Embolic Stroke of Undetermined Source: Approaches in Risk Stratification for Cardioembolism

Stroke ◽  
2021 ◽  
Author(s):  
Aditya Bhat ◽  
Vipul Mahajan ◽  
Henry H.L. Chen ◽  
Gary C.H. Gan ◽  
Octavio M. Pontes-Neto ◽  
...  
Keyword(s):  
Ischemic Stroke ◽  
Clinical Practice ◽  
Risk Stratification ◽  
Patient Outcomes ◽  
Cardiac Imaging ◽  
Embolic Stroke ◽  
Current Evidence ◽  
Stroke Recurrence ◽  
Stroke Mechanism ◽  
Review Current

Ischemic stroke is a leading cause of morbidity and mortality worldwide. Embolic stroke of undetermined source has been recently proposed to categorize nonlacunar ischemic strokes without confirmed etiology after adequate investigation with a likely embolic stroke mechanism. A strategy of empirical anticoagulation for embolic stroke of undetermined source patients is attractive but may only be beneficial in a select subset of patients. Strategies which would help identify the subset of embolic stroke of undetermined source patients most likely to have cardioembolic origin of stroke, and hence benefit from anticoagulation, are needed. This article will review current evidence which may be useful in the development of a risk stratification approach based on arrhythmia monitoring, cardiac imaging, and clinical risk stratification. This approach may be beneficial in clinical practice in improving patient outcomes and reducing stroke recurrence in this population; however, further work is required with active trials underway.

scholarly journals High-Sensitivity Cardiac Troponin T for Risk Stratification in Patients With Embolic Stroke of Undetermined Source

Stroke ◽  
2020 ◽  
Vol 51 (8) ◽  
pp. 2386-2394 ◽  
Author(s):  
Jan F. Scheitz ◽  
Guillaume Pare ◽  
Lesly A. Pearce ◽  
Hardi Mundl ◽  
W. Frank Peacock ◽  
...  
Keyword(s):  
Ischemic Stroke ◽  
Risk Stratification ◽  
Cardiac Troponin ◽  
Troponin T ◽  
High Sensitivity ◽  
Embolic Stroke ◽  
Cardiac Troponin T ◽  
Reference Limit ◽  
End Point ◽  
Upper Reference Limit

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.

scholarly journals Potential Embolic Sources and Outcomes in Embolic Stroke of Undetermined Source in the NAVIGATE-ESUS Trial

Stroke ◽  
2020 ◽  
Vol 51 (6) ◽  
pp. 1797-1804 ◽  
Author(s):  
George Ntaios ◽  
Lesly A. Pearce ◽  
Roland Veltkamp ◽  
Mukul Sharma ◽  
Scott E. Kasner ◽  
...  
Keyword(s):  
Ischemic Stroke ◽  
Recurrent Stroke ◽  
Factor Xa ◽  
Left Ventricular ◽  
Embolic Stroke ◽  
Stroke Recurrence ◽  
Recurrence Rates ◽  
Unique Identifier ◽  
Treatment Groups ◽  
All Cause Mortality

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.

A score to predict one-year risk of recurrence after acute ischemic stroke

2020 ◽  
pp. 174749302093278
Author(s):  
Davide Strambo ◽  
Alexandros Zachariadis ◽  
Dimitris Lambrou ◽  
Ghil Schwarz ◽  
Gaia Sirimarco ◽  
...  
Keyword(s):  
Ischemic Stroke ◽  
Acute Ischemic Stroke ◽  
Cox Regression ◽  
Stroke Recurrence ◽  
Cerebrovascular Lesions ◽  
Cox Regression Analysis ◽  
Prognostic Tool ◽  
Derivation Cohort ◽  
One Year ◽  
Stroke Mechanism

Background An acute ischemic stroke carries a substantial risk of further recurrences. We aimed at developing and validating a prognostic tool to predict one-year stroke recurrence after acute ischemic stroke. Methods An integer score was derived by Cox regression analysis on a hospital-referred cohort of 3246 acute ischemic stroke patients from Switzerland, and tested for external validity in three similar independent cohorts from Athens ( n = 2495), Milan ( n = 1279), and Helsinki ( n = 714) by means of calibration and discrimination. Results In the derivation cohort, the recurrence rate was 7% ( n = 228/3246). We developed a nine-point score comprising: previous stroke or transient ischemic attack (1-point), stroke mechanism (small vessel disease and unknown mechanism: 0-points; rare stroke mechanism: 3-points; other mechanisms: 1-point), pre-stroke antiplatelets (1-point), active malignancy (2-points), chronic cerebrovascular lesions on imaging (1-point) and absence of early ischemic changes on first imaging (1-point). In the derivation cohort, the one-year risk of re-stroke was 3.0% (95%CI 1.9–4.1) in 932 (29%) patients with a score 0–1, 7.2% (6.1–8.3) in 2038 (63%) with a score 2–4, and 19.2% (14.6–23.9) in 276 (8%) with a score ≥ 5. The score calibrated well in the Athens (recurrences = 208/2495), but not in the Helsinki (recurrences = 15/714) or Milan (recurrences = 65/1279) cohorts. The AUC was 0.67 in the derivation cohort, and 0.56, 0.70, and 0.63 in the Athens, Helsinki, and Milan cohorts, respectively. Conclusion We developed a score to predict one-year stroke recurrence risk in patients with acute ischemic stroke. Since the score was not completely validated when applied to external datasets where it displayed poor to fair calibration and discrimination, additional efforts are required to ameliorate our accuracy for predicting stroke recurrence, by better refining this prognostic tool or developing new ones. Clinical and radiological markers of established cerebrovascular disease and stroke etiology were better predictors than the usual demographic vascular risk factors.

Abstract T MP51: Relation of Spontaneous Microembolic Signals to Stratification of Risk, Recurrence and Morbi-mortality of Ischemic Stroke by Transcranial Doppler: A Prospective Trial

Stroke ◽  
2015 ◽  
Vol 46 (suppl_1) ◽  
Author(s):  
Rodrigo Bazan ◽  
Gabriel P Braga ◽  
Silméia G Bazan ◽  
João C Hueb ◽  
Marcone L Sobreira ◽  
...  
Keyword(s):  
Risk Factors ◽  
Ischemic Stroke ◽  
Risk Stratification ◽  
Acute Phase ◽  
Transcranial Doppler ◽  
Prospective Trial ◽  
Ambulatory Monitoring ◽  
Stroke Recurrence ◽  
Carotid Disease ◽  
Symptomatic Carotid

Background: The role of spontaneous microemboli signals (MES) by Transcranial Doppler (TCD) in the acute phase of stroke has been studied little and has potential application for locating emboligenic source and for predicting risk. We assessed the hypothesis that investigating MES prevalence in the acute phase of stroke is related to risk stratification, stroke recurrence and morbi-mortality. Methods: This is an analytic observational study of a single non-concurrent cohort with 111 patients diagnosed with ischemic stroke of anterior circulation in the first 48 hours of ictus. All patients underwent monitoring of the middle cerebral arteries by TCD for at least 30 minutes. The examiner who conducted the monitoring was unaware of the risk stratification of the patient (single-blinded). Then, the examination record was independently analyzed by two neurologists to identify the MES. After monitoring, risk stratification was carried out for all patients by complementary examinations; the recurrence and morbi-mortality were evaluated by ambulatory monitoring for months. The relation between risk factors, stratified for risk with MES was obtained by Odds-Ratio taking into consideration confounding factors (thrombolysis and anticoagulation level) at the moment of monitoring, and the relation of MES to stroke recurrence and morbi-mortality by multiple regression logistics, considering values statistically significant if p<0.05. Results: Of the 111 patients studied, 70 were male (63.1%), 90 white (81.1%), with median age of 68 years. The MES frequency was 7% in the total sample. There was a relation between MES and symptomatic carotid disease (OR=22.7;CI95%=(4.1-125.7);p<0.001), shorter time between ictus and monitoring commencement (OR=12.4; CI95%=(1.4-105.4);p=0.02), and stroke recurrence (OR=16.83;CI95%=(2.01-141);p=0.009). MES was not significantly related to morbi-mortality (OR=1.7;CI95%=(0.28-10.90);p=0.547), or to such risk factors as cardioembolic source or atrial fibrillation. Conclusions: It was found that MES detection shows higher correlation with symptomatic carotid disease, and shorter time between ictus and monitoring commencement, in addition to the presence of MES as a predictor for stroke occurrence.

scholarly journals Association of Electrocardiographic P-Wave Markers and Atrial Fibrillation in Embolic Stroke of Undetermined Source

2020 ◽  
pp. 1-8
Author(s):  
Tony Y.W. Li ◽  
Leonard Leong L. Yeo ◽  
Jamie Sin Ying Ho ◽  
Aloysius S. Leow ◽  
Mark Y. Chan ◽  
...  
Keyword(s):  
Atrial Fibrillation ◽  
Risk Stratification ◽  
Ischaemic Stroke ◽  
Recurrent Stroke ◽  
Embolic Stroke ◽  
P Wave ◽  
Stroke Recurrence ◽  
Atrial Remodeling ◽  
P Wave Dispersion ◽  
New Onset

<b><i>Background:</i></b> Several P-wave indices are thought to represent underlying atrial remodeling and have been associated with ischaemic stroke even in the absence of atrial fibrillation (AF). However, the utility of these P-wave indices in predicting outcomes in patients with embolic stroke of undetermined source (ESUS) has not been studied. The aim of this study is to examine these different P-wave indices towards predicting new-onset AF and stroke recurrence in a cohort of patients with ESUS, thereby demonstrating the value of these electrocardiographic markers for stroke risk stratification. <b><i>Methods:</i></b> Between October 2014 and October 2017, consecutive patients diagnosed with ESUS were followed for new-onset AF and ischaemic stroke recurrence. The various P-wave indices, namely, the P-terminal force in the precordial lead V1 (PTFV1), P-wave duration, P-wave dispersion, interatrial blocks, and P-wave axis, were assessed on the initial electrocardiogram on presentation and studied for their relation to eventual AF detection and recurrent stroke. <b><i>Results:</i></b> 181 ischaemic stroke patients with ESUS were recruited and followed up for a median duration of 2.1 years. An abnormal PTFV1 was associated with occult AF detection but not with recurrent ischaemic strokes. No significant association was observed between the other P-wave indices with either occult AF or stroke recurrence. <b><i>Conclusion:</i></b> PTFV1 is associated with AF detection but not recurrent strokes in ESUS patients and can be a useful electrocardiographic marker for further risk stratification in ESUS patients.

scholarly journals Anticoagulation and Risk of Stroke Recurrence in Patients with Embolic Stroke of Undetermined Source Having No Potential Source of Embolism

2020 ◽  
Vol 49 (6) ◽  
pp. 601-608
Author(s):  
Noriko Sato ◽  
Ryu Matsuo ◽  
Fumi Kiyuna ◽  
Kuniyuki Nakamura ◽  
Jun Hata ◽  
...  
Keyword(s):  
Ischemic Stroke ◽  
Proportional Hazards Model ◽  
Recurrent Stroke ◽  
Oral Anticoagulants ◽  
Anticoagulation Therapy ◽  
Cox Proportional Hazards Model ◽  
Embolic Stroke ◽  
Stroke Recurrence ◽  
Potential Source ◽  
Reduced Risk

<b><i>Background:</i></b> This study aimed to determine whether use of oral anticoagulants (OACs) was associated with a reduced risk of recurrent stroke compared with use of antiplatelets (APs) in patients with embolic stroke of undetermined source (ESUS) having no potential source of embolism. <b><i>Methods:</i></b> Of 8,790 patients with acute ischemic stroke registered at 7 centers in the Fukuoka Stroke Registry from June 2007 to May 2017, we included 681 patients (mean age 69.7 [SD 14.1] years, 48.3% men) who experienced ESUS without a potential source of embolism and received OAC alone or AP alone. We estimated hazard ratios (HRs) and 95% confidential intervals (CIs) of recurrent ischemic stroke or any stroke after discharge using a Cox proportional hazards model and Fine and Gray model. <b><i>Results:</i></b> During a mean follow-up of 3.4 (SD 1.7) years, event rates of recurrent ischemic stroke were 4.4 per 100 person-years in 489 patients treated with AP and 2.0 per 100 person-years in 192 patients treated with OAC. OAC use was associated with a reduced risk of recurrent ischemic stroke, even after adjusting for potential confounding factors (multivariable-adjusted HR [95% CI], 0.42 [0.23–0.80]) and when additionally considering death as a competing risk (0.45 [0.24–0.85]). The reduced risk of recurrent ischemic stroke was still observed in patients treated with OAC (0.32 [0.15–0.67]) in reference to propensity score-matched patients treated with AP. These associations were maintained for all types of stroke, including ischemic and hemorrhagic stroke. <b><i>Conclusions:</i></b> This nonrandomized observational study suggests that anticoagulation therapy might be associated with a reduced risk of recurrent stroke compared with antiplatelet therapy in patients with ESUS in whom no potential source of embolism was identified. Further study should be performed in consideration of a potential source of embolism even in patients with ESUS.

Abstract 25: Left Atrial Volume Index is Associated With Atrial Fibrillation and Recurrent Stroke in Embolic Stroke of Undetermined Source (ESUS)

Stroke ◽  
2020 ◽  
Vol 51 (Suppl_1) ◽  
Author(s):  
Jamie S Ho ◽  
Ching-Hui Sia ◽  
Yushan Boi ◽  
Anthia S Foo ◽  
Mayank Dalakoti ◽  
...  
Keyword(s):  
Ischemic Stroke ◽  
Left Atrial ◽  
Recurrent Stroke ◽  
Left Atrial Volume ◽  
Embolic Stroke ◽  
Volume Index ◽  
Stroke Recurrence ◽  
Atrial Volume ◽  
Left Atrial Volume Index ◽  
Kaplan Meier

In ESUS, the relationship between atrial cardiopathy, occult AF and embolic stroke risk remains unclear. Studies suggest that left atrial volume index (LAVi) may be a better estimate of atrial cardiopathy than LA diameter. We explored LAVi as a marker of occult AF detection and ischemic stroke recurrence. Methods: From 2015-2017, consecutive ESUS patients diagnosed based on consensus criteria were studied. LAVi was measured using the Biplane Area-Length Method on TTE by trained cardiologists. Clinical outcomes measured were occult AF detection and ischemic stroke recurrence in a time-to-event analysis. Kaplan-Meier curves were constructed to compare outcomes in those with high versus low LAVi at optimized cut-off values. Results: 199 consecutive ESUS patients were followed up for 2.2±1.0 years. 9 patients were excluded due to technically inadequate views. Increased LAVi was associated with AF detection (36.63mL/m 2 ± 12.2 vs 26.93mL/m 2 ± 9.6) and stroke recurrence (32.13mL/m 2 ± 9.3 vs 27.23mL/m 2 ± 10.1). On multivariate regression adjusting for age, sex, hypertension and diabetes mellitus, LAVI was independently associated with AF detection (OR 1.08, CI 95% 1.03-1.14; p=0.003) and stroke recurrence (OR 1.05, CI 95% 1.01-1.10; p=0.026). Kaplan-Meier curves showed significant differences in occult AF (log-rank 8.67, p=0.003) and stroke recurrence (log-rank 5.31, p=0.021) between high (>27.7ml/m 2 ) and low LAVi (≤27.7ml/m 2 ) groups. Conclusion: Increased LAVi in ESUS patients was associated with AF detection and stroke recurrence, suggesting that this may be a useful echocardiographic marker to identify high-risk patients who may potentially benefit from anticoagulation.

scholarly journals Stroke recurrence in the different subtypes of ischemic stroke. The importance of the intracranial disease

2018 ◽  
Vol 76 (10) ◽  
pp. 649-653 ◽  
Author(s):  
Marcos C Lange ◽  
Gustavo Ribas ◽  
Valeria Scavasine ◽  
Renata Dal-Prá Ducci ◽  
Danielle C. Mendes ◽  
...  
Keyword(s):  
Ischemic Stroke ◽  
Recurrence Rate ◽  
Brazilian Population ◽  
Stroke Recurrence ◽  
Large Artery ◽  
Stroke Patients ◽  
Vessel Occlusion ◽  
Undetermined Etiology ◽  
Stroke Mechanism

ABSTRACT The aim of the study was to analyze the long-term recurrence rate in patients with a first-ever ischemic stroke secondary to intracranial large artery atherosclerosis (LAA) in a Brazilian population. Methods: All stroke patients admitted to the hospital between October 2012 and September 2015 were evaluated. The stroke mechanism subtypes were classified as cardioembolism, LAA, small-vessel occlusion, other determined etiologies, and stroke of undetermined etiology. Results: The 359 first-ever ischemic stroke patients were followed up for a mean time of 21.6 ± 15.1 months. The LAA intracranial (38.9%) and extracranial (24.6%) stroke patients presented with a higher stroke recurrence. Intracranial LAA [HR, 10.2 (3.6–29.1); p < 0.001] and extracranial LAA [HR, 5.05 (1.79–14.2); p = 0.002] were the only conditions to show positive correlation with the recurrence rate, after adjusting for risk factors, thrombolysis, and National Institutes of Health Stroke Scale score at admission. Conclusion: Intracranial LAA presents a higher incidence of recurrence of ischemic stroke when compared with other etiologies in a Southern Brazilian population.

Abstract T MP39: Could Difficult-to-treat Hypertension Be a Predictor of Bad Outcome in Ischemic Stroke?

Stroke ◽  
2015 ◽  
Vol 46 (suppl_1) ◽  
Author(s):  
Pedro Colla Machado ◽  
Maria C Zurru ◽  
Ariel Luzzi ◽  
Laura Brescacin ◽  
Claudia Alonzo ◽  
...  
Keyword(s):  
Blood Pressure ◽  
Ischemic Stroke ◽  
Clinical Practice ◽  
Stroke Prevention ◽  
Demographic Data ◽  
Stroke Recurrence ◽  
Vascular Risk ◽  
Stroke Patients ◽  
Blood Pressure Targets ◽  
Adherence To Medication

Background and purpose: hypertension is the vascular risk factor most commonly related to stroke, making antihypertensive treatment a cornerstone of stroke prevention. Achieving targets of clinical practice guidelines could be difficult in some patients, requiring combination of drugs to maintain these goals. We aimed to evaluate the relationship between difficult-to-treat hypertension (DTTH) and stroke outcomes. Methods: acute ischemic stroke patients were prospectively included in PROTEGE-ACV, a multidisciplinary secondary stroke prevention program. Demographic data, vascular risk factors (VRF) profile and control, and stroke outcome (disability, mortality and stroke recurrence) were evaluated 30 days after stroke. Difficult-to-treat hypertension was defined as those requiring more than two drugs in hypertension management. Results: we analyzed data of the 1194 stroke patients included between December 2006 and December 2013. We found 186 DTTH patients, who had higher burden of VRF and poorer pre-stroke control (table); they had higher admission blood pressure (0 drugs 146/82 mmHg, 1 drug 151/84, 2 drugs 154/83, 3 drugs 153/83, 4 drugs 169/88; p 0.001 for SBP, 0.26 for DBP) and pulse pressure (63 mmHg, 66 mmHg, 70 mmHg, 67 mmHg, 81 mmHg respectively; p 0.0006). These patients had also worst 30-day outcome: m-Rankin >1 (24% in no-DTTH vs 54% in DTTH, 0.0001), mortality (1% vs 16%, p 0.001), composite disability + all cause death (44% vs 73%, p 0.001). We found no difference in early stroke recurrence. Conclusion: the number of drugs necessary to treat hypertension could be useful to identify barriers to achieve blood pressure targets for vascular disease prevention, as vascular aging, hemodynamic changes, adherence to medication and healthy lifestyle. This indicator is easy to collect and could help to decision making in daily clinical practice.

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