MR Evidence of Cardiac Inflammation Post-Stroke

Study Overview
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Brief Summary
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The present study is an investigator initiated, single-centre, prospective, proof-of-concept cohort study aiming to enroll 44 patients with acute middle cerebral artery (MCA) ischemic stroke, involving the right (n=22) and left (n=22) MCA territories and 24 control patients with acute focal neurological symptoms but no evidence of acute brain infarct on DWI-MRI.

Detailed Description
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The present study is an investigator-initiated, single-center, prospective cohort study. The study aims to enroll 44 patients with acute/subacute middle cerebral artery (MCA) ischemic stroke. The investigators will compare inflammatory markers among 44 patients with MCA ischemic stroke within 10 days post-stroke vs. 60±15 days post-stroke. Other measures to be determined at both time points include B-Type Natriuretic Peptide and systemic inflammatory markers.

Official Title
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Magnetic Resonance Imaging Evidence of Cardiac Inflammation Post-Stroke

Conditions
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Stroke, Ischemic, Inflammation, Myocardial Injury

Intervention / Treatment
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* Diagnostic Test: Gadolinium-enhanced cardiac MRI
* Diagnostic Test: B Natriuretic Peptide
* Diagnostic Test: Systemic inflammatory markers


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: • Acute ischemic stroke in the right or left MCA territory. Acute ischemic stroke is defined as acute onset focal symptoms matching an acute brain infarct documented on Head computed tomography or diffusion-weighted imaging (DWI) MRI of the brain showing restricted diffusion. Exclusion Criteria: History of known atrial fibrillation, prior myocardial infarction, coronary artery disease, heart failure, prior cardiovascular surgery or percutaneous intervention. Previous stroke (occurred within 3 months before the index event) Impaired renal function defined as a creatinine clearance <97 mL/min in men or <88 mL/min in women, according to the Cockcroft formula. hs-TnT >100 on routine acute stroke baseline bloodwork upon admission. Clinically or neurologically unstable patients as per the treating physician. Ongoing infection or recent infection within the previous 3 months Surgery within 3 months before the stroke Concurrent and active inflammatory conditions (connective tissue diseases, rheumatological disease, etc.) or use of anti-inflammatory medications Pregnancy, Stage IV renal insufficiency, eGFR <30, and any other contraindications to the use of gadolinium. Stroke with symptomatic hemorrhagic transformation Subjects will be excluded if they fail the LHSC standard MRI screening questionnaire (cardiac pacemakers/wires, aneurysm clips, shunt/surgical clips, shrapnel/bullets, dentures or metal braces, intra-uterine devices, heart valves, ear implants, prostheses, medication patches such as Nicoderm, Habitrol, or Transderm-Nitro, claustrophobia, history of a head or eye injury involving metal fragments.

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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No

Study Plan
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How is the study designed?
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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Cases (Ischemic stroke): Left and right middle cerebral artery ischemic stroke<br>Patients presenting with acute onset focal neurological deficits and DWI-MRI evidence of an acute brain infarct of the left or right middle cerebral artery ischemic stroke. | Diagnostic Test: Gadolinium-enhanced cardiac MRI<br>* Cardiac magnetic resonance imaging (MRI) with a protocol designed to measure myocardial inflammation and fibrosis.<br>Diagnostic Test: B Natriuretic Peptide<br>* Measurement of B Natriuretic Peptide on patients' blood samples at 10 and 60+/-15 days.<br>Diagnostic Test: Systemic inflammatory markers<br>* Measurement of a panel of 92 systemic inflammatory markers on patients' blood samples at 10 and 60+/-15 days.<br>|
| Controls (TIA): Patients with acute focal neurological symptoms without brain infarct on MRI.<br>Patients presenting with acute onset focal neurological deficits presumed to be of vascular origin, WITHOUT DWI-MRI evidence of an acute brain infarct. | Diagnostic Test: Gadolinium-enhanced cardiac MRI<br>* Cardiac magnetic resonance imaging (MRI) with a protocol designed to measure myocardial inflammation and fibrosis.<br>Diagnostic Test: B Natriuretic Peptide<br>* Measurement of B Natriuretic Peptide on patients' blood samples at 10 and 60+/-15 days.<br>Diagnostic Test: Systemic inflammatory markers<br>* Measurement of a panel of 92 systemic inflammatory markers on patients' blood samples at 10 and 60+/-15 days.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The severity of left ventricular myocardial inflammation on cardiac MRI within 10 days post-stroke | Proportion of left ventricular myocardium showing inflammatory changes on gadolinium-enhanced cardiac MRI | Within 10 days of stroke onset | 
| The extent of left ventricular fibrosis measured on gadolinium-enhanced cardiac MRI within 10 days of stroke onset | Proportion of left ventricular myocardium showing fibrosis on gadolinium-enhanced cardiac MRI | Within 10 days of stroke onset | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Changes in left ventricular inflammation measured on gadolinium-enhanced cardiac MRI at 10 and 60±15 days post-stroke | Quantification of left ventricular inflammation measured on gadolinium-enhanced cardiac MRI | At 60±15 days compared to first 10 days | 
| Change in B-Type Natriuretic Peptide (NT-proBNP) levels in the second measurement performed at 60±15 days post-stroke relative to the plasma sample drawn within 10 days. | Change in levels of NT-proBNP between 10 and 60±15 days post-stroke | At 60±15 days compared to first 10 days | 
| Change in systemic inflammatory markers between 10 and 60±15 days post-stroke | High-performance protein biomarker panel for following 92 inflammatory biomarkers in pg/mL ADA; ARTN; AXIN1; NGF; CCL13; CCL19; CCL2; CCL20; CCL23; CCL25; CCL28; CCL3; CCL4; CCL7; CCL8; CXCL10; CXCL11; CXCL5; CXCL6; CXCL9; CDCP1; CASP8; CST5; DNER; CCL11; EIF4EBP1; FGF19; FGF21; FGF23; FGF5; FLT3LG; CX3CL1; GDNF; CXCL1; HGF; IFNG; IL1A; IL10; IL10RA; IL10RB; IL12B; IL13; IL15RA; IL17A; IL17C; IL18; IL18R1; IL2; IL2RB; IL20; IL20RA; IL22RA1; IL24; IL33; IL4; IL5; IL6; IL7; CXCL8; MMP1; KITLG; LIF; LIFR; LTA; CSF1; SIRT2; CD244;NTF3;NRTN;OSM;CD274;S100A12;TGFA;STAMBP;SLAMF1;MMP10;SULT1A1;CD6;CD5;CD8A;TSLP;TGFB1;TNF;TNFSF10;TNFSF11;TNFSF12;TNFSF14;TNFRSF11B;CD40;TNFRSF9;PLAU;VEGFA | At 60±15 days compared to first 10 days | 
| Changes in left atrial inflammation measured on gadolinium-enhanced cardiac MRI at 10 and 60±15 days post-stroke | Quantification of left atrial inflammation measured on gadolinium-enhanced cardiac MRI | At 60±15 days compared to first 10 days | 
| Changes in left atrial fibrosis measured on gadolinium-enhanced cardiac MRI at 10 and 60±15 days post-stroke | Quantification of left atrial fibrosis measured on gadolinium-enhanced cardiac MRI | At 60±15 days compared to first 10 days |