Breathing-Maneuver-Induced Myocardial Oxygenation Reserve Validated by FFR (B-MORE)

Study Overview
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Brief Summary
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The study aims to determine a diagnostic marker for regionally impaired myocardial oxygenation response in patients with suspected coronary artery stenosis.

Detailed Description
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This observational applied research international study aims to assess the validity of breathing maneuvers as a vasoactive maneuver and Oxygenation-Sensitive Cardiac Magnetic Resonance Imaging (OS-CMR) in a patient population. OS-CMR results will be compared to the clinical gold standard of Fractional Flow Reserve (FFR) and instant wave-free ratio (iFR) as a secondary objective, to determine if this non-invasive, no pharmaceutical agent imaging technique can identify areas of oxygenation deficit in myocardium perfused by a stenosed coronary artery.

Official Title
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Breathing-Maneuver-Induced Myocardial Oxygenation Reserve Validated by FFR (B-MORE)

Conditions
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Coronary Artery Stenosis

Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Healthy Participants Age: > 40y No known current or pre-existing significant medical problems that would affect the cardiovascular or respiratory system. CAD Patients Age > 18 y Indication for invasive coronary angiography based on symptoms and a test positive for inducible coronary ischemia, or previous coronary angiography. Exclusion Criteria: ALL participants: General MRI contraindications: Pacemakers, defibrillating wires, implanted defibrillators, intracranial aneurysm clips, metallic foreign bodies in the eyes, knowledge or suspicion of pregnancy. Consumption of caffeine (coffee, tea, cocoa, chocolate, energy drink) during the 12 hours prior to the exam. Regular nicotine consumption during the last 6 months. Patients only Vasoactive medication (e.g. nitro) during the 12 hours prior to the exam Contraindications to adenosine (2nd or 3rd A-V block, sinus node disease, asthma, bronchoconstrictive diseases). Acute Coronary Syndrome (ACS), or previous Coronary Artery Bypass Surgery Previous myocardial infarction within 1 month Clinically unstable condition Significant or uncontrolled arrhythmia

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 |
| --- | --- |
| Age matched Healthy participants (150)<br>Healthy Participants Age: > 40y No known current or pre-existing significant medical problems that would affect the cardiovascular or respiratory system | |
| Coronary Artery Disease (CAD) Patients (200)<br>Coronary Artery Disease (CAD) Patients Age > 18 y Patients with an Indication for invasive coronary angiography based on symptoms and a test positive for inducible coronary ischemia, or previous coronary angiography. | |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| B-MORE: Diagnostic cut-off - Relative change of myocardial signal intensity | To obtain a diagnostic cut-off of the mean Breathing-Maneuver-induced Myocardial Oxygenation REserve (B-MORE) of a coronary territory as defined by the relative change of myocardial signal intensity (delta SI[%]) in oxygenation-sensitive CMR (OS-CMR) images, at the 15s and 30s time point of a post-hyperventilation breath-hold for detecting an associated severe coronary artery stenosis as defined by FFR of less than 0.75 or a QCA assessment of >0.75, as compared to the global delta SI[%] in age-matched healthy volunteers | 2019-2022 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 30sec B-MORE Cut-off | A student's t-test will assess a cut-off of the Breathing maneuver induced Myocardial Oxygenation REserve (MORE), at the 30s time point of the breath hold, for a region perfused by a stenosed coronary artery (FFR / iFR or QCA >0.75) as compared to a healthy coronary artery (FFR / iFR or QCA <0.75), within a patient. | 2019-2022 | 
| Heart rate response to hyperventilation. | Markers of diagnostic accuracy will be obtained to assess the accuracy the heart rate response to hyperventilation. | 2019-2022 | 
| Myocardial strain response at the 15s and 30s time point during breath-hold | Markers of diagnostic accuracy will be obtained to assess the accuracy of the myocardial strain response at the 15s and 30s time point of the breath-hold | 2019-2022 | 
| Accuracy of B-MORE and strain response at the 15s and 30s time point of the breath-hold | Markers of diagnostic accuracy will be obtained to assess the accuracy of a combination of the B-MORE and the strain response at the 15s and 30s time point of the breath-hold | 2019-2022 | 
| B-MORE - strain response at 15s and 30s time breath hold and Heart rate response | Markers of diagnostic accuracy will be obtained to assess the accuracy of a combination of the B-MORE, the strain response at the 15s and 30s time point of the breath-hold, and the heart rate response to hyperventilation | 2019-2022 | 
| Relationship between B-MORE vs heart rate response to hyperventilation | A student's t-test will assess the relationship between B-MORE results and heart rate response to hyperventilation | 2019-2022 | 
| Relationship between myocardial strain and Heart rate | A student's t-test will assess the relationship between the strain response at the 15 and 30 s timepoints and heart rate response to hyperventilation | 2019-2022 | 
| Relationship between B-MORE and myocardial strain measurements -each coronary territory | A student's t-test will assess the relationship between B-MORE results and myocardial strain measurements (circumferential, longitudinal, and radial) at the 15s and 30s time point for each coronary territory. | 2019-2022 | 
| Global relationship between B-MORE results and myocardial strain measurements | A student's t-test will assess the global relationship between B-MORE results and myocardial strain measurements (circumferential, longitudinal, and radial). | 2019-2022 | 
| Relationship between B-MORE and QCA | Pearson's correlation coefficient will be obtained to assess the relationship between B-MORE results at the 15s and 30s time point of the breath-hold and Quantitative Coronary Angiography (QCA) measurements for each coronary territory. | 2019-2022 | 
| Relationship between B-MORE and FFR / iFR | Pearson's correlation coefficient will be obtained to assess the relationship between B-MORE results at the 15 s and 30s time point of the breath-hold and FFR / iFR measurements for each coronary territory. | 2019-2022 | 
| Relationship between B-MORE (15s and 30s) vs QCA | Pearson's correlation coefficient will be obtained to assess the relationship between B-MORE results after hyperventilation and Quantitative Coronary Angiography (QCA) measurements for each coronary territory. | 2019-2022 | 
| Relationship between B-MORE vs FFR - iFR each coronary territory | To assess the relationship between B-MORE results after hyperventilation and FFR / iFR measurements for each coronary territory. | 2019-2022 | 
| Relationship between B-MORE vs T1/T2 mapping | Pearson's assess the relationship between B-MORE results and global T1/T2 mapping measurements. | 2019-2022 | 
| Breathing maneuver - Clinical feasibility | Recorded time, exclusion rate due to inability to perform the breathing maneuvers, will be reported for clinical feasibility during MRI and while performing iFR. Any serious adverse effects of the breathing maneuver will be reported for safety. | 2019-2022 | 
| B-MORE analysis intra and inter-reader reproducibility | Correlation coefficients will be obtained to evaluate the intra- and inter-reader reproducibility of B-MORE. | 2019-2022 |