BACKGROUND: Calcified nodule (CN) has a unique plaque morphology, in which an area of nodular calcification causes disruption of the fibrous cap with overlying luminal thrombus. CN is reported to be the least frequent cause of acute coronary thrombosis, and the pathogenesis of CN has not been well studied. OBJECTIVES: The purpose of this study is to provide a comprehensive morphologic assessment of the CN in addition to providing an evolutionary perspective as to how CN causes acute coronary thrombosis in patients with acute coronary syndromes. METHODS: A total of 26 consecutive CN lesions from 25 subjects from our autopsy registry were evaluated. Detailed morphometric analysis was performed to understand the plaque characteristics of CN and nodular calcification. RESULTS: The mean age was 70 years, with a high prevalence of diabetes and chronic kidney disease. CNs were equally distributed between men and women, with 61.5% of CNs found in the right coronary artery (n = 16), mainly within its mid-portion (56%). All CNs demonstrated surface nonocclusive luminal thrombus, consisting of multiple nodular fragments of calcification, protruding and disrupting the overlying fibrous cap, with evidence of endothelial cell loss. The degree of circumferential sheet calcification was significantly less in the culprit section (89° [interquartile range: 54° to 177°]) than in the adjacent proximal (206° [interquartile range: 157° to 269°], p = 0.0034) and distal (240° [interquartile range: 178° to 333°], p = 0.0004) sections. Polarized picrosirius red staining showed the presence of necrotic core calcium at culprit sites of CNs, whereas collagen calcium was more prevalent at the proximal and distal regions of CNs. CONCLUSIONS: Our study suggests that fibrous cap disruption in CN with overlying thrombosis is initiated through the fragmentation of necrotic core calcifications, which is flanked-proximally and distally-by hard, collagen-rich calcification in coronary arteries, which are susceptible to mechanical stress.
BACKGROUND: Calcified nodule (CN) has a unique plaque morphology, in which an area of nodular calcification causes disruption of the fibrous cap with overlying luminal thrombus. CN is reported to be the least frequent cause of acute coronary thrombosis, and the pathogenesis of CN has not been well studied. OBJECTIVES: The purpose of this study is to provide a comprehensive morphologic assessment of the CN in addition to providing an evolutionary perspective as to how CN causes acute coronary thrombosis in patients with acute coronary syndromes. METHODS: A total of 26 consecutive CN lesions from 25 subjects from our autopsy registry were evaluated. Detailed morphometric analysis was performed to understand the plaque characteristics of CN and nodular calcification. RESULTS: The mean age was 70 years, with a high prevalence of diabetes and chronic kidney disease. CNs were equally distributed between men and women, with 61.5% of CNs found in the right coronary artery (n = 16), mainly within its mid-portion (56%). All CNs demonstrated surface nonocclusive luminal thrombus, consisting of multiple nodular fragments of calcification, protruding and disrupting the overlying fibrous cap, with evidence of endothelial cell loss. The degree of circumferential sheet calcification was significantly less in the culprit section (89° [interquartile range: 54° to 177°]) than in the adjacent proximal (206° [interquartile range: 157° to 269°], p = 0.0034) and distal (240° [interquartile range: 178° to 333°], p = 0.0004) sections. Polarized picrosirius red staining showed the presence of necrotic core calcium at culprit sites of CNs, whereas collagen calcium was more prevalent at the proximal and distal regions of CNs. CONCLUSIONS: Our study suggests that fibrous cap disruption in CN with overlying thrombosis is initiated through the fragmentation of necrotic core calcifications, which is flanked-proximally and distally-by hard, collagen-rich calcification in coronary arteries, which are susceptible to mechanical stress.
Authors: Makoto Araki; Seung-Jung Park; Harold L Dauerman; Shiro Uemura; Jung-Sun Kim; Carlo Di Mario; Thomas W Johnson; Giulio Guagliumi; Adnan Kastrati; Michael Joner; Niels Ramsing Holm; Fernando Alfonso; William Wijns; Tom Adriaenssens; Holger Nef; Gilles Rioufol; Nicolas Amabile; Geraud Souteyrand; Nicolas Meneveau; Edouard Gerbaud; Maksymilian P Opolski; Nieves Gonzalo; Guillermo J Tearney; Brett Bouma; Aaron D Aguirre; Gary S Mintz; Gregg W Stone; Christos V Bourantas; Lorenz Räber; Sebastiano Gili; Kyoichi Mizuno; Shigeki Kimura; Toshiro Shinke; Myeong-Ki Hong; Yangsoo Jang; Jin Man Cho; Bryan P Yan; Italo Porto; Giampaolo Niccoli; Rocco A Montone; Vikas Thondapu; Michail I Papafaklis; Lampros K Michalis; Harmony Reynolds; Jacqueline Saw; Peter Libby; Giora Weisz; Mario Iannaccone; Tommaso Gori; Konstantinos Toutouzas; Taishi Yonetsu; Yoshiyasu Minami; Masamichi Takano; O Christopher Raffel; Osamu Kurihara; Tsunenari Soeda; Tomoyo Sugiyama; Hyung Oh Kim; Tetsumin Lee; Takumi Higuma; Akihiro Nakajima; Erika Yamamoto; Krzysztof L Bryniarski; Luca Di Vito; Rocco Vergallo; Francesco Fracassi; Michele Russo; Lena M Seegers; Iris McNulty; Sangjoon Park; Marc Feldman; Javier Escaned; Francesco Prati; Eloisa Arbustini; Fausto J Pinto; Ron Waksman; Hector M Garcia-Garcia; Akiko Maehara; Ziad Ali; Aloke V Finn; Renu Virmani; Annapoorna S Kini; Joost Daemen; Teruyoshi Kume; Kiyoshi Hibi; Atsushi Tanaka; Takashi Akasaka; Takashi Kubo; Satoshi Yasuda; Kevin Croce; Juan F Granada; Amir Lerman; Abhiram Prasad; Evelyn Regar; Yoshihiko Saito; Mullasari Ajit Sankardas; Vijayakumar Subban; Neil J Weissman; Yundai Chen; Bo Yu; Stephen J Nicholls; Peter Barlis; Nick E J West; Armin Arbab-Zadeh; Jong Chul Ye; Jouke Dijkstra; Hang Lee; Jagat Narula; Filippo Crea; Sunao Nakamura; Tsunekazu Kakuta; James Fujimoto; Valentin Fuster; Ik-Kyung Jang Journal: Nat Rev Cardiol Date: 2022-04-21 Impact factor: 49.421
Authors: Anne Cornelissen; Daniela T Fuller; Raquel Fernandez; Xiaoqing Zhao; Robert Kutys; Elizabeth Binns-Roemer; Marco Delsante; Atsushi Sakamoto; Ka Hyun Paek; Yu Sato; Rika Kawakami; Masayuki Mori; Kenji Kawai; Teruhiko Yoshida; Khun Zaw Latt; Clint L Miller; Paul S de Vries; Frank D Kolodgie; Renu Virmani; Myung Kyun Shin; Maarten Hoek; Jurgen Heymann; Jeffrey B Kopp; Avi Z Rosenberg; Harry R Davis; Liang Guo; Aloke V Finn Journal: Arterioscler Thromb Vasc Biol Date: 2021-05-27 Impact factor: 10.514