Reduced shear stress and disturbed flow may lead to coronary aneurysm and thrombus formations

Kawasaki disease (KD) is an acute systemic inflammatory illness that occurs predominately in children <5 years of age. The reported incidence varies widely depending on the ethnicity of the population and the method of case ascertainment. Recent reports would suggest the annual incidence is ≈20 to 25 per 100 000 children <5 years of age in North America, with the highest reported incidence of 188 being in Japan, where the disease was first described in 1967.1 The illness is self-limited and of unknown cause, but is complicated by a systemic vasculitis with a predilection for small- to medium-sized arteries, particularly the coronary arteries. The majority of patients will have either transient coronary artery dilation or no coronary artery luminal changes as noted on echocardiography. Long-term prognosis for these patients is considered to be excellent. Coronary artery aneurysms occur in 25% of patients, but the prevalence is reduced to ≈4% for patients treated with intravenous immunoglobulin infusion within 10 days of illness onset. Aneurysms are associated with an intense inflammatory cell infiltrate, destruction of the internal elastic lamina, and smooth muscle cell death. Coronary artery involvement is usually maximal within 6 to 8 weeks after the acute episode. Regression of aneurysms can occur primarily through myointimal proliferation, although the arterial structure and function remains abnormal,2 and there is an important ongoing risk of stenoses and occlusions.3 Long-term cardiology assessment and management is required, and some of these patients may require revascularization procedures or, rarely, cardiac transplantation. KD has become the most prevalent acquired cardiac disease in children in developed countries. Article see p 60 Although coronary artery complications are the predominant cause of morbidity and mortality, other cardiovascular abnormalities can occur. Valvulitis is a less prevalent complication, and there have been case reports of important long-term aortic and …

Giant Thrombotic Right Coronary Aneurysm in an Infant with Undiagnosed Incomplete Kawasaki Disease and Rapidly Progressive Cardiovascular Collapse

Resection of Giant Coronary Artery Aneurysms in a Takayasu's Arteritis Patient

Giant Aneurysm of the Left Atrial Branch of the Left Circumflex Artery With Fistula

Background: The Etanercept as Adjunctive Treatment for Acute Kawasaki Disease study, a phase 3 randomized placebo-controlled clinical trial, evaluated etanercept, a TNF-alpha inhibitor, as an adjunct to IVIg for Kawasaki Disease (KD). In children presenting with coronary artery (CA) aneurysm, etanercept resulted in reduction in progression of CA dilation and earlier aneurysm regression compared to placebo. Following study conclusion, our institution implemented etanercept as a first line IVIg adjunctive treatment for patients presenting with early CA aneurysm formation. Hypothesis: Real world use with etanercept as adjunct to IVIg in children with KD and CA aneurysm shows high patient compliance, is safe and results in early CA regression. Methods: We reviewed charts and echocardiograms for all children admitted to Seattle Children’s Hospital from 5/2019 to 4/2024 and treated with etanercept for KD with CA aneurysms at presentation (Z-score ≥2.5 per AHA aneurysm definition). Etanercept is injected subcutaneously at 0.8 mg/kg with IVIg at diagnosis and then with 2 repeat weekly doses at outpatient visits. Results: Thirty-six patients with KD and CA aneurysms received at least one dose of etanercept. Sixteen (44%) were &lt;1 year of age, 17 (47%) were diagnosed with incomplete KD and 5 (14%) were ‘IVIg refractory.’ Four patients responded to a second IVIg dose and two patients received additional biologic agents. Thirty-two patients completed the 3-dose course of etanercept, with outpatient doses administered 6.6±1.5 days (mean±SD) and 13.5±2.3 days after the first. Seven patients had giant CA aneurysms (Z-score ≥10) requiring anticoagulation. In patients with giant aneurysms and at least 6-month follow-up, all aneurysms regressed to below the threshold for requiring anticoagulation beyond aspirin. Of 31 children with long-term follow-up echocardiograms available, 19 had complete resolution (Z-score &lt;2.5) of CA dilation by 6 months, 22 by 1 year, and 29 by 2-year follow-up. No severe or serious adverse events were attributed to etanercept. Conclusions: Etanercept for KD with early CA aneurysms was delivered safely and with high compliance. CA aneurysm regression occurred in most patients with marked reduction in giant CA aneurysms by 6 months. These real-world data support the use of etanercept as an intensification therapy for preventing persistence of CA aneurysms in KD.

Cardiac Surgery Committee for Development of Guidelines for Medical Treatment of Acute Kawasaki Disease

BackgroundThe incidence of Kawasaki disease has been increasing since it was first reported by Tomisaku Kawsasaki in 1967. Among complications of the condition, the formation of coronary artery aneurysms is...

Chronic granulomatous disease (CGD) is a rare inherited immunodeficiency characterized by microbicidal dysfunction due to a defect in nicotinamide adenine dinucleotide phosphate oxidase in neutrophils. Patients with CGD have abnormalities in cytokine production and apoptosis leading to prolonged inflammation, which is related to the susceptibility to autoimmune or inflammatory diseases such as sarcoidosis, Crohn’s disease, systemic lupus erythematosus, Behcet’s disease, and Henoch‐Schonlein purpura. 1

Objective To observe the mid- and long-term changes of giant coronary artery aneurysm(GCAA) caused by Kawasaki disease(KD) and to provide preventive basis for cardiac accidents of KD-affected adolescents. Methods Twelve cases of KD with GCAA [10 boys, 2 girls; 1-10 years old; mean age: (4.05±2.50) years old] were followed up by coronary angiography (CAG), echocardiography and electrocardiogram for 2-10 years to and the changes of the coronary artery lesion were analyzed. Results The findings showed that 2 cases were single coronary artery aneurysm and 10 cases had multiple coronary artery aneurysms on both sides by echocardiography.Among them 8 cases showed segmental stenosis in the right coronary artery with varying degrees by coronary angiography, including 3 cases with coronary recanalization after right coronary artery complete occlusion, 4 cases with segmental local stenosis, and 1 case with thrombotic occlusion and tufted neovascularization.And in 9 cases of coronary artery aneurysms were still present after treatment, and among them the blood flow filling in 4 cases was slowing down in the left anterior descending arteries.Only 1 case with coronary artery aneurysms on both sides became expanded mildly, without stenosis or other lesions.In this observation, all of the cases had no symptoms or any activity limitation.One case was found pathologic Q wave and the other 11 cases left normal by resting electrocardiogram.The results of resting electrocardiogram in 11 cases were normal by pharmacologic stress electrocardiogram except that 1 case showed multi-lead S-T segment depression and T wave flat.Compared with coronary angiography in the same period, 12 cases showed proximal morphological changes in coronary artery and 5 cases with wall motion abnormalities by echocardiography.This study showed that echocardiography was not sensitive enough for mid- and distal-stenosis examination because it failed to provide any useful information for 4 cases affected by segmental stenosis and neovascularization. Conclusions The GCAA caused by KD will be lasting for a long time after acute stage, including persisting GCAA, recovering GCAA, occlusion, stenosis and neovascularization.The sensitivity of echocardiography and electrocardiogram are not enough to find coronary morphology and function of KD sequelae damages.CAG is important for follow-up observations of KD with GCAA. Key words: Kawasaki disease; Giant coronary artery aneurysm; Coronary angiography; Follow-up

Background: Children with giant coronary artery aneurysms (CAA) after Kawasaki disease (KD) are at substantial risk of thrombosis. There are currently no evidence-based guidelines for optimal thromboprophylactic therapy in these children. Methods: The North American Kawasaki Disease Registry was queried to identify all patients with giant CAA (maximum coronary artery z-score &gt;10) and their antithrombotic therapy. Freedom from thrombosis was modelled using the Kaplan-Meier method; thrombotic complication rate was calculated per patient-year/month of follow-up. Results: n=202 patients with giant CAA were included, of whom 28 (14%) experienced either coronary artery thrombosis with or without myocardial infarction. Freedom from thrombotic complications was 92%, 85% and 79% at 3 months, 5 and 10 years after diagnosis, respectively. Non-pharmacological factors associated with increased risk of thrombotic complications included higher maximum coronary artery z-scores (HR: 1.7/+10 SD, p&lt;0.001), higher number of coronary artery branches with giant CAA (HR: 2.6/branch, p&lt;0.001), higher number of discrete CAA (HR: 1.4/aneurysm, p=0.001) and presence of complex CAA (involving the bifurcation or non-discrete; HR: 3.0, p=0.05). A total of 982 patient-years of follow-up were available for analysis (11% low molecular weight heparin (LMWH), 32% warfarin, 57% antiplatelet alone). All patients were maintained on ASA, with 47 patients (23%) also receiving clopidogrel. Patients while on LMWH had the highest event rate, at 1 event per 13 patient-years, compared to 1 per 39 on warfarin and 1 per 33 on no anticoagulant. However, LMWH was predominantly prescribed immediately after the acute phase, which is also the highest risk phase for thrombosis. When limiting analysis to events within 3 months of the acute phase, patients on LMWH had the lowest event rate at 1 per 46 patient-months, compared to 1 per 27 on warfarin and 1 per 33 on no anticoagulant (p=NS). Conclusions: Current thromboprophylaxis strategies in patients with giant CAA have suboptimal efficacy, and residual thrombosis risk persists. New anticoagulants/antiplatelet agents should be assessed in this population to determine if they provide better, safer and more tolerable thromboprophylaxis.

A 20-year-old woman visited our cardiology clinics for regular follow-up of Kawasaki disease. She was diagnosed with a giant coronary aneurysm at age 4. Her last coronary angiography was obtained 6 years before her current admission. To investigate the status of her coronary aneurysm, contrast-enhanced coronary computed tomographic (CT) angiography was performed with a 16-slice CT scanner. The CT was performed with retrospective …

Objective To explore whether the warfarin and aspirin combination therapy can prevent cardiovascular events in patients with giant coronary artery aneurysm (GCAA) caused by Kawasaki disease(KD). Methods Children who had been diagnosed as GCAA secondary to KD in Beijing Children's Hospital Affiliated to Capital Medical University between Jan.1998 and Aug.2012 were enrolled in this study.They were divided into the warfarin plus aspirin group (combination group) and aspirin group.The combination group used the therapy of warfarin and small dose aspirin in the long-term anticoagulation treatment, while the aspirin group used small dosage of aspirin without warfarin.Both groups were followed at the time points of 2nd week, 1st month, 3rd month, 6th month, and 1st year after discharge of the acute stage.Then these children were followed every 6 months.Data on each followed-up included clinical manifestations, coronary artery aneurysm recovery situation and complications. Results (1)The onset age of GCAA caused by KD ranged from 3 months to 13 years and 3 months.Infants who were ≤1 year old and children who were ≥5 years old were more susceptible to this disease, their proportion were both 23.1%. (2)The distribution of GCAA in both groups were similar.GCAA most commonly occurred in the right coronary artery, then the left anterior descending coronary artery, and then the main trunk of left coronary artery, the left circumflex artery was rarely affected.(3) Coronary artery aneurysm in 17 cases(53.1%) retracted in the warfarin combined with aspirin group, while 5 cases(41.7%) in the aspirin group.Fifteen cases(46.9%) in the combination group hadn't obvious change, while the aspirin group got 7 cases(58.3%). (4)During the follow-up, 2 children(6.3%)complicated with intracoronary thromboses in the combination group, while 3 cases(25.0%) in the aspirin group.One case(3.1%) in the combination group suffered myocardial infarction, while 3 cases(25.0%)in the asprin group.Two cases (16.7%) in the aspirin group died, while none in the combination group.Coronary artery stenosis occurred in 2 cases (16.7%) in the aspirin group, while 1 case (3.1%) in the combination group.One child had coronary artery occlusion in the aspirin group, while none in the combination group.(5)The combination group had 1 case of serious bleeding event, subarachnoid hemorrhage.In addition, there were 8 cases of nasal bleeding, a total of 19 person-time.There was no serious bleeding event in the aspirin group, only 3 person-time small mount of nasal bleeding. Conclusions Althought warfarin plus aspirin therapy for the long-term anticoagulation treatment in GCAA caused by KD can not affect the retraction of GCAA, it may decrease the incidence of thrombosis, myocardial infarction and mortality.Bleeding complication is more common during the application of wafarin.Therefore the dose of warfarin should be tailored in various children according to the clinical situation, and bleeding complication should be monitored. Key words: Kawasaki disease; Giant coronary artery aneurysm; Warfarin; Anticoagulation therapy; Prognosis

We report a case of sudden death due to rupture of a giant right coronary artery aneurysm, likely a sequela of remote Kawasaki disease, in a young woman with Down syndrome. The decedent was a 28 year old female with trisomy 21 who was found deceased in the backyard pool. An autopsy disclosed an enlarged heart with 400 ml of clotted blood in the pericardial sac and undiagnosed giant coronary artery aneurysms involving the left anterior descending, left circumflex, and right coronary artery, with rupture of the latter artery. The histologic findings were consistent with remote Kawasaki disease. Giant coronary artery aneurysms are a rare complication of Kawasaki disease, infectious vasculitis, and atherosclerosis, among other causes. While Kawasaki disease is typically considered a disease of children, late-onset complications should be considered in the differential diagnosis of young adults with myocardial infarction, coronary aneurysm, or sudden death.

Objective: To summarize the clinical features, middle-and long-term prognosis of Kawasaki disease (KD) with giant coronary artery aneurysm (GCAA). Methods: In this retrospective cohort study, a cross-sectional analysis was conducted on 101 KD children with GCAA in the KD with GCAA database established by Beijing Children's Hospital, Capital Medical University in 2004. GCAA was diagnosed as coronary artery absolute lumen diameter ≥8.0 mm. All patients were followed up regularly. The endpoint was the time of last follow-up or the death time. T test or χ2 test was used for comparison between groups. Results: A total of 101 KD children with GCAA were enrolled, including 82 males (81.2%) and 19 females (18.8%). The age of disease onset was 2.5 (1.0, 4.5) years. The follow-up duration was 4.5 (2.7, 7.5) years, with a longest of 19 years. All children received routine treatment with aspirin and warfarin, and clopidogrel was added in severe cases. At the end of follow-up, 13 cases (12.9%) had cardiac enlargement, 11 cases (10.9%) developed heart failure, 13 cases (12.9%) experienced myocardial infarction, 2 cases (2.0%) underwent coronary artery bypass graft and 6 cases (5.9%) died. A total of 170 coronary arteries were involved, including 24 (14.1%) GCAAs on the main trunk of left coronary artery, 10 (5.9%) GCAAs on left circumflex, 57 (33.5%) GCAAs on left anterior descending, 78 (45.9%) GCAAs on the middle segments of right coronary artery, and 1 (0.6%) GCAA in the distal segments of right coronary artery. Eleven cases (10.9%) recovered with the coronary artery absolute lumen diameter of all GCAAs below 4.0 mm. Among 170 branches with GCAAs, 28 (16.5%) regressed below 4.0 mm. No significant difference was found in the regression rates between right and left GCAA (18.7% (17/91) vs. 13.9% (11/79), χ²=2.473, P=0.116). There was no statistically significant difference in retraction between unilateral GCAA and bilateral GCAA (16.1% (9/56) vs. 4.4% (2/45), χ2=2.381, P=0.123). Conclusions: GCAA of KD occurred more common in the middle segments of right and left anterior descending coronary arteries. The incidence of adverse cardiac events and the mortality rate in children with GCAA complicated with KD was high. Their long-term prognosis was poor.

Patient: Male, 64-year-oldFinal Diagnosis: Huge coronary aneurysmSymptoms: Chest discomfort • dyspneaMedication: Losar 25 mg twice daily • Amlodipine 5 mg twice daily • Aspirin 80 mg daily • Atorovastatin 20 mg daily • Pantaprazole 20 mg dailyClinical Procedure: Coronary artery bypass graft surgerySpecialty: Cardiac Surgery • CardiologyObjective:Rare diseaseBackground:Giant coronary artery aneurysm (GCAA) is a rare disease, with an incidence of 0.02% in the general population. GCAA is defined as when the diameter of the coronary artery is more than 4 times the adjacent part or more than 8 mm. There are several causes of GCAA, with atherosclerosis being the most common. Patients with giant coronary artery aneurysms can be asymptomatic or develop chest pain, dyspnea, and palpitations. Complications of GCCA include myocardial infarction, thrombosis, and sudden death, so early treatment is necessary to prevent mortality. There is no standard surgical approach for a giant coronary artery aneurysm.Case Report:A 64-year-old man with hypertension, opium addiction, morbid obesity (body weight 151 kg and BMI 46), and benign prostate hyperplasia presented with a giant coronary aneurysm in coronary angiography. The patient underwent cardiac surgery, and a 42-mm coronary aneurysm was detected. The aneurysm had many orifices that opened to the left main coronary artery, left circumflex artery, LAD, the diagonal branch of the LAD, and the septal branch of the LAD. Aneurysmectomy and coronary artery bypass graft were successfully performed.Conclusions:Giant coronary artery aneurysms are rare. Patients with giant coronary artery aneurysms may experience sudden death due to myocardial infarction and other cardiovascular complications due to ischemia. Because it is rare, there is no standard surgical approach for a giant coronary artery aneurysm. Further studies need to focus on standardized surgical management of patients with giant coronary artery aneurysms.