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Multicenter Study
. 2018 May 7;172(5):e180030.
doi: 10.1001/jamapediatrics.2018.0030. Epub 2018 May 7.

Association of Severity of Coronary Artery Aneurysms in Patients With Kawasaki Disease and Risk of Later Coronary Events

Masaru Miura  1   2 , Tohru Kobayashi  3 , Tetsuji Kaneko  2 , Mamoru Ayusawa  4 , Ryuji Fukazawa  5 , Naoya Fukushima  1 , Shigeto Fuse  6 , Kenji Hamaoka  7 , Keiichi Hirono  8 , Taichi Kato  9 , Yoshihide Mitani  10 , Seiichi Sato  11 , Shinya Shimoyama  12 , Junko Shiono  13 , Kenji Suda  14 , Hiroshi Suzuki  15 , Jun Maeda  16 , Kenji Waki  17 ; The Z-score Project 2nd Stage Study Group; Hitoshi Kato  3 , Tsutomu Saji  18 , Hiroyuki Yamagishi  16 , Aya Ozeki  2 , Masako Tomotsune  2 , Makiko Yoshida  2 , Yohei Akazawa  19 , Kentaro Aso  20 , Shouzaburoh Doi  21 , Yoshi Fukasawa  9 , Kenji Furuno  22 , Yasunobu Hayabuchi  23 , Miyuki Hayashi  5 , Takafumi Honda  24 , Norihisa Horita  25 , Kazuyuki Ikeda  7 , Masahiro Ishii  26 , Satoru Iwashima  27 , Masahiro Kamada  28 , Masahide Kaneko  3 , Hiroshi Katyama  29 , Yoichi Kawamura  30 , Atushi Kitagawa  26 , Akiko Komori  4 , Kenji Kuraishi  31 , Hiroshi Masuda  3 , Shinichi Matsuda  32 , Satoshi Matsuzaki  19 , Sayaka Mii  33 , Tomoyuki Miyamoto  34 , Yuji Moritou  28 , Noriko Motoki  19 , Kiyoshi Nagumo  35 , Tsuneyuki Nakamura  36 , Eiki Nishihara  31 , Yuichi Nomura  37 , Shohei Ogata  26 , Hiroyuki Ohashi  10 , Kenichi Okumura  29 , Daisuke Omori  38 , Tetsuya Sano  39 , Eisuke Suganuma  32 , Tsutomu Takahashi  40 , Shinichi Takatsuki  18 , Atsuhito Takeda  41 , Masaru Terai  24 , Manatomo Toyono  42 , Kenichi Watanabe  15 , Makoto Watanabe  5 , Masaki Yamamoto  43 , Kenichiro Yamamura  44
Affiliations
Multicenter Study

Association of Severity of Coronary Artery Aneurysms in Patients With Kawasaki Disease and Risk of Later Coronary Events

Masaru Miura et al. JAMA Pediatr. .

Abstract

Importance: Few studies with sufficient statistical power have shown the association of the z score of the coronary arterial internal diameter with coronary events (CE) in patients with Kawasaki disease (KD) with coronary artery aneurysms (CAA).

Objective: To clarify the association of the z score with time-dependent CE occurrence in patients with KD with CAA.

Design, setting, and participants: This multicenter, collaborative retrospective cohort study of 44 participating institutions included 1006 patients with KD younger than 19 years who received a coronary angiography between 1992 and 2011.

Main outcomes and measures: The time-dependent occurrence of CE, including thrombosis, stenosis, obstruction, acute ischemic events, and coronary interventions, was analyzed for small (z score, <5), medium (z score, ≥5 to <10; actual internal diameter, <8 mm), and large (z score, ≥10 or ≥8 mm) CAA by the Kaplan-Meier method. The Cox proportional hazard regression model was used to identify risk factors for CE after adjusting for age, sex, size, morphology, number of CAA, resistance to initial intravenous immunoglobulin (IVIG) therapy, and antithrombotic medications.

Results: Of 1006 patients, 714 (71%) were male, 341 (34%) received a diagnosis before age 1 year, 501 (50%) received a diagnosis between age 1 and 5 years, and 157 (16%) received a diagnosis at age 5 years or older. The 10-year event-free survival rate for CE was 100%, 94%, and 52% in men (P < .001) and 100%, 100%, and 75% in women (P < .001) for small, medium, and large CAA, respectively. The CE-free rate was 100%, 96%, and 79% in patients who were not resistant to IVIG therapy (P < .001) and 100%, 96%, and 51% in patients who were resistant to IVIG therapy (P < .001), respectively. Cox regression analysis revealed that large CAA (hazard ratio, 8.9; 95% CI, 5.1-15.4), male sex (hazard ratio, 2.8; 95% CI, 1.7-4.8), and resistance to IVIG therapy (hazard ratio, 2.2; 95% CI, 1.4-3.6) were significantly associated with CE.

Conclusions and relevance: Classification using the internal diameter z score is useful for assessing the severity of CAA in relation to the time-dependent occurrence of CE and associated factors in patients with KD. Careful management of CE is necessary for all patients with KD with CAA, especially men and IVIG-resistant patients with a large CAA.

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Conflict of interest statement

Conflict of Interest Disclosures: Drs Miura, Kobayashi, Ayusawa, and Fuse received an honorarium from the Japan Blood Products Organization and Teijin Pharma Limited Nihon Pharmaceutical Co. Drs Miura, Kobayashi, Kato, and Ayusawa received an honorarium from the Mitsubishi Tanabe Pharma Corporation. No other disclosures are reported.

Figures

Figure 1.
Figure 1.. Kaplan-Meier Survival Curves for Coronary Events in the Classification by the Internal Diameter z Score of Coronary Artery Aneurysms in Male and Female Patients
A, Coronary event–free survival rates for male patients. B, Coronary event–free survival rates for female patients. The survival curves were significantly different among the 3 groups (P < .001, log rank test of equality). Small, internal diameter z score of coronary artery aneurysms of less than 5; medium, z score of 5 to 10 and actual internal diameter of less than 8 mm; and large, z score of 10 or more or actual internal diameter of 8 mm or more.
Figure 2.
Figure 2.. Kaplan-Meier Survival Curves for Major Adverse Cardiac Events in the Classification by the Internal Diameter z Score of Coronary Artery Aneurysms in Male and Female Patients
A, Major adverse cardiac event–free survival rates for male patients. B, Major adverse cardiac event–free survival rates for female patients. The survival curves were significantly different among the 3 groups (P < .001, log rank test of equality). Small, internal diameter z score of coronary artery aneurysms of less than 5; medium, z score of 5 to 10 and actual internal diameter of less than 8 mm; and large, z score of 10 or more or actual internal diameter of 8 mm or more.
See this image and copyright information in PMC

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