Insulin Resistance and Coronary Microvascular Dysfunction in Patients with Myocardial Ischemia and Non-obstructive Coronary Artery Disease

This is a prospective, experimental, single-center, explorative study designed to assess the correlation between coronary microvascular disfunction and insulin resistance in patients with INOCA. Patients identified as eligible for the protocol will be asked for written informed consent to participate in the study. Participants will undergo multimodality diagnostic tests as per standard clinical practice and international recommendations: 1. Fasting glucose, fasting insulin, HOMA index, glycated haemoglobin and oral glucose tolerance test (OGTT) will be assessed to rule out diabetes. 2. Transthoracic echocardiography will be performed to evaluate cardiac function and cardiac remodeling. 3. Coronary angiography will be performed to rule out obstructive CAD defined as angiographic stenosis ≥ 70% of one or more main epicardial coronary arteries (defined as vessels with diameter \>2.0 mm) and/or fractional flow reserve (FFR) ≤ 0,80 as indicated by the latest European Guidelines. 4. In case of angiographic evidence of unobstructive CAD, participants will undergo coronary microvascular function assessment using standard coronary pressure guidewire as indicated by the latest European Guidelines according to the recently described Fullphysiology method. If clinically indicated, in case of suspected epicardial or microvascular spasm, endothelial-dependent vasomotor function will be evaluated using a standard vasoreactivity test based on incremental doses of acetylcoline infusion as indicated by the latest European Guidelines. 5. Patients will undergo hyperinsulinemic-euglycemic clamp test at Diabetology Unit of AOUI Verona to evaluate insulin resistance and the metabolic risk. In patients with no clinical concerns, adequate pharmacological washout from betablockers, ace inhibitors, sartans and/or calcium antagonists will be considered before performing the clamp test. 6. Patients will undergo clinical follow up at 6 and 12 months via outpatient clinic or telephone contacts. Fasting glucose, fasting insulin, HOMA index and glycated haemoglobin will be re-assessed at 12 months. 7. Transthoracic echocardiography will be repeated at 12 months.