Clinical trial NCT03050346: Breathing-Induced Myocardial Oxygenation Reserve
Official title: Breathing-Induced Myocardial Oxygenation Reserve - Pilot Study (B-MORE-Pilot)
Study type: OBSERVATIONAL
Overall status: COMPLETED
Conditions: Coronary Artery Disease
Keywords: Magnetic Resonance Imaging
Coronary Artery Disease
Apnea
Hyperventilation
BOLD
Breathing Maneuvers
Myocardial Oxygenation
Lead sponsor: McGill University Health Centre/Research Institute of the McGill University Health Centre
Sponsor class: OTHER
Collaborators: name: University Hospital Heidelberg
name: Groote Schuur Hospital
name: King's College London
name: University of Wisconsin, Madison
name: Jewish General Hospital
First posted: 2017-02-10
Enrollment: 113
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Observational model: OTHER
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: Consecutive patients scheduled for a coronary angiography on the basis of cardiac symptoms and a test positive for inducible coronary ischemia, who show one-vessel or two-vessel CAD at coronary angiography.

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.

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.

Eligibility criteria: 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

Primary outcomes:
measure: 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.
timeFrame: OS-CMR with breathing maneuvers will last about 5-10 minutes
Secondary outcomes:
measure: Relationship between OS-SI changes during OS-CMR with breathing-maneuvers and Fractional Flow Reserve (FFR) measurements in CAD patients
timeFrame: OS-CMR with breathing maneuvers will last about 5-10 minutes
measure: Relationship between OS-SI changes during OS-CMR with breathing-maneuvers and Quantitative Coronary Angiography (QCA) measurements in CAD patients
timeFrame: OS-CMR with breathing maneuvers will last about 5-10 minutes
measure: Presence of side effects during OS-CMR with breathing maneuvers
timeFrame: OS-CMR with breathing maneuvers will last about 5-10 minutes
measure: Clinical feasibility of OS-CMR with breathing maneuvers
timeFrame: OS-CMR with breathing maneuvers will last about 5-10 minutes
Other outcomes:
Locations:
city: Madison
country: United States
facility: University of Wisconsin
state: Wisconsin
city: Montreal
country: Canada
facility: Jewish General Hospital
state: Quebec
city: Montreal
country: Canada
facility: McGill University Health Centre
state: Quebec
city: Heidelberg
country: Germany
facility: University Hospital Heidelberg
city: Cape Town
country: South Africa
facility: Groote Schuur Hospital
city: London
country: United Kingdom
facility: King's College London
Study officials:
affiliation: McGill University Health Centre/Research Institute of the McGill University Health Centre
name: Matthias Friedrich, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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. doi: 10.1161/01.CIR.0000095271.08248.EA. Epub 2003 Oct 13.
citation: 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.
citation: Friedrich MG, Karamitsos TD. Oxygenation-sensitive cardiovascular magnetic resonance. J Cardiovasc Magn Reson. 2013 May 24;15(1):43. doi: 10.1186/1532-429X-15-43.
citation: 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.
citation: 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.
citation: 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.
citation: 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.
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