Microvascular Recovery With Ultrasound in Myocardial Infarction (MRUSMI) Post PCI Trial

Study Overview
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Brief Summary
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The investigators propose to test the effectiveness of a technique that uses a modified commercially available ultrasound system used for cardiac imaging, and a commercially available ultrasound contrast agent (microbubbles) to break up the blood clots that cause heart attacks. The ultrasound and microbubbles will be applied as soon as possible to patients presenting to the emergency department, after an EKG confirms that a heart attack is ongoing. Patients who provide emergent consent will be randomized to either conventional therapy for a heart attack, or conventional therapy and ultrasound with microbubbles. The ultrasound will be applied both before and after emergent heart catheterization, in order to break up the blood clots that are not only in the artery supplying the heart muscle, but also in the small branches (capillaries) that are fed by this artery. Following the randomized treatment, patients will be followed for the development of any complications (recurrent heart attack, heart failure, or need for defibrillator placement) as well as by echo and cardiac MRI to determine how much heart muscle was salvaged by the treatment.

Detailed Description
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The investigators propose to test the effectiveness of a technique that uses a modified commercially available ultrasound system used for cardiac imaging, and a commercially available ultrasound contrast agent (microbubbles) to break up the blood clots that cause heart attacks. The ultrasound and microbubbles will be applied as soon as possible to patients presenting to the emergency department, after an EKG confirms that a heart attack is ongoing. Patients who provide emergent consent will be randomized to either conventional therapy for a heart attack, or conventional therapy and ultrasound with microbubbles. The ultrasound will be applied both before and after emergent heart catheterization, in order to break up the blood clots that are not only in the artery supplying the heart muscle, but also in the capillaries that are fed by this artery. Following the randomized treatment, patients will be followed for the development of any complications (recurrent heart attack, heart failure, or need for defibrillator placement) as well as by echo and cardiac MRI to determine how much heart muscle was salvaged by the treatment. A total of 250 patients will be enrolled and followed at two different sites. Randomization will be stratified at each study site. The initial site enrolling patients will be University of Sao Paulo Medical School. The other is Vrije Universiteit (VU) University Medical Center in Amsterdam.

Official Title
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Effect of Diagnostic Echocardiogram on Microvascular Recovery Following Acute STEMI

Conditions
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STEMI, Chest Pain

Intervention / Treatment
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* Procedure: percutaneous intervention (PCI)
* Drug: Microbubbles
* Procedure: Ultrasound


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patients presenting to participating centers with chest pain and EKG evidence of an acute STEMI (two contiguous leads with >0.1 millivolt (mV) ST elevation or >0.1 ST depression in V2-V4) will be asked to participate. The inclusion criteria will be: Age ≥30 years. Eligible for emergent PCI/antithrombotic/antiplatelet therapy. Adequate apical and/or parasternal images by echocardiography. No contraindications or hypersensitivities to ultrasound contrast agents. Exclusion Criteria: Known or suspected hypersensitivity to ultrasound contrast agent used for the study. Cardiogenic Shock Life expectancy of less than two months or terminally ill. Known severe cardiomyopathy. Known bleeding diathesis or contraindication to glycoprotein 2b/3a inhibitors, anticoagulants, or aspirin Known large right to left intracardiac shunts.

Ages Eligible for Study
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Minimum Age: 30 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: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Ultrasound and microbubbles<br>Patients who provide emergent consent will be randomized to either conventional therapy for a heart attack, or conventional therapy and ultrasound with microbubbles. The ultrasound will be applied both before and after emergent heart catheterization, in order to break up the blood clots that are not only in the artery supplying the heart muscle, but also in the small branches (capillaries) that are fed by this artery. | Procedure: percutaneous intervention (PCI)<br>* Successful PCI with the patent vessel and at least Thrombolysis in Myocardial Infarction (TIMI) 2 flow in the left anterior descending artery (LAD) post-PCI.<br>Drug: Microbubbles<br>* The agents will be divided into two separate doses (two vials per study), and mixed with approximately 29 milliliters of saline (approximately a 2.0-4.0% infusion). The first dilution will be administered pre PCI therapy, and the second dilution infused immediately post PCI. Since Optison is less stable in saline, an alternative approach will be to give the Optison as intermittent 0.1 milliliter boluses followed by 3-5 saline flushes over 10 seconds. The entire duration of each treatment before PCI will be up to 30 minutes depending on time constraints in getting to the catheterization laboratory, while the duration of treatment immediately after PCI will be 30 minutes.<br>* Other names: OPTISON™ (Perflutren Protein-Type A Microspheres Injectable Suspension, USP) manufactured by General Electric Global Research;Procedure: Ultrasound<br>* Intermittent high Mechanical Index (MI) impulses (0.8-1.4 MI; Frequency 1.0-1.7 MegaHertz (MHz); pulse duration 4-44 microseconds) will be administered over the microvasculature where there are wall motion abnormalities and a perfusion defect using an imaging plane that best aligns itself with the risk area<br>|
| Other: Standard of care<br>Emergent PCI/antithrombotic/antiplatelet therapy with Echocardiogram to assess Left Ventricular Ejection Fraction (LVEF) and Aspirin, Plavix, or Direct Thrombin Inhibitor. | Procedure: percutaneous intervention (PCI)<br>* Successful PCI with the patent vessel and at least Thrombolysis in Myocardial Infarction (TIMI) 2 flow in the left anterior descending artery (LAD) post-PCI.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Six month event free survival (EFS) | The time from the start of treatment to first cardiac event or death as a first event. Cardiac events include, congestive heart failure, life threatening arrhythmias, and need for prophylactic defibrillator (primary and secondary). | 6 months | 
| Myocardial salvageability index | The difference between extent of delayed enhancement by Gd MRI and the T2 weighted double or triple inversion spin echo assessment of risk area (defined above). | Prior to hospital discharge (48-72 hours) | 
| Frequency of left ventricular remodeling | Defined as a 20% increase in end diastolic volume at the six month follow up biplane contrast enhanced echocardiogram compared to the pre-discharge contrast enhanced echocardiogram | 6 month follow-up | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Safety of contrast in this setting | Assessed by any alterations on oxygen saturation or hemodynamic effects acutely related to ultrasound contrast administration | at the time of procedure to 6 month follow-up | 
| Frequency of > 50% ST segment resolution by EKG at six hours post PCI. | Frequency of > 50% ST segment, (a key indicator for both myocardial ischaemia and necrosis if it goes up or down) resolution by EKG at six hours post PCI. | 6 hours post PCI | 
| Area under the Creatine Phosphokinase (CPK) versus time curve | Quantifies infarct size | at time of procedure | 
| Overall survival (OS) | Defined as the time from the start of randomized treatment to death from any cause. | From date of randomization until the date of first documented progression or date of death from any cause, whichever comes first, assessed up to 120 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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segment elevation myocardial infarctions (STEMIs),, sonothrombolysis, reperfusion, percutaneous intervention (PCI),, antithrombotic therapy,, antiplatelet therapy,