Non‐obstructive carotid atherosclerosis and patent foramen ovale in young adults with cryptogenic stroke

Jaffre, Aude; Guidolin, Brigitte; Ruidavets, Jean Bernard; Nasr, Nathalie; Larrue, Vincent

doi:10.1111/ene.13275

Cited by 27 publications

(15 citation statements)

References 22 publications

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“…18,23 This hypothesis is supported by several studies that highlighted the significance of non-stenotic carotid plaques as a cause of ischemic stroke. 36--43…”

Section: Discussionmentioning

confidence: 99%

Identification of patients with embolic stroke of undetermined source and low risk of new incident atrial fibrillation: The AF-ESUS score

Ntaios

Perlepe

Lambrou

et al. 2020

International Journal of Stroke

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Background and aims Only a minority of patients with Embolic Stroke of Undetermined Source (ESUS) receive prolonged cardiac monitoring despite current recommendations. The identification of ESUS patients who have low probability of new diagnosis of atrial fibrillation (AF) could potentially support a strategy of more individualized allocation of available resources and hence, increase their diagnostic yield. We aimed to develop a tool that can identify ESUS patients who have low probability of new incident AF. Methods We performed multivariate stepwise regression in a pooled dataset of consecutive ESUS patients from three prospective stroke registries to identify predictors of new incident AF. The coefficient of each independent covariate of the fitted multivariable model was used to generate an integer-based point scoring system. Results Among 839 patients (43.1% women, median age 67.0 years) followed-up for a median of 24.3 months (2999 patient-years), 125 (14.9%) had new incident AF. The proposed score assigns 3 points for age ≥ 60 years; 2 points for hypertension; −1 point for left ventricular hypertrophy reported at echocardiography; 2 points for left atrial diameter >40 mm; −3 points for left ventricular ejection fraction <35%; 1 point for the presence of any supraventricular extrasystole recorded during all available 12-lead standard electrocardiograms performed during hospitalization for the ESUS; −2 points for subcortical infarct; −3 points for the presence of non-stenotic carotid plaques. The rate of new incident AF during follow-up was 1.97% among the 42.3% of the cohort who had a score of ≤0, compared to 26.9% in patients with > 0 (relative risk: 13.7, 95%CI: 5.9--31.5). The area under the curve of the score was 84.8% (95%CI: 79.9--86.9%). The sensitivity and negative predictive value of a score of ≤0 for new incident AF during follow-up were 94.9% (95%CI: 89.3--98.1%) and 98.0% (95%CI: 95.8--99.3%), respectively. Conclusions The proposed AF-ESUS score has high sensitivity and high negative predictive value to identify ESUS patients who have low probability of new incident AF. Patients with a score of 1 or more may be better candidates for prolonged automated cardiac monitoring. Clinical trial registration URL: https://www.clinicaltrials.gov / Unique identifier: NCT02766205.

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“…18,23 This hypothesis is supported by several studies that highlighted the significance of non-stenotic carotid plaques as a cause of ischemic stroke. 36--43…”

Section: Discussionmentioning

confidence: 99%

Identification of patients with embolic stroke of undetermined source and low risk of new incident atrial fibrillation: The AF-ESUS score

Ntaios

Perlepe

Lambrou

et al. 2020

International Journal of Stroke

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“…In addition, the AF‐ESUS (Prediction of Atrial Fibrillation after Embolic Stroke of Undetermined Source) study showed that new incident AF is less frequently detected in patients with ESUS and carotid plaques compared to those without [18]. Similarly, in young adults with cryptogenic stroke, carotid plaques were associated with the absence of PFO [41]. Both latter studies show that carotid plaques act as a competing stroke aetiology to other established stroke aetiologies, and hence, support their role as an underlying cause of ESUS.…”

Section: Discussionmentioning

confidence: 99%

Data‐driven machine‐learning analysis of potential embolic sources in embolic stroke of undetermined source

Ntaios

Weng

Perlepe

et al. 2020

Euro J of Neurology

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Background and purpose: Hierarchical clustering, a common 'unsupervised' machine-learning algorithm, is advantageous for exploring potential underlying aetiology in particularly heterogeneous diseases. We investigated potential embolic sources in embolic stroke of undetermined source (ESUS) using a data-driven machine-learning method, and explored variation in stroke recurrence between clusters. Methods: We used a hierarchical k-means clustering algorithm on patients' baseline data, which assigned each individual into a unique clustering group, using a minimum-variance method to calculate the similarity between ESUS patients based on all baseline features. Potential embolic sources were categorised into atrial cardiopathy, atrial fibrillation, arterial disease, left ventricular disease, cardiac valvulopathy, patent foramen ovale (PFO) and cancer. Results: Among 800 consecutive ESUS patients (43.3% women, median age 67 years), the optimal number of clusters was four. Left ventricular disease was most prevalent in cluster 1 (present in all patients) and perfectly associated with cluster 1. PFO was most prevalent in cluster 2 (38.9% of patients) and associated significantly with increased likelihood of cluster 2 [adjusted odds ratio: 2.69, 95% confidence interval (CI): 1.64-4.41]. Arterial disease was most prevalent in cluster 3 (57.7%) and associated with increased likelihood of cluster 3 (adjusted odds ratio: 2.21, 95% CI: 1.43-3.13). Atrial cardiopathy was most prevalent in cluster 4 (100%) and perfectly associated with cluster 4. Cluster 3 was the largest cluster involving 53.7% of patients. Atrial fibrillation was not significantly associated with any cluster. Conclusions: This data-driven machine-learning analysis identified four clusters of ESUS that were strongly associated with arterial disease, atrial cardiopathy, PFO and left ventricular disease, respectively. More than half of the patients were assigned to the cluster associated with arterial disease.

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“…In a study of 68 patients with embolic stroke, including 45 ESUS, the presence of high-risk plaque features on carotid ultrasound (ulceration, thickness ≥ 3 mm, and echolucency) was independently associated with detection of atrial fibrillation on admission or during follow-up (OR = 4.5, 95% CI: 1.0–19.6) ( 41 ). Fourth, in some patients with ESUS diagnosed using the current clinical definition, non-stenotic carotid plaques often coexist with other potential causes of stroke, including atrial fibrillation (8.5%) ( 15 ), intracranial atherosclerosis (8.4%) ( 42 ), PFO (5–9%) ( 43 , 44 ), and atrial cardiopathy (2.4%) ( 45 ).…”

Section: Challenges Of Establishing Causal Link With Strokementioning

confidence: 99%

Non-stenotic Carotid Plaques in Embolic Stroke of Unknown Source

et al. 2021

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Embolic stroke of unknown source (ESUS) represents one in five ischemic strokes. Ipsilateral non-stenotic carotid plaques are identified in 40% of all ESUS. In this narrative review, we summarize the evidence supporting the potential causal relationship between ESUS and non-stenotic carotid plaques; discuss the remaining challenges in establishing the causal link between non-stenotic plaques and ESUS and describe biomarkers of potential interest for future research. In support of the causal relationship between ESUS and non-stenotic carotid plaques, studies have shown that plaques with high-risk features are five times more prevalent in the ipsilateral vs. the contralateral carotid and there is a lower incidence of atrial fibrillation during follow-up in patients with ipsilateral non-stenotic carotid plaques. However, non-stenotic carotid plaques with or without high-risk features often coexist with other potential etiologies of stroke, notably atrial fibrillation (8.5%), intracranial atherosclerosis (8.4%), patent foramen ovale (5–9%), and atrial cardiopathy (2.4%). Such puzzling clinical associations make it challenging to confirm the causal link between non-stenotic plaques and ESUS. There are several ongoing studies exploring whether select protein and RNA biomarkers of plaque progression or vulnerability could facilitate the reclassification of some ESUS as large vessel strokes or help to optimize secondary prevention strategies.

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Non‐obstructive carotid atherosclerosis and patent foramen ovale in young adults with cryptogenic stroke

Abstract: This study demonstrates that NOCA is common in young adults with CS. NOCA is negatively associated with PFO. Detecting NOCA is an important component of stroke investigation in young adults.

Cited by 27 publications

References 22 publications

Identification of patients with embolic stroke of undetermined source and low risk of new incident atrial fibrillation: The AF-ESUS score

Identification of patients with embolic stroke of undetermined source and low risk of new incident atrial fibrillation: The AF-ESUS score

Data‐driven machine‐learning analysis of potential embolic sources in embolic stroke of undetermined source

Non-stenotic Carotid Plaques in Embolic Stroke of Unknown Source

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