Int J Cardiovasc Imaging (2007) 23:389–392 DOI 10.1007/s10554-006-9144-1

B RI E F C O M M U N I C A T I O N

Multislice CT coronary angiography for the detection of burden, morphology and distribution of atherosclerotic plaques in the left main bifurcation Gasto´n A. Rodriguez-Granillo Æ Miguel A. Rosales Æ Elina Degrossi Æ Ine´s Durbano Æ Alfredo E. Rodriguez

Received: 23 May 2006 / Accepted: 25 July 2006 / Published online: 23 September 2006  Springer Science+Business Media B.V. 2006

Abstract The aim of the study was to explore the differences in plaque burden at different segments of the left main bifurcation and its relationship with the bifurcation angle using high-resolution multislice CT coronary angiography (MSCT). Patients were evaluated using a 40-row MSCT scanner. One observer assessed the localization, severity and distribution of plaques within the left main (LMCA) bifurcation, whereas another observer defined the angle. Fifty patients were included. The mean heart rate was 59.8 ± 7.1. Seventeen (34%) patients presented at least wall irregularities in the LMCA and in the ostial LCx, whereas the ostial LAD was affected in 32 (64%) patients. More than 90% of plaques were located opposite to the flow divider. The median bifurcation angle was 88.5
(IQR 68.8
, 101.4
). Of the 18 patients with a normal ostial LAD, 13 (72%) had a bifurcation angle < 88.5
, whereas the 63% of the patients with any LAD disease had an angle

G. A. Rodriguez-Granillo (&) Æ M. A. Rosales Æ E. Degrossi Æ I. Durbano Department of Cardiovascular Imaging, Otamendi Hospital, Buenos Aires, Argentina e-mail: [email protected] A. E. Rodriguez Interventional Cardiology Department, Otamendi Hospital, Buenos Aires, Argentina

‡ 88.5
(P = 0.018). In conclusion, at the left main bifurcation, atherosclerotic plaques are commonly located at the ostial LAD and opposite to the flow divider. The angle of the left main bifurcation and the presence of plaques within the bifurcation are closely related. Keywords Multislice Æ Angiography Æ Shear stress Æ Computed tomography

During the past few decades, both ex vivo and in vivo studies have shown that the flow pattern has an impact in the development and progression of atherosclerosis. This has been particularly shown at bifurcation sites, where the physiological laminar flow is transiently impaired, giving rise to low-oscillatory shear stress (LOSS) and subsequent plaque growth at the region opposite to the flow-divider [1, 2]. It has been previously established that an inverse relationship exists between LOSS and the thickness of the vessel wall [2]. The pathophysiology of such phenomenon can be briefly explained by the fact that LOSS induces a loss of the physiological flow-oriented alignment of the endothelial cells, thus causing an enhancement of the expression of adhesion molecules and a weakening of cell junctions, ultimately leading to an increase in permeability to lipids and macrophages [2–4].

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The angulation of the bifurcation might have an effect on shear stress and consequently on plaque size. A wider bifurcation angle might be related to higher turbulence and LOSS, whereas a narrow angle might be more prone to present laminar flow. Intravascular ultrasound studies have demonstrated that atherosclerotic disease has a predilection for the outer wall of the left main coronary artery (LMCA) bifurcation, sparing the flow-divider [1, 5]. Nevertheless, the potential impact of the angulation can only be studied in vivo by means of non-invasive imaging techniques that provide a 3D reconstruction of the bifurcation. Multislice computed tomography (MSCT) coronary angiography has evolved as a tool to identify the extent, morphology and distribution of atherosclerotic plaques in the coronary tree [6, 7]. We thus sought to explore the differences in plaque burden at different segments of the left main bifurcation and its relationship with the degree of the bifurcation angle. During a 3-month period, 64 patients were studied in our institution using MSCT angiography. Three patients were excluded due to bad quality acquisition, five were not included due to the presence of stents within the left main bifurcation, and six due to the presence of ramus intermedius. Only patients with sinus rhythm capable of achieving a breath-hold of 15 s were included. Informed consent was obtained from all patients. All scans were performed using a 40-row MSCT scanner (Brilliance 40, Philips, The Netherlands). A bolus of 100–125 ml of iodinated contrast material (Optiray, Ioversol 350 mg/ml, Mallinckrodt, St. Louis, U.S.A.) was injected through an arm vein (rate: 5–6 ml/s). The scan parameters were a collimation detector of 40 · 0.625 mm, a rotation time of 0.4 s, pitch of 0.2 mm, tube voltage 120 kV and mAs of 600– 1000. Images were acquired using ECG-gating in order to reduce motion artifacts. The bolus track technique was applied to synchronize the arrival of contrast to the coronary arteries with the acquisition start. 3D volume rendering techniques and 3D reconstruction of the entire coronary tree were used to calculate the angle of the bifurcation

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Int J Cardiovasc Imaging (2007) 23:389–392

Fig. 1 Left main coronary artery with a narrow bifurcation angle and no detectable atherosclerotic plaques (panel A). Panel B depicts a wider angle with an eccentric calcified plaque involving the wall opposite from the flow divider in the left anterior descending (LAD) and an additional eccentric mixed plaque opposite from the flow divider in the left circumflex (LCx)

(Fig. 1) using a caliper tool provided by customized software (Brilliance Extended Workstation, Philips, The Netherlands). The same observer re-analyzed the cases using the same methodology to evaluate the intra-observer agreement. Curved 2D multiplanar reconstructions were used to assess the severity, distribution and characteristics of coronary plaques. Plaques were classified as calcified when they corresponded to areas of high attenuation; as non-calcified when they corresponded to low density areas that could be differentiated from perivascular fat, and as mixed when they encompassed both components. One observer assessed the localization, severity (normal: no luminal narrowing; wall irregularities: < 20% lumen narrowing; nonsignificant: ‡ 20– < 50% lumen narrowing; or significant: ‡ 50% lumen narrowing), characterization and distribution (opposite or on the same side of the flow divider) of plaques within the LMCA bifurcation, whereas a second equally experienced observer independently defined the angle using the average between two projections. Segments were therefore prospectively divided in two groups, according to the median of the angle.

Int J Cardiovasc Imaging (2007) 23:389–392

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The ostial left anterior descending (LAD) and left circumflex (LCx) were defined as the carina and the immediate 3 mm distal segment, since the flow in this area is still influenced by the bifurcation. Lesions were classified as non-ostial when located between 3 mm and 5 mm from the ostium. Discrete variables are presented as counts and percentages. Continuous variables are presented as mean ± SD or median (25th, 75th percentile) when indicated. Comparisons between groups were performed using v2 tests. A P value < 0.05 (two-sided) was considered to indicate statistical significance. The intra-observer agreement was assessed using the Bland–Altman method. Limits of agreement were determined by the mean difference ± 2 SD of the mean difference. Fifty patients were finally included in the analysis. The mean scan time and mAs were 16.4 ± 1.6 s and 743 ± 121.9 mAs, respectively. Baseline characteristics are depicted in Table 1. The mean age was 64 ± 9.1 years and 44 (88%) patients were male. Thirty patients (60%) were studied as control of stents not involving the LMCA bifurcation, and 2 (4%) were screened for CAD due to the presence of multiple risk factors. Eigthteen patients (36%) presented with stable angina. The mean heart rate was 59.8 ± 7.1 bpm. Seventeen (34%) patients presented at least wall irregularities in the LMCA and in the LCx, whereas the LAD was affected in 32 (64%) patients (Table 2). The characteristics of the detected plaques are shown in Table 2. It is Table 1 Baseline demographics (n = 50) n (%) Age (years) Male Hypercolesterolemia Hypertension Previous smoking Current smoking Diabetes Previous myocardial infarction Clinical presentation Control/screeninga Stable angina a

64 ± 44 37 26 12 6 5 12

9.1 (88) (74.0) (52.0) (24.0) (12.0) (10.0%) (24.0)

32 (64%) 18 (36%)

These patients were studied as control of stents not involving the LMCA bifurcation, or screened for CAD due to the presence of multiple risk factors. MI refers to myocardial infarction

noteworthy that more than 90% of plaques were located in the vessel wall opposite to the flow divider. The median bifurcation angle was 88.5
(interquartile range 68.8
, 101.4
). Of the 18 patients with a normal ostial LAD, 13 (72%) had a bifurcation angle < 88.5
, whereas the 63% of the patients with any LAD disease (wall irregularities, non-significant and significant lesions) had an angle ‡ 88.5
(v2 = 0.018). Of the 33 patients with a normal ostial LCx, 19 (58%) had a bifurcation angle < 88.5
, whereas the 65% of the patients with any LCx disease had an angle ‡ 88.5
(P = 0.136). Finally, of the 33 patients with a normal LMCA, 20 (61%) had a bifurcation angle < 88.5
, whereas the 71% of the patients with any LMCA disease had an angle ‡ 88.5
(P = 0.037). With regards to the intra-observer variability, the mean calculated angle was 87.8 ± 22.3
and 87.2 ± 21.0
for the first and second observations, respectively, with a mean difference between observations of 0.64 ± 7.8
. The Bland–Altman chart depicts the good intra-observer agreement for angle measurements, with narrow limits of agreement (Fig. 2). The present study extends earlier findings on atheroma distribution within the left main bifurcation by means of high resolution, noninvasive MSCT angiography. Atherosclerotic plaques were commonly located at the ostial LAD, whereas the LMCA and the ostial LCx were less frequently affected. In line with previous reports using intravascular ultrasound [1, 5], ostial plaques were commonly eccentric and located opposite to the flow divider. Furthermore, a relationship was found between the angle of the left main bifurcation and the presence of plaques within the bifurcation, particularly in the ostial LAD. Shear stress patterns were not measured in the present study. However, it has been widely established that the region opposite to the flow-divider is characterized by a LOSS that promotes atherogenesis, whereas the flow divider is subjected to laminar flow and high shear stress. The present study shows the ability of non-invasive coronary imaging to depict the potential effect of fluid dynamics on the local characteristics and distribution of atherosclerotic plaques

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Table 2 The characteristics of the detected plaques Presence and severity of lesions at the left main bifurcation (n = 50) Lumen narrowing LMCA Ostial LAD Ostial LCx

‡ 50% 3 (6.0) P = 0.003 5 (10.0) 6 (12.0)

50–20% 7 (14.0) P = 0.011 22 (44.0) 5 (10.0)

1–20% 7 (14.0) P = 0.010 5 (10.0) 6 (12.0)

Normal 33 (66.0) P = 0.010 18 (36.0) 33 (66.0)

Characteristics of lesions at the left main bifurcation (n = 50)

LMCA Ostial LAD Ostial LCx

Plaquesa

No calcium

Calcified

Mixed

Eccentric

Opposite

Ostial

17 (34.0) 32 (64.0) 17 (34.0)

4 (23.5) 11 (34.4) 6 (33.3)

5 (29.4) 10 (31.3) 5 (27.8)

8 (47.1) 11 (34.4) 7 (38.9)

16 (94.1) 30 (93.8) 15 (93.8)

– 30 (93.8) 15 (93.8)

– 28 (87.5) 14 (93.3)

a

Presence of at least wall irregularities. Data are presented as counts (percentages). LMCA, LAD and LCx refer to left main, left anterior descending and left circumflex coronary arteries. P values arise from chi square tests performed in order to find associations between the presence of lesions in one vessel with the presence of lesions in other vessel

3.

4.

Fig. 2 The Bland–Altam plot depicts a good intraobserver agreement with a mean difference of 0.64
and narrow limits of agreement

within the left main bifurcation. Further larger studies are warranted to evaluate the potential prognostic implications of these findings.

5.

6.

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