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Insights from intravascular ultrasound on pathophysiology of acute coronary syndromes

Gary S. Mintz
Akiko Maehara

Arch Med Sci 2010; 6, 1A: S 15–S 24
Online publish date: 2010/01/26
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Of the various thrombosis-prone morphologies, thin-capped fibroatheromas account for the majority (approximately 70%) of events [1, 2]. Thin-capped fibroatheromas are reported to have the following pathologic features: (1) positive remodeling, (2) a fibrous cap less than 100 microns (and perhaps less than 65 microns) at its minimum thickness, (3) a large lipid/necrotic core often containing hemorrhage and/or calcification, (4) speckled or diffuse calcification (not enough to increase plaque stability although the absence of any calcium is also rare in rupture-prone plaques), (5) abundant intra-plaque vasovasorum, and (6) macrophage infiltration of the thin fibrous cap [3-5]. The resolution of intravascular ultrasound (IVUS, 100-150 microns, at best, axially) limits its ability to detect and measure a rupture-prone thin fibrous cap – especially when this fibrous cap is intact and the trailing edge indistinguishable from the underlying plaque. Intravascular ultrasound cannot detect plaque inflammation. Without contrast injection, IVUS cannot detect vasovasorum.
The next most common thrombosis-prone morphology is an erosion. An erosion is, to some extent, a histopathologic diagnosis of exclusion [3-5]. There is no fibrous cap, positive remodeling is absent, and there is minimal inflammation. Other than the lack of positive remodeling, none of the histopathologic features of erosions can be detected by IVUS. A more rare type of vulnerable plaque is a superficial calcified nodule within or very close to the fibrous cap of the plaque that can protrude through to rupture the cap. It is readily detected by IVUS.
To date, only one IVUS study has attempted to predict plaque instability [6]. Instead, to study lesion characteristics that are associated with plaque vulnerability, almost all IVUS analyses have either (1) compared stable vs. unstable patients or ruptured vs. nonruptured plaques or (2) have reported histopathologic-equivalent findings. While these approaches have limitations, there are important lessons.

During the development and progression of atherosclerosis, the external elastic membrane (EEM) cross-sectional area (CSA) may increase; this is termed “positive” or “outward” or “expansive” remodeling, and (among other things) it limits the impact of plaque accumulation on lumen compromise. In positively remodeled lesions there can be a large plaque burden despite little lumen compromise (Figure 1); a large plaque burden should not be confused with a significant stenosis. Conversely, the EEM CSA may decrease; this has been termed “negative” or “inward” or “constrictive” remodeling, and it can contribute to stenosis formation apart from plaque accumulation.
However, IVUS assessments of remodeling in unstable lesions have been based on studies performed at a single point in time comparing the lesion to proximal and/or distal reference segments, not on serial (baseline and follow-up) analyses. (Static and serial assessment of coronary remodeling may be discordant; therefore, the two cannot be used interchangeably when evaluating lesion stability. [7]) A number of definitions of remodeling have been proposed (Figure 1):
• lesion EEM CSA/reference EEM CSA; if the lesion EEM CSA is greater than the reference EEM CSA (index > 1.0), there is positive remodeling; if the lesion EEM CSA is smaller than the reference EEM CSA (index < 1.0), there is intermediate/ negative remodeling [8, 9];
• some authors set the above threshold higher to define positive remodeling as an index > 1.05, negative remodeling as an index < 0.95, and intermediate remodeling as an index between 0.95 and 1.05 [10];
• other authors have calculated a “theoretical interpolated” lesion EEM CSA based on the size of the proximal and distal reference EEM, tapering, and the axial location of the lesion relative to the two references; positive remodeling is a lesion EEM CSA greater than the “theoretical interpolated” EEM CSA [11, 12];
• Nishioka proposed the following classification: positive remodeling as a lesion EEM CSA greater than the proximal reference, negative remodeling as a lesion EEM CSA smaller than the distal reference, and intermediate remodeling as a lesion EEM CSA intermediate between the proximal and distal references [13].
One confusing aspect of these various definitions is that they can result in an individual lesion being classified as positive remodeling by one definition, but not by another one. This is because of (1) limitations resulting from reference site selection, reference site plaque burden, vessel tapering, etc.; (2) the fact that the reference segments have, themselves, undergone remodeling changes; and (3) the necessity to select a single lesion site cross-section for comparison with the reference segment while the remodeling index may vary along the length of the lesion. Nevertheless, assuming that consistent rules are followed, any one of these definitions is useful for studying populations or for assessing clinical-pathophysiologic correlations. Furthermore, lesions with the greatest positive or negative remodeling tend to be classified as such by all of the above definitions while the greatest disagreement occurs in lesions with intermediate remodeling (those with a remodeling index close to 1.0).
Positive remodeling in unstable lesions
In pathologic, angioscopic, radiofrequency-IVUS, and optical imaging studies, positive remodeling is strongly associated with unstable lesion morphologies. These have included plaque rupture, yellow plaque color, thrombus formation, presence and size of the lipid/necrotic core, and biomechanical lesion instability [5, 14-18]. There is also consistent IVUS data indicating that acute coronary syndrome (ACS) lesions more often have positive remodeling characteristics compared to either chronic stable angina lesions or to control plaques elsewhere in the coronary tree [10, 19-22]. Third, within the length of a single lesion, the site of plaque rupture has the largest remodeling index [23]. Finally, (1) positive remodeling has been associated with new lesion formation in patients with stable angina undergoing single vessel intervention [24]; (2) CK-MB elevation after percutaneous coronary intervention [25]; (3) no reflow in primary infarct angioplasty [26, 27]; (4) recurrent ischemia within one month after thrombolysis for acute myocardial infarction [28]; (5) target lesion revascularization in patients undergoing nonstent intervention [8]; (6) major adverse coronary events in patients with unstable angina undergoing any form of revascularization [29]; and (7) in-hospital complications and major adverse coronary events in patients with stable angina undergoing intervention [24]. Thus, the current cumulative evidence indicates that positively remodeled lesions are more biologically active than intermediate or negatively remodeled lesions; and positive remodeling is a marker for future clinical instability.
Nevertheless, not all culprit lesions in ACS patients are positively remodeled; for example, the absence of positive remodeling in an acute setting may indicate that the culprit lesion morphology is one of plaque erosion rather than rupture, especially if there are no IVUS features of a ruptured plaque. There is evidence that diabetes mellitus and advanced patient age are associated with less positive remodeling [30, 31].

Plaque composition
Grey scale IVUS studies consistently show more hypoechoic plaque in lesions of ACS patients compared to patients with stable angina (Figure 1) [10, 32-34]. However, greyscale IVUS cannot reliably assess either the lipid content or the necrotic core of a plaque even using sophisticated image densitometric analysis [35].
Extensive calcification is uncommon in most IVUS studies of unstable lesions [10, 32-34]. Similarly, in one necropsy series of patients after sudden coronary deaths, over 50% of thin-cap atheromas showed either no calcium or only speckled calcium while 65% of actual ruptures demonstrated speckled calcium [4]. Finally, in vitro biomechanical models have shown that in contrast to lipid pools which dramatically increase fibrous cap stresses, calcium does not seem to affect the mechanical stability of the atheroma although it does appear that mildly to moderately calcified plaques are the ones most prone to rupture [5, 36]. Recently IVUS analyses have suggested that spotty calcification – multiple, small-sized calcium deposits – is more common in acute myocardial infarction lesions [37, 38]. Radiofrequency IVUS analysis suggests that these small calcium deposits may be evidence of previous plaque rupture (the necrotic core “dumps” calcium).
There is, therefore, a paradox. Electron-beam computed tomographic (EBCT) studies have shown that the magnitude of coronary calcium is predictive of coronary events [39, 40]. If IVUS studies show that calcium is not related to plaque instability and that calcium is less common or less dense in plaques associated with ACS, what is the explanation for the predictive value of EBCT coronary calcium and subsequent events? Both pathologic and IVUS studies have shown that coronary calcium rarely occurs in the absence of coronary atherosclerosis and that overall plaque burden is roughly proportional to the amount of calcium [41-43]. Total arterial plaque burden is an important determinant of events and patient outcomes [1, 2]; presumably, a greater plaque burden increases the probability that an unstable lesion will develop.
Recent studies have focused on attenuated plaque – hypoechoic plaque with deep ultrasound attenuation – in patients with ACS (Figure 2). In an as yet unpublished study (Lee S-Y, personal communication) attenuated plaque was observed in 39.6% of STEMI vs. 17.6% of non-STEMI, but in no patients with stable angina. In ACS patients with attenuated plaques (1) the level of c-reactive protein (CRP) was higher; (2) angiographic thrombus and initial coronary flow < TIMI 2 were more common; and (3) and IVUS thrombus, positive remodeling, and plaque rupture were more common. Attenuated plaque appears to contain thrombus and microcalcification and to be associated with an increased risk of distal embolization post-intervention [44].
Finally, while the diagnosis of thrombus by IVUS must be considered presumptive [9], many studies have also reported more IVUS-evident thrombus in ACS lesions [45, 46] ACS patients who are troponin (+) have more evidence of thrombus than ACS patients who are troponin (–) [47]. The association of thrombus and clinical instability in patients with ruptured plaques has also been reported by Maehara et al. [23].

Plaque rupture
Intravascular ultrasound features of a ruptured plaque are consistent with histology – a cavity that communicated with the lumen with an overlying residual fibrous cap fragment (Figure 3) [22, 23, 48-51]. The highest rates of IVUS-detected plaque ruptures in ACS patients approach the frequency found on autopsy. It is unclear why the post-rupture fibrous cap remnant is easier to see than the fibrotic cap pre-rupture. Possibilities include (1) the remnant is thicker than pre-rupture similar to a rubber band that has been stretched and then released, (2) plaque and thrombus components adhere to the remnant increasing its thickness and echogenecity, and (3) the remnant is surrounded by blood and not other plaque components unless the cavity fills with thrombus to create limitations similar to pre-rupture.
In one large series of 300 IVUS plaque ruptures in 257 arteries in 254 patients, approximately two-third of fibrous caps ruptures were at the lateral attachment to the vessel wall, and one-third rupture in the middle of the fibrotic cap [23]. Rupture in the middle of the fibrous cap requires significantly more stress compared to rupture at the lateral attachment to the vessel wall. Almost all angiographic complex lesions – either ulceration, intimal flap, lumen irregularity, thrombus, and aneurysm – are associated with IVUS ruptured plaques validating the commonly used Ambrose angiographic identification of ACS lesions [23, 52, 53]. However, the converse is not true; and angiography can miss plaque ruptures especially multiple discrete plaque ruptures in the same artery.
Von Birgelen et al. showed that the size of the ruptured plaque cavity was larger in lesions with positive remodeling and had a linear relation with lesion plaque and EEM size and with the reference dimensions, but not with the degree of lumen narrowing [54]. Unlike IVUS, histopathologic necropsy study rarely shows a distinct cavity (Virmani R, personal communication). In vivo coronary flow may displace the flap into the lumen (IVUS), or in vitro the flap may be displaced toward the residual plaque (histology).

Culprit and non-culprit ruptured plaques
Intravascular ultrasound studies have reported culprit lesion ruptured plaques in a varying percentage of ACS patients that seems to average slightly less than 50% [51, 55-57]. Rioufol et al. reported a series of 24 acute coronary syndrome patients with three-vessel IVUS imaging [51]. In this report there were 50 ruptured plaques: 9 (37.5%) within the culprit lesion and 41 at nonculprit sites including 16 patients with ruptures in two arteries and 3 patients with ruptures in all three arteries. Thus, surprisingly, most of the ruptured plaques were at sites remote from the culprit lesion; and 79% of patients had a secondary (remote) plaque rupture. However, these findings have not been confirmed by other investigators. For example, Hong et al. studied all three major epicardial arteries in 235 patients: 122 during acute infarct intervention and 113 in patients with stable angina. Primary plaque ruptures were present in 80 infarct patients (66%) and in 31 stable angina patients (27%); secondary (non-infarct-related or non-target artery) plaque ruptures were seen in 21 patients with acute myocardial infarction (17%) and in 6 patients with stable angina (5%) [57]. Studies by Tanaka et al. and Sumitsuji et al. were more in keeping with the report by Hong than the report by Rioufol [58, 59].
There are several possible reasons for the varying frequency of primary and secondary plaque ruptures among these different studies: (1) errors in identifying the culprit site; (2) the presence of thrombi that obscured the ruptured plaque cavity and the fibrous cap remnant; (3) the limited sensitivity of IVUS in detecting plaque rupture, especially small plaque ruptures; (4) lesions responsible for symptomatic ACS may not contain ruptured plaques, but merely large, bulky, hypoechoic plaques or erosive morphology; (5) some fibrous cap remnants may be below the threshold of IVUS resolution or lie too close to the transducer; and/or (6) some plaque ruptures may have an atypical IVUS appearance. However, there does appear to be an association between ACS and multiple plaque ruptures (regardless of the frequency) and between CRP and plaque rupture in ACS patients [56-58].
Symptomatic versus asymptomatic ruptured plaques
Not all ruptured plaques are associated with acute events [23]. Furthermore, secondary, non-culprit plaque ruptures are, by definition, asympto-matic; and there is now serial IVUS evidence that nonculprit ruptured plaques can heal or progress to form a stenosis without causing an acute event [60, 61] supporting the hypothesis that plaque rupture may be one of the mechanisms of stenosis progression, even in the absence of an acute event [62-65].
Fujii et al. compared the morphology of culprit ruptured plaques in ACS patients with “incidental” ruptured plaques [46]. Multivariate analysis identified smaller minimum lumen area and presence of thrombus as independent predictors of plaque ruptures that caused ACS events (Figure 4). This suggested that plaque rupture, itself, did not lead to symptoms. Instead, it was the association of plaque rupture with a smaller lumen area and/or lumen-compromising thrombus formation that led to acute symptoms. However, Maehara et al. showed that the minimum lumen area was usually not at the rupture site, but proximal to the minimum lumen site in 47% and distal to the minimum lumen site in 27% [23].
Most lesions causing an acute event arise from previous angiographically mild stenoses. This has lead to the misconception that vulnerable plaques are insignificant plaques. Fujii et al. used IVUS to study 112 ruptured plaques to create a pre-rupture “profile” of vulnerable plaques [66]. The narrowest coefficient of variance were for lesion EEM area, maximum plaque thickness, and plaque burden; reference lumen area; and remodeling index; conversely, there was a great variability in measures of calcification and lumen compromise (minimum lumen area and area stenosis). Thus, symptomatic plaque ruptures did not occur at minimal disease sites. Rather, vulnerable (rupture-prone) plaques predictably had significant plaque accumulation and remodeling and occurred in larger arteries. It was only the degree of lumen compromise that was variable. Furthermore, both angiographic and IVUS studies have shown that the likelihood that any one lesion will lead to an event is related to its baseline stenosis severity [67-69]. This is nicely explained by the following statement from Kern and Meier: “Because the aggregate risk of rupture associated with many non-significant lesions (each with an admittedly lower individual risk potential) exceeds that of the fewer significant lesions, a myocardial infarction will more likely originate from a nonsignificant lesion” [70]. Thus, lumen dimensions should not be ignored in assessing unstable lesions; and chronically stenotic plaques with severe calcification, old thrombus, and eccentric lumens are included in the list of vulnerable plaque types [1, 2].
Ruptured plaque location
Hong et al. reported the location of culprit and secondary plaque ruptures in 392 patients, 231 with ACS and 161 with stable angina [71]. The distance between each coronary plaque rupture segment and the respective coronary ostium was measured with motorized IVUS transducer pullback. Overall, 83% of LAD plaque ruptures were predominantly located between 10 and 40 mm from the LAD ostium, LCX plaque ruptures were evenly distributed in the entire LCX tree, and 48% of RCA plaque ruptures were located between 10 and 40 mm from the RCA ostium and another 32% were located >70 mm from the ostium (Figure 5). Wang et al. reported the angiographic location of acute epicrdial thrombosis in 208 patients with STEMI [72]; occlusions tended to cluster within the proximal third of each of the vessels: LAD, LCX, and RCA. The difference between the angiographic study of Wang et al. and the IVUS study of Hong et al. was attributed to the paucity of sidebranches in the RCA leading to retrograde propagation of post-rupture thrombosis so that the site of acute angiographic occlusion in the RCA was often proximal to the more-distal site of plaque rupture.

Predicting vulnerable plaques
As mentioned at the beginning of this review, only one study has attempted to use greyscale IVUS to predict plaque instability. Yamagishi et al. retrospectively examined 114 coronary sites in 106 patients without significant stenosis by angiography (< 50% diameter stenosis) [6]. During the follow-up period of 21.8 ±6.4 months, 12 patients had an acute coronary event at a previously examined coronary plaque. These pre-existing plaques were eccentric with a plaque burden of 67 ±9% and a lumen area of 6.7 ±3.0 mm2, and eight of them had a shallow hypoechoic area. While the many IVUS studies of unstable and/or ruptured plaques and patients with ACS have shown the consistent results summarized above, no one has reproduced these prospective observations.
Recent radiofrequency-based, IVUS-derived technologies such as palpography and virtual histology are being studied for their potential to predict individual lesion plaque rupture. The PROSPECT Trial enrolled 700 patients with an ACS event, and three-vessel IVUS imaging was performed after treatment of the culprit lesion in order to relate baseline imaging – angiography, IVUS, and the new radiofrequency-IVUS derived technologies of palpography and virtual histology – to late events in an attempt to predict patients and lesions at risk for subsequent ACS.

1. Naghavi M, Libby P, Falk E, et al. From vulnerable plaque to vulnerable patient: a call for new definitions and risk assessment strategies: Part I. Circulation 2003; 108: 1664-72.
2. Naghavi M, Libby P, Falk E, et al. From vulnerable plaque to vulnerable patient: a call for new definitions and risk assessment strategies: Part II. Circulation 2003; 108: 1772-8.
3. Virmani R, Kolodgie FD, Burke AP, Farb A, Schwartz SM. Lessons from sudden coronary death: a comprehensive morphological classification scheme for atherosclerotic lesions. Arterioscler Thromb Vasc Biol 2000; 20: 1262-75.
4. Kolodgie FD, Burke AP, Farb A, et al. The thin-cap fibroatheroma: a type of vulnerable plaque: the major precursor lesion to acute coronary syndromes. Curr Opin Cardiol 2001; 16: 285-92.
5. Burke AP, Virmani R, Galis Z, Haudenschild CC, Muller JE. 34th Bethesda Conference: Task force #2 – What is the pathologic basis for new atherosclerosis imaging techniques? J Am Coll Cardiol 2003; 41: 1874-86.
6. Yamagishi M, Terashima M, Awano K, et al. Morphology of vulnerable coronary plaque: insights from follow-up of patients examined by intravascular ultrasound before an acute coronary syndrome. J Am Coll Cardiol 2000; 35: 106-11.
7. Sipahi I, Tuzcu EM, Schoenhagen P, et al. Static and serial assessments of coronary arterial remodeling are discordant: an intravascular ultrasound analysis from the Reversal of Atherosclerosis with Aggressive Lipid Lowering (REVERSAL) trial. Am Heart J 2006; 152: 544-50.
8. Dangas G, Mintz GS, Mehran R, et al. Preintervention arterial remodeling as an independent predictor of target-lesion revascularization after nonstent coronary intervention: an analysis of 777 lesions with intravascular ultrasound imaging. Circulation 1999; 99: 3149-54.
9. Mintz GS, Nissen SE, Anderson WD, et al. American College of Cardiology Clinical Expert Consensus Document on Standards for Acquisition, Measurement and Reporting of Intravascular Ultrasound Studies (IVUS). A report of the American College of Cardiology Task Force on Clinical Expert Consensus Documents. J Am Coll Cardiol 2001; 37: 1478-92.
10. Schoenhagen P, Ziada KM, Kapadia SR, Crowe TD, Nissen SE, Tuzcu EM. Extent and direction of arterial remodeling in stable versus unstable coronary syndromes: an intravascular ultrasound study. Circulation 2000; 101: 598-603.
11. Burke AP, Kolodgie FD, Farb A, Weber D, Virmani R. Morphological predictors of arterial remodeling in coronary atherosclerosis. Circulation 2002; 105: 297-303.
12. Iyisoy A, Schoenhagen P, Balghith M, et al. Remodeling pattern within diseased coronary segments as evidenced by intravascular ultrasound. Am J Cardiol 2002; 90: 636-8.
13. Nishioka T, Luo H, Eigler NL, Berglund H, Kim CJ, Siegel RJ. Contribution of inadequate compensatory enlargement to development of human coronary artery stenosis: an in vivo intravascular ultrasound study. J Am Coll Cardiol 1996; 27: 1571-6.
14. Smits PC, Pasterkamp G, de Jaegere PP, de Feyter PJ, Borst C. Angioscopic complex lesions are predominantly compensatory enlarged: an angioscopy and intracoronary ultrasound study. Cardiovasc Res 1999; 41: 458-64.
15. Takano M, Mizuno K, Okamatsu K, Yokoyama S, Ohba T, Sakai S. Mechanical and structural characteristics of vulnerable plaques: analysis by coronary angioscopy and intravascular ultrasound. J Am Coll Cardiol 2001; 38: 99-104.
16. Rodriguez-Granillo GA, Serruys PW, Garcia-Garcia HM, et al. Coronary artery remodelling is related to plaque composition. Heart 2006; 92: 388-91.
17. Kume T, Okura H, Kawamoto T, et al. Relationship between coronary remodeling and plaque characterization in patients without clinical evidence of coronary artery disease. Atherosclerosis 2008; 197: 799-805.
18. Ohayon J, Finet G, Gharib AM, et al. Necrotic core thickness and positive arterial remodeling index: emergent biomechanical factors for evaluating the risk of plaque rupture. Am J Physiol Heart Circ Physiol 2008; 295: H717-27.
19. Gyöngyösi M, Yang P, Hassan A, et al. Arterial remodelling of native human coronary arteries in patients with unstable angina pectoris: a prospective intravascular ultrasound study. Heart 1999; 82: 68-74.
20. Nakamura M, Nishikawa H, Mukai S, et al. Impact of coronary artery remodeling on clinical presentation of coronary artery disease: an intravascular ultrasound study. J Am Coll Cardiol 2001; 37: 63-9.
21. Schoenhagen P, Vince DG, Ziada KM, et al. Association of arterial expansion (expansive remodeling) of bifurcation lesions determined by intravascular ultrasonography with unstable clinical presentation. Am J Cardiol 2001; 88: 785-7.
22. von Birgelen C, Klinkhart W, Mintz GS, et al. Plaque distribution and vascular remodeling of ruptured and nonruptured coronary plaques in the same vessel: an intravascular ultrasound study in vivo. J Am Coll Cardiol 2001; 37: 1864-70.
23. Maehara A, Mintz GS, Bui AB, et al. Morphologic and angiographic features of coronary plaque rupture detected by intravascular ultrasound. J Am Coll Cardiol 2002; 40: 904-10.
24. Wexberg P, Gyöngyösi M, Sperker W, et al. Pre-existing arterial remodeling is associated with in-hospital and late adverse cardiac events after coronary interventions in patients with stable angina pectoris. J Am Coll Cardiol 2000; 36: 1860-9.
25. Mehran R, Dangas G, Mintz GS, et al. Atherosclerotic plaque burden and CK-MB enzyme elevation after coronary interventions: intravascular ultrasound study of 2256 patients. Circulation 2000; 101: 604-10.
26. Tanaka A, Kawarabayashi T, Nishibori Y, et al. No-reflow phenomenon and lesion morphology in patients with acute myocardial infarction. Circulation 2002; 105: 2148-52.
27. Kotani J, Mintz GS, Castagna MT, et al. Usefulness of preprocedural coronary lesion morphology as assessed by intravasuclar ultrasound in predicting thrombolysis in myocardial infarction frame count after percutaneous coronary intervention in patients with Q-wave acute myocardial infarction. Am J Cardiol 2003; 91: 870-2.
28. Gyöngyösi M, Wexberg P, Kiss K, et al. Adaptive remodeling of the infarct-related artery is associated with recurrent ischemic events after thrombolysis in acute myocardial infarction. Coron Artery Dis 2001; 12: 167-72.
29. Gyongyosi M, Yang P, Hassan A, et al. Intravascular ultrasound predictors of major adverse cardiac events in patients with unstable angina. Clin Cardiol 2000; 23: 507-15.
30. Hassani SE, Mintz GS, Fong HS, et al. Negative remodeling and calcified plaque in octogenarians with acute myocardial infarction: an intravascular ultrasound analysis. J Am Coll Cardiol 2006; 47: 2413-9.
31. Nicholls SJ, Tuzcu EM, Kalidindi S, et al. Effect of diabetes on progression of coronary atherosclerosis and arterial remodeling: a pooled analysis of 5 intravascular ultrasound trials. J Am Coll Cardiol 2008; 52: 255-62.
32. Hodgson JM, Reddy KG, Suneja R, Nair RN, Lesnefsky EJ, Sheehan HM. Intracoronary ultrasound imaging: correlation of plaque morphology with angiography, clinical syndrome and procedural results in patients undergoing coronary angioplasty. J Am Coll Cardiol 1993; 21: 35-44.
33. Rasheed Q, Nair RN, Sheehan HM, Hodgson JM. Coronary artery plaque morphology in stable angina and subsets of unstable angina: an in vivo intracoronary ultrasound study. Int J Card Imaging 1995; 11: 89-95.
34. Fukuda D, Kawarabayashi T, Tanaka A, et al. Lesion characteristics of acute myocardial infarction: an investigation with intravascular ultrasound. Heart 2001; 85: 402-6.
35. Prati F, Arbustini E, Labellarte A, et al. Correlation between high frequency intravascular ultrasound and histomorphology in human coronary arteries. Heart 2001; 85: 567-70.
36. Huang H, Virmani R, Younis H, Burke AP, Kamm RD, Lee RT. The impact of calcification on the biomechanical stability of atherosclerotic plaques. Circulation 2001; 103: 1051-6.
37. Ehara S, Kobayashi Y, Yoshiyama M, et al. Spotty calcification typifies the culprit plaque in patients with acute myocardial infarction: an intravascular ultrasound study. Circulation 2004; 110: 3424-9.
38. Fujii K, Carlier SG, Mintz GS, et al. Intravascular ultrasound study of patterns of calcium in ruptured coronary plaques. Am J Cardiol 2005; 96: 352-7.
39. Arad Y, Spadaro LA, Goodman K, Newstein D, Guerci AD. Prediction of coronary events with electron beam computed tomography. J Am Coll Cardiol 2000; 36: 1253-60.
40. Guerci AD, Arad Y. Electron beam computed tomography for the diagnosis and prognosis of coronary artery disease. Circulation 2001; 103: E87-7.
41. Mintz GS, Pichard AD, Popma JJ, et al. Determinants and correlates of target lesion calcium in coronary artery disease: a clinical, angiographic and intravascular ultrasound study. J Am Coll Cardiol 1997; 29: 268-74.
42. Sangiorgi G, Rumberger JA, Severson A, et al. Arterial calcification and not lumen stenosis is highly correlated with atherosclerotic plaque burden in humans: a histologic study of 723 coronary artery segments using nondecalcifying methodology. J Am Coll Cardiol 1998; 31: 126-33.
43. Tinana A, Mintz GS, Weissman NJ. Volumetric intravascular ultrasound quantification of the amount of atherosclerosis and calcium in nonstenotic arterial segments. Am J Cardiol 2002; 89: 757-60.
44. Okura H, Taguchi H, Kubo T, et al. Atherosclerotic plaque with ultrasonic attenuation affects coronary reflow and infarct size in patients with acute coronary syndrome: an intravascular ultrasound study. Circ J 2007; 71: 648-53.
45. Hodgson JM, Reddy KG, Suneja R, Nair RN, Lesnefsky EJ, Sheehan HM. Intracoronary ultrasound imaging: correlation of plaque morphology with angiography, clinical syndrome and procedural results in patients undergoing coronary angioplasty. J Am Coll Cardiol 1993; 21: 35-44.
46. Fujii K, Kobayashi Y, Mintz GS, et al. Intravascular ultrasound assessment of ulcerated ruptured plaques: a comparison of culprit and nonculprit lesions of patients with acute coronary syndromes and lesions in patients without acute coronary syndromes. Circulation 2003; 108: 2473-8.
47. Fuchs S, Stabile E, Mintz GS, et al. Intravascular ultrasound findings in patients with acute coronary syndromes with and without elevated troponin I level. Am J Cardiol 2002; 89: 1111-3.
48. Ge J, Chirillo F, Schwedtmann J, et al. Screening of ruptured plaques in patients with coronary artery disease by intravascular ultrasound. Heart 1999; 81: 621-7.
49. Nagai T, Luo H, Atar S, et al. Intravascular ultrasound imaging of ruptured atherosclerotic plaques in coronary arteries. Am J Cardiol 1999; 83: 135-7.
50. von Birgelen C, Klinkhart W, Mintz GS, et al. Size of emptied plaque cavity following spontaneous rupture is related to coronary dimensions, not to the degree of lumen narrowing. A study with intravascular ultrasound in vivo. Heart 2000; 84: 483-8.
51. Rioufol G, Finet G, Ginon I, et al. Multiple atherosclerotic plaque rupture in acute coronary syndrome: a three-vessel intravascular ultrasound study. Circulation 2002; 106: 804-8.
52. Ambrose JA, Winters SL, Arora RR, et al. Coronary angiographic morphology in myocardial infarction: a link between the pathogenesis of unstable angina and myocardial infarction. J Am Coll Cardiol 1985; 6: 1233-8.
53. Ambrose JA, Winters SL, Arora RR, et al. Angiographic evolution of coronary artery morphology in unstable angina. J Am Coll Cardiol 1986; 7: 472-8.
54. von Birgelen C, Klinkhart W, Mintz GS, et al. Size of emptied plaque cavity following spontaneous rupture is related to coronary dimensions, not to the degree of lumen narrowing. A study with intravascular ultrasound in vivo. Heart 2000; 84: 483-8.
55. Fukuda D, Kawarabayashi T, Tanaka A, et al. Lesion characteristics of acute myocardial infarction: an investigation with intravascular ultrasound. Heart 2001; 85: 402-6.
56. Sano T, Tanaka A, Namba M, et al. C-reactive protein and lesion morphology in patients with acute myocardial infarction. Circulation 2003; 108: 282-5.
57. Hong MK, Mintz GS, Lee CW, et al. Comparison of coronary plaque rupture between stable angina and acute myocardial infarction: a three-vessel intravascular ultrasound study in 235 patients. Circulation 2004; 110: 928-33.
58. Tanaka A, Shimada K, Sano T, et al. Multiple plaque rupture and C-reactive protein in acute myocardial infarction. J Am Coll Cardiol 2005; 45: 1594-9.
59. Sumitsuji S, Kobayashi Y, Okura H, et al. Multiple plaque ruptures are not frequent in acute coronary syndrome: A three-vessel intravascular ultrasound study. J Am Coll Cardiol 2004; 43: 74A.
60. Rioufol G, Gilard M, Finet G, Ginon I, Boschat J, André-Fouët X. Evolution of spontaneous atherosclerotic plaque rupture with medical therapy: long-term follow-up with intravascular ultrasound. Circulation 2004; 110: 2875-80.
61. Hong MK, Mintz GS, Lee CW, et al. Serial intravascular ultrasound evidence of both plaque stabilization and lesion progression in patients with ruptured coronary plaques: effects of statin therapy on ruptured coronary plaque. Atherosclerosis 2007; 191: 107-14.
62. Kaski JC, Chester MR, Chen L, Katritsis D. Rapid angiographic progression of coronary artery disease in patients with angina pectoris. The role of complex stenosis morphology. Circulation 1995; 92: 2058-65.
63. Chester MR, Chen L, Kaski JC. The natural history of unheralded complex coronary plaques. J Am Coll Cardiol 1996; 28: 604-8.
64. Yokoya K, Takatsu H, Suzuki T, et al. Process of progression of coronary artery lesions from mild or moderate stenosis to moderate or severe stenosis: A study based on four serial coronary arteriograms per year. Circulation 1999; 100: 903-9.
65. Burke AP, Kolodgie FD, Farb A, et al. Healed plaque ruptures and sudden coronary death: evidence that subclinical rupture has a role in plaque progression. Circulation 2001; 103: 934-40.
66. Fujii K, Mintz GS, Carlier SG, et al. Intravascular ultrasound profile analysis of ruptured coronary plaques. Am J Cardiol 2006; 98: 429-35.
67. Ellis S, Alderman E, Cain K, Fisher L, Sanders W, Bourassa M. Prediction of risk of anterior myocardial infarction by lesion severity and measurement method of stenoses in the left anterior descending coronary distribution: a CASS Registry Study. J Am Coll Cardiol 1988; 11: 908-16.
68. Little WC, Constantinescu M, Applegate RJ, et al. Can coronary angiography predict the site of a subsequent myocardial infarction in patients with mild-to-moderate coronary artery disease? Circulation 1988; 78: 1157-66.
69. Abizaid AS, Mintz GS, Mehran R, et al. Long-term follow-up after percutaneous transluminal coronary angioplasty was not performed based on intravascular ultrasound findings: importance of lumen dimensions. Circulation 1999; 100: 256-61.
70. Kern MJ, Meier B. Evaluation of the culprit plaque and the physiological significance of coronary atherosclerotic narrowings. Circulation 2001; 103: 3142-9.
71. Hong MK, Mintz GS, Lee CW, et al. The site of plaque rupture in native coronary arteries: a three-vessel intravascular ultrasound analysis. J Am Coll Cardiol 2005; 46: 261-5.
72. Wang JC, Normand SL, Mauri L, Kuntz RE. Coronary artery spatial distribution of acute myocardial infarction occlusions. Circulation 2004; 110: 278-84.
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