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

The goal of this prospective study is to assess the correlation between coronary microvascular disfunction and insulin resistance in patients with INOCA.

Patients with ANOCA and without diabetes will undergo invasive coronary microvascular assessment through coronary angiography and insulin resistance assessment through hyperinsulinemic-euglycemic clamp test.

Patients enrolled in the study will be followed for a period of 2 years to monitor their clinical status.

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.

Eligibility Criteria:
Inclusion Criteria:

* Aged over 18 years.
* Cardiac chest pain with evidence of myocardial ischemia at noninvasive myocardial stress imaging and clinical indication to diagnostic coronary angiography
* Willing and able to give informed consent for participation in the study

Exclusion Criteria:

* Obstructive CAD (defined as more than 70% luminal stenosis and/or FFR ≤0.80 in 1 or more epicardial vessels).
* History of previous myocardial infarction, percutaneous revascularization or coronary-aortic bypass graft (CABG) surgery.
* Diagnosis of type II diabetes.
* BMI ≥ 35 kg/m2.
* Stage IV and V of chronic kidney disease (eGFR ≤ 30 ml/min, estimated through CKD - EPI Creatinine Equation).
* Allergy or other contraindication to iodinated contrast and/or gadolinium and/or adenosine.
* Chronic resting O2 saturation ≤ 85%.
* Pregnancy or suspected pregnancy.