Analysis of the Efficacy of Cardiac Ischemic Postconditioning With New Clinical End-points Using Novel Biomarkers

Study Overview
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Brief Summary
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The aim of the present study was to investigate the efficacy of ischemic postconditioning in acute myocardial infarction patients. The safety of patients enrolled in the study was ensured during the entire study. Over 18 years old men and women were enrolled in the study who arrived to 2 of the most acknowledged Hungarian cardiac centres due to acute myocardial infarction and fulfilled all inclusion and exclusion criteria as per protocol. Patients in the order of their arrival were assigned either to control or post conditioned groups by turns. Medical treatment of the control group was done according to standard Percutaneous Coronary Intervention (PCI) guidelines, i.e. there was no further intervention after artery opening for 8 minutes, then stenting was performed. In the post conditioned group, after reperfusion has been confirmed, the coronary artery was occluded by inflation of the stent balloon 4 times (for 1-1 minute) followed by 1-1-minute reperfusion repeatedly to induce ischemic postconditioning. Postconditioning procedure was followed by stenting as in the control group. All other interventions and treatments in both patient groups were identical according to guidelines.

Detailed Description
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Over 18 years old men and women were enrolled in the study who arrived to 2 of the most acknowledged Hungarian cardiac centres due to acute myocardial infarction and fulfilled all inclusion and exclusion criteria as per protocol. Patients in the order of their arrival were assigned either to control or post conditioned groups by turns. After closing patient enrolment, further subgrouping will be performed in case sufficient group size has been achieved as follows: (1) normal, control, (2) normal, post conditioned, (3) hypercholesterolemic, not treated with statins, control, (4) hypercholesterolemic, not treated with statins, post conditioned, (5) statin treated, control, (6) statin treated, post conditioned. Characterisation of postconditioning is performed by the following parameters: Blood tests 5 minutes before as well as 8, 60 minutes, 24 hours, and 3 months after PCI to measure nitrotyrosine, a biomarker of peroxynitrite formation (nitrosative stress) by ELISA; B-type natriuretic peptide, a biomarker of heart failure by ELISA; matrix metalloproteinase activities (MMP-2 and MMP-9) putative biomarkers of cardiac remodelling by zymography; microRNA expression pattern by sequencing and its validation by quantitative real-time polymerase chain reaction (PCR). Routine laboratory tests 6, 12 and 48 hours after PCI including creatine kinase (CKMB) and cardiac troponin T (cTnT). ECG immediately after recanalization and intervention after 60 and 90 minutes, then 12, 24, 36 and 48 hours later 12-lead ECG is registered. Echocardiography: 48 hours after intervention, standard view to judge left ventricle segments movement disorders Angiography: Blush, Syntax score, and ischemic risk zone (area at risk, AAR) are determined cardiac late enhancement magnetic resonance (MR) imaging to determine infarct size At 3-month follow-up visit the following parameters were measured: echocardiography for restitution assessment, cardiac late enhancement MR imaging to determine infarct size and cardiac function, blood sampling for above mentioned biochemical laboratory tests

Official Title
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Evaluation of the Efficacy and Biochemical Characteristics of Ischemic Postconditioning in Patients With Acute Myocardial Infarction Undergoing Percutaneous Coronary Intervention

Conditions
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Acute Myocardial Infarction With ST Elevation

Intervention / Treatment
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* Procedure: Postconditioning
* Device: Percutaneous coronary intervention


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Subject must be >18 years of age Myocardial infarction with elevated ST Chest pain onset less than 12 hours before PCI concordant ST elevation (>0,1 mV) in at least 2 ECG leads Occluded main proximal or middle main coronary ('Thrombolysis In Myocardial Infarction' flow grade: 0) diagnosed with coronarography Coronary opened by PCI (TIMI 2 flow grade) Awake, conscious, co-operating patient, who is able to retain his breath for 10 sec Signed Patient Information Leaflet and Patient Informed Consent Form Exclusion Criteria: Cardiogenic shock Previous myocardial infarction in the area of the occluded coronary artery Occluded coronary with visible collateral branches Lack of co-operation Current left or right bundle branch block (LBBB) Malignant ventricle arrhythmia or atrial fibrillation Killip class > 2 Known renal failure

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 80 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Basic Science
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: postconditioning<br>Patients that underwent postconditioning after primary percutaneous coronary intervention. | Procedure: Postconditioning<br>* The protocol of primary PCI followed by stenting is executed according to the descriptions according to the majority of relevant scientific literature on postconditioning studies and in accordance with the most recent guidelines. In the post conditioned group, after recanalization, the artery is occluded by inflation of stent balloon (4 times for 1-1 minute) followed by 1-1-minute reperfusion, repeatedly. Eight minutes after the start of examination, angiography is made in order to determine blood flow. Intervention is finished by the operator and another angiographic image is made (identical to initial standard projection).<br>|
| Other: control<br>Patients that underwent primary percutaneous coronary intervention. | Device: Percutaneous coronary intervention<br>* Percutaneous coronary intervention as per European Society of Cardiology guidelines.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Cardiac magnetic resonance imaging | Left and right ventricular function, myocardial scar, transmurality, diffusion spectrum imaging (DSI) measurement and evaluation | 3 months after acute myocardial infarction | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Echocardiography measurement of Cardiac Ejection Fraction | Measurement of Cardiac Ejection Fraction using Teicholz and Simpson methods on both study arms. | 48 hours and 3 months after acute myocardial infarction | 
| Echocardiography measurement of cardiac left ventricular segments for wall motion abnormalities | Calculation of cardiac wall motion score index on both study arms. | 48 hours and 3 months after acute myocardial infarction | 
| Laboratory measurement of blood Nitrotyrosine levels. | Laboratory measurement of Nitrotyrosine levels in blood samples with ELISA on both study arms. | 5 minutes before PCI as well as 8 minutes after, 60 minutes, 6, 12, 24, 48 hours, and 3 months after acute myocardial infarction | 
| Laboratory measurement of blood MMP activity. | Laboratory measurement of MMP activity in blood samples with zymography on both study arms. | 5 minutes before PCI as well as 8 minutes after, 60 minutes, 6, 12, 24, 48 hours, and 3 months after acute myocardial infarction | 
| Laboratory characterization of microRNA patterns with microRNA array | Laboratory characterization of microRNA expression pattern in blood samples with with microRNA array on both study arms. | 5 minutes before PCI as well as 8 minutes after, 60 minutes, 6, 12, 24, 48 hours, and 3 months after acute myocardial infarction | 
| Validation of selected microRNA with quantitative real-time PCR | Out of the differentially expressed microRNAs identified in Outcome 6, up to 10 different miRNAs will be selected for further validation of their specific expression change (expressed by fold-change) by quantitative real-time PCR in up to 10 randomly selected patients on both study arms, respectively. | 5 minutes before PCI as well as 8 minutes after, 60 minutes, 6, 12, 24, 48 hours, and 3 months after acute myocardial infarction | 
| Electrocardiography ST segment post-procedure evaluation | Distortion in ST segment amplitude in millivolt (mV) and duration measured in milliseconds (ms) after procedure measured by 12-lead Electrocardiography (ECG) will be evaluated on both study arms. | Post-procedure 60, 90 minutes, and 12, 24, 48 hours. | 
| Electrocardiography T wave post-procedure evaluation | Distortion in T wave amplitude in millivolt (mV) and duration measured in milliseconds (ms) after procedure measured by 12-lead Electrocardiography (ECG) will be evaluated on both study arms. | Post-procedure 60, 90 minutes, and 12, 24, 48 hours. | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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MRI, ischemic postconditioning, acute myocardial infarction, Investigator Initiated Trial, PCI, biomarker, coronary artery disease, ischemic, postconditioning, infarction, infarct size, area at risk, coronary occlusion, balloon catheter, percutaneous coronary intervention