ABSTRACT: Objective. We used intravascular ultrasound (IVUS) and virtual histology (VH) to assess the differences of plaque burden and composition between target coronary arteries containing the culprit lesion and non-target coronary arteries.
Methods. Sixty patients referred for acute (n = 19) or elective (n = 41) coronary angiography were included. The target vessel containing the culprit lesion was identified by angiography. A non-target coronary artery was chosen for comparison. The first 4 cm of each vessel were analyzed with IVUS and VH.
Results. Total plaque burden was higher in the target vessel compared to the non-target vessel (52.4% vs. 45.9%, a relative difference of 14.2%; p Conclusions. We conclude that in patients with relevant coronary artery disease, plaque burden and the amount of necrotic core material are greater in the target vessel. There is a strong correlation of plaque composition between target and non-target coronary arteries.
J INVASIVE CARDIOL 2009;21:584–587
Key words: virtual histology, IVUS, acute coronary syndrome, stable angina
Plaque rupture occurring in high-risk coronary artery lesions is the most frequent cause of acute coronary syndromes (ACS). It is not only stenosis severity, but plaque composition as well that have been shown to be important predictors of ACS.1–3 Therefore, gray-scale intravascular ultrasound (IVUS) has been used to characterize the extent and distribution of atherosclerotic coronary artery plaques.4,5 However, since both lipid-rich and fibrous plaques express low echogenicity, they are difficult to differentiate solely by IVUS.6,7 Additional radiofrequency ultrasound backscatter signals as provided by the Virtual Histology™ (VH) IVUS system (Volcano Corp., San Diego, California) improve accuracy in the determination of plaque morphology.8,9 It has been demonstrated that VH IVUS correlates well with histopathology10 and has a 93–96% ex-vivo accuracy when used to identify four different types of atherosclerotic plaques (fibrous, fibrofatty, dense calcium, necrotic core).8 Data comparing plaque extent and composition of different vessels in the same patient are sparse. We examined patients referred for acute or elective coronary angiography with IVUS and VH. We intended to determine the difference in plaque burden and composition between target vessels and non-target vessels.
Patients and Methods
Study protocol and study population. In a prospective study, consecutive patients referred for acute (i.e., unstable angina pectoris or acute myocardial infarction [AMI]) or elective coronary angiography were enrolled. Patients in cardiogenic shock and hemodynamically unstable patients dependant on inotropes were not included. Patients were included if there was a clear culprit vessel present with a distal culprit lesion causing an ACS or angina pectoris. Patients whose coronary artery anatomy was not suitable for IVUS or whose culprit lesion was within the proximal 4 cm of the target vessel were excluded. This way, we avoided including the culprit lesion in our IVUS analysis. A total of 125 patients were screened, 65 were excluded and the remaining 60 patients were included for analysis. The study was approved by the local ethics committee and all patients gave written informed consent.
The target and a non-target vessels were analyzed with IVUS and VH. The non-target vessel was chosen as follows: in cases where the culprit vessel was the left anterior descending coronary artery (LAD), the comparison was the circumflex coronary artery (CX), and vice versa, if suitable for IVUS examination. In 4 cases, the right coronary artery (RCA) had to be chosen instead. In the remaining cases where the culprit vessel was the RCA, the comparison vessel was either the LAD or the CX, chosen at random. The target vessel and the comparison vessel were studied with IVUS and VH in ACS patients after thrombolysis in myocardial infarction (TIMI) 3 flow was achieved.
Intravascular ultrasound and virtual histology. IVUS and IVUS-VH data were acquired using an Eagle Eye
® Gold Catheter (20 MHz) and an automatic pullback device (Volcano Corp.). In every patient, the proximal 4 cm of the target and non-target vessels were investigated. The pullback rate was 1 mm/second and the frames were acquired elecrocardiographic (ECG)-gated/R-wave-triggered (thus, in a patient with a heart rate of 60 beats/minute, 40 frames were analyzed; in a patient with a heart rate of 75 beats/minute, 50 frames were analyzed, and so on). Data were stored on DVD and B-mode IVUS images were analyzed offline by two trained investigators (ST, YS), using custom software (Volcano Therapeutics). They were blinded to clinical and fluoroscopic data. Lumen and vessel borders were manually corrected. Thereafter, parameters were calculated automatically by custom software using data from all analyzed frames and plaques were characterized as fibrous, fibrolipidic, necrotic core and calcified.8 Plaque volume was calculated as the sum of fibrous, fibrolipidic, calcified, necrotic tissue and media volume. Plaque burden was calculated as the plaque volume divided by the sum of plaque volume and lumen volume. Vessel volume was calculated as the sum of lumen and plaque volume. Plaque burden was calculated as the plaque volume divided by vessel volume. In addition to volumes, relative plaque composition was determined as total plaque volume divided by the particular (i.e., fibrous, fibrolipidic, calcified, necrotic core) plaque volume.
Statistical analysis. Statistical analysis was performed using SPSS version 15 software (SPSS, Inc., Chicago, Illinois). If not indicated otherwise, data are presented as mean ± standard deviation. Continuous variables were analyzed using a paired student’s t-test. Correlation coefficients were calculated using Pearson’s correlation. For all tests, a two-sided p-value Results
A total of 60 patients were included, of whom 19 were referred for acute and 41 for elective coronary angiography. Complete baseline characteristics including medication at the time of hospital admission and cardiovascular risk factors are presented in Table 1. Mean age was 60 ± 9 years and 80% of the patients were male. Patients presented with three-vessel disease (n = 24), two-vessel disease24 or one-vessel disease.
12 Target vessel was the LAD in 31, the CX in 15 and the RCA in 14 patients. Non-target vessels chosen for comparison were: LAD/CX/RCA in 20/35/5 patients, respectively.
Comparison of IVUS data. Table 2 lists IVUS data on target and non-target coronary arteries. Lumen measurements did not differ (no difference in minimal lumen diameter, minimal lumen cross-sectional area [CSA] or lumen volume between the two groups). Vessel volume was higher in the target vessels (601 ± 157 mm3 vs. 527 ± 168 mm
3, a relative difference of 14%; p = 0.007). Plaque volume (313 ± 93 mm3 vs. 247 ± 102 mm
3, a relative difference of 27%; p Comparison of VH data. Table 3 compares VH data on target and non-target vessels. Absolute fibrous, calcified and necrotic-core plaque volume was significantly higher in target than in non-target vessels. Comparing plaque composition, plaques consisted mainly of fibrous material (54.3% and 55.4% for target and non-target vessels, respectively; p = ns). The relative amount of necrotic-core plaques was significantly higher in target vessels, whereas non-target vessels contained more fibrolipidic plaques. All four plaque types correlated significantly with target and non-target vessels. The relative plaque composition yielded stronger correlations than the absolute plaque volumes. The relative amount of calcified and fibrolipidic plaques yielded the strongest correlation between target and non-target vessels (r = 0.70, p Differences between acute and elective patients. Table 4 and Figure 1 compare differences between patients referred for elective coronary angiography and acute patients. Figure 1 visualizes the relative amount of calcified plaques in target and non-target vessels in elective and acute patients separately. The correlation was stronger in elective than in acute patients.
In Table 4, VH data are listed for patients referred for acute and elective coronary angiography separately. Absolute and percentage plaque volumes were similar in acute and elective patients. Due to the higher plaque burden in target vessels, absolute necrotic core and fibrous plaque volumes were higher in target than in non-target vessels.
Discussion
Acute coronary events are a leading cause of morbidity and mortality, and atherosclerotic plaque composition plays an important role in the development of coronary events. Furthermore, it has been previously shown that ACS frequently arise from atherosclerotic lesions with only mild or moderate obstruction.
11,12 Plaque composition, therefore, is of major importance.
This study has made a number of observations regarding the qualitative and quantitative plaque composition in target vessels containing the (distal) culprit lesion and non-target vessels. They may be summarized as follows: 1) average plaque area and plaque burden were higher in target vessels; 2) plaque composition was similar in target and non-target vessels, but target vessels exhibited a greater amount of necrotic core material compared to non-target vessels, whereas plaques in non-target vessels were composed of a greater amount of fibrolipidic plaques; 3) vessel volume was greater in target vessels due to a larger amount of atheroma volume. There were no differences in luminal volume between target and non-target vessels; 4) the absolute amount of necrotic core was significantly higher in target vessels than in non-target vessels. This finding may be of importance since it has been shown that lesions with a large amount of necrotic core covered with a thin fibrous cap are prone to plaque rupture.
1,2 Due to the strong correlation of plaque composition between target and non-target vessels, patients with a large amount of necrotic core material in their target vessels may be at higher risk for an acute coronary event in their non-target vessels. All these differences between target and non-target vessels were observed, even without inclusion of the culprit lesion in the analysis of the target vessel.
It is difficult to compare these findings to previous studies because literature comparing different vessels in the same patient is sparse. Rodriguez-Granillo et al
13 compared plaque composition of non-target lesions in patients with acute or stable clinical presentation. They found that patients presenting with ACS had a higher percentage of necrotic core in plaques of their non-culprit vessels than patients referred for elective coronary angiography. In a recently published study,
14 atherosclerotic plaques of target and non-target vessels were compared by VH IVUS and multi-slice computed tomography (MSCT). In this study, no difference was observed between plaque composition in the target and non-target arteries. However, the results of these studies cannot be directly compared to our results since both studies analyzed plaques of target and non-target vessels including the culprit lesion, whereas in our study, we analyzed the proximal 4 cm of a vessel and no culprit lesion was included. Although we found a greater amount of necrotic core material in target vessels, we also were able to demonstrate that plaque composition was closely correlated between target and non-target vessels. These findings suggest that plaque composition varies between different patients, but seems to be very similar in different coronary arteries in the same patients (i.e., high inter-individual variability, but low intra-individual variability). This was equally true for acute and elective patients.
Study limitations. The number of acute patients in this study is small, thus significant differences in plaque composition and morphology between target and non-target vessels may have been missed. In addition, 52% of the screened subjects were excluded based on study selection criteria and this may have resulted in selection bias. Patients with a proximal lesion were excluded, therefore our findings cannot be generalized to the entire patient population. However, we believe that inclusion of the culprit into analysis of the target vessel may lead to even greater differences between plaque burden and probably plaque composition.
Most of the previous studies compared IVUS and VH data on different plaques and not of the entire proximal vessel segment making direct comparison to other studies difficult. Only the proximal 40 mm of each vessel was analyzed. However, we analyzed about 50 frames for each vessel (i.e., 100 frames per patient), leading to very exact results regarding plaque volume and composition.
Conclusion
We conclude that in patients with relevant coronary artery disease, plaque burden and the amount of necrotic core material are greater in target vessels. There is a strong plaque composition correlation between target and non-target coronary arteries in patients referred for acute or elective coronary angiography.
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