Remote Myocardial Ischemic Preconditioning in Humans

Study Overview
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Brief Summary
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Ischemic preconditioning (IP) has been shown in animal studies to increase the myocardial tolerance to subsequent ischemia. Our primary hypothesis is that remote IP reduces myocardial ischemic injury during PCI.

Detailed Description
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Our primary hypothesis is that remote IP reduces myocardial ischemic injury during PCI. We will also test the hypotheses that IP diminishes the inflammatory response to PCI, and that higher baseline blood endothelial progenitor cell counts are predictive of a favorable response to IP. Aim 1: To evaluate whether remote ischemic preconditioning reduces the frequency of myonecrosis (troponin T≥0.03 ng/ml following PCI). Aim 2: To evaluate whether remote ischemic preconditioning reduces the inflammatory response to PCI (post PCI hsCRP level). Aim 3: To evaluate whether pre-procedure circulating endothelial progenitor cell counts correlate with the effect of remote ischemic preconditioning on myonecrosis. Background: Percutaneous coronary intervention (PCI) frequently results in ischemic myonecrosis. Ischemic preconditioning (IP) has been shown in animal studies to increase the myocardial tolerance to subsequent ischemia. Our primary hypothesis is that remote IP reduces myocardial ischemic injury during PCI. Aims: The aims of the study are to assess in patients with coronary artery disease requiring PCI, whether remote IP reduces: 1) the frequency of myonecrosis; and 2) the inflammatory response to PCI; and 3) whether the effect of IP correlates with pre-procedure circulating endothelial progenitor cell counts. Methods: The study is a prospective, randomized trial to assess the efficacy of remote IP as adjunctive non-pharmacological therapy for PCI in patients with stable or unstable angina. Remote IP will be performed by 3 cycles of 3-minutes of arm ischemia alternating with 3- minutes of reperfusion of the arm immediately before PCI. Myonecrosis and inflammation will be detected by measuring serum troponin T and high sensitivity C-reactive protein, respectively. Blood EPC counts will also be measured before the procedure.

Official Title
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Remote Myocardial Ischemic Preconditioning in Humans

Conditions
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Coronary Artery Ischemia

Intervention / Treatment
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* Device: Blood pressure cuff
* Device: blood pressure cuff


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patients will be eligible for randomization if they meet the following criteria: Age ≥ 18 years Clinically indicated elective or urgent PCI Exclusion Criteria: Patients will be ineligible for the study if one or more of the following conditions exist: Pre-PCI Troponin T ≥ 0.03 Systemic hypotension (systolic <90 mmHg) or cardiogenic shock Presence of an arteriovenous fistula or lymphedema of either arm Currently enrolled in other active cardiovascular investigational studies Severe endocrine, hepatic, renal, disorders Pregnancy or lactation Inability to provide consent Federal Medical Center inmates Inability or unwillingness to provide informed consent

Ages Eligible for Study
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Minimum Age: 18 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: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: 1<br>Arm ischemia will be induced using a blood pressure cuff that will be placed around the upper part of the arm, and inflated to 200 mm Hg for 3-minutes and then deflated for 3-minutes | Device: Blood pressure cuff<br>* Arm ischemia will be induced using a blood pressure cuff that will be placed around the upper part of the arm, and inflated to 200 mm Hg for 3-minutes and then deflated for 3-minutes<br>* Other names: sphygmomanometer;|
| Sham Comparator: 2<br>3-cycles of cuff inflation (10 mmHg)-deflation will also be performed in the control group for similar durations without inducing ischemia | Device: blood pressure cuff<br>* 3-cycles of cuff inflation (10 mmHg)-deflation will also be performed in the control group for similar durations without inducing ischemia<br>* Other names: sphygmomanometer;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Post PCI myonecrosis measured as a maximum troponin T ≥0.03 |  | 16 hours post PCI | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Post PCI myonecrosis measured as an elevation in creatine kinase MB fraction (CK-MB> 1 X upper limit of normal) |  | 16 hours post procedure | 
| Magnitude of ST segment elevation on an intracoronary electrocardiogram during balloon inflation |  | During PCI procedure | 
| Coronary perfusion measured as coronary flow reserve derived from TIMI frame counts |  | During PCI | 
| Blood high sensitivity C-reactive protein level |  | Immediately prePCI | 
| Blood endothelial progenitor cell counts (EPC) |  | Immediately prePCI | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Angioplasty, Transluminal, Percutaneous Coronary, Coronary Artery Disease, Coronary Occlusion