Koyama Yutaro, Miura Masaru, Kobayashi Tohru, Hokosaki Tatsunori, Suganuma Eisuke, Numano Fujito, Furuno Kenji, Shiono Junko, Ebata Ryota, Fuse Shigeto, Fukazawa Ryuji, Mitani Yoshihide
Department of Cardiology, Tokyo Metropolitan Children's Medical Center, 2-8-29 Musashidai, Fuchu, Tokyo, 183-8561, Japan.
Department of Data Science, Clinical Research Center, National Center for Child Health and Development, Tokyo, Japan.
Eur J Pediatr. 2023 Feb;182(2):633-640. doi: 10.1007/s00431-022-04719-x. Epub 2022 Nov 25.
The long-term prognosis of patients with Kawasaki disease (KD) complicated by coronary artery aneurysms (CAA) is still unclear. The present, multicenter registry study aimed to study the factors associated with coronary events (CE) and determine an appropriate management method for patients with KD complicated with CAA. Patients with KD with onset after 2015 and with a medium-sized or large CAA having an actual diameter ≥ 4 mm or a Z-score ≥ 5.0 at 30 days and later after KD onset were included in the annual survey. The primary endpoint was the time-dependent incidence of CE. Associated factors were also examined. In total, 179 patients from 53 centers were enrolled and followed up for a median of 501 days. The median age at KD onset was 2.2 years, 137 patients were male (77%), 47 had incomplete KD (26%), and 36 had large CAA (20%). CE occurred in 13 patients (7%; 95% confidence interval: 4-12%); eight (62%) experienced CE within 1 year, and all the patients experienced a CE within 2 years. All but one patient received antiplatelet drugs and warfarin. Patients with a large CAA had significantly more CAA (2.8 vs. 1.7, p < 0.001), more cases of warfarin use (86% vs. 43%, p < 0.001), and were more likely to have CE (28% vs. 2%, p < 0.001) than those with a medium-sized CAA. On univariate Cox regression analysis, the factors significantly associated with CE were large CAA (hazard ratio (HR): 17.0), three or more CAA (HR: 23.3), and beaded CAA (HR: 15.9). Multivariable Cox regression analysis revealed that the only associated factor was a large CAA.
Patients with a large CAA were more likely to have a CE within 2 years. Antithrombotic therapy with warfarin did not eliminate the CE risk, and better therapies are desirable.
• Coronary artery aneurysms are a serious complication of Kawasaki disease, and coronary events are sometimes fatal. • In previous, retrospective studies in Japan, large aneurysms, male sex, and refractoriness to initial immunoglobulin therapy were considered risk factors for coronary events.
• Of 179 patients with a medium sized or large aneurysm, 13 (7%) experienced coronary events, all of which occurred within 2 years of onset. Factors significantly associated with coronary events were large aneurysms, three or more aneurysms, and beaded aneurysms.
川崎病（KD）合并冠状动脉瘤（CAA）患者的长期预后仍不明确。本多中心登记研究旨在探讨与冠状动脉事件（CE）相关的因素，并确定KD合并CAA患者的合适管理方法。纳入2015年后发病、KD发病30天及以后实际直径≥4mm或Z评分≥5.0的中型或大型CAA的KD患者进行年度调查。主要终点是CE的时间依赖性发生率。还检查了相关因素。共有来自53个中心的179例患者入组，中位随访501天。KD发病时的中位年龄为2.2岁，137例患者为男性（77%），47例为不完全KD（26%），36例为大型CAA（20%）。13例患者发生CE（7%；95%置信区间：4 - 12%）；8例（62%）在1年内发生CE，所有患者均在2年内发生CE。除1例患者外，所有患者均接受了抗血小板药物和华法林治疗。与中型CAA患者相比，大型CAA患者的CAA明显更多（2.8对1.7，p < 0.001），华法林使用病例更多（86%对43%，p < 0.001），发生CE的可能性也更大（28%对2%，p < 0.001）。单因素Cox回归分析显示，与CE显著相关的因素是大型CAA（风险比（HR）：17.0）、3个或更多CAA（HR：23.3）和串珠状CAA（HR：15.9）。多变量Cox回归分析显示，唯一的相关因素是大型CAA。
大型CAA患者在2年内发生CE的可能性更大。华法林抗栓治疗并未消除CE风险，需要更好的治疗方法。
• 冠状动脉瘤是川崎病的严重并发症，冠状动脉事件有时是致命的。• 在日本以往的回顾性研究中，大型动脉瘤、男性以及对初始免疫球蛋白治疗的难治性被认为是冠状动脉事件的危险因素。
• 在179例中型或大型动脉瘤患者中，13例（7%）发生冠状动脉事件，所有事件均在发病后2年内发生。与冠状动脉事件显著相关的因素是大型动脉瘤、3个或更多动脉瘤以及串珠状动脉瘤。
