Dr. Johri (CINQ) is Awarded CIHR for: Combining Intraplaque Neovascularization with Risk Stratification by Carotid Stress Echo (The CIRCE Study)

Stress echo (SE) is one of the most accessible tests used to select patients for angiography, but suffers from moderate sensitivity and specificity for cardiovascular (CV) outcomes. In Ontario alone, of the >100,000 SEs performed every year, 90% are normal, and patients may have little follow-up. It is estimated that 3-5% (~4,000 patients/year) of those with a negative SE have a major adverse cardiovascular event(MACE) within 3 years. We have demonstrated that adding carotid plaque assessment by ultrasound to the SE is feasible and improves testing with a net reclassification improvement (NRI) of 25% for coronary artery disease (CAD). We reported that activity of plaque adds further discriminatory power for predicting CAD and MACE. Plaques can be assessed by intraplaque neovascularization (IPN), which occurs in response to hypoxia or inflammation within the lesion. IPN occurs when vessels grow from the vasa vasorum into the lesion, resulting in a fragile and leaky network at risk of rupture and hemorrhage. IPN of carotid arterial plaque can now be quantified using ultrasound contrast. We hypothesize that addition of carotid IPN detection at the time of SE will enhance risk prediction for MACE. We plan to demonstrate that plaque inflammatory activity, detected by IPN serves as a powerful imaging biomarker of CAD and CV events to improve the sensitivity of SE.

This is a prospective, parallel, 6-centre study assessing IPN + SE in 1500 consecutive outpatients referred for SE. Patients will be recruited from a community-based cardiac clinic, and the Universities of Queen’s, Dalhousie, Calgary, Toronto, and RUMC(Chicago). The NPV and sensitivity of IPN + SE for ruling out CAD will be determined. Follow-up will be 3-year MACE. The proposal is founded upon a simple, inexpensive, and safe addition to the workflow of an existing non-invasive test. Extensive work to date indicates that plaque assessment added to SE will enhance stratification to reduce referral for unnecessary angiography and better identify patients at risk. This multi-center study of IPN + SE is expected to show increased predictive power for MACE, establishing a new standard for CV risk stratification.

The CIRCE study was the top ranked proposal in its committee and awarded the 2020/2021 CIHR Project grant led by Queen’s University.

Recommendations for the Assessment of Carotid Arterial Plaque by Ultrasound for the Characterization of Atherosclerosis and Evaluation of Cardiovascular Risk: From the American Society of Echocardiography

Amer M Johri, Vijay Nambi, Tasneem Z Naqvi, Steven B Feinstein, Esther S H Kim, Margaret M Park, Harald Becher, Henrik Sillesen

J Am Soc Echocardiogr 2020;33:917-33


Atherosclerotic plaque detection by carotid ultrasound provides cardiovascular disease risk stratification. The advantages and disadvantages of two-dimensional (2D) and three-dimensional (3D) ultrasound methods for carotid arterial plaque quantification are reviewed. Advanced and emerging methods of carotid arterial plaque activity and composition analysis by ultrasound are considered. Recommendations for the standardization of focused 2D and 3D carotid arterial plaque ultrasound image acquisition and measurement for the purpose of cardiovascular disease stratification are formulated. Potential clinical application towards cardiovascular risk stratification of recommended focused carotid arterial plaque quantification approaches are summarized.

New publication by CINQ

Combined Femoral and Carotid Plaque Burden Identifies Obstructive Coronary Artery Disease in Women.

Colledanchise KN, Mantella LE, Bullen M, Hétu MF, Abunassar J, Johri AM. (2019) J Am Soc Echocardiogr. (in press).



It remains difficult to assess cardiovascular risk in symptomatic women. The development of femoral plaque precedes adverse cardiovascular events. However, associations of femoral plaque burden with coronary artery disease (CAD) severity and extent are unknown. The aim of this study was to determine sex-specific plaque quantification markers by vascular ultrasound for identifying significant, obstructive CAD.


In this cross-sectional study, 500 participants (34% women) underwent carotid and femoral ultrasound following coronary angiography. Maximal plaque height and total plaque area were quantified. Logistic regression was used to determine associations of plaque burden with significant, obstructive CAD (≥50% stenosis), when adjusted for age and cardiac risk factors. CAD prediction was evaluated using receiver operating characteristic areas under the curve (AUCs).


Two hundred thirty-one men (70%) and 78 women (46%) had significant CAD. A combined assessment of femoral bifurcation and carotid maximal plaque height was the most accurate identifier of CAD in men (AUC = 0.773, cutoff ≥ 2.7 mm, 87% sensitivity, 53% specificity) but a poorer indicator of CAD in women (AUC = 0.659, P < .01). In contrast, the strongest identification of CAD in women was achieved by a combined analysis of common femoral and carotid total plaque area (AUC = 0.764, cutoff ≥ 42.0 mm2, 86% sensitivity, 53% specificity). At this value, more than half of women with false-positive stress test results were correctly identified as having no significant CAD.


Combined femoral and carotid plaque burden assessments effectively ruled out significant disease in both sexes. Vascular ultrasound may have particular value for cardiovascular risk stratification in women, in whom traditional screening tools are less effective.


Femoral Quantification Manuscript