We demonstrated that high-risk coronary plaque as detected on CTA in patients presenting to the ED with acute chest pain was associated with ACS independently and incrementally to the presence of significant CAD and clinical risk assessment. Our results suggested that CTA-based assessment of high-risk plaque improved diagnosis of ACS in patients with acute chest pain who otherwise had no ECG or enzymatic evidence of ischemia or infarction.
Our understanding of morphological features of high-risk plaque stems primarily from the histology studies of patients who died of sudden cardiac death. The histological features of the culprit plaques included large necrotic core, higher macrophage count, positive remodeling, speckled calcium, and thin fibrous cap. Similar morphological features (positive remodeling, larger plaque area, spotty calcium, and large necrotic core) were observed with intravascular imaging in culprit lesions of ACS.
The direct comparison of CTA features of high-risk plaque to virtual histology intravascular ultrasound (IVUS-VH) is challenging. In the PROSPECT (Providing Regional Observations to Study Predictors of Events in the Coronary Tree) trial, the researchers demonstrated that lesions associated with recurrent ACS were characterized by a plaque burden ≥70%, by a minimal luminal area ≤4.0 mm, or as thin-cap fibroatheroma. CTA characteristics of high-risk plaque in our study did not exactly correlate to IVUS-VH measurements. However, the presence of a minimal luminal area ≤4.0 mm often correlates with significant stenosis, and we demonstrated that significant stenosis was an independent predictor of ACS. We did not perform quantitative analysis of plaques, which is necessary for the calculation of plaque burden. However, there is a correlation between positive remodeling and large plaque burden. Finally, the spatial resolution of CTA does not permit the detection of thin-cap fibroatheroma. However, the presence of the napkin-ring sign was very specific for the presence of advanced atheroma.
High-risk plaque features have been the target of noninvasive imaging with CTA. An early CTA study showed the feasibility of detecting high-risk plaque. The culprit plaques of ACS were often positively remodeled and had larger plaque burden compared with similarly stenotic plaques in patients with stable angina. Subsequent studies extended this observation and showed an association of plaque features such as large plaque burden, positive remodeling, spotty calcium, low HU plaque, and napkin-ring sign with ACS and with an increased risk of future cardiovascular events. Limited data exist on the role of high-risk plaque for early diagnosis of ACS in the acute chest pain population.
We found that one-third of the patients with acute chest pain had high-risk plaque, with spotty calcium as the most frequent high-risk plaque feature (32.0%), followed by positive remodeling (11.7%), low HU plaque (8.5%), and napkin-ring sign (5.5%). The prevalence of high-risk plaque features observed in our study in the acute chest pain population is similar to that of other CTA studies (5% to 15%) performed in populations of patients undergoing invasive coronary angiography, in larger unselected patient populations, and in nonculprit vessels of patients with ACS (PROSPECT trial). The reported prevalence of spotty calcium varied more dramatically in the published data (0% to 43%), most likely as a result of differences in the definition of spotty calcium. In addition, we observed a prevalence of coronary atherosclerosis defined as any coronary plaque in 55.5% of patients, nonobstructive CAD in 46.0% of patients, and significant stenosis ≥50% in 9.5% of patients, mostly consistent with other single-center and multicenter trials in acute chest pain. Overall, our results demonstrated that the prevalence of high-risk plaque and its associations with CAD and ACS in the acute chest pain setting are generalizable to multiple centers and CT vendors, and they were also in accordance with observations in stable chest pain syndromes as well as in nonculprit vessels of patients with ACS undergoing percutaneous coronary interventions.
The assessment of patients presenting with acute chest pain, but without objective signs of ischemia or MI, remains a diagnostic challenge. In patients who present with acute chest pain, exclusion of a significant coronary stenosis and plaque by CTA has a high sensitivity and negative predictive value for ACS and allows early discharge. However, ACS cannot be ruled out in a significant portion of patients in whom coronary plaques are present, reducing the specificity of CTA. Significant coronary stenosis was detected in approximately 10% and 4% of patients in 2 large multicenter trials, respectively. However, ACS or major adverse cardiovascular events developed in only approximately 4% and 1% of patients. Conversely, the sensitivity of ≥50% stenosis for the detection of ACS was 77% in the ROMICAT-I trial. In the ROMICAT-II study, we found a very similar result, with ≥50% stenosis detected in 78% of patients with ACS. This finding concurs with those of previous invasive angiographic studies that observed an absence of significant stenosis in 12% to 14% of patients with ACS. The limited diagnostic accuracy of CTA using the traditional criterion of significant stenosis might increase frequency of downstream testing and interventions. A potential means to improve CTA diagnostic accuracy is by adding the assessment of high-risk plaque to stenosis, which improved the diagnostic assessment of patients with acute chest pain in the present study.
The value of high-risk plaque for the diagnosis of ACS in patients with significant stenosis was demonstrated in the ROMICAT-I trial. A score including positive remodeling, spotty calcium, volume of low HU plaque, and stenosis length had a good discriminatory capacity for ACS during index hospitalization but was limited to only those with significant stenosis on CTA. The addition of high-risk plaque features showed a potential to refine the diagnosis of ACS by CTA. The current study demonstrated that high-risk plaque features assessed by a qualitative read of CTA images were independent and incremental to significant stenosis and clinical risk assessment for predicting ACS during the index hospitalization. Although stenosis remained the strongest predictor of ACS, high-risk plaque was associated with a 9-fold increase in the likelihood of ACS after adjustment for the presence of stenosis ≥50% and clinical risk assessment.
The inclusion of high-risk plaque improved the detection of ACS in patients with mild stenosis (1% to 49%). All patients with mild stenosis and ACS had at least 1 high-risk plaque feature. We suggest that patients with mild stenosis and high-risk plaque cannot be safely discharged from the ED. Further evaluation with serial troponins and additional testing will be necessary. While awaiting further work-up, providers should consider aggressive medical therapy (e.g., dual antiplatelet therapy). On the other side of the spectrum, there are patients with significant stenosis. Patients with significant stenosis on CTA cannot be discharged from the ED after initial troponin and ECG. In our study, the presence of high-risk plaque was incremental to stenosis for the prediction of ACS. Therefore, providers should consider aggressive medical therapy and invasive coronary angiography in patients with significant stenosis and high-risk plaque. In patients with stenosis, but no high-risk plaque, providers should consider further work-up to confirm the significance of the stenosis (e.g., stress test or invasive coronary angiography with fractional flow reserve). However, these strategies have not been tested in prospectively designed clinical studies, and further studies are required to include them in routine clinical practice.
The low number of ACS outcomes (n = 37) limited our ability to perform subanalyses and include additional variables in the multivariable models. Recent studies have demonstrated the additional value of quantitative analysis of plaque by CTA; we performed qualitative assessment of stenosis and high-risk plaque. The decision to use qualitative assessment was motivated by the fact that this approach could be more feasible in routine clinical practice because it adds minimal time for the assessment and does not require specific software and hardware. We restricted our analysis to the 4 most established high-risk plaque features (positive remodeling, low HU plaque, napkin-ring sign, and spotty calcium).