Myocardial Ischemia Without Obstructive Coronary Stenoses

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.

• Cumulative incidence of any death [Time frame: Up to 5 years]
• Cumulative incidence of cardiac death [Time frame: Up to 5 years]
• Cumulative incidence of nonfatal myocardial infarction [Time frame: Up to 5 years]
• Cumulative incidence of ischemia-driven revascularization [Time frame: Up to 5 years]
• Safety of invasive comprehensive coronary functional testing with adenosine and acetylcholine [Time frame: During procedure]
• Emergency room visit due to angina episode [Time frame: Up to 5 years]