113 The MICORDIS study MBV regulation using MCE in combination with hyperinsulinemia induced by the hyperinsulinemic-euglycemic (HE) clamp and dobutamine-induced stress in ANOCA patients compared to healthy controls. METHODS Study design and participants The MICORDIS-study is a single-center observational cross-sectional cohort study of ANOCA patients compared to sex- and age-matched healthy controls. (ICTRP Search Portal (who.int), unique identifier NL-OMON23861). The study was approved by the institutional ethics committee on human research of the Amsterdam UMC, and conducted in adherence to the Declaration of Helsinki and the Medical Research Involving Human Subjects Act (WMO). We electively screened adult ANOCA-patients with long-standing angina and documented non-obstructive coronary artery disease (CAD) at the outpatient cardiology clinic of the Amsterdam University Medical Centers (UMC). Eligible candidates (Supplemental Table 1) were invited to participate. The healthy control group was simultaneously recruited via posters and local media. The control group underwent screening for exclusion criteria using transthoracic echocardiography, electrocardiography and laboratory tests, ensuring a clean medical history and ruling out severe heart disease and impaired kidney function. The study design of the MICORDIS study has been published previously.14 In brief, the study protocol consisted of two testing days (Day A and Day B) with multimodality imaging and pathophysiological tests to gather comprehensive data on MBV. Patients were instructed to withhold intake of calcium channel blockers, β-blockers, and long-acting nitrates for two days prior to both study days. All patients underwent coronary angiography (CAG) to exclude obstructive coronary artery disease (defined as fractional flow reserve ≤0.80), with CFT to identify coronary vasospasm (epicardial and/or microvascular), and CMD,15,16 using a guide wire equipped with a pressure sensor and Doppler crystal (ComboWire, XT, Philips-Volcano, San Diego, CA) to perform CFT. Acetylcholine was administered manually through intracoronary bolus injections in incremental doses (2, 20, 100, and 200 μg) into the left anterior descending (LAD) artery. If no vasospasm occurred in the LAD during assessment, a single dose of 80 μg acetylcholine was administered in the right coronary artery (RCA). Vasospasm was defined by the presence of recognizable chest pain and ischemic changes on the surface electrocardiograph (ECG), with >90% epicardial vasoconstriction on CAG, differentiating between epicardial and microvascular spasm. Coronary pressure and flow measurements were obtained both at rest and during hyperemia, induced by the administration of 150 μg adenosine. CMD was defined as CFR ≤2,5 and/or a hyperemic microvascular resistance >2.5 mmHg/ cm/s as described.14 Microvascular angina (MVA) comprises microvascular spasm and/ 6
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