AID-ANGIO is an observational, prospective, single arm, longitudinal study. Its objective is to investigate the diagnostic yield of the systematic use of a diagnostic strategy hierarchically addressing both obstructive and non-obstructive causes of myocardial ischaemia in an all-comers population of patients with chronic coronary syndromes (CCS) undergoing invasive coronary angiography (ICA). Angiographically severe-grade stenosis (≥70%) can be safely considered flow-limiting without further physiological assessment. Conversely, by means of a pressure guidewire, intermediate-grade stenosis would be evaluated with fractional flow reserve (FFR) and/or non-hyperaemic pressure ratios (NHPR) in order to determine if they are physiologically relevant. Those patients with non-obstructive CAD or normal epicardial coronary arteries would undergo functional coronary tests to investigate the presence of microcirculatory and vasomotor coronary disorders, which would account for non-obstructive causes of ischaemia. The main hypothesis of AID-ANGIO study states that, in patients with CCS referred to ICA, the application of a structured strategy -including ICA, physiological assessment of intermediate-grade stenosis and functional coronary tests- leads to a high diagnostic accuracy.

AID-ANGIO is designed as an observational, prospective, single arm, longitudinal study, intended to assess the diagnostic yield of a hierarchical strategy which investigates both obstructive and non-obstructive causes of myocardial ischaemia in patients with CCS at the time of ICA. The diagnostic algorithm starts with an ICA. Angiographically severe-grade stenosis (≥70%) can be safely considered flow-limiting without further physiological assessment. Conversely, by means of a pressure guidewire, intermediate-grade stenosis should be evaluated with FFR and/or NHPR in order to determine if they are physiologically significant. Those patients with non-obstructive CAD or normal epicardial coronary arteries should undergo functional coronary tests to investigate the presence of microcirculatory and vasomotor coronary disorders, which would account for non-obstructive causes of ischaemia. The pressure guidewire to be used in the whole physiological evaluation (both epicardial and microvascular divisions) is the PressureWire X (Abbott) with a Coroventis Coroflow Cardiovascular System (Abbot) console.

After obtaining patients' informed consent, enrolment would encompass two steps. Firstly, a conventional ICA would be performed, according to standard practice. Then, obtained images would be displayed to patient's referring clinicians. They would be asked to identify epicardial stenosis affecting those vessels susceptible of revascularization, if they would be ≥ or <70%, and, in those <70%, if they would think they could be physiologically relevant. They would also be asked about the tentative therapeutic approach they would suggest, only taking into account patient's clinical information and ICA images. All this information would be collected in a written document to which the interventional team would be blinded. Subsequently, AID strategy would continue to be applied as previously described. Information gathered at the end of it would be written in a separated document by the interventional team. Next, referring physician and interventional team would together review the case, considering clinical information, ICA images and all findings from AID strategy application. Suitable cases for coronary artery bypass grafting (CABG), would also be discussed with a cardiovascular surgeon.

The AID-ANGIO study has a main hypothesis and two secondary hypotheses:

• Main hypothesis: In patients with CCS referred to ICA, the application of a structured AID strategy -including ICA, physiological assessment of intermediate-grade stenosis and functional coronary tests- leads to a high diagnostic accuracy.
• Secondary hypothesis (1): In patients with CCS referred to ICA, the application of a structured AID strategy leads to a significant change in their treatment.
• Secondary hypothesis (2): In patients with CCS referred to ICA, the application of a structured AID strategy increases the number of patients diagnosed with coronary microvascular dysfunction (CMD).

Inclusion Criteria:

• Patients with CCS, referred to ICA by their clinicians, suffering from angina and/or positive evidence of ischaemia in non-invasive tests and/or presence of CAD in computed tomography angiography.

Exclusion Criteria:

• Age <18 or >90 years old.
• Pregnancy.
• Severe left ventricle systolic dysfunction (LVEF ≤30%) or congestive heart failure.
• Any concomitant severe valve disease. Severely decreased renal function (glomerular filtration rate <30 mL/min/1.73 m2).
• Previous CABG.
• Presence of any anatomic features hampering intracoronary instrumentation with pressure guidewires.
• Contraindications to the administration of adenosine (asthma, 2nd or 3rd grade atrioventricular block without pacemaker, history of a non-ablationed accessory pathway-mediated tachycardia) or acetylcholine (asthma, 2nd or 3rd grade atrioventricular block without pacemaker, paroxysmal atrial fibrillation).

All-comer study population of patients with CCS referred to ICA.