The aim of the present study will be to identify different phenotypes of microvascular dysfunction and their associations with the severity of anginal symptoms assessed through the Seattle Angina Questionnaire(SAQ-7).

After administration of unfractionated heparin (100UI/Kg), a special pressure guide (Pressure Wire X, Abbott), equipped with a distal sensor capable of measuring pressure and temperature, will be introduced inside the anterior descending branch (IVA) of the left coronary artery and hyperemia will be induced by intravenous infusion of adenosine. The IMR will be calculated using the thermodilution technique, and is given by the product between the mean distal pressure, in the left anterior descending coronary artery, and the mean transit time (Tmn) during maximal hyperemia.

During the procedure, additional coronary physiological indices will be calculated such as:

• Quiescent full cycle flow ratio (RFR), - Fractional flow reserve (FFR),
• Coronary flow reserve (CFR)

In order to identify different phenotypes of microvascular dysfunction, as follows:

• Phenotype A: Patients with IMR>25, CFR <2 and FFR>0.80 (concordant pure-microvascular pathological results)
• Phenotype B: patients with IMR>25, CFR>2 and FFR>0.80 (increased microvascular hyperemic resistance, maintenance of microvascular reactivity)
• Phenotype C: Patients with IMR 25, CFR 2 and FFR>0.80 (normal hyperemic resistance and reduced reactivity) All these phenotypes can also be combined with pathological FFR measures (<0.80) (phenotypes A1, B1, C1).

Inclusion Criteria:

Patients who meet all of the following criteria will be considered for study participation:

Age ≥18 and <85 years. Chronic coronary syndrome (including patients with anginal equivalents) Angina CCS class II-IV Evidence of inducible reversible ischemia in noninvasive trials

Availability of the following measurements:

• Microvascular resistance index (IMR)
• Quiescent full cycle flow ratio (RFR),
• fractional flow reserve (FFR),
• Coronary flow reserve (CFR) Willingness to participate and sign the informed consent document prior to the procedure.

Exclusion Criteria:

At least one of the following:

Pregnancy or breastfeeding. Medical or psychological conditions that would compromise proper and orderly participation.

Left ejection fraction less than 30% Prior coronary artery bypass surgery (CABG) Decompensated congestive heart failure (CHF) Chronic or acute renal failure with creatinine >2mg/dl Severe valve disease Patients with comorbidities limiting life expectancy to less than one year.

Patients of both sexes, aged between 18 and 85 years, with clinical indication to perform a diagnostic coronary angiography, according to the current guidelines of the European Society of Cardiology will be enrolled. (ESC)