Relation of Ruptured Plaque Culprit Lesion Phenotype and Outcomes in Patients With ST Elevation Acute Myocardial Infarction

Relation of Ruptured Plaque Culprit Lesion Phenotype and Outcomes in Patients With ST Elevation Acute Myocardial Infarction Sang Wook Kim, MDa,*, Young Joon Hong, MDb, Gary S. Mintz, MDc, Sung Yun Lee, MDd, Jun Hyung Doh, MDd, Seong Hoon Lim, MDe, Hyun Jae Kang, MDf, Seung Woon Rha, MDg, Jung Sun Kim, MDh, Wang-Soo Lee, MDa, Seong Jin Oh, MDi, Sahng Lee, MDj, Joo Yong Hahn, MDk, Jin Bae Lee, MDl, Jang Ho Bae, MDm, Seung Ho Hur, MDn, Seung Hwan Han, MDo, Myung Ho Jeong, MDb, and Young Jo Kim, MDp We used virtual histology intravascular ultrasound (VH-IVUS) to assess culprit plaque rupture in 172 patients with ST-segment elevation acute myocardial infarction. VH-IVUSdefined thin-capped fibroatheroma (VH-TCFA) had necrotic core (NC) >10% of plaque area, plaque burden >40%, and NC in contact with the lumen for >3 image slices. Ruptured plaques were present in 72 patients, 61% of which were located in the proximal 30 mm of a coronary artery. Thirty-five were classified as VH-TCFA and 37 as non-VHTCFA. Vessel size, lesion length, plaque burden, minimal lumen area, and frequency of positive remodeling were similar in VH-TCFA and non-VH-TCFA. However, the NC areas within the rupture sites of VH-TCFAs were larger compared to non-VH-TCFAs (p ⴝ 0.002), while fibrofatty plaque areas were larger in non-VH-TCFAs (p <0.0001). Ruptured plaque cavity size was correlated with distal reference lumen area (r ⴝ 0.521, p ⴝ 0.00002), minimum lumen area (r ⴝ 0.595, p <0.0001), and plaque area (r ⴝ 0.267, p ⴝ 0.033). Sensitivity and specificity curve analysis showed that a minimum lumen area of 3.5 mm2, a distal reference lumen area of 7.5 mm2, and a maximum NC area of 35% best predicted plaque rupture. Although VH-TCFA (35 of 72) was the most frequent phenotype of plaque rupture in ST-segment elevation myocardial infarction, plaque rupture also occurred in non-VH-TCFA: pathologic intimal thickening (8 of 72), thick-capped fibroatheroma (1 of 72), and fibrotic (14 of 72) and fibrocalcified (14 of 72) plaque. In conclusion, not all culprit plaque ruptures in patients with ST-segment elevation myocardial infarction occur as a result of TCFA rupture; a prominent fibrofatty plaque, especially in a proximal vessel, may be another form of vulnerable plaque. Further study should identify additional factors causing plaque rupture. © 2012 Elsevier Inc. All rights reserved. (Am J Cardiol 2012;109: 794 –799) Rupture of a thin-capped fibroatheroma can lead to thrombosis, acute coronary syndromes, and sudden cardiac death. However, autopsy studies have suggested that nonthin-capped fibroatheromas may also be “vulnerable,” and rupture of a thin fibrous cap overlying a lipid core is not the only pathway to a coronary thrombus.1– 4 Conversely, healing of a ruptured plaque may be a mechanism of stenosis progression without causing an acute event,5 while sudden a

Chung-Ang University Hospital, Seoul; bChonnam National University Hospital, Gwangju, Korea; cCardiovascular Research Foundation, New York, New York; eInje University, Ilsan Paik Hospital, Ilsan; dDankook University Hospital, Cheonan; fSeoul National University Hospital; gKorea University, Guro Hospital; hYonsei University, Severance Hospital, Seoul; i NHIMC Ilsan Hospital, Ilsan; jEul Ji University Hospital, Daecheon; k Samsung Medical Center, Seoul; lCatholic University Medical Center, Daegu; mKonyang University Hospital, Daegeon; nKeimyung University Hospital, Daegu; oGacheon University, Gil Hospital, Incheon; and pYeungnam University Hospital, Daegu, Korea. Manuscript received August 8, 2011; revised manuscript received and accepted October 31, 2011. *Corresponding author: Tel: 822-62992871; fax: 822-8230160. E-mail address: [email protected] (S.W. Kim). 0002-9149/12/$ – see front matter © 2012 Elsevier Inc. All rights reserved. doi:10.1016/j.amjcard.2011.10.042

progression may indicate a more complex lesion, thrombus, plaque rupture, or erosion in the setting of an acute event.6,7 Virtual histology intravascular ultrasound (VH-IVUS) assesses plaque composition8 –11 and defines atherosclerotic lesion phenotype, including thin-capped fibroatheroma.12,13 There are only a few reports of the use of VH-IVUS in acute ST-segment elevation myocardial infarction (STEMI). In this study, we used VH-IVUS to evaluate the phenotype underlying culprit lesion plaque rupture in patients with STEMI who underwent primary percutaneous coronary intervention. Methods Overall, 200 consecutive, prospectively studied patients with acute STEMI underwent primary percutaneous coronary intervention with VH-IVUS imaging of the culprit lesion at 15 centers in Korea. Of these, 172 were amenable to analysis. Bifurcation lesions, ostial lesions, vein graft lesions, arteries with previous stent placement, and preIVUS debulking or plaque modification procedures were excluded. Standard coronary risk factors were collected, www.ajconline.org

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Figure 1. Ruptured plaque in (A) VH-TCFA and (B) non-VH-TCFA). mLAD ⫽ middle left anterior descending coronary artery; pLAD ⫽ proximal left anterior descending coronary artery; dRCA ⫽ distal right coronary artery; mRCA ⫽ middle right coronary artery; pRCA ⫽ proximal right coronary artery.

including age, gender, hypertension (medication treated only), diabetes mellitus (including medication-treated and diet-controlled diabetes or fasting blood glucose level ⬎126 mg/dl), hypercholesterolemia (medication treated or measured ⬎240 mg/dl), current smoking (within the past 12 months), and family history of coronary artery disease (myocardial infarction in a first-degree relative aged ⬍60 years). The protocol was approved by each institutional review board; written informed consent was obtained from all patients. Coronary angiography was performed after 200 ␮g of intracoronary nitroglycerin and analyzed with an automated edge detection algorithm (AI 1000; GE Medical Systems, Milwaukee, WI) using standard protocols. Minimal lumen diameter, % diameter stenosis, reference vessel diameter, and Thrombolysis In Myocardial Infarction (TIMI) grade were measured before intervention. The culprit lesion was identified by the combination of electrocardiographic findings, left ventricular wall motion abnormalities, and angiographic lesion morphology. Thrombus aspiration was performed before IVUS imaging using an aspiration catheter (Kaneka Corporation, Osaka, Japan) according to operator discretion, but typically for large thrombi. A commercially available VH-IVUS system (Volcano Therapeutics, Rancho Cordova, California) and 20-MHz transducers were used for all IVUS examinations. After intracoronary administration of 200 ␮g nitroglycerin, the IVUS catheter was advanced 10 mm distal to the target lesion, and imaging was performed retrograde to the

aorto-ostial junction using an electrocardiographically gated automatic pullback device. Grayscale IVUS analysis was performed according to the criteria of the American College of Cardiology clinical expert consensus document on IVUS.14 A ruptured plaque contained a cavity that communicated with the lumen with an overlying residual fibrous cap fragment. Positive remodeling was a lesion/mean reference external elastic membrane area ⬎1.05. Two experienced analysts (S.W.K, Y.J.H.) reviewed the VH-IVUS pullback to assess lesion phenotype and make precise measurements by defining the 2 standard VH-IVUS regions of interest: the inner border (lumen, excluding IVUS-detectable thrombus) and outer border (external elastic membrane). VH-IVUS analyses assessed fibrotic tissue, fibrofatty plaque, necrotic core (NC), and dense calcium, and each component was reported in absolute amounts and as percentages of plaque area. The mean plaque area was measured over the entire length of the lesion. Culprit lesion phenotype was classified as pathologic intimal thickening, VH-IVUS-defined thin-capped fibroatheroma (VH-TCFA), thick-capped fibroatheroma, and fibrotic and fibrocalcific plaque.15 Statistical analysis was performed using SAS version 9.1 (SAS Institute Inc., Cary, North Carolina). Continuous variables are presented as mean ⫾ SD, and data were normally distributed and compared using Student’s t test. Logistic regression identified variables to predict plaque rupture. Using sensitivity and (1 ⫺ specificity) curves, the optimal

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Figure 1. (continued)

threshold of vessel area was identified to predict plaque rupture. Receiver-operating characteristic curves were used to compare the accuracy of indicator variables. Multivariate logistic analysis was used to identify the most important factor to plaque rupture. A p value ⬍0.05 was considered statistically significant. Results Overall, plaque ruptured was observed in 72 of 172 (41%) patients with acute STEMI (Figure 1). Of these, 35 had an underlying phenotype of VH-TCFA, and 37 had non-VH-TCFA phenotype. Overall, 61% of ruptured plaques (44 of 72) were located in the proximal 30 mm of a coronary artery. Clinical demographics of overall cohort are listed in Table 1. As shown in Table 2, VH-TCFAs were identified in 37.8% of patients (65 of 172), while 62.2% (107 of 172) were non-VH-TCFAs. Plaque rupture was seen in 53.8% of VH-TCFAs (35 of 65) compared to 34.5% of non-VHTCFAs (37 of 107) (p ⫽ 0.009). Although a VH-TCFA (n ⫽ 35) was the most frequent phenotype underlying the 72 plaque ruptures in the 172 patients with STEMI, non-VHTCFA phenotype included pathologic intimal thickening in 8, thick-cap fibroatheroma in 1, fibrotic plaque in 14, and fibrocalcified plaque in 14. Vessel size, lesion length, plaque burden, minimal lumen area (MLA), and frequency of positive remodeling (57% [20 of 35] vs 56% [21 of 37], p ⫽ 0.57) were similar in VH-TCFA and non-VH-TCFA

plaque ruptures (Table 2). The sizes of ruptured plaque cavities were similar (p ⫽ 0.177), while the MLA of the underlying plaque at the rupture site (excluding the superficial thrombus) was smaller in non-VH-TCFA than in VHTCFA (p ⫽ 0.016). Ruptured plaque cavity size was correlated with distal reference lumen area (r ⫽ 0.521, p ⫽ 0.00002), MLA (r ⫽ 0.595, p ⬍0.0001), and plaque area (r ⫽ 0.267, p ⫽ 0.033). VH-IVUS findings are listed in Table 3. The % mean NC area (over the length of the lesion) was greater in the VH-TCFA than the non-VH-TCFA group (p ⫽ 0.002). Analysis of plaque composition at the rupture site showed larger % NC area in VH-TCFA (p ⬍0.0001), while % fibrofatty area was greater in non-VH-TCFA (p ⫽ 0.006). Sensitivity and specificity curve analysis showed that an MLA of 3.5 mm2, a distal reference lumen area of 7.5 mm2 (Figure 2), and a maximum NC area of 35% best predicted plaque rupture in STEMI culprit lesions. Receiver-operating characteristic analysis showed that the distal reference lumen area and maximal NC area were predictive of plaque rupture (distal reference lumen area: area under the curve [AUC] 0.636, 95% confidence interval [CI] 0.539-0.732; % maximal NC area: AUC 0.434, 95% CI 0.327-0.540; maximal NC area: AUC 0.630, 95% CI 0.507-0.753; MLA: AUC 0.544, 95% CI 0.443-0.644). However, multivariate logistic analysis identified distal reference lumen area to be the most important factors contributing to plaque rupture (Table 4).

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Table 2 Grayscale intravascular ultrasound measurements of overall cohort

Table 1 Clinical demographics of overall cohort Variable

VH-TCFA (n ⫽ 65)

Non-VH-TCFA (n ⫽ 107)

p Value

Age (years) Men Diabetes mellitus Hypertension Current smoker Hypercholesterolemia* Coronary artery treated LAD LCX RCA Number of narrowed coronary arteries; 1 2 3 TIMI grade 0 1 2 3 Before intervention Lesion length (mm) Minimal lumen diameter (mm) Reference vessel diameter (mm) Diameter stenosis (%)

60 ⫾ 11 55 (85%) 15 (23%) 28 (43%) 31 (48%) 20 (31%)

58 ⫾ 12 90 (84%) 23 (21%) 43 (40%) 60 (56%) 23 (22%)

0.439 1.0 0.838 0.731 0.491 0.284

24 10 31

71 12 24

0.001

0.255 27 17 21

38 44 25

33 5 10 17

45 6 26 30

20.16 ⫾ 8.89 0.54 ⫾ 0.73

21.78 ⫾ 9.93 0.76 ⫾ 0.54

0.359 0.067

3.32 ⫾ 0.74

3.04 ⫾ 0.55

0.028

84.27 ⫾ 19.03

75.09 ⫾ 17.66

0.009

0.789

Data are expressed as mean ⫾ SD or as number (percentage). LAD ⫽ left anterior descending coronary artery; LCX ⫽ left circumflex coronary artery; RCA ⫽ right coronary artery. * Medication treated or measured ⬎240 mg/dl.

The follow-up duration of the study population was 702 ⫾ 354 days after treatment with drug-eluting stents. In-hospital death occurred in 2 patients in the VH-TCFA group and in 3 patients in the non-VH-TCFA group; all were due to cardiogenic shock. However, no deaths were recorded during 1 year of follow-up. Follow-up coronary angiography was performed in 42 patients (58%). One patient had a nonfatal myocardial infarction, and no patient had stent thrombosis. The rate of target lesion revascularization was 1 in 42, and the rate of target vessel revascularization was 2 in 42. Overall, the cumulative rate of major adverse clinical events was low in treated ruptured plaques in patients with acute STEMI. Discussion The main findings of the present study are as follows: (1) non-VH-TCFAs are common in acute STEMI; (2) VHTCFAs show more frequent plaque rupture, but plaque ruptures also occur in patients with non-VH-TCFAs; and (3) the ruptured plaque VH-TCFA phenotype has a larger NC, while non-VH-TCFA ruptured plaque phenotypes have more fibrofatty plaque. Although plaque rupture is suspected in sudden coronary death from thrombosis, rupture of a thin fibrous cap overlying a lipid core is not always seen.1– 4 Conversely, healed

Variable Proximal reference segment EEM area (mm2) Lumen area (mm2) Plaque area (mm2) Plaque burden (%) Lesion site Lesion length (mm) Mean EEM area (mm2) Mean lumen area (mm2) Mean plaque area (mm2) Mean plaque burden (%) MLA site EEM area (mm2) Lumen area (mm2) Plaque area (mm2) Remodeling index Maximal NC site EEM area (mm2) Lumen area (mm2) Plaque area (mm2) Plaque burden (%) Remodeling index Distal reference segment EEM area (mm2) Lumen area (mm2) Plaque area (mm2)

Lesion length (mm) Proximal reference segment EEM area (mm2) Lumen area (mm2) Plaque area (mm2) Plaque burden (%) Ruptured plaque site EEM area (mm2) Lumen area (mm2) Plaque area (mm2) Plaque burden (%) Remodeling index Ruptured cavity (mm2) Distal reference segment EEM area (mm2) Lumen area (mm2) Plaque area (mm2) Plaque burden (%)

VH-TCFA (n ⫽ 65)

Non-VH-TCFA (n ⫽ 107)

p Value

20.5 ⫾ 5.4 10.8 ⫾ 4.1 9.7 ⫾ 4.1 46.8 ⫾ 14.0

18.3 ⫾ 6.2 10.6 ⫾ 4.7 7.7 ⫾ 3.0 42.1 ⫾ 11.3

0.019 0.731 0.001 0.033

22.2 ⫾ 10.0 16.7 ⫾ 5.7 6.4 ⫾ 2.7 10.3 ⫾ 4.0 60.5 ⫾ 9.7

23.7 ⫾ 11.5 15.1 ⫾ 6.1 6.2 ⫾ 2.8 8.9 ⫾ 3.9 56.6 ⫾ 10.3

0.459 0.094 0.686 0.030 0.017

17.2 ⫾ 6.7 3.9 ⫾ 2.2 13.4 ⫾ 5.9 1.0 ⫾ 0.3

14.5 ⫾ 6.2 3.8 ⫾ 2.1 10.6 ⫾ 5.0 0.9 ⫾ 0.2

0.009 0.893 0.003 0.328

18.9 ⫾ 5.9 6.6 ⫾ 2.8 12.3 ⫾ 4.5 64.7 ⫾ 10.9 1.1 ⫾ 0.3

16.4 ⫾ 6.5 6.0 ⫾ 3.0 10.5 ⫾ 4.6 63.2 ⫾ 11.1 1.1 ⫾ 0.2

0.014 0.188 0.013 0.379 0.402

14.0 ⫾ 6.2 7.8 ⫾ 3.5 6.2 ⫾ 3.7

13.0 ⫾ 6.3 7.5 ⫾ 3.9 5.5 ⫾ 3.4

0.332 0.631 0.241

Ruptured VH-TCFA (n ⫽ 35)

Ruptured non-VH-TCFA (n ⫽ 37)

18.8 ⫾ 6.9

22.2 ⫾ 9.9

0.143

21.4 ⫾ 5.6 11.1 ⫾ 4.1 10.3 ⫾ 4.2 47.8 ⫾ 12.1

18.8 ⫾ 5.2 10.1 ⫾ 3.4 8.72 ⫾ 3.5 45.9 ⫾ 12.7

0.063 0.305 0.108 0.540

19.2 ⫾ 5.3 7.4 ⫾ 2.7 11.8 ⫾ 3.8 61.1 ⫾ 10.6 1.1 ⫾ 0.2 1.1 ⫾ 1.0

17.5 ⫾ 6.1 5.9 ⫾ 2.3 11.7 ⫾ 5.5 64.2 ⫾ 13.4 1.1 ⫾ 0.3 0.8 ⫾ 0.7

0.240 0.016 0.916 0.295 0.711 0.177

15.7 ⫾ 6.8 8.8 ⫾ 4.3 6.9 ⫾ 3.7 42.8 ⫾ 13.3

13.8 ⫾ 5.5 7.7 ⫾ 3.1 6.1 ⫾ 3.3 42.5 ⫾ 11.8

0.219 0.269 0.329 0.936

EEM ⫽ external elastic membrane.

ruptures may be a mechanism of stenosis progression5 or may be seen in stable angina or asymptomatic patients.16 Symptoms may depend on the severity of the underlying stenosis or on thrombus formation, not just on plaque rupture.16,17 IVUS detects plaque rupture in approximately 30% to 70% of culprit lesions in acute myocardial infarction.16 –19 In the present study, ruptured plaques were observed in 41% of patients with STEMI. There was a larger NC in ruptured plaques associated with VH-TCFA versus more fibrofatty plaque and a worse underlying stenosis

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Table 3 Virtual histology intravascular ultrasound measurements Variable Lesion segment Mean fibrotic plaque (mm2) Mean fibrofatty plaque (mm2) Mean NC (mm2) Mean dense calcium (mm2) Mean fibrotic plaque (%) Mean fibrofatty plaque (%) Mean NC (%) Mean dense calcium (%) Maximal NC site Fibrotic plaque (mm2) Fibrofatty plaque (mm2) NC (mm2) Dense calcium (mm2) Fibrotic plaque (%) Fibrofatty plaque (%) NC (%) Dense calcium (%)

Lesion segment Mean fibrotic plaque (mm2) Mean fibrofatty plaque (mm2) Mean NC (mm2) Mean dense calcium (mm2) Mean fibrotic plaque (%) Mean fibrofatty plaque (%) Mean NC (%) Mean dense calcium (%) Ruptured plaque site Fibrotic plaque (mm2) Fibrofatty plaque (mm2) NC (mm2) Dense calcium (mm2) Fibrotic plaque (%) Fibrofatty plaque (%) NC (%) Dense calcium (%)

VH-TCFA (n ⫽ 65) 4.35 ⫾ 2.43 0.74 ⫾ 0.63

Non-VH-TCFA p Value (n ⫽ 107) 3.73 ⫾ 2.40 0.71 ⫾ 0.80

0.111 0.801

1.76 ⫾ 1.19 1.00 ⫾ 0.66 ⬍0.0001 0.71 ⫾ 0.56 0.53 ⫾ 0.44 0.033 56.30 ⫾ 11.08 59.82 ⫾ 13.07 0.067 8.85 ⫾ 5.13 10.70 ⫾ 6.18 0.04 22.18 ⫾ 7.98 16.05 ⫾ 7.24 ⬍0.0001 10.83 ⫾ 6.95 9.29 ⫾ 6.57 0.162 4.17 ⫾ 2.55 3.78 ⫾ 2.51 0.339 0.37 ⫾ 0.36 0.50 ⫾ 0.88 0.204 3.73 ⫾ 1.98 2.06 ⫾ 1.02 ⬍0.0001 1.26 ⫾ 1.03 0.99 ⫾ 0.76 0.07 42.21 ⫾ 12.47 49.30 ⫾ 15.85 0.002 3.84 ⫾ 3.09 5.57 ⫾ 5.16 0.019 39.46 ⫾ 10.04 29.81 ⫾ 9.91 ⬍0.0001 14.62 ⫾ 9.60 14.74 ⫾ 10.17 0.939 Ruptured VH-TCFA (n ⫽ 35)

Ruptured non-VH-TCFA (n ⫽ 37)

5.20 ⫾ 2.50 0.85 ⫾ 0.58

4.84 ⫾ 2.75 0.89 ⫾ 0.69

1.84 ⫾ 1.16 1.13 ⫾ 0.61 0.80 ⫾ 0.72 0.63 ⫾ 0.51 58.09 ⫾ 11.11 60.47 ⫾ 14.53 9.30 ⫾ 4.94 10.93 ⫾ 6.56 21.25 ⫾ 7.78 15.49 ⫾ 6.63 10.19 ⫾ 7.78 9.26 ⫾ 7.04

Figure 2. Sensitivity and specificity curves to predict plaque ruptures in 172 patients. Table 4 Logistic regression analysis of plaque rupture Variable

Standardized Estimate 2

0.586 0.814 0.004 0.293 0.459 0.263 0.002 0.613

4.80 ⫾ 2.58 4.96 ⫾ 2.77 0.812 0.57 ⫾ 0.55 1.27 ⫾ 1.26 0.006 2.64 ⫾ 1.29 1.61 ⫾ 1.10 0.001 0.79 ⫾ 0.70 0.59 ⫾ 0.63 0.214 52.25 ⫾ 13.54 58.12 ⫾ 12.02 0.066 5.68 ⫾ 4.91 12.29 ⫾ 8.65 0.0003 30.65 ⫾ 10.38 20.37 ⫾ 9.19 ⬍0.0001 11.35 ⫾ 11.20 9.20 ⫾ 9.73 0.407

NC ⫽ necrotic core.

(smaller underlying MLA) in non-VH-TCFA ruptures. Patients with STEMI and plaque rupture more frequently had underlying VH-TCFA phenotype, but combining patients with STEMI with and without plaque rupture, non-VHTCFA was more prevalent. Large occlusive thrombi can be found either angiographically or histologically in transmural infarction.20 –22 A fresh thrombus shows low echogenicity similar to that of saline, but an organized thrombus is more echogenic.23 The composition of intramural thrombus is often heterogenous, showing features of organization, lytic changes, and fresh thrombus in the same tissue fragment.24 The echogenic pattern of organized thrombus is more closely related to that of loose fibrous tissue.25 Thrombus aspiration is associated with a high rate of retrieval of thrombotic material.26 Mac-

Distal reference lumen area (mm ) MLA (mm2) Maximal fibrous plaque (%) Maximal fibrofatty plaque (%) Maximal NC (%) Maximal dense calcium (%)

0.2937 ⫺0.0978 0.00969 ⫺0.1454 ⫺0.0893 ⫺0.173

roscopic thrombi are removed in 70% to 90% of cases.27–29 Thrombus is typically included in the region of interest on VH-IVUS because it is hard to differentiate the border between organized thrombus and fibrous plaque.30 Although aspiration thrombectomy used in the present study, has a high success rate to remove intracoronary thrombus, the thrombi can complicate the grayscale and VH-IVUS analyses. Although we tried to exclude intraluminal thrombus when drawing VH-IVUS contours (especially lumen contours), some residual thrombus may have been included in the region of interest. The accuracy of VH-IVUS analysis is reduced in the setting of intracoronary thrombus. We could not assess coronary plaque erosion, because of the limited resolution of IVUS. We excluded ambiguous plaque ruptures with prominent thrombus. Thrombectomy itself can affect plaque morphology and the accuracy of the data. There might be cultural differences contributing to the primary findings in this Asian population. The right coronary artery was larger, but vessel size was predictive of plaque rupture and may represent a confounding factor. Not all culprit plaque ruptures in patients with STEMI occur as a result of thin-capped fibroatheroma rupture; some occur in the setting of other lesion phenotypes. VH-TCFAs are more common in larger vessels with a greater % NC area. However, prominent fibrofatty plaque, especially in a proximal vessel, may be another form of vulnerable plaque. Further study should identify additional factors causing plaque rupture. 1. Naghavi M, Libby P, Falk E, Casscells SW, Litovsky S, Rumberger J, Badimon JJ, Stefanadis C, Moreno P, Pasterkamp G, Fayad Z, Stone

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