Measurement of Matrix Metalloproteinase Activation Post Myocardial Infarction

Study Overview
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Brief Summary
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This study is designed to look at the measurement and prediction of changes in the heart following a heart attack.

Detailed Description
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Patients who are admitted to Yale New Haven Hospital with first acute myocardial infarction within the onset of 12 hours of symptoms will be eligible for this study and referred by their physician for this study. Subjects will be screened with medical interview and physical exam for eligibility. Clinical data will be obtained for demographic purposes including: EKG upon admission, serum cardiac markers, basic metabolic panel, cardiac catheterization report and recent echocardiography report. All standard medications will be allowed which include diuretics, ACE/Ang-II inhibitors, nitrates/hydralazine, digoxin, low dose aspirin, beta-blockers, calcium channel antagonists, anticoagulants and anti-arrhythmic agents. A 10cc blood sample will be drawn from a peripheral vein at 3 days post myocardial infarction into chilled EDTA tubes, plasma decanted and placed at -70 degrees C until MMP/TIMP assays are performed. These samples will be sent to collaborators at the Medical University of South Carolina for high sensitivity plasma assays developed at MUSC for MMP-1, -13, -8, -2, -9 and TIMP-1, -2, -4. [1] These assays will be performed in Core C and detailed description of specificity of these measurements is described. In addition, indices of collagen synthesis and degradation, through the use of telopeptide measurements will be measured in these plasma samples. Nitroglycerin resting Tl-201 myocardial perfusion imaging will be performed between 2-5 days after myocardial infarction. Subjects will have a peripheral intravenous line placed and will be injected with 2.5-3.5mCi of Tl-201. The Tl-201 given will be a slightly lower dosage than the standard clinical protocol of Yale New Haven Hospital nuclear cardiology lab because of improved reconstruction algorithms with CT will allow lower doses of radioactive isotopes. Resting myocardial perfusion images will be acquired 5 minutes post-injection on a multislice helical SPECT/CT (GE Infinia Hawkeye) followed by a CT scan. A redistribution image will be performed 4 hours after thallium administration. Each SPECT scan will take approximately 25 minutes. Perfusion defect size will be quantified using the Yale C-Q method previously described [2]. Transthoracic echocardiography will be performed at 2-5 days post-MI and 28 days after MI in standard apical and parasternal views using a commercial ultrasound system either Phillips 7500 or IE33 ultrasound imaging system with an S3 transducer. The transducer will be placed on the apical and/or parasternal location on the chest and ECG-gated images will be obtained during a breath hold. Each acquisition will be performed in zoom mode at 40 Hz, over the entire LV in 4 cardiac cycles with 40 frames per cardiac cycle. Image data will be captured in digital form and will be backed up on DVDs. NOTE: No patient HIPPA data will be saved on the DVD. Left ventricular ejection fraction (LVEF), end-diastolic volume (LVEDV), and end-systolic volume (LVESV) will be measured. The echocardiograms will be used to determine LV mass, LV cavity size and regional thickening. Patients will undergo MRI with gadolinium contrast in the GE Signa 1.5 tesla magnetic resonance image scanner located in the Yale-New Haven Hospital MRI Center, using standard ECG-gated cine gradient echo, and echo-planar, phase contrast and MR tagged imaging sequences. Electrocardiographic monitoring will be maintained during the magnetic resonance imaging. MRI scans will occur between 2-5 days post-MI. The first acquisitions to be performed will be combined cine-gradient echo/cine phase velocity approach that will obtain both the magnitude images required for our segmentation and shape-based tracking as well as contrast data for finding midwall myocardial velocities in a single image acquisition. This sequence will yield adjacent 5 mm thick axial images with in plane resolution of approximately 1.6mm x 1.6mm. We will acquire 16-20 cardiac phase per location. Patients will receive 0.1 mmol/kg of standard gadolinium contrast in a peripheral IV. The acquisition will apply inversion recovery preparatory pulse to null normal myocardium, followed by a segmented k-space gradient echo acquisition. We anticipate that all of the proposed magnetic resonance imaging for each subject will be completed within 2 hours. The technologist or doctor operating the scanner will be able to see the subject. The operator will maintain contact by voice with the subjects. None of the aforementioned procedures are considered experimental and individually, may or may not be part of the subjects' standard of care post myocardial infarction. During each part of the step of image acquisition, there will be a physician present. All data will be transferred via network to the image processing laboratory for analysis and will not include any projected personal information.

Official Title
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Measurement of Matrix Metalloproteinase Activation Post Myocardial Infarction

Conditions
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Acute Myocardial Infarction

Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Diagnosis of acute myocardial infarction characterized by (1) greater than 30 minutes of chest pain; (2) ST elevation in 2 contiguous leads greater than 2mV; and (3) elevated serum markers greater than three times the normal value. Males or females 18 years of age or older. Adequate intravenous access in one arm. Willing to comply with the requirements of the protocol. Provided written informed consent to participate in the study. Exclusion Criteria: History of significant co-morbidity requiring hospitalization separate from acute myocardial infarction (i.e. metastatic cancer). History of/current structural heart disease. Arrhythmia History of previous myocardial infarction History of coronary revascularization Cardiogenic shock Hypotension Renal failure (creatinine >2mg/dl) or hyperkalemia (serum potassium > 5.5mg/dl) History of allergic reaction to gadolinium Contraindication to undergo MR imaging (pacemaker, metallic implants, etc) History of claustrophobia Pregnant or breast-feeding, or (if pre-menopausal), not practicing acceptable method of birth control. History of any other conditions, which in the judgment of the investigator, are likely to hinder or confuse study conduct or to pose a safety concern to the patient. Resting HR >110 Chronic tetracycline or doxycycline use Ongoing/active rheumatic disease requiring significant anti-inflammatory agents, steroids or immunosuppression Not capable of 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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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| 1<br>Left ventricular ejection fraction (LVEF) patients will be compared at two time-points, 2-5 days and 4 weeks after acute MI. | |
| 2<br>End-diastolic volume (LVEDV) patients will be compared at two time-points, 2-5 days and 4 weeks after acute MI. | |
| 3<br>End-systolic volume (LVESV) patients will be compared at two time-points, 2-5 days and 4 weeks after acute MI. | |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| To predict left ventricular remodeling after myocardial infarction using serum matrix metalloproteinase measurement with Tl201 SPECT/CT hybrid imaging and MRI. |  | 1 day |