Coronary Physiological Assessment Protocol
This is our standard clinical protocol that is used in all patients with angina and nonobstructive coronary arteries to identify an ischemic substrate. All patients undergo coronary angiography followed by intravenous (IV) adenosine assessment. Only patients with fractional flow reserve (FFR) >0.80 were included in this study. Coronary flow reserve (CFR) was calculated as the ratio of hyperemic average peak velocity (APV) in response to adenosine (140 μg/kg/min) and resting APV, with a value of <2.5 used to diagnose endothelium-independent microvascular dysfunction. Patients then underwent assessment with intracoronary (IC) acetylcholine (ACh) infusion (18 μg/mL), and ACh flow reserve (AChFR) was calculated as the ratio of volumetric coronary blood flow (CBF) during ACh infusion and CBF during rest. Volumetric CBF, in turn, was calculated as 0.5 × APV × cross-sectional area 5 mm distal to the Doppler sensor. AChFR ≤1.5 was diagnostic of endothelium-dependent microvascular dysfunction. Patients with CFR <2.5 and/or AChFR ≤1.5 were defined as having coronary microvascular dysfunction (CMD).