Beyond Stenosis: CT-Identified Plaque Types Aid in Identifying Ischemic Lesions

January 13, 2015

NEW YORK, NY — Anatomical characteristics of atherosclerotic plaque help provide additional information beyond the extent of coronary stenosis in the prediction of ischemia in patients with stable coronary artery disease, according to the results of a new study[1].

In a study performed in 252 stable patients, positive arterial remodeling and the presence of a necrotic lipid-rich core, which were both assessed using computed tomography (CT) angiography, were associated with coronary lesions that cause ischemia, report investigators.

Senior investigator Dr James Min (Weill Cornell Medical College, New York) said the study was designed to help researchers understand the underlying atherosclerotic plaque characteristics and what these physiologic parameters mean to ischemia in patients with symptomatic coronary disease. The simple paradigm of "stenosis vs no stenosis" for identifying ischemic lesions is clearly insufficient, so their aim has been to understand the various morphologic features of the coronary plaque, features that serve as surrogate markers for the underlying physiology within the coronary artery, he said.

"And that physiology can be something as general as a transition or transformation of the coronary atherosclerotic plaque or it may represent measures of the local environment, such as endothelial dysfunction," Min told heartwire .

The study, which was published January 12, 2015 in JACC: Cardiovascular Imaging with first author Dr Hyung-Bok Park (Weill Cornell Medical College), included stable patients with coronary artery disease undergoing invasive coronary angiography and CT angiography. Lesion ischemia was assessed using fractional flow reserve (FFR) during invasive angiography and performed for 407 coronary lesions. With CT angiography, a lesion was considered obstructive if the coronary stenosis was 50% or greater.

The researchers assessed specific adverse characteristics of the atherosclerotic plaque: aggregate plaque volume (%); positive remodeling; low-attenuation plaque, which served as a marker of the necrotic lipid-laden plaque core; and microcalcifications. The microcalcifications are difficult to see by CT given the spatial-resolution limitations, so investigators used intraplaque spotty calcification as a surrogate. These measures, explained Min, have been previously documented in pathologic and prior CT studies to be "prognostically implicated in acute coronary syndrome."

Compared with nonischemic lesions, those that caused ischemia had a greater stenosis, longer length, larger plaque volume, higher aggregate plaque volume, higher rates of positive remodeling, low-attenuation plaque, and spotty calcification. In a multivariate analysis, obstructive stenosis, lesion length, positive remodeling, and low-attenuation plaque were associated with ischemia, but spotty calcification was not.

"What we found was that the spotty calcifications actually weren't that strongly predictive," Min said. "Positive arterial remodeling, however, and to a certain degree low-attenuation plaque, added to the prediction of whether or not a specific plaque caused ischemia."

When investigators stratified the lesions by stenosis, positive remodeling was a predictor of ischemia for all lesions, but aggregate plaque volume and low-attenuation plaque were associated only with ischemia for lesions with >50% stenosis, the conventional threshold for determining whether a lesion is angiographically severe.

In contrast, the presence of a greater number of morphologic characteristics and positive remodeling were predictive of ischemia in lesions with stenoses >50% and those <50%. The absence of these plaque characteristics was associated with a lower prevalence of ischemia, "even for highly stenotic coronary lesions," report investigators.

Adding to the Risk Prediction Model

In an editorial[2], Dr Antonio Colombo (San Raffaele Scientific Institute, Milan, Italy) and Dr Vasileios Panoulas (Imperial College London, UK) note the investigators showed an improvement in the area-under-the-curve (AUC) for predicting functionally significant lesions after incorporating the adverse plaque characteristics in the risk-prediction model.

"The data carefully collected and analyzed by the authors support the notion that simple lumen analysis has multiple limitations," they write. "Invasive coronary angiography, an established 'gold standard' in lumen analysis, is gradually losing ground when compared with other diagnostic tools such as coronary CT angiography or intravascular ultrasound (IVUS) [that are] able to look 'beyond the lumen.' "

They editorialists suggest a CT report should provide information on the type and number of adverse lesion characteristics, as these might aid in the decision-making process regarding the next steps, particularly for patients with borderline lesions. In the future, when high-resolution CT imaging combines an anatomic assessment of lesion characteristics with perfusion (or even CT-based FFR), coronary CT angiography might turn out to be a "one-stop" test for detecting and providing a hemodynamic evaluation of coronary disease," say the editorialists.

To heartwire , Min said that in clinical studies a CT-based FFR assessment has been shown to be the best diagnostic tool physicians have to noninvasively identify ischemic lesions in patients with coronary disease. The clinical assessment of atherosclerotic plaque characteristics, such as in this study, will become more and more important as physicians look beyond whether patients have plaque or not or whether or not they have a coronary stenosis.

"I think on top of the FFR-CT, the atherosclerotic plaque characteristics will be imperative to look at," said Min.

Speaking with heartwire , Dr John Reilly (Ochsner Foundation Hospital Center, New Orleans), who was not affiliated with the study, noted that CT angiography is a useful noninvasive tool for physicians. He pointed out that the researchers used 50% as the cut point for identifying obstructive coronary disease. "While this is clinically acceptable, it does not address whether the lesion is ischemia producing," he said. "I would like to know if a lesion of 75% stenosis had been used, would the assessment of these plaque characteristics have added anything to the risk-prediction model? The answer to this could help guide treatment strategy."

Reilly pointed out that cardiac CT has the potential to save some patients from having a more invasive angiogram. While FFR is an excellent tool for determining ischemia in intermediate lesions, it remains an invasive test for patients. If physicians could get that same information, either with the plaque characteristics outlined in this study or with CT-based FFR, it would help reduce the number of patients undergoing angiograms who do not need revascularization.

Min serves as a consultant to HeartFlow and Abbott Vascular, serves on the medical advisory board for GE Healthcare and Arineta, and holds ownership in MDDX. Disclosures for the coauthors are listed in the article. Colombo and Panoulas report they have no relevant financial relationships.


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