New Technology

What Should We Do About Lipid Core Plaque? The InfraReDx LipiScan IVUS and the CANARY Trial

Cath Lab Digest talks with CANARY trial investigators.
Cath Lab Digest talks with CANARY trial investigators.
Combining grayscale intravascular ultrasound (IVUS) with near-infrared (NIR) lipid core plaque detection technology, the LipiScan IVUS system (InfraReDx, Burlington, Mass.) utilizes the same set-up and workflow of current IVUS systems. But, in addition to IVUS data, the NIR spectroscopy component provides a highly accurate, immediate sign of the presence or absence of lipid core plaque. IVUS images and NIR spectroscopy Chemograms™ can be obtained simultaneously and are available immediately upon conclusion of imaging pullback. On a Chemogram, a lipid core plaque is visualized as bright yellow. The CANARY trial will investigate the use of distal embolic protection when stenting lesions shown by NIR spectroscopy to have a high lipid core volume. Cath Lab Digest talks with CANARY trial investigators.
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Emmanouil S. Brilakis, MD, PhD, FACC, FAHA, FESC, FSCAI, Director, Cardiac Catheterization Laboratory, VA North Texas Health Care System; Associate Professor of Medicine, The University of Texas Southwestern Medical Center at Dallas, Division of Cardiology, Dallas, Texas
For the first time, we have a clinically approved tool, the LipiScan IVUS (NIR spectroscopy), to look at plaque composition in the cath lab. Clinical use of this technology is rapidly evolving. Our institution has been using the LipiScan system for about two years. It is fairly easy to use, similar to using an intravascular ultrasound (IVUS) catheter. It takes very little time to advance into the vessel and obtain images. There is a very low risk of complications. We are using the LipiScan in several different clinical scenarios. The first is to select the stent length in order to optimize lesion coverage and minimize geographical miss. Especially when lesion borders are not very discrete by angiography, NIR spectroscopy can tell us if lipid core plaque is present and whether it extends further away from the particular vessel segment we may be thinking of stenting. We may use slightly longer stents in these cases in order to completely cover the lipid core plaque, because there have been reports that stenting in the middle of a lipid core plaque may predispose the patient to stent thrombosis.1 A second clinical scenario when LipiScan can be useful is in patients without significant coronary disease by angiography. Such patients may have 30, 40, or 50% blockages, not enough to require stenting. Yet, in some of these patients, NIR spectroscopy has shown a large volume of lipid core plaque, which we think could indicate a high risk of future events. For these patients, we are more likely to intensify medical therapy, meaning aggressive lipid lowering and aggressive antiplatelet therapy. A third potential use of the NIR technology is to predict the risk of myocardial infarction after a percutaneous coronary intervention. Several recent reports suggest that plaques with a rich lipid core may be more likely cause a periprocedural myocardial infarction, likely due to distal embolization.2-5 There was an abstract presented at the American College of Cardiology (ACC) meeting this year showing that patients with a lipid core plaque were more likely to get a myocardial infarction after a percutaneous coronary intervention.6 There are now several cases, either printed or in press, showing that if a large lipid core plaque detected by NIR spectroscopy is stented, distal embolization occurs.7-8 There are several strategies to prevent or treat this complication. One is to give vasodilators that open up the distal microvessels and let the particulates go through; another is to use embolic protection devices, a novel concept that will be investigated in the upcoming CANARY trial. The CANARY trial will look at whether modifying the interventional strategy, based on NIR spectroscopy, to include a distal protection device will improve clinical outcomes. CANARY will be a 50-patient pilot study. Half will be randomized to receive a FilterWire embolic protection device (Boston Scientific Corp.) before stenting and the other half will not have a FilterWire. In native coronaries, embolic protection studies such as EMERALD and DEDICATION, among others, were done in patients with acute ST-elevation myocardial infarction (STEMI), in the hopes that it might prevent the extent of the infarction and improve outcomes. These trials, which used a FilterWire, were negative, showing no benefit whatsoever. However, embolic protection was used indiscriminately in these trials, in every STEMI patient, regardless of angiographic findings and regardless of plaque composition. CANARY will include stable patients who are not acutely infarcting and the FilterWire will only be used in lesions with large lipid core plaque by NIR spectroscopy. This is a more tailored approach to lesions at high risk of causing embolization and MI. Currently our institution does have a protocol in which we use an embolic protection device in large, lipid plaques. We are finding that debris is captured from most of those plaques after putting in a stent (Figure 4). Finally, NIR spectroscopy can be a very powerful research tool. Most current studies examining the response of coronary atherosclerotic plaque to various therapies, mainly lipid-lowering agents, are utilizing intravascular ultrasonography and look at changes in plaque volume and thickness. This is a fairly non-specific approach, since it is the lipid content of the plaque that is the primary target of the therapy. Using NIR spectroscopy allows direct measurement of lipid core plaque changes in the coronary artery wall. We have recently shown excellent reproducibility of the NIR spectroscopy findings that further supports its use in longitudinal plaque modification studies.9-10 As one example of how near-infrared spectroscopy can empower clinicians and investigators treating coronary artery disease, we recently found that saphenous vein graft lesions located in the graft body usually have lipid core plaques, whereas ostial and distal anastomotic lesions usually do not.11 Moreover, intermediate saphenous vein graft lesions often have significant amount of lipid. These lesions have high risk to progress and cause symptoms, or even graft occlusion, which is why, based on these findings, we designed and recently started a National Institutes of Health (NIH)-sponsored trial, the “Effect of Extended-Release Niacin on Saphenous Vein Graft Atherosclerosis (ALPINE-SVG)” study (http://clinicaltrials.gov/ct2/show/NCT01221402). ALPINE-SVG is utilizing NIR spectroscopy to evaluate the effect of extended release niacin in intermediate saphenous vein graft lesions. We believe that use of niacin may halt progression or even cause regression of lipid core plaques in treated saphenous vein grafts, and that use of the NIR spectroscopy catheter will help us clearly demonstrate these effects. NIR spectroscopy is very easy to implement into decision-making during a cardiac catheterization case, because it immediately provides a footprint of the coronary artery, highlighting the presence of any lipid plaques without the need to manually process the image. Clearly, more studies are needed to further clarify and refine the utilization of coronary NIR spectroscopy, but this is a robust clinical tool that has the potential to transform our cardiac catheterization practice. Dr. Brilakis can be contacted at esbrilakis@yahoo.com Disclosure: Dr. Brilakis reports speaker honoraria from St. Jude Medical, consulting fees from Medicure, research support from Abbott Vascular and his spouse is an employee of Medtronic.

References

1. Waxman S, Freilich MI, Suter MJ, et al. A case of lipid core plaque progression and rupture at the edge of a coronary stent: elucidating the mechanisms of drug-eluting stent failure. Circ Cardiovasc Interv 2010;3:193-196. 2. Uetani T, Amano T, Ando H, et al. The correlation between lipid volume in the target lesion, measured by integrated backscatter intravascular ultrasound, and post-procedural myocardial infarction in patients with elective stent implantation. Eur Heart J 2008;29:1714-1720. 3. Kawamoto T, Okura H, Koyama Y, et al. The relationship between coronary plaque characteristics and small embolic particles during coronary stent implantation. J Am Coll Cardiol 2007;50:1635-1640. 4. Kawaguchi R, Oshima S, Jingu M, et al. Usefulness of virtual histology intravascular ultrasound to predict distal embolization for ST-segment elevation myocardial infarction. J Am Coll Cardiol 2007;50:1641-1646. 5. Uetani T, Amano T, Kunimura A, et al. The association between plaque characterization by CT angiography and post-procedural myocardial infarction in patients with elective stent implantation. J Am Coll Cardiol Img 2010;3:19-28. 6. Maini B, Brilakis E, Kim M, et al. Association of large lipid core plaque detected by near infrared spectroscopy with post percutaneous coronary intervention myocardial infarction. J Am Coll Cardiol 2010;55:A179.E1672. 7. Goldstein JA, Grines C, Fischell T, et al. Coronary embolization following balloon dilation of lipid-core plaques. JACC: Cardiovascular Imaging 2009;2:1420-1424. 8. Schultz CJ, Serruys PW, van der Ent M, et al. First-in-man clinical use of combined near-infrared spectroscopy and intravascular ultrasound: a potential key to predict distal embolization and no-reflow? J Am Coll Cardiol 2010;56:314. 9. Garcia BA, Wood F, Cipher D, Banerjee S, Brilakis ES. Reproducibility of near-infrared spectroscopy for the detection of lipid core coronary plaques and observed changes after coronary stent implantation. Catheter Cardiovasc Interv 2010;76(3):359-365. 10. Abdel-Karim AR, Rangan BV, Banerjee S, Brilakis ES. Inter-catheter reproducibility of near-infrared spectroscopy for the in-vivo detection of coronary lipid core coronary plaques. Catheter Cardiovasc Interv 2010:in press. 11. Wood FO, Badhey N, Garcia B, et al. Analysis of saphenous vein graft lesion composition using near-infrared spectroscopy and intravascular ultrasonography with virtual histology. Atherosclerosis 2010;212(2):528-533.
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James A. Goldstein, MD, FACC, Director of Cardiac Research and Education William Beaumont Hospital, Royal Oak, Michigan
The LipiScan IVUS catheter is the first validated, FDA-approved device for the detection of lipid core plaque. We believe the LipiScan IVUS will prove to be a very powerful technique and will become the best-in-class IVUS instrument available clinically. It is designed just like an IVUS catheter, both in structure and use. It’s simple, easy to use, and the data comes up right away. The results are easy to interpret. The most exciting aspect of the combined LipiScan IVUS catheter is that it gives you the well-established benefits of IVUS data (the presence of plaque, volume and architectural characteristics with respect to positive remodeling), along with compositional data regarding the presence or absence of a lipid core plaque. Lipid composition by itself is something we are all concerned about, since we know the presence of a lipid core plaque versus a fibrous cap is associated with a variety of potential procedural complications, as well as long-term issues. A lipid core plaque is associated with more rapid plaque progression in general. It is associated with abrupt plaque instability, potentially leading to coronary syndromes and sudden coronary death. From an intraprocedural standpoint, lipid core plaques are also felt to be the greatest risk for distal embolization during angioplasty and stenting, potentially increasing morbidity and mortality associated with percutaneous interventions. Approximately 10-15% of stenting procedures are complicated by periprocedural myocardial infarction (MI), felt to be predominantly attributable to distal embolization from plaque material. Cholesterol content is considered one major culprit; thrombus the other. It is presumed that mechanical disruption of lipid core plaque acts as a ‘cheese grater,’ or some people describe it as popping a pimple. Essentially, the pressure and mechanical effects of a stent are being exerted over a plaque that may be filled with a large volume of friable cholesterol material. This material can then express itself into the lumen and go downstream, clogging up the microvasculature in that distal circulation and causing a periprocedural MI. The goal of the CANARY trial is to determine whether a distal protection device will prevent some of the complications we are all concerned about while stenting high-volume lipid core plaque lesions. Based on the results of the compositional data from NIR spectroscopy, 50 patients undergoing percutaneous revascularization with lesions containing a large amount of lipid core plaque will be randomized to either routine care, which would be stenting alone without a distal protection device, or stenting with a distal protection device. The ultimate ‘holy grail’ would be to be able to identify vulnerable plaques that are non-flow-limiting, but are lipid-laden, and have architectural characteristics that, together with the composition, suggest they may be vulnerable lesions that could lead to future events. We don’t yet have data on these applications, but we feel the LipiScan will be helpful in making decisions with respect to the length of the vessel to stent, choosing the precise length of stent to implant, and potentially identifying lesions at risk for distal embolization during percutaneous intervention. The CANARY trial is an important step forward as we look to clarify pathways for clinical use of the LipiScan IVUS catheter. Dr. Goldstein can be contacted at jgoldstein@beaumont.edu Disclosure: Dr. Goldstein reports he is a consultant for and has some equity in InfraReDx.
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Eric R. Powers, MD, FACC, Professor of Medicine Director, Acute Coronary Syndrome Center, Medical University of South Carolina, Charleston, South Carolina
To date, in interventional cardiology, the information we use to treat patients has mainly arisen through angiography, intravascular ultrasound, and physiologic measurements. Lacking has been information about what is in the arterial wall, and how it might influence the use of stents and the results of the stenting procedure itself. The LipiScan IVUS catheter provides us with a brand-new set of information about what is actually in the plaque. We think that it must be critical in determining the outcome of stenting procedures, critical meaning the acute effects of stenting with immediate complications and results, but also, long-term effects. NIR spectroscopy is the first technology to allow us to take information about plaque composition and apply it to the stenting procedure. It is still very much unknown, but it has to be helpful. The idea behind the CANARY trial is that knowing what’s inside the plaque will predict short-term complications. Whether that will turn out to be true or not, obviously, we have to wait and see, but the overlying rationale is that plaque composition is an important determinant for short- and long-term results. Now we have the ability to see what is inside the plaque. The question is, how is this information important, and how do we adjust what we do? We will see whether CANARY is a step forward. It is a good hypothesis and we do think knowing there is lipid inside the plaque will affect short-term results, but again, we first have to find out by doing the trial. There was one particularly dramatic patient that has been part of the rationale for our interest in this technology. This patient had a great deal of lipid extending beyond the area of stenosis. The strategy was to just put a stent across the stenotic segment, which means that the edges of the stent actually cut into the lipid pool. It was not a tightly blocked part of the artery, but NIR spectroscopy definitely showed a lipid pool present. When we finished stenting, we saw a definite disruption of the plaque. I imagine the metal edge of the stent cut into this lipid core. Angiographically, because it was not a good result, we put another stent on that spot to cover it up. I do think it is probable that if we had not covered all of the lipid shown by NIR spectroscopy, that the patient would have had an event, either in the short or long term. One of the hypotheses of the CANARY trial is that if we stent into these lipid core plaques, some of that lipid core will in fact be embolized downstream. The strategy of how to deal with that lipid might be to place a protection device downstream to catch any debris that comes out of the plaque. It might be to avoid stenting any lipid cores. It might be to cover the whole lipid core and use some other strategy. So again, exactly how the it will work out when the whole trial is done is unpredictable, but it does seem that a lipid core plaque will have an effect and needs to be accounted for in our strategy. Exactly what that strategy will be — whether it is distal protection, more stent, less stent, whether the stent has to be different in order to cover the lipid core — is unknown, but the reason is because we have never had the capability to register the presence of lipid core plaque. Interventional cardiology does extremely well now. The short-term and long-term results are very good, but we still have room for improvement. Using angiography alone has brought us to where we are, but to make the next step forward, we need to know more about the plaque and the artery. I think the combination of IVUS and NIR spectroscopy will be the way to do that. The LipiScan catheter can show us the structure of the artery through IVUS and also the constitutents of the artery, meaning lipid, through NIR spectroscopy. It is going to be a valuable technology to move us into the next phase of interventional cardiology. From a purely technical point of view, the LipiScan IVUS is very straightforward. It is quick, simple, and uses techniques we are all familiar with from using IVUS. What’s exciting about the LipiScan IVUS system is that it is the first time we can have information about what’s inside the plaque. In order to continue to perfect interventional cardiology, it seems certain that plaque composition is information we need, although how best to apply it remains undetermined. The CANARY trial may tell us, but even if the trial is not particularly revealing, that will not be a blow against the concept of looking at lipid. It will just mean that we haven’t quite figured out the right way to test it. Preventing embolization, preventing short-term complications, may not be the application for identifying lipid in the plaque. It is obviously a good guess, and it’s a good step to take, but like all research, it may be going down the wrong path. If so, we will have to find a different path. I am quite sure that knowing there is lipid in the plaque will be of value. We just have to figure out what that value is. Dr. Powers can be contacted at powerse@musc.edu. Disclosure: Dr. Powers reports no conflicts of interest regarding the content herein.
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Kendrick A. Shunk MD, PhD, FSCAI, Department of Medicine, Division of Cardiology, University of California, San Francisco and San Francisco VA Medical Center, San Francisco, California
We have been using the LipiScan for a few months, in perhaps 35-40 cases. We are very comfortable with the catheter; it is something that can be done relatively quickly and easily. The LipiScan catheter is very akin to intravascular ultrasound (IVUS) in terms of what is required of the staff. We have frequently been using it prior to placing a stent, not because there is any good demonstrated data to support a strategy regarding what we find, but mainly because we are trying to learn about this technology. We have seen some interesting cases where very large lipid pools are identified. In some cases, it has led to confirmation of our treatment strategy. There have also been some interesting speculations about how to manage large lipid cores in areas that might not be severely stenosed, but are adjacent to a culprit stenosis, such as using potentially longer stents to cover the entire affected area. We have certainly seen the phenomenon of a large, otherwise unanticipated, lipid pool identified with the LipiScan catheter that is not necessarily visible on angiogram or even on IVUS. In cases where we have repeated the LipiScan at the end of the aggressive stenting and post dilatation, and seen that the lipid core has disappeared, it correlates very strongly with a periprocedural MI. This observation (not only at our center) has led to the CANARY trial hypothesis that embolic protection used in the presence of a large lipid pool may prevent periprocedural MIs. We had one patient with a critical culprit lesion in the circumflex, and a moderate lesion in the left anterior descending artery (LAD). Fractional flow reserve (FFR) of the LAD was borderline positive. We used NIR spectroscopy and saw a very large lipid pool, nearly circumferential, associated with the lesion in the LAD. This was a case where we thought long and hard about stenting. This patient was entirely statin-naïve when he came in with his acute circumflex event. Even though the FFR was positive, with the information provided by NIR spectroscopy, we decided to delay intervention. We brought the patient back for his procedure two months later, after having high-dose statin therapy. Is this strategy a worthwhile one to advocate? We don’t know, but again, NIR spectroscopy is causing us to consider potential strategies to reduce the risk of periprocedural MI, although as yet, none of these strategies has been tested in a clinical trial. There are some attractive hypotheses being generated that are testable and could eventually lead to changes in PCI practice, such as embolic protection as it is being studied in the CANARY trial. Combining functional study data such as FFR with the risk of embolization judged by LipiScan could potentially help determine whether to stent a borderline lesion or whether to wait and do it at a later time. Dr. Shunk can be contacted at kendrick.shunk@va.gov. Disclosure: Dr. Shunk reports that he receives research support from InfraRedx, and the opinions expressed are his own and not those of the Federal Government.
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Gregg W. Stone, MD, Director of Cardiovascular Research and Education, Center for Interventional Vascular Therapy, New York-Presbyterian Hospital/Columbia University Medical Center; Professor of Medicine, Columbia University College of Physicians and Surgeons; Vice Chairman of the Cardiovascular Research Foundation, New York, New York
Distal embolization is a relatively common phenomenon that can occur in 10-20% of patients, although it is usually mild. Severe distal embolization can cause no reflow, which can cause a large myocardial infarction (MI). Lesions likely to embolize include very soft, lipid-rich plaques, with a large, necrotic core. We have learned about these plaques with intravascular ultrasound (IVUS), optical coherence tomography, virtual histology and now, with the combination IVUS/NIR infrared spectroscopy LipiScan catheter. The LipiScan may be one of the best modalities to identify embolization-prone lesions. Preliminary data does suggest that by using the LipiScan, we can predict which patients will suffer periprocedural MIs. If a lesion is likely to embolize and cause a periprocedural MI, what can be done? One idea is to do the procedure with an embolic protection device, capturing the embolized material and removing it before it clogs up the distal vasculature and causes a heart attack. In the CANARY pilot trial, a relatively small trial of 50 patients, we will be identifying these types of lesions at relatively high risk of embolization. Patients will be randomized in a 1:1 fashion to distal protection with the FilterWire (Boston Scientific Corp.) versus standard angioplasty. Trial investigators will be able to meausure lipid core plaque size and volume, called the ‘lipid core burden index.’ A series of 65 patients has shown that a lipid core burden index of greater than 600 leads to a markedly increased risk of periprocedural MI. In CANARY, the LipiScan system will automatically calculate the lipid core burden index. If the patient meets the criteria, they will be randomized. CANARY is the first step as we seek to learn whether distal embolic protection should be standard of care in native coronary arteries. The expectation is that with the LipiScan IVUS, we can predict which vessels are at high risk for distal embolization. If CANARY is positive or strongly trending toward positive, it will most likely lead to a larger study of 200-300 patients, which would lead to a definitive label and widespread use. NIR technology was originally developed to try and identify so-called vulnerable plaques, the type of plaques that will rupture, have thrombus form on them, and cause future heart attacks or sudden cardiac death. The LipiScan is very good at identifying lipid-rich plaque. In fact, it is the only device approved by the FDA to identify this specific type of plaque in the coronary arteries, a breakthrough achievement. Now, the question is, what do we do when we see one of these plaques? What does it actually mean? We are very confident that it means the presence of a large amount of lipid, but does that mean we should treat with more intensive statin therapy? Does that mean we should prophylactically stent it? Does that mean we shouldn’t stent it, but in fact, go out of our way not to treat it, because it is fragile and friable? We are just starting to try and understand the implications of these findings. Dr. Stone can be contacted at gstone@crf.org Disclosure: Dr. Stone reports research support from InfraReDx.