Stress perfusion cardiovascular magnetic resonance (CMR) imaging is an established non-invasive imaging test for detection of obstructive coronary artery disease (CAD). Fully automated quantitative perfusion CMR (QP CMR) is a new technical advancement, which offers measurement of myocardial blood flow in CMR. Additionally, recent innovations have introduced various contrast-agent-free methods for CAD assessment, such as stress T1 mapping reactivity (∆T1) and oxygen-sensitive CMR (OS CMR). These methods might eliminate the necessity for contrast administration in clinical practice, simplifying, reducing time, invasiveness and costs in evaluating patients with suspected obstructive CAD. The ADVOCATE-CMR study aims to validate QP CMR, ∆T1 and OS CMR imaging against invasive fractional flow reserve (FFR) for detection of obstructive CAD. The study also aims to head-to-head compare the diagnostic accuracy of these CMR techniques with the conventional visual assessment of stress perfusion CMR and to correlate them to short- and long-term clinical outcomes.

Study design: Single-center, observational, prospective, cross-sectional cohort study performed at the Amsterdam University Medical Centers - Location VUmc.

Study population: 182 symptomatic patients with suspected obstructive CAD (without a previous CAD history), scheduled for invasive coronary angiography (ICA) according to the decision of the treating clinician.

Methods:

1. CMR image acquisition prior to clinically scheduled ICA, using the following pulse sequences: cine imaging, OS-CMR with breathing maneuvers, adenosine-stress and rest T1 mapping, adenosine-stress and rest QP-CMR, late gadolinium enhancement;
2. Fractional flow reserve (FFR), instantaneous wave-free ratio (iFR), ratio between proximal and distal coronary pressures over entire resting cycle period (Pd/Pa ratio), coronary flow reserve (CFR) and index of microcircular resistance (IMR) in all main coronary arteries during ICA;
3. Follow-up CMR according to the abovementioned protocol 3 months after ICA (or 3 months after revascularization, if performed separately more than 1 day following ICA);
4. Clinical follow-up - 3, 6 months, 1 and 3 years after ICA or revascularization (if performed separately more than 1 day following ICA)

Inclusion criteria:

• Suspected obstructive coronary artery disease
• No documented prior history of coronary artery disease
• Clinical referral for invasive coronary angiography according to the referring clinician's decision
• Competent adult (age ≥18 years)
• Signed informed consent

Exclusion criteria:

• Acute coronary syndrome
• History of coronary revascularization (percutaneous coronary intervention or coronary artery bypass grafting surgery)
• History of coronary artery disease or acute coronary syndrome (myocardial infarction, unstable angina)
• Use of sildenafil or dipyridamole that cannot be terminated
• Pregnancy or lactation
• Allergic reaction to iodized contrast
• Concurrent or prior (within last 30 days) participation in other research studies using interventional drugs
• Extensive comorbidities (i.e. cancer, other severe chronic diseases)
• Contraindication for cardiac magnetic resonance with gadolinium-based contrast agent (including severe claustrophobia, magnetic resonance unsafe implants/devices or MR conditional devices not suitable for 3T scanner, severe renal failure with estimated glomerular filtration rate<30 mL/min/1,73 m2, known hypersensitivity for gadolinium-based contrast agent)
• Contraindications for adenosine usage (including hypersensitivity to adenosine/dipyridamole/regadenoson, second or third degree atrio-ventricular block, sick sinus syndrome, sinus bradycardia (heart rate <40 bpm), long QT syndrome, severe hypertension (> 220/120 mmHg), systolic blood pressure <90mmHg, concomitant use of dipyridamole, severe asthma or severe chronic obstructive pulmonary disease)

182 symptomatic patients with suspected obstructive CAD (without a previous CAD history), scheduled for invasive coronary angiography according to the decision of the treating clinician.