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.

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.

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

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.