Patient description: A 46-year-old man presents with dizziness and frequent headaches. He has a family history of CAD, but no other cardiovascular risk factors such as smoking, high blood pressure, and diabetes mellitus and is physically active. The patient's LDL-C and HDL-C levels were 545 and 53 mg/dL, respectively. His fasting glucose and triglyceride levels (85 and 158 mg/dL, resp.) were within normal limits. The patient reported no use of lipid-lowering medications. Neck auscultation revealed a systolic murmur 3+/6+ in the neck, radiating to the skull. Ultrasonography of the carotid arteries, revealed severe stenosis in the left internal carotid artery (LICA), as well as moderate stenosis in the right internal carotid artery (RICA) estimated between 40% and 50%. For the LICA, the peak-systolic (PSV) and end-diastolic velocity (EDV) cutoff values were 208.5 cm/s and 54.5 cm/s, respectively; RICA PSV was 91.72 cm/s and RICA EDV was 37.37 cm/s. Plaque was observed in the anterior and posterior walls of the internal carotid artery and common carotid artery, which were characterized as bulky plates extending to the middle third of the internal coronary arteries (ICAs) and as predominantly echogenic and hyperechoic, with less than 50% of the area being echolucent with uneven surfaces.

Clinical trial eligibility criteria: eligible ages (years): 18.0-999.0,  Coronary Artery Disease Patient-specific 1. Clinical presentation: stable angina, unstable angina, non-ST segment-elevation myocardial infarction (NSTEMI) (Braunwald classification of unstable angina, see Attachment 2) or recent STEMI (>48 hours before enrollment). 2. Patient is scheduled for coronary catheterization with or without percutaneous coronary intervention. 3. Age ≥18 years. 4. Patient is able to read, understand, and sign the informed consent document. 5. Patient agrees to all protocol related procedures, including follow-up through 3 years. Lesion-specific 1. The patient has at least one intermediate coronary lesion to be assessed by FFR and VH-IVUS, defined as a lesion with a visually-estimated diameter stenosis ≥40% to <80% with a visually-estimated angiographic reference segment diameter of 2.75 mm 0 mm. 2. There may only be one study lesion in the major epicardial coronary artery or its branches. All other stenosis in this epicardial coronary artery or its branches must be <40% by visual angiographic assessment. E.g.., if the lesion is in the Left Anterior Descending(LAD), there may be no other significant lesions (≥40%) in the LAD, septals or diagonal branches. A single lesion may have normal or nearly normal appearing segments within the lesion as long as it is contained within one CASS segment. Moreover, a single lesion may span two or more CASS segments as long as there is no normal or nearly normal appearing segments >5mm in length within the lesion. However, if a diseased lesion extends across two or more CASS segments and has one or more >5 mm lengths of normal or nearly normal appearing segments within the lesion, then it is considered 2 separate lesions, and may not be enrolled. 3. More than 1 intermediate lesion per patient may be enrolled, as long as each lesion meets the entry as a study lesion (e.g. one intermediate lesion in 1, 2 or 3 unique epicardial coronary arteries (LAD vs. LCX vs. RCA), with FFR and VH-IVUS performed in each vessel. Thus, up to 3 lesions may be enrolled per patient (one in each major epicardial coronary artery). 4. PCI of any lesion in the target vessel (the main epicardial coronary artery or any of its branches) may not have been performed in the preceding 1 year (including during the index procedure) and may not be planned within the next 1 year. 5. Patients undergoing PCI of non-study lesions in non-study target vessels during the index procedure may be enrolled if one or more qualifying intermediate lesion is otherwise present in a different epicardial vessel, but PCI of all non-study lesions must be performed first (including staged procedures) and must be successful and uncomplicated before formal enrollment into this study. The PCI cannot occur in the epicardial coronary artery or its branches containing the intermediate lesion Successful PCI is defined as residual diameter stenosis of <50% in all treated lesions with Thrombolysis in Myocardial Infarction (TIMI) -3 flow in all treated vessels Uncomplicated PCI is defined as the absence of intra-procedural chest pain or ST-segment changes lasting >10 minutes, sustained vessel closure, slow or no reflow, side branch loss, distal embolization, perforation, residual dissection (>type B), or requirement for cardiopulmonary resuscitation, cardioversion or defibrillation, pacemaker insertion, intubation, intra-aortic balloon insertion or intravenous pressors. Patient-specific  Prior CABG at any time. 2. The patient is likely to undergo PCI, CABG or other cardiac surgical procedure within 1 year of the procedure. 3. ST-segment elevation myocardial infarction within 48 hours of the procedure. 4. Cardiogenic shock defined as systolic blood pressure <90 mmHg lasting >30 minutes, not responding to intravenous fluids, and/or requiring intravenous pressors or an intra-aortic balloon pump or other hemodynamic support device. 5. Heart failure as defined by New York Heart Association class III or IV (see Attachment 2). 6. Respiratory failure requiring intubation or supplementary oxygen. 7. Left ventricular ejection fraction <30% as determined by 2D echo, nuclear testing, magnetic resonance imaging (MRI), or left ventriculography. 8. Any moderate or severe cardiac valve disease. 9. Cerebrovascular accident or transient ischemic attack (TIA) within the past 60 days, or any permanent neurologic deficit. 10. Chronic renal insufficiency (serum creatinine > 2.5mg/dl). 11. History of drug abuse or alcohol abuse or any other condition making it unlikely that the patient will comply with all study procedures, including follow-up for 3 years 12. Any condition with expected survival <2 years. 13. Pregnant or nursing patients and those who plan pregnancy in the period up to 1 year following the index procedure. Female patients of child-bearing potential must have a negative pregnancy test done within 7 days prior to the index procedure. 14. Patients currently participating in another study of an investigational drug or device which has not yet reached its primary endpoint. 15. Oral intake by the patient of any caffeinated beverage within 4 hours of the procedure 16. Use within 12 hours of theophylline, aminophylline or any xanthine derivative. Lesion-specific An unprotected left main coronary stenosis is present (visually assessed %DS ≥40%, whether or not requiring treatment). The study lesion cannot be a left main lesion. 2. The intermediate lesion is in a vessel with thrombus, moderate or severe calcification, angulation, or tortuosity. PCI may be performed in such non target vessels or lesions prior to study enrollment, however, as long as successful and uncomplicated, after which the patient is enrolled in the study. 3. The study lesion is an ostial lesion (within 5 mm of the aorta or the distal left main coronary artery) or is bifurcation lesion requiring planned dual stenting