The role of high power ultrasound in restoring blood flow for patients presenting with a major heart attack.

INTERVENTION: The intervention is the focused application of high mechanical index ultrasound to the heart while the patient is receiving an intravenous infusion of a microbubble contrast known as "Definity®". “Definity®" is an injectable cardiovascular ultrasound contrast agent comprised of lipid‐coated echogenic microbubbles filled with octafluoropropane gas that enhances clinicians’ view of the left ventricle of the heart during an echocardiogram to aid with diagnosis. Contrast Dosage The commercially‐available microbubbles (Definity®) to be utilized for these studies will be manufactured by Lantheus Medical. In each session, one vial (1.5 millilitres) will be mixed with approximately 48.5 millilitres of saline (approximately a 3% infusion) and then infused at the rate of 1 2ml/min (adjusted with image quality). The Pre‐PCI infusion will last for 10 minutes, while the post‐PCI infusion will last for 20 minutes. This dose and duration will be exactly the same for the intervention group and the sham echo group. The pre‐Sonothrombolysis/Sham intervention in all groups will be administered 10 minutes prior to the PCI, and will end immediately prior to the PCI procedure commencing. The post Sonothrombolysis/sham will be administered immediately after the PCI and will continue for 20 minutes. The intervention will be administered by an imaging cardiologist or a cardiology sernior registrar (advanced trainee) who is competent at delivering sonothrombolysis. All echocardiographic images for both intervention groups and sham control groups will be recorded and stored on a secure drive for further analysis. Sham Echocardiography ‐ This sham procedure is our trial's placebo group. This group will receive a Definity contrast infusion at exactly the same CONDITION: Cardiovascular ‐ Coronary heart disease Cardiovascular ‐ Other cardiovascular diseases Ischaemic Heart Disease;ST Elevation Myocardial Infarction;Coronary Microvascular Dysfunction;Microvascular Obstruction;Heart Failure; ; Ischaemic Heart Disease ; ST Elevation Myocardial Infarction ; Coronary Microvascular Dysfunction ; Microvascular Obstruction ; Heart Failure PRIMARY OUTCOME: Infarct Size will be assessed on Cardiac Magnetic Resonance (CMR) Imaging as the volume of late Gadolinium enhancement (expressed as % of total myocardium)[At 3 days and 6 months (Primary endpoint) post intervention] Infarct size will be measured by cardiographic determination of the left ventricular Ejection Fraction on cardiac magnetic resonance imaging[At 3 days and 6 months (Primary endpoint) post intervention] SECONDARY OUTCOME: Angiographic Recanalization rate determined by invasive angiography[Assessed with the first diagnostic images of invasive angiography during the initial presentation] Change in Index of microvascular resistance (IMR) ‐> invasive measure which is obtained during invasive angiography using a pressure wire and thermodilution set‐up. It will be performed by the interventional cardiologist[Immediately after completion of the primary percutaneous coronary intervention, and then again after the post‐PCI definity contrast infusion while the patient is still on the table (approximately 20 minutes later)] Chest pain as rated on a Likert scale of 1‐10 INCLUSION CRITERIA: ‐ Chest Pain with ST segment elevation >0.1 mV in two contiguous leads ‐ Eligible for emergent PCI/antithrombotic/antiplatelet therapy. ‐ Adequate apical and/or parasternal images by echocardiography. ‐ No contraindications or hypersensitivities to ultrasound contrast agents. ; [Immediately post percutaneous coronary intervention] Event‐Free Survival (EFS), defined as the time from the start of treatment to first Major Adverse Cardiac Event (MACE) or death as a first event. Cardiac events include left ventricular remodelling, death, non‐fatal myocardial infarction (recurrence), congestive heart failure, ventricular arrhythmias and need for prophylactic defibrillator (primary and secondary). This will be collected through clinical visits, electronic medical records and telephone follow‐up.[3 days, 1 month and 6 months post percutaneous coronary intervention] Global longitudinal strain (GLS) as assessed by echocardiography[3 days and 6 months post percutaneous coronary intervention] Left Ventricular Ejection Fraction as assessed by echocardiography[at 3 days and 6 months post percutaneous intervention] Quality of Life Score, as assessed by the EQ‐5D instrument[Assessed 3 days, 1 month and 6 months post percutaneous coronary intervention] Safety Endpoint: Arrhythmias during the administration of sonothrombolysis as measured by continuous ECG monitoring.[Measured for the total duration of the patient being in the cardiology cath lab during their primary percutaneous coronary intervention, as well as during both intervention/sham echos] Safety Endpoint: Arrhythmias during the index admission as assessed by cardiac telemetry during the patient's stay, as well as daily 12 lead ECGs[Measured for 3 days of admission post percutaneous intervention.] Sizes of microvascular obstruction as assessed on cardiac magnetic resonance imaging[3 days post percutaneous coronary intervention, and 6 months post percutaneous coronary intervention] The rate of ST‐segment resolution assessed on the ECG [Assessed immediately post percutaneous coronary intervention.]