Identification of New Markers of Atrial Myopathy in Patients With Embolic Stroke of Undetermined Source (ESUS) From MRI 4D Data

Study Overview
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Brief Summary
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Atrial myopathy is considered to be the underlying cause of a large proportion of embolic strokes of undetermined source. However, the definition of this atrial condition is not well delineated while its identification could lead to prescription on anticoagulation in order to avoid stroke recurences. This study aims to identify new markers of atrial myopathy and choosed a multi parametric approach with electrical, echographical, biological and 4D flow CMR derived markers.

Official Title
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Identification of New Markers of Atrial Myopathy in Patients With Embolic Stroke of Undetermined Source (ESUS) From MRI 4D Data

Conditions
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Embolic Stroke of Undetermined Source

Intervention / Treatment
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* Other: 4D Flow MRI
* Other: Medical consultation with 12 leads ECG
* Other: Holter ECG
* Other: Trans thoracic echocardiography
* Biological: Blood sample
* Other: Standard MRI


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Groupe1:Ischemic embolic stroke of undetermined source (ESUS) according to TOAST criteria (N =10) Age ≥ 18 years old Non-gap ischemic stroke diagnosed on MRI or CT scan of the brain (gap stroke defined as a cerebral infarction ≤ 1.5 cm / ≤2.0 cm on diffusion sequences). No major cardio-embolic source (episode of atrial fibrillation or flutter > 6min, intracardiac thrombus, LVEF <30 percent recent myocardial infarction (<4 weeks), mitral stenosis, valvular vegetation or infectious endocarditis). Absence of atherosclerosis causing stenosis ≥ 50 percent of the lumen of the intra or extra cranial arteries that vascularise the infarcted cerebral area. No other specific cause identified (arteritis, arterial dissection, migraine/vaso-spasm, toxic cause). Affiliation to a social security scheme Patient who signed the consent Group 2: Non-paroxysmal AF (N=10) Age ≥ 18 years old Subject with documented non-paroxysmal AF Affiliation to a social security scheme Patient who signed the consent Group 3: Healthy volunteers (N=10) Pre-inclusion criteria : Age ≥ 45 years old Patient with no documented cardiac or neuro-vascular history Affiliation to a social security scheme Patient who signed the consent Registration on the VRB file (Volontaires Recherches Biomédicales, https://vrb.sante.gouv.fr) or response to the published announcement Criteria for inclusion : ECG in sinus rhythm Holter ECG: no AF Normal Trans thoracic echocardiography Patient with no neuro-vascular history Group 4: Stroke-ESUS or non-paroxysmal AF with cardiac MRI (N=10) Age ≥ 18 years old Subject with a documented stroke-ESUS or documented non-paroxysmal FA Subject with cardiac MRI Affiliation to a social security scheme Subject having given its non-opposition Exclusion Criteria: Groupe1: Ischemic embolic stroke of undetermined source (ESUS) according to TOAST criteria (N =10) Risk of pregnancy or pregnancy (proven on interrogation data or pregnancy test). Contraindication to MRI ferromagnetic material (in particular pacemaker, implantable defibrillator, cardiac valve prosthesis, cochlear implant, neuro-stimulator, implanted automated injection material, intraocular metallic foreign body, neurosurgical and vascular clips, claustrophobia) Less than 8 weeks after implantation of a stent Subject participating in another intervention research including a period of exclusion still in progress at the pre-inclusion stage. Group 2: Non-paroxysmal AF (N=10) Risk of pregnancy or pregnancy (proven on interview data or pregnancy test). Contraindication to MRI ferromagnetic material (in particular pacemaker, implantable defibrillators, cardiac valve prosthesis, cochlear implant, neurostimulators, implanted automated injection equipment, intraocular metallic foreign body, neurosurgical and vascular clips, claustrophobia). Less than 8 weeks after implantation of a stent Subject participating in another intervention research including a period of exclusion still in progress at the pre-inclusion stage. Group 4: Stroke-ESUS or non paroxysmal AF with cardiac MRI (N=10) History of neuro-vascular or cardiac pathology Risk of pregnancy or pregnancy (proven on interrogation data or pregnancy test). Contraindication to MRI (ferromagnetic material (in particular pacemaker, implantable defibrillator, cardiac valve prosthesis, cochlear implant, neuro-stimulator, implanted automated injection material, intraocular metallic foreign body, neurosurgical and vascular clips, claustrophobia) Subject participating in another intervention research including a period of exclusion still in progress at the pre-inclusion stage.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Basic Science
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Patients with embolic strokes of undetermined source.<br>Patients over 18 years old, with embolic strokes of undetermined source, fulfilling the TOAST criteria. The intervention consists of a 4D Flow MRI. | Other: 4D Flow MRI<br>* Acquisitions of MR imagining with special contrast phase CMR sequences. There is no need for agent contrast injection. The CMR is performed at the time of inclusion.<br>|
| Experimental: Patients with non-paroxysmal AF.<br>Patients over 18 years old, with non-paroxysmal AF. The intervention consists of a 4D Flow MRI. | Other: 4D Flow MRI<br>* Acquisitions of MR imagining with special contrast phase CMR sequences. There is no need for agent contrast injection. The CMR is performed at the time of inclusion.<br>|
| Active Comparator: Heathy volunteers<br>The control group will include volunteers over 45 years old with no history of cardio-vascular or neuro-vascular disease. The last will be certified by a pre inclusion protocol containing a medical consultation, a Holter ECG and a trans-thoracic echocardiography. The age of 45 was chosen to get comparable age group and set the analyses free of the age-related effect on the cardiac hemodynamic. The intervention consists of an ECG, holter ECG, Trans thoracic echocardiography ETT, Blood sample and 4D Flow MRI. | Other: 4D Flow MRI<br>* Acquisitions of MR imagining with special contrast phase CMR sequences. There is no need for agent contrast injection. The CMR is performed at the time of inclusion.<br>Other: Medical consultation with 12 leads ECG<br>* Collection of medical history, treatment, physical examination and realization of a 12 leads ECG.<br>Other: Holter ECG<br>* 48 hours ECG recording<br>Other: Trans thoracic echocardiography<br>* Trans thoracic echocardiography with standard measures performes in the core lab.<br>Biological: Blood sample<br>* Blood sample in a peripheral vein, send to medical laboratory to dosage of NT pro BNP and troponin serum level.<br>|
| Experimental: ESUS and non-paroxysmal AF patients with cardiac MRI<br>ESUS and non-paroxysmal AF patients (fulfilling the group 1 et 2 criteria) and who had had cardiac MRI, in a retrospective way. It corresponds to retrospective inclusion of patients which had MRI in the year before the beginning of the study. | Other: Standard MRI<br>* Acquisitions of MR imagining<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Mean flow velocities in the left atrium | Velocity magnitude (cm/s) for all atrial voxels and all cardiac frames will be plotted in a histogram and normalized by the total number of voxels to allow comparisons between subjects | One Day | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Maximal flow velocities in the left atrium | Velocity magnitude (cm/s) for all atrial voxels and all cardiac frames will be plotted in a histogram and normalized by the total number of voxels to allow comparisons between subjects. Local peak velocity will be obtained by averaging 5 percent of all maximum values. | One Day | 
| Left atrium stasis | Velocity magnitude (cm/s) for all atrial voxels and all cardiac frames will be plotted in a histogram and normalized by the total number of voxels to allow comparisons between subjects. Local peak velocity will be obtained by averaging 5 percent of all maximum values | One Day | 
| Vortex size | Vortices in the isolated LA chamber were detectedusing the Lambda2 (λ2) method, which is an objective and widelyaccepted method to identify 3D vortice. | One Day | 
| Left atrium volume | Extracted from 3D MR reconstruction, expressed in mL/m2 of body surface area. | One Day | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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MRI, Atrial Myopathy, Atrial Fibrillation, ESUS, blood velocity, left atrium