New Technologies to Determine Carotid Plaque Vulnerability: A Pilot Study to Assess Contrast-Enhanced Ultrasound (CEUS) and Strain Deformation Imaging in Patients of Known or Suspected Coronary Artery Disease

This is a prospective cohort study. - Participating Site(s) (principal investigators in parentheses) that will be enrolling patients will be: Mayo Clinic Rochester site (PI: Sharon Mulvagh, MD). Only subjects who provide their informed consent will be included. Patients will be prospectively identified at the time they present to the echocardiography laboratory and scheduled to undergo exercise or dobutamine stress testing for the reason of known or suspected CAD. The patients will undergo a carotid artery ultrasound with and without contrast, carotid artery strain imaging and stress echo with contrast in same setting as detailed in study flow chart. MRI will be performed in a subset of a randomly selected patient (50 pts) to ascertain the diagnostic accuracy of CEUS in plaque identification. All patients will be followed up by reviewing electronic medical records (EMR) and/ or phone contact using standardized approved questionnaire survey at 6 and 12 and 24 months after ultrasound studies have been completed. The outcome is major adverse cardiac events (MACE) including cardiac death, acute coronary syndrome (ACS), unstable angina pectoris, nonfatal acute myocardial infarction, and stroke. Study eligibility criteria: age ≥ 18 years, suspected or known to have CAD and referred to stress echo lab. Study Exclusion criteria: Previous carotid surgery or angioplasty; Stroke, cardiogenic shock, pulmonary hypertension, heart failure; other serious disease; Prior contraindication to contrast agent.

1.Study Procedures: Carotid artery ultrasound (2D and CEUS) will be performed during the resting phase of stress echocardiography in each patient. Transthoracic SE [exercise or dobutamine] will be performed by an experienced sonographer/echocardiographer according to the American Society of Echocardiography recommendations.

2.Imaging protocol: Commercially available ultrasound system (Vivid, GE Medical Systems, Milwaukee, WI, USA) equipped with phased-array transducers, and contrast imaging technology will be utilized. OptisonTM (GE Healthcare Inc., Princeton, NJ)] will be used for CEUS and left ventricular opacification (LVO) for wall motion score index (WMSI). 2D carotid US, carotid strain, CEUS and Contrast SE will be performed in succession. The contrast agent will be administered per package insert guideline for dosing. The commercially available real time coherent pulse imaging (CPI) low Mechanical index contrast imaging schemes will be utilized.

1. Standard carotid ultrasound: Longitudinal and short axis images of each carotid artery will be acquired and digitally stored for off line strain analysis. The short axis images will be acquired 1.5 cm from the bifurcation.
2. Carotid CEUS: The contrast agent will be injected via a peripheral vein as a bolus per package insert. The appearance of the contrast effect will be observed inside the lumen of the carotid artery within 15-30 seconds after the injection. A real-time contrast-enhanced carotid cine-loop (longitudinal and short axis) including images obtained at least 3 seconds before and 5 minutes after the appearance of the contrast effect in the lumen of the carotid artery, will be acquired and digitally stored for off line analysis. The entire imaging session will be digitized and recorded on videotape and digitally for subsequent offline analysis. All echocardiographic measures will be made in a blinded fashion by a single observer.
3. MRI: 50 pts will be randomly selected to undergo Carotid MRI within the same episode of care (+/- 4 weeks) to determine the diagnostic accuracy of CEUS in identifying a vulnerable atherosclerotic plaque and neovascularization.The carotid imaging protocol will involve a standard 2D carotid ultrasound imaging and CEUS imaging as follows.

3.Trial Variables: