Prof. Gregg W. Stone: A new direction for intracoronary imaging—how to accurately identify vulnerable plaques?

 

Editor's note: With the technological progress and indications expansion of percutaneous coronary intervention (PCI), the guiding role of coronary artery functionality and intracavitary imaging technology in PCI has become more and more prominent. During the CIT2021 Conference, Professor Gregg W. Stone from Mount Sinai Hospital, new york, USA was invited to give a detailed introduction on "Imaging identification method of vulnerable plaque".

《International Circulation》: The main cause of acute coronary syndrome (ACS) is vulnerable plaque.Therefore, the identification of vulnerable plaque has become a hot spot in contemporary research. So, what are the common technical methods for clinical identification of plaque?

Professor Gregg W. Stone: Sure. So we've learned over the last several decades that it's really vulnerable plaques that place the patients at risk for acute myocardial infarction and sudden cardiac death. And we need to identify these vulnerable plaques before they thrombose in the coronary tree to be able to improve outcomes for patients. So we have a range of both non-invasive and invasive techniques that we can use to identify vulnerable plaque. For the non-invasive techniques, CT angiography is really the most commonly used method. And it's not perfect because of its relatively poor resolution, but when you see findings such as low attenuation plaque and positive remodeling, napkin-ring sign, and spotty calcification, you have a good idea that that's probably a vulnerable plaque when multiple of those features are present.

With invasive imaging, we have grayscale, intravascular ultrasound, radio frequency intravascular ultrasound, or virtual histology, optical coherence tomography, and near-infrared spectroscopy. And all of those look at different components of the vulnerable plaque, which is usually a thin cap fibroatheroma, histologically, to detect either the large lipid content, the well organized necrotic core, the thin fibrous cap, or the large plaque burden.

《International Circulation》: At present, the imaging recognition methods for vulnerable plaques are becoming more diversified and refined. Would you please share us the research direction and progress of your team in this field?

Professor Gregg W. Stone: So, we recently completed our second PROSPECT study. And the PROSPECT studies have been large scale prospective, multi-modality, natural history studies of the entire coronary tree in patients who are presented with acute coronary syndromes to identify, angiographically, mild non-flow limiting lesions that cause future events for patients. 

And in the first PROSPECT study—which was really the first study of its type—we used virtual histology. That is radio frequency intravascular ultrasound. And we identified that a large plaque burden, a thin cap fibroatheroma—by virtual histology specifications—and a small minimal luminal area by ultrasound were the strongest predictors of vulnerable plaque.

In the second PROSPECT study, we used near infrared spectroscopy along with grayscale ultrasound. And we confirmed that large plaque burden was a very important predictor of subsequent events. But also, a very intense lipid deposit, a so-called maximum lipid core burden index over any 4 mm segment of greater than or equal to about 325—meaning about 32.5 percent lipid—was a strong predictor of vulnerable plaque. And it was really when both of those characteristics were present that both the patient and the lesion itself were at very, very high risk.

So now the question is if we identify vulnerable plaques—and we can identify them for certainty—what do we do about them? Should we intensify medical therapy or should we even consider focal treatment like a stent or a scaffold? And we performed a pilot study called the PROSPECT ABSORB study, where we randomized 182 of these vulnerable plaques to the Absorb bioresorbable scaffold versus just medical therapy alone. 

And with follow up to four years, we found that, one, at two years we safely enlarged the lumen. And, you know, these are soft lesions, the scaffold expands very easily.  And so it was a very safe procedure. We created a new 210 micron neo-cap of new tissue on top of the old thin fibrous cap. And even though this small study—182 randomized patients—was not powerful clinical events, there was a strong trend towards a 62 percent reduction in randomized lesion related major adverse cardiovascular events over 4 years, from approximately 10 percent to 4 percent. So what we really need now is large scale randomized trials of stent or scaffold based treatment of vulnerable plaques.

《International Circulation》: What is effect of PCI for the treatment of vulnerable plaques and can it improve the prognosis of patients?

Professor Gregg W. Stone: Right. So that's what we just talked about in PROSPECT ABSORB, that PCI vulnerable plaques can induce neointimal hyperplasia and therefore put a new thick fibrous cap on top of the old thin fibrous cap. That is basically the theory. It will normalize wall stress across the lesion and, hopefully, lead to less atheroma progression and less propensity to rupture. And in the randomized PROSPECT ABSORB pilot, it seemed like even using the thick strut first generation Absorb bioresorbable scaffold, that this was very safe to do safely in large lumen and was associated with improved clinical outcomes in 4 years. But we need an adequately powered randomized trial to see if that will work out and if we can safely treat these lesions and reduce cardiovascular events.

In the meantime, I think that it's very reasonable to intensify medical therapy in patients with vulnerable plaques, especially very high risk patients. Although we don't really know how far to push that. Do you use expensive PCSK9 inhibitors to reduce the LDL to 20 mg/dL if you can only get it down to 70, for example, with statins? So, we don't know. There's a lot more research to be done.

《International Circulation》: What is your opinion about the new development direction of intra-coronary imaging in the future? 

Professor Gregg W. Stone: Yeah. So I think that intra-coronary imaging is very important to optimize the results, one, of the patients that we're treating now that we're implanting stents in. And whether you use intravascular ultrasound or optical coherence tomography or near infrared spectroscopy—we can clearly get better outcomes with stent implantation with intra-coronary imaging. Our stents have gotten so good, we probably cannot make stent outcomes that much better just by improving the stent itself. But by using intra-coronary imaging, we can implant the stent much better, make sure we're not leaving any dissections at the edges or residual untreated disease, and make sure we optimize stent expansion.

In addition—as we've talked about—intra-coronary imaging may be very important to detect and identify vulnerable plaques, the ones that are not flow limiting that we cannot detect with either angiography or physiologic lesion assessment but still place patients at risk for future plaque thrombosis, acute coronary syndromes, myocardial infarctions, and sudden death. And if we can identify those lesions, then we can identify which patients need, again, more intensive medical therapy, and possibly even focal stent treatment.