Predicting Coronary Plaque Rupture: New Review IDs High-Risk Signs

Shelley Wood

May 07, 2014

BUDAPEST, HUNGARY — Researchers who first told CT imagers to beware the "napkin-ring sign" have now published a comprehensive review of the features seen on coronary computed-tomography angiography (CCTA) that can help identify coronary plaques at risk of rupture[1].

In their report, published online April 22, 2014 in Nature Reviews Cardiology, Dr Pál Maurovich-Horvat (Semmelweis University, Budapest, Hungary) and colleagues argue there is a role for CCTA that goes beyond ruling out coronary stenosis.

To heartwire , Maurovich-Horvat summarized the features on CCTA that are key to identifying vulnerable plaques, including the telltale "napkin-ring sign" that he and colleagues have described previously.

"Some of the CCTA plaque features are more important than others to identify high-risk plaques and to predict adverse cardiovascular events. Low CT attenuation, positive remodeling, and the napkin-ring sign indicate [a] five- to 20-fold increase in the risk of suffering ACS," Maurovich-Horvat explained in an email.

To further improve the prognostic value of CCTA to identify high-risk plaques, however, it is necessary to combine different quantitative and qualitative plaque characteristics—for example, plaque volume and napkin-ring sign—with functional information, such as fractional flow reserve (FFR) or endothelial shear stress, he added.

Looking for Trouble

Currently, cardiac imagers are not typically looking for these things on routine CCTA or using them to guide therapeutic decision making, he noted.

"In this review, we sought to raise awareness that CCTA has much more to offer than a simple 'rule-out-coronary-stenosis' test. We believe that coronary plaque assessment provides a unique opportunity to tailor preventive therapies based on patient-specific information." For example, large plaque burden with high-risk features might warrant intensified statin therapy, Maurovich-Horvat explained.

In the paper, the authors suggest that combining functional and morphological features could lead to a "vulnerable plaque score" that could help predict the likelihood of plaque rupture and sudden luminal thrombosis. For a tool to be able to generate an actionable "score," plaque assessment would have to be automated and combined with fluid-dynamic simulations, they note. As a first step, large longitudinal imaging trials are needed that can link plaque scores to clinical events.

Calls for Outcomes Studies

Most, if not all, publications on the topic of vulnerable plaques conclude with a call for outcomes studies, and this latest review is no exception. But Maurovich-Horvat pointed out to heartwire that a number of recently published CCTA studies, summarized in the review, can already be used to influence decision making and "facilitate the routine use of information regarding coronary atherosclerosis provided by CCTA to guide therapies."

What's more, the trials needed to fill in the gaps, particularly with regard to outcomes, are already well on their way.

"The Prospective Multicenter Imaging Study for Evaluation of Chest Pain (PROMISE) trial has completed the enrollment of 10 000 patients," Maurovich-Horvat noted. "The main goal of this pragmatic trial is to define the most cost-effective diagnostic workup of patients with stable chest pain. However, there will also be a huge opportunity in this trial to test the prognostic value of various plaque features to predict acute coronary syndromes."

Another is the Genetic Loci and the Burden of Atherosclerotic Lesions (GLOBAL) study, now enrolling with an estimated completion date of December 2014. In GLOBAL, up to 10 000 patients are undergoing CCTA for plaque assessment as well as a "panomic" analysis that includes genomics, epigenomics, proteomics, metabolomics, and lipidomics.

"The trillions of data points collected from the CCTA plaque assessment and the panomic analyses will be evaluated with bioinformatics techniques to identify novel pathways and factors contributing to coronary plaque development," Maurovich-Horvat said. "If these trials proved to be successful, CCTA might step up as first choice of imaging technique for patients with stable chest pain and, in combination with panomics data, it might even be used to screen asymptomatic, high-risk patients."

Enthusiasm and Progress

It's an oft-heard complaint that enthusiasm for CCTA has outstripped the science supporting it, but Maurovich-Horvat points out that the technology is itself evolving at a breakneck pace. He expects that new detector panel technologies in combination with model-based iterative reconstruction will improve the spatial and contrast resolution of the CT scanners in the coming years. In the shorter term, "I think that the biggest breakthroughs will happen in the arena of image postprocessing," he predicted.

Asked why he and his colleagues felt it was time for a new review addressing progress in the area of plaque characterization, Maurovich-Horvat stressed the fast-paced progress in this field, now reaching a "renaissance" due to advances in CT hardware and software.

"Plaque assessment with CCTA had its golden era 15 years ago, when the first images acquired by four-slice scanners proved that we can image coronary atherosclerosis noninvasively. . . . Now we can literally look inside the plaques and model hemodynamics in the coronary tree. This is what we describe in our review, and we try to convince the reader that CCTA provides much more information regarding plaques than meets the eye."

The authors disclosed having no competing interests.

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