The root cause of heart attacks and strokes is atherosclerosis, the hardening and thickening of blood vessels due to the presence of "plaque" which is a build-up of fat and cholesterol in the walls of vessels. To diagnose heart disease, patients receive a stress test to find out if they require surgery. Up to 52% of patients receiving an angiogram (surgery) to look at plaque blockages in the heart are found to be normal (no blockage). Patients who are suspected of having heart disease often undergo a stress test, which helps cardiologists decide if the patient has heart disease, but stress tests can give false results. In Ontario alone, 90% are stress tests are found to be normal and patients are sent home with little follow-up. Of these 3-5% (~4,000 patients/year) will have a major cardiovascular event (heart attack, surgery, or death) within 3 years. We need to improve the stress test accuracy to reduce cardiac outcome. We now know that it is not just the total amount of plaque that leads to heart attacks and strokes, but the composition of the plaque that can lead to breakage causing a heart attack. Plaques are soft and fragile, and typically contain fat and small leaky blood vessels within their cores. If we are able to identify patients that have leaky plaques using ultrasound, we may be able to improve the accuracy of stress testing. We propose a study looking at the combination of stress testing (assessing heart function) and neck ultrasound (assessing plaque composition), to identify patients at risk for cardiovascular events (heart attacks and death). We will enrol patients from 6 sites across Canada and follow-them for cardiac outcome for 3 years.

Primary Aim: To determine if carotid intraplaque neovascularization score (IPN) combined with stress echo (SE) [IPN+SE] enhances prediction of 3-year major adverse cardiovascular events (MACE) compared to SE alone.

Objectives: 1) The % change in test sensitivity of IPN+SE for predicting 3-year MACE compared with SE alone. 2) The Net Reclassification Improvement (NRI) for MACE will be determined (patients "missed" by the SE, but captured as high risk for MACE by IPN).

Inclusion Criteria:

1. Men and women >18 years;
2. Referred for a clinically indicated SE for assessment of ischemia and risk stratification;
3. Able and willing to give informed consent.

Exclusion Criteria:

1. Emergency procedure, or active acute coronary syndrome (active chest pain, ischemic electrocardiogram changes, or cardiac enzyme elevation);
2. Referral for viability, pulmonary hypertension, or valve assessment;
3. Referral outside of the normal working hours;
4. History of significant CAD: percutaneous coronary intervention (PCI), coronary artery bypass graft (GABG), or coronary angioplasty;
5. History of stroke or myocardial infarction (MI);
6. Known or documented hypersensitivity or allergy to perflutren (DEFINITY® contrast agent);
7. Known or documented allergy to Polyethylene Glycol (Peg) a component of DEFINITY®;
8. History of carotid surgery (endarterectomy or stenting);
9. Any serious medical condition or complication from the stress test that according to the investigator could interfere with the carotid scan or optimal care;
10. Currently pregnant or breastfeeding;
11. Previous enrolment into the study.

Low to intermediate risk outpatient subjects referred for stress echo (SE) for assessment of ischemia and risk stratification will be screened for inclusion.