MR Evidence of Cardiac Inflammation Post-Stroke

Recruiting

• Conditions: Stroke, Ischemic; Inflammation; Myocardial Injury
• Interventions: Diagnostic Test: Gadolinium-enhanced cardiac MRI; Diagnostic Test: B Natriuretic Peptide; Diagnostic Test: Systemic inflammatory markers

• Registration Number: NCT05714618
• Lead Sponsor: Lawson Health Research Institute

Brief Summary

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

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.

Study Timeline

• Study Start: 2021-10-01
• Study First Submitted: 2022-01-31
• Study First Submitted QC: 2023-02-03
• Study First Posted: 2023-02-06
• Status Verified: 2023-10
• Last Update Submitted: 2023-10-04
• Last Update Posted: 2023-10-05
• Primary Completion: 2024-06-16
• Study Completion: 2024-12-31

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 44

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.

Study & Design

• Study Type: OBSERVATIONAL
• Study Design: Not specified

Arm && Interventions

Group	Intervention	Description
Controls (TIA): Patients with acute focal neurological symptoms without brain infarct on MRI.	Gadolinium-enhanced cardiac MRI	Patients presenting with acute onset focal neurological deficits presumed to be of vascular origin, WITHOUT DWI-MRI evidence of an acute brain infarct.
Cases (Ischemic stroke): Left and right middle cerebral artery ischemic stroke	B Natriuretic Peptide	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.
Controls (TIA): Patients with acute focal neurological symptoms without brain infarct on MRI.	B Natriuretic Peptide	Patients presenting with acute onset focal neurological deficits presumed to be of vascular origin, WITHOUT DWI-MRI evidence of an acute brain infarct.
Cases (Ischemic stroke): Left and right middle cerebral artery ischemic stroke	Gadolinium-enhanced cardiac MRI	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.
Controls (TIA): Patients with acute focal neurological symptoms without brain infarct on MRI.	Systemic inflammatory markers	Patients presenting with acute onset focal neurological deficits presumed to be of vascular origin, WITHOUT DWI-MRI evidence of an acute brain infarct.
Cases (Ischemic stroke): Left and right middle cerebral artery ischemic stroke	Systemic inflammatory markers	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.

Primary Outcome Measures

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

Secondary Outcome Measures

Name	Time	Method
Changes in left ventricular inflammation measured on gadolinium-enhanced cardiac MRI at 10 and 60±15 days post-stroke	At 60±15 days compared to first 10 days	Quantification of left ventricular inflammation measured on gadolinium-enhanced cardiac MRI
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.	At 60±15 days compared to first 10 days	Change in levels of NT-proBNP between 10 and 60±15 days post-stroke
Change in systemic inflammatory markers between 10 and 60±15 days post-stroke	At 60±15 days compared to first 10 days	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
Changes in left atrial fibrosis measured on gadolinium-enhanced cardiac MRI at 10 and 60±15 days post-stroke	At 60±15 days compared to first 10 days	Quantification of left atrial fibrosis measured on gadolinium-enhanced cardiac MRI
Changes in left atrial inflammation measured on gadolinium-enhanced cardiac MRI at 10 and 60±15 days post-stroke	At 60±15 days compared to first 10 days	Quantification of left atrial inflammation measured on gadolinium-enhanced cardiac MRI

Trial Locations

Locations (1)

Heart & Brain Lab, Western University; 🇨🇦 London, Ontario, Canada