Embolic strokes of undetermined source: the case for a new clinical construct

Hart, Robert G.; Diener, Hans Christoph; Coutts, Shelagh B.; Easton, J. Donald; Granger, Christopher B.; O’Donnell, Martin; Sacco, Ralph L.; Connolly, Stuart J.

doi:10.1016/s1474-4422(13)70310-7

Cited by 1,343 publications

(1,271 citation statements)

References 140 publications

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“…These factors may explain some unusual features of their population including a relatively high proportion of ESUS compared with other noncardioembolic subtypes and the high proportion of women. The relative prevalence of cryptogenic stroke observed in other studies compared with the arterial subtypes included in this study suggests that ESUS should make up about one third of the sample rather than the 47% observed 1. Similarly, pooled cohort studies demonstrate a female proportion of 42% in ESUS compared with the slight predominance of women observed (51.9%) 3…”

supporting

confidence: 47%

“…ESUS has been operationally defined as a nonlacunar stroke not associated with significant stenosis in a feeding artery in the absence of a high‐risk cardioembolic source or other known cause. A significant advance is the elaboration of a pragmatic set of investigations required to meet the definition by the Cryptogenic Stroke/ESUS Working Group 1. The construct has generated interest for the potential to illuminate the otherwise murky concept of cryptogenic stroke, and while some would argue that concept remains fuzzy, some clarity is emerging 3, 4, 5.…”

mentioning

confidence: 99%

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Embolic Stroke of Uncertain Source: An Entity Slowly Coming Into Focus

Sharma

2017

JAHA

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supporting

confidence: 47%

mentioning

confidence: 99%

Embolic Stroke of Uncertain Source: An Entity Slowly Coming Into Focus

Sharma

2017

JAHA

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“…Despite extensive pathogenic workup, approximately one third of acute ischemic strokes are classified as cryptogenic 1, 2. Observational studies have demonstrated a strong association between patent foramen ovale (PFO) and cryptogenic stroke,3, 4 suggesting that paradoxical embolism through a PFO may be an important cause of otherwise unexplained ischemic strokes, notably in younger patients 5, 6.…”

Section: Introductionmentioning

confidence: 99%

Closure, Anticoagulation, or Antiplatelet Therapy for Cryptogenic Stroke With Patent Foramen Ovale: Systematic Review of Randomized Trials, Sequential Meta‐Analysis, and New Insights From the CLOSE Study

Turc

Calvet

Guérin

et al. 2018

JAHA

123

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BackgroundWe conducted a systematic review and meta‐analysis of randomized controlled trials (RCTs) comparing patent foramen ovale (PFO) closure, anticoagulation, and antiplatelet therapy to prevent stroke recurrence in patients with PFO‐associated cryptogenic stroke.Methods and ResultsWe searched Medline, Cochrane Library, and EMBASE through March 2018. The primary outcome was stroke recurrence. Pooled incidences, hazard ratios, and risk ratios (RRs) were calculated in random‐effects meta‐analyses. PFO closure was associated with a lower risk of recurrent stroke compared with antithrombotic therapy (antiplatelet therapy or anticoagulation: 3560 patients from 6 RCTs; RR=0.36, 95% CI: 0.17–0.79; I2=59%). The effect of PFO closure on stroke recurrence was larger in patients with atrial septal aneurysm or large shunt (RR=0.27, 95% CI, 0.11–0.70; I2=42%) compared with patients without these anatomical features (RR=0.80, 95% CI, 0.43–1.47; I2=12%). Major complications occurred in 2.40% (95% CI, 1.03–4.25; I2=77%) of procedures. New‐onset atrial fibrillation was more frequent in patients randomized to PFO closure versus antithrombotic therapy (RR=4.33, 95% CI, 2.37–7.89; I2=14%). One RCT compared PFO closure versus anticoagulation (353 patients; hazard ratio=0.14, 95% CI, 0.00–1.45) and 2 RCTs compared PFO closure versus antiplatelet therapy (1137 patients; hazard ratio=0.18, 95% CI, 0.05–0.63; I2=12%). Three RCTs compared anticoagulation versus antiplatelet therapy, with none showing a significant difference.Conclusions PFO closure is superior to antithrombotic therapy to prevent stroke recurrence after cryptogenic stroke. The annual absolute risk reduction of stroke was low, but it has to be tempered by a substantial time at risk (at least 5 years) in young and middle‐aged patients. PFO closure was associated with an increased risk of atrial fibrillation.

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“…Therefore, there could be a referral bias because of the feature of our institute as a university hospital, and the distribution of infarct location could be different from that in the general patient population with stroke. However, we used established criteria for the diagnosis of ESUS1 and have consecutively enrolled the patients; the mean follow‐up of patients was ≈1 year, with a minimum follow‐up of 3 months. Accordingly, the detection rate of subclinical AT/AF corresponded well to those of the previous publications, which suggests that the patient population in the present study should not be strongly biased 13, 14.…”

Section: Discussionmentioning

confidence: 99%

High Incidence of Atrial Fibrillation After Embolic Stroke of Undetermined Source in Posterior Cerebral Artery Territory

Makimoto

Kurt

Gliem

et al. 2017

JAHA

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BackgroundSubclinical atrial fibrillation is one possible cause of embolic stroke of undetermined source (ESUS). It remains to be elucidated if a specific infarction site has a predictive value for detecting subclinical atrial fibrillation. We aimed to investigate the predictive value of infarction site in patients with ESUS for the detection of atrial tachyarrhythmia (AT) using an insertable cardiac monitor.Methods and ResultsConsecutive 146 patients (84 men; aged 62±12 years) underwent insertable cardiac monitor implantation after diagnosis of ESUS. The detection of AT >30 seconds was evaluated. The ESUS infarction sites were categorized into internal carotid artery and vertebral artery (VA) territories, with ophthalmic artery, anterior cerebral artery, and middle cerebral artery as internal carotid artery subterritories, and posterior cerebral artery and other vertebrobasilar arteries as VA subterritories. During a median follow‐up of 387 days, AT was detected in 33 patients (23%). Subclinical AT detection was significantly more frequent after VA territorial infarction opposed to internal carotid artery infarction (20/57 [35%] versus 13/89 [15%]; P=0.0039). Kaplan‐Meier analysis demonstrated a significantly higher AT detection rate after VA infarction (log‐rank, P=0.0076). Regression analysis revealed that VA territorial infarction, and particularly posterior cerebral artery area infarction, was an independent predictor of AT detection.ConclusionsPatients with ESUS in the posterior cerebral artery territory had a higher rate of subclinical AT detection than those with other infarct localizations. Our data suggest that the possible usefulness of ESUS site to identify candidates for direct oral anticoagulation should be confirmed in future research.

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Embolic strokes of undetermined source: the case for a new clinical construct

Cited by 1,343 publications

References 140 publications

Embolic Stroke of Uncertain Source: An Entity Slowly Coming Into Focus

Embolic Stroke of Uncertain Source: An Entity Slowly Coming Into Focus

Closure, Anticoagulation, or Antiplatelet Therapy for Cryptogenic Stroke With Patent Foramen Ovale: Systematic Review of Randomized Trials, Sequential Meta‐Analysis, and New Insights From the CLOSE Study

High Incidence of Atrial Fibrillation After Embolic Stroke of Undetermined Source in Posterior Cerebral Artery Territory

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