Atorvastatin Safety in Kawasaki Disease Patients With Coronary Artery Aneurysms

Statins (HMG-CoA reductase inhibitors) may decrease inflammation in postacute Kawasaki disease (KD) complicated by coronary artery aneurysm (CAA) and promote vascular remodeling. There are limited data on their safety in young children. Twenty patients with CAAs after KD (median CAA z-score = +25) were treated with 5/10 mg atorvastatin daily for a median of 2.5 years (range 0.5–6.8) starting at a median of 2.3 years (range 0.3–8.9) after acute KD (median age 9.3 years [range 0.7–14.3]). Compliance with treatment was excellent: only one patient reported minor side effects (joint pain, no change in medication). Average total cholesterol before atorvastatin was 3.73 ± 0.84 mmol/L and after atorvastatin was 3.21 ± 0.46 mmol/L (relative decrease ?14 %, p = 0.02); low-density lipoprotein cholesterol was 1.99 ± 0.76 mmol/L before and only 1.49 ± 0.27 mmol/L after (relative decrease ?20 %, p = 0.04); high-density lipoprotein was 1.39 ± 0.36 mmol/L before and 1.30 ± 0.27 mmol/L after (relative decrease ?4 %, p = 0.35); and triglycerides were 0.71 ± 0.28 mmol/L before and 0.71 ± 0.18 mmol/L after (relative decrease ?5 %, p = 0.38). Nine of 20 patients (45 %) experienced at least 1 episode of hypocholesterolemia (total cholesterol <3.1 mmol/L), and 2 patients required atorvastatin dose lowering. Transient mild increase of liver enzymes (aspartate aminotransferase/alanine aminotransferase 45–60 U/L) were seen in 7 of 20 (35 %) patients with no patients experiencing more severe increases. Only one patient experienced increased creatine phosphokinase levels (>500 U/L). Serial measurements of age- and sex-specific percentiles of weight (estimated change: 1.4 [2.7] % per year, p = 0.60), height (estimated change: ?3.2 [3.2] % per year, p = 0.32), and body mass index (estimated change: 1.0 [2.9] % per year, p = 0.73) showed no association between anthropomorphic growth and atorvastatin treatment. Atorvastatin use in very young children with KD is safe but should be closely monitored.     

Prognostic Significance of the Size of Coronary Artery Aneurysms in Kawasaki Disease

The prognosis of coronary artery aneurysms complicating Kawasaki disease was assessed by serial coronary angiography in 33 patients. They underwent initial angiography with four months, and one or two follow-up angiographies between 11 months to 6.3 years after the onset of the illness. 'Ihese patients had 69 coronary aneurysms at the initial study. The maximal diameter of the aneurysms was expressed as a percent of the normal value. Of 44 aneurysms with a diameter less than 300% of normal, 43 were found to have regressed on follow-up. Of 13 aneurysms with a diameter 300 to 400% of normal, four were proved to have regressed, eight persisted and one stenosed. Of 12 aneurysms with a diameter 400% of normal or more, one was found to have regressed, four persisted, two stenosed and five obstmcted. Thus, the prognosis of aneurysms less than 300% of normal in diameter is excellent, whereas that of aneurysms 400% of normal or more in diameter is serious.     

川崎病并冠状动脉损害的危险因素

目的探讨川崎病(KD)并冠状动脉损害(CAL)的危险因素。方法收集1999年1月-2001年12月住院的145例KD患儿的临床资料,分析无CAL93例和CAL52例患儿的实验室检查资料及治疗、随访结果。结果无CAL组发热日程(8.7±3.4)d.血沉(79.5±34.6)mm/1h,CAL组发热日程(11.5±4.8)d,血沉(91.9±36.6)mm/1h,两组比较差异有显著性(P<0.01,0.05)。发病10d内接受静脉注射人血丙种球蛋白(IVIG)治疗患儿CAL发生率为18.8%(18/96),未予IVIG治疗患儿CAL发生率为69.4%(34/49),两者比较差异有显著性(P<0.001)。随访并CAL患儿38例,冠状动脉扩张20例均恢复正常;14例冠状动脉瘤中12例恢复正常,2例缩小;4例巨大冠状动脉瘤2例缩小,另2例超过2年仍未恢复。结论KD并CAL与热程过长及血沉显著增快密切相关,病程早期未予IVIG治疗的患儿并CAL的危险性明显增高,应用IVIG治疗对防治冠状动脉损害有重要作用。     

Ruptured Giant Aneurysm of the Left Anterior Descending Coronary Artery in Kawasaki Disease

This report describes Kawasaki disease (KD) in a rare autopsy case showing three uncommon phenomena: rapid aneurysmal development, ruptured giant aneurysm, and abscesses such as neutrophil aggregations, all contributing to the unpreventable sudden death of patients with KD. For a 5-year-old boy, KD was diagnosed on day 5 of his illness. His aneurysm was enlarged to a diameter of 18 mm on day 12, and the boy died on day 13. Aggregations of neutrophils containing myeloperoxidase and neutrophil elastase were scattered in chains over the aneurysmal wall of coronary artery, suggesting that destruction of the wall by an enzyme may have caused the rupture of the aneurysm.     

Angiospermic Changes of Coronary Aneurysms in Kawasaki Disease

The fate of coronary aneurysms in Kawasaki disease or MCLS was examined by follow-up studies on 9 patients with multiple bilateral aneurysms in the coronary arteries demonstrated by coronary arteriography. Their ages at the time if first examination ranged from 0.3 to 11 years (mean, 4.1 years). The mean interval between the onset of acute illness and the initial examination was 15.8 months, and the mean interval between the first and second examination was 17.9 months. Eight of the nine patients received anticoagulants between examinations. The second coronary arteriogram showed morphologic changes of the aneueysm from the time of the first examination: changes were seen in the right coronary artery area in 8 patients (89%) and in the left coronary artery area in 7 patients. These morphologuic changes seemed to be mainly secondary to thrombus formation, calcification, stenosis and/or obstruction of the aneuryms. Thus, coronary aneuryms in Kawasaki disease were transformed despite the use of anticoagulants. It is considered that multiple large coronary aneurysms will not healed or disappear, but are simply transformed as a result of their thrombosis and/or calcification.     

Measurements of Coronary Artery Aneurysms Due to Kawasaki Disease by Dual-Source Computed Tomography (DSCT)

Diameters of coronary artery aneurysms (CAAs) complicating acute phase KD can strongly predict the long-term prognosis of coronary artery lesions (CAL). Recently, computed tomographic angiography (CTA) has been used to detect CAL, and the purpose of this study was to determine whether coronary artery diameters measurements by CTA using dual-source computed tomography (DSCT) can be used instead of coronary angiogram (CAG) measurements. Twenty-five patients (22 males and three females) with CAL due to KD, who had undergone both CTA and CAG within one year, were retrospectively evaluated between 2007 and 2013. A prospective electrocardiogram-triggered CTA was performed on a DSCT (SOMATOM^® Definition, Siemens Healthcare, Germany). Two pediatric cardiologists independently measured the diameters of CAAs twice in each maximum intensity projection (MIP), curved multiplaner reconstruction (MPR) and CAG. We measured 161 segments in total (segment 1–3, 5–7, 11, 13). Diagnostic accuracy was expressed as κ coefficient. A Bland–Altman analysis was also used to assess the intra-observer, inter-observer and inter-modality agreement. The diagnostic quality of CTA was excellent (κ = 0.93). Excellent inter-observer agreement for the diameters of CAAs was obtained for MIP, MPR and CAG and for the intra-observer agreement. The inter-modality agreement was also excellent in measurements of CAA (MPR–CAG: y = 0.9x + 0.40, r = 0.97, p < 0.0001 MIP–CAG: y = x + 0.1, r = 0.94, p < 0.0001). These values in normal coronary arteries were also obtained. We found a significant correlation between CTA and CAG in measuring the coronary arteries. We conclude that measuring coronary artery diameters by CTA is reliable and useful.     

Multidetector Row Computed Tomography for Follow-Up of Patients with Coronary Artery Aneurysms Due to Kawasaki Disease

Multidetector row computed tomography (MDCT) coronary angiography was performed using a 16-slice MDCT scanner in three children with coronary aneurysms due to Kawasaki disease. Patients were given a -blocker. Following contrast injection, all data were acquired during a 20-second breathhold. Results were compared with those of conventional coronary angiography performed previously. MDCT provided clear visualization of coronary artery aneurysms, with coronary calcifications but which had not yet progressed to stenotic lesions. Because MDCT allows noninvasive detection and exclusion of coronary obstructions, it may be able to replace repeat conventional angiography as a follow-up study for children with coronary artery disease.     

Competition Between Native Flow and Graft Flow After Coronary Artery Bypass Grafting. Impact on Indications for Coronary Artery Bypass Grafting for Localized Stenosis with Giant Aneurysms Due to Kawasaki Disease

We report the postoperative course of native and graft flow after coronary artery bypass grafting (CABG) in two patients with giant aneurysms and localized stenosis due to Kawasaki disease (KD). Although both patients had undergone CABG to the left anterior descending artery (LAD) with the left internal thoracic artery (ITA), at 5 and 10 years old, respectively, the ITA grafts were occluded 1 month postsurgery. However, when the two patients suffered complete occlusion of the native LAD more than 10 years after surgery, angiograms showed that the ITA grafts had reopened. We believe that this postoperative course reflects competition between the native artery flow and graft flow after CABG. CABG in patients with severely delayed coronary flows or recurrence of thrombus in giant aneurysms was ineffective in preventing myocardial infarction or damage. We conclude that CABG in giant aneurysm without significant localized stenosis should be avoided.     

川崎病并冠状动脉损害的诊断和治疗

川崎病是好发于5岁以下儿童、原因不明的全身性血管炎,其主要并发症为冠状动脉损伤.冠状动脉瘤破裂、心肌梗死为其主要死亡原因.现对川崎病并冠状动脉损伤的病理、诊断、治疗及预后等方面的新进展进行总结.     

川崎病冠状动脉病变的影像学诊断

川崎病的主要并发症与心血管,特别是冠状动脉系统有关.在未经治疗的川崎病病例中冠状动脉瘤发生率占20％～30％,在经过IVIG及阿司匹林治疗的病例中约占5％.超声心动图已成为川崎病急性期及恢复期诊断及随访评估冠状动脉扩张等心血管并发症的标准诊断技术.急性期冠状动脉病变的超声心动图表现有冠状动脉扩张、冠状动脉瘤及管壁周围回声增强.冠状动脉内径测值与正常值比较对川崎病的诊断与治疗起关键作用.冠状动脉内径的正常范围受年龄、体表面积的影响,并存在地区人群间差异.超声心动图诊断远端冠状动脉病变、冠状动脉狭窄或闭塞病变的敏感性不够高.近年来磁共振血管造影及CT技术迅速发展成为重要的心血管诊断方法.多层CT对川崎病冠状动脉病变诊断效果优于超声心动图及磁共振血管造影.多层CT显像受心率及呼吸影响.选择性冠状动脉造影仍然是显示冠状动脉病变的金标准,但有一定的风险.     

Coronary Artery Dilatation in Toxic Shock-Like Syndrome: The Kawasaki Disease Shock Syndrome

Kawasaki disease is a common systemic vasculitis of childhood that may result in life-threatening coronary artery abnormalities. Despite an overlap of clinical features with toxic shock syndrome, children with Kawasaki disease generally do not develop shock. We report two cases of older children who presented with a toxic shock-like illness, and were diagnosed with Kawasaki disease when coronary artery abnormalities were found on echocardiography, in keeping with the recently described ‘Kawasaki disease shock syndrome’. Clinicians should consider Kawasaki disease in all children presenting with toxic shock and assess for coronary artery damage.     

Angiogenesis in Fatal Acute Kawasaki Disease Coronary Artery and Myocardium

Angiogenesis has been shown to be dysregulated in coronary artery (CA) aneurysms in the chronic phase of Kawasaki disease (KD). Neovascularization may occur in inflammatory-related vascular diseases because many angiogenesis mediators are secreted by inflammatory cells. We hypothesized that inflammation of the acute KD CA aneurysm could lead to dysregulation of angiogenesis mediators and subsequent neovascularization. To investigate this hypothesis, acute fatal KD cardiac tissues were immunostained for angiogenic inducers and inhibitors. Microvessel density was determined and the degree of inflammation assessed. Marked inflammation and angiogenesis were found in acute KD CA aneurysms and myocardium, with the highest microvessel density seen in patients who died 2–3 weeks after onset of the disease. Expression of proangiogenic proteins was higher than expression of inhibitors in KD CA aneurysms and myocardium. Angiogenesis mediators were localized to inflammatory cells in the myointima, adventitia, and myocardium. We conclude that significant neovascularization occurs in acute KD CA aneurysms and myocardium much sooner after onset of the disease than has been previously reported, that multiple angiogenesis factors are involved, and that dysregulation of angiogenesis likely contributes to KD vasculopathy. Presented in poster formats at the Pediatric Academic Society’s annual conference 5/04 in San Francisco, CA, USA May 2003     

Ring-Calcification of Giant Coronary Artery Aneurysm of an 11-Year-Old Child with History of Kawasaki Disease

We present radiographic images of ring-calcification of a giant aneurysm of the left main coronary artery in a child, 7 years after the initial diagnosis of Kawasaki disease, as well as acute medical management and surgical bypass of the obstructed left anterior descending coronary artery.