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

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

Study Overview

• Status: Recruiting
• Conditions: Coronary Artery Stenosis

Detailed Description

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.

• Study Type: Observational
• Enrollment (Estimated): 350

Contacts and Locations

• Study Contact: Name: Elizabeth Konidis; Phone Number: 37305 514 934-1934; Email: elisavet.konidis@muhc.mcgill.ca
• Study Contact Backup: Name: Adonis Rodaros; Phone Number: 37305 514 934-1934; Email: adonis.rodaros@muhc.mcgill.ca

Study Locations

• Canada
  • Quebec
    • Montreal, Quebec, Canada, H4A 3J1
      • Recruiting
      • McGill University Health Center
      • Contact: Elizabeth Konidis; Phone Number: 37305 514 934-1934; Email: elisavet.konidis@muhc.mcgill.ca
      • Contact: Matthias G Friedrich, MD; Phone Number: 514 934-1934; Email: mgfriedrich@gmail.com

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 14 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: Yes

• Sampling Method: Non-Probability Sample

Study Population

Study population will be composed of patients with suspected or known CAD and healthy volunteers. The primary group will consist of patients with 1- or 2-vessel CAD. Patients diagnosed with 3-vessel or no obstructive disease in an angiography visit after the CMR exam will be included as a sub-group, with not more than 25% of the study population being in this group. Healthy volunteers will serve to act as a control for the assessment of a diagnostic cut-off.

Patient who performed the CMR and then the angiography, who are deemed to have no obstructive (no vessel) CAD or 3-vessel CAD, will be assigned to a subgroup of the study. No vessel disease will be those who have no vessel stenosis of >0.75. 3-vessel disease will be those who have a stenosis of >0.75 in all three coronary arteries.

Description

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

Study Plan

How is the study designed?

Design Details

• Observational Models: Other
• Time Perspectives: Prospective

Number of groups / cohorts

2

Cohorts and Interventions

Group / Cohort
Age matched Healthy participants (150); 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); 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?

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

Collaborators and Investigators

• Sponsor: McGill University Health Centre/Research Institute of the McGill University Health Centre
• Investigators: Principal Investigator: Matthias G Friedrich, MD, Reseach Institute of the McGill University health Center

Study record dates

Study Major Dates

• Study Start (Actual): July 4, 2019
• Primary Completion (Estimated): December 1, 2024
• Study Completion (Estimated): December 1, 2024

Study Registration Dates

• First Submitted: October 11, 2019
• First Submitted That Met QC Criteria: October 11, 2019
• First Posted (Actual): October 15, 2019

Study Record Updates

• Last Update Posted (Actual): October 24, 2024
• Last Update Submitted That Met QC Criteria: October 22, 2024
• Last Verified: October 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Vascular Diseases; Cardiovascular Diseases; Heart Diseases; Coronary Disease; Myocardial Ischemia; Coronary Stenosis
• Other Study ID Numbers: 2019-4137

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No