clinical trials.
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Lyons, John, Kyle R. Piller, Juan Miguel Artigas-Azas, Omar Dominguez-Dominguez, Pablo Gesundheit, Michael Köck, Martina Medina-Nava, Norman Mercado-Silva, Arely Ramírez García, and Kearstin M. Findley. "Distribution and current conservation status of the Mexican Goodeidae (Actinopterygii, Cyprinodontiformes)." ZooKeys 885 (November 4, 2019): 115–58. http://dx.doi.org/10.3897/zookeys.885.38152.
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The current distribution and abundance of the 40 species of Goodeidae fishes known from Mexico are described, and a total of 84 Evolutionarily Significant Units (ESUs) is designated within these species. Two species and four ESUs are likely extinct with no captive populations, and three species and eight ESUs are probably extinct in the wild but have at least one captive population in Mexico, the United States, or Europe. Of the 35 extant species, the analyses indicate that nine should be considered as critically endangered, 14 as endangered, nine as vulnerable, and only three as least concern. Twenty-seven of these species have experienced substantial declines in distribution or abundance or both since 2000, and only eight appear to have remained relatively stable. Of the 72 extant ESUs, our analyses indicate that 29 should be considered as critically endangered, 21 as endangered, 18 as vulnerable, and only four as least concern. Brief summaries of the historic and current distributions and abundance of each species are provided, as well as ESU. Three strategies are recommended to conserve Mexican goodeids: protect the best-quality remaining habitats where goodeids still persist, restore degraded habitat and re-introduce species or ESUs where practical, and establish captive populations to ensure continued survival of the many species and ESUs that will almost inevitably go extinct in the coming years. Limited resources require cooperation and collaboration between scientists, conservationists, and aquarium hobbyists for successful captive maintenance.
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Diener, Hans-Christoph, Aurauma Chutinet, J. Donald Easton, Christopher B. Granger, Eva Kleine, Lars Marquardt, Juliane Meyerhoff, Andrea Zini, and Ralph L. Sacco. "Dabigatran or Aspirin After Embolic Stroke of Undetermined Source in Patients With Patent Foramen Ovale." Stroke 52, no. 3 (March 2021): 1065–68. http://dx.doi.org/10.1161/strokeaha.120.031237.
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Background and Purpose: Patent foramen ovale (PFO) may increase the risk of embolic stroke of undetermined source (ESUS). Guidelines suggest anticoagulation may be more effective than antiplatelets in preventing stroke in patients with ESUS and PFO when interventional closure is not performed. Methods: Patients with ESUS randomized to dabigatran (150/110 mg BID) or aspirin (100 mg QD) from the RE-SPECT ESUS study (Randomized, Double-Blind, Evaluation in Secondary Stroke Prevention Comparing the Efficacy and Safety of the Oral Thrombin Inhibitor Dabigatran Etexilate Versus Acetylsalicylic Acid in Patients With Embolic Stroke of Undetermined Source) were included. The rate of recurrent stroke (primary end point) and ischemic stroke was reported for patients with and without baseline PFO. A meta-analysis comparing the effects of anticoagulant and antiplatelet therapy on ischemic stroke in patients with PFO was updated to include RE-SPECT ESUS. Results: PFO was present in 680 of 5388 (12.6%) patients with documented PFO status. The risk of recurrent stroke with dabigatran versus aspirin was similar in patients with and without PFO ( P for interaction, 0.8290). In patients with PFO, the meta-analysis found no statistically significant difference between anticoagulant and antiplatelet therapy (odds ratio, 0.70 [95% CI, 0.43–1.14]) for ischemic stroke. Conclusions: There is insufficient evidence to recommend anticoagulation over antiplatelet therapy for patients with ESUS and a PFO. More data are needed to guide antithrombotic therapy in this population. Registration: URL: https://www.clinicaltrials.gov . Unique identifier: NCT02239120.
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Modolo, Gabriel Pinheiro, Juli Thomaz De Souza, Fernanda Cristina Winckler, Natalia Cristina Ferreira, Marcos Cristiano Lange, Wagner Mauad Avelar, Marcos Ferreira Minicucci, et al. "Embolic stroke of undetermined source (ESUS) cohort of Brazilian patients in a university hospital." Arquivos de Neuro-Psiquiatria 77, no. 5 (May 2019): 315–20. http://dx.doi.org/10.1590/0004-282x20190045.
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ABSTRACT Embolic stroke of undetermined source (ESUS) is an important group of cryptogenic strokes that are in evidence due recent ongoing trials. We reviewed medical records at discharge from the stroke unit of all patients who met ESUS criteria and attended our institution between February 2016 and July 2017. Among 550 stroke patients, 51 had ESUS. We found that hypertension (60%), diabetes mellitus (34%), and smoking (36%) were the most prevalent risk factors. The mean National Institutes of Health Stroke Scale (NIHSS) scores were 7 at admission and 4 at discharge, while median scores on the modified Rankin scale were 0 and 2 at admission and discharge, respectively. Our sample had similar ages, risk factors prevalence and NIHSS scores at admission and discharge when compared with European and North American cohorts. Although a small cohort, our study suggests that the ESUS population is similar in countries with different health financing.
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Tan, Benjamin Y. Q., Jamie Sin Ying Ho, Ching-Hui Sia, Yushan Boi, Anthia S. M. Foo, Mayank Dalakoti, Mark Y. Chan, et al. "Left Atrial Volume Index Predicts New-Onset Atrial Fibrillation and Stroke Recurrence in Patients with Embolic Stroke of Undetermined Source." Cerebrovascular Diseases 49, no. 3 (2020): 285–91. http://dx.doi.org/10.1159/000508211.
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Introduction: It is unclear which surrogate of atrial cardiopathy best predicts the risk of developing a recurrent ischemic stroke in embolic stroke of undetermined source (ESUS). Left atrial diameter (LAD) and LAD index (LADi) are often used as markers of left atrial enlargement in current ESUS research, but left atrial volume index (LAVi) has been found to be a better predictor of cardiovascular outcomes in other patient populations. Objective: We aim to compare the performance of LAVi, LAD, and LADi in predicting the development of new-onset atrial fibrillation (AF) and stroke recurrence in ESUS. Methods: Between October 2014 and October 2017, consecutive patients diagnosed with ESUS were followed for new-onset AF, ischemic stroke recurrence, and a composite outcome of occult AF and stroke recurrence. LAVi and LADi were measured by transthoracic echocardiogram; “high” LAVi was defined as ≥35 mL/m2 in accordance with American Society of Echocardiography guidelines. Results: 185 ischemic stroke patients with ESUS were recruited and followed for a median duration of 2.1 years. Increased LAVi was associated with new-onset AF detection (aOR 1.08; 95% CI 1.03–1.14; p = 0.003) and stroke recurrence (aOR 1.05; 95% CI 1.01–1.10; p = 0.026). Patients with “high” LAVi had a higher likelihood of developing a composite of AF detection and stroke recurrence (HR 3.45; 95% CI 1.55–7.67; p = 0.002). No significant association was observed between LADi and either occult AF or stroke recurrence. Conclusions: LAVi is associated with new-onset AF and stroke recurrence in ESUS patients and may be a better surrogate of atrial cardiopathy.
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Grätzel, Philipp. "ESUS-Patienten: Antikoagulation auf Basis der Vorhoffibrose?" CardioVasc 20, no. 4 (September 2020): 19–20. http://dx.doi.org/10.1007/s15027-020-2146-4.
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UCHIYAMA, Shinichiro. "Antithrombotic therapy for cerebral embolism: How to interpret the results of NAVIGATE ESUS and RE-SPECT ESUS trials." Japanese Journal of Thrombosis and Hemostasis 30, no. 6 (2019): 828–36. http://dx.doi.org/10.2491/jjsth.30.828.
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Ohya, Yuichiro, Masato Osaki, Shigeru Fujimoto, Juro Jinnouchi, Takayuki Matsuki, Satomi Mezuki, Masaya Kumamoto, et al. "Usefulness of Transesophageal Echocardiography for Predicting Covert Paroxysmal Atrial Fibrillation in Patients with Embolic Stroke of Undetermined Source." Cerebrovascular Diseases Extra 9, no. 3 (September 20, 2019): 98–106. http://dx.doi.org/10.1159/000502713.
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Background: Covert paroxysmal atrial fibrillation (CPAF) is a major cause of embolic stroke of undetermined source (ESUS). However, detecting PAF during hospitalization in these patients is difficult. Objectives: This study aimed to determine whether findings of transesophageal echocardiography (TEE) during hospitalization are associated with later detection of PAF in patients with ESUS. Method: We retrospectively studied 348 patients with ESUS who were admitted to our hospital within 1 week of onset. These patients met the criteria of ESUS, underwent TEE during hospitalization, and were followed up for at least 1 year. Results: We found PAF in 35 (10.0%) patients. In patients with PAF, spontaneous echo contrast (SEC) and low left atrial appendage flow (LAAF) by TEE and enlargement of the left atrial dimension (LAD) by transthoracic echocardiography were identified more frequently compared with those who did not have PAF. In multivariate analysis, SEC and an LAD ≥42 mm were independently associated with later detection of PAF (p < 0.05). An association of LAAF <46.9 cm/s and PAF was marginal (p = 0.09). The specificity of the combined finding of SEC and/or LAAF with that of LAD increased up to 90%, while that of LAD alone was 70%. Conclusions: The findings of TEE during hospitalization may be useful for identifying patients at increased risk of CPAF in patients with ESUS.
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Jung, Moonki, Jin-Seok Kim, Ju Hyeon Song, Jeong-Min Kim, Kwang-Yeol Park, Wang-Soo Lee, Sang Wook Kim, Gregory YH Lip, and Seung Yong Shin. "Usefulness of P Wave Duration in Embolic Stroke of Undetermined Source." Journal of Clinical Medicine 9, no. 4 (April 15, 2020): 1134. http://dx.doi.org/10.3390/jcm9041134.
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The investigation of the potential association between ischemic stroke and subclinical atrial fibrillation (SCAF) is important for secondary prevention. We aimed to determine whether SCAF can be predicted by atrial substrate measurement with P wave signal-averaged electrocardiography (SAECG). We recruited 125 consecutive patients with embolic stroke of undetermined source (ESUS) and 125 patients with paroxysmal atrial fibrillation as controls. All participants underwent P wave SAECG at baseline, and patients with ESUS were followed up with Holter monitoring and electrocardiography at baseline, 3, 6, and 12 months after discharge and every 6 months thereafter. In the ESUS group, 32 (25.6%) patients were diagnosed with SCAF during follow-up. There were no significant differences between the groups regarding atrial substrate. P wave duration (PWD) was a significant predictor of SCAF. Stroke recurrence occurred in 22 patients (17.6%), and prolonged PWD (≥ 135 ms) predicted stroke recurrence more robustly than SCAF detection. In ESUS patients, PWD can be a useful biomarker to predict SCAF and to identify patients who are more likely to have a recurrent embolic stroke associated with an atrial cardiopathy. Further research is needed for supporting the utility and applicability of PWD.
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Karliński, Michał. "What after cryptogenic stroke – NOAC for everyone or ICM for some?" In a good rythm 4, no. 49 (February 10, 2019): 25–27. http://dx.doi.org/10.5604/01.3001.0013.0505.
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Atrial fibrillation (AF) is by far the most common cause of stroke with cardiovascular etiology. It is commonly believed that a significant proportion of ischemic strokes of an unknown cause are in fact also embolic (ESUS). This leads to consideration that patients after ESUS are potential candidates for chronic NOAC treatment. However, the therapeutic strategy constructed in such a simple way has been verified negatively in recent randomized trials. It is uncertain whether the pharmaceutical industry will be interested in continuing research in a subpopulation of ESUS patients with a particularly high risk of AF. However, it is now possible to strive for extended ECG monitoring aimed at detecting paroxysmal AF that is not detected by standard post-stroke diagnostic workup. In both scenarios, pragmatic and economic considerations make it necessary to develop a method of proper patients selection. The discussed analysis of data collected during the CRYSTAL-AF study, discussed by me, allows to better understand the imperfection of the current thinking about ESUS and provides information that may development the creation of an optimal model for dealing with this group of patients.
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Scheitz, Jan F., Guillaume Pare, Lesly A. Pearce, Hardi Mundl, W. Frank Peacock, Anna Czlonkowska, Mukul Sharma, et al. "High-Sensitivity Cardiac Troponin T for Risk Stratification in Patients With Embolic Stroke of Undetermined Source." Stroke 51, no. 8 (August 2020): 2386–94. http://dx.doi.org/10.1161/strokeaha.120.029628.
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Background and Purpose: Optimal secondary prevention for patients with embolic stroke of undetermined source (ESUS) remains unknown. We aimed to assess whether high-sensitivity cardiac troponin T (hs-cTnT) levels are associated with major vascular events and whether hs-cTnT may identify patients who benefit from anticoagulation following ESUS. Methods: Data were obtained from the biomarker substudy of the NAVIGATE ESUS trial, a randomized controlled trial testing the efficacy of rivaroxaban versus aspirin for secondary stroke prevention in ESUS. Patients were dichotomized at the hs-cTnT upper reference limit (14 ng/L, Gen V, Roche Diagnostics). Cox proportional hazard models were computed to explore the association between hs-cTnT, the combined cardiovascular end point (recurrent stroke, myocardial infarction, systemic embolism, cardiovascular death), and recurrent ischemic stroke. Results: Among 1337 patients enrolled at 111 participating centers in 18 countries (mean age 67±9 years, 61% male), hs-cTnT was detectable in 95% and at/above the upper reference limit in 21%. During a median follow-up of 11 months, the combined cardiovascular end point occurred in 68 patients (5.0%/y, rivaroxaban 28 events, aspirin 40 events; hazard ratio, 0.67 [95% CI, 0.41–1.1]), and recurrent ischemic stroke occurred in 50 patients (4.0%/y, rivaroxaban 16 events, aspirin 34 events, hazard ratio 0.45 [95% CI, 0.25–0.81]). Annualized combined cardiovascular end point rates were 8.2% (9.5% rivaroxaban, 7.0% aspirin) for those above hs-cTnT upper reference limit and 4.8% (3.1% rivaroxaban, 6.6% aspirin) below with a significant treatment modification ( P =0.04). Annualized ischemic stroke rates were 4.7% above hs-cTnT upper reference limit and 3.9% below, with no suggestion of an interaction between hs-cTnT and treatment ( P =0.3). Conclusions: In patients with ESUS, hs-cTnT was associated with increased cardiovascular event rates. While fewer recurrent strokes occurred in patients receiving rivaroxaban, outcomes were not stratified by hs-cTn results. Our findings support using hs-cTnT for cardiovascular risk stratification but not for decision-making regarding anticoagulation therapy in patients with ESUS. Registration: URL: https://www.clinicaltrials.gov . Unique identifier: NCT02313909.
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Strambo, Davide, Gaia Sirimarco, Stefania Nannoni, Kalliopi Perlepe, George Ntaios, Kostantinos Vemmos, and Patrik Michel. "Embolic Stroke of Undetermined Source and Patent Foramen Ovale." Stroke 52, no. 5 (May 2021): 1643–52. http://dx.doi.org/10.1161/strokeaha.120.032453.
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Background and Purpose: The Risk of Paradoxical Embolism (RoPE) score stratifies patients with stroke according to the probability of having a patent foramen ovale (PFO), which (through Bayes theorem and simple assumptions) can be used to estimate the probability that a PFO is pathogenic in a given subgroup of patients with specific features (ie, a given RoPE score value): a higher PFO prevalence corresponds to a higher probability that a PFO is pathogenic. Among alternative mechanisms in embolic stroke of undetermined source (ESUS), the actual stroke cause may be covert atrial fibrillation. We aimed to validate the RoPE score in a large ESUS population and investigate the rate of stroke recurrence and new incident atrial fibrillation during follow-up according to PFO status and RoPE score. Methods: We pooled data of consecutive patients with ESUS from 3 prospective stroke registries. We assessed RoPE score’s calibration and discrimination for the presence of PFO (and consequently for the probability that it is pathogenic). Multivariate logistic regression analysis was performed to identify factors associated with PFO. Results: Among 455 patients with ESUS (median age 59 years), 184 (40%) had PFO. The RoPE score’s area under the receiver operating characteristic curve was 0.75. In addition to RoPE score variables, absence of left ventricular hypertrophy, absence of atherosclerosis, and infratentorial lesions were independently associated with PFO. In patients with PFO and RoPE 7 to 10, PFO and RoPE 0 to 6, and without PFO, new incident atrial fibrillation rate was 3.1%, 20.5%, and 31.8%, respectively (log-rank test=6.28, P =0.04). Stroke recurrences in patients with likely pathogenic PFO were not statistically different from other patients. Conclusions: This multicenter study validates the RoPE score to predict the presence/absence of PFO in patients with ESUS, which strongly suggests that RoPE score is helpful in identifying patients with ESUS with pathogenic versus incidental PFOs. Left ventricular hypertrophy, atherosclerosis, and infratentorial stroke may further improve the score. Low RoPE scores were associated with more incidental atrial fibrillation during 10-year follow-up.
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Dooley, Melissa M., and Tamara Braghieri. "Take the path of least resistance with ESUs." OR Nurse 2, no. 2 (February 2008): 37–39. http://dx.doi.org/10.1097/01.orn.0000310512.47660.c0.
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Häusler, Karl Georg. "Sekundärprävention nach ESUS: Dabigatran nicht wirksamer als Acetylsalicylsäure." InFo Neurologie & Psychiatrie 21, no. 10 (October 2019): 22–23. http://dx.doi.org/10.1007/s15005-019-0168-1.
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Geisler, Tobias, Annerose Mengel, Ulf Ziemann, and Sven Poli. "Management of Embolic Stroke of Undetermined Source (ESUS)." Drugs 78, no. 8 (May 8, 2018): 823–31. http://dx.doi.org/10.1007/s40265-018-0912-8.
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Lima, Camilla S., Rafael F. Magalhães, and Fabricio R. Santos. "Conservation issues using discordant taxonomic and evolutionary units: a case study of the American manatee (Trichechus manatus, Sirenia)." Wildlife Research 48, no. 5 (2021): 385. http://dx.doi.org/10.1071/wr20197.
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The delimitation of evolutionarily significant units (ESUs) frequently results in controversy, but prioritising populations with evolutionary independence is essential for effective in situ conservation management. The American manatee (Trichechus manatus) is distributed along subtropical and tropical coastal waters from Florida (USA) to Alagoas (Brazil), and two subspecies are traditionally recognised, namely, T. m. latirostris, restricted to the Florida peninsula, and T. m. manatus, found in the remaining areas. However, this subspecific classification is not supported by genetic and morphologic evidence, which, rather, recognises two deeply differentiated populations or ESUs called Atlantic (Brazil) and Caribbean (from Venezuela to Florida). In this viewpoint paper, we compare both intraspecific divisions of T. manatus and the conservation implications. First, we used all available mtDNA evidence to test the genealogical clustering of the two American manatee ESUs by using a tree-based coalescent method. Second, we have used different models under a coalescent framework to estimate the historic gene flow among manatee populations. The analysis of the spatial distribution of mtDNA clusters confirmed the existence of the two suggested ESUs, rather than the two claimed subspecies. Furthermore, the best model to explain historic migration indicates that Brazilian manatees belong to an isolated population, whereas Florida and Caribbean populations are connected by more recent gene flow. These results have confirmed that T. manatus of the Caribbean, Gulf of Mexico and Florida belong to the same deme or Caribbean ESU, and the relatively isolated population inhabiting the Atlantic coast of Brazil belongs to the Atlantic ESU. Furthermore, both ESUs are separated by an interspecific hybrid zone (with the Amazonian manatee) located around the mouth of the Amazon River towards the Guianas coastline. The subdivision of two ESUs is also highly supported by karyotypic, morphological and ecological data, and is in clear disagreement with the traditional subspecies designations and the IUCN priorities, which manages Brazilian manatees as part of the Antillean manatee subspecies (T. m. manatus). Rather, Brazilian manatees should be considered as a full priority for conservation and require further taxonomic research; because of their deep history of isolation, they present high genetic and morphologic differentiation from all other American manatees.
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Kutlubaev, M. A., and E. N. Khasanova. "Current approaches to diagnosis and prevention of ishemic stroke." Clinical Medicine (Russian Journal) 96, no. 5 (October 12, 2018): 389–96. http://dx.doi.org/10.18821/0023-2149-2018-96-5-389-396.
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Etiology ofembolic stroke is very heterogeneous. It could be related to large vessel disease, small vessel disease, thromboembolism of cardiac origin. Clarification of etiology of stroke is important prerequisite for adequate selection of its secondary prevention measures. Standard work-up allows identification of its etiology in 60-90% of cases. 1n the rest 10-40% of cases stroke is considered cryptogenic. The majority of cryptogenic strokes are embolic. In keeping with this, a concept of embolic stroke of undetermined source (ESUS) was suggested. 1n the paper authors review most sigificant causes of ESUS. Occult atrial fibrillation is one of the common cause of ESUS. 1t could be detected only by means of long term ECG monitoring. Standard 24-hour ECG monitoring after stroke detects around 5% of cases ofpreviously unknown paroxysmal atrial fibrillation, while long-term monitoring of ECG allows detection ofparoxysmal atrial fibrillation in 15% of cases. Patent foramen ovale could lead to stroke in patients with deep vein thrombosis in the legs and pelvis due to paradoxical embolism. Atherosclerosis of aortic arch is observed in the half ofpeople older than 45 years. Large, ulcerated, non-calcified or floating atheromas could cause a stroke. Malignant tumors could lead to cerebral embolism through non-bacterial thrombotic endocarditis. Tumor embolism into cerebral arteries could also be seen in rare cases. The rate of cerebral embolism is high in mixomas. Approaches to diagnosis and secondary prevention of ESUS are discussed in the paper.
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Israel, Carsten, Alkisti Kitsiou, Malik Kalyani, Sameera Deelawar, Lucy Ekosso Ejangue, Andreas Rogalewski, Christoph Hagemeister, Jens Minnerup, and Wolf-Rüdiger Schäbitz. "Detection of atrial fibrillation in patients with embolic stroke of undetermined source by prolonged monitoring with implantable loop recorders." Thrombosis and Haemostasis 117, no. 10 (2017): 1962–69. http://dx.doi.org/10.1160/th17-02-0072.
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SummaryRecently, the clinical entity 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 suffer from asymptomatic atrial fibrillation (AF), terminating spontaneously and thus eluding detection. Implantable loop recorders (ILR) with automatic AF detection algorithms can detect short-lasting, subclinical AF. The aim of this study was to prospectively assess and predict AF detection in patients with ESUS using ILR with daily remote interrogation. Patients with acute ESUS received an ILR, were seen every 6 months and additionally interrogated their ILR daily using remote monitoring. The incidence of AF detection was assessed and parameters which might predict AF detection (clinical and from magnetic resonance tomography) were analysed. ILR implantation was performed in 123 patients on average 20 days after stroke. During a mean follow-up of 12.7±5.5 months, AF was documented and manually confirmed in 29 of 123 patients (23.6%). First AF detection occurred on average after 3.6±3.4 months of monitoring. Patients with AF were on average older, had a higher CHA2DS2-VASc score and more often cerebral microangiopathy. In conclusion, AF can be documented in approximately 25% of patients with the diagnosis of ESUS after careful work-up within a year of monitoring by an ILR and daily remote interrogation. This had important therapeutic consequences (initiation of anticoagulation for secondary stroke prevention) in these patients.
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Ntaios, George, Gregory Y. H. Lip, Konstantinos Vemmos, Eleni Koroboki, Efstathios Manios, Anastasia Vemmou, Ana Rodríguez-Campello, et al. "Age- and sex-specific analysis of patients with embolic stroke of undetermined source." Neurology 89, no. 6 (July 7, 2017): 532–39. http://dx.doi.org/10.1212/wnl.0000000000004199.
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Objective:To investigate whether the correlation of age and sex with the risk of recurrence and death seen in patients with previous ischemic stroke is also evident in patients with embolic stroke of undetermined source (ESUS).Methods:We pooled datasets of 11 stroke registries from Europe and America. ESUS was defined according to the Cryptogenic Stroke/ESUS International Working Group. We performed Cox regression and Kaplan-Meier product limit analyses to investigate whether age (<60, 60–80, >80 years) and sex were independently associated with the risk for ischemic stroke/TIA recurrence or death.Results:Ischemic stroke/TIA recurrences and deaths per 100 patient-years were 2.46 and 1.01 in patients <60 years old, 5.76 and 5.23 in patients 60 to 80 years old, 7.88 and 11.58 in those >80 years old, 3.53 and 3.48 in women, and 4.49 and 3.98 in men, respectively. Female sex was not associated with increased risk for recurrent ischemic stroke/TIA (hazard ratio [HR] 1.15, 95% confidence interval [CI] 0.84–1.58) or death (HR 1.35, 95% CI 0.97–1.86). Compared with the group <60 years old, the 60- to 80- and >80-year groups had higher 10-year cumulative probability of recurrent ischemic stroke/TIA (14.0%, 47.9%, and 37.0%, respectively, p < 0.001) and death (6.4%, 40.6%, and 100%, respectively, p < 0.001) and higher risk for recurrent ischemic stroke/TIA (HR 1.90, 95% CI 1.21–2.98 and HR 2.71, 95% CI 1.57–4.70, respectively) and death (HR 4.43, 95% CI 2.32–8.44 and HR 8.01, 95% CI 3.98–16.10, respectively).Conclusions:Age, but not sex, is a strong predictor of stroke recurrence and death in ESUS. The risk is ≈3- and 8-fold higher in patients >80 years compared with those <60 years of age, respectively. The age distribution in the ongoing ESUS trials may potentially influence their power to detect a significant treatment association.
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Ntaios, George, Lesly A. Pearce, Roland Veltkamp, Mukul Sharma, Scott E. Kasner, Eleni Korompoki, Haralampos Milionis, et al. "Potential Embolic Sources and Outcomes in Embolic Stroke of Undetermined Source in the NAVIGATE-ESUS Trial." Stroke 51, no. 6 (June 2020): 1797–804. http://dx.doi.org/10.1161/strokeaha.119.028669.
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Background and Purpose— Emboli in embolic stroke of undetermined source (ESUS) may originate from various potential embolic sources (PES), some of which may respond better to anticoagulation, whereas others to antiplatelets. We analyzed whether rivaroxaban is associated with reduction of recurrent stroke compared with aspirin in patients with ESUS across different PES and by number of PES. Methods— We assessed the presence/absence of each PES (atrial cardiopathy, atrial fibrillation, arterial atherosclerosis, left ventricular dysfunction, cardiac valvulopathy, patent foramen ovale, cancer) in NAVIGATE-ESUS (New Approach Rivaroxaban Inhibition of Factor Xa in a Global Trial Versus ASA to Prevent Embolism in Embolic Stroke of Undetermined Source) participants. Prevalence of each PES, as well as treatment effect and risk of event for each PES were determined. Results by number of PES were also determined. The outcomes were ischemic stroke, all-cause mortality, cardiovascular mortality, and myocardial infarction. Results— In 7213 patients (38% women, mean age 67years) followed for a median of 11 months, the 3 most prevalent PES were atrial cardiopathy (37%), left ventricular disease (36%), and arterial atherosclerosis (29%). Forty-one percent of all patients had multiple PES, with 15% having ≥3 PES. None or a single PES was present in 23% and 36%, respectively. Recurrent ischemic stroke risk was similar for rivaroxaban- and aspirin-assigned patients for each PES, except for those with cardiac valvular disease which was marginally higher in rivaroxaban-assigned patients (hazard ratio, 1.8 [95% CI, 1.0–3.0]). All-cause mortality risks were similar across treatment groups for each PES while too few myocardial infarctions and cardiovascular deaths occurred for meaningful assessment. Increasing number of PES was not associated with increased stroke recurrence nor all-cause mortality, and outcomes did not vary between rivaroxaban- and aspirin-assigned patients by number of PES. Conclusions— A large proportion of patients with ESUS had multiple PES which could explain the neutral results of NAVIGATE-ESUS. Recurrence rates between rivaroxaban- and aspirin-assigned patients were similar across the spectrum of PES. Registration— URL: https://www.clinicaltrials.gov ; Unique identifier: NCT02313909.
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Rodríguez Lucci, Federico, and Sebastián F. Ameriso. "Accidente cerebrovascular embólico de origen indeterminado. El concepto ESUS." Neurología Argentina 10, no. 2 (April 2018): 98–102. http://dx.doi.org/10.1016/j.neuarg.2017.11.004.
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Ladeira, Filipa, Raquel Barbosa, André Caetano, Marcelo D. Mendonça, Sofia Calado, and Miguel Viana-Baptista. "Embolic stroke of unknown source (ESUS) in young patients." International Journal of Stroke 10, SA100 (October 2015): 165. http://dx.doi.org/10.1111/ijs.12596.
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Shirai, Y., S. Toi, M. Kubota, U. Adachi, and K. Kitagawa. "Endothelial dysfunction in embolic stroke of undetermined source (ESUS)." Journal of the Neurological Sciences 381 (October 2017): 996. http://dx.doi.org/10.1016/j.jns.2017.08.2808.
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Humphreys, Aelys M., and Timothy G. Barraclough. "The evolutionary reality of higher taxa in mammals." Proceedings of the Royal Society B: Biological Sciences 281, no. 1783 (May 22, 2014): 20132750. http://dx.doi.org/10.1098/rspb.2013.2750.
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Species are generally regarded as a fundamental unit of biodiversity. By contrast, higher taxa such as genera and families, while widely used as biodiversity metrics and for classification and communication, are generally not believed to be shaped by shared evolutionary processes in the same way as species. We use simulations to show that processes which are important for emergence of evolutionarily significant units (ESUs) at the species level, namely geographical isolation and ecological divergence, can generate evolutionary independence above the species level and thereby lead to emergence of discrete phylogenetic clusters (higher ESUs). Extending phylogenetic approaches for delimiting evolutionarily significant species to broader phylogenetic scales, we find evidence for the existence of higher ESUs in mammals. In carnivores, euungulates and lagomorphs the hierarchical level of units detected correspond, on average, to the level of family or genus in traditional taxonomy. The units in euungulates are associated with divergent patterns of body mass, consistent with occupation of distinct ecological zones. Our findings demonstrate a new framework for studying biodiversity that unifies approaches at species and higher levels, thus potentially restoring higher taxa to their historical status as natural entities.