|Year : 2018 | Volume
| Issue : 1 | Page : 1-7
Atherosclerotic plaque composition and significance of nonculprit intermediate coronary lesions. Intravascular ultrasound and quantitative coronary angiography study in acute coronary syndrome
Helmy H El Ghawaby, Mohamed A Shawki, Ahmed H Mowafi, Akram M Abd Elbary, Farouk M Faris
Department of Critical Care, Faculty of Medicine, Cairo University, Cairo, Egypt
|Date of Web Publication||24-Jan-2018|
Helmy H El Ghawaby
Department of Critical Care, Faculty of Medicine, Cairo University, Cairo, 11562
Source of Support: None, Conflict of Interest: None
Background Detection of potentially vulnerable plaques inducing acute coronary syndrome (ACS) improves prevention of cardiovascular events. We aimed at using intravascular ultrasound (IVUS) for morphological assessment, anatomical significance of atherosclerotic plaques of nonculprit intermediate coronary lesions and correlation with quantitative coronary angiography (QCA) in ACS.
Patients and methods 2IVUS was performed on 61 nonculprit intermediate coronary lesions in 28 patients diagnosed with non-ST-elevation ACSs. Percent area stenosis more than 70% was the cutoff value for intervention.
Results The mean age was 53.2±9.1 years, men=20 (71.4%). Culprit vessels represent 42% of affected vessels. Higher lipid content was found in lesions of culprit vessels (P<0.001). Six lesions were revascularized based on IVUS measures (QCA accuracy=90.1%, sensitivity=77.8%, and negative predictive value=85%). Minimal lumen area (MLA) and plaque burden are the main predictors for lesion anatomical significance with [P<0.001, odds ratio=0.25, 95% confidence interval (CI)=0.12–0.55] and (P=0.011, odds ratio=2.0, 95%CI=1.2–3.3), respectively. There was a positive strong correlation between QCA minimal lumen diameter and MLA (P<0.001, r=0.695). An inverse moderate correlation was seen between QCA minimal lumen diameter and percent area stenosis (P<0.001, r=−0.449). There was a significant concordance between QCA and IVUS regarding percent stenosis (P=0.01, intraclass correlation coefficient=0.451, 95%CI=0.084–0.67), while there was disconcordance in measurement of the lesion length (P=0.2, intraclass correlation coefficient=0.22, 95%CI=−0.3–0.53).
Conclusion IVUS might be valuable for the assessment of nonculprit lesions in ACS. There is high vulnerability for plaque rupture in intermediate lesions of culprit vessels. MLA and plaque burden are the main predictors for lesion anatomical significance. QCA is a reliable tool for detecting severity of coronary artery disease.
Keywords: acute coronary syndrome, intermediate lesions, intravascular ultrasound, minimal lumen area, quantitative coronary angiography, vulnerable plaques
|How to cite this article:|
El Ghawaby HH, Shawki MA, Mowafi AH, Abd Elbary AM, Faris FM. Atherosclerotic plaque composition and significance of nonculprit intermediate coronary lesions. Intravascular ultrasound and quantitative coronary angiography study in acute coronary syndrome. Res Opin Anesth Intensive Care 2018;5:1-7
|How to cite this URL:|
El Ghawaby HH, Shawki MA, Mowafi AH, Abd Elbary AM, Faris FM. Atherosclerotic plaque composition and significance of nonculprit intermediate coronary lesions. Intravascular ultrasound and quantitative coronary angiography study in acute coronary syndrome. Res Opin Anesth Intensive Care [serial online] 2018 [cited 2019 Mar 25];5:1-7. Available from: http://www.roaic.eg.net/text.asp?2018/5/1/1/223830
| Introduction|| |
Recent evidence proposed that acute coronary syndromes (ACSs) frequently arise from erosion of vulnerable plaques and subsequent thrombosis ,. Previous studies have noted that histologic thumbprints of these vulnerable plaques showed a high lipid core area and a thin fibrous cap ,.
The main challenge faced is that ACS often arises from lesions with only mild to moderate stenosis. Accordingly, disclosure of potentially vulnerable plaques may promote prevention of cardiovascular events ,,,,.
Intravascular ultrasound (IVUS) is a fast developing instrument in cross-sectional visualization of coronary arteries and assessment of the atherosclerotic plaques in vivo ,,.
Although quantitative coronary angiography (QCA) has reduced the visual error, the coronary compensatory remodeling makes angiography a deceptive method to estimate atherosclerotic burden ,.
Studies using IVUS had confirmed the diffuse nature of coronary atherosclerosis, which makes the reference vessel appear angiographically normal ,.
Furthermore, IVUS is helpful in determining true morphologic severity of intermediate coronary lesions and guidance of management strategies for these lesions .
| Aim|| |
The objectives of this study were to investigate the morphology and severity of atherosclerotic plaques of nonculprit intermediate lesions in ACSs, and to identify the correlation between QCA and IVUS.
| Patients and methods|| |
An observational cross-sectional study approach included 28 patients admitted at the Critical Care Department, Faculty of Medicine, Cairo University with ACSs including unstable angina and non-ST-segment elevation myocardial infarction (MI) and coronary angiography showed nonculprit intermediate lesions defined as a luminal narrowing with a diameter stenosis greater than or equal to 40% but less than or equal to 70% . The institutional ethics committee approved the protocol.
Exclusion criteria were acute ST elevation MI, cardiogenic shock, bleeding disorders, previous coronary artery bypass grafting, renal impairment and in-stent restenosis.
After routine examination and history taking, all patients were subjected to evaluation of BMI, risk stratification of the patients using thrombolysis in MI risk score, and laboratory assessment of cardiac enzymes including troponin.
All patients signed a written consent about the nature of the study before transferring to the catheterization laboratory. The diagnostic angiograms were done through transfemoral approach.
Angiographic data were assessed visually by at least two experienced operators to determine the percent diameter stenosis. Detected stenoses were viewed in two orthogonal projections in an end diastolic frame. Lesions of more than 70% stenosis were defined as significant lesions and lesions of less than 40% stenosis were defined as nonsignificant lesions .
Nonculprit intermediate lesions analyzed by:
- QCA: reference diameter, minimal luminal diameter, percent diameter stenosis, and lesion length were measured as the mean of the values obtained from the two projections in end diastolic images using the contrast-filled catheter for calibration. The minimum lumen diameter was calculated from the angiographic projections with the tightest stenosis and the reference diameter was measured from an angiographically normal segment proximal to the lesion or distal for ostial lesions.
- IVUS: we used iLAB TM System 1.2 Ultrasound Imaging System 90539386-01A (2009; iMAP & ATLANTIS SR Pro by Boston Scientific Corporation, Marlborough, MA 01752-1234, Massachusetts, USA). Imaging was performed using a 40 MHz, 6 F compatible catheters (Atlantis SR Pro).
Following intracoronary infusion of nitroglycerine (100–200 µg) to minimize vasospasm, the rapid exchange IVUS catheters were introduced in the coronary over a standard 0.014 inch guide wire.
Based on images depicted during pullback, the lesion was defined as the image slice with the smallest lumen cross-sectional area (CSA).
The measurements were performed according to the guidelines of the American College of Cardiology for the acquisition, measurement, and reporting of IVUS studies  by two experienced IVUS readers. Cross-sectional images were quantified for lumen CSA, minimum lumen diameter, maximum lumen diameter, external elastic membrane (EEM) CSA, atheroma CSA, plaque burden, proximal reference, distal reference using the software included with the IVUS system. Length measurements=number of frames×pullback speed .
The remodeling index was defined as the ratio of EEM CSA at the measured lesion (minimum luminal site) to reference EEM CSA (the average of the proximal and distal reference segments). Remodeling index more than 1 mean positive remodeling whereas remodeling index less than 1 means negative remodeling ,,,,,,.
After acquisition of the color coded maps, the percentage fibrous area (fibrous area/plaque area), the percentage lipid area (lipid area/plaque area), and the percentage calcific area were automatically counted using commercially available computer software (iMAP).
Percutaneous coronary intervention was performed for nonculprit intermediate lesions with percent area stenosis more than 70%.
Precoded data was entered using ‘Microsoft Office Excel Software’ (Redmond, Washington, USA) program (2010) for windows. Data were then transferred to the statistical package for the social sciences software program, version 21 (SPSS; SPSS Inc., Chicago, Illinois, USA) to be statistically analyzed. Data were summarized using mean, SD, median, and inter quartile range for quantitative variables and frequency and percentage for qualitative ones. Comparison between groups was performed using independent sample t-test or one-way analysis of variance with Tukey’s post-hoc test for quantitative variables and χ2 or Fisher’s exact tests for qualitative ones. Pearson’s correlation coefficients were calculated to get the association between different quantitative variables. Reliability of measurements was tested with two-way mixed model intraclass correlation coefficient (ICC) for average measurement agreement. The agreement between modalities was evaluated by means of ICC. Logistic regression analysis was performed to explore the significant predictors of revascularization. P values of less than 0.05 were considered statistically significant, and less than 0.01 were considered highly significant.
| Results|| |
The study was performed on 61 nonculprit intermediate lesions in 28 patients with non-ST elevation ACS. The average age of the patients was 53.2±9.1 years, and 20 (71.4%) were men. Twelve (42.9%) patients who had dyslipidemia, 17 (60.7%) were smokers, 16 (57.1%) had high blood pressure, eight (28.6%) had diabetes, and six (21.4%) had a family history of coronary artery disease. Eighteen (46.3%) patients had thrombolysis in MI risk of greater than or equal to 3 for unstable angina or non-ST-elevation MI. Patients were subjected to coronary angiography because of the presence of myocardial ischemia in the form of ECG changes, perfusion defects on technetium 99mTc sestamibi (MIBI) (Nuclear Consultants Inc., St. Louis, Missouri, USA) single-photon emission computed tomography (SPECT) and regional wall motion abnormalities on echocardiography.
Multivessel disease was observed in 60.8% of patients, two-vessel disease in 32.2%, and one-vessel disease in only 7% of patients. Culprit vessels represent 42.1% whereas nonculprit vessels represent 57.9% of total affected vessels. Totally, 30 lesions were present in the proximal segments, 23 lesions in the midsegments, and eight lesions in the distal segments of the affected vessels.
Morphologic changes by intravascular ultrasound
Investigating the morphology of intermediate coronary lesions has shown that the lesions in the proximal segments of the coronary vessels had significantly higher calcific content than the lesions in distal segments (P=0.048) as shown in [Figure 1].
Interestingly, IVUS showed statistically significant higher lipidic content in lesions of culprit vessels (vulnerable plaque) (P<0.001), whereas there was a statistically significant higher calcific content in lesions of nonculprit vessels (P<0.001) as shown in [Figure 2].
Positive remodeling was observed in 27 (44.3%) lesions and negative remodeling in 34 (55.7%).
Based on IVUS calculations, the operator changed the decision regarding six intermediate lesions which were initially (by QCA) supposed to be deferred for medical treatment. From these results, it had been shown that QCA accuracy is 90.1%, sensitivity was 77.8%, and negative predictive value equals 85%.
Further analysis of IVUS data by backward stepwise regression model showed that minimal lumen area (MLA) and plaque burden are the main predictors for lesion anatomical significance with [P<0.001, odds ratio=0.25, 95% confidence interval (CI)=0.12–0.55] and (P=0.011, odds ratio=2.0, 95%CI=1.2–3.3), respectively.
A comparison of QCA data between lesions for deferral of intervention and those for revascularization has shown that minimal lumen diameter was significantly lower (P=0.002) in the revascularization group; however, percent diameter stenosis was significantly higher in the revascularization group than that in the deferral group (P=0.02).
Additionally, MLA was significantly lower and percent area stenosis was significantly higher in revascularization group than in deferral group (P<0.001) when comparing IVUS data.
Quantitative intravascular ultrasound versus quantitative coronary angiography
Correlation between IVUS and QCA measures demonstrated a significant positive strong correlation between QCA minimal lumen diameter and minimum lumen diameter measured by IVUS at the site of lesion (P<0.001, r=0.704) as in [Figure 3], a significant positive strong correlation between QCA minimal lumen diameter and MLA measured by IVUS at the site of lesion (P<0.001, r=0.695) as shown in [Figure 4], a significant inverse moderate correlation between QCA minimal lumen diameter and percent area stenosis measured by IVUS at the site of lesion (P<0.001, r=−0.449) as shown in [Figure 5], a significant positive weak correlation between QCA percent stenosis and percent area stenosis measured by IVUS (P=0.021, r=0.295) as shown in [Figure 6], and a significant concordance between QCA and IVUS regarding percent stenosis (P=0.01, ICC=0.451, 95%CI=0.084–0.670). There was a significant positive moderate correlation between QCA reference diameter and proximal reference maximum vessel diameter by IVUS (P=0.013, r=0.358).
|Figure 3 Correlation between QCA minimal lumen diameter and IVUS lesional minimal lumen diameter.|
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|Figure 4 Correlation between QCA minimal lumen diameter and MLA measured by IVUS.|
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|Figure 5 Correlation between QCA minimal lumen diameter and percent area stenosis.|
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|Figure 6 Correlation between QCA percent stenosis and percent area stenosis.|
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A comparison of the IVUS and angiography results has shown a significant underestimation of the lesion length by angiography as there was no significant correlation between lesion length measured by QCA and that measured by IVUS (P=0.333, r=0.126) and a disconcordance between both of them regarding measurement of lesion length (P=0.2, ICC=0.22, 95%CI=−0.300–0.532).
| Discussion|| |
The current study demonstrates that IVUS is a safe and useful tool for therapy guidance in patients with angiographically intermediate coronary artery disease.
There are several reports showing the details of the plaques that caused ACS by use of IVUS. It was reported that 30% of ruptured plaques were hypoechoic, 31% hyperechoic, and 39% were mixed plaque .
Plaque rupture is related to the process in which fibrous caps over the lipid core become fragile .
A clinicopathologic study indicated that the echolucency of the plaque could represent the presence of a lipid-rich core , where metaloproteinases are associated with erosion of the fibrous cap . Therefore, one might hypothesize that the presence of the echolucent zone might be emblematic of plaque vulnerability.
This concept of lesion vulnerability has changed the clinical approach to diagnosing and treating coronary artery diseases, since the odds of an adverse event are not directly related to the severity of coronary artery stenosis ,. For example, revascularization of stenotic lesions in clinically stable patients might not affect long-term survival ,,,,.
The present study confirms the above concept as intermediate lesions in culprit vessels showed significantly higher lipid content and significantly lower calcific content than the intermediate lesions in nonculprit vessels.
These results are consistent with data obtained by Yamagishi et al. , who examined 12 intermediate coronary lesions in ACS patients and showed an echolucent zone within the plaque in 10 of the 12 sites.
On the contrary, in Pundziute et al. , 97 coronary plaques were detected by IVUS in 25 ACS patients. No differences were observed between plaque composition in culprit and nonculprit arteries on virtual histology IVUS. Plaques of the two groups of arteries showed no differences in the amount of fibrotic tissue, fibrofatty tissue, dense calcium, and necrotic core. This inconsistency may be because of the use of different devices, technologies, and subsequent specificity and sensitivity.
Another important finding in our study was that most of the lesions (49.2%) were located in the proximal segments of the examined arteries. Numerous pathological, angiographic, and imaging studies have shown a similar, proximal predisposition of thin-capped fibroatheroma (TCFAs), acute occlusions, or plaque ruptures ,,,,,. This tendency of advanced plaques to develop preferentially in these locations has been explained by the low shear stress conditions that induce the migration of lipid and monocytes into the vessel wall leading to the progression of the lesion toward a plaque with high risk of rupture .
A recent study has shown that all lesions derived from or related to plaque rupture show positive remodeling, which may represent an important surrogate for detecting lesion vulnerability .
Conversely, most of the intermediate lesions in our study showed negative remodeling (55.7%), which was consistent with the results of Koo et al.  and Fernandes et al. . Besides, lesions of total occlusion or erosion exhibited negative remodeling .
The decision to intervene on a lesion is frequently made in the catheterization laboratory based on the visual estimation of the lesion’s severity. Lesions with more than 70% stenosis on visual quantification are usually considered hemodynamically significant and submitted to intervention. However, data from pressure wire evaluation of lesions with less than 70% compromise of luminal diameter have shown that they are also frequently associated with impaired flow reserve and myocardial ischemia ,. Moreover, previous IVUS studies have demonstrated the correlation between an MLA less than 4.0 mm2 and decreased fractional flow reserve, whereas an MLA greater than or equal to 4.0 mm2 was correlated with a preserved fractional flow reserve and favorable outcomes with deferral of invasive intervention .
In this study, we applied an IVUS-guided strategy to perform or defer revascularization of angiographically intermediate coronary lesions as ∼10% of the lesions diagnosed as moderate by conventional angiography had, in fact, severe stenosis by the adopted IVUS criterion percent area stenosis more than 70%.
The most obvious finding revealed from the analysis of our data is that MLA and plaque burden were the main predictors for lesion significance for revascularization.
These results are in agreement with those obtained by Koo et al.  which showed that MLA was the main determinant of functionally significant stenosis.
Furthermore, Kang et al.  compared QCA and IVUS with stress myocardial SPECT. Independent determinants for a positive SPECT were in-segment angiographic diameter stenosis and in-segment IVUS-MLA.
Our research has shown a significant positive strong correlation between QCA minimal lumen diameter and minimum lumen diameter at the site of lesion measured by IVUS and a significant correlation and concordance between QCA and IVUS regarding the measurement of percent stenosis.
This result is in agreement with Abizaid et al.  in which 122 patients underwent angiographic and IVUS assessment of the severity of left main coronary artery disease and confirmed that the lesion site minimal lumen diameter by QCA correlated well with IVUS.
Angiography usually underestimates the lesion length because it could not detect atherosclerotic compromise in the reference segments. In our research, this was supported by finding no correlation or reliability between QCA and IVUS regarding measurements of lesions length. This is in agreement with Bourantas et al. , which showed that QCA tended to underestimate the length of stenosis.
It was conducted in a nonrandomized manner and, therefore, suffers from the limitations associated with its design. Besides, the small number of patients is because of the high cost of IVUS-guided coronary intervention in a developing country.
| Conclusion|| |
Our study shows that IVUS is a safe method to accurately assess the degree of disease in the coronary lesions that appear indeterminate by angiography in patients with ACS.
It showed that intermediate lesions in culprit vessels had high lipid content and less calcific content indicating high vulnerability for plaque rupture. IVUS is a helpful tool in planning the management of intermediate lesions and QCA may be a reliable tool for the detection of coronary artery disease severity.
Financial support and sponsorship
Conflicts of interest
There are no conflicts of interest.
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[Figure 1], [Figure 2], [Figure 3], [Figure 4], [Figure 5], [Figure 6]