State-of-the-Art Review
Advances in Coronary Computed Tomographic Angiographic Imaging of Atherosclerosis for Risk Stratification and Preventive Care

https://doi.org/10.1016/j.jcmg.2023.02.002Get rights and content

Highlights

  • Significant advances in coronary CTA now allow for detailed measurement of atherosclerosis and could be very helpful to guide preventive care, including automated quantification of stenosis severity and atherosclerotic plaque and its compositional subgroups.

  • Coronary artery dimensions vary by age, sex, heart size, coronary dominance, and race and ethnicity. Accordingly, quantification programs excluding smaller arteries affect accuracy for women, patients with diabetes, and other patient subsets.

  • Limited prognostic evidence is available to report on the thresholds for high-risk status on the basis of newer automated measurements of atherosclerotic plaque.

  • The promise of automation with coronary CTA enhances the feasibility of imaging of atherosclerosis and the possibility of coronary CTA-guided preventive care.

Abstract

The diagnostic evaluation of coronary artery disease is undergoing a dramatic transformation with a new focus on atherosclerotic plaque. This review details the evidence needed for effective risk stratification and targeted preventive care based on recent advances in automated measurement of atherosclerosis from coronary computed tomography angiography (CTA). To date, research findings support that automated stenosis measurement is reasonably accurate, but evidence on variability by location, artery size, or image quality is unknown. The evidence for quantification of atherosclerotic plaque is unfolding, with strong concordance reported between coronary CTA and intravascular ultrasound measurement of total plaque volume (r >0.90). Statistical variance is higher for smaller plaque volumes. Limited data are available on how technical or patient-specific factors result in measurement variability by compositional subgroups. Coronary artery dimensions vary by age, sex, heart size, coronary dominance, and race and ethnicity. Accordingly, quantification programs excluding smaller arteries affect accuracy for women, patients with diabetes, and other patient subsets. Evidence is unfolding that quantification of atherosclerotic plaque is useful to enhance risk prediction, yet more evidence is required to define high-risk patients across varied populations and to determine whether such information is incremental to risk factors or currently used coronary computed tomography techniques (eg, coronary artery calcium scoring or visual assessment of plaque burden or stenosis). In summary, there is promise for the utility of coronary CTA quantification of atherosclerosis, especially if it can lead to targeted and more intensive cardiovascular prevention, notably for those patients with nonobstructive coronary artery disease and high-risk plaque features. The new quantification techniques available to imagers must not only provide sufficient added value to improve patient care, but also add minimal and reasonable cost to alleviate the financial burden on our patients and the health care system.

Section snippets

Potential Targets for Comparing Coronary CTA Atherosclerosis Measurements

Many coronary CTA measures have substantive research correlating atherosclerotic plaque with pathologic findings in sudden cardiac death, in invasive imaging (eg, intravascular ultrasound [IVUS]) in acute coronary syndromes (ACS), or for risk stratification for major CAD events. The concept that coronary CTA can similarly measure these previously identified high-risk features—from pathology or invasive imaging or related to major CAD events—is integral to the use of coronary CTA to guide

Traditional Semiautomated Approaches for Quantification of Atherosclerotic Plaque

Methods for quantifying atherosclerotic plaque have been available for many years, but given the lengthy time required for manual measurement (from 20 minutes to 6 or more hours, depending on the extent of atherosclerosis), application has been limited to the research setting. On coronary CTA, atherosclerotic plaque is measured in coronary arteries and branches >1.5-2.0 mm in diameter. Moreover, atherosclerosis is defined as tissue >1 mm2 within or adjacent to the lumen that is discriminated

Visual Markers of High-Risk Atherosclerotic Plaque Associated With ACS

Additional visually identified markers have been correlated with ACS, either at the time of the event or as precursor features. These high-risk ACS features are generally assessed visually but have played a prominent role in the evidence base for the utility of coronary CTA in assessing atherosclerotic plaque.16, 17, 18, 19, 20 In general, the evidence to define features of ACS on coronary CTA is largely descriptive, noting a higher burden of noncalcified plaque that also identifies those at a

Newer Artificial Intelligence Methods for Coronary CTA Quantification of Atherosclerosis

In this section, we focus our discussion on newer evidence on automated segmentation of coronary arteries to improve overall diagnostic efficiency (ie, time to diagnosis) and accurate measurement of obstructive and nonobstructive atherosclerosis. There are older reports on this subject, but in this review, we focus on the clinical approaches to automated coronary CTA measurement. Recent advances in automated software solutions for coronary CTA have received Food and Drug Administration

Accuracy of Quantifying Coronary Stenosis with Coronary CTA

Accurate measurement of stenosis severity is critical to making interventional decisions, including whether percutaneous or surgical decisions can be guided by coronary CTA measurements. Comparisons among quantitative measurements of stenosis severity have been reported, with several approaches using a machine learning algorithm that is based on the geometry and shape of the coronary lumen.26 This approach yielded a high degree of concordance, on a per lesion level, with an area under the curve

Correlating Coronary CTA Quantification of Atherosclerotic Plaque with Invasive Coronary Imaging

There is a robust body of evidence from both invasive and pathologic techniques of the role of specific coronary atherosclerotic plaque features as precursors to ACS.33, 34, 35, 36, 37, 38 The optimal scenario would be that patients with specific coronary CTA features strongly predictive of near-term risk of ACS undergo intervention, thus averting this future incident ACS event. To date, evidence is limited on the correlation between pathologic findings and coronary CTA, with 1 report

Accuracy of Coronary CTA Quantification for Prediction of Future ACS

To offset the untoward consequences of progressive atherosclerosis and ACS risk, coronary CTA measures must also be uniquely additive to prognostication,59, 60, 61, 62, 63 including characteristics of coronary atherosclerotic plaque that cause future ACS. There are differences between the pathologic correlates of ACS and what can be measured by coronary CTA. A comparison of pathologic and invasive measures of ACS vs coronary CTA is shown in Figure 4.

Considerable knowledge gaps exist relating

Limitations to Automated Coronary CTA Interpretation

Of foremost concern with regard to quantification of coronary CTA findings is that image quality must be in the good to excellent range. From the ISCHEMIA (International Study of Comparative Health Effectiveness with Medical and Invasive Approaches) trial, nearly 30% of scans were of suboptimal quality (ie, with image artifact, stents, or excessive calcification).66,67 Additionally, each quantitative software program has been applied in varied (and often highly selected) patient groups and with

Evidence Needed to Devise Coronary CTA-Guided Preventive Care Strategies

Current evidence is insufficient to provide specific image-guided therapeutic strategies. However, by allowing better identification of higher-risk patients, it is likely that imaging features could play a larger role in selection of patients for various therapeutic agents. Future research for quantitative plaque analysis may assess the efficacy of various therapeutic agents. Evidence to date supports that plaque regression by coronary CTA or IVUS is an important surrogate outcome (Table 2).87,

Future Application of CT Plaque Analysis

Future research will need to target younger individuals where the focus is on early detection and intervention of at-risk atherosclerotic plaque with enrollment from diverse populations including a large proportion of women and patients of diverse race and ethnicity. We envision that plaque analysis could be used in the following types of trials:

  • 1.

    Prognostic studies: Assessment of the association of plaque burden/plaque type with incident CAD events. Adequate image quality is essential for serial

Important Considerations for the Coronary CTA Imager

When considering these newer applications for atherosclerotic imaging, the core questions to the imager are whether the added expense would enhance the care of patients referred to them and whether their referring physicians are eager to integrate these data into preventive care. Coronary CTA is a relatively inexpensive procedure, and many of these quantitative programs will add considerable cost beyond that of the index test. Thus, at the heart of decisions to use quantitative software

Concluding Statements

A summary of evidence on newer approaches for automated coronary CTA interpretation reveals that the data are “under development.” The strengths and limitations of quantitative measurements with coronary CTA are highlighted in the Central Illustration. Certainly, many issues are related to limited available data and to unknowns about how reliable these novel techniques are as an aid to the coronary CTA reader. Considerable evidence is required for these quantitative techniques to become an

Funding Support and Author Disclosures

Dr Blankstein has served as a consultant for Caristo Inc, Elucid Inc, HeartFlow Inc, and Nanox AI. Dr Leipsic has served as a consultant for and has stock options in HeartFlow and Circle CV Imaging. Dr Shaw has received speaker honoraria from HeartFlow and Elucid Imaging. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose.

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    Todd Villines, MD, served as Guest Editor for this paper.

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