Breathing-Induced Myocardial Oxygenation Reserve

Study Overview
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Brief Summary
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This is a clinical trial to test the clinical feasibility and safety of a novel CMR protocol, combined with a specific breathing maneuver to identify myocardial regions exposed to severe coronary artery stenosis.

Detailed Description
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This is a clinical trial to test the clinical feasibility and safety of a novel CMR protocol. It aims to investigate a new Cardiovascular Magnetic Resonance (CMR) technique, called oxygenation-sensitive CMR (OS-CMR). OS-CMR is a T2*-sensitive CMR sequence based on the so-called blood-oxygen-level-dependent (BOLD) effect. Because de-oxygenated hemoglobin acts as an endogenous paramagnetic contrast agent, the signal intensity (SI) in OS-CMR images is linearly correlated with hemoglobin oxygenation in the tissue. An increase in deoxyhemoglobin results in an drop in SI in OS-CMR images, while an increase in tissue oxygenation results in an increase in SI. Therefore, OS-CMR has been found capable of assessing myocardial oxygenation and is being increasingly used to identify the vascular response of the coronary circulation to different stimuli. Very recently, OS-CMR was used to identify the coronary vascular response to specific breathing maneuvers. Specifically, a marked increase of myocardial oxygenation was observed during a long breath-hold following a 60s period of hyperventilation. The combination of these two maneuvers appear to induce consistent and detectable changes of myocardial oxygenation, based on CO2-mediated coronary vasoconstriction and vasodilation, while being well tolerated by participants. In this study, the investigators will use breathing maneuvers as coronary vasoactive stimuli to assess the myocardial oxygenation changes induced by such maneuvers with OS-CMR. The investigators aim to assess if the breathing-induced relative increase of myocardial oxygenation (Breathing-induced Myocardial Oxygenation REserve, B-MORE) in a coronary territory is clinically feasible to serve as a marker for the severity of coronary artery stenosis. Moreover, the investigators will assess the feasibility and safety of OS-CMR with breathing maneuvers in patients with suspected coronary artery disease in a multi-center setting.

Official Title
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Breathing-Induced Myocardial Oxygenation Reserve - Pilot Study (B-MORE-Pilot)

Conditions
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Coronary Artery Disease

Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Age > 18 y Informed consent as documented by signature (Appendix Informed Consent Form) Indication for invasive coronary angiography based on symptoms and a test positive for inducible coronary ischemia One-vessel or two-vessel CAD at coronary angiography (For healthy volunteers: absence of current or pre-existing cardiovascular and lung disease and absence of medication with cardiovascular effects) Exclusion Criteria: General MRI contraindications (i.e pacemakers, defibrillating wires, implanted defibrillators, intracranial aneurysm clips, metallic foreign bodies in the eyes, knowledge or suspicion of pregnancy) Acute Coronary Syndrome (ACS) or other acute cardiac injury within 4 weeks Previous myocardial infarction, percutaneous coronary intervention or coronary artery bypass surgery Hemodynamically unstable conditions Significant or uncontrolled arrhythmias Lack of ability to follow commands Vasoactive medication (e.g. nitro or ß blockers) or nutrition with caffeine (coffee, tea, cocoa, chocolate, energy drink) during the 12 h before the exam Non-ischemic cardiomyopathy Severe Pulmonary Disease

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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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| CAD patients<br>Consecutive patients scheduled for a coronary angiography on the basis of cardiac symptoms and a test positive for inducible coronary ischemia, who are affected by one-vessel or two-vessel CAD at the time of the OS-CMR with breathing maneuvers (HVBH). | |
| Healthy subjects<br>Subjects without current or pre-existing cardiovascular and lung disease and absence of medication with cardiovascular effects. | |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Comparison of myocardial oxygenation signal intensity changes (OS-SI) changes between healthy and post-stenotic myocardium during OS-CMR with breathing-maneuvers in CAD patients. | Myocardial oxygenation signal intensity changes (OS-SI) changes between healthy and post-stenotic myocardium during OS-CMR with breathing-maneuvers | OS-CMR with breathing maneuvers will last about 5-10 minutes | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Relationship between OS-SI changes during OS-CMR with breathing-maneuvers and Fractional Flow Reserve (FFR) measurements in CAD patients | Myocardial oxygenation signal intensity changes (OS-SI) changes during OS-CMR with breathing-maneuvers and its relation to Fractional Flow Reserve (FFR) measurements | OS-CMR with breathing maneuvers will last about 5-10 minutes | 
| Relationship between OS-SI changes during OS-CMR with breathing-maneuvers and Quantitative Coronary Angiography (QCA) measurements in CAD patients | Myocardial oxygenation signal intensity changes (OS-SI) changes during OS-CMR with breathing-maneuvers and its relation to Quantitative Coronary Angiography (QCA) measurements | OS-CMR with breathing maneuvers will last about 5-10 minutes | 
| Presence of side effects during OS-CMR with breathing maneuvers | side effects experienced by the participants during breathing maneuvers | OS-CMR with breathing maneuvers will last about 5-10 minutes | 
| Clinical feasibility of OS-CMR with breathing maneuvers | Number of participants who voluntarily stopped the maneuver prior to completion and scan time of the image acquisition protocol. | OS-CMR with breathing maneuvers will last about 5-10 minutes | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Magnetic Resonance Imaging, Coronary Artery Disease, Apnea, Hyperventilation, BOLD, Breathing Maneuvers, Myocardial Oxygenation