Vulnerable Plaques by CT

Abstract & Commentary

By Jonathan Abrams, MD, Professor of Medicine, Division of Cardiology, University of New Mexico, Albuquerque. Dr. Abrams serves on the speaker's bureau for Merck, Pfizer, and Parke-Davis.

Source: Motoyama S, et al. Multislice computed tomographic characteristics of coronary lesions in acute coronary syndromes. J Am Coll Cardiol 2007;50:319-326.

The increasing use of 64-slice computed tomography or MSCT is beginning to significantly impact the medical literature. This study, from Japan; Irvine, California; and Gaithersburg, Maryland, is an early effort of utilizing MSCT to evaluate "vulnerable" coronary arteries that could cause an acute coronary syndrome (ACS).

Coronary Plaque Evaluation by MSCT: The authors suggest that a ruptured coronary plaque is likely to be very similar in composition to a vulnerable, but non-ruptured plaque that has yet to become eroded or rupture, and that such imaging signatures can be assessed using high-quality imaging technology to identify lesions that are at high risk for causing a subsequent coronary event. While interest in plaque composition and imaging is very high at the present time, it remains unclear if current imaging capability allows for detection of a variety of important plaque characteristics. There are numerous catheter-based technologies and techniques being applied to help answer important questions relating to plaque vulnerability. These include optical coherence tomography, intravascular magnetic resonance, thermography, and most familiar, intravascular ultrasound or IVUS. The authors state, "Recent improvements in CT technology and the advent of multislice computed CT have spurred interest in non-invasive detection of morphologic characteristics of vulnerable plaques." This study began in 2004 with the utilization of 0.5mm X 16-slice CT; 56 of the 71 ACS patients enrolled had no further imaging; 15 individuals were added to the original cohort, resulting in a total of 71 patients; the latter group all had 64-slice imaging. The cohort was derived from screening of 441 patients. Individuals were classified as having stable or unstable angina, as well as acute coronary syndrome (ACS), which was defined by elevation of troponin or unstable angina pectoris. Stable angina patients with single vessel disease who had undergone a coronary angiogram were studied. STEMI patients were included if they were evaluated greater than 24 hours from the onset of chest pain and were symptom free. Coronary angiograms were used to identify the culprit lesion as well as to define other angiographic parameters. Of the 71 patients, 10 had STEMI, 9 had NSTEMI, 19 had unstable angina, and 33 had stable angina. Invasive procedures were performed on a majority of the patients. The MSCT protocol utilized is highly technical; readers interested in tomography details should refer to the article. Characteristics identified and analyzed include coronary artery remodeling (positive remodeling relates to increase in coronary artery diameter at a plaque site that is at least 10% larger than the adjacent reference segment). Plaques were analyzed by the presence or absence of calcification as well as IVUS analysis. Spotty and large calcifications were analyzed. Vessels were assessed as to presence of soft or fibrous plaque. Only patients imaged with the 64-slice unit were included for an IVUS analysis. Individuals who interpreted this study were blinded to clinical status. Sensitivity, specificity, positive/negative predictive values, and diagnostic accuracy were assessed for each vessel.

Results: All 71 patients had comparable baseline characteristics (age, gender, or presence of diabetes/hypertension/hyperlipidemia, smoking and obesity). Positive expansive remodeling was noted in the large majority of culprit lesions (87%). Spotty calcification was noted in 63%. Culprit lesions had a large lipid core, with calcification seen in 22%. Stable angina patients demonstrated a low likelihood of positive remodeling, and plaques characterized as soft. While spotty calcification was observed in 21%, larger calcium plaques were found in 55%. Remodeling was significantly greater in ACS lesions vs stable angina. Stable angina patients were much more likely to have large calcifications; most were unlikely to demonstrate positive remodeling. Spotty calcification was found in 2/3 of ACS lesions, whereas stable angina patients had spotty calcifications only 1/5 of the time. Positive remodeling demonstrated the best sensitivity, specificity, and predictive values; correlation with soft plaque and spotty calcification was common. Plaques that demonstrated positive remodeling, spotty calcification, and soft plaque by IVUS had a positive predictive value of being associated with an acute event of 95%.

The authors conclude that culprit legions in ACS show positive remodeling, plaque lesions with a significant lipid core; all characteristics not associated with stable angina. Positive remodeling was the most important predictor of a culprit lesion, as noted by many others. Such lesions were associated with lipid cores consisting of soft plaque or necrotic core. Nevertheless, the authors state "extreme caution should be exercised in labeling low attenuation… in a plaque as soft plaque or necrotic core." The authors suggest that IVUS imaging in evaluation of plaque as soft vs non-soft needs to be improved, and that 64-slice imaging is a better technique for identification of culprit legions. Presence of positive remodeling, soft plaque or obvious lipid, and spotty calcification are highly predictive of a causal ACS event, whereas absence of all 3 features had a very high negative predictive value. The authors suggest that characteristics consistent with a not yet disrupted vulnerable plaque are likely to be the site of a subsequent acute event. They point out that the plaque and necrotic core sizes are the most important determinants of plaque vulnerability. The larger the plaque extent and necrotic core size, the higher the likelihood of the plaque to rupture. Ruptured plaques that have disrupted and healed are highly likely to demonstrate narrowing of the cross-sectional area of > 50-75%.

Many plaques with a necrotic core occupy an extensive area. Plaque volume may be enormous "without compromising the lumen size to greater than 40%." This phenomena is related to positive outward remodeling, and confirms the widely observed phenomena that acute myocardial infarction often arises from a non-obstructive plaque. Pathological features of hemorrhage, large necrotic core, macrophage inflammation and calcification are characteristics of vascular remodeling. Such plaques are called TCFA or thin cap fibro-atheroma. Stable plaques generally show no expansive remodeling and even negative shrinkage. The literature indicates that most TCFA occur in the proximal or mid-portion of a coronary artery and furthermore that "the number of vulnerable plaques present in any patient is small." These features make "an effort to detect vulnerable plaque justifiable." The authors suggest that individuals with a high-event likelihood i.e., > 20% over 10 years, "may constitute the most appropriate population to be subjected to MSCT for potential identification of vulnerable plaques." Thus, candidates for imaging with renal impairment, diabetes, or peripheral vascular disease should be considered for coronary imaging with MSCT. Identification of vulnerable plaque in such individuals "may place the subjects at a very high risk (probably in excess of 15%) of developing acute coronary events per year. This will be the key role for coronary imaging." The authors acknowledge that it is difficult to differentiate between thrombus or lipid-rich plaques from fibrous plaques just on the basis of plaque attenuation, as many lesions have complex pathologies. They acknowledge that the long-term implications of a vulnerable plaque identified by MSCT is unclear, and much more data will be needed. The authors appropriately suggest that more imaging will be seen as hospitals and cardiology groups acquire 64-slice imaging equipment.

Commentary

It is clear that hospitals around the country are eagerly acquiring 64-slice CT units. It is not yet clear how accurate and reliable such imaging is for so-called vulnerable plaque. Limitations of this study included the small percentage of patients who underwent imaging analysis with a 64-slice unit, and the modest size of the series. This study, as well as others in the literature, is concordant with the view that stable vs unstable plaque characteristics within the coronary circulation may be predictive of vulnerable plaque and subsequent plaque rupture, and that features of fibrous or stable plaque as assessed by multi-slice CT may imply "protection" from acute plaque ruptures, although such vessels are likely to be implicated in chronic stable angina. We do not have specific therapies that differ for vulnerable plaque vs stable plaque; there is general acceptance that all patients with coronary disease, even if relatively low risk, should be treated vigorously with lipid lowering, aspirin, and perhaps beta blockers and ACE inhibitors. It is attractive to use the new powerful imaging techniques in clinical practice. If some of the technologies currently being tested in many centers including MSCT turn out to be valuable, this will change the focus of our efforts from treating the clinical event to even more aggressive prevention.