Does New Dual-Modality Imaging Come Closer to Uncovering Vulnerable Plaques?

A new intravascular imaging technology combining optical coherence tomography (OCT) and near-infrared autofluorescence (NIRAF) in a single catheter has joined the search for a way to reliably identify vulnerable atherosclerotic plaques, a first-in-human study shows. 

The NIRAF signal was negative or low in plaques considered to be low-risk based on OCT and elevated in plaques with high-risk OCT features, including thin-cap fibroatheroma, plaque rupture, and fibroatheroma associated with in-stent restenosis, report Giovanni Ughi, PhD (Massachusetts General Hospital, Boston, MA), and colleagues. 

The biological sources of the high NIRAF signals are not clear yet, but a prior cadaver study showed a correlation between NIRAF signals and necrotic core-rich plaques, Farouc Jaffer, MD, PhD (Massachusetts General), one of the senior authors of the study, told TCTMD. 

“This may be a new way to . . . enhance our ability to detect high-risk plaques and potentially improve on predicting outcomes,” Jaffer said. If it can be proven that patients with NIRAF-rich plaques are at greater risk for future events, he added, “that will be very, very useful in terms of enhancing targeted therapy or starting to think about prevention with new therapies.”

The findings were published online March 9, 2016, ahead of print in JACC: Cardiovascular Imaging.

Two-in-One Imaging

Although intravascular OCT provides microstructural images of the arteries, it gives limited information on the molecular composition of plaque, including the presence of a necrotic core. “This ambiguity is problematic, as many studies have shown that a definitive diagnosis of necrosis is needed to distinguish the most advanced, progression-prone lesions,” the authors note.  

That is where NIRAF comes in, providing complementary information on the molecular composition of plaques. In the current study, the researchers used a novel device combining OCT and NIRAF in a single 2.6-Fr catheter to image the coronary arteries of 12 patients with CAD who were undergoing PCI at Mass General. The imaging procedure is identical to current intravascular OCT and yields synchronized data from the two modalities. Any center with familiarity with OCT could use the device, Jaffer said. 

Good-quality data were obtained from 17 total arteries without any complications. The NIRAF signal was high in five of those arteries, low-to-moderate in four, and negative in the remaining eight. 

Strong NIRAF signals were seen only in regions of high-risk plaque according to OCT, including areas with lipid-containing plaques, thin fibrous caps, and rupture with thrombus. These signals also were only found in areas of high macrophage-rich inflammation, but not all regions with high levels of inflammation had elevated NIRAF signals.

“Although our data allow a preliminary assessment of the associations between the NIRAF signal and plaque morphology and microstructure, the small size of this study and our inability to acquire specimens for advanced tissue analysis prevent us from making definitive conclusions about the biological or molecular nature of the NIRAF signal,” the authors write.  

Vulnerable Plaque Concept  

Jaffer said future studies will be larger, include more complex patients (the 12 patients in this study all had relatively low-risk presentations with Canadian Classification System class II/III angina), and explore whether the NIRAF signal improves the understanding of pathophysiology and prognosis.  

The first step toward potentially incorporating OCT-NIRAF into routine clinical decision making, he said, is to use the technology in natural history studies like those occurring in PROSPECT II and the Lipid-Rich Plaque Study, both of which are evaluating a combined imaging modality including IVUS and near-infrared spectroscopy (NIRS).

If OCT-NIRAF is shown to have additional predictive value, “then it will be part of the tool box to help apply intravascular imaging to understand prognosis and risk,” Jaffer said. 

The vulnerable plaque concept—that plaques most likely to rupture and cause events can be identified and potentially treated to prevent poor outcomes—remains controversial, and there have not been studies showing that it is possible identify high-risk plaques that will cause events in a relatively short timeframe, Jaffer noted. 

“However, we really haven’t had the technology to really understand if we could comprehensively assess the artery or plaques in order to do this,” he added, pointing out that IVUS is currently the only modality to provide data for natural history studies. “While IVUS is not sufficient for predicting risk to change clinical practice, it is certainly possible that as we combine a host of technologies—and the field is really moving toward multimodal imaging, ideally in a single catheter—our ability to predict is going to be enhanced.” 

Thus, just because the vulnerable plaque concept has not been proven yet, it does not mean the concept is invalid, Jaffer said. “I definitely, whole-heartedly support aggressive medical therapy. We have to treat this as a systemic illness,” he continued. “However, there are still patients who despite optimal medical therapy will present with progressive coronary disease that is lesion specific. And given that some of these events can be quite severe or lead to bypass, it’s certainly still worthy of investigation to understand if there are ways to prevent progression from happening.” 

A Long Way to the End of the Tunnel

Gary Mintz, MD (Cardiovascular Research Foundation, New York, NY), told TCTMD that even though he believes in the existence of vulnerable plaques, he remains skeptical about the prospects of identifying and treating them, citing several obstacles.  

Referring to OCT-NIRAF, he said “the technologic advancement is impressive, the images are impressive, and the fact that it’s clinically useable is impressive.” 

But whether the new technology brings the field closer to identifying and treating vulnerable plaques remains uncertain, he said. “This is not even close yet,” Mintz said, calling the study a proof of concept. Future investigations will have to determine whether the identification of vulnerable plaques using OCT-NIRAF is correct and has high positive and negative predictive value for subsequent events, he said. Only then could a therapeutic study be designed to assess the utility of treating those lesions.  

“Does it get us closer to the identification of vulnerable plaque? In theory, yes. But we have to be prudent,” Mintz said, adding that it would take several years for this or any other technology to approach clinical utility. 

When asked whether the quest to identify vulnerable plaques and treat them is worthwhile, Mintz said, “I tend to be a little skeptical, because I see all the hurdles involved.” 

In particular, he said, vulnerable plaques can change over time—stabilizing, healing, or rupturing. And even when they rupture, it probably does not result in symptoms in the majority of cases, he said. “There’s a dynamic natural history to the development and resolution of vulnerable plaques.”  

Another issue is that there is currently no device designed specifically as focal therapy to treat vulnerable plaques, and the best approach may be a drug anyway, Mintz said. 

And finally, “going on a fishing expedition looking for vulnerable plaques” and then treating them with focal therapy has to be shown to be superior to using drugs alone, he said, noting that there is a small risk of complications any time an instrument is placed in an artery. 

“So that’s why I’m a bit of a skeptic,” he said. “It’s not that I deny the concept, it’s that I can’t see my way to the end of the tunnel that will make this a routine approach in patients.” 

• Ughi GJ, Wang H, Gerbaud E, et al. First-in-human dual-modality OCT and near-infrared autofluorescence imaging of coronary artery disease. J Am Coll Cardiol Img. 2016;Epub ahead of print. 

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