Data from human autopsy studies have showed that thrombosis of a ruptured plaque with a large necrotic core, inflammatory cells and a thin fibrous cap, the so-called thin cap fibroatheroma (TCFA), represents the main mechanism for acute coronary syndrome (ACS). Optical coherence tomography (OCT) is an imaging technique that provides high-resolution, cross-sectional images of tissue in situ. The resolution of OCT (10 um) is appropriate for measuring a cap thickness less than65 μm, and even the plaque macrophage density. 68Ga-DOTA-(Tyr3)-octreotate/NaI3-octreotide(68Ga-DOTA-TATE/NOC) Positron Emission Tomography (PET)/Computed Tomography coronary angiography (CTCA), targeting the somatostatin receptor subtype-2 selectively expressed by M1 macrophages may show coronary inflammation. The SHORE protocol aims at evaluating the synergy between OCT and 68Ga-DOTA-TATE/NOC in predicting coronary plaque progression as assessed by CTCA

ACS are the leading cause of mortality and morbidity in the western world. Despite recommended therapies, after experiencing an ACS episode patients still have an increased cardiovascular risk during follow up. In the CLIMA study OCT criteria of plaque vulnerability at non-culprit sites such as minimum luminal area <3.5mm2, fibrous cap thickness <75 µm, lipid arc extension >180° and macrophage infiltration was associated with an increased risk of cardiac death and myocardial infarction (HR 7.54, 95%CI 3.1-18.6).

Of the 36 OCT defined vulnerable plaques only 7 were associated with events showing a very low positive predictive value (19%). Yet, among the 577 plaques with macrophages accumulation only the 5.2% was associated with the endpoint. The lack of reliable information on plaque inflammation could represent the miss point to better link high risk plaques to plaque progression and/or rupture. Recent studies showed that inflammation in coronary plaques may be measured by means 68Ga-DOTATATE/PET targeting the somatostatin receptor subtype-2 selectively expressed by M1 macrophages.

Thus the investigators aim to evaluate the in vivo natural history of coronary plaques characterized from both the morphological (OCT) and inflammatory (68Ga-DOTATATE PET/CTCA) point of view in patients with ACS and at least 1 intermediated coronary lesion as assessed by FFR/iFR

Inclusion Criteria:

• Male or female participants > 50 years old
• Able to give written, informed consent and to lie flat
• Presentation of ACS within ~2 weeks
• At least 1 intermediate (30-80% diameter stenosis) non-culprit coronary artery lesion on angiography, managed medically as clinically indicated (i.e.: negative FFR/iFR)

Exclusion Criteria:

• Women of child bearing potential not using adequate contraception
• Contrast allergy or contrast-nephropathy
• Uncontrolled atrial fibrillation
• Chronic kidney disease (eGFR <30 l/min/1.73m2)
• 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
• Coronary vessels that could not be adequately imaged
• Severe valvular heart disease
• Any medical condition, in the opinion of the investigator, that prevents the participant from lying flat during scanning, or from participating in the study.

This protocol has been designed in collaboration with researchers in the United Kingdom, with the intention of combining data from the SHORE study with the Residual Inflammation and Plaque Progression Long-term Evaluation (RIPPLE; NCT04073810) study that is jointly sponsored by the University of Cambridge and Cambridge University Hospitals NHS Trust, UK.

Data will be available after the recruiting phase and till the end of the study

Only investigators of the Ripple study will have access to the data

The coronary OCT images acquired will be analyzed off-line by an independent imaging core laboratory (Euroimage Research, Rome, Italy), using validated review stations. OCT-defined plaque classification was performed according to an international consensus statement and validated criteria.

PET-CT and CT coronary angiography images will be analyzed off-line in an experienced imaging laboratory by our collaborators at the University of Cambridge.