Immunometabolic Pattern of Intermittent Hypoxia During ST-segment Elevation Myocardial Infarction

Not Applicable

• Conditions: Myocardial Ischemic-reperfusion Injury

• Registration Number: NCT05230966
• Lead Sponsor: Clinical Hospital Center Rijeka

Brief Summary

The aim of this study is to characterize the protective pattern of intermittent hypoxia, angina pectoris and remote ischemic conditioning, in reperfusion injury by determining and monitoring the plasma immunometabolic parameters of patients with STEMI. This could contribute to better understanding of this phenotypic pattern with translation into clinical practice.

Detailed Description

In acute myocardial infarction with ST segment elevation (STEMI), lethal reperfusion injury of the myocardium, caused by percutaneous coronary intervention (PCI), represents additional and irreversible damage due to ischemic heart muscle reperfusion that contributes to the final size of the infarct zone by up to 50%. The size of the infarcted area is the major determinant for the long-term prognosis and heart failure progression in patients with STEMI. Cardioprotection from ischemic - reperfusion myocardial injury (MIRI) can be regulated by its own innate physiological adaptive mechanisms like intermittent hypoxia achieved by the method of conditioning that includes short sublethal ischemic and reperfusion episodes.

The known natural clinical equivalent of intermittent hypoxia and the starting point in understanding the underlying mechanism is angina pectoris (AP).

Intermittent hypoxia is a protective mechanism against heart ischemic-reperfusion injury with reduced tissue damage and consequently better outcome in patients with STEMI. For the purpose of this work, a cardioprotective pattern was defined that includes immunometabolic factors as parameters for assessing the state of intermittent hypoxia on which the success of the application of the method of remote ischemic conditioning (RIC) is based.

Study Timeline

• Status Verified: 2022-01
• Study First Submitted: 2022-01-12
• Study First Submitted QC: 2022-01-28
• Last Update Submitted: 2022-01-28
• Study Start: 2022-02-01
• Study First Posted: 2022-02-09
• Last Update Posted: 2022-02-09
• Primary Completion: 2022-12-01
• Study Completion: 2023-03-02

Recruitment & Eligibility

• Status: UNKNOWN
• Sex: All
• Target Recruitment: 25

Inclusion Criteria

For group 1:

1. Acute coronary syndrome; angina pectoris (chest pain with negative troponin T with or without changes in electrocardiographic findings);
2. Monovascular disease, preocclusive stenosis with TIMI(thrombolysis in myocardial infarction) > 1 on the left main or anterior descending branch of the left coronary artery
3. Visually estimated diameter of the epicardial coronary artery from 2.5 mm to 4.0 mm

For group 2:

1. Acute myocardial infarction with ST-segment elevation (ST-segment elevation> 0.1 mV in two or more leads, or> 0.2 mV in V1-V3) <6 hours from the onset of chest pain
2. Symptoms of angina pectoris preceding acute myocardial infarction
3. Monovascular disease, occlusion or preocclusive stenosis of the anterior descending branch of the left coronary artery with TIMI <1 flow in STEMI;
4. After opening the artery and setting the stent TIMI> 2 flow
5. Visually estimated epicardial coronary artery diameter up to 2.5 mm to 4.0 mm

For groups 3 and 4:

1. Acute myocardial infarction with ST-segment elevation (ST-segment elevation> 0.1 mV in two or more leads, or> 0.2 mV in V1-V3) <6 hours from the onset of chest pain
2. No symptoms of angina pectoris preceding acute myocardial infarction
3. Monovascular disease, occlusion or preocclusive stenosis of the anterior descending branch of the left coronary artery with TIMI <1 flow in STEMI;
4. After opening the artery and stent placement TIMI> 2 flow
5. Visually estimated diameter of the epicardial coronary artery from 2.5 mm to 4.0 mm

For all groups:

1. Age of patients over 18 years
2. Signed written informed consent to be included in the survey

Exclusion Criteria

1. Cardiac arrest before or after PCI;
2. Cardiogenic shock;
3. Previous myocardial infarction or revascularization of the heart;
4. Anginal pain before the onset of STEMI in patients to be subjected to RIC;
5. Patients with end-stage renal or hepatic disease, diabetics with developed micro and macrovascular complications, oncology patients;
6. Significant collaterals in the area of the occluded artery (Rentrop gradus> 1);
7. Previous use of nitrates and corticosteroids;
8. Pregnant or breastfeeding women;
9. Iodine allergy (contrast media);
10. Increase in body temperature > 37.5 ° C
11. Participation in another clinical trial

Randomly selected (coin toss) patients will be randomized to group 3 and 4, respectively, for percutaneous coronary intervention with or without RIC

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Primary Outcome Measures

Name	Time	Method
Measurement of the concentration and dynamics of cardiac myosin binding protein C (cMyBP-C)	24 hour	Serum concentrations (ng/ml) will be measured at four time points 0. - after coronary angiography and before PCI; 1. - 1 hour after PCI; 2. - 12 hours after PCI and 3. - 24 hours after PCI.
Measurement of the concentration and dynamics of metabolic parameter, glycine	24 hour	Serum concentrations (μmol/l) will be measured at four time points 0. - after coronary angiography and before PCI; 1. - 1 hour after PCI; 2. - 12 hours after PCI and 3. - 24 hours after PCI.
Measurement of the concentration and dynamics of immunological parameter, transforming growth factor beta (TGF beta)	24 hour	Serum concentrations (ng/ml) will be measured at four time points 0. - after coronary angiography and before PCI; 1. - 1 hour after PCI; 2. - 12 hours after PCI and 3. - 24 hours after PCI.
Measurement of the concentration and dynamics of troponin T (Trop T)	24 hour	Serum concentrations (ng/ml) will be measured at four time points 0. - after coronary angiography and before PCI; 1. - 1 hour after PCI; 2. - 12 hours after PCI and 3. - 24 hours after PCI.
Measurement of the concentration and dynamics of metabolic parameter, succinate	24 hour	Serum concentrations (μM) will be measured at four time points 0. - after coronary angiography and before PCI; 1. - 1 hour after PCI; 2. - 12 hours after PCI and 3. - 24 hours after PCI.
Measurement of the concentration and dynamics of immunological parameter, interleukin 1 beta (IL-1 beta)	24 hour	Serum concentrations (pg/ml) will be measured at four time points 0. - after coronary angiography and before PCI; 1. - 1 hour after PCI; 2. - 12 hours after PCI and 3. - 24 hours after PCI.
Measurement of the concentration and dynamics of oxidation/mitochondrial parameter, hypoxia-induced factor 1 alpha (HIF 1α)	24 hour	serum concentrations (pg/ml) will be measured at four time points 0. - after coronary angiography and before PCI; 1. - 1 hour after PCI; 2. - 12 hours after PCI and 3. - 24 hours after PCI.
Measurement of the concentration and dynamics of immunological parameter, monocyte chemoattraction protein 1 (MCP-1)	24 hour	Serum concentrations (pg/ml) will be measured at four time points 0. - after coronary angiography and before PCI; 1. - 1 hour after PCI; 2. - 12 hours after PCI and 3. - 24 hours after PCI.
Measurement of the concentration and dynamics of metabolic parameter, kynurenine	24 hour	Serum concentrations (μmol/l) will be measured at four time points 0. - after coronary angiography and before PCI; 1. - 1 hour after PCI; 2. - 12 hours after PCI and 3. - 24 hours after PCI.
Measurement of the concentration and dynamics of creatine kinase-MB (CK-MB)	24 hour	Serum concentrations (ng/ml) will be measured at four time points 0. - after coronary angiography and before PCI; 1. - 1 hour after PCI; 2. - 12 hours after PCI and 3. - 24 hours after PCI.

Secondary Outcome Measures

Name	Time	Method
The changes in serum values of immunometabolic parameters and creatine kinase-MB	24 hour	The data of immunometabolic parameters at baseline and during follow up period (measured at 0, 1, 12 and 24 hours after the intervention) in three groups of patients with PCI will be compared with a degree of tissue damage creatine kinase-MB.
The changes in serum values of immunometabolic parameters and troponin T	24 hour	The data of immunometabolic parameters at baseline and during follow up period (measured at 0, 1, 12 and 24 hours after the intervention) in three groups of patients with PCI will be compared with a degree of tissue damage troponin T
The changes in serum values of immunometabolic parameters and left heart ejection fraction	7 day	The data of immunometabolic parameters at baseline and during follow up period (measured at 0, 1, 12 and 24 hours after the intervention) in three groups of patients with PCI will be compared with functional assessment of the heart muscle, ejection fraction (%).
The changes in serum values of immunometabolic parameters in PCI groups and the group of healthy volunteers	24 hour	The data of immunometabolic parameters at baseline and during follow up period (measured at 0, 1, 12 and 24 hours after the intervention) in three groups of patients with PCI will be compared with the group of healthy volunteers in whom the RIC method was used.
The changes in serum values of immunometabolic parameters in PCI groups and angina pectoris (AP) group	24 hour	The data of immunometabolic parameters at baseline and during follow up period (measured at 0, 1, 12 and 24 hours after the intervention) in three groups of patients with PCI will be compared with the data of patients diagnosed with angina pectoris (AP).