Key Points
-
Ex vivo studies of the coronary arteries have demonstrated the accuracy of optical coherence tomography imaging for definition of plaque characteristics
-
Whereas thin fibrous caps and necrotic cores indicate that plaques are susceptible to rupture, no characteristic features are known to identify plaques amenable to erosion
-
Clinical identification of plaques that cause acute coronary events is now feasible; such events might be characterized as being associated with ruptured or intact fibrous caps
-
Randomized studies might enable us to establish the safety of avoiding stent implantation in acute coronary events associated with intact fibrous caps
-
Randomized studies might also establish whether pre-emptive treatment of plaques vulnerable to rupture would prevent acute events
Abstract
In published post-mortem pathological studies, more than two-thirds of acute coronary events are associated with the rupture of lipid-rich, voluminous, and outwardly remodelled plaques covered by attenuated and inflamed fibrous caps in the proximal part of coronary arteries. Superficial erosion of the plaques is responsible for most of the remaining events; the eroded plaques usually do not demonstrate much lipid burden, do not have thin fibrous caps, are not positively remodelled, and are not critically occlusive. Both noninvasive and invasive imaging studies have been performed to clinically define the plaque characteristics in acute coronary syndromes in an attempt to identify the high-risk plaque substrate susceptible to development of an acute coronary event. Optical coherence tomography (OCT)âan intravascular imaging modality with high resolutionâcan be used to define various stages of plaque morphology, which might allow its use for the identification of high-risk plaques vulnerable to rupture, and their amenability to pre-emptive interventional treatment. OCT might also be employed to characterize plaque pathology at the time of intervention, to provide a priori knowledge of the mechanism of the acute coronary syndrome and, therefore, to enable improved management of the condition.
This is a preview of subscription content, access via your institution
Access options
Subscribe to this journal
Receive 12 print issues and online access
209,00 ⬠per year
only 17,42 ⬠per issue
Buy this article
- Purchase on SpringerLink
- Instant access to full article PDF
Prices may be subject to local taxes which are calculated during checkout









Similar content being viewed by others
References
Narula, J. 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. 61, 1041â1051 (2013).
Burke, A. P. et al. Coronary risk factors and plaque morphology in men with coronary disease who died suddenly. N. Engl. J. Med. 336, 1276â1282 (1997).
Narula, J. & Strauss, H. W. The popcorn plaques. Nat. Med. 13, 532â534 (2007).
Kolodgie, F. D. et al. Intraplaque hemorrhage and progression of coronary atheroma. N. Engl. J. Med. 349, 2316â2325 (2003).
Hansson, G. K. Inflammation, atherosclerosis, and coronary artery disease. N. Engl. J. Med. 352, 1685â1695 (2005).
Burke, A. P., Kolodgie, F. D., Farb, A., Weber, D. & Virmani, R. Morphological predictors of arterial remodeling in coronary atherosclerosis. Circulation 105, 297â303 (2002).
Varnava, A. M., Mills, P. G. & Davies, M. J. Relationship between coronary artery remodeling and plaque vulnerability. Circulation 105, 939â943 (2002).
Glagov, S., Weisenberg, E., Zarins, C. K., Stankunavicius, R. & Kolettis, G. J. Compensatory enlargement of human atherosclerotic coronary arteries. N. Engl. J. Med. 316, 1371â1375 (1987).
Narula, J. et al. Arithmetic of vulnerable plaques for noninvasive imaging. Nat. Clin. Pract. Cardiovasc. Med. 5 (Suppl. 2), S2âS10 (2008).
Honda, Y. & Fitzgerald, P. J. Intravascular imaging technologies. Circulation 117, 2024â2037 (2008).
Lowe, H. C., Narula, J., Fujimoto, J. G. & Jang, I. K. Intracoronary optical diagnostics current status, limitations, and potential. JACC Cardiovasc. Interv. 4, 1257â1270 (2011).
Regar, E., Schaar, J. A., Mont, E., Virmani, R. & Serruys, P. W. Optical coherence tomography. Cardiovasc. Radiat. Med. 4, 198â204 (2003).
Yabushita, H. et al. Characterization of human atherosclerosis by optical coherence tomography. Circulation 106, 1640â1645 (2002).
Tearney, G. J. et al. Quantification of macrophage content in atherosclerotic plaques by optical coherence tomography. Circulation 107, 113â119 (2003).
Virmani, R., Kolodgie, F. D., Burke, A. P., Farb, A. & Schwartz, S. M. Lessons from sudden coronary death: a comprehensive morphological classification scheme for atherosclerotic lesions. Arterioscler. Thromb. Vasc. Biol. 20, 1262â1275 (2000).
Stary, H. C. et al. A definition of initial, fatty streak, and intermediate lesions of atherosclerosis: a report from the Committee on Vascular Lesions of the Council on Arteriosclerosis, American Heart Association. Circulation 89, 2462â2478 (1994).
Velican, C. A dissecting view on the role of the fatty streak in the pathogenesis of human atherosclerosis: culprit or bystander? Med. Interne 19, 321â337 (1981).
Kolodgie, F. D., Burke, A. P., Nakazawa, G. & Virmani, R. Is pathologic intimal thickening the key to understanding early plaque progression in human atherosclerotic disease? Arterioscler. Thromb. Vasc. Biol. 27, 986â989 (2007).
Tearney, G. J. et al. Consensus standards for acquisition, measurement, and reporting of intravascular optical coherence tomography studies: a report from the international working group for intravascular optical coherence tomography standardization and validation. J. Am. Coll. Cardiol. 59, 1058â1072 (2012).
Stary, H. C. et al. A definition of advanced types of atherosclerotic lesions and a histological classification of atherosclerosis: a report from the Committee on Vascular Lesions of the Council on Arteriosclerosis, American Heart Association. Circulation 92, 1355â1374 (1995).
Falk, E., Nakano, M., Bentzon, J. F., Finn, A. V. & Virmani, R. Update on acute coronary syndromes: the pathologists' view. Eur. Heart J. 34, 719â728 (2013).
Kolodgie, F. D. et al. The thin-cap fibroatheroma: a type of vulnerable plaque: the major precursor lesion to acute coronary syndromes. Curr. Opin. Cardiol. 16, 285â292 (2001).
Davies, M. J. & Thomas, A. C. Plaque fissuringâthe cause of acute myocardial infarction, sudden ischaemic death, and crescendo angina. Br. Heart J. 53, 363â373 (1985).
Yonetsu, T. et al. In vivo critical fibrous cap thickness for rupture-prone coronary plaques assessed by optical coherence tomography. Eur. Heart J. 32, 1251â1259 (2011).
Siegel, R. J., Swan, K., Edwalds, G. & Fishbein, M. C. Limitations of postmortem assessment of human coronary artery size and luminal narrowing: differential effects of tissue fixation and processing on vessels with different degrees of atherosclerosis. J. Am. Coll. Cardiol. 5, 342â346 (1985).
Prati, F. 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. 31, 401â415 (2010).
Kolodgie, F. D. et al. Pathologic assessment of the vulnerable human coronary plaque. Heart 90, 1385â1391 (2004).
van Soest, G. et al. Pitfalls in plaque characterization by OCT: image artifacts in native coronary arteries. JACC Cardiovasc. Imaging 4, 810â803 (2011).
Burke, A. P. et al. Plaque rupture and sudden death related to exertion in men with coronary artery disease. JAMA 281, 921â926 (1999).
Burke, A. P. et al. Pathophysiology of calcium deposition in coronary arteries. Herz 26, 239â244 (2001).
Tanaka, A. et al. Morphology of exertion-triggered plaque rupture in patients with acute coronary syndrome: an optical coherence tomography study. Circulation 118, 2368â2373 (2008).
Farb, A. et al. Coronary plaque erosion without rupture into a lipid core: a frequent cause of coronary thrombosis in sudden coronary death. Circulation 93, 1354â1363 (1996).
Kolodgie, F. D. et al. Differential accumulation of proteoglycans and hyaluronan in culprit lesions: insights into plaque erosion. Arterioscler. Thromb. Vasc. Biol. 22, 1642â1648 (2002).
Ozaki, Y. et al. Coronary CT angiographic characteristics of culprit lesions in acute coronary syndromes not related to plaque rupture as defined by optical coherence tomography and angioscopy. Eur. Heart J. 32, 2814â2823 (2011).
Karanasos, A., Ligthart, J. M., Witberg, K. T. & Regar, E. Calcified nodules: an underrated mechanism of coronary thrombosis? JACC Cardiovasc. Imaging 5, 1071â1072 (2012).
Burke, A. P. et al. Healed plaque ruptures and sudden coronary death: evidence that subclinical rupture has a role in plaque progression. Circulation 103, 934â940 (2001).
Glaser, R. et al. Clinical progression of incidental, asymptomatic lesions discovered during culprit vessel coronary intervention. Circulation 111, 143â149 (2005).
Moreno, P. R. & Narula, J. Thinking out of the lumen: FFR vs. intravascular imaging for MACE prediction. J. Am. Coll. Cardiol. 63, 1141â1144 (2014).
Stone, G. W. & Narula, J. The myth of the mild vulnerable plaques. JACC Cardiovasc. Imaging 6, 1124â1126 (2013).
Niccoli, G. et al. Are the culprit lesions severely stenotic? JACC Cardiovasc. Imaging 6, 1108â1114 (2013).
Stone, G. W. et al. A prospective natural-history study of coronary atherosclerosis. N. Engl. J. Med. 364, 226â235 (2011).
Calvert, P. A. 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 4, 894â901 (2011).
Cheng, J. M. et al. In vivo detection of high-risk coronary plaques by radiofrequency intravascular ultrasound and cardiovascular outcome: results of the ATHEROREMO-IVUS study. Eur. Heart J. 35, 639â647 (2014).
Kato, K. 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 5, 433â440 (2012).
Kubo, T. et al. Assessment of culprit lesion morphology in acute myocardial infarction: ability of optical coherence tomography compared with intravascular ultrasound and coronary angioscopy. J. Am. Coll. Cardiol. 50, 933â939 (2007).
Kubo, T. et al. Multiple coronary lesion instability is patients with acute myocardial infarction as determined optical coherence tomography. Am. J. Cardiol. 105, 318â322 (2010).
Jang, I. K. et al. In vivo characterization of coronary atherosclerotic plaque by use of optical coherence tomography. Circulation 111, 1551â1555 (2005).
Yonetsu, T. et al. In vivo critical fibrous cap thickness for rupture-prone coronary plaques assessed by optical coherence tomography. Eur. Heart J. 32, 1251â1259 (2011).
Tanaka, A. et al. Morphology of exertion-triggered plaque rupture in patients with acute coronary syndrome: an optical coherence study. Circulation 118, 2368â2373 (2008).
Hattori, K. et al. Impact of statin therapy on plaque characteristics as assessed by serial OCT, grayscale and integrated backscatter-IVUS. JACC Cardiovasc. Imaging 5, 169â177 (2012).
Takarada, S. et al. Effect of statin therapy on coronary fibrous-cap thickness in patients with acute coronary syndrome assessment by optical coherence tomography study. Atherosclerosis 202, 491â497 (2009).
Tearney, G. J. et al. Quantification of macrophage content in atherosclerotic plaques by optical coherence tomography. Circulation 107, 113â119 (2003).
MacNeill, B. D. et al. Focal and multi-focal plaque macrophage distributions in patients with acute and stable presentations of coronary artery disease. J. Am. Coll. Cardiol. 44, 972â979 (2004).
Wykrzykowska, J. J. et al. Plaque sealing and passivation with a mechanical self-expanding low outward force nitinol vshield device for the treatment of IVUS and OCT-derived thin cap fibroatheromas (TCFAs) in native coronary arteries: report of the pilot study vShield Evaluated at Cardiac hospital in Rotterdam for Investigation and Treatment of TCFA (SECRITT). EuroIntervention 8, 945â954 (2012).
Onuma, Y. et al. Intracoronary optical coherence tomography and histology at 1 month and 2, 3, and 4 years after implantation of everolimus-eluting bioresorbable vascular scaffolds in a porcine coronary artery model: an attempt to decipher the human optical coherence tomography images in the absorb trial. Circulation 122, 2288â2300 (2010).
Jia, H. et al. In vivo diagnosis of plaque erosion and calcified nodule in patients with acute coronary syndrome by intravascular optical coherence tomography. J. Am. Coll. Cardiol. 62, 1748â1758 (2013).
Braunwald E. Coronary plaque erosion: recognition and management. JACC Cardiovasc. Imaging 6, 288â289 (2013).
Prati, F. et al. OCT-based diagnosis and management of STEMI associated with intact fibrous cap. JACC Cardiovasc. Imaging 6, 283â287 (2013).
Marder, V. J. et al. Safety of catheter-delivered plasmin in patients with acute lower extremity arterial or bypass graft occlusion: phase I results. J. Thromb. Haemost. 10, 985â991 (2012).
Liu, L. et al. Imaging the subcellular structure of human coronary atherosclerosis using micro-optical coherence tomography. Nat. Med. 17, 1010â1014 (2011).
Liang, S. et al. Intravascular atherosclerotic imaging with combined fluorescence and optical coherence tomography probe based on a double-clad fiber combiner. J. Biomed. Opt. 17, 070501 (2012).
Vinegoni, C. et al. Indocyanine green enables near-infrared fluorescence imaging of lipid-rich, inflamed atherosclerotic plaques. Sci. Transl. Med. 3, 84ra45 (2011).
Acknowledgements
St. Jude Medical (USA) and Terumo Corporation (Japan) provided the major source of research funds for the ex vivo optical coherence tomography/optical frequency domain imaging study, with other support from CVPath Institute, Inc., USA. F.O. is supported by a research fellowship from the Uehara Memorial Foundation (Japan).
Author information
Authors and Affiliations
Contributions
F.O., F.P., and J.N. researched data for the article. M.J., R.V., and J.N. substantially contributed to discussion of content. F.O., M.J., R.V., and J.N. wrote the manuscript. M.J., F.P., R.V., and J.N. reviewed and edited the manuscript before submission.
Corresponding author
Ethics declarations
Competing interests
M.J. receives honoraria from Abbott Vascular, Biotronik, Medtronic, and St. Jude Medical, and is a consultant for Biotronik and Cardionovum. R.V. receives research support from Abbott Vascular, BioSensors International, Biotronik, Boston Scientific, Medtronic, MicroPort Medical, OrbusNeich Medical, SINO Medical Technology, and Terumo Corporation. She also has speaking engagements with Merck, receives honoraria from Abbott Vascular, Boston Scientific, Lutonix, Medtronic, and Terumo Corporation, and is a consultant for 480 Biomedical, Abbott Vascular, Medtronic, and W.L. Gore. J.N. has received research grants (to his institution in the form of imaging equipment) from GE Healthcare and Philips Healthcare, and has received honoraria from GE Healthcare and Philips Healthcare as a member of their advisory boards. F.O. and F.P. declare no competing interests.
Rights and permissions
About this article
Cite this article
Otsuka, F., Joner, M., Prati, F. et al. Clinical classification of plaque morphology in coronary disease. Nat Rev Cardiol 11, 379â389 (2014). https://doi.org/10.1038/nrcardio.2014.62
Published:
Issue Date:
DOI: https://doi.org/10.1038/nrcardio.2014.62