Coronary Artery Microcalcification: Imaging and Clinical Implications
Abstract
:1. Introduction
2. Pathology
3. Imaging Atherosclerosis
4. Imaging Plaque Morphology
5. Imaging Disease Activity
6. Confocal Imaging of Microcalcifications
7. Conclusions
Funding
Conflicts of Interest
Consent for Publication
References
- Piepoli, M.F.; Hoes, A.W.; Agewall, S.; Albus, C.; Brotons, C.; Catapano, A.L.; Graham, I.; Cooney, M.-T.; Cosyns, B.; Deaton, C.; et al. 2016 European Guidelines on cardiovascular disease prevention in clinical practice. The Sixth Joint Task Force of the European Society of Cardiology and Other Societies on Cardiovascular Disease Prevention in Clinical Practice. Eur. Heart J. 2016, 37, 2315–2381. [Google Scholar] [CrossRef] [PubMed]
- The SCOT-HEART Investigators. Coronary CT Angiography and 5-Year Risk of Myocardial Infarction. N. Engl. J. Med. 2018, 3799, 924–933. [Google Scholar]
- Hecht, H.; Blaha, M.J.; Berman, D.S.; Nasir, K.; Budoff, M.; Leipsic, J.; Shaw, L.J.; Blankstein, R.; Narula, J.; Rumberger, J. Clinical indications for coronary artery calcium scoring in asymptomatic patients: Expert consensus statement from the Society of Cardiovascular Computed Tomography. J. Cardiovasc. Comput. Tomogr. 2017, 11, 157–168. [Google Scholar] [CrossRef] [PubMed]
- Greenland, P.; Bonow, R.O.; Brundage, B.H.; Budoff, M.J.; Eisenberg, M.J.; Grundy, S.M. ACCF/AHA 2007 clinical expert consensus document on coronary artery calcium scoring by computed tomography in global cardiovascular risk assessment and in evaluation of patients with chest pain. J. Am. Coll. Cardiol. 2007, 49, 378–402. [Google Scholar] [CrossRef] [PubMed]
- Stone, N.J.; Robinson, J.G.; Lichtenstein, A.H.; Merz, C.N.B.; Blum, C.B.; Eckel, R.H.; McBride, P.; Goldberg, A.C.; Gordon, D.; Levy, D.; et al. 2013 ACC/AHA Guideline on the Treatment of Blood Cholesterol to Reduce Atherosclerotic Cardiovascular Risk in Adults: A Report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines. J. Am. Coll. Cardiol. 2014, 63, 2889–2934. [Google Scholar] [CrossRef] [PubMed]
- Niccoli, G.; Stefanini, G.G.; Capodanno, D.; Crea, F.; Ambrose, J.A.; Berg, R. Are the culprit lesions severely stenotic? JACC Cardiovasc. Imaging 2013, 6, 1108–1114. [Google Scholar] [CrossRef]
- Stone, G.W.; Maehara, A.; Lansky, A.J.; De Bruyne, B.; Cristea, E.; Mintz, G.S.; Parise, H.; Mehran, R.; McPherson, J.; Farhat, N.; et al. A prospective natural-history study of coronary atherosclerosis. N. Engl. J. Med. 2011, 364, 226–235. [Google Scholar] [CrossRef]
- Marzilli, M.; Merz, C.N.B.; Boden, W.E.; Bonow, R.O.; Capozza, P.G.; Chilian, W.M.; Patel, M.R.; DeMaria, A.N.; Guarini, G.; Huqi, A.; et al. Obstructive coronary atherosclerosis and ischemic heart disease: an elusive link! J. Am. Coll. Cardiol. 2012, 60, 951–956. [Google Scholar] [CrossRef]
- Maurovich-Horvat, P.; Ferencik, M.; Voros, S.; Merkely, B.; Hoffmann, U. Comprehensive plaque assessment by coronary CT angiography. Nat. Rev. Cardiol. 2014, 11, 390–402. [Google Scholar] [CrossRef]
- Ylä-Herttuala, S.; Bentzon, J.F.; Daemen, M.; Falk, E.; Garcia-Garcia, H.M.; Herrmann, J.; Hoefer, I.; Jukema, J.W.; Krams, R.; Kwak, B.R.; et al. Stabilisation of atherosclerotic plaques. Position paper of the European Society of Cardiology (ESC) Working Group on atherosclerosis and vascular biology. Thromb. Haemost. 2011, 106, 1–19. [Google Scholar]
- Tian, J.; Dauerman, H.; Toma, C.; Samady, H.; Itoh, T.; Kuramitsu, S.; Hu, S.; Domei, T.; Jia, H.; Vergallo, R.; et al. Prevalence and Characteristics of TCFA and Degree of Coronary Artery Stenosis: An OCT, IVUS, and Angiographic Study. J. Am. Coll. Cardiol. 2014, 64, 672–680. [Google Scholar] [CrossRef] [PubMed]
- Nicoll, R.; Henein, M.Y. Arterial calcification: Friend or foe? J. Am. Coll. Cardiol. 2013, 167, 322–327. [Google Scholar] [CrossRef] [PubMed]
- Virmani, R.; Kolodgie, F.D.; Burke, A.P.; Farb, A.; Schwartz, S.M. Lessons from sudden coronary death. Arterioscler. Thromb. Vasc. Biol. 2000, 20, 1262–1275. [Google Scholar] [CrossRef] [PubMed]
- Arbab-Zadeh, A.; Nakano, M.; Virmani, R.; Fuster, V. Acute coronary events. Circulation 2012, 125, 1147–1156. [Google Scholar] [CrossRef] [PubMed]
- Falk, E.; Nakano, M.; Bentzon, J.F.; Finn, A.V.; Virmani, R. Update on acute coronary syndromes: The pathologists’ view. Eur. Heart J. 2013, 34, 719–728. [Google Scholar] [CrossRef]
- Shah, P.K. Pathophysiology of coronary thrombosis: Role of plaque rupture and plaque erosion. Prog. Cardiovasc. Dis. 2002, 44, 357–368. [Google Scholar] [CrossRef]
- Partida, R.A.; Libby, P.; Crea, F.; Jang, I.-K. Plaque erosion: A new in vivo diagnosis and a potential major shift in the management of patients with acute coronary syndromes. Eur. Heart J. 2018, 39, 2070–2076. [Google Scholar] [CrossRef]
- Sakakura, K.; Nakano, M.; Otsuka, F.; Ladich, E.; Kolodgie, F.D.; Virmani, R. Pathophysiology of Atherosclerosis Plaque Progression. Heart Lung Circ. 2013, 22, 399–411. [Google Scholar] [CrossRef] [Green Version]
- Wang, T.; Butany, J. Pathogenesis of atherosclerosis. Diagn. Histopathol. 2017, 23, 473–478. [Google Scholar] [CrossRef]
- Bentzon, J.F.; Otsuka, F.; Virmani, R.; Falk, E. Mechanisms of Plaque Formation and Rupture. Circ. Res. 2014, 114, 1852–1866. [Google Scholar] [CrossRef]
- Burke, A.P.; Kolodgie, F.D.; Farb, A.; Weber, D.; Virmani, R. Morphological Predictors of Arterial Remodeling in Coronary Atherosclerosis. Circulation 2002, 105, 297–303. [Google Scholar] [CrossRef] [PubMed]
- Wu, M.; Rementer, C.; Giachelli, C.M. Vascular Calcification: An Update on Mechanisms and Challenges in Treatment. Calcif. Tissue Int. 2013, 93, 365–373. [Google Scholar] [CrossRef] [PubMed]
- Sage, A.P.; Tintut, Y.; Demer, L.L. Regulatory mechanisms in vascular calcification. Nat. Rev. Cardiol. 2010, 7, 528–536. [Google Scholar] [CrossRef] [PubMed]
- Otsuka, F.; Kramer, M.C.A.; Woudstra, P.; Yahagi, K.; Ladich, E.; Finn, A.V.; Joner, M.; de Winter, R.J.; Kolodgie, F.D.; Wight, T.N.; et al. Natural progression of atherosclerosis from pathologic intimal thickening to late fibroatheroma in human coronary arteries: A pathology study. Atherosclerosis 2015, 241, 772–782. [Google Scholar] [CrossRef] [Green Version]
- Kubo, T.; Maehara, A.; Mintz, G.S.; Doi, H.; Tsujita, K.; Choi, S.Y.; Rogers, J.H.; Katoh, O.; Nasu, K.; Koenig, A.; 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, 1590–1597. [Google Scholar] [CrossRef]
- Weber, C.; Noels, H. Atherosclerosis: Current pathogenesis and therapeutic options. Nat. Med. 2011, 17, 1410. [Google Scholar] [CrossRef]
- Moriya, J. Critical roles of inflammation in atherosclerosis. J. Cardiol. 2019, 73, 22–27. [Google Scholar] [CrossRef] [Green Version]
- Libby, P.; Tabas, I.; Fredman, G.; Fisher, E.A. Inflammation and its Resolution as Determinants of Acute Coronary Syndromes. Circ. Res. 2014, 114, 1867–1879. [Google Scholar] [CrossRef] [Green Version]
- Tabas, I.; García-Cardeña, G.; Owens, G.K. Recent insights into the cellular biology of atherosclerosis. J. Cell Biol. 2015, 209, 13–22. [Google Scholar] [CrossRef]
- Hansson, G.K.; Hermansson, A. The immune system in atherosclerosis. Nat. Immunol. 2011, 12, 204–212. [Google Scholar] [CrossRef]
- Otsuka, F.; Sakakura, K.; Yahagi, K.; Joner, M.; Virmani, R. Has our understanding of calcification in human coronary atherosclerosis progressed? Arterioscler. Thromb. Vasc. Biol. 2014, 34, 724–736. [Google Scholar] [CrossRef] [PubMed]
- Kolodgie, D.F.; Burke, P.A.; Farb, K.A.; Gold, H.K.; Yuan, J.; Narula, J.; Virmani, R.; Finn, A.; Aloke, V. The thin-cap fibroatheroma: A type of vulnerable plaque: The major precursor lesion to acute coronary syndromes. Curr. Opin. Cardiol. 2001, 16, 285–292. [Google Scholar] [CrossRef] [PubMed]
- Cheruvu, P.K.; Finn, A.V.; Gardner, C.; Caplan, J.; Goldstein, J.; Stone, G.W.; Muller, J.E.; Virmani, R. Frequency and distribution of thin-cap fibroatheroma and ruptured plaques in human coronary arteries: A pathologic study. J. Am. Coll. Cardiol. 2007, 50, 940–949. [Google Scholar] [CrossRef] [PubMed]
- Virmani, R.; Burke, A.P.; Kolodgie, F.D.; Farb, A. Pathology of the Thin-Cap Fibroatheroma. J. Interv. Cardiol. 2003, 16, 267–272. [Google Scholar] [CrossRef] [PubMed]
- Maldonado, N.; Kelly-Arnold, A.; Vengrenyuk, Y.; Laudier, D.; Fallon, J.T.; Virmani, R.; Weinbaum, S.; Cardoso, L. A mechanistic analysis of the role of microcalcifications in atherosclerotic plaque stability: Potential implications for plaque rupture. Am. J. Physiol. Heart Circ. Physiol. 2012, 303, H619–H628. [Google Scholar] [CrossRef] [PubMed]
- Finn, A.V.; Nakano, M.; Narula, J.; Kolodgie, F.D.; Virmani, R. Concept of Vulnerable/Unstable Plaque. Arterioscler. Thromb. Vasc. Biol. 2010, 30, 1282–1292. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Yonetsu, T.; Kakuta, T.; Lee, T.; Takahashi, K.; Kawaguchi, N.; Yamamoto, G.; Isobe, M.; Koura, K.; Hishikari, K.; Iesaka, Y.; et al. In vivo critical fibrous cap thickness for rupture-prone coronary plaques assessed by optical coherence tomography. Eur. Heart J. 2011, 32, 1251–1259. [Google Scholar] [CrossRef]
- Tian, J.; Hou, J.; Xing, L.; Yonetsu, T.; Kato, K.; Jang, I.K.; Lee, H.; Zhang, S.; Yu, B.; Jang, I.K. Significance of intraplaque neovascularisation for vulnerability: Optical coherence tomography study. Heart 2012, 98, 1504–1509. [Google Scholar] [CrossRef]
- Kume, T.; Okura, H.; Kawamoto, T.; Akasaka, T.; Toyota, E.; Watanabe, N.; Yoshida, K.; Neishi, Y.; Sukmawan, R.; Sadahira, Y. Relationship between coronary remodeling and plaque characterization in patients without clinical evidence of coronary artery disease. Atherosclerosis 2008, 197, 799–805. [Google Scholar] [CrossRef]
- Kröner, E.S.; van Velzen, J.E.; Boogers, M.J.; Siebelink, H.M.J.; Schalij, M.J.; Kroft, L.J.; Schuijf, J.D.; de Roos, A.; van der Wall, E.E.; Jukema, J.W. Positive remodeling on coronary computed tomography as a marker for plaque vulnerability on virtual histology intravascular ultrasound. Am. J. Cardiol. 2011, 107, 1725–1729. [Google Scholar] [CrossRef]
- Varnava, A.M.; Mills, P.G.; Davies, M.J. Relationship between coronary artery remodeling and plaque vulnerability. Circulation 2002, 105, 939–943. [Google Scholar] [CrossRef] [PubMed]
- Aikawa, E.; Nahrendorf, M.; Figueiredo, J.-L.; Swirski, F.K.; Shtatland, T.; Kohler, R.H.; Jaffer, F.A.; Aikawa, M.; Weissleder, R. Osteogenesis associates with inflammation in early-stage atherosclerosis evaluated by molecular imaging in vivo. Circulation 2007, 116, 2841–2850. [Google Scholar] [CrossRef] [PubMed]
- Nicoll, R.; Henein, M. Arterial calcification: A new perspective? Int. J. Cardiol. 2017, 228, 11–22. [Google Scholar] [CrossRef] [PubMed]
- New, S.; Aikawa, E. Cardiovascular Calcification—An Inflammatory Disease. Circ. J. 2011, 75, 1305–1313. [Google Scholar] [CrossRef] [PubMed]
- Mori, H.; Torii, S.; Kutyna, M.; Sakamoto, A.; Finn, A.V.; Virmani, R. Coronary artery calcification and its progression: What does it really mean? JACC Cardiovasc. Imaging 2018, 11, 127–142. [Google Scholar] [CrossRef] [PubMed]
- Ikeda, K.; Souma, Y.; Akakabe, Y.; Kitamura, Y.; Matsuo, K.; Shimoda, Y.; Matsubara, H.; Ueyama, T.; Matoba, S.; Yamada, H.; et al. Macrophages play a unique role in the plaque calcification by enhancing the osteogenic signals exerted by vascular smooth muscle cells. Biochem. Biophys. Res. Commun. 2012, 425, 39–44. [Google Scholar] [CrossRef] [PubMed]
- New, S.E.P.; Goettsch, C.; Aikawa, M.; Marchini, J.F.; Shibasaki, M.; Yabusaki, K.; Aikawa, E.; Libby, P.; Shanahan, C.M.; Croce, K. Macrophage-derived matrix vesicles: An alternative novel mechanism for microcalcification in atherosclerotic plaques. Circ. Res. 2013, 113, 72–77. [Google Scholar] [CrossRef]
- Boulanger, C.M.; Loyer, X.; Rautou, P.-E.; Amabile, N. Extracellular vesicles in coronary artery disease. Nat. Rev. Cardiol. 2017, 14, 259. [Google Scholar] [CrossRef]
- Roijers, R.B.; Debernardi, N.; Cleutjens, J.P.M.; Schurgers, L.J.; Mutsaers, P.H.A.; van der Vusse, G.J. Microcalcifications in early intimal lesions of atherosclerotic human coronary arteries. Am. J. Pathol. 2011, 178, 2879–2887. [Google Scholar] [CrossRef]
- Chatrou, M.L.L.; Cleutjens, J.P.; van Der Vusse, G.J.; Roijers, R.B.; Mutsaers, P.H.A.; Schurgers, L.J. Intra-section analysis of human coronary arteries reveals a potential role for micro-calcifications in macrophage recruitment in the early stage of atherosclerosis. PLoS ONE 2015, 10, e0142335. [Google Scholar] [CrossRef]
- Nadra, I.; Mason, J.C.; Philippidis, P.; Florey, O.; Smythe, C.D.; McCarthy, G.M.; Haskard, D.O.; Landis, R.C. Proinflammatory activation of macrophages by basic calcium phosphate crystals via protein kinase C and MAP kinase pathways. Circ. Res. 2005, 96, 1248–1256. [Google Scholar] [CrossRef] [PubMed]
- Abdelbaky, A.; Corsini, E.; Figueroa, A.L.; Fontanez, S.; Subramanian, S.; Ferencik, M.; Tawakol, A.; Brady, T.J.; Hoffmann, U. Focal arterial inflammation precedes subsequent calcification in the same location. Circ. Cardiovasc. Imaging 2013, 6, 747–754. [Google Scholar] [CrossRef] [PubMed]
- Dykun, I.; Lehmann, N.; Kälsch, H.; Möhlenkamp, S.; Moebus, S.; Budde, T.; Mahabadi, A.A.; Seibel, R.; Grönemeyer, D.; Jöckel, K.-H.; et al. Statin medication enhances progression of coronary artery calcification: the heinz nixdorf recall study. J. Am. Coll. Cardiol. 2016, 68, 2123–2125. [Google Scholar] [CrossRef] [PubMed]
- Nakahara, T.; Dweck, M.R.; Narula, N.; Pisapia, D.; Narula, J.; Strauss, H.W. Coronary artery calcification: From mechanism to molecular imaging. JACC Cardiovasc. Imaging 2017, 10, 582–593. [Google Scholar] [CrossRef] [PubMed]
- Reutelingsperger, C.; Schurgers, L. Coronary Artery Calcification A Janus-Faced Biomarker? JACC Cardiovasc. Imaging 2018, 11, 1324–1326. [Google Scholar] [CrossRef] [PubMed]
- Huang, H.; Virmani, R.; Younis, H.; Burke, A.P.; Kamm, R.D.; Lee, R.T. The impact of calcification on the biomechanical stability of atherosclerotic plaques. Circulation 2001, 103, 1051–1056. [Google Scholar] [CrossRef] [PubMed]
- Evangelos, D.; George, K.; Lourdes Victoria, Q.-S.; Paraskevi, F.; Theodoros, T. The anti-inflammatory effects of statins on coronary artery disease: an updated review of the literature. Curr. Cardiol. Rev. 2017, 13, 209–216. [Google Scholar]
- Tahara, N.; Kai, H.; Ishibashi, M.; Nakaura, H.; Kaida, H.; Baba, K.; Imaizumi, T.; Hayabuchi, N. Simvastatin attenuates plaque inflammation: evaluation by fluorodeoxyglucose positron emission tomography. J. Am. Coll. Cardiol. 2006, 48, 1825–1831. [Google Scholar] [CrossRef]
- Henein, M.; Granåsen, G.; Wiklund, U.; Schmermund, A.; Guerci, A.; Erbel, R.; Raggi, P. High dose and long-term statin therapy accelerate coronary artery calcification. Int. J. Cardiol. 2015, 184, 581–586. [Google Scholar] [CrossRef]
- Lee, S.-E.; Chang, H.-J.; Sung, J.M.; Park, H.B.; Heo, R.; Rizvi, A.; Conte, E.; Lin, F.Y.; Kumar, A.; Hadamitzky, M. Effects of statins on coronary atherosclerotic plaques: The PARADIGM study. JACC Cardiovasc. Imaging 2018, 11, 1475–1484. [Google Scholar] [CrossRef]
- Houslay, E.S.; Cowell, S.J.; Prescott, R.J.; Reid, J.; Burton, J.; Northridge, D.B.; Newby, D.E.; Boon, N.A. Progressive coronary calcification despite intensive lipid-lowering treatment: A randomised controlled trial. Heart 2006, 92, 1207–1212. [Google Scholar] [CrossRef] [PubMed]
- Shioi, A.; Ikari, Y. Plaque calcification during atherosclerosis progression and regression. J. Atheroscler. Thromb. 2018, 25, 294–303. [Google Scholar] [CrossRef] [PubMed]
- Hattori, K.; Ozaki, Y.; Ismail, T.F.; Okumura, M.; Naruse, H.; Kan, S.; Hashimoto, T.; Ishikawa, M.; Kawai, T.; Ohta, M.; et al. Impact of statin therapy on plaque characteristics as assessed by serial oct, grayscale and integrated backscatter–IVUS. JACC Cardiovasc. Imaging 2012, 5, 169–177. [Google Scholar] [CrossRef] [PubMed]
- Puri, R.; Nicholls, S.J.; Shao, M.; Kataoka, Y.; Uno, K.; Kapadia, S.R.; Nissen, S.E.; Tuzcu, E.M. Impact of statins on serial coronary calcification during atheroma progression and regression. J. Am. Coll. Cardiol. 2015, 65, 1273–1282. [Google Scholar] [CrossRef] [PubMed]
- Zheng, G.; Chen, J.; Lin, C.; Huang, X.; Lin, J. Effect of statin therapy on fibrous cap thickness in coronary plaques using optical coherence tomography: A systematic review and meta-analysis. J. Interv. Cardiol. 2015, 28, 514–522. [Google Scholar] [CrossRef] [PubMed]
- Shemesh, J.; Apter, S.; Itzchak, Y.; Motro, M. Coronary calcification compared in patients with acute versus in those with chronic coronary events by using dual-sector spiral CT. Radiology 2003, 226, 483–488. [Google Scholar] [CrossRef]
- Otsuka, F.; Finn, A.V.; Virmani, R. Do vulnerable and ruptured plaques hide in heavily calcified arteries? Atherosclerosis 2013, 229, 34–37. [Google Scholar] [CrossRef] [PubMed]
- Halon, D.A.; Lavi, I.; Barnett-Griness, O.; Rubinshtein, R.; Zafrir, B.; Azencot, M.; Lewis, B.S. Plaque morphology as predictor of late plaque events in patients with asymptomatic type 2 diabetes: A long-term observational study. JACC Cardiovasc. Imaging 2019, 12, 1353–1363. [Google Scholar] [CrossRef]
- Maldonado, N.; Kelly-Arnold, A.; Cardoso, L.; Weinbaum, S. The explosive growth of small voids in vulnerable cap rupture cavitation and interfacial debonding. J. Biomech. 2013, 46, 396–401. [Google Scholar] [CrossRef]
- Cardoso, L.; Kelly-Arnold, A.; Maldonado, N.; Laudier, D.; Weinbaum, S. Effect of tissue properties, shape and orientation of microcalcifications on vulnerable cap stability using different hyperelastic constitutive models. J. Biomech. 2014, 47, 870–877. [Google Scholar] [CrossRef] [Green Version]
- Hutcheson, J.D.; Maldonado, N.; Aikawa, E. Small entities with large impact: Microcalcifications and atherosclerotic plaque vulnerability. Curr. Opin. Lipidol. 2014, 25, 327–332. [Google Scholar] [CrossRef] [PubMed]
- Rogers, M.A.; Aikawa, E. Cardiovascular calcification: artificial intelligence and big data accelerate mechanistic discovery. Nature Rev. Cardiol. 2019, 16, 261–273. [Google Scholar] [CrossRef] [PubMed]
- Reith, S.; Milzi, A.; Dettori, R.; Marx, N.; Burgmaier, M. Predictors for target lesion microcalcifications in patients with stable coronary artery disease: An optical coherence tomography study. Clin. Res. Cardiol. 2018, 107, 763–771. [Google Scholar] [CrossRef] [PubMed]
- Hutcheson, J.D.; Goettsch, C.; Bertazzo, S.; Maldonado, N.; Ruiz, J.L.; Goh, W.; Quillard, T.; Yabusaki, K.; Faits, T.; Bouten, C.; et al. Genesis and growth of extracellular-vesicle-derived microcalcification in atherosclerotic plaques. Nat. Mater. 2016, 15, 335. [Google Scholar] [CrossRef] [PubMed]
- Kelly-Arnold, A.; Maldonado, N.; Laudier, D.; Aikawa, E.; Cardoso, L.; Weinbaum, S. Revised microcalcification hypothesis for fibrous cap rupture in human coronary arteries. Proc. Natl. Acad. Sci. USA 2013, 110, 10741–10746. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Cardoso, L.; Weinbaum, S. Changing views of the biomechanics of vulnerable plaque rupture: A review. Ann. Biomed. Eng. 2014, 42, 415–431. [Google Scholar] [CrossRef] [PubMed]
- Cilla, M.; Monterde, D.; Pena, E.; Martinez, M.A. Does microcalcification increase the risk of rupture? Proc. Inst. Mech. Eng. Part H J. Eng. Med. 2013, 227, 588–599. [Google Scholar] [CrossRef] [PubMed]
- Burgmaier, M.; Milzi, A.; Dettori, R.; Burgmaier, K.; Marx, N.; Reith, S. Co-localization of plaque macrophages with calcification is associated with a more vulnerable plaque phenotype and a greater calcification burden in coronary target segments as determined by OCT. PLoS ONE 2018, 13, e0205984. [Google Scholar] [CrossRef] [PubMed]
- Ruiz, J.L.; Weinbaum, S.; Aikawa, E.; Hutcheson, J.D. Zooming in on the genesis of atherosclerotic plaque microcalcifications. J. Physiol. 2016, 594, 2915–2927. [Google Scholar] [CrossRef] [Green Version]
- Pu, J.; Mintz, G.S.; Biro, S.; Lee, J.B.; Sum, S.T.; Madden, S.P.; Stone, G.W.; Burke, A.P.; Zhang, P.; He, B.; et al. Insights into echo-attenuated plaques, echolucent plaques, and plaques with spotty calcification: Novel findings from comparisons among intravascular ultrasound, near-infrared spectroscopy, and pathological histology in 2,294 human coronary artery segments. J. Am. Coll. Cardiol. 2014, 63, 2220–2233. [Google Scholar] [CrossRef]
- Kataoka, Y.; Wolski, K.; Uno, K.; Puri, R.; Tuzcu, E.M.; Nissen, S.E.; Nicholls, S.J. Spotty calcification as a marker of accelerated progression of coronary atherosclerosis: Insights from serial intravascular ultrasound. J. Am. Coll. Cardiol. 2012, 59, 1592–1597. [Google Scholar] [CrossRef] [PubMed]
- Ehara, S.; Kobayashi, Y.; Yoshiyama, M.; Shimada, K.; Shimada, Y.; Fukuda, D.; Naruko, T.; Nakamura, Y.; Yamashita, H.; Yamagishi, H.; et al. Spotty calcification typifies the culprit plaque in patients with acute myocardial infarction. Circulation 2004, 110, 3424–3429. [Google Scholar] [CrossRef] [PubMed]
- Calvert, P.A.; Obaid, D.R.; O’Sullivan, M.; Shapiro, L.M.; McNab, D.; Densem, C.G.; West, N.E.; Schofield, P.M.; Braganza, D.; Clarke, S.C.; 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, 894–901. [Google Scholar] [CrossRef] [PubMed]
- Libby, P.; Pasterkamp, G. Requiem for the ‘vulnerable plaque’. Eur. Heart J. 2015, 36, 2984–2987. [Google Scholar] [CrossRef] [PubMed]
- Arbab-Zadeh, A.; Fuster, V. The myth of the “vulnerable plaque”: transitioning from a focus on individual lesions to atherosclerotic disease burden for coronary artery disease risk assessment. J. Am. Coll. Cardiol. 2015, 65, 846–855. [Google Scholar] [CrossRef] [PubMed]
- Rothwell, P.M.; Villagra, R.; Gibson, R.; Donders, R.; Warlow, C.P. Evidence of a chronic systemic cause of instability of atherosclerotic plaques. Lancet 2000, 355, 19–24. [Google Scholar] [CrossRef]
- Goldstein, J.A.; Demetriou, D.; Grines, C.L.; Pica, M.; Shoukfeh, M.; O’Neill, W.W. Multiple complex coronary plaques in patients with acute myocardial infarction. N. Engl. J. Med. 2000, 343, 915–922. [Google Scholar] [CrossRef]
- Rachel, N.; Michael, H. Extensive coronary calcification: A clinically unrecognised condition. Curr. Vasc. Pharmacol. 2010, 8, 701–705. [Google Scholar]
- Dweck, M.R.; Aikawa, E.; Newby, D.E.; Tarkin, J.M.; Rudd, J.H.; Narula, J.; Fayad, Z.A. Noninvasive molecular imaging of disease activity in atherosclerosis. Circ. Res. 2016, 119, 330–340. [Google Scholar] [CrossRef]
- Mintz, G.S. Intravascular imaging of coronary calcification and its clinical implications. JACC Cardiovasc. Imaging 2015, 8, 461–471. [Google Scholar] [CrossRef]
- Yun, K.H.; Mintz, G.S.; Farhat, N.; Marso, S.P.; Taglieri, N.; Verheye, S.; Dressler, O.; Foster, M.C.; Margolis, M.P.; Templin, B.; 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, 471–477. [Google Scholar] [CrossRef] [PubMed]
- Youssef, G.; Kalia, N.; Darabian, S.; Budoff, M.J. Coronary calcium: New insights, recent data, and clinical role. Curr. Cardiol. Rep. 2013, 15, 325. [Google Scholar] [CrossRef] [PubMed]
- Nicoll, R.; Wiklund, U.; Zhao, Y.; Diederichsen, A.; Mickley, H.; Ovrehus, K.; Cademartiri, F.; Zamorano, P.; Gueret, P.; Schmermund, A.; et al. The coronary calcium score is a more accurate predictor of significant coronary stenosis than conventional risk factors in symptomatic patients: Euro-CCAD study. Int. J. Cardiol. 2016, 207, 13–19. [Google Scholar] [CrossRef] [PubMed]
- Sandfort, V.; Bluemke, D.A. CT calcium scoring. History, current status and outlook. Diagn. Interv. Imaging 2017, 98, 3–10. [Google Scholar] [CrossRef] [PubMed]
- Shemesh, J.; Tenenbaum, A.; Fisman, E.Z.; Koren-Morag, N.; Grossman, E. Coronary calcium in patients with and without diabetes: First manifestation of acute or chronic coronary events is characterized by different calcification patterns. Cardiovasc. Diabetol. 2013, 12, 161. [Google Scholar] [CrossRef] [PubMed]
- McClelland, R.L.; Jorgensen, N.W.; Budoff, M.; Blaha, M.J.; Post, W.S.; Kronmal, R.A.; Folsom, A.R.; Bild, D.E.; Shea, S.; Liu, K.; et al. 10-Year Coronary Heart Disease Risk Prediction Using Coronary Artery Calcium and Traditional Risk Factors: Derivation in the MESA (Multi-Ethnic Study of Atherosclerosis) With Validation in the HNR (Heinz Nixdorf Recall) Study and the DHS (Dallas Heart Study). J. Am. Coll. Cardiol. 2015, 66, 1643–1653. [Google Scholar]
- Criqui, M.H.; Denenberg, J.O.; Ix, J.H.; McClelland, R.L.; Wassel, C.L.; Rifkin, D.E.; Allison, M.A.; Rifkin, D.E.; Carr, J.J.; Budoff, M.J. Calcium density of coronary artery plaque and risk of incident cardiovascular events. JAMA 2014, 311, 271–278. [Google Scholar] [CrossRef]
- Criqui, M.H.; Knox, J.B.; Denenberg, J.O.; Forbang, N.I.; McClelland, R.L.; Novotny, T.E.; Allison, M.A.; Sandfort, V.; Waalen, J.; Blaha, M.J. Coronary artery calcium volume and density: potential interactions and overall predictive value: The multi-ethnic study of atherosclerosis. JACC Cardiovasc. Imaging 2017, 10, 845–854. [Google Scholar] [CrossRef]
- Knuuti, J.; Wijns, W.; Saraste, A.; Capodanno, D.; Barbato, E.; Funck-Brentano, C.; Agewall, S.; Prescott, E.; Storey, R.F.; Deaton, C.; et al. 2019 ESC Guidelines for the diagnosis and management of chronic coronary syndromes: The Task Force for the diagnosis and management of chronic coronary syndromes of the European Society of Cardiology (ESC). Eur. Heart J. 2019, 1–71. [Google Scholar] [CrossRef]
- Thomsen, C.; Abdulla, J. Characteristics of high-risk coronary plaques identified by computed tomographic angiography and associated prognosis: A systematic review and meta-analysis. Eur. Heart J. Cardiovasc. Imaging 2015, 17, 120–129. [Google Scholar] [CrossRef]
- Van Velzen, J.E.; de Graaf, F.R.; de Graaf, M.A.; Schuijf, J.D.; Kroft, L.J.; de Roos, A.; Schalij, M.J.; Reiber, J.H.C.; Bax, J.J.; Jukema, J.W.; et al. Comprehensive assessment of spotty calcifications on computed tomography angiography: Comparison to plaque characteristics on intravascular ultrasound with radiofrequency backscatter analysis. J. Nucl. Cardiol. 2011, 18, 893. [Google Scholar] [CrossRef] [PubMed]
- Saremi, F.; Achenbach, S. Coronary plaque characterization using CT. Am. J. Roentgenol. 2015, 204, W249–W260. [Google Scholar] [CrossRef] [PubMed]
- Obaid, D.R.; Calvert, P.A.; Gopalan, D.; Parker, R.A.; Hoole, S.P.; West, N.E.; Bennett, M.R.; Goddard, M.; Rudd, J.H.F. Atherosclerotic plaque composition and classification identified by coronary computed tomography. Circ. Cardiovasc. Imaging 2013, 6, 655–664. [Google Scholar] [CrossRef] [PubMed]
- Motoyama, S.; Ito, H.; Sarai, M.; Kondo, T.; Kawai, H.; Nagahara, Y.; Naruse, H.; Harigaya, H.; Kan, S.; Anno, H.; et al. Plaque characterization by coronary computed tomography angiography and the likelihood of acute coronary events in mid-term follow-up. J. Am. Coll. Cardiol. 2015, 66, 337–346. [Google Scholar] [CrossRef] [PubMed]
- Adamson, P.D.; Newby, D.E. Non-invasive imaging of the coronary arteries. Eur. Heart J. 2019, 40, 2444–2454. [Google Scholar] [CrossRef] [PubMed]
- Cho, I.; Chang, H.-J.; Sung, J.M.; Pencina, M.J.; Lin, F.Y.; Dunning, A.M.; Callister, T.Q.; Achenbach, S.; Berman, D.S.; Shaw, L.J.; et al. Coronary computed tomographic angiography and risk of all-cause mortality and nonfatal myocardial infarction in subjects without chest pain syndrome from the confirm registry (coronary CT angiography evaluation for clinical outcomes: an international multicenter registry). Circulation 2012, 126, 304–313. [Google Scholar] [PubMed]
- Fleg, J.L.; Stone, G.W.; Fayad, Z.A.; Granada, J.F.; Hatsukami, T.S.; Kolodgie, F.D.; Waxman, S.; Ohayon, J.; Pettigrew, R.; Sabatine, M.S.; et al. Detection of high-risk atherosclerotic plaque: Report of the NHLBI working group on current status and future directions. JACC Cardiovasc. Imaging 2012, 5, 941–955. [Google Scholar] [CrossRef] [PubMed]
- Fujii, K.; Hao, H.; Shibuya, M.; Imanaka, T.; Fukunaga, M.; Miki, K.; Hirota, S.; Tamaru, H.; Sawada, H.; Naito, Y.; et al. Accuracy of OCT, grayscale IVUS, and their combination for the diagnosis of coronary TCFA: An ex vivo validation study. JACC Cardiovasc. Imaging 2015, 8, 451–460. [Google Scholar] [CrossRef]
- Van Soest, G.; Marcu, L.; Bouma, B.E.; Regar, E. Intravascular imaging for characterization of coronary atherosclerosis. Curr. Opin. Biomed. Eng. 2017, 3, 1–12. [Google Scholar] [CrossRef]
- Tearney, G.J.; Regar, E.; Akasaka, T.; Adriaenssens, T.; Barlis, P.; Bezerra, H.G.; Costa, M.A.; Bouma, B.; Bruining, N.; Chowdhary, S.; 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. 2012, 59, 1058–1072. [Google Scholar] [CrossRef] [PubMed]
- Jang, I.-K.; Tearney, G.J.; MacNeill, B.; Takano, M.; Moselewski, F.; Iftima, N.; Bouma, B.E.; Shishkov, M.; Houser, S.; Aretz, H.T.; et al. In vivo characterization of coronary atherosclerotic plaque by use of optical coherence tomography. Circulation 2005, 111, 1551–1555. [Google Scholar] [CrossRef] [PubMed]
- Milzi, A.; Burgmaier, M.; Burgmaier, K.; Hellmich, M.; Marx, N.; Reith, S. Type 2 diabetes mellitus is associated with a lower fibrous cap thickness but has no impact on calcification morphology: An intracoronary optical coherence tomography study. Cardiovasc. Diabetol. 2017, 16, 152. [Google Scholar] [CrossRef] [PubMed]
- Tearney, G.J.; Yabushita, H.; Houser, S.L.; Aretz, H.T.; Jang, I.K.; Schlendorf, K.H.; Bouma, B.E.; Kauffman, C.R.; Shishkov, M.; Halpern, E.F.; et al. Quantification of macrophage content in atherosclerotic plaques by optical coherence tomography. Circulation 2003, 107, 113–119. [Google Scholar] [CrossRef] [PubMed]
- Sinclair, H.; Bourantas, C.; Bagnall, A.; Mintz, G.S.; Kunadian, V. OCT for the Identification of Vulnerable Plaque in Acute Coronary Syndrome. JACC Cardiovasc. Imaging 2015, 8, 198–209. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Habara, M.; Otsuka, F.; Tsuchikane, E.; Terashima, M.; Nasu, K.; Kinoshita, Y.; Matsuo, H.; Murata, A.; Suzuki, Y.; Kawase, Y.; et al. In vivo tissue characterization of human atherosclerotic plaques by optical coherence tomography: A directional coronary atherectomy study with histopathologic confirmation. Int. J. Cardiol. 2018, 268, 1–10. [Google Scholar] [CrossRef] [PubMed]
- Prati, F.; Romagnoli, E.; Gatto, L.; La Manna, A.; Burzotta, F.; Ozaki, Y.; Taglieri, N.; Marco, A.; Boi, A.; Fineschi, M.; et al. Relationship between coronary plaque morphology of the left anterior descending artery and 12 months clinical outcome: The CLIMA study. Eur. Heart J. 2019. [Google Scholar] [CrossRef]
- Hoshi, T.; Sato, A.; Akiyama, D.; Hiraya, D.; Sakai, S.; Shindo, M.; Aonuma, K.; Mori, K.; Minami, M. Coronary high-intensity plaque on T1-weighted magnetic resonance imaging and its association with myocardial injury after percutaneous coronary intervention. Eur. Heart J. 2015, 36, 1913–1922. [Google Scholar] [CrossRef]
- Noguchi, T.; Yamada, N.; Kawasaki, T.; Tanaka, A.; Yasuda, S. Detection of high-risk atherosclerotic plaques by magnetic resonance imaging. Circ. J. 2013, 77, 1975–1983. [Google Scholar] [CrossRef]
- Kanaya, T.; Noguchi, T.; Otsuka, F.; Asaumi, Y.; Kataoka, Y.; Morita, Y.; Nishimura, K.; Miura, H.; Nakao, K.; Fujino, M.; et al. Optical coherence tomography-verified morphological correlates of high-intensity coronary plaques on non-contrast T1-weighted magnetic resonance imaging in patients with stable coronary artery disease. Eur. Heart J. Cardiovasc. Imaging 2018, 20, 75–83. [Google Scholar] [CrossRef]
- Dweck, M.R.; Puntmann, V.O.; Vesey, A.T.; Fayad, Z.A.; Nagel, E. MR imaging of coronary arteries and plaques. JACC Cardiovasc. Imaging 2016, 9, 306–316. [Google Scholar] [CrossRef]
- Jansen, C.H.P.; Perera, D.; Wiethoff, A.J.; Phinikaridou, A.; Razavi, R.M.; Rinaldi, A.; Redwood, S.; Marber, M.S.; Greil, G.F.; Nagel, E.; et al. Contrast-enhanced magnetic resonance imaging for the detection of ruptured coronary plaques in patients with acute myocardial infarction. PLoS ONE 2017, 12, e0188292. [Google Scholar] [CrossRef] [PubMed]
- Matsumoto, K.; Ehara, S.; Hasegawa, T.; Sakaguchi, M.; Otsuka, K.; Yoshikawa, J.; Shimada, K. Localization of coronary high-intensity signals on T1-weighted MR imaging: Relation to plaque morphology and clinical severity of angina pectoris. JACC Cardiovasc. Imaging 2015, 8, 1143–1152. [Google Scholar] [CrossRef] [PubMed]
- Xie, Y.; Kim, Y.-J.; Pang, J.; Kim, J.S.; Yang, Q.; Wei, J.; Merz, C.N.B.; Shah, P.K.; Nguyen, C.T.; Deng, Z.; et al. Coronary atherosclerosis T1-weighed characterization with integrated anatomical reference: comparison with high-risk plaque features detected by invasive coronary imaging. JACC Cardiovasc. Imaging 2017, 10, 637–648. [Google Scholar] [CrossRef] [PubMed]
- Wurster, T.; Landmesser, U.; Engel, L.-C.; Bigalke, B.; Makowski, M. Coronary vessel wall imaging: State of the art and future directions. Curr. Cardiovasc. Imaging Rep. 2019, 12, 16. [Google Scholar] [CrossRef]
- Andrews, J.P.M.; Fayad, Z.A.; Dweck, M.R. New methods to image unstable atherosclerotic plaques. Atherosclerosis 2018, 272, 118–128. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Robson, P.M.; Dweck, M.R.; Trivieri, M.G.; Abgral, R.; Karakatsanis, N.A.; Contreras, J.; Fayad, Z.A.; Gidwani, U.; Narula, J.P.; Fuster, V.; et al. Coronary artery PET/MR imaging: Feasibility, limitations, and solutions. JACC Cardiovasc. Imaging 2017, 10, 1103–1112. [Google Scholar] [CrossRef] [PubMed]
- Evans, N.R.; Tarkin, J.M.; Chowdhury, M.M.; Warburton, E.A.; Rudd, J.H.F. PET imaging of atherosclerotic disease: advancing plaque assessment from anatomy to pathophysiology. Curr. Atheroscler. Rep. 2016, 18, 30. [Google Scholar] [CrossRef] [PubMed]
- Irkle, A.; Vesey, A.T.; Lewis, D.Y.; Skepper, J.N.; Bird, J.L.; Dweck, M.R.; Brindle, K.M.; Joshi, F.R.; Gallagher, F.A.; Warburton, E.A.; et al. Identifying active vascular microcalcification by 18F-sodium fluoride positron emission tomography. Nat. Commun. 2015, 6, 7495. [Google Scholar] [CrossRef] [Green Version]
- Li, L.; Li, X.; Jia, Y.P.; Fan, J.; Wang, H.; Fan, C.; Yan, M.; Wu, L.; Si, X.; Hao, X.; et al. Sodium-fluoride PET-CT for the non-invasive evaluation of coronary plaques in symptomatic patients with coronary artery disease: A cross-correlation study with intravascular ultrasound. Eur. J. Nucl. Med. Mol. Imaging 2018, 45, 2181–2189. [Google Scholar] [CrossRef]
- Dweck, M.R.; Chow, M.W.L.; Joshi, N.V.; Williams, M.C.; Jones, C.; Fletcher, A.M.; Boon, N.A.; Richardson, H.; White, A.; McKillop, G.; et al. Coronary arterial 18F-sodium fluoride uptake: A novel marker of plaque biology. J. Am. Coll. Cardiol. 2012, 59, 1539–1548. [Google Scholar] [CrossRef]
- Creager, M.D.; Hohl, T.; Hutcheson, J.D.; Moss, A.J.; Schlotter, F.; Blaser, M.C.; Tavares, A.A.; Park, M.-A.; Lee, L.H.; Singh, S.A.; et al. 18F-Fluoride Signal Amplification Identifies Microcalcifications Associated with Atherosclerotic Plaque Instability in Positron Emission Tomography/Computed Tomography Images. Circ. Cardiovasc. Imaging 2019, 12, e007835. [Google Scholar] [CrossRef] [PubMed]
- Joshi, N.V.; Vesey, A.T.; Williams, M.C.; Shah, A.S.; Calvert, P.A.; Craighead, F.H.; van Beek, E.J.; Yeoh, S.E.; Wallace, W.; Salter, D.; et al. 18F-fluoride positron emission tomography for identification of ruptured and high-risk coronary atherosclerotic plaques: A prospective clinical trial. Lancet 2014, 383, 705. [Google Scholar] [CrossRef]
- Fiz, F.; Morbelli, S.; Piccardo, A.; Bauckneht, M.; Ferrarazzo, G.; Pestarino, E.; Marini, C.; Democrito, A.; Riondato, M.; Villavecchia, G.; et al. F-18-NaF uptake by atherosclerotic plaque on PET/CT imaging: Inverse correlation between calcification density and mineral metabolic activity. J. Nucl. Med. 2015, 56, 1019–1023. [Google Scholar] [CrossRef] [PubMed]
- De Oliveira-Santos, M.; Castelo-Branco, M.; Silva, R.; Gomes, A.; Chichorro, N.; Abrunhosa, A.; Ferreira, M.J.; Donato, P.; de Lima, J.P.; Pego, M.; et al. Atherosclerotic plaque metabolism in high cardiovascular risk subjects—A subclinical atherosclerosis imaging study with F-18-NaF PET-CT. Atherosclerosis 2017, 260, 41–46. [Google Scholar] [CrossRef] [PubMed]
- Derlin, T.; Tóth, Z.; Papp, L.; Wisotzki, C.; Apostolova, I.; Habermann, C.R.; Klutmann, S.; Mester, J. Correlation of Inflammation Assessed by 18F-FDG PET, Active Mineral Deposition Assessed by 18F-Fluoride PET, and Vascular Calcification in Atherosclerotic Plaque: A Dual-Tracer PET/CT Study. J. Nucl. Med. 2011, 52, 1020–1027. [Google Scholar] [CrossRef] [PubMed]
- Pelletier-Galarneau, M.; Ruddy, T.D. Molecular imaging of coronary inflammation. Trends Cardiovasc. Med. 2019, 29, 191–197. [Google Scholar] [CrossRef] [PubMed]
- Pawley, J.B. (Ed.) Handbook of Biological Confocal Microscopy, 3rd ed.; Springer: Berlin/Heidelberg, Germany, 2006. [Google Scholar]
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Vancheri, F.; Longo, G.; Vancheri, S.; Danial, J.S.H.; Henein, M.Y. Coronary Artery Microcalcification: Imaging and Clinical Implications. Diagnostics 2019, 9, 125. https://doi.org/10.3390/diagnostics9040125
Vancheri F, Longo G, Vancheri S, Danial JSH, Henein MY. Coronary Artery Microcalcification: Imaging and Clinical Implications. Diagnostics. 2019; 9(4):125. https://doi.org/10.3390/diagnostics9040125
Chicago/Turabian StyleVancheri, Federico, Giovanni Longo, Sergio Vancheri, John S. H. Danial, and Michael Y. Henein. 2019. "Coronary Artery Microcalcification: Imaging and Clinical Implications" Diagnostics 9, no. 4: 125. https://doi.org/10.3390/diagnostics9040125