Primary adjunctive corticosteroid therapy is associated with improved outcomes for patients with Kawasaki disease with coronary artery aneurysms at diagnosis

2020 ◽  
pp. archdischild-2020-319810 ◽  
Author(s):  
Kevin G Friedman ◽  
Kimberlee Gauvreau ◽  
Annette Baker ◽  
Mary Beth Son ◽  
Robert Sundel ◽  
...  
Keyword(s):  
Coronary Artery ◽  
Kawasaki Disease ◽  
Corticosteroid Therapy ◽  
Initial Treatment ◽  
Treatment Resistance ◽  
Primary Treatment ◽  
Z Score ◽  
Coronary Artery Aneurysms ◽  
Reactive Protein ◽  
Randomised Controlled

ObjectivePatients with Kawasaki disease (KD) with coronary artery enlargement at diagnosis are at the highest risk for persistent coronary artery aneurysms (CAAs) and may benefit from primary adjunctive anti-inflammatory therapy beyond intravenous immunoglobulin (IVIG). We evaluate the effect of primary adjunctive corticosteroid therapy on outcomes in patients with CAA at diagnosis.DesignSingle-centre, retrospective review.PatientsPatients with KD diagnosed within 10 days of fever onset and with baseline CA z-score ≥2.5.InterventionsPrimary treatment with IVIG (n=162) versus IVIG plus corticosteroids (n=48).Main outcome measuresTreatment resistance (persistent fever >36 hours after initial treatment), CAA regression rate.ResultsOf the 92 patients with KD who received corticosteroids at our institution from 2012 to 2019, 48 met the inclusion criteria for primary adjunctive therapy. The corticosteroid group was younger and had larger baseline CAAs compared with historical controls. Demographics and laboratory values were otherwise similar between groups. The corticosteroid group had a less treatment resistance (4% vs 30%, p=0.003) and a greater improvement in C reactive protein. After adjusting for baseline CA z-score, age and baseline bilateral versus unilateral CAA, the corticosteroid group had a higher odds of (OR 2.77 (1.04, 7.42), p=0.042) and a shorter time to CAA regression (HR 1.94 (1.27, 2.96), p=0.002).ConclusionPrimary adjunctive corticosteroid therapy is associated with decreased initial treatment resistance, greater improvement in inflammatory markers and higher likelihood of CAA regression in patients who have CAA at diagnosis. Multi-centre, randomised controlled trials are needed to confirm the benefits of corticosteroids in patients with CAA at diagnosis and to compare corticosteroids with other adjunctive therapies.

scholarly journals Prediction of Coronary Artery Aneurysms in Children With Kawasaki Disease Before Starting Initial Treatment

2021 ◽  
Vol 9 ◽  
Author(s):  
Ching-Ying Huang ◽  
Nan-Chang Chiu ◽  
Fu-Yuan Huang ◽  
Yen-Chun Chao ◽  
Hsin Chi
Keyword(s):  
Coronary Artery ◽  
Kawasaki Disease ◽  
Predictive Value ◽  
Primary Treatment ◽  
C Reactive Protein ◽  
Coronary Artery Aneurysms ◽  
Reactive Protein ◽  
Clinical Challenge ◽  
Z Scores ◽  
Sensitivity Specificity

Background: Precisely predicting coronary artery aneurysms (CAAs) remains a clinical challenge. We aimed to investigate whether coronary dimensions adjusted for body surface area (Z scores) on baseline echocardiography and clinical variables before primary treatment could predict the presence of late CAAs.Methods: We conducted a retrospective study including children hospitalized for Kawasaki disease and received intravenous immunoglobulin within 10 days of illness. We defined late CAAs as a maximum Z score (Zmax) ≥2.5 of the left main, right, or left anterior descending coronary artery at 11–60 days of illness. Associations between late CAAs and clinical parameters and baseline maximum Z scores were analyzed.Results: Among the 314 included children, 31 (9.9%) had late CAAs. Male, higher C-reactive protein, and higher baseline Zmax were risk factors of late CAAs. Late CAAs were significantly associated with baseline Zmax ≥2.0 vs. <2.0 (25 [32.5%] vs. 6 [2.5%], P < 0.001). The odds ratio for late CAAs among the patients with baseline Zmax ≥2.0 vs. <2.0 was 18.5 (95% confidence interval, 7.23 to 47.41, P < 0.001). The sensitivity, specificity, positive predictive value, and negative predictive value of baseline Zmax ≥2.0 for the presence of later CAAs were 80.6, 81.6, 32.5, and 97.5%, respectively.Conclusions: Findings from this study suggest that Zmax ≥2.0 of coronary arteries on baseline echocardiography may be used to predict children at a high risk of late CAAs and allow for targeted early intensification therapy.

Abstract 221: Use of Statins in Patients with Coronary Artery Aneurysms: A Pilot Study from the North American Kawasaki Disease Registry

Circulation ◽  
2015 ◽  
Vol 131 (suppl_2) ◽  
Author(s):  
Michael Khoury ◽  
Michael A Portman ◽  
Cedric Manlhiot ◽  
Anne Fournier ◽  
Rejane F Dillenburg ◽  
...  
Keyword(s):  
Coronary Artery ◽  
Pilot Study ◽  
Kawasaki Disease ◽  
Linear Regression ◽  
North American ◽  
Z Score ◽  
Disease Registry ◽  
Coronary Artery Aneurysms ◽  
The North ◽  
Significant Difference

Background: Statins have been considered as therapy for children with coronary artery aneurysms (CAA) after Kawasaki disease (KD), due to potential beneficial pleiotropic effects which might influence chronic vascular processes and inflammation. Methods: The North American Kawasaki Disease Registry was queried to identify patients who have received statins in the first 6 months following the convalescent phase of KD. Each identified patient was matched by age, gender and CAA z score to 3 patients who were statin-naïve (controls). Linear regression models adjusted for repeated measures and maximum coronary involvement were used to determine an association of statin use with longitudinal changes in coronary artery diameter z-score. Kaplan-Meier analysis was used to compare freedom from angiographically-confirmed stenosis or interventions. Results: Of 29 patients with KD and CAA (maximum coronary artery z-score >10) who received statins at any time (of n=621, 5%), 10 (9 males) patients were started within 6 months of the acute KD episode. The mean age at KD was 6.3±3.4 years (5.4±3.5 for controls, p=0.57). Mean maximum CAA z-score was 36±14 (vs. 29±16, p=0.20); 90% of statin patients and 87% of matched controls had CAAs in 3 or more branches. Linear regression analysis of 442 serial echocardiograms showed that maximum CAA z-score decreased by -1.5 (95%CI: -2.7; -0.4) SD/year (p=0.008) for control patients compared to -2.9 (95%CI: -4.4; -1.4) SD/year (p<0.001) for statin treated patients. The difference between the rate of change of CAA z-score for statin vs. control patients did not reach statistical significance (controls vs. statins: +1.4 SD/year, 95%CI: -0.6; +3.4, p=0.18). n=7 patients (3 on statin, 4 controls) developed stenosis or had revascularization, with no significant difference between groups (HR for statin group: 2.2 (0.4-11.4), p=0.41). Conclusions: This underpowered pilot study suggests that equipoise likely exists with regards to statin therapy in children with KD and CAA, and that a formal registry-nested trial might be considered.

Abstract 225: Variations in Pharmacological Management of Children with Coronary Artery Aneurysms after Kawasaki Disease: A Study from the North American Kawasaki Disease Registry

Circulation ◽  
2015 ◽  
Vol 131 (suppl_2) ◽  
Author(s):  
Elif Seda Selamet Tierney ◽  
Andrew S Mackie ◽  
Brian W McCrindle ◽  
Mathew Mathew ◽  
Kathryn R Armstrong ◽  
...  
Keyword(s):  
Coronary Artery ◽  
Kawasaki Disease ◽  
North American ◽  
Beta Blockers ◽  
Practice Variation ◽  
Z Score ◽  
Disease Registry ◽  
Coronary Artery Aneurysms ◽  
Pharmacological Management ◽  
The North

Background: The pharmacological management of coronary artery aneurysms (CAA) associated with Kawasaki disease (KD) is based on imperfect evidence, which may lead to considerable practice variation. Methods: Pharmacological management of patients included in the North American Kawasaki Disease Registry was reviewed. The Registry included data for 621 patients with CAA after KD (280 patients with maximum CAA z-score between 2.5-5.0, 139 with z-score 5.0-10.0 and 202 with z-score >10.0) followed at 20 medical centers. Practice variation regarding acute treatment, anti-inflammatory agents, statins, beta-blockers, antiplatelet therapy and anticoagulation were assessed. Results: Considerable practice variation existed between centers. During the acute phase, 93% of patients received at least one dose of IVIG (range: 80-100%), with 23% (range: 12-50%) receiving additional immunomodulatory treatment (22% additional IVIG, 17% steroids, 4% infliximab). Use of a 3 rd course of IVIG was infrequent (2%). All centers reported using additional IVIG or steroids for IVIG-resistant patients, but only 6 centres reported any experience with infliximab (2 commonly, 4 infrequent). Routine use of non-steroidal anti-inflammatory agents was limited to 2 centres, with 4 additional sites reporting infrequent use (10% of patients). Statins (5%), beta blockers (4%) and abciximab (3%) were mostly used by a single centre and was limited to patients with giant CAAs. Aspirin was the primary antiplatelet modality for 97% of patients, clopidogrel (10% of all patients, 23% in giant CAA) was routinely prescribed to patients with giant CAAs at 6 centres, with 2 more centres reporting infrequent use and the remainder not reporting any use. For patients with giant CAA (z-score>10.0), 46% were maintained on an antiplatelet agent alone, 17% additionally were on low molecular weight heparin(LMWH), 12% on warfarin and 25% had initially received LMWH and were later switched to warfarin. Conclusions: Given the important variations in management between centres and the poor evidence base, randomized controlled trials examining outcomes and nested in a high-quality collaborative registry may be an efficient strategy to address this gap.

scholarly journals AB0735 POLYMORPHISMS OF GENES CD14, C-REACTIVE PROTEIN, FIBRINOGEN BETA CHAIN, ASSOCIATED WITH THE DEVELOPMENT OF KAWASAKI DISEASE AND CORONARY ARTERY ANEURYSMS IN CHILDREN FROM CENTRAL RUSSIA

2021 ◽  
Vol 80 (Suppl 1) ◽  
pp. 1397.2-1397
Author(s):  
M. Kantemirova ◽  
S. Kurbanova ◽  
Y. Novikova ◽  
A. Glazyrina ◽  
M. Azova ◽  
...  
Keyword(s):  
Coronary Artery ◽  
Kawasaki Disease ◽  
Gene Polymorphism ◽  
Control Group ◽  
Beta Chain ◽  
C Reactive Protein ◽  
Coronary Artery Aneurysms ◽  
Allele Distribution ◽  
Reactive Protein ◽  
Significant Difference

Background:Kawasaki disease (KD) is a multifactorial disease with a genetic predisposition, systemic vasculitis complicated by the formation of coronary artery aneurysms (CAA). Its pathogenesis is based on immune inflammation with an increase in the concentration of pro-inflammatory cytokines, the level of C-reactive protein (CRP), and coagulation disorder.Objectives:to search for polymorphisms of genes cluster of differentiation CD14, CRP, fibrinogen beta chain (FGB), associated with the KD development and a predisposition to the CAA formation among patients with KD living in Moscow and the Moscow region.Methods:genotyping for gene polymorphisms CD14 –159 C>T (rs2569190), CRP 3872 C>T (rs1205), FGB – 455 G>A (rs1800790) by PCR in 31 children 1 month – 10 years old (median age 19 months [9,0; 38,5]) with KD, among them, in 10 patients the disease was complicated by CAA formation according to echocardiography, and 30 children of the control group.Results:Three out of six investigated SNPs showed statistically significant difference in genotype and allele distribution: СRP C3872T, CD14 C159T and FGB G455A. CRP gene polymorphism: in patients with KD significantly less frequent is homozygous type TT (RR 0,22, 95% CI: 0,05–0,91, p=0,0168).CD14 gene polymorphism: in control group heterozygous genotype CT is predominant, (RR 0,58, 95% CI: 0,4–0,83, p=0,0017) among patients with KD homozygous genotypes CC and TT are predominant. (RR 3,61, 95% CI: 1,14–11,49, p=0,0057).FGB gene polymorphism: genotype GA is predominant in control group (RR 0,48, 95% CI: 0,26–0,9, p=0,0149). In patients with KD significantly less frequent is homozygous type GG (RR 1,69, 95% CI: 1,03–2,8, p=0,0297).We didn’t find any significant difference in genotype and allele distribution in KD patients with and without CA lesions.Conclusion:statistically significant differences (p<0,05) were revealed in the distribution of genotypes for polymorphisms of the CD14 –159 C>T, CRP 3872 C>T and FGB –455 G>A genes among patients with KD and children of the control group; when comparing the results of KD patients with CAA and the control group, statistically significant differences (p<0,05) were revealed only in the polymorphism CD14 –159 C>T. It can be assumed that these polymorphisms are associated with the development of KD and CAA in these patients.Disclosure of Interests:None declared

Abstract 17092: Coronary Artery Aneurysms Are More Common in Post-COVID-19 Multisystem Inflammatory Syndrome in Children (MIS-C) Than Pre-Pandemic Kawasaki Disease

Circulation ◽  
2020 ◽  
Vol 142 (Suppl_3) ◽  
Author(s):  
Justin M Pick ◽  
Shuo Wang ◽  
Sharon Wagner-Lees ◽  
Sarah Badran ◽  
Jacqueline R Szmuszkovicz ◽  
...  
Keyword(s):  
Coronary Artery ◽  
Kawasaki Disease ◽  
Statistical Significance ◽  
Significant Rise ◽  
Z Score ◽  
Coronary Artery Aneurysms ◽  
Delayed Reaction ◽  
Z Scores ◽  
Valve Function ◽  
Inflammatory Syndrome

Introduction: Multisystem Inflammatory Syndrome in Children (MIS-C) is thought to be a delayed reaction to SARS-CoV-2 exposure. Coronary artery aneurysms (CAA) have been described in the MIS-C diagnostic criteria, with many symptoms mimicking Kawasaki disease (KD). Our institution has seen a significant rise in KD-like illness during the current COVID-19 pandemic. Objectives: We sought to describe the variation in coronary artery (CA) involvement between traditional KD and post-COVID-19 pandemic KD/MIS-C cases. Methods: We identified children admitted to our center with KD from April to June 2016 - 2017 and those with MIS-C/KD from April 1 - June 6, 2020, with review of clinical and echocardiogram data. Presence of CAA (any CA z-score ≥ +2.5), z-scores of the left main (LMCA), left anterior descending (LAD), and right coronary artery (RCA), and presence of cardiac and valvar dysfunction were evaluated. Nonparametric Wilcoxon rank sum test was used to compare the groups. Results: There were 26 patients in the 2016-17 KD group and 24 in the 2020 KD/MIS-C group; results are shown in Table 1. The groups had similar median age, and 2016-17 KD patients were more likely to be male. 2020 KD/MIS-C patients were more likely to have CAA than 2016-17 KD patients (54% vs 26%, p=0.05). The LAD had larger median z-score in 2020 KD/MIS-C than KD (p=0.017). RCA and LMCA z-scores of 2020 KD/MIS-C patients tended to be larger than 2016-17 KD but did not reach statistical significance (p=0.097, p=0.07 respectively). More 2020 KD/MIS-C patients had cardiac dysfunction, not statistically significant (13% vs 0%, p=NS), with no differences in valve function or effusion. Conclusions: Our spring 2020 cohort of MIS-C/KD patients had higher incidence of CAA, particularly larger LAD z-scores than those with KD pre-COVID-19 pandemic. Coronary arteries should be thoroughly assessed in patients presenting with MIS-C symptoms. Future studies are needed to determine long term outcomes in this cohort.

Abstract O.58: Medium-term Outcomes of Coronary Artery Aneurysms after Kawasaki Disease: A Study from the North American Kawasaki Disease Registry

Circulation ◽  
2015 ◽  
Vol 131 (suppl_2) ◽  
Author(s):  
Brian W McCrindle ◽  
Cedric Manlhiot ◽  
Kristen Sexson ◽  
Pei-Ni Jone ◽  
Mathew Mathew ◽  
...  
Keyword(s):  
Coronary Artery ◽  
Kawasaki Disease ◽  
North American ◽  
Z Score ◽  
Disease Registry ◽  
Coronary Artery Aneurysms ◽  
Luminal Diameter ◽  
The North ◽  
Increased Risk ◽  
Over Time

Background: One of the main impediments to conceiving and planning studies in children with coronary artery aneurysms (CAA) after Kawasaki disease (KD) is the lack of normative data regarding the prevalence of outcomes over time and risk factors. Methods: The North American Kawasaki Disease Registry was used to determine the prevalence of multiple clinically important outcomes of CAA after KD. All analyses were stratified by severity of CAA (small CAA with z-score = 2.5-5, medium with z-score = 5-10 and giant with z-score >10). All analyses were performed using non-parametric survival analysis. Results: n=621 patients submitted to the Registry had complete follow-up data and were included in the analysis (280 [45%] small CAA, 139 [22%] medium and 202 [33%] giant). Time-related freedom from multiple outcomes stratified by type of CAA are reported in the Table. Reduction in z-scores was strongly associated with the initial size of the lesion, with smaller lesions being more likely to decrease to a normal dimension over time. Thrombosis and stenosis were infrequent in patients without giant CAA. For those patients with giant CAA, the risk of thrombosis, myocardial infarction, angiographically-confirmed stenosis and revascularization was substantial and persisted up to 10 years after diagnosis. In addition to larger luminal diameter, other factors associated with increased risk of adverse outcomes included larger CAA longitudinal area and complex CAA (vs. isolated lesions). Conclusions: Only patients with giant CAA are at substantial risk of adverse clinical outcomes; future trials of pharmacological therapy targeting thrombosis and stenosis risk should focus on these patients.

Abstract 125: Steroid Treatment in the Acute Phase of Kawasaki Disease in Mexican Children. Are they Useful?

Circulation ◽  
2015 ◽  
Vol 131 (suppl_2) ◽  
Author(s):  
Miguel Garcia-Dominguez ◽  
Luis M Garrido-Garcia
Keyword(s):  
Coronary Artery ◽  
Kawasaki Disease ◽  
Intravenous Immunoglobulin ◽  
Initial Treatment ◽  
Ivig Treatment ◽  
Cardiac Complications ◽  
Primary Therapy ◽  
Coronary Artery Aneurysms ◽  
Steroid Group ◽  
Increased Risk

Background: Intravenous immunoglobulin (IVIG) and aspirin is the standard initial therapy in the treatment of Kawasaki disease (KD), which is proven to decrease the incidence of coronary artery aneurysms from 25% to less than 5%. There is increasing evidence for steroid therapy as adjunctive primary therapy with IVIG especially in those patients who are at increased risk of coronary artery aneurysms and in patients with risk of IVIG resistance. However, clinical trials evaluating the use of corticosteroids plus IVIG have produced confusing results. Objective: To evaluate the clinical efficacy and safety of steroids plus intravenous immunoglobulin (IVIG) combination therapy (IVIG+S) for the initial treatment of patients with KD to prevent coronary artery aneurysms (CAA) compared with the standard treatment with intravenous immunoglobulin plus aspirin (IVIG+A) in a Children’s Hospital in Mexico City. Material and Methods: An observational, comparative, retrospective and case-control study of all patients treated with IVIG for KD in our Institution from August 1995 to May 2014. The clinical presentation, laboratory results and coronary artery abnormalities in the IVIG+S and the IVIG+A groups were analyzed and compared. Results: We studied 295 patients with KD treated with IVIG, 136 (46.1%) received IVIG+A treatment and 159 (53.9%) received IVIG+S treatment. We didn’t found adverse reactions in the patients treated with steroids. The IVIG+S group were older 43.25 ± 43.04 than the non-steroid group 32.07 ± 24.51 (p < 0.008). Steroids were commonly use in incomplete cases (p < 0.059) and in patients with cardiac complications at diagnosis: pericardial effusion (p < 0.056) and pericarditis (p < 0.013). The steroid group has slightly more days of fever after the IVIG treatment 1.27 ± 1.51 days vs. 0.93 ± 0.924 days (p < 0.028). We found no difference in the development of CAA in both groups. (p = 0.221) Conclusions: There were no differences in the development of CAA with the use of steroids in the initial treatment of KD. Nevertheless steroids were used more commonly in incomplete forms of KD and in more severely affected patients, which could reflect the lack of difference in the development of CAA in both groups.

Abstract O.41: Assessment of Kawasaki Disease Risk Scores for Predicting Coronary Artery Aneurysms at a North American Center

Circulation ◽  
2015 ◽  
Vol 131 (suppl_2) ◽  
Author(s):  
Mary Beth F Son ◽  
Kimberlee Gauvreau ◽  
Susan Kim ◽  
Alexander Tang ◽  
Fatma Dedeoglu ◽  
...  
Keyword(s):  
Logistic Regression ◽  
Coronary Artery ◽  
High Risk ◽  
Kawasaki Disease ◽  
Clinical Laboratory ◽  
Disease Risk ◽  
Risk Scores ◽  
Z Score ◽  
Coronary Artery Aneurysms ◽  
Z Scores

Aim: To assess the performance of established Japanese risk scores (RS) to identify patients (pts) with Kawasaki disease (KD) at high-risk for developing coronary artery aneurysms (CAA). Methods: We reviewed clinical, laboratory and echocardiographic (echo) data for pts with KD treated with IVIG from 1/2006 to 5/2014. We defined CAA as z score ≥2.5 in the right coronary artery (RCA) or left anterior descending artery (LAD) at 4-8 weeks of illness. Relationships with Kobayashi, Sano, Egami and Harada RS and CAA were examined. The maximum z score of LAD or RCA (zMax) at baseline was a covariate in logistic regression. The discrimination of each model was assessed using the c statistic. Results: Of 268 pts with complete data, 173 (65%) were male and median age was 3.1 y (range 0.1-14.1 y). At diagnosis, 74 (28%) had ≤3 classical criteria for KD, and 70 pts (26%) received IVIG retreatment. On baseline echo, 75 pts (27%) had a zMax ≥ 2.0. CAA occurred in 15 pts (5.6%). The Harada RS predicted development of CAA (low risk = 0% (0/80), high risk=9% (12/140), p=0.005), but the Kobayashi, Sano, and Egami RS were not associated with CAA. CAA were associated with baseline zMax ≥2.0 vs. <2.0 (12 [16%] vs. 3 [2%], respectively, p<0.001) and as a covariate in logistic regression (Table 1). Conclusions: With the exception of the Harada score, established RS were ineffective at predicting the development of CAA at a cosmopolitan center. Baseline z scores were highly associated with CAA. However, adding baseline z scores to a logistic regression model did not improve discrimination of the RS.

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