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| Name | Class |
|---|---|
| Cambridge University Hospitals NHS Foundation Trust | OTHER |
| Wellcome Trust | OTHER |
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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.
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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Myocardial infarction | Patients with recent MI |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| PET imaging | Diagnostic Test | Coronary 68Ga-DOTATATE PET-MRI or PET-CT at baseline and 3 months |
|
| 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 |
| 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 |
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Inclusion Criteria:
Exclusion Criteria:
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Patients with recent myocardial infarction and medically managed non-culprit coronary artery disease
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| Name | Affiliation | Role |
|---|---|---|
| Jason M Tarkin, MBBS PhD | University of Cambridge | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| University of Cambridge | Cambridge | United Kingdom |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 28385306 | Background | Tarkin JM, Joshi FR, Evans NR, Chowdhury MM, Figg NL, Shah AV, Starks LT, Martin-Garrido A, Manavaki R, Yu E, Kuc RE, Grassi L, Kreuzhuber R, Kostadima MA, Frontini M, Kirkpatrick PJ, Coughlin PA, Gopalan D, Fryer TD, Buscombe JR, Groves AM, Ouwehand WH, Bennett MR, Warburton EA, Davenport AP, Rudd JH. Detection of Atherosclerotic Inflammation by 68Ga-DOTATATE PET Compared to [18F]FDG PET Imaging. J Am Coll Cardiol. 2017 Apr 11;69(14):1774-1791. doi: 10.1016/j.jacc.2017.01.060. | |
| 25977567 |
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| ID | Term |
|---|---|
| D050197 | Atherosclerosis |
| D009203 | Myocardial Infarction |
| D003324 | Coronary Artery Disease |
| D007249 | Inflammation |
| ID | Term |
|---|---|
| D001161 | Arteriosclerosis |
| D001157 | Arterial Occlusive Diseases |
| D014652 | Vascular Diseases |
| D002318 | Cardiovascular Diseases |
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Not provided
| ID | Term |
|---|---|
| D049268 | Positron-Emission Tomography |
| ID | Term |
|---|---|
| D014055 | Tomography, Emission-Computed |
| D007090 | Image Interpretation, Computer-Assisted |
| D003952 | Diagnostic Imaging |
| D019937 | Diagnostic Techniques and Procedures |
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Blood specimens
| Coronary CT angiography | Diagnostic Test | CTCA at baseline and 2 years |
|
| Cardiac MRI | Diagnostic Test | Cardiac MRI at 1 year |
|
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 |
| Background |
| Pedersen SF, Sandholt BV, Keller SH, Hansen AE, Clemmensen AE, Sillesen H, Hojgaard L, Ripa RS, Kjaer A. 64Cu-DOTATATE PET/MRI for Detection of Activated Macrophages in Carotid Atherosclerotic Plaques: Studies in Patients Undergoing Endarterectomy. Arterioscler Thromb Vasc Biol. 2015 Jul;35(7):1696-703. doi: 10.1161/ATVBAHA.114.305067. Epub 2015 May 14. |
| 20080898 | Background | Rominger A, Saam T, Vogl E, Ubleis C, la Fougere C, Forster S, Haug A, Cumming P, Reiser MF, Nikolaou K, Bartenstein P, Hacker M. In vivo imaging of macrophage activity in the coronary arteries using 68Ga-DOTATATE PET/CT: correlation with coronary calcium burden and risk factors. J Nucl Med. 2010 Feb;51(2):193-7. doi: 10.2967/jnumed.109.070672. Epub 2010 Jan 15. |
| 36697134 | Derived | Corovic A, Wall C, Nus M, Gopalan D, Huang Y, Imaz M, Zulcinski M, Peverelli M, Uryga A, Lambert J, Bressan D, Maughan RT, Pericleous C, Dubash S, Jordan N, Jayne DR, Hoole SP, Calvert PA, Dean AF, Rassl D, Barwick T, Iles M, Frontini M, Hannon G, Manavaki R, Fryer TD, Aloj L, Graves MJ, Gilbert FJ, Dweck MR, Newby DE, Fayad ZA, Reynolds G, Morgan AW, Aboagye EO, Davenport AP, Jorgensen HF, Mallat Z, Bennett MR, Peters JE, Rudd JHF, Mason JC, Tarkin JM. Somatostatin Receptor PET/MR Imaging of Inflammation in Patients With Large Vessel Vasculitis and Atherosclerosis. J Am Coll Cardiol. 2023 Jan 31;81(4):336-354. doi: 10.1016/j.jacc.2022.10.034. |
| D017202 |
| Myocardial Ischemia |
| D006331 | Heart Diseases |
| D007238 | Infarction |
| D007511 | Ischemia |
| D010335 | Pathologic Processes |
| D013568 | Pathological Conditions, Signs and Symptoms |
| D009336 | Necrosis |
| D003327 | Coronary Disease |
| D003933 | Diagnosis |
| D007089 | Image Enhancement |
| D010781 | Photography |
| D011877 | Radionuclide Imaging |
| D014054 | Tomography |
| D003947 | Diagnostic Techniques, Radioisotope |