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.
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.