Clin Res Cardiol (2010) 99:83–91 DOI 10.1007/s00392-009-0077-2
ORIGINAL PAPER
Intravascular ultrasound radiofrequency analysis of the lesion segment profile in ACS patients Andreas Ko¨nig Æ Øyvind Bleie Æ Johannes Rieber Æ Philip Jung Æ Thomas M. Schiele Æ Hae-Young Sohn Æ Marcus Leibig Æ Uwe Siebert Æ Volker Klauss
Received: 4 December 2008 / Accepted: 4 September 2009 / Published online: 19 September 2009 Ó Springer-Verlag 2009
Abstract Background Intravascular ultrasound radiofrequency analysis (IVUS-RF) characterizes plaque components as necrotic core (NC) and dense calcium (DC). The aim of this study was to perform an IVUS-RF derived analysis of the lesion segment profile in acute coronary syndrome (ACS) patients. Therefore, we compared the site of the minimum lumen area—cross sectional area (mla-CSA) with the worst lesion site—CSA (ws-CSA) defined by the maximum NC site. Methods We performed IVUS-RF derived plaque composition and plaque-type classification analysis in 48 ACS patients with 48 culprit (CL) and 69 non-culprit lesions (NCL).
A. Ko¨nig (&) J. Rieber P. Jung T. M. Schiele H.-Y. Sohn M. Leibig V. Klauss Division of Cardiology, Department of Medicine, Medizinische Klinik und Poliklinik, Ludwig-Maximilians-Universita¨t, Ziemssenstr. 1, Campus Innenstadt, 80336 Munich, Germany e-mail:
[email protected] Ø. Bleie Department of Heart Disease, Haukeland University Hospital, Bergen, Norway U. Siebert Department of Public Health, Medical Decision Making and Health Assessment, Medical Informatics and Technology, University of Health Sciences, 6060 Hall, Austria U. Siebert Institute for Technology Assessment and Department of Radiology, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA
Results The plaque dimension of the mla- and ws-CSA was significantly different regarding the lumen area (5.18 ± 2.09 mm2 vs. 6.72 ± 2.73 mm2, p = 0.0013) and the vessel area (14.80 ± 5.86 mm2 vs. 17.15 ± 4.94 mm2, p = 0.0142). The absolute plaque composition was also significantly different regarding the DC tissue (0.71 ± 0.57 mm2 vs. 0.98 ± 0.54 mm2, p = 0.0102) and the NC tissue (1.41 ± 1.28 mm2 vs. 1.85 ± 1.37 mm2, p = 0.0469). The plaque-type classification revealed significantly more thin cap fibroatheroma (TCFA) lesions at the ws-CSA compared to the mla-CSA (n = 53/89.8% vs. n = 26/44.1%, p \ 0.0001). In the majority of the CL and NCL lesion segments the ws-CSA was located proximal to the mla-CSA compared to the distal location (n = 65/55.6% vs. n = 23/19.7%). Conclusions In the majority of the lesion segments in ACS patients the ws-CSA is not identical with the mlaCSA. The ws-CSA compared to mla-CSA presented with significantly more NC and DC tissue resulting in a higher amount of TCFA lesions. Keywords Acute coronary syndrome Intravascular ultrasound Radiofrequency analysis Plaque composition Lesion profile
Introduction Cardiovascular diseases with acute coronary syndrome (ACS) are the main causes of morbidity and mortality in the western world [1]. Histo-pathologic data suggest that the plaque composition is a key determinant of the propensity of atherosclerotic lesions to undergo plaque rupture. The reason for ACS is very often the spontaneous rupture of vulnerable plaques as thin cap fibroatheroma
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(TCFA) with subsequent thrombus formation [2, 3]. At the site of plaque rupture the size of necrotic core was even increased and the fibrous cap was thinner compared to TCFA [3]. According to angiographic studies plaque ruptures are caused by non-flow limiting coronary lesions [4, 5]. On the other hand, histo-pathological studies could show that the underlying lesions for plaque rupture are often severe [6, 7]. Recent intravascular ultrasound (IVUS) studies showed large and lipid-core containing plaques together with positive coronary remodeling at the site of plaque rupture, regardless of the degree of stenosis [8]. The relationship between coronary remodeling and plaque composition was shown in histo-pathologic and also clinical studies [9, 10]. An IVUS profile analysis showed more necrotic core at the plaque rupture site compared to the minimum lumen area site [11]. In addition, IVUS studies could show that the site of minimum lumen area is not necessarily the culprit site of the lesion [12]. IVUS-radiofrequency analysis (IVUS-RF) provides in vivo quantitative analysis of four plaque components as fibrotic and fibro-fatty tissue, necrotic core, and dense calcified tissue [13, 14]. The accuracy of IVUS-RF compared to histo-pathology to detect the necrotic core and the dense calcium tissue was 88.3 and 96.5%, respectively [15]. Recent IVUS-RF studies showed controversial data about the coronary plaque composition related to clinical presentation of ACS and stable patients [16–18]. One study analyzing the plaque composition at the site with the minimum lumen area showed less necrotic core tissue in lesion sites with positive remodeling [19]. The aim of this study is to perform an IVUS-RF derived analysis of the lesion segment profile in ACS patients. Therefore, we compared the site with the minimum lumen area to the IVUS-RF derived most diseased lesion site.
Patients and methods Patient population The study cohort consisted of patients from the Global VH registry who underwent heart catheterization between spring 2004 and December 2006 and patients from the Cardiac Catheterization Laboratory of the Medizinische Klinik and Poliklinik of the Ludwig-Maximilians-Universita¨t in Munich, Germany. The VH-registry has a cross sectional, multi-center, and non-randomized design. The objective of the registry was to evaluate correlations between intravascular ultrasound radiofrequency analysis (IVUS-RF) data by lesion specific plaque composition analysis, patient-related clinical presentation and, cardiovascular risk factors. Coronary angiography and IVUS-RF were performed in all patients. The present study was conducted in accordance
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with the Declaration of Helsinki. Written informed consent was obtained from each patient. The present study was approved by the Local Medical Ethics Committee. We analyzed consecutive and unselected non-ST elevation myocardial infarction (NSTEMI) patients from the VHregistry and our own patient cohort in whom a pre-intervention IVUS pullback could be performed. The clinical characteristics and procedural data of the ACS patients are shown in Table 1. The used abbreviations and definitions are shown in Table 2. Methods IVUS-RF imaging was standardized by a commercially available electronic IVUS catheter (EagleEyeTM catheter;2.9F/20 MHz) and a continuous motorized pullback of 0.5 mm/s within the infarct-related coronary artery. Only native coronary arteries, without stented segments, were investigated by plaque composition analysis by pre-intervention studies. The plaque composition was determined by off-line IVUS-RF analysis. Tissue maps were reconstructed from RF data classifying coronary plaques into its major components as fibrotic (FI), fibro-fatty (FF), dense calcified (DC), and necrotic core (NC) [20]. The accuracy of this method for plaque composition analysis is described earlier [15, 21].
Table 1 Patient clinical and lesion characteristics Clinical presentation n = 48 pts.
ACS pts.
Age, years
60.6 ± 12.4
Male
30 (62.5%)
Hypertension
29 (60.4%)
Diabetes
11 (22.9%)
Insulin dependent
4 (8.3%)
Lipid disorder
30 (62.5%)
Prior MI
4 (8.3%)
Congestive heart failure
4 (8.3%)
Family history
21 (43.8%)
Current smoker Target coronary artery
22 (45.8%)
LAD
19 (39.6%)
RCA
24 (50.0%)
LCX
5 (10.4%)
Lesion Angiographic thrombus
18 (37.5%)
All data are expressed as numbers (%), except age, presented as mean ± SD MI myocardial infarction, LAD left anterior descending artery, RCA right coronary artery, LCX left circumflex artery
Clin Res Cardiol (2010) 99:83–91 Table 2 Abbreviations and definitions Clinical ACS
Acute coronary syndrome
NSTEMI
Non-ST-elevation myocardial infarction
CL
Culprit lesion, infarct-related
NCL
Non-culprit lesion, non-infarct-related
Lesion-site mla-CSA
Minimum lumen area-CSA
ws-CSA
Worst-site, most diseased-CSA, maximum necrotic core site (greatest % NC area)
Imaging parameter IVUS-RF
IVUS-radiofrequency analysis
EEM-area
External elastic membrane-area, vessel area
LA
Lumen area
PA
Plaque area
PB
Plaque burden
RI
Remodeling index
Plaque type FP
Fibrotic plaque
FC ThCFA
Fibrotic calcific plaque Thick cap fibroatheroma
TCFA
Thin cap fibroatheroma
Plaque components FI
Fibrotic
FF
Fibro-fatty
NC
Necrotic core
DC
Dense calcified
CSA cross-sectional area, IVUS intravascular ultrasound
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IVUS-RF plaque and lesion analysis The lesion analysis was performed within the IVUSinterrogated coronary artery for the infarct-related (culprit lesion, CL) and the non-infarct-related (non-culprit lesion, NCL) lesions in ACS patients as identified by angiographic morphology and IVUS findings. The lesion segments were defined by a plaque burden (plaque area/EEM) exceeding 40% or maximum plaque thickness C0.5 mm over three consecutive frames limited by the first reference site (\40% plaque burden) in the proximal and distal direction, as described previously [22]. The IVUS data, as the absolute coronary dimensions, external elastic membrane area (EEM), lumen area (LA), plaque area (PA), plaque burden (PB), and remodeling index (RI), were calculated as described previously [22]. The IVUS and IVUS-RF parameters are shown in Fig. 1. The plaque type was determined by IVUS-RF based on histo-pathological studies [6] as follows: fibrotic (FP) and fibrotic-calcific plaque (FC), thick cap fibroatheroma (ThCFA), and thin cap fibroatheroma (TCFA). The FP was defined by predominantly FI tissue with less NC, FF and DC tissue (\10%). The FC plaque was defined by DC tissue ([10%) with less NC tissue (\10%). ThCFA were defined by a confluent area of NC ([10%) not in contact with the coronary lumen on three consecutive frames compared to TCFA demonstrating a confluent area of NC ([10%) in contact with the coronary lumen [23, 24]. TCFA were divided according to the presence of calcium (C10% area) or presence of one or multiple necrotic layers.
Fig. 1 IVUS and IVUS-RF parameter. This figure shows IVUS and IVUS-RF images. Upper line: Large eccentric plaque morphology. The IVUS parameters are depicted. Lower line: The corresponding IVUSRF image depicts colour-coded the specific plaque components. The four major plaque components are represented with red for necrotic core, green for fibrotic area, yellow for fibro-fatty area and white for dense calcified tissue
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Within the lesion segment, the plaque type and plaque composition of specific lesion sites as the minimum lumen area—cross sectional area (mla-CSA) and the IVUS-RF derived most diseased site (worst site, ws-CSA) were analyzed. The ws-CSA was defined as the site with the maximum necrotic core tissue (greatest % NC area) within the interrogated lesion segment (CL and NCL). In addition, the IVUS-RF parameters were analyzed depending on the proximal or distal localization of the wsCSA related to the mla-CSA. Statistical analysis The clinical, procedural, and IVUS-RF data were analyzed using SAS statistical software (JMPÒ 7.0.1). The continuous variables were expressed as mean ± SD and the categorical data were expressed as proportions. The continuous data were compared using Student’s t-test for normally distributed data and a Mann–Whitney U test for skewed data. Intra-individual comparisons were performed using the Wilcoxon test. The comparison of categorical data and frequency of occurrence was performed with Fisher’s Exact test. A p value \0.05 was considered statistically significant.
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1.27 ± 1.59 mm2/, p = 0.377), vessel area (DVA, CL: 2.48 ± 3.03 mm2/NCL: 1.81 ± 2.44 mm2, p = 0.217), PA (DPA, CL: 0.92 ± 2.38 mm2/NCL: 0.54 ± 1.44 mm2, p = 0.310), and plaque burden (DPB, CL: 3.82 ± 6.24%/ NCL: 2.58 ± 5.51%, p = 0.286). Plaque composition profile The analysis of CL and NCL segments revealed significantly more absolute DC and NC tissues at the ws-CSA, whereas the relative plaque composition analysis showed a significantly higher amount of NC and DC tissues and a significantly lower amount of Fi and FF tissues in the wsCSA compared to the mla-CSA. The differentiation in CL and NCL segments demonstrated the same plaque composition pattern in both lesion groups, see Table 3. In the majority of the analyzed segments the ws-CSA was located proximal to the mla-CSA. This lesion pattern was more pronounced in the CL compared to the NCL segments. The ws-CSA was less frequently located distal to the mla-CSA, see Table 4. When the ws-CSA was located proximal to the mlaCSA, the amount of TCFA was not significantly different compared to the distal location (n = 31/47.7% vs. n = 10/ 43.5%, p = 0.834). The distance between the mla- and the ws-CSA was not significantly different in CL compared to
Results Lesion characteristics
Table 3 Plaque composition at the mla-CSA and the ws-CSA in culprit and non-culprit lesions
Beside the culprit lesions within the lesion segments of the ACS patients, 18 patients presented with 1 additional nonculprit lesion (NCL), 15 patients had 2 additional NCL and 7 patients had 3 NCL. In eight patients only the culprit lesion without any NCL was detected. The coronary interventions were mainly performed in the right coronary artery (RCA/50%) and the left anterior descending artery (LAD/39.6%). In 32/48 (66.7%) patients the CL segment compared to the NCL segments was located proximal.
Plaque composition
Lesion segment profile
mla-CSA
ws-CSA
p value
All lesions, n = 117 FI area, mm2
3.63 ± 2.66
3.57 ± 2.63
0.8745
FF area, mm2
1.04 ± 1.21
0.86 ± 1.06
0.3059
DC area, mm2
0.44 ± 0.52
0.69 ± 0.59
0.0015
2
NC area, mm FI, % FF, %
0.98 ± 1.10
1.42 ± 1.30
0.0049
59.26 ± 14.33 15.55 ± 11.43
54.43 ± 12.08 12.48 ± 9.52
0.0063 0.0377
DC, %
8.51 ± 11.09
11.18 ± 8.48
0.0346
NC, %
16.67 ± 12.02
21.92 ± 11.15
0.0007
Culprit lesions, n = 48
The ws-CSA had significantly larger EEM area (16.86 ± 5.45 mm2 vs. 14.87 ± 5.13 mm2, p = 0.009) and lumen area (6.90 ± 2.65 mm2 vs. 5.57 ± 2.29 mm2, p \ 0.001) compared to the mla-CSA. In addition, the ws-CSA revealed significantly more positive coronary remodeling (1.11 ± 0.17 vs. 1.02 ± 0.17, p = 0.001). The plaque area was not significantly different (9.96 ± 4.65 mm2 vs. 9.31 ± 4.44 mm2, p = 0.307). The difference of the lesion CSA dimensions between ws- and mla-CSA was analyzed after differentiation in CL (n = 48) and NCL (n = 69) for lumen area (DLA, CL: 1.56 ± 1.64 mm2/NCL:
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FI area, mm2
4.9 ± 3.14
5.0 ± 3.2
0.8706
FF area, mm2
1.37 ± 1.49
1.11 ± 1.20
0.4798
DC area, mm2
0.66 ± 0.63
0.95 ± 0.65
0.0624
NC area, mm2
1.53 ± 1.48
2.11 ± 1.55
0.0660
Non-culprit lesions, n = 69 FI area, mm2
2.92 ± 2.04
2.73 ± 1.74
0.5825
FF area, mm2
0.84 ± 0.97
0.71 ± 0.94
0.4075
DC area, mm2
0.31 ± 0.40
0.53 ± 0.50
0.0032
NC area, mm2
0.65 ± 0.62
1.00 ± 0.91
0.0109
All data are expressed as mean ± standard deviation or percentage (%)
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Table 4 Lesion segment analysis in ACS patients
Table 5 Plaque classification at the site of the mla- and ws-CSA in culprit and non-culprit lesions
Clinical presentation n = 48 pts. Culprit lesions TCFA, ws-CSA
Plaque type classification 48
Same Distal
ws-CSA
p value
Culprit lesions, n = 48 FP
13 (27.1%)
1 (2.1%)
0.0033
FC
3 (6.3%)
0 (0%)
0.2405
34 (70.8%)
ThCFA
16 (33.3%)
12 (25%)
0.6219
9 (18.8%)
TCFA
16 (33.3%)
35 (72.9%)
0.0007
FP FC
38 (55.1%) 3 (4.4%)
16 (23.2%) 3 (4.4%)
0.0002 1.000
ThCFA
15 (21.7%)
24 (34.8%)
0.0882
TCFA
13 (18.8%)
26 (37.7%)
0.0339
35 (72.9%)
Worst site vs. minimum lumen area-CSA Proximal
mla-CSA
5 (10.4%)
Non-culprit lesions
69
TCFA, ws-CSA
26 (37.7%)
Worst site vs. minimum lumen area-CSA Proximal Same
31 (44.9%) 20 (29%)
Distal
18 (26.1%)
Non-culprit lesions, n = 69
FP fibrotic plaque, FC fibro-calcific plaque, ThCFA thick cap fibroatheroma, TCFA thin cap fibroatheroma
Qualitative IVUS-RF analysis
Categorical data are expressed as number and frequencies (%) and tested with Fisher’s Exact test
NCL segments (5.7 ± 5.7 mm vs. 5.3 ± 5.5 mm, p = 0.490). The location of the ws-CSA did not determine the lesion length (proximal ws-CSA: 17 ± 9.4 mm vs. distal ws-CSA: 17.3 ± 11.2 mm, p = 0.798) or the distance to the mla-CSA (proximal ws-CSA: 6.1 ± 6.4 mm vs. distal ws-CSA: 4.4 ± 3.9 mm, p = 0.110).
Table 6 Lesion site analysis of TCFA lesions in ACS patients IVUS-RF parameter
mla-CSA n = 29
ws-CSA n = 61
p value
CSA, mm2
Plaque type classification The amount of TCFA lesions was significantly higher in CL compared to NCL of ACS patients (53.1 vs. 28.3%, p \ 0.01). TCFA lesions were significantly more frequent at sites of ws-CSA than at sites of mla-CSA in both CL (72.9 vs. 33.3%, p \ 0.001) and NCL (37.7 vs. 18.8%, p = 0.034). Significantly more fibrotic plaques were found at the mla-CSA compared to the ws-CSA (CL, 27.1 vs. 2.1%, p = 0.003 and NCL, 55.1 vs. 23.2%, p \ 0.001), see Table 5. The TCFA lesions at the ws-CSA compared to the mla-CSA showed significantly more lumen and vessel area. The absolute and relative plaque composition did not show any significant difference, see Table 6. The subdivision of TCFA lesions with multiple necrotic layers (n = 60) revealed a higher amount in the ws-CSA compared to the mla-CSA (n = 44/73.3% vs. n = 16/26.7%, p = 0.050). This type of TCFA at the ws-CSA was more often proximal located compared to the distal location (n = 31/51.7% vs. n = 16/26.7%, p \ 0.01). In 13 TCFA lesions the location was identical with the mla-CSA.
Discussion The present study performed a profile analysis of ACS lesions according to IVUS-RF derived plaque composition
Lumen area
4.82 ± 2.32
6.90 ± 2.73
0.0013
Vessel area Plaque area
13.77 ± 4.18 8.95 ± 3.40
17.46 ± 4.88 10.56 ± 4.42
0.0015 0.1067
Plaque burden, %
64.70 ± 10.58
59.85 ± 12.28
0.0888
CSA, mm2 FI area
2.72 ± 1.71
3.55 ± 2.53
0.1369
FF area
0.43 ± 0.48
0.70 ± 0.90
0.1632
DC area
0.96 ± 0.50
1.00 ± 0.56
0.7210
NC area
1.75 ± 1.36
1.83 ± 1.29
0.8015
FI area
45.96 ± 12.76
48.31 ± 10.78
0.3943
FF area
7.28 ± 7.09
9.68 ± 7.61
0.1819
IVUS-RF, %
DC area
17.62 ± 8.12
15.48 ± 7.05
0.2309
NC area
29.13 ± 12.15
26.53 ± 10.77
0.3352
Continuous data are presented as mean value ± standard deviation Plaque components: FI fibrous, FF fibro-fatty, DC dense calcified, NC necrotic core
analysis. The IVUS-RF reconstruction showed significantly different plaque dimensions and plaque composition at the most diseased site compared to the minimum lumen area site within the lesion segments of culprit and non-culprit lesions in ACS patients. The main difference was a positive coronary remodeling process, higher lumen area, and a higher amount of DC and NC tissue at the ws-CSA.
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Lesion characteristics In the majority of the patients multiple non-culprit lesions were detected beside the culprit lesion segment. In a considerable number of patients these lesions were classified as TCFA or ThCFA lesions, respectively. TCFA lesions are seen as high-risk lesions for plaque rupture according to histopathological studies [2, 3]. This finding corresponds to the incidence of multiple plaque ruptures in ACS patients as seen by recent angiographic and IVUS studies [25, 26]. The proximal location of the culprit compared to the nonculprit lesion in the majority of the analyzed patients of our study (n = 32/48 pts.; 66.7%) is confirmed by angiographic, IVUS, and histopathological studies [27–29]. IVUS-RF lesion profile NC tissue is seen as a risk factor for the evolution of highrisk lesions as TCFA and ThCFA and therefore according to histopathological studies as risk factor for plaque rupture. In our study the highest amount of NC tissue was not detected at the mla-site suggesting that in the majority of the ACS events the plaque ruptures are triggered distant to the mla-CSA. Only in the minority of the CL and NCL lesions in our study, the ws-CSA was identical with the mla-CSA (n = 29/24.8%). There exists a considerable length of distance between the ws-CSA and the mla-CSA. Previous IVUS-studies had shown a different location of the plaque rupture site and the minimum lumen area in ACS patients [11]. Our IVUS-RF analysis confirms this finding. In our study the ws-CSA was located more frequently proximal to the mla-CSA, but in a considerable number of lesions also distal. Since we can assume that the ws-CSA of the lesion segment represents the culprit site of the lesion, the significantly different lesion dimensions at the ws-CSA compared to the mla-CSA as seen in our study, confirm the known remodeling behavior of prerupture lesions that has been shown in earlier IVUS studies [12]. As shown in previous IVUS studies the minimum lumen area site does not necessarily represent the rupture site of the culprit or non-culprit lesion segment in the majority of the patients. According to these data the minimum lumen area site in our study is characterized by a higher amount of fibrotic tissue in absolute and relative measurements and a higher incidence of fibrotic plaques. This lesion pattern was not significantly different in the culprit and non-culprit lesions, respectively. Recent IVUS studies have shown the plaque rupture in the majority of the patients at the proximal third of the lesion segment, followed by distal and medial location. The proximal location of plaque rupture was related to obstructive thrombus formation in ACS patients [30]. In our study the ws-CSA was predominantly located proximal
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to the mla-CSA, especially in the CL segments (see Table 4). Lesion progression by thrombus formation Most of the plaque ruptures take place at the site of an underlying TCFA. The plaque rupture enables the thrombus formation after contact of the blood with the lipid-rich core of the plaque. These processes are triggered by inflammatory cells [31]. Histopathological studies showed that subclinical plaque ruptures usually do not lead to occlusive thrombus formation [32]. Owing to the thrombus formation post plaque rupture, the mural thrombi trigger collagen synthesis and contribute to plaque progression towards fibrotic plaque morphology [33]. Therefore, subclinical episodes of plaque rupture may explain the development of fibrous lesions beside the atheromatous, lipid-rich plaques. Histologic data showed that the majority of thrombotic events are clinically silent and lead to a clinical event after several plaque ruptures [34]. In addition, serial IVUS studies showed that healing processes of plaque ruptures can be responsible for lesion progression [35]. The data from our study showing mainly fibrotic plaque composition and fibrotic lesions proximal and distal to the worst-site CSA or culprit site could confirm this concept. The organization of thrombus material and its replacement by fibrous and collagen tissue as a consequence can lead to luminal obstruction possibly exceeding that of the culprit site, as shown in Fig. 2. According to histopathological studies the necrotic core is the main substrate for all ThCFA and TCFA lesions. After plaque rupture with subsequent thrombus formation, the lesion will either undergo progression of plaque burden and lead to stable angina or lead to ACS. In the majority of the patients the plaque rupture occurs at the site of previously ruptured plaques [34]. The IVUS-RF derived calcified TCFA lesion with multiple necrotic layers is the in vivo equivalent to this histopathological finding [6]. However, our analysis showed that this type of high-risk lesion was also found distant to the mla-CSA (proximal: n = 31/51.7% vs. distal: n = 16/26.7%, p \ 0.01) suggesting that the thrombotic organization can occur in proximal and distal directions. Potential clinical implications As a consequence, coronary angiography alone will not detect the exact location of the ws-CSA in the majority of the patients and therefore cannot predict the exact length of the lesion segment. We know from histo-pathological studies that the culprit lesion extends often further than the stented segment. In these patients a considerable risk
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Fig. 2 Relation of the ws-CSA of the lesion segment compared to the mla-CSA. This figure represents the predominantly lesion segment profile in culprit lesions of acute coronary syndrome patients. The worstsite (ws) cross-sectional area regarding the amount of necrotic and dense calcified tissue is located proximal to the minimum lumen area (mla). This site is the suspected site of the plaque rupture. a, b, and d exemplify fibrotic plaques. c depicts exemplary a thin cap fibroatheroma (TCFA) lesion with several layers of necrotic core. The mla-site is distant from the TCFA lesion. The IVUS mla can correspond to the angiographically visible minimum lumen diameter (mld)
exists for future thrombotic events. The reason for increased in-stent restenosis in ACS patients [36] might be the incomplete coverage of the high-risk lesion. Until now it is not clear as to how often we miss the culprit-site of the lesion segment during angiographic guidance of stent implantation. Besides, it is not clear if uncovered lesion segments with potential high-risk lesions have an impact on distal embolization, stent thrombosis, in-stentrestenosis, or plaque progression. Recent studies could show a significant relation between NC dimensions and markers for coronary microembolization [37]. The preintervention IVUS-RF analysis would have the potential to identify the whole segment length with inclusion of the IVUS-RF derived worst site CSA even if angiographically invisible. Limitations The limited resolution of the IVUS-RF analysis in the detection of the fibrous cap could lead to an overestimation of TCFA lesions and therefore lead to arbitrary decisions for plaque-type classification in a small number of patients regarding the thick and thin cap fibroatheroma. In this study only pre-interventional IVUS studies were included. The exclusion of tighter ACS lesions that cannot be crossed by an IVUS catheter may lead to an underestimation of the described differences. A differential diagnosis of soft plaque material and intraluminal organizing thrombotic tissue is not yet possible by radiofrequency analysis. Thrombus detection could be helpful to detect the exact extent and also origin of the plaque rupture.
Due to the limited resolution of IVUS-RF in the detection of fibrous cap, this modality alone is probably not sufficient for detecting TCFA. The combined use of optical coherence tomography and IVUS-RF might be a feasible approach for evaluating TCFA.
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