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

Not Applicable

Recruiting

• Conditions: Coronary Microvascular Dysfunction; Coronary Microvascular Disease; Insulin Resistance
• Interventions: Diagnostic Test: Thermodilution based assessment of coronary microcirculation; Diagnostic Test: Hyperinsulinemic-euglycemic Clamp test

• Registration Number: NCT06597851
• Lead Sponsor: Azienda Ospedaliera Universitaria Integrata Verona

Brief Summary

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.

Detailed Description

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.

Study Timeline

• Study Start: 2024-06-24
• Status Verified: 2024-09
• Study First Submitted: 2024-09-12
• Study First Submitted QC: 2024-09-12
• Last Update Submitted: 2024-09-12
• Study First Posted: 2024-09-19
• Last Update Posted: 2024-09-19
• Primary Completion: 2025-06-30
• Study Completion: 2026-06-30

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 40

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.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Non-diabetic patients with ANOCA	Thermodilution based assessment of coronary microcirculation	* Thermodilution based assessment of coronary microcirculation with the derivation of CFR and IMR * Hyperinsulinemic euglycemic clamp for insulin resistance assessment
Non-diabetic patients with ANOCA	Hyperinsulinemic-euglycemic Clamp test	* Thermodilution based assessment of coronary microcirculation with the derivation of CFR and IMR * Hyperinsulinemic euglycemic clamp for insulin resistance assessment

Primary Outcome Measures

Name	Time	Method
Correlation between coronary microvascular dysfunction and insulin resistance	At baseline	Correlation between the index of microcirculatory resistance (IMR) and the M-value evaluated with the hyperinsulinemic-euglycemic clamp test as a measure of insulin resistance

Secondary Outcome Measures

Name	Time	Method
Correlation in vasomotor function in patients with and without IR	At baseline	Difference in vasomotor dysfunction at vasoreactivity test with acetylcholine in patients with and without IR
Adverse clinical events	12 months	Composite of cardiovascular death, new hospitalization for HF and/or ACS during follow-up

Trial Locations

Locations (1)

Azienda Ospedaliera Universitaria di Verona; 🇮🇹 Verona, VR, Italy