Abstract
The concept of the vulnerable atherosclerotic plaque first developed through histological evaluation of post-mortem coronary arteries has been significantly advanced in recent years by new imaging modalities. Imaging has: 1) verified histological findings, 2) identified features that are associated with unstable plaque, 3) followed plaques over time to study the dynamic nature of vulnerable plaque, 4) predicted clinical events based on imaging features, 5) tested the impact of medical interventions on plaque morphology. This review will summarize the major findings of imaging studies with a focus on how the knowledge base of vulnerable plaque has been advanced.
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Roger VL, Go AS, Lloyd-Jones DM, et al. Heart disease and stroke statistics–2011 update: a report from the American Heart Association. Circulation. 2011;123(4):e18–e209.
Davies MJ. The pathophysiology of acute coronary syndromes. Heart. 2000;83(3):361–6.
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(5):1262–75.
Narula J, Nakano M, Virmani R, et al. Histopathologic characteristics of atherosclerotic coronary disease and implications of the findings for the invasive and noninvasive detection of vulnerable plaques. J Am Coll Cardiol. 2013;61(10):1041–51. Further refinement of the definition of a thin-cap fibroatheroma by necropsy evaluation..
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(2):H717–727.
Arbustini E, Grasso M, Diegoli M, et al. Coronary atherosclerotic plaques with and without thrombus in ischemic heart syndromes: a morphologic, immunohistochemical, and biochemical study. Am J Cardiol. 1991;68(7):36B–50B.
Voros S, Rinehart S, Qian Z, et al. Coronary atherosclerosis imaging by coronary CT angiography: current status, correlation with intravascular interrogation and meta-analysis. JACC Cardiovasc Imaging. 2011;4(5):537–48.
Rogers IS, Tawakol A. Imaging of coronary inflammation with FDG-PET: feasibility and clinical hurdles. Curr Cardiol Rep. 2011;13(2):138–44.
Rosa GM, Bauckneht M, Masoero G, et al. The vulnerable coronary plaque: update on imaging technologies. Thromb Haemost. 2013;110(4):706–22.
Prati F, Regar E, Mintz GS, et al. Expert review document on methodology, terminology, and clinical applications of optical coherence tomography: physical principles, methodology of image acquisition, and clinical application for assessment of coronary arteries and atherosclerosis. Eur heart J. 2010;31(4):401–15.
Yabushita H, Bouma BE, Houser SL, et al. Characterization of human atherosclerosis by optical coherence tomography. Circulation. 2002;106(13):1640–5.
Tearney GJ, Yabushita H, Houser SL, et al. Quantification of macrophage content in atherosclerotic plaques by optical coherence tomography. Circulation. 2003;107(1):113–9.
Sanon S, Dao T, Sanon VP, Chilton R. Imaging of vulnerable plaques using near-infrared spectroscopy for risk stratification of atherosclerosis. Curr Atheroscler Rep. 2013;15(2):304.
Thieme T, Wernecke KD, Meyer R, et al. Angioscopic evaluation of atherosclerotic plaques: validation by histomorphologic analysis and association with stable and unstable coronary syndromes. J Am Coll Cardiol. 1996;28(1):1–6.
Takano M, Jang IK, Inami S, et al. In vivo comparison of optical coherence tomography and angioscopy for the evaluation of coronary plaque characteristics. Am J Cardiol. 2008;101(4):471–6.
Ambrose JA, Tannenbaum MA, Alexopoulos D, et al. Angiographic progression of coronary artery disease and the development of myocardial infarction. J Am Coll Cardiol. 1988;12(1):56–62.
Cutlip DE, Chhabra AG, Baim DS, et al. Beyond restenosis: five-year clinical outcomes from second-generation coronary stent trials. Circulation. 2004;110(10):1226–30.
Glaser R, Selzer F, Faxon DP, et al. Clinical progression of incidental, asymptomatic lesions discovered during culprit vessel coronary intervention. Circulation. 2005;111(2):143–9.
Hoffmann U, Moselewski F, Nieman K, et al. Noninvasive assessment of plaque morphology and composition in culprit and stable lesions in acute coronary syndrome and stable lesions in stable angina by multidetector computed tomography. J Am Coll Cardiol. 2006;47(8):1655–62.
Pflederer T, Marwan M, Schepis T, et al. Characterization of culprit lesions in acute coronary syndromes using coronary dual-source CT angiography. Atherosclerosis. 2010;211(2):437–44.
Hernando L, Corros C, Gonzalo N, et al. Morphological characteristics of culprit coronary lesions according to clinical presentation: insights from a multimodality imaging approach. Int J Cardiovasc Imaging. 2013;29(1):13–21.
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(20):2473–8.
Madder RD, Smith JL, Dixon SR, Goldstein JA. Composition of target lesions by near-infrared spectroscopy in patients with acute coronary syndrome versus stable angina. Circ Cardiovasc Interv. 2012;5(1):55–61. One of the first clinical papers to use NIRS showing that patients with acute coronary syndromes have lesions with high lipid core plaque compared to patients with stable angina..
Madder RD, Goldstein JA, Madden SP, et al. Detection by Near-Infrared Spectroscopy of Large Lipid Core Plaques at Culprit Sites in Patients With Acute ST-Segment Elevation Myocardial Infarction. JACC Cardiovasc Interv. 2013;6(8):838–46.
Jang IK, Tearney GJ, MacNeill B, et al. In vivo characterization of coronary atherosclerotic plaque by use of optical coherence tomography. Circulation. 2005;111(12):1551–5.
Kubo T, Imanishi T, Kashiwagi M, et al. Multiple coronary lesion instability in patients with acute myocardial infarction as determined by optical coherence tomography. Am J Cardiol. 2010;105(3):318–22.
Yonetsu T, Kakuta T, Lee T, et al. In vivo critical fibrous cap thickness for rupture-prone coronary plaques assessed by optical coherence tomography. Eur Heart J. 2011;32(10):1251–9.
Tanaka A, Imanishi T, Kitabata H, et al. Morphology of exertion-triggered plaque rupture in patients with acute coronary syndrome: an optical coherence tomography study. Circulation. 2008;118(23):2368–73.
Toutouzas K, Tsiamis E, Karanasos A, et al. Morphological characteristics of culprit atheromatic plaque are associated with coronary flow after thrombolytic therapy: new implications of optical coherence tomography from a multicenter study. JACC Cardiovasc Interv. 2010;3(5):507–14. Study showing that an acute myocardial infarction can be caused by rupture of fibroatheromas not specifically defined as TCFAs..
Ino Y, Kubo T, Tanaka A, et al. Difference of culprit lesion morphologies between ST-segment elevation myocardial infarction and non-ST-segment elevation acute coronary syndrome: an optical coherence tomography study. JACC Cardiovasc Interv. 2011;4(1):76–82.
Kato K, Yonetsu T, Kim SJ, et al. Nonculprit plaques in patients with acute coronary syndromes have more vulnerable features compared with those with non-acute coronary syndromes: a 3-vessel optical coherence tomography study. Circ Cardiovasc Imaging. 2012;5(4):433–40.
Hong MK, Mintz GS, Lee CW, et al. Comparison of virtual histology to intravascular ultrasound of culprit coronary lesions in acute coronary syndrome and target coronary lesions in stable angina pectoris. Am J Cardiol. 2007;100(6):953–9.
Fujii K, Carlier SG, Mintz GS, et al. Intravascular ultrasound study of patterns of calcium in ruptured coronary plaques. Am J Cardiol. 2005;96(3):352–7.
Kashiwagi M, Tanaka A, Kitabata H, et al. Feasibility of noninvasive assessment of thin-cap fibroatheroma by multidetector computed tomography. JACC Cardiovasc Imaging. 2009;2(12):1412–9.
Kroner ES, van Velzen JE, Boogers MJ, et al. Positive remodeling on coronary computed tomography as a marker for plaque vulnerability on virtual histology intravascular ultrasound. Am J Cardiol. 2011;107(12):1725–9.
Maurovich-Horvat P, Schlett CL, Alkadhi H, et al. The napkin-ring sign indicates advanced atherosclerotic lesions in coronary CT angiography. JACC Cardiovasc Imaging. 2012;5(12):1243–52. While coronary computed tomography does not have the resolution of invasive imaging modalities to discern fibrous cap thickness, necrotic core size, and other classic histologic features of high risk lesions, there are other unique imaging features that are associated with high risk lesions. In this paper, a ring-like pattern of low attenuation termed the napkin-ring sign was shown to identify high risk lesions with a high specificity compared to histological evaulation..
Nishio M, Ueda Y, Matsuo K, et al. Detection of disrupted plaques by coronary CT: comparison with angioscopy. Heart. 2011;97(17):1397–402.
Kitabata H, Tanaka A, Kubo T, et al. Relation of microchannel structure identified by optical coherence tomography to plaque vulnerability in patients with coronary artery disease. Am J Cardiol. 2010;105(12):1673–8.
Uemura S, Ishigami K, Soeda T, et al. Thin-cap fibroatheroma and microchannel findings in optical coherence tomography correlate with subsequent progression of coronary atheromatous plaques. Eur Heart J. 2012;33(1):78–85.
MacNeill BD, Jang IK, Bouma BE, et al. Focal and multi-focal plaque macrophage distributions in patients with acute and stable presentations of coronary artery disease. J Am Coll Cardiol. 2004;44(5):972–9.
Rogers IS, Nasir K, Figueroa AL, et al. Feasibility of FDG imaging of the coronary arteries: comparison between acute coronary syndrome and stable angina. JACC Cardiovasc Imaging. 2010;3(4):388–97.
Kim SW, Hong YJ, Mintz GS, et al. Relation of ruptured plaque culprit lesion phenotype and outcomes in patients with ST elevation acute myocardial infarction. Am J Cardiol. 2012;109(6):794–9. This paper showed that lower risk lesions (non-TCFAs) are associated with plaque rupture, including thick cap fibroatheroma, fibro-calcified plaque, and pathologic intimal thickening..
Sanidas EA, Maehara A, Mintz GS, et al. Angioscopic and virtual histology intravascular ultrasound characteristics of culprit lesion morphology underlying coronary artery thrombosis. Am J Cardiol. 2011;107(9):1285–90.
Kubo T, Maehara A, Mintz GS, et al. The dynamic nature of coronary artery lesion morphology assessed by serial virtual histology intravascular ultrasound tissue characterization. J Am Coll Cardiol. 2010;55(15):1590–7. This paper shows that in patients with stable angina, high risk plaques over time can regress to lower risk features, with 75 % of thin cap fibroatheromas showing signs of stabilization or healing over time..
Zhao Z, Witzenbichler B, Mintz GS, et al. Dynamic nature of nonculprit coronary artery lesion morphology in STEMI: a serial IVUS analysis from the HORIZONS-AMI trial. JACC Cardiovasc Imaging. 2013;6(1):86–95. As opposed to the Kubo (2010) et al. paper showing that patients with stable angina have high risk plaques that tend to regress over time, in a more high risk patient population presenting with ST elevation myocardial infarctions, lesions tend advance to higher risk features over time. These two papers would suggest that patient specific features, such as a potential background milieu of higher inflammation, will determine whether high risk lesions will progress and cause clinical syndromes or regress over time..
Ohtani T, Ueda Y, Mizote I, et al. Number of yellow plaques detected in a coronary artery is associated with future risk of acute coronary syndrome: detection of vulnerable patients by angioscopy. J Am Coll Cardiol. 2006;47(11):2194–200.
Takano M, Inami S, Ishibashi F, et al. Angioscopic follow-up study of coronary ruptured plaques in nonculprit lesions. J Am Coll Cardiol. 2005;45(5):652–8.
Patel D, Hamamdzic D, Llano R, et al. Subsequent development of fibroatheromas with inflamed fibrous caps can be predicted by intracoronary near infrared spectroscopy. Arterioscler Thromb Vasc Biol. 2013;33(2):347–53.
Papadopoulou SL, Neefjes LA, Garcia-Garcia HM, et al. Natural history of coronary atherosclerosis by multislice computed tomography. JACC Cardiovasc Imaging. 2012;5(3 Suppl):S28–37.
Inoue K, Motoyama S, Sarai M, et al. Serial coronary CT angiography-verified changes in plaque characteristics as an end point: evaluation of effect of statin intervention. JACC Cardiovasc Imaging. 2010;3(7):691–8.
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(1):107–14.
Nissen SE, Nicholls SJ, Sipahi I, et al. Effect of very high-intensity statin therapy on regression of coronary atherosclerosis: the ASTEROID trial. JAMA. 2006;295(13):1556–65.
Nasu K, Tsuchikane E, Katoh O, et al. Effect of fluvastatin on progression of coronary atherosclerotic plaque evaluated by virtual histology intravascular ultrasound. JACC Cardiovasc Interv. 2009;2(7):689–96.
Takarada S, Imanishi T, Kubo T, et al. Effect of statin therapy on coronary fibrous-cap thickness in patients with acute coronary syndrome: assessment by optical coherence tomography study. Atherosclerosis. 2009;202(2):491–7.
Motoyama S, Sarai M, Harigaya H, et al. Computed tomographic angiography characteristics of atherosclerotic plaques subsequently resulting in acute coronary syndrome. J Am Coll Cardiol. 2009;54(1):49–57.
Yamamoto H, Kitagawa T, Ohashi N, et al. Noncalcified atherosclerotic lesions with vulnerable characteristics detected by coronary CT angiography and future coronary events. J Cardiovasc Comput Tomogr. 2013;7(3):192–9.
Stone GW, Maehara A, Lansky AJ, et al. A prospective natural-history study of coronary atherosclerosis. N Engl J Med. 2011;364(3):226–35. A pivotal natural history study using VH-IVUS and following 697 patients who presented with an acute coronary syndrome for three years, this study defined high risk plaque features assocated with subsequent events caused by initially non-culprit lesions. Most of these lesions were angiographically mild at baseline (mean diameter stenosis of 32 %) but had a plaque burden over 70 %, a minimal luminal area of 4.0 mm^2, or were classified as a thin cap fibroatheroma. If a lesion had all three high risk features, the future event rate rose to 18.2 %..
Yun KH, Mintz GS, Farhat N, et al. Relation between angiographic lesion severity, vulnerable plaque morphology and future adverse cardiac events (from the Providing Regional Observations to Study Predictors of Events in the Coronary Tree study). Am J Cardiol. 2012;110(4):471–7.
Calvert PA, Obaid DR, O'Sullivan M, et al. Association between IVUS findings and adverse outcomes in patients with coronary artery disease: the VIVA (VH-IVUS in Vulnerable Atherosclerosis) Study. JACC Cardiovasc Imaging. 2011;4(8):894–901.
Stone PH, Saito S, Takahashi S, et al. Prediction of progression of coronary artery disease and clinical outcomes using vascular profiling of endothelial shear stress and arterial plaque characteristics: the PREDICTION Study. Circulation. 2012;126(2):172–81. In this study of 506 patients presenting with an acute coronary syndrome, three vessel VH-IVUS as well as a computational assessment of enothelial shear stress was performed and a subset of 374 patients had a routine follow up study in 6–10 months. Similar to PROSPECT, a large baseline plaque burden predicted the progression of lesions. Interestingly, adding the low endothelial shear stress computation to baseline plaque burden doubled the positive predictive value to predict progression from 22 % to 41 %..
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Robert S. Fenning and Robert L. Wilensky declare that they have no conflict of interest.
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Fenning, R.S., Wilensky, R.L. New Insights into the Vulnerable Plaque from Imaging Studies. Curr Atheroscler Rep 16, 397 (2014). https://doi.org/10.1007/s11883-014-0397-1
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DOI: https://doi.org/10.1007/s11883-014-0397-1