Prediction of AF in ESUS

NCT ID: NCT02766205

Last Updated: 2018-10-17

Basic Information

• Recruitment Status: UNKNOWN
• Total Enrollment: 500 participants
• Study Classification: OBSERVATIONAL
• Study Start Date: 2016-06-30
• Study Completion Date: 2019-07-31

Brief Summary

The aim of the proposed study is to identify predictors of covert atrial fibrillation (AF) in Embolic Stroke of Undetermined Source (ESUS) patients and develop a prognostic score for the identification of covert AF in this population.

Detailed Description

A new clinical entity termed Embolic Stroke of Undetermined Source (ESUS) was recently introduced by the Cryptogenic Stroke/ESUS International Working Group, which describes stroke patients for whom the source of embolism remains undetected despite thorough investigation; potential embolic sources include diseases of the mitral and aortic valves, the left cardiac chambers, the proximal cerebral arteries of the aortic arch and the venous system via paradoxical embolism. ESUS has been proposed as a potential therapeutic entity with a possible indication for anticoagulation, a hypothesis which is currently tested in two randomized controlled trials.

ESUS is defined as a visualized non-lacunar brain infarct in the absence of a) extracranial or intracranial atherosclerosis causing ≥50% luminal stenosis in arteries supplying the area of ischaemia, b) major-risk cardioembolic source, and c) any other specific cause of stroke (e.g. arteritis, dissection, migraine/vasospasm, drug misuse). Major risk sources of cardioembolism include permanent or paroxysmal atrial fibrillation, sustained atrial flutter, intracardiac thrombus, prosthetic cardiac valve, atrial myxoma or other cardiac tumours, mitral stenosis, recent (<4 weeks) myocardial infarction, left ventricular ejection fraction less than 30%, valvular vegetations, or infective endocarditis.

Recently, our group presented a descriptive analysis of an ESUS population derived from the Athens Stroke Registry. Among the overall ischemic stroke population, 10% of patients were classified as ESUS. These strokes were of mild-moderate severity and covert AF was identified as the underlying etiopathogenetic mechanism in approximately 40% of ESUS patients. The mortality risk in ESUS patients is lower compared to patients with cardioembolic stroke despite similar rates of stroke recurrence.

Also, the risk of stroke recurrence is higher in ESUS patients than in patients with non-cardioembolic strokes which could be a sign that the current antithrombotic strategy of treating ESUS patients with antiplatelets is suboptimal. Indeed, currently, it is not clear whether antiplatelets or anticoagulants are the ideal antithrombotic strategy in ESUS. Recently, two international, phase III, double-blind, randomized, controlled clinical trial were launched aiming to investigate whether anticoagulant treatment is superior to antiplatelet treatment for the secondary prevention in ESUS patient : the Randomized Evaluation in Secondary stroke Prevention Comparing the Thrombin inhibitor dabigatran etexilate versus aspirin in Embolic Stroke of Undetermined Source (RE-SPECT ESUS) trial and the NAVIGATE trial will compare dabigatran etexilate and rivaroxaban respectively to aspirin in ESUS patients.

It would be clinically useful to identify the predictors of covert AF in the ESUS population as this could possibly influence the choice of antithrombotic treatment, e.g. anticoagulants in ESUS patients at high risk of covert AF, and antiplatelets for ESUS patients with low risk of covert AF.

Conditions

Embolic Stroke of Undetermined Source

Study Design

• Observational Model Type: COHORT
• Study Time Perspective: OTHER

Eligibility Criteria

Inclusion Criteria

• 1. Embolic stroke of undetermined source (ESUS) defined as:

• Ischemic stroke (including transient ischemic attack with positive neuroimaging) visualized by brain CT or MRI that is not lacunar (i.e., subcortical infarct ≤1.5 cm), and
• Absence of cervical carotid atherosclerotic stenosis (or vertebral and basilar artery stenosis in case of posterior circulation stroke), that is ≥ 50%, or occlusion in arteries supplying the area of ischemia in CT or magnetic resonance (MR) angiography or ultrasound, and
• No history of AF, no documented AF on 12-lead electrocardiogram (ECG) or episode of AF lasting 6 minutes or longer detected after ≥ 24-hour cardiac rhythm monitoring (Holter or telemetry), and
• No intra-cardiac thrombus on transthoracic echocardiography, and
• No other specific cause of stroke identified by routine clinical care (e.g., arteritis, dissection, migraine/vasospasm, drug abuse)
• 2. Age ≥18 years
• 3. Written informed consent

Exclusion Criteria

• 1. ≥ 50% luminal stenosis or occlusion in arteries supplying the area of ischemia
• 2. History of AF
• 3. Life expectancy less than 6 months

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

University of Lausanne

OTHER

Sponsor Role: collaborator

University of Athens

OTHER

Sponsor Role: collaborator

University of Thessaly

OTHER

Sponsor Role: lead

Responsible Party

George Ntaios

MD, MSc (ESO Stroke Medicine), PhD, FESO, Assistant Professor of Internal Medicine, Medical School, University of Thessaly, Larissa University Hospital

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

George Ntaios, MD, PhD

Role: PRINCIPAL_INVESTIGATOR

Medical School, University of Thessaly, Larissa University Hospital

Locations

Department of Clinical Therapeutics, University of Athens, Alexandra Hospital

Athens, , Greece

Medical School, University of Thessaly, Larissa University Hospital

Larissa, , Greece

Centre Cérébrovasculaire, Service de Neurologie, Département des Neurosciences Cliniques, Centre Hospitalier Universitaire Vaudois and University of Lausanne

Lausanne, , Switzerland

Countries

Greece; Switzerland

References

Hart RG, Diener HC, Coutts SB, Easton JD, Granger CB, O'Donnell MJ, Sacco RL, Connolly SJ; Cryptogenic Stroke/ESUS International Working Group. Embolic strokes of undetermined source: the case for a new clinical construct. Lancet Neurol. 2014 Apr;13(4):429-38. doi: 10.1016/S1474-4422(13)70310-7.

Reference Type: BACKGROUND

PMID: 24646875 (View on PubMed)

Ntaios G, Papavasileiou V, Milionis H, Makaritsis K, Vemmou A, Koroboki E, Manios E, Spengos K, Michel P, Vemmos K. Embolic Strokes of Undetermined Source in the Athens Stroke Registry: An Outcome Analysis. Stroke. 2015 Aug;46(8):2087-93. doi: 10.1161/STROKEAHA.115.009334. Epub 2015 Jul 9.

Reference Type: BACKGROUND

PMID: 26159795 (View on PubMed)

Ntaios G, Papavasileiou V, Milionis H, Makaritsis K, Manios E, Spengos K, Michel P, Vemmos K. Embolic strokes of undetermined source in the Athens stroke registry: a descriptive analysis. Stroke. 2015 Jan;46(1):176-81. doi: 10.1161/STROKEAHA.114.007240. Epub 2014 Nov 6.

Reference Type: BACKGROUND

PMID: 25378429 (View on PubMed)

Diener HC, Easton JD, Granger CB, Cronin L, Duffy C, Cotton D, Brueckmann M, Sacco RL; RE-SPECT ESUS Investigators. Design of Randomized, double-blind, Evaluation in secondary Stroke Prevention comparing the EfficaCy and safety of the oral Thrombin inhibitor dabigatran etexilate vs. acetylsalicylic acid in patients with Embolic Stroke of Undetermined Source (RE-SPECT ESUS). Int J Stroke. 2015 Dec;10(8):1309-12. doi: 10.1111/ijs.12630. Epub 2015 Sep 30.

Reference Type: BACKGROUND

PMID: 26420134 (View on PubMed)

Kitsiou A, Sagris D, Schabitz WR, Ntaios G. Validation of the AF-ESUS score to identify patients with embolic stroke of undetermined source and low risk of device-detected atrial fibrillation. Eur J Intern Med. 2021 Jul;89:135-136. doi: 10.1016/j.ejim.2021.04.003. Epub 2021 May 2. No abstract available.

Reference Type: DERIVED

PMID: 33952425 (View on PubMed)

Ntaios G, Weng SF, Perlepe K, Akyea R, Condon L, Lambrou D, Sirimarco G, Strambo D, Eskandari A, Karagkiozi E, Vemmou A, Korompoki E, Manios E, Makaritsis K, Vemmos K, Michel P. Data-driven machine-learning analysis of potential embolic sources in embolic stroke of undetermined source. Eur J Neurol. 2021 Jan;28(1):192-201. doi: 10.1111/ene.14524. Epub 2020 Oct 7.

Reference Type: DERIVED

PMID: 32918305 (View on PubMed)

Ntaios G, Perlepe K, Lambrou D, Sirimarco G, Strambo D, Eskandari A, Karagkiozi E, Vemmou A, Korompoki E, Manios E, Makaritsis K, Vemmos K, Michel P. Identification of patients with embolic stroke of undetermined source and low risk of new incident atrial fibrillation: The AF-ESUS score. Int J Stroke. 2021 Jan;16(1):29-38. doi: 10.1177/1747493020925281. Epub 2020 May 19.

Reference Type: DERIVED

PMID: 32423317 (View on PubMed)

Leventis I, Perlepe K, Sagris D, Sirimarco G, Strambo D, Georgiopoulos G, Eskandari A, Karagkiozi E, Vemmou A, Koroboki E, Manios E, Makaritsis K, Vemmos K, Michel P, Ntaios G. Characteristics and outcomes of Embolic Stroke of Undetermined Source according to stroke severity. Int J Stroke. 2020 Oct;15(8):866-871. doi: 10.1177/1747493020909546. Epub 2020 Mar 2.

Reference Type: DERIVED

PMID: 32122289 (View on PubMed)

Perlepe K, Sirimarco G, Strambo D, Eskandari A, Karagkiozi E, Vemmou A, Koroboki E, Manios E, Makaritsis K, Vemmos K, Michel P, Ntaios G. Left atrial diameter thresholds and new incident atrial fibrillation in embolic stroke of undetermined source. Eur J Intern Med. 2020 May;75:30-34. doi: 10.1016/j.ejim.2020.01.002. Epub 2020 Jan 15.

Reference Type: DERIVED

PMID: 31952983 (View on PubMed)

Ntaios G, Perlepe K, Lambrou D, Sirimarco G, Strambo D, Eskandari A, Karagkiozi E, Vemmou A, Koroboki E, Manios E, Makaritsis K, Vemmos K, Michel P. Prevalence and Overlap of Potential Embolic Sources in Patients With Embolic Stroke of Undetermined Source. J Am Heart Assoc. 2019 Aug 6;8(15):e012858. doi: 10.1161/JAHA.119.012858. Epub 2019 Jul 31.

Reference Type: DERIVED

PMID: 31364451 (View on PubMed)

Ntaios G, Perlepe K, Sirimarco G, Strambo D, Eskandari A, Karagkiozi E, Vemmou A, Koroboki E, Manios E, Makaritsis K, Michel P, Vemmos K. Carotid plaques and detection of atrial fibrillation in embolic stroke of undetermined source. Neurology. 2019 Jun 4;92(23):e2644-e2652. doi: 10.1212/WNL.0000000000007611. Epub 2019 May 8.

Reference Type: DERIVED

PMID: 31068479 (View on PubMed)

Other Identifiers

WI211961

Identifier Type: -

Identifier Source: org_study_id