Advanced Cardiac Imaging To Predict Embolic Stroke On Brain MRI: A Pilot Study

Sponsor

Tulane University (Other)

Overall Status

Recruiting

CT.gov ID

NCT04769310

Collaborator

(none)

120

Enrollment

Location

Arm

23.2

Anticipated Duration (Months)

5.2

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

Demonstrating the pathophysiological link between Left Atrial (LA) and Left Atrial Appendage (LAA) pathology and embolic strokes in non-Atrial Fibrillation (AF) individuals represents a major advance in stroke prevention strategies. Instead of relying on non-specific criteria for stroke risk assessment, the investigators propose to identify individuals with high-risk of embolic stroke using imaging criteria that reflect the underlying pathophysiology of embolic stroke of cardiac origin. the investigators can therefore lay the groundwork for future anticoagulation strategies for stroke prevention beyond AF.

Condition or Disease	Intervention/Treatment	Phase
Atrial Fibrillation Stroke Stroke, Cardiovascular Vascular Cognitive Impairment Strokes Thrombotic Stroke, Ischemic	Device: Cardiac and Brain MRI	N/A

Detailed Description

The investigators propose a cross-sectional cohort study, where individuals with no history of AF and with a Congestive heart failure, Hypertension, Age ≥ 75 years, Diabetes mellitus, Stroke or transient ischemic attack (TIA), Vascular disease, Age 65 to 74 years, Sex category score (CHA2DS2VASC) ≥3, type II diabetes, congestive heart failure or a history of stroke/TIA will be included. Data on demographics, personal health habits, medications, and medical history will be obtained by interviewing participants and reviewing the electronic medical records. All participants will undergo a Cardiac Magnetic Resonance imaging (CMR) to assess for markers of LA and LAA pathology. Markers of LA and LAA pathology that will be studied include: LA fibrosis level, LA functional parameters, LA shape characteristics, and LAA characteristics (including morphology, orifice area and flow velocity). Additionally, all participants will undergo a brain Magnetic Resonance Imaging (MRI) at the same visit to assess for the presence of embolic-appearing brain infarcts, regardless of previous stroke-related symptoms.

The investigators will analyze the association between each cardiac imaging feature and the prevalence of embolic-appearing strokes on brain MRI to determine whether patients with higher LA and LAA remodeled features are more likely to have embolic-appearing brain infarcts on MRI. The LA and LAA pathology imaging features with the strongest statistical association will be used to develop an imaging predictive score capable of identifying patients with the highest risk of embolic stroke.

All brain and cardiac imaging data will be assessed by experienced operators at Tulane Medical Center facilities. Operators analyzing CMR will be blinded to brain MRI results, and operators assessing brain MRI will be blinded to CMR results. The study will include a single center study at Tulane Medical Center and Clinics, with investigators from different medical specialties, and the proper facilities and equipment to conduct the project accurately and safely. The investigators expect a recruitment of 120 subjects over a period of 18 months from both cardiology and neurology clinics to complete the study.

Study Design

Study Type:

Interventional

Anticipated Enrollment :

120 participants

Allocation:

N/A

Intervention Model:

Single Group Assignment

Intervention Model Description:

All patients will undergo a CMR to evaluate for LA and LAA high-risk features on either a 1.5 or 3 Tesla clinical MR scanner. CMR protocol will include Cine MRI, contrast-enhanced (CE) MR Angiography (MRA), time-resolved 2D phase-contrast (PC) MRI, and 3D late gadolinium enhancement (LGE) involving gadolinium injection. Gadolinium is a contrast product that helps define areas of fibrosis in the LA. Brain MRI will be used for the detection of embolic infarcts assessed on high-resolution brain MRI acquisitions. The high-resolution brain MRI with no contrast will include the following sequences for most accurate assessment of embolic lesions: 3D T1 Magnetization Prepared Rapid Acquisition Gradient Echo (MPRAGE), 3D fluid attenuated inversion recovery (FLAIR), diffusion weighted imaging (DWI), apparent diffusion coefficient maps (ADC), and susceptibility weighted imaging (SWI).All patients will undergo a CMR to evaluate for LA and LAA high-risk features on either a 1.5 or 3 Tesla clinical MR scanner. CMR protocol will include Cine MRI, contrast-enhanced (CE) MR Angiography (MRA), time-resolved 2D phase-contrast (PC) MRI, and 3D late gadolinium enhancement (LGE) involving gadolinium injection. Gadolinium is a contrast product that helps define areas of fibrosis in the LA. Brain MRI will be used for the detection of embolic infarcts assessed on high-resolution brain MRI acquisitions. The high-resolution brain MRI with no contrast will include the following sequences for most accurate assessment of embolic lesions: 3D T1 Magnetization Prepared Rapid Acquisition Gradient Echo (MPRAGE), 3D fluid attenuated inversion recovery (FLAIR), diffusion weighted imaging (DWI), apparent diffusion coefficient maps (ADC), and susceptibility weighted imaging (SWI).

Masking:

None (Open Label)

Primary Purpose:

Diagnostic

Official Title:

Advanced Cardiac Imaging To Predict Embolic Stroke On Brain MRI: A Pilot Study

Actual Study Start Date :

Apr 26, 2021

Anticipated Primary Completion Date :

Apr 1, 2023

Anticipated Study Completion Date :

Apr 1, 2023

Arms and Interventions

Arm	Intervention/Treatment
Other: Patient arm All patients will undergo a CMR to evaluate for LA and LAA high-risk features on either a 1.5 or 3 Tesla clinical MR scanner. Gadolinium injection will be administered. Gadolinium is a contrast product that helps define areas of fibrosis in the LA. High-resolution brain MRI with no contrast will include the following sequences for most accurate assessment of embolic lesions: 3D T1 MPRAGE, 3D FLAIR, DWI, ADC, and SWI	Device: Cardiac and Brain MRI A CMR to evaluate for LA and LAA high-risk features on either a 1.5 or 3 Tesla clinical MR scanner will be used. Gadolinium injection will be administered. Gadolinium is a contrast product that helps define areas of fibrosis in the LA. High-resolution brain MRI with no contrast will include the following sequences for most accurate assessment of embolic lesions: 3D T1 MPRAGE, 3D FLAIR, DWI, ADC, and SWI

Arm

Intervention/Treatment

Other: Patient arm

All patients will undergo a CMR to evaluate for LA and LAA high-risk features on either a 1.5 or 3 Tesla clinical MR scanner. Gadolinium injection will be administered. Gadolinium is a contrast product that helps define areas of fibrosis in the LA. High-resolution brain MRI with no contrast will include the following sequences for most accurate assessment of embolic lesions: 3D T1 MPRAGE, 3D FLAIR, DWI, ADC, and SWI

Device: Cardiac and Brain MRI

A CMR to evaluate for LA and LAA high-risk features on either a 1.5 or 3 Tesla clinical MR scanner will be used. Gadolinium injection will be administered. Gadolinium is a contrast product that helps define areas of fibrosis in the LA. High-resolution brain MRI with no contrast will include the following sequences for most accurate assessment of embolic lesions: 3D T1 MPRAGE, 3D FLAIR, DWI, ADC, and SWI

Outcome Measures

Primary Outcome Measures

The presence of covert embolic cerebral infarcts [Day1]
The covert embolic cerebral infarcts are defined as the presence of asymptomatic non-lacunar embolic infarct (acute or chronic based on MRI appearance), in the cortex, and juxtacortical regions, and cerebellum. They will be identified using brain MRI.

Secondary Outcome Measures

Number of counts of lacunar covert infracts [Day1]
Covert lacunar infarcts are asymptomatic infarct < 15mm in greatest diameter in subcortical brain regions. They will be identified by size and location using brain MRI images.
Number of counts of lacunar symptomatic infracts [Day1]
Symptomatic lacunar infarcts are symptomatic infarct < 15mm in greatest diameter in subcortical brain regions. They will be identified by size and location using brain MRI images.
Number of counts of embolic symptomatic infracts [Day1]
Symptomatic non-lacunar embolic infarcts are symptomatic infarcts of any size in the cortex or infarcts >15 mm in greatest diameter in subcortical lesions. They will be identified by size and location using brain MRI images.

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 120 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

Male or female patients
18 Years and older
No history of atrial fibrillation
CHA2DS2VASC score ≥3
History pf type II diabetes
History of congestive heart failure or a history of transient ischemic attack (TIA)/stroke without an otherwise defined stroke etiology such as large vessel or small vessel disease

Exclusion Criteria:

History of atrial fibrillation
Patients who had a clinically symptomatic acute stroke within the last 30-days
Any health-related gadolinium/MRI contraindication (including previous allergic reaction to Gadolinium, pacemakers, defibrillators, other devices/implants contraindicated for MRI)
Estimated glomerular filtration rate (eGFR) cutoff in patients with Chronic kidney disease (CKD) where gadolinium cannot be used equals an eGFR <30 ml/min
Weighing > 300 lbs (as CMR image quality decreases due to increased body mass index)
Current pregnancy or breastfeeding
Cognitive impairment preventing the patient from giving an informed consent