Breathing-Induced Myocardial Oxygenation Reserve

Coronary Artery Disease Clinical Trial

— B-MORE-Pilot  

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03050346
• Other study ID #: 15-398-MUHC
• Status: Completed
• Start date: January 2016
• Est. completion date: March 24, 2022

Study information

• Verified date: October 2022
• Source: McGill University Health Centre/Research Institute of the McGill University Health Centre
• Contact: n/a
• Is FDA regulated: No
• Study type: Observational

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 113
• Est. completion date: March 24, 2022
• Est. primary completion date: June 2019
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Coronary Artery Disease
• Coronary Disease
• Myocardial Ischemia
• Respiratory Aspiration

Locations

Country	Name	City	State
Canada	Jewish General Hospital	Montreal	Quebec
Canada	McGill University Health Centre	Montreal	Quebec
Germany	University Hospital Heidelberg	Heidelberg
South Africa	Groote Schuur Hospital	Cape Town
United Kingdom	King's College London	London
United States	University of Wisconsin	Madison	Wisconsin

Sponsors (6)

Lead Sponsor	Collaborator
McGill University Health Centre/Research Institute of the McGill University Health Centre	Groote Schuur Hospital, Jewish General Hospital, King's College London, University Hospital Heidelberg, University of Wisconsin, Madison

Countries where clinical trial is conducted

United States,  Canada,  Germany,  South Africa,  United Kingdom, 

References & Publications (11)

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. — View Citation

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. — View 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. — View Citation

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. — View 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. Epub 2003 Oct 13. — View 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. — View 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. — View 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. — View Citation

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. — View Citation

Neill WA, Hattenhauer M. Impairment of myocardial O2 supply due to hyperventilation. Circulation. 1975 Nov;52(5):854-8. — View Citation

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. — View Citation

* Note: There are 11 references in all — Click here to view all references

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	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
Secondary	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
Secondary	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
Secondary	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