Residual Inflammation and Plaque Progression Long-term Evaluation

Study Overview
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Brief Summary
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Inflammation drives atherosclerotic plaque rupture triggering most acute coronary syndromes. Despite advances in diagnosis and management of atherosclerosis, patients with myocardial infarction (MI) remain at increased risk of recurrent events. The RIPPLE study aims to examine the relationship between residual coronary inflammation detected by 68Ga-DOTATATE PET in patients treated for MI to long-term plaque progression measured by CT coronary angiography (CTCA). The association between infarct-related myocardial 68Ga-DOTATATE PET and myocardial function and viability will also be assessed.

Detailed Description
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While vascular inflammation can be detected using 18F-FDG PET, this method lacks inflammatory cell specificity and is unreliable for coronary imaging because of high background signals from the myocardium. Upregulation of somatostatin receptor subtype-2 (SST2) occurs in activated macrophages, offering a novel inflammation imaging target. 68Ga-DOTATATE, an SST2 PET tracer with low myocardial binding, shows promise for imaging coronary inflammation. Having previously demonstrated increased 68Ga-DOTATATE signals in coronary atherosclerotic lesions post-MI, we now aim to study the natural history of residual arterial inflammation in non-culprit arteries and better understand how 68Ga-DOTATATE signals relate to plaque morphology, progression and rupture. Residual infarct-related myocardial inflammation and its association with ischemic myocardial remodelling will also be examined.

Official Title
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Residual Inflammation and Plaque Progression Long-term Evaluation

Conditions
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Atherosclerosis, Myocardial Infarction, Coronary Artery Disease, Inflammation

Intervention / Treatment
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* Diagnostic Test: PET imaging
* Diagnostic Test: Coronary CT angiography
* Diagnostic Test: Cardiac MRI


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Male or female participants >18 years old Able to give written, informed consent and to lie flat First-presentation of myocardial infarction within  2 weeks At least mild non-culprit coronary artery disease on angiography, managed medically Exclusion Criteria: Women of child bearing potential not using adequate contraception Contrast allergy or contrast-nephropathy Uncontrolled atrial fibrillation Chronic kidney disease (eGFR <30 mL/min/1.73 m2) Any medical condition, in the opinion of the investigator, that prevents the participant from lying flat during scanning, or from participating in the study Uncontrolled chronic inflammatory disorder History of recent malignancy deemed relevant to the study by the investigator Current use of systemic corticosteroids Previous coronary artery bypass grafting surgery (CABG) or percutaneous coronary intervention (PCI) before the index event Contraindication to coronary angiography Requires CABG or staged non-culprit artery PCI

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 99 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 |
| --- | --- |
| Myocardial infarction<br>Patients with recent MI | Diagnostic Test: PET imaging<br>* Coronary 68Ga-DOTATATE PET-MRI or PET-CT at baseline and 3 months<br>Diagnostic Test: Coronary CT angiography<br>* CTCA at baseline and 2 years<br>Diagnostic Test: Cardiac MRI<br>* Cardiac MRI at 1 year<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 68Ga-DOTATATE PET vs. plaque progression | Comparison of non-culprit coronary artery 68Ga-DOTATATE tissue-to-blood ratio at 12 weeks post-MI in patients with plaque progression (changes in low attenuation plaque volume and total atheroma volume) after 2 years measured by CTCA versus those without | 2 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 68Ga-DOTATATE PET vs. CTCA-defined plaque morphology | Comparison of coronary 68Ga-DOTATATE imaging to changes in plaque morphology measured by CTCA | 2 years | 
| 68Ga-DOTATATE PET vs. intravascular imaging | Comparison of 68Ga-DOTATATE imaging to plaque morphology defined by high-resolution intravascular imaging performed during invasive coronary angiography | Baseline | 
| 68Ga-DOTATATE PET vs. hsCRP | Comparison of 68Ga-DOTATATE PET to high-sensitivity C-reactive protein | 2 years | 
| 68Ga-DOTATATE PET vs left ventricular myocardial function | Comparison of myocardial 68Ga-DOTATATE PET to left ventricular size and function | 1 year | 
| 68Ga-DOTATATE PET vs myocardial tissue characterization | Comparison of myocardial 68Ga-DOTATATE PET to myocardial scarring and oedema | 1 year |