Asymptomatic myocardial infarction in Kawasaki disease: Long-term prognosis

Summary Eight patients with Kawasaki disease who had sustained asymptomatic myocardial infarction 8–15 years ago (mean, 13.1 years) were reexamined by various noninvasive cardiac function tests to assess long-term prognosis.At present, electrocardiograms (ECGs) are normal in six patients. However, all eight patients had a prolonged preejection period (PEP) to left ventricular ejection time (LVET) ratio 30 s after amylnitrate (AN) inhalation. Six patients had perfusion defects by exercise thallium-201 myocardial scintigraphy, and two patients developed ST segment depression in treadmill exercise testing.These patients are symptom-free even though their physical activity has not been restricted. Yet they proved to have serious abnormalities suggesting sequelae of myocardial infarction or existing myocardial ischemia. Judging from the results of noninvasive cardiac function tests and recently performed coronary angiography, five of the eight patients require coronary bypass surgery.     

Case-control study of giant coronary aneurysms due to Kawasaki disease

BACKGROUND: Epidemiologic features of the formation of giant coronary aneurysm due to Kawasaki disease and its risk factors are not still clear. METHODS: One hundred and five patients with giant coronary aneurysms were selected from the 15th and 16th nationwide surveys of Kawasaki disease in Japan. With all other patients reported from the same hospital as a control group, odds ratios (OR) were calculated for some potential risk factors. RESULTS: Some factors affecting the formation of giant coronary aneurysms were revealed. Of these factors, the following were considered to be useful for the treatment of patients with Kawasaki disease: male sex (OR compared with females = 1.99), 0 years old (OR compared with 1-2 years = 1.71), visiting the hospital on 1-3 days of illness (OR compared to 4-6 days = 1.72), leukocyte count (OR with 1000 /mm3 increase = 0.56), neutrophil concentration among leukocyte (OR with 10% increase = 1.11), hemoglobin concentration (OR with 1 mg/dL increase = 0.73), alanine aminotransferase level (ALT; OR with 10 IU/dL increase = 1.02) and serum sodium level (OR with 1 mEq/L increase = 0.80). CONCLUSIONS: The observation of 105 cases with giant coronary aneurysms due to Kawasaki disease reported in the nationwide survey provides information about some risk factors and other considerations about the aneurysms.     

儿童川崎病致巨大冠状动脉瘤伴血栓形成一例

患儿女,9岁10个月。因巨大冠状动脉(简称冠脉)瘤1年余入我院。患儿于13个月前无明显诱因而发热,体温达39~40℃,双眼结膜及咽部充血,2 d后左颈部淋巴结肿大,约1·5 cm×1·0 cm大小,并有触痛。于发热第6天出现口唇潮红、杨梅舌、手足硬性水肿,转诊上级医院,诊断为“川崎病(Kawasak i d isease,KD)”。行二维超声心动图(2-d im ensional echocard iography,2DE)检查示“巨大冠脉瘤(coronary arterial aneurysm,CAA)”,即予大剂量静脉免疫球蛋白(intravenous immunoglobu lin,IVIG,40 g/d,共用2 d)及阿司匹林治疗。约于病程第8天热退,第9…     

川崎病并发巨大冠状动脉瘤的远期预后研究

目的探讨川崎病(KD)并发GCAA患儿的远期预后,为进一步探索KD引起心血管损害后期的诊断治疗提供依据。方法选取2001年5月至2006年5月在广州市妇女儿童医疗中心儿童医院诊断为KD并发冠状动脉损害的患儿为研究对象。依据冠状动脉损害严重程度分为冠状动脉扩张(CAD)组、中小冠状动脉瘤(CAA)组和巨大冠状动脉瘤(GCAA)组。随访起止时间为急性期出院后至2009年5月。所有纳入随访的患儿均于急性期出院后6个月、1年、2年和3年各随访超声心动图1次,观察冠状动脉形态;对急性期3个月后常规超声心动图提示冠状动脉形态未恢复患儿行ATP负荷超声心动图及冠状动脉造影检查,观察心脏室壁运动、左右冠状动脉血流储备和冠状动脉分支病变情况。死亡患儿行尸解及冠状动脉病理学检查。结果CAD组纳入166例,中小CAA组纳入59例,GCAA组纳入15例。①随访3年时超声心动图显示GCAA组2/15例(13.3%)恢复正常,显著低于CAD组和中小CAA组(P均0.001);GCAA组1例(6.7%)显示冠状动脉扩张;10例(66.7%)表现为CAA,其中3例为GCAA,3例合并冠状动脉狭窄或闭塞。②ATP负荷超声心动图显示,GCAA组室壁运动异常的发生率显著高于CAD组(6/9例vs8/55例,P0.001),与CAA组差异无统计学意义(6/9例vs17/31例,P0.05);非参数检验提示,3组间室壁运动异常发生率有统计学差异,以GCAA组发生率较高(Z=-4.2,P0.001)。③GCAA组6/15例行冠状动脉造影,4/6例仍存在CAA,1/6例GCAA退缩为轻度CAD。5/6例出现冠状动脉狭窄或(和)闭塞,其中1例闭塞后再通,1例合并侧支血管形成。④GCAA组死亡2例,尸解冠状动脉大体可见,左右冠状动脉各分支呈串珠样膨大,瘤样扩张的冠状动脉管腔内可见充满暗红色血栓样物质,管壁显著增厚。冠状动脉分支和前降支病理学检查均显示:内膜增厚,炎症细胞浸润。结论KD并发GCAA患儿的预后较差,冠状动脉损害可持续存在;后期可发生冠状动脉狭窄或闭塞,导致缺血性心脏病;常规超声心动图与ATP负荷超声心动图、冠状动脉造影结合应用,对KD并发GCAA的远期随访有重要意义。     

川崎病合并巨大冠状动脉瘤101例中长期随访

目的总结分析川崎病合并巨大冠状动脉瘤(GCAA)患儿的临床特点及中长期预后。方法回顾性队列研究。自首都医科大学附属北京儿童医院2004年建立的川崎病冠状动脉瘤随诊患儿队列中选择符合标准的101例GCAA患儿进行总结。GCAA诊断标准为冠状动脉瘤内径≥8.0 mm,患儿均完成定期随诊。随访终点为患儿最后一次随诊或死亡时间。组间比较采用t检验或χ²检验。结果101例符合纳入标准GCAA患儿入选研究对象,其中男82例(81.2%)、女19例(18.8%);发病年龄2.5(1.0,4.5)岁,随访时间4.5(2.7,7.5)年,最长19年。患儿常规接受阿司匹林、华法林治疗,严重者另加氯吡格雷。截至随访终点,13例(12.9%)患儿出现心脏增大,11例(10.9%)合并心功能不全,13例(12.9%)发生心肌梗死,2例(2.0%)接受冠状动脉搭桥术,6例(5.9%)死亡。受累冠状动脉共170支,位于左侧主干24支(14.1%),左回旋支10支(5.9%),左前降支57支(33.5%),右侧冠状动脉中段78支(45.9%),右侧冠状动脉远段1支(0.6%)。11例(10.9%)患儿GCAA内径回缩至4.0 mm及以下;受累的170支冠状动脉中,28支(16.5%)冠状动脉内径回缩到4.0 mm及以下。左侧、右侧GCAA回缩情况差异无统计学意义[18.7%(17/91)比13.9%(11/79),χ²=2.473,P=0.116]。单侧GCAA与双侧GCAA患儿回缩情况差异无统计学意义[16.1%(9/56)比4.4%(2/45),χ²=2.381,P=0.123]。结论川崎病GCAA以右冠状动脉中段、左冠状动脉前降支最常见,患儿心血管事件发生率及病死率较高,预后欠佳。     

Strict management of a pregnant patient with giant coronary artery aneurysm due to Kawasaki disease

Coronary artery aneurysms (CAA) may occur in Kawasaki disease (KD). Patients with giant CAA (diameter >8 mm), in particular, have higher risk of myocardial infarction. Previous reports have demonstrated the necessity of anticoagulation therapy in such cases. The management of patients with KD complicated by giant CAA later in life, however, remains controversial. Here, we describe the strict management in the case of a 28‐year‐old pregnant Japanese woman with KD with giant CAA (diameter, 11 mm). Instead of warfarin, the patient was given low‐dose aspirin and i.v. unfractionated heparin during pregnancy to prevent thrombosis in the giant CAA. At 38 weeks of gestation, she had spontaneous delivery of a healthy baby. No thrombotic or bleeding complications were observed. The strict anticoagulation therapy resulted in successful pregnancy and delivery without any adverse events.     

Cytokines predict coronary aneurysm formation in Kawasaki disease patients

In this study, we measured serially the serum levels of cytokines including interleukin-6 (IL-6), IL-8, soluble IL-2 receptor (sIL-2R) and tumour necrosis factor (TNF-) in 60 patients with Kawasaki disease (KD) and evaluated the clinical significance of these cytokines in predicting coronary aneurysm formation. Of the 60 patients, 12 were complicated with coronary aneurysm. Blood samples were collected within the 1st week after onset of fever, then once a week for the 1st month, and once a month for another 5 months. The serum levels of IL-6, IL-8, sIL-2R and TNF were measured using an ELISA or RIA method. Our results show that the changes in serum IL-6 and IL-8 were faster than those of sIL-2R and TNF. Within the 1st week, the serum levels of IL-6 and IL-8 were significantly higher in the patients with than in those without coronary aneurysm (P<0.001). In addition, the serum levels of IL-6 and IL-8 obtained in the 1st week were highly correlated (P<0.001) with those of C-reactive protein and erythrocyte sedimentation rate, and the serum levels of sIL-2R and TNF were also increased at the 1st week reaching the highest level in the 2nd week. In the 2nd week, the serum levels of sIL-2R and TNF were significantly higher in the patients with than in those without coronary aneurysm (P<0.05). These findings suggest that the serum levels of IL-6 and IL-8 obtained in the 1st week may serve as useful parameters in predicting coronary aneurysm formation in KD patients.     

川崎病冠状动脉病变的远期预后观察

目的观察川崎病(KD)伴冠状动脉病变(CAD)的远期恢复情况.方法对262例确诊KD住院患儿,于急期或亚急期行心电图及超声心动图检查,并于病程不同时期(6个月至10年)进行复查.结果急期和亚急期行心电图检查262例异常74例.随访中低电压全部恢复,3例重度冠状动脉瘤患儿心肌缺血持续存在.超声心动图检查发现CAD50例,随访6个月至10年,33例恢复,6例未愈,11例失访.无CAD的KD患儿随访结果正常.结论CAD的KD患儿约60%在10年内痊愈,阿斯匹林需持续用至痊愈.     

Grown-up Kawasaki disease patients who have giant coronary aneurysms

Background  

Many Kawasaki disease (KD) patients have reached adulthood in Japan. The current status of adult patients who have giant coronary aneurysms with KD is not well understood.     

Long-term outcome of coronary abnormalities in patients after Kawasaki disease

From January 1973 through December 1992, a total of 302 patients (183 males, 119 females) with Kawasaki disease (KD) underwent coronary angiography. The age at onset of KD ranged from 2 months to 12.3 years (median 1.4 years). The age at the first angiographic evaluation ranged from 6 months to 17 years (median 3.5 years). Most of the patients (85%) had suffered from KD before 1985 and thus were treated without benefit of γ-globulin. Follow-up varied from 6 months to 25.8 years (median 13.6 years). Coronary abnormalities were confirmed in 71 (23.5%) of 302 patients; the left coronary artery (LCA) alone was involved in 36 cases, the right coronary artery (RCA) alone in 10 cases, and both arteries in 25 cases. Serial angiographic evaluation of the 42 cases revealed different attitudes in the progress of coronary abnormalities. All large aneurysms showed a tendency to regress, although some progressed to stenotic lesions. Moderate aneurysms stayed unchanged, regressed, or progressed to stenosis or obstruction. Small aneurysm never became stenotic and frequently regressed to normal internal diameter. aneurysms of the RCA tended to regress relatively early during the follow-up period, whereas those of the LCA gradually progressed to stenotic lesions. In 7 of 35 patients with RCA lesions, aneurysms progressed to complete obstruction and subsequent recanalization within 0.5 to 7.7 years (median 3.6 years) after the onset of KD. Most of the patients with coronary artery sequelae after KD remain asymptomatic. Serial angiographic observation is indicated for those patients who develop large coronary aneurysms during the acute phase of KD. The standard 12-lead electrocardiogram, chest roentgenogram, and exercise stress test are less sensitive for detecting and evaluating patients with coronary sequelae. For the screening of myocardial ischemia after KD, stress thallium 201 scintigraphy with dipyridamole infusion is recommended.     

Coronary aneurysm in Kawasaki syndrome: incidence and prognosis

Out of 10 pediatric patients with coronary aneurysms after Kawasaki-syndrome 9 were reinvestigated 1 to 9 years after their initial illness. Out of 21 aneurysms of all types and sizes 2 showed early and 1 late, silent thrombosis leading to myocardial infarction. 8 aneurysms regressed spontaneously and another 8 became smaller. The tendency to regress or to decrease in diameter war greatest in the group of patients with a low Asai-Score and initially small aneurysms. Myocardial infarction was only seen in the group of giant aneurysms (over 8 mm of diameter). A simple prophylaxis with anti-platelet agents does not seem to be adequate especially in over-sized aneurysms. Those should be prevented now by gamma-globulin therapy. If they occur, however, thrombosis should be prevented by the use of anticoagulants.     

Correlates of coronary artery aneurysm formation in patients with Kawasaki disease

Factors potentially associated with the formation or prevention of coronary artery aneurysms were investigated in 77 children with Kawasaki disease. The patients were divided into two groups. Group A consisted of those who developed coronary artery aneurysms and group B consisted of those who did not. The patients who developed aneurysms had a significantly longer duration of fever and a significantly lower minimum hemoglobin concentration than those who did not develop aneurysm. In patients who developed aneurysms, aspirin therapy was begun significantly later in the course of the illness compared with those who did not develop aneurysms. We suggest that the timing of the initiation of aspirin therapy may be important in the prevention of coronary artery aneurysms in patients with Kawasaki disease. We believe that it may be important to establish the diagnosis of Kawasaki disease as early as possible and to institute aspirin therapy at an appropriate dosage.     

儿童川崎病并冠状动脉瘤冠状动脉造影及心脏超声长期随访

川崎病(Kawasaki disease,KD)基本病理改变为全身性血管炎,主要侵犯大、中血管,其中冠状动脉(简称冠脉)是最常受损的血管,冠状动脉瘤(coro-     

冠状动脉造影追踪观察川崎病引起的巨大冠状动脉瘤

目的 探讨川崎病(KD)导致的巨大冠状动脉瘤(GCAA)的中远期变化特点,为此类儿童进入青少年期后心血管意外事件的防治提供依据.方法 采用冠状动脉造影(CAG)、超声心动图及心电图检查对12例急性期合并GCAA的KD患儿[男10例,女2例;发病年龄1～10(4.05±2.50)岁]进行2～10年追踪观察,分析该组患儿冠状动脉损害的变化特点.结果 本组患儿除2例急性期超声心动图诊断为单发右冠状动脉巨大瘤外,其余10例均为双侧多发冠状动脉瘤.随访CAG发现8例出现右冠状动脉节段性狭窄,其中右冠状动脉闭塞并桥样新生血管形成3例,多节段局域性狭窄4例,右冠状动脉全程编织样损害(血栓性闭塞并簇状新生血管)1例.本组9例冠状动脉瘤经治疗后仍有不同程度的存在,其中4例左前降支瘤远端血流充盈明显减慢.仅1例患儿(1/12) CAG见双侧冠状动脉瘤回缩至轻度扩张,未见狭窄及其他改变.本组12例患儿随访2 ～ 10年,均无自觉症状,活动未受限.静息心电图1例发现病理Q波,其余11例结果正常.静息心电图正常的11例患儿行药物负荷心电图检查仅1例出现多导联S-T段下移及T波低平;与同期CAG比较,超声心动图检出12例患儿冠状动脉近段形态改变,5例发现可疑室壁运动异常,但对观察冠状动脉中、远段狭窄欠敏感;对4例冠状动脉闭塞并新生血管形成的病例,超声观察均未能提示.结论 KD引起的GCAA损害可在急性期后长期存在.表现为GCAA持续存在、回缩、冠状动脉闭塞、局部狭窄及血管再形成等.本病缺乏临床表现,常规心电图及超声心动图对KD后遗症期冠状动脉形态及功能损害检查欠敏感,CAG对本病的追踪观察有重要价值.