Coronary atherosclerosis is the most common cause of ischaemic heart disease. About 40-50% of patients with symptoms and documented ischaemia on non-invasive tests do not show obstructive coronary artery disease on coronary angiography. This cause of ischaemic heart disease called INOCA (Ischemic Non-Obstructive Coronary Artery), far from having a benign prognosis, is associated with an increase in major adverse cardiac events (MACE) as well as increased functional limitation. The current European Society of Cardiology clinical practice guidelines for the management of chronic coronary syndrome establish for the first time a IIa recommendation for the invasive analysis of coronary flow reserve (CFR) and microvascular resistance index (MRI) in symptomatic patients with INOCA. The acetylcholine (Ach) test, based on intracoronary (ic) administration, is established as indication IIb for the assessment of micro or macrovascular vasospasm in patients with suspected vasospastic angina (VSA) (4). A national multicentre registry would allow us to determine the prevalence of INOCA and its different endotypes in our setting.

Multicentre, observational, longitudinal, prospective study on INOCA patients undergoing invasive coronary function testing.

Microvascular angina (MVA) is defined according to the standardized diagnostic criteria of COVADIS (Coronary Vasomotion Disorders International Study Group): symptoms of myocardial ischaemia, unobstructed coronary arteries and demonstrated coronary microvascular dysfunction (CFR < 2 and/or IMR >25), or microvascular spasm on Ach test. Diagnosis of coronary microvascular spasm requires provocation and reproduction of symptoms, ischaemic EKG changes, in the absence of epicardial spasm during ACh testing. The diagnosis of VSA requires that 3 conditions are met during ACh testing: 1) clinically significant epicardial vasoconstriction (≥90%); 2) reproduction of chest pain; and 3) ischaemic EKG changes.

Definition of adverse events: Myocardial infarction (MI) will be defined according to the fourth universal definition and subclassified according to type. Ischaemia revascularization will be defined as all percutaneous coronary intervention (PCI) or Coronary Artery Bypass Grafting (CABG) occurring after the baseline procedure and justified by recurrent symptoms or objective evidence of significant ischaemia on non-invasive stress tests. Heart failure will be defined as a hospital admission > 24 hours with any of the following symptoms and signs: worsening dyspnea, fatigue, fluid overload, pulmonary oedema, elevated venous pressure and need for intravenous diuretics or inotropics. Visits to the emergency department for chest pain will be considered to be those in which there is suspicion of a coronary cause.

All events will be identified and quantified from patient records, including inpatient ward admissions and emergency department visits.

Inclusion Criteria:

• Patients > 18 years.
• Anginal symptoms.
• Anginal equivalent with positive myocardial ischaemia test.
• Absence of obstructive coronary artery disease (diameter stenosis <50% or >50% with a FFR>0.80).
• Patients undergoing invasive coronary function test.
• Signed informed consent.

Exclusion Criteria:

• Failure to meet inclusion criteria.
• Patients with moderate-severe valvular heart disease.
• Patients with structural heart disease.
• Elevation of markers of myocardial necrosis.

Patients with angina and no obstructive coronary artery disease on coronary angiography, as well as those with angina equivalent symptoms and ischaemia on non-invasive tests (exercise stress test, cardiac magnetic resonance imaging, stress echocardiography, SPECT) in the absence of obstructive coronary artery disease, will be prospectively included. They must have undergone an invasive coronary function test. The absence of obstructive coronary artery disease will be defined as the presence of stenosis with a diameter <50% or >/= 50% and a negative functional test.