Occurrence Of Coronary Artery Aneurysms Research Articles

Сучасні підходи до діагностики та лікування Хвороби Кавасакі (огляд літератури)

Kawasaki disease (KD) is a vasculitis of unknown origin, accompanied by fever and mucocutaneous syndrome, predominantly found in infants. KD is the most common cause of acquired heart disease in children in developed countries, which is complicated by the occurrence of coronary artery aneurysms in 25% of untreated patients due to coronary artery vasculitis. The aim is to analyze the guidelines of the American Heart Association, the Single Hub and Access Point for Paediatric Rheumatology in Europe (SHARE), as well as Japanese instructions on modern approaches to the diagnosis and treatment of Kawasaki disease. Clinical studies show that this rate decreases to ∼4% during treatment with intravenous immunoglobulin. Although some new studies show worse outcomes despite immunoglobulin treatment, especially in infants under 12 months of age. The complexity and heterogeneity of the course of KD, a wide differential diagnosis and the lack of a specific diagnostic tests are often serious obstacles on the way to diagnosis. Taking into account some differences in American, European, and Japanese guidelines for the treatment of KD, we consider it appropriate to follow European guidelines, which are most similar to American ones and are best suited for Europeans. The authors declare no conflict of interest.

Very early onset of coronary artery aneurysm in a 3-month infant with Kawasaki disease: a case report and literature review

BackgroundKawasaki disease (KD) is a medium vessel vasculitis, of unknown etiology, typically presenting in children younger than 5 years of age. Prolonged fever (at least five days) is a major clinical criterion of KD, while cardiac involvement may occur in up to 25% of patients, generally in the second week of the disease.Case presentationWe describe the case of KD developing in a 3-month infant, with an early occurrence of coronary artery aneurysm after only 3 days of fever, complicated by thrombosis, requiring aggressive treatments.ConclusionsTime of development of cardiac complications can be different in young infants with KD and both diagnostic criteria and treatment indications should be individualized in this class of age.

Kawasaki Disease and Coronary Artery Involvement: A Narrative Review

Kawasaki disease is a systemic vasculitis with a risk of developing coronary artery lesions if left untreated. Kawasaki disease can be diagnosed clinically with classical symptoms (conjunctivitis, rash, lymphadenopathy, mucositis, edema of hands and feet), but predicting the risk of developing coronary artery aneurysm remains challenging. The coronary sequelae of Kawasaki disease have significant morbidity and mortality and are the second most common cause of acquired cardiac disease in children. Several genetic and immune factors are involved in the inflammation of coronary artery lesions in Kawasaki disease. Inositol trisphosphate 3-Kinase (ITPKC), Foxp3+, circular RNAs, mannose-binding lectin 2 (MBL2), complement factor H (CFH), kininogen 1 (KNG1), serpin family C member 1 (SERPINC1) and fibronectin 1 (FN1) are the essential genes identified in the pathogenesis of coronary artery lesions in Kawasaki disease. The addition of methylprednisolone to a combination of aspirin and intravenous immunoglobulins and biological agents like anakinra, etanercept, infliximab, and immunosuppressants like cyclosporine prevents the occurrence of coronary artery aneurysms in Kawasaki disease. Since the coronary artery lesions form the second most common cause of acquired cardiac disease in children and the incidence of myocardial infarction is a late complication, the risk stratification for coronary artery aneurysms and follow-up protocols for the prevention of cardiac thrombosis were proposed by the American Heart Association in 2017.

The immunopathogenesis of SARS-CoV-2 infection in children: diagnostics, treatment and prevention.

Symptoms and outcomes for paediatric COVID‐19 differ vastly from those for adults, with much lower morbidity and mortality. Immunopathogenesis drives severe outcomes in adults, and it is likely that age‐related differences in both the innate and specific immune responses underlie much of the variation. Understanding the protective features of the paediatric immune system may be crucial to better elucidate disease severity in adult COVID‐19 and may pave the way for novel therapeutic approaches. However, as well as uncommon cases of severe paediatric acute COVID‐19, there have been children who have presented with delayed multisystem inflammation, including cardiac, gastrointestinal, skin, mucosa and central nervous system involvement. The occurrence of coronary artery aneurysms has drawn comparisons with Kawasaki Disease, but similarities with the inflammatory phase of adult acute COVID‐19 have also been drawn. In this review, we summarise findings from studies investigating pre‐existing immunity, cytokine profiles, innate, B‐cell, antibody, T‐cell and vaccine responses in children with acute COVID‐19 and multisystem inflammation, compared with COVID‐19 adults and controls. We further consider the relevance to therapeutics in the context of limited evidence in children and highlight key questions to be answered about the immune response of children to SARS‐CoV‐2.

Hemodynamic Mechanism of Coronary Artery Aneurysm High Occurrence on Right Coronary Artery.

The abnormal diameter of the coronary artery is twice or more than the normal diameter, which is a coronary artery aneurysm (CAA). According to the clinical statistics, CAA shows high occurrence on right coronary artery (RCA). The most common cause of CAA in adults is atherosclerosis, which destroys the elastic fibers in the middle layer of the blood vessel. Under the intravascular pressure, the weak wall bulges outward and form CAA. This article aims to explain the hemodynamic mechanism of coronary artery aneurysm shows high occurrence on RCA. Occurrence of CAA was simulated by the volume growth of coronary artery. Firstly, a 0–3D multi-scale model of normal coronary artery was constructed to obtain the hemodynamic environments of coronary artery. Then, fluid-structure interaction of normal and atherosclerotic blood vessel was performed to obtain volume growth rate of the coronary artery. Atherosclerosis was simulated by modifying Young’s modulus in middle layer of the blood vessel. Finally, creep simulation was performed to compare the deformation of the blood vessels under the accumulation of time. Under normal condition, the volume growth rate of the RCA is 2.28 times and 1.55 times of the LAD and the LCX. After atherosclerosis, the volume growth rate of the RCA was 2.69 times and 2.12 times of the LAD and the LCX. And the volume growth rate of the RCA was 3.85 times and 3.45 times of the LAD and the LCX after further deepening of atherosclerosis. The expansion time above the average volume growth rate of the RCA, the LAD and the LCX respectively were 0.194, 0.168 and 0.179 s. The RCA is 2.06 times the original, the LAD and LCX are 1.53 times and 1.56 times after 10 years in creep simulation. It can be concluded that the RCA is more prone to aneurysms originated from the larger expansion of the RCA under normal physiological condition, and the larger expansion is magnified under atherosclerosis condition with destroyed vessel elasticity, and further magnified during the time accumulated viscoelastic creep to develop to aneurysm eventually.

Risk factors of immunoglobulin resistance and coronary complications in children with Kawasaki disease.

The risk of immunoglobulin resistance is still likely to occur in Kawasaki disease (KD) despite adequate treatment. The Kobayashi score (KS) is used to predict unresponsiveness to treatment although the usefulness of the score in populations other than Asian seems to be debatable. The analysis of clinical and laboratory parameters predisposing to immunoglobulin resistance and coronary complica-tions in children hospitalised due to KD. The data of children hospitalised due to KD between 2003 and 2016 underwent analysis. Clinical and laboratory parameters were analysed, including all parameters present in KS in relation to the risk of intravenous immunoglobulin (IVIG) resistance and the occurrence of coronary complications in the form of aneurysms and dilatations. Seventy-three children (51 boys; aged 1.5-135 months) with KD were hospitalised. In eight (11%) patients IVIG re-sistance was observed. We reported aneurysms or coronary dilatations in 13 (17.8%) children. The criterion for increased risk of IVIG resistance based on KS (≥ 4 points) was fulfilled by 21 (29%) children. Resistance to IVIG and coronary complications were observed in four (19.1%) and two (9.5%) children with the score ≥ 4 points, respectively, and four (7.7%) and 11 (21.6%) from the group < 4 points in KS, respectively. The prevalence of IVIG resistance and coronary artery complications was not different between the group with ≥ 4 and the group with < 4 points (p = 0.22, p = 0.32, respectively). A higher risk of IVIG resistance was confirmed in children with a longer duration of fever (13.0 days with IVIG resistance vs. 9.2 days with a good response to IVIG, p = 0.04). For the prediction of the occurrence of coronary artery aneurysms the following were of great importance: the day of diagnosis (which was usually the day of the beginning of treatment), the number of symptoms, and the maximal platelet count (p = 0.001; p = 0.019 and p = 0.026, respectively). In our study population we did not demonstrate the usefulness of KS to predict IVIG resistance or the risk of the occurrence of coronary artery aneurysms. However, prolonged fever, late diagnosis, poorly symptomatic course of the disease, and a high platelet count at the time of the follow-up remain independent risk factors.

Abstract 88: Pentraxin 3 in Coronary Artery Lesions in Kawasaki Disease

Although vascular inflammation is an important feature of Kawasaki disease (KD), the usefulness of local inflammatory markers as biomarkers for KD is unknown. Pentraxin 3 (PTX3), soluble lectin-like oxidized low density lipoprotein receptor 1 (sLOX-1) and matrix metraloproteinase-9 (MMP-9) are biomarkers of inflammation of vascular components. Objective: We tested whether plasma concentrations of PTX3, sLOX-1 or MMP-9 would be a useful biomarker for detecting high risk patient of coronary artery aneurysm (CAA) in KD and compared with serum level of interleukin-6 (IL-6) and IL-18. The ability of the assays to identify KD patients at risk for CAA was analyzed. Methods: PTX3, sLOX-1, MMP-9, IL-6 and IL-18 concentrations of 50 KD patients at different four clinical points were analyzed. Point A represented on admission; B, pre-IVIG; A+B, before IVIG; C, after IVIG; D, after fever resolution. Each concentration was compared with the rate of occurrence of CAA and IVIG unresponsiveness. Results: Each value was evaluated in 50 KD patients (2 with CAA, 48 without CAA). Three patients were treated without IVIG, 17 with one course of IVIG, and six with two IVIGs, two with three IVIGs, respectively. At the points A+B, C, D means for PTX3 were; 33.4, 11.7, 9.00 ng/ml, mean for MMP-9; 34.6, 19.2, 24.2 ng/ml, mean for sLOX-1; 3.82, 2.33, 2.25 ng/ml, respectively. Levels of PTX3 (p&lt;0.001) and MMP-9 (p&lt;0.05) were significantly higher in before IVIG than after IVIG; whereas levels of sLOX-1, as well as those of IL-6 and IL-18 were comparable between before and after IVIG. PTX3 were well correlated with IL-6 level (R2=0.73). Both cases with extraordinary high PTX3 levels at admission of 91.8 and 65.3 ng/ml were complicated with coronary artery aneurysms, even though they were treated by three courses of IVIG. The level of plasma PTX3 was significant related with the course numbers of IVIG (p&lt;0.05). Conclusion: Levels of PTX3 and MMP-9 appear to be associated with clinical course of KD. Levels of PTX3 were correlated with the severity of disease; how many doses of IVIG enough to resolve fever. An extraordinary high PTX3 level might be suggestive of the existence of CAA. These data suggest that PTX3 can be a candidate biomarker for prediction of unresponsiveness and CAA formation in patients with KD.

Guideline-Concordant Treatment of Kawasaki Disease With Immunoglobulin and Aspirin and the Incidence of Coronary Artery Aneurysm.

Current guidelines for Kawasaki disease (KD) recommend intravenous immunoglobulin infusion and echocardiography. However, no previous studies have evaluated the relationship between the treating hospital's concordance with guidelines and the prevention of coronary artery aneurysm in patients with KD. KD patients between 2010 and 2013 were identified in a Japanese national inpatient database. Guideline concordance was defined as the proportions of patients who received echocardiography as well as treatment with both immunoglobulin and aspirin, which were divided into quartiles. Multivariable logistic regression analysis was conducted to examine the association between the guideline concordance and the occurrence of coronary artery aneurysm with adjustment for patient backgrounds. In sum, 20 156 patients with KD were identified. The very high (>83.3%) concordance group had a lower rate of coronary artery aneurysm than the very low (<59.0%) concordance group (4.9% vs 9.9%; odds ratio, 0.45; 95% CI, 0.27 to 0.74; P = .002). All patients with KD should be treated according to the guidelines.

Global gene expression profiling identifies new therapeutic targets in acute Kawasaki disease.

BackgroundGlobal gene expression profiling can provide insight into the underlying pathophysiology of disease processes. Kawasaki disease (KD) is an acute, self-limited vasculitis whose etiology remains unknown. Although the clinical illness shares certain features with other pediatric infectious diseases, the occurrence of coronary artery aneurysms in 25% of untreated patients is unique to KD.MethodsTo gain further insight into the molecular mechanisms underlying KD, we investigated the acute and convalescent whole blood transcriptional profiles of 146 KD subjects and compared them with the transcriptional profiles of pediatric patients with confirmed bacterial or viral infection, and with healthy control children. We also investigated the transcript abundance in patients with different intravenous immunoglobulin treatment responses and different coronary artery outcomes.ResultsThe overwhelming signature for acute KD involved signaling pathways of the innate immune system. Comparison with other acute pediatric infections highlighted the importance of pathways involved in cell motility including paxillin, relaxin, actin, integrins, and matrix metalloproteinases. Most importantly, the IL1β pathway was identified as a potential therapeutic target.ConclusionOur study revealed the importance of the IL-1 signaling pathway and a prominent signature of innate immunity and cell migration in the acute phase of the illness.Electronic supplementary materialThe online version of this article (doi:10.1186/s13073-014-0102-6) contains supplementary material, which is available to authorized users.

Incidence and natural history of coronary artery aneurysm developing after drug-eluting stent implantation

There is a growing concern about the occurrence of coronary artery aneurysms (CAAs) after drug-eluting stent (DES) implantation and their long-term course. We assessed the occurrence and the factors affecting the long-term outcome of DES-associated CAA. We analyzed 3,612 consecutive patients (4,419 lesions) who underwent follow-up angiography after DES implantation. All 34 CAAs (0.76% per lesion) in 29 patients (0.8% per patient) were detected at follow-up, and the mean elapsed time from DES implantation to CAA diagnosis was 414 ± 213 days. Angiographically, CAAs developed almost exclusively in complex (type B2/C) de novo lesions (30 [88.2%] of 34 lesions), and lesion length was significantly greater in patients with CAA than without CAA (26.9 ± 9.03 vs 23.1 ± 7.14 mm; P = .004). Myocardial infarction with stent thrombosis occurred in 5 patients with CAA (17.2%), 4 of whom were on aspirin only without clopidogrel. Although CAAs rarely develop after DES implantation and show mostly favorable clinical courses, long-term maintenance of clopidogrel therapy might be required to minimize occurrence of adverse clinical events resulting from stent thrombosis.

Prevalence of Coronary Artery Lesions on the Initial Echocardiogram in Kawasaki Syndrome

To determine whether coronary artery lesions (ectasia and aneurysm) are commonly observed on the initial echocardiogram of patients with acute Kawasaki syndrome, whether coronary artery ectasia and/or aneurysms occur more frequently in patients with incomplete Kawasaki syndrome than in those patients with complete findings, and whether earlier diagnosis and treatment of Kawasaki syndrome are associated with less frequent occurrence of coronary artery ectasia and/or aneurysm. A retrospective medical record review. A tertiary care pediatric hospital. One hundred patients treated for Kawasaki syndrome between July 1, 1998, and June 30, 2003, who were identified by a medical record search. Prevalence of coronary artery lesions (ectasia and aneurysm) on the initial and subsequent echocardiograms. Forty-four percent of patients had a coronary artery lesion (31% with ectasia, 13% with aneurysm) on the initial echocardiogram. Patients with incomplete Kawasaki syndrome were treated significantly later (median, 10 days) and had a significantly higher occurrence of coronary artery aneurysms over the course of their illness (37%) than those with complete Kawasaki syndrome, who were treated at a median of 7 days (P<.001) and had a 12% aneurysm occurrence (P = .009). Patients treated by day 7 of illness had a less frequent occurrence of aneurysm (6%) compared with those patients treated between days 8 and 10 of illness (27%) (P = .03). Coronary artery lesions are frequently detected on the initial echocardiogram of children with Kawasaki syndrome. If future studies show ectasia to have a relatively high degree of specificity for Kawasaki syndrome, the initial echocardiography may be a useful adjunctive diagnostic test.

Immunologic aspects of Kawasaki disease: Implications for pathogenesis and therapy

Summary: Kawasaki disease (KD) is an acute vasculitis primarily affecting infants and young children. It is characterized by prolonged fever, bilateral nonexudative conjunctivitis, induration and erythema of the hands and feet, inflammation of the lips and oropharynx, polymorphous skin rash, and cervical lymphadenopathy. Left untreated, up to 30% of cases may be associated with the development of coronary artery abnormalities. Reports that high-dose intravenous immune globulin (IVIG) significantly reduces the occurrence of coronary artery aneurysms in patients with KD suggest that immunologic processes play a significant role in the pathogenesis of this syndrome. An immunologic basis for KD is further supported by the observation of a T-cell imbalance during the acute phase of the disease and the increased production of cytokines that occurs during the acute phase but not during convalescence. Histologic evaluation of vascular lesions reveals adhesion of leukocytes to the endothelial wall, infiltration of neutrophils and mononuclear cells, and the expression of class II major histocompatibility complex antigens on coronary artery endothelium. It also has been demonstrated that during the acute phase, there is an appearance of circulating antibodies cytotoxic to endothelial cells that have been activated with interleukin-1, tumor necrosis factor-α, or interferon-γ but not to unstimulated cells. These observations have led us to postulate that endothelial cell injury requires (1) the induction of new endothelial cell antigens in response to increased cytokine production and (2) the generation of antibodies directed against these antigens. A number of multicenter trials have demonstrated that high-dose IVIG in combination with aspirin effectively reduces the prevalence of coronary artery abnormalities. The mechanism by which IVIG reduces vasculitis is not precisely known. However, there is evidence that the clinical benefit of IVIG in KD is derived from immunoregulatory effects that work to reduce cytokine secretion and thus reverse endothelial activation.

Treatment of Kawasaki syndrome: A comparison of two dosage regimens of intravenously administered immune globulin

Because intravenously administered immune globulin (IVIG) is effective in reducing the incidence of coronary artery aneurysms in Kawasaki syndrome when given at a dose of 400 mg/kg daily for 4 days, we undertook a multicenter clinical trial comparing two dosage regimens of IVIG. Patients were randomly assigned to receive IVIG at either 400 mg/kg daily for 4 days (22 patients) or 1 gm/kg as a single dose (22 patients). All patients received aspirin therapy, and all were enrolled within 7 days of onset of fever. The presence of coronary artery aneurysms was evaluated by means of two-dimensional echocardiography before infusion; at days 4 to 6, 14 to 21, and 42 to 49 after infusion; and at 1 year. Coronary artery aneurysms were detected in 3 of the 44 patients, including one patient receiving 400 mg/kg and two patients receiving 1 gm/kg (p value not significant). No giant aneurysms were detected. No major side effects occurred with either dosage regimen. Patients receiving the 1 gm/kg dose had a faster resolution of fever and were discharged from the hospital approximately 1 day sooner than the 400 mg/kg group (p = 0.01). Although the relatively small sample size in this trial does not allow for a more definitive statement regarding the occurrence of coronary artery aneurysms, it appears that the 1 gm/kg dose is associated with a more rapid clinical improvement and a shorter hospital stay.