B-MORE-Pilot: Breathing-Induced Myocardial Oxygenation Reserve
Study Details
Study Description
Brief Summary
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.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
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Detailed Description
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.
Study Design
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| CAD patients 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). |
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| Healthy subjects Subjects without current or pre-existing cardiovascular and lung disease and absence of medication with cardiovascular effects. |
Outcome Measures
Primary Outcome Measures
- 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. [OS-CMR with breathing maneuvers will last about 5-10 minutes]
Myocardial oxygenation signal intensity changes (OS-SI) changes between healthy and post-stenotic myocardium during OS-CMR with breathing-maneuvers
Secondary Outcome Measures
- Relationship between OS-SI changes during OS-CMR with breathing-maneuvers and Fractional Flow Reserve (FFR) measurements in CAD patients [OS-CMR with breathing maneuvers will last about 5-10 minutes]
Myocardial oxygenation signal intensity changes (OS-SI) changes during OS-CMR with breathing-maneuvers and its relation to Fractional Flow Reserve (FFR) measurements
- Relationship between OS-SI changes during OS-CMR with breathing-maneuvers and Quantitative Coronary Angiography (QCA) measurements in CAD patients [OS-CMR with breathing maneuvers will last about 5-10 minutes]
Myocardial oxygenation signal intensity changes (OS-SI) changes during OS-CMR with breathing-maneuvers and its relation to Quantitative Coronary Angiography (QCA) measurements
- Presence of side effects during OS-CMR with breathing maneuvers [OS-CMR with breathing maneuvers will last about 5-10 minutes]
side effects experienced by the participants during breathing maneuvers
- Clinical feasibility of OS-CMR with breathing maneuvers [OS-CMR with breathing maneuvers will last about 5-10 minutes]
Number of participants who voluntarily stopped the maneuver prior to completion and scan time of the image acquisition protocol.
Eligibility Criteria
Criteria
Inclusion Criteria:
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Age > 18 y
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Informed consent as documented by signature (Appendix Informed Consent Form)
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Indication for invasive coronary angiography based on symptoms and a test positive for inducible coronary ischemia
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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:
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General MRI contraindications (i.e pacemakers, defibrillating wires, implanted defibrillators, intracranial aneurysm clips, metallic foreign bodies in the eyes, knowledge or suspicion of pregnancy)
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Acute Coronary Syndrome (ACS) or other acute cardiac injury within 4 weeks
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Previous myocardial infarction, percutaneous coronary intervention or coronary artery bypass surgery
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Hemodynamically unstable conditions
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Significant or uncontrolled arrhythmias
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Lack of ability to follow commands
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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
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Non-ischemic cardiomyopathy
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Severe Pulmonary Disease
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | University of Wisconsin | Madison | Wisconsin | United States | 53792 |
| 2 | Jewish General Hospital | Montreal | Quebec | Canada | 3755 |
| 3 | McGill University Health Centre | Montreal | Quebec | Canada | H4A 3J1 |
| 4 | University Hospital Heidelberg | Heidelberg | Germany | 69120 | |
| 5 | Groote Schuur Hospital | Cape Town | South Africa | 7935 | |
| 6 | King's College London | London | United Kingdom | WC2R 2LS |
Sponsors and Collaborators
- McGill University Health Centre/Research Institute of the McGill University Health Centre
- University Hospital Heidelberg
- Groote Schuur Hospital
- King's College London
- University of Wisconsin, Madison
- Jewish General Hospital
Investigators
- Principal Investigator: Matthias Friedrich, MD, McGill University Health Centre/Research Institute of the McGill University Health Centre
Study Documents (Full-Text)
None provided.More Information
Publications
- Arnold JR, Karamitsos TD, Bhamra-Ariza P, Francis JM, Searle N, Robson MD, Howells RK, Choudhury RP, Rimoldi OE, Camici PG, Banning AP, Neubauer S, Jerosch-Herold M, Selvanayagam JB. Myocardial oxygenation in coronary artery disease: insights from blood oxygen level-dependent magnetic resonance imaging at 3 tesla. J Am Coll Cardiol. 2012 May 29;59(22):1954-64. doi: 10.1016/j.jacc.2012.01.055.
- Chauhan A, Mullins PA, Taylor G, Petch MC, Schofield PM. Effect of hyperventilation and mental stress on coronary blood flow in syndrome X. Br Heart J. 1993 Jun;69(6):516-24.
- Fischer K, Guensch DP, Friedrich MG. Response of myocardial oxygenation to breathing manoeuvres and adenosine infusion. Eur Heart J Cardiovasc Imaging. 2015 Apr;16(4):395-401. doi: 10.1093/ehjci/jeu202. Epub 2014 Oct 21.
- Friedrich MG, Karamitsos TD. Oxygenation-sensitive cardiovascular magnetic resonance. J Cardiovasc Magn Reson. 2013 May 24;15:43. doi: 10.1186/1532-429X-15-43. Review.
- Friedrich MG, Niendorf T, Schulz-Menger J, Gross CM, Dietz R. Blood oxygen level-dependent magnetic resonance imaging in patients with stress-induced angina. Circulation. 2003 Nov 4;108(18):2219-23. Epub 2003 Oct 13.
- Guensch DP, Fischer K, Flewitt JA, Friedrich MG. Impact of intermittent apnea on myocardial tissue oxygenation--a study using oxygenation-sensitive cardiovascular magnetic resonance. PLoS One. 2013;8(1):e53282. doi: 10.1371/journal.pone.0053282. Epub 2013 Jan 3.
- Guensch DP, Fischer K, Flewitt JA, Yu J, Lukic R, Friedrich JA, Friedrich MG. Breathing manoeuvre-dependent changes in myocardial oxygenation in healthy humans. Eur Heart J Cardiovasc Imaging. 2014 Apr;15(4):409-14. doi: 10.1093/ehjci/jet171. Epub 2013 Sep 27.
- Luu JM, Friedrich MG, Harker J, Dwyer N, Guensch D, Mikami Y, Faris P, Hare JL. Relationship of vasodilator-induced changes in myocardial oxygenation with the severity of coronary artery stenosis: a study using oxygenation-sensitive cardiovascular magnetic resonance. Eur Heart J Cardiovasc Imaging. 2014 Dec;15(12):1358-67. doi: 10.1093/ehjci/jeu138. Epub 2014 Aug 7.
- Nakao K, Ohgushi M, Yoshimura M, Morooka K, Okumura K, Ogawa H, Kugiyama K, Oike Y, Fujimoto K, Yasue H. Hyperventilation as a specific test for diagnosis of coronary artery spasm. Am J Cardiol. 1997 Sep 1;80(5):545-9.
- Neill WA, Hattenhauer M. Impairment of myocardial O2 supply due to hyperventilation. Circulation. 1975 Nov;52(5):854-8.
- Sueda S, Saeki H, Otani T, Ochi N, Kukita H, Kawada H, Matsuda S, Uraoka T. Investigation of the most effective provocation test for patients with coronary spastic angina: usefulness of accelerated exercise following hyperventilation. Jpn Circ J. 1999 Feb;63(2):85-90.
- 15-398-MUHC