Washington, DC - Two studies appearing in the September 4, 2007 issue of the Journal of the American College of Cardiology offer new insights into one of the holy grails of cardiovascular medicine: identifying plaques that are vulnerable to rupture [1,2].

In one study, Japanese researchers led by Dr Takashi Kubo (Wakayama Medical University, Japan) compared the ability of intravascular ultrasound (IVUS)—the gold standard in invasive imaging for the diagnosis of CAD—with a relative newcomer in arterial imaging, intravascular optical coherence tomography (OCT). Widely used by ophthalmologists to image the eye because of its micrometer resolution and ability to penetrate several millimeters of tissue, OCT is also used for art analysis and conservation because it can "see" through multiple layers of paint. More recently, researchers have developed intravascular OCT to visualize the composition of arterial stenoses and plaques with the aim of identifying thin-capped fibroatheromas (TCFAs) more likely to rupture. According to the authors, OCT produces images with a resolution that is 10 times higher than that of IVUS.

For their study, Kubo et al used IVUS, OCT, and coronary angioscopy to assess culprit lesions in 30 patients with AMI. They report that OCT was better than the two other imaging modalities at identifying cases of plaque rupture and of fibrous cap erosion and was the only modality that could estimate fibrous cap thickness, which was a mean of 49 µm.

"The present study using OCT demonstrates that the thin fibrous cap and large lipid core must be important characteristics to represent vulnerable plaque in AMI," the authors conclude. "Optical coherence tomography is a powerful modality for evaluation of vulnerable coronary plaque in vivo, and it may provide a great opportunity to understand the mechanism of AMI onset."

In the second study, Dr Pavan K Cheruvu (Harvard University, Boston, MA) and colleagues set out to clarify the frequency and distribution of TCFAs. Cheruvu et al analyzed more than 3600, 3-mm longitudinal sections of coronary arteries, taken from 50 hearts at autopsy: in total, almost 11 m worth of tissue. They found 23 TCFAs and 19 ruptured plaques, most of which were found in the proximal third of the major coronary arteries, confirming earlier studies suggesting that ruptured plaques that produce the lesions that cause ACS and sudden death originate in the proximal section of the same coronary artery. Ruptured plaques and TCFAs were also relatively infrequent, found in less than 3% of the total artery lengths analyzed, and for the most part clustered within two nonoverlapping 20-mm segments or less.

"The findings of the present study are of considerable importance for the ongoing debate regarding the focal vs systemic features of the mechanism through which atherosclerosis produces clinical events," the authors write. "Our finding of a focal distribution of suspected precursor lesions supports efforts to develop novel tools to identify these structures that may occur at sites with and without flow-limiting stenoses. If such locations could be identified and treated by focal, regional, or systemic therapy, it may be possible to reduce the high incidence of secondary coronary events that currently occur in ACS patients despite application of the best therapeutic options available."

To heartwire, Cheruvu commented that the knowledge that TCFAs appear to occur primarily in a limited, focal distribution in the coronary tree has a number of important clinical implications. "First, it promotes future efforts of research into how systemic inflammatory processes of atherogenesis give rise to focal areas of thrombosis. Second, it supports efforts to develop a clinical tool that can reliably detect TCFAs. Such a tool may improve the risk-stratification of patients who appear to have no flow limitations on angiography and enable the prediction of what are now 'sudden' coronary events. Third, and finally, once TCFAs can be located and identified, current strategies of treatment may be modified to alter the pathobiology of these lesions and lessen their risk of thrombosis. These approaches might involve validated combinations of focal and/or systemic therapies, with a goal of reducing the currently high incidence of secondary coronary events in ACS patients."

In an accompanying editorial, Drs Patrick Serruys (Thoraxcenter, Rotterdam, the Netherlands) and colleagues hail the two studies for providing new and "essential" information about "plaques that cause acute coronary thrombotic occlusion and their postulated precursors, TCFAs" [3].

Serruys et al point out that there is little consensus among clinicians and pathologists as to just how thin the cap of a plaque must be to predict "imminent" plaque rupture: both Kubo and Cheruvu used a cutoff of 65 µm or less to define a TCFA. As such, the mean thickness of 49 µm (with a standard deviation of 21 µm) reported by Kubo et al is important new information, the editorialists note.

But they also urge caution in extrapolating the findings from both studies. For Kubo et al's studies, Serruys et al point out that the authors do not report intra- and interobserver variability in classifying plaques as calcified or lipid-rich/necrotic, something that is notoriously difficult to do with OCT. Cheruvu et al's paper, they note, is not in keeping with other studies that suggest the number of TCFAs is higher in people with ACS. Necrotic core sizes were also smaller in Cheruvu et al's study than previously reported.

While both papers add important new information to the field, Serruys and colleagues emphasize that the ultimate goal of identifying TCFAs in danger of imminent rupture must be coupled with the pursuit of clinical strategies to prevent those events. These would have to involve reinforcing the vessel wall with enough strength to prevent rupture but enough flexibility to permit lumen geometry to change. Also critical are drugs or other methods to reduce the necrotic core, as well as the means to promote endothelial regeneration and a return to functionality, they conclude.