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

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.

Study Overview

• Status: Recruiting
• Conditions: Embolic Stroke of Undetermined Source
• Intervention / Treatment: Other: 4D Flow MRI; Other: Medical consultation with 12 leads ECG; Other: Holter ECG; Other: Trans thoracic echocardiography; Biological: Blood sample; Other: Standard MRI

• Study Type: Interventional
• Enrollment (Estimated): 40
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Philippe CHEVALIER, Pr; Phone Number: +33 4.72.35.70.27; Email: philippe.chevalier@chu-lyon.fr
• Study Contact Backup: Name: Sihem BEN AOUICHA, PhD; Phone Number: +33 4 72 35 69 42; Email: Sihem.ben-aouicha@chu-lyon.fr

Study Locations

• France
  • Bron, France, 69677
    • Not yet recruiting
    • Service d'urgences neuro-vasculaires, service de neurologie vasculaire Hôpital neurologique Pierre Wertheimer
    • Contact: Laura MECHTOUFF, MD; Phone Number: +33 4.72.35.67.47; Email: laura.mechtouff@chu-lyon.fr
  • Bron, France, 69677
    • Not yet recruiting
    • Service Imagerie médicale Hôpital neurologique Pierre Wertheimer
    • Contact: Philippe DOUEK, Pr; Phone Number: +33 4.72.35.72.33; Email: philippe.douek@chu-lyon.fr
  • Bron, France, 69677
    • Recruiting
    • Service rythmologie, Hôpital cardiologique Louis Pradel
    • Contact: Philippe CHEVALIER, Pr; Phone Number: +33 4.72.35.70.17; Email: philippe.chevalier@chu-lyon.fr
    • Contact: Sihem BEN AOUICHA, PhD; Phone Number: +33 4.72.35.76.77; Email: sihem.ben-aouicha@chu-lyon.fr

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: Yes

Description

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.

Study Plan

How is the study designed?

Design Details

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

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Patients with embolic strokes of undetermined source.; 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; 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.
Experimental: Patients with non-paroxysmal AF.; Patients over 18 years old, with non-paroxysmal AF. The intervention consists of a 4D Flow MRI.	Other: 4D Flow MRI; 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.
Active Comparator: Heathy volunteers; 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; 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.; Other: Medical consultation with 12 leads ECG; Collection of medical history, treatment, physical examination and realization of a 12 leads ECG.; Other: Holter ECG; 48 hours ECG recording; Other: Trans thoracic echocardiography; Trans thoracic echocardiography with standard measures performes in the core lab.; Biological: Blood sample; Blood sample in a peripheral vein, send to medical laboratory to dosage of NT pro BNP and troponin serum level.
Experimental: ESUS and non-paroxysmal AF patients with cardiac MRI; 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; Acquisitions of MR imagining

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Hospices Civils de Lyon
• Investigators: Principal Investigator: Philippe CHEVALIER, Pr, Chief of the Arrhythmia Unit at the Academic Hospital of Lyon

Study record dates

Study Major Dates

• Study Start (Actual): March 1, 2021
• Primary Completion (Estimated): September 1, 2024
• Study Completion (Estimated): September 1, 2024

Study Registration Dates

• First Submitted: January 15, 2021
• First Submitted That Met QC Criteria: January 20, 2021
• First Posted (Actual): January 22, 2021

Study Record Updates

• Last Update Posted (Actual): September 21, 2023
• Last Update Submitted That Met QC Criteria: September 20, 2023
• Last Verified: June 1, 2023

More Information

Terms related to this study

• Keywords: MRI; Atrial Fibrillation; ESUS; Atrial Myopathy; left atrium; blood velocity
• Additional Relevant MeSH Terms: Cardiovascular Diseases; Vascular Diseases; Cerebrovascular Disorders; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Musculoskeletal Diseases; Neuromuscular Diseases; Ischemic Stroke; Stroke; Muscular Diseases; Embolic Stroke
• Other Study ID Numbers: 69HCL20_0790

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No