Coronary Microvascular Disease, Coronary Microvascular Dysfunction, Insulin Resistance
Conditions
Keywords
Coronary Microvascular Dysfunction, Coronary Microvascular Disease, Insulin Resistance, INOCA, ANOCA, CMD, hyperinsulinemic-euglycemic clamp test
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.
Interventions
DIAGNOSTIC_TESTThermodilution based assessment of coronary microcirculation
Coronary microvascular assessment with the derivation of CFR, IMR and MRR will be performed using a standard pressure/thermodilution guidewire.
DIAGNOSTIC_TESTHyperinsulinemic-euglycemic Clamp test
Infusion of insulin and glucose adjusting rate of glucose infusion to maintaine plasma glucose around 90 mg/dL by monitoring plasma glucose levels every 5-10 minutes
Sponsors
Azienda Ospedaliera Universitaria Integrata Verona
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
DIAGNOSTIC
Masking
NONE
Intervention model description
Prospective, experimental, single-arm, explorative study. The study aims to perform a functional study of the coronary microcirculation with pressure guides, in patients with angina and non obstructive coronary artery disease. Also a tranthoracic echocardiography will be performed. Following this, the patient will undergo hyperinsulinemic-euglycemic clamp test to evaluate insulin resistance and the metabolic risk. The primary endpoint is to assess the correlation between the index of microcirculatory resistance and the M-value evaluated with clamp test as a measure of insulin resistance. Follow up will continue up to 1 year from enrollment through telephone contacts, outpatient visits and review of clinical data.
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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
| Measure | Time frame | Description |
|---|---|---|
| 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 |
Countries
Italy
Contacts
Primary ContactNatascia Antonioli
Outcome results
None listed