Coronary-related myocardial ischemia can result from obstructive epicardial stenosis or non-obstructive causes including coronary microcirculatory dysfunction and vasomotor disorders. This prospective study has been created in order to provide knowledge in the field of non-obstructive coronary artery disease.

All-comer patients referred for coronary physiological assessment with pressure-flow measurements and acetylcholine endothelial function test, aimed to investigate different aspects of non-obstructive coronary artery disease, will be enrolled. Coronary hemodynamics during adenosine or acetylcholine evaluation will be measured either with a physiology wire equipped with pressure and temperature sensors (Abbott), or with a physiology wire equipped with pressure sensor and Doppler (Philips). Non-endothelium-dependent functional assessment will be performed with intravenous or intracoronary adenosine administration following the standard practice. Endothelium-dependent functional assessment will be performed with intracoronary acetylcholine bolus administration following the standard practice, which includes continuous 12-lead ECG monitorization. Microcirculatory dysfunction and vasomotor disorders will be diagnosed according to the criteria from the last European expert consensus on Ischaemia with Non-Obstructive Coronary Arteries (INOCA). Medical therapy will be adjusted on the basis of physiology study results and patients will be followed at 30 days, 1-, 2- and 5-years either at the outpatient clinic or by telephone contact. The Seattle Questionnaire of Angina will be applied during follow-up for obtaining an objective characterisation of the angina status.

OBJECTIVES OF THE STUDY:

• To investigate the coronary hemodynamics across the spectrum of coronary microcirculatory dysfunction.
• To investigate the coronary hemodynamics across the spectrum of vasomotor disorders.
• To investigate the impact of coronary microcirculatory dysfunction on clinical outcomes and patient symptoms at long-term follow-up.
• To investigate the impact of coronary vasomotor disorders on clinical outcomes and patient symptoms at long-term follow-up.
• To investigate the impact of a stratified medical therapy (guided by invasive physiology study) on patient symptoms.
• To investigate the role of microcirculatory dysfunction and vasomotor disorders in different settings of ischemic heart disease (i.e., recurrent angina despite successful percutaneous coronary intervention; myocardial infarction without obstructive coronary artery disease; left ventricular dysfunction (either systolic or diastolic) with or without heart failure).
• To develop new, alternative methods aimed to assess the coronary microcirculation.
• To investigate the role of myocardial bridging on myocardial ischemia generating mechanisms.
• To document safety of intracoronary testing in routine clinical practice.

Inclusion Criteria:

• Written informed consent available.
• Age ≥ 18 years.
• Patient eligible for invasive physiological assessment with adenosine and / or acetylcholine.

Exclusion Criteria:

• Hemodynamic instability.
• Anticipated technical issues for physiology wire measurements.
• Culprit vessel of acute coronary syndrome
• Contraindications for adenosine administration.
• Contraindications for acetylcholine test.
• Reduced life expectancy (less than 1 year).

The target population consists of patients with clinically indicated invasive physiological measures of coronary pressure and flow with adenosine and acetylcholine for the assessment of myocardial ischemia.

The study contemplates the possibility of sharing data with other researchers who have similar objectives. IPD to be shared includes demographic data, vessel characteristics, invasive coronary physiology data and outcome measures, appropriately anonymized.

Throughout the development of the study