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- †South Australian Health and Medical Research Institute, University of Adelaide, Adelaide, Australia
- ‡Department of Cardiovascular Medicine, Cleveland Clinic, Cleveland, Ohio
- ↵∗Reprint requests and correspondence:
Dr. Stephen J. Nicholls, South Australian Health and Medical Research Institute, P.O. Box 11060, Adelaide, South Australia 5001, Australia.
At school we all learned of the tale from Greek mythology of Icarus, who while trying to escape from Crete ignored the warnings of his father and flew too close to the sun. His wings of feather and wax melted and he fell to the sea, where he drowned. This tale is often told as a warning of the perils of overambition. It is ironic how our desire to advance new approaches in cardiovascular medicine so commonly reaches a similarly futile outcome.
One such area that continues to stimulate our desire to push the boundaries is the ability to visualize atherosclerotic plaque in vivo. This has been stimulated by the fundamental role played by atherosclerosis in the pathogenesis of ischemic cardiovascular events. Although we have developed tools enabling the visualization of coronary atheroma in vivo, we have remained somewhat dissatisfied, convinced that there must be more to the disease than depicted by more traditional methods of coronary imaging.
We have become increasingly focused on the role of the “vulnerable plaque” underlying acute ischemic events, on the basis of elegant reports from pathology studies. These reports tell us that a large plaque containing lipid, inflammatory cells and necrotic debris, in association with a thin fibrous cap and positive arterial wall remodeling, represents the typical plaque encountered at the culprit site in patients with myocardial infarction (1,2). This has stimulated enormous interest in the development of imaging tools to identify such lesions (3).
These reports have also described that not all acute events are accompanied by areas of plaque rupture. Rather, in some instances pathologists describe the presence of fibrous cap erosion overlying a plaque appearing less vulnerable in terms of its histological phenotype (4). Although plaque erosion seems to be more common in female subjects, younger patients, and smokers, there remains little evolution in our ability to image these lesions in vivo or to develop additional biomarkers for more effective prediction of these events.
In parallel with increasing interest in the various plaque phenotypes implicated in acute ischemic events, there have been considerable technological advances in arterial wall imaging. These techniques enable direct visualization of the entire burden of atherosclerotic plaque within the artery wall, with the potential to provide incremental plaque characterization beyond measures of plaque burden. These modalities have primarily focused on the demonstration of features implicated in plaque vulnerability such as the necrotic and lipid components of plaque. It remains to be determined what role these techniques will play in clinical practice or development of novel anti-atherosclerotic therapies.
A recent advance in vascular imaging has witnessed the use of optical coherence tomography (OCT), a light-based modality that images the superficial aspects of the vessel wall with the highest resolution noted to date. As a result, there has been a steep proliferation in the use of OCT in the characterization of coronary artery disease in the catheterization laboratory. In addition to its role in aiding percutaneous coronary intervention, there is hope that it will also provide important biological insights into the natural history of atherosclerotic plaque in the artery wall.
In this issue of the Journal, Jia et al. (5) report the findings of a systematic review of 126 patients who underwent intracoronary OCT imaging before percutaneous coronary intervention of a culprit lesion in the setting of an acute coronary syndrome. Of particular interest, plaque erosions were observed at the culprit site in nearly one-third of patients. These individuals were younger and more likely to present with non–ST-segment elevation myocardial infarctions and whose culprit lesions contained smaller lipid pools, thicker fibrous caps, and less-severe diameter stenosis on angiography.
These observations reflect an important addition to our ability to characterize atherosclerotic plaque in vivo. For the first time, we seem to be able to reliably visualize plaque erosion before the vessel ends up in the hands of the pathologist. Or have we? The findings do need to be considered with the caveat that they reflect observations consistent with a consensus statement on how to interpret OCT imaging, much of which is drawn from relatively sparse histological validation. As with all new modalities that propose to demonstrate plaque features beyond burden, we must continue to ask ourselves to what degree are we convinced that what we think we are seeing is really what is present in the vessel? As the use of OCT will continue to increase, we must ensure that there continues to be ongoing validation of its observations (6).
Accepting that the features demonstrated on OCT do accurately represent plaque characteristics that they are reported to, what do we do with the findings? What are the implications for the ability to image plaque erosions in the catheterization laboratory? Does this change how we manage patients in the acute setting or as a means of secondary prevention? If it doesn't, how does that influence our interest in such imaging? Most importantly, our major objective is to prevent these events from occurring in the first place. Are we any closer to being able to predict plaque erosion, to triage patients to more aggressive preventive therapies? Furthermore, can we detect serial changes in response to novel anti-atherosclerotic agents, and are such changes clinically meaningful? At least for now, the answer is sadly “no.” Whether such advances actually change what we do and ultimately what happens to patients remains to be determined. However, such steps are vital if we are to seriously integrate such imaging approaches into our research and clinical armamentarium.
Arterial wall imaging with light-based techniques provides a unique opportunity to advance our ability to characterize atherosclerosis and its relationship to vascular risk. Our challenge is to develop broad strategies that effectively advance the utility of these findings rather than being too absorbed with the “light,” while adding to an ever-growing pile of cardiovascular advances that fail to advance the field.
↵∗ Editorials published in the Journal of the American College of Cardiology reflect the views of the authors and do not necessarily represent the views of JACC or the American College of Cardiology.
Dr Nicholls has received research support from St. Jude, Volcano, AstraZeneca, Anthera, Eli Lilly, Novartis, Resverlogix, Amgen, and LipoScience; and is a consultant for AstraZeneca, Takeda, Merck, Roche, Omthera, Resverlogix, Amgen, Eli Lilly, CSL Behring, and Boehringer Ingelheim. Dr. Puri has reported that he has no relationships relevant to the contents of this paper to disclose. Steve Nissen, MD, served as Guest Editor for this paper.
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