Kawasaki Disease and Clinical Outcome Disparities Among Black Children.

OBJECTIVE: To determine whether Black children with Kawasaki disease exhibit disparities in prevalence, sequelae, and response to intravenous gamma globulin (IVIG) treatment. STUDY DESIGN: International Classification of Diseases codes were used to identify children with Kawasaki disease admitted to a tertiary center in the southeastern US. Subjects diagnosed and treated according to American Heart Association criteria were included. Demographic, laboratory, clinical, and echocardiographic data from the electronic medical record (2000-2015) were compared between Blacks and Whites. RESULTS: Data from 369 subjects (52% Whites and 48% Blacks) were included in our analysis. No significant differences related to timely admission, IVIG treatment, or coronary artery (CA) abnormalities during hospitalization were observed. Blacks showed lower IVIG response rates than Whites for patients administered IVIG within 10 days of fever onset (86.6% vs 95.6%; P = .007). Blacks received more ancillary drugs (9.6% vs 2.6%; P = .003), and endured longer hospitalizations (mean, 5 ± 3.9 days vs 3.4 ± 2.2 days; P = .001). Blacks presented with higher C-reactive protein level and erythrocyte sedimentation rate and lower hemoglobin, albumin, and sodium levels. Blacks had a higher proportion of persistent CA abnormalities than Whites at second follow-up echocardiogram (14.5% vs 6.3%; P = .03), and at third follow-up echocardiogram (21.2% vs 6.9%; P = .01). CONCLUSIONS: Compared with White children, Black children with Kawasaki disease had higher IVIG refractory prevalence, more severe inflammation, more ancillary treatments, and longer hospitalizations. Despite no racial differences in time to diagnosis or initial treatment, there was greater CA abnormality persistence among Black children at follow-up.

Assessment of myocardial function by two-dimensional speckle tracking echocardiography in patients with Kawasaki disease: a mid-term follow-up study.

BACKGROUND: Myocardial impairment proved by histological studies persists in late convalescent phase Kawasaki disease patients. Whether Kawasaki disease-induced myocardial lesions can be detected in an earlier time is not well explored. In this study, we aimed to evaluate left ventricular (LV) myocardial function by two dimensional speckle tracking echocardiography (2DSTE) in late convalescent phase Kawasaki disease patients. METHODS: A total of 68 Kawasaki disease patients during mid-term phase including 47 with no coronary artery aneurysm (NCAA) and 21 with coronary artery aneurysm (CAA), and 60 controls with age matched were consecutively enrolled. RESULTS: No significant differences on conventional echocardiographic LV systolic function indices were found among group comparison. Compared with controls, Kawasaki disease patients had lower global longitudinal stain (GLS) and global circumferential stain (GCS). In subgroup analysis, both those with CAA and without CAA had lower GLS, lower GCS, higher amino-terminal propeptide of type III procollagen (PIIINP) and higher carboxyterminal propeptide of procollagen type I (PIPC) than in controls. GLS had significantly negative correlations with PIIINP (r = -0.69, P = 0.002) and PIPC (r = -0.82, P = 0.000). CONCLUSION: Subclinical myocardial dysfunction in mid-term follow-up Kawasaki disease patients existed regardless of coronary artery status despite normal measurements of LV systolic function by routine echocardiography, and myocardial fibrosis may play a contributed role in this subclinical myocardial function impairment. 2DSTE is a valuable imaging modality for detecting regional and global myocardial dysfunction in Kawasaki disease patients in an early time.

Coronary artery assessment in Kawasaki disease with dual-source CT angiography to uncover vascular pathology.

BACKGROUND: Kawasaki disease (KD) is a vasculitis with formation of coronary artery aneurysms (CAAs) that can lead to myocardial ischemia. Echocardiography is the primary imaging modality for the coronary arteries despite limited visualization. Coronary angiography (CAG) is the gold standard yet invasive with high-radiation exposure. To date however, state-of-the-art CT scanners enable high-quality low-dose coronary computed tomographic angiography (cCTA) imaging. The aim of our study in KD is to report (i) the diagnostic yield of cCTA compared to echocardiography, and (ii) the radiation dose. METHODS AND RESULTS: We collected data of KD patients who underwent cCTA. cCTA findings were compared with echocardiography results. In 70 KD patients (median age 15.1 years [0.5-59.5 years]; 78% male; 38% giant CAA), the cCTA identified 61 CAAs, of which 34 (56%, with a Z score > 3, in 22 patients) were not detected by echocardiography. In addition, the left circumflex (aneurysmatic in 6 patients) was always visible upon cCTA and not detected upon echocardiography. Calcifications, plaques, and/or thrombi were visualized by cCTA in 25 coronary arteries (15 patients). Calcifications were seen as early as 2.7 years after onset of disease. In 5 patients, the cCTA findings resulted in an immediate change of treatment. The median effective dose (ED) in millisievert differed significantly (p < 0.01) between third-generation dual-source and other CT scanners (1.5 [0.3-9.4] (n = 56) vs 3.8 [1.7-20.0] (n = 14)). CONCLUSIONS: The diagnostic yield of third-generation dual-source cCTA combined with reduced radiation exposure makes cCTA a favorable diagnostic modality to complete the diagnosis and long-term treatment indications for KD. KEY POINTS: • cCTA is a favorable diagnostic modality to complete the diagnosis and long-term treatment indications for Kawasaki disease. • Kawasaki disease patients with proven coronary artery involvement on echocardiography require additional imaging.

Assessment of the impact of isolated coronary artery ectasia on left ventricular functions with 3D speckle-tracking echocardiography.

BACKGROUND: Coronary artery ectasia (CAE) is an angiographic definition of coronary artery pathology in which the diameter of the ectatic segment measures more than 1.5 times the diameter of an adjacent healthy reference segment. No previous study has reported on the use of 3D-STE for assessing the left ventricular (LV) functions in patients with isolated CAE. As a result of this, we aimed to evaluate the effects of isolated CAE on LV functions using 3D-STE in the present study. METHODS: Ninety-one patients with isolated CAE and 90 controls who proved to have normal coronary angiograms were enrolled to the study. 3D-STE was performed and GLS, GCS, GAS, and GRS were obtained for every subject after coronary angiography. RESULTS: The mean age of the patients was 61.75 ± 10.02 years, and 71.8% were male. GLS, GCS, GAS, and GRS were significantly depressed in the isolated CAE group than in the control group (P < .001; P < .001; P = .001; and P = .001, respectively). ROC analyses were performed to find out the ideal strain cut off values to predict the presence of isolated CAE. A GLS value of >-16 has 92.1 % sensitivity, 88.5 % specificity; and a GCS value of >-20 has 86.7 % sensitivity, 89.2 % specificity to detect the presence of isolated CAE. CONCLUSION: Isolated CAE has a considerable negative effect on LV functions as evaluated by 3D-strain parameters, and 3D-STE could be an effective method to detect early stage myocardial impairment in patients with isolated CAE.

Doença de Kawasaki Recidivante / Recurrent Kawasaki Disease

Objetivou-se descrever as características clínicas, laboratoriais e epidemiológicas da Doença de Kawasaki (DK) recorrente e identificar possíveis fatores de risco. Trata-se de estudo retrospectivo do tipo caso-controle. Foi feita análise dos prontuários de pacientes com DK acompanhados de janeiro de 2012 a dezembro de 2018 em ambulatório especializado de um hospital pediátrico terciário em Brasília - DF. Foram incluídas 154 crianças; dez (6,5%) apresentaram recidiva da DK. A incidência de recidiva encontrada foi mais alta do que consta em literatura, provavelmente devido ao acompanhamento regular em um centro especializado. Não foram identificados fatores de risco relevantes para recidiva.(AU)

The objective of this study was to describe the clinical, laboratory and epidemiological characteristics of recurrent Kawasaki Disease (KD) and to identify possible risk factors. It is a retrospective case-control study.The medical records of patients with KD were analyzed from January 2012 to December 2018 in a specialized outpatient clinic of a pediatric tertiary hospital in Brasília - DF. Of 154 children included, ten (6.5%)had recurrence of KD. The incidence of recurrence was higher than reported in the literature, probably due to regular follow-up at a specialized center. No relevant risk factors for recurrence were identified.(AU)

Impact of Socioeconomic Status on Outcomes of Patients with Kawasaki Disease.

OBJECTIVE: To evaluate the association of neighborhood socioeconomic status (SES) with time to intravenous immunoglobulin treatment, length of stay (LOS), and coronary artery aneurysms (CAAs) in patients with Kawasaki disease. STUDY DESIGN: We examined the relationship of SES in 915 patients treated at a large academic center between 2000 and 2017. Neighborhood SES was measured using a US census-based score derived from 6 measures related to income, education, and occupation. Linear and logistic regression were used to examine the association of SES with number of days of fever at time of treatment, LOS, and CAA. RESULTS: Patients in the lowest SES quartile were treated later than patients with greater SES (7 [IQR 5, 9] vs 6 [IQR 5, 8] days, P = .01). Patients in the lowest SES quartile were more likely to be treated after 10 days of illness, with an OR 1.9 (95% CI 1.3-2.8). In multivariable analysis, SES remained an independent predictor of the number of days of fever at time of treatment (P = .01). Patients in the lowest SES quartile had longer LOS than patients with greater SES (3 [IQR 2, 5] vs 3 [IQR 2, 4], P = .007). In subgroup analysis of white children, those in the lowest SES quartile vs quartiles 2-4 were more likely to develop large/giant CAA 17 (12%) vs 30 (6%), P = .03. CONCLUSIONS: Lower SES is associated with delayed treatment, prolonged LOS, and increased risk of large/giant CAA. Novel approaches to diagnosis and education are needed for children living in low-SES neighborhoods.

Comprehensive left ventricular myocardial deformation assessment in children with Kawasaki disease.

OBJECTIVE: Children with Kawasaki disease (KD) with persistent coronary artery aneurysms (CAAs) can develop chronic vasculopathy and subsequent myocardial ischemia. Early detection of this process is challenging. Myocardial deformation analysis can detect early alterations in myocardial performance. We aim to determine whether there are differences in myocardial deformation between KD patients with and without CAAs. DESIGN: This is a cross-sectional study of 123 echocardiograms performed on 103 children with KD. Myocardial deformation was measured with two-dimensional speckle tracking (2DSTE). The echocardiograms were divided into groups according to the KD phase in which they were performed: acute, subacute, and convalescent/chronic. The convalescent/chronic phase group was then divided based on the presence or absence of CAAs. Left ventricular (LV) global longitudinal strain (GLS), global longitudinal strain rate (GLSSR), global circumferential strain (GCS), global circumferential systolic strain rate (GCSSR), peak torsion, and torsion rate were measured. RESULTS: The numbers of echocardiograms analyzed in each of the KD phase groups were: 31 acute, 25 subacute, and 67 convalescent/chronic. Myocardial deformation was within normal limits in all groups. However, GLSSR, GCSSR, peak torsion, and torsion rate were lower in the convalescent/chronic phase group than in the acute phase group (mean, -1.37 ± 0.24 vs -1.55 ± 0.21 1/s; -1.63 ± 0.27 vs -1.84 ± 0.35 1/s; 2.49 ± 1.13 vs 3.41 ± 2.60 °/cm, and 21.97 ± 8.36 vs 26.69 ± 10.86 °/cm/s; P < .05 for all). The convalescent/chronic phase subgroup with CAAs had lower GLSSR and GCSSR than the subgroup without CAAs (mean, -1.23 ± 0.22 vs -1.42 ± 0.22 1/s; -1.46 ± 0.25 vs -1.68 ± 0.26 1/s, P < .05 for both). CONCLUSIONS: Children in the convalescent/chronic phase of KD have a subtle decrease in strain rate when compared to the acute phase, although within the normal range. This decrease is more pronounced in children with CAAs than those without CAAs. Longitudinal studies are needed to discern whether low-normal strain rate predicts decreased myocardial function in the long term.

Coronary aneurysms in the acute patient: Incidence, characterization and long-term management results.

BACKGROUND: Coronary aneurysms (1.5 times dilation the reference-vessel) are uncommon and have been diagnosed with increasing frequency with coronary angiography. The incidence varies from 1.5% to 5%. Reported complications are multiple: thrombosis, distal embolization, rupture and vasospasm, causing ischemia, heart failure or arrhythmias. However, the natural history and prognosis remains obscure. We aimed to describe the characteristics of acute patients with coronary aneurysms. METHODS: Prospective coronariography registry of patients with the diagnosis of coronary aneurysm between 2002 and 2013. Among 51,555 consecutive coronary angiograms, 414 patients with aneurysms were reported, of which 256 were considered acute (82% NSTE-ACS). RESULTS: Predominantly male (80%, mean age 65.5years), cardiovascular risk factors were common (hypertension 65%, dyslipidemia 65%, obesity 25%, diabetes mellitus 28.5%, and smokers 67%). With frequent coronary stenoses (94%), mostly with one aneurysm (80%), it was observed more frequently in the anterior descending artery. After a median follow-up of 52months, 53 died (14 cardiac causes) and 42% presented a cardiovascular event. Complications from the aneurysm were found in 4. The duration of dual antiplatelet therapy, LVEF, age and peripheral vascular disease highlighted in the multivariate analysis of death. CONCLUSION: The presence of coronary aneurysms in patients undergoing coronary angiography with an acute event is low. Patients who present them also have a large burden of atherosclerotic risk factors. In the long-term, the probability of cardiovascular complications is high, but only a small proportion are due to the aneurysm itself. A more intense and prolonged antithrombotic treatment may result in lower mortality rates.

Clinical assessment of coronary arteries in Kawasaki disease: Focus on echocardiographic assessment.

Echocardiography is an excellent noninvasive imaging modality for evaluation and follow-up of cardiac lesions, especially coronary artery changes occurring as a result of Kawasaki disease. The information obtained has prognostic implications and can be complemented with other modes of imaging for risk stratification and optimization of both medical and interventional therapy. The aim of this article is to describe the time line of echocardiographic follow-up of patients affected with Kawasaki disease. The classification of coronary artery changes and transthoracic echocardiographic views recommended for detailed evaluation of the coronary arteries are delineated in detail in this report.

Assessment of Coronary Artery Aneurysms Caused by Kawasaki Disease Using Transluminal Attenuation Gradient Analysis of Computerized Tomography Angiograms.

Patients with coronary artery aneurysms (CAAs) resulting from Kawasaki disease (KD) are at risk for thrombosis and myocardial infarction. Current guidelines recommend CAA diameter ≥8 mm as the criterion for initiating systemic anticoagulation. Transluminal attenuation gradient (TAG) analysis has been proposed as a noninvasive method for evaluating functional significance of coronary stenoses using computerized tomography angiography (CTA), but has not previously been used in CAA. We hypothesized that abnormal hemodynamics in CAA caused by KD could be quantified using TAG analysis. We studied 23 patients with a history of KD who had undergone clinically indicated CTA. We quantified TAG in the major coronary arteries and aneurysm geometry was characterized using maximum diameter, aneurysm shape index, and sphericity index. A total of 55 coronary arteries were analyzed, 25 of which had at least 1 aneurysmal region. TAG in aneurysmal arteries was significantly lower than in normal arteries (-23.5 ± 10.7 vs -10.5 ± 9.0, p = 0.00002). Aneurysm diameter, aneurysm shape index, and sphericity index were weakly correlated with TAG (r2 = 0.01, p = 0.6; r2 = 0.15, p = 0.06; r2 = 0.16, p = 0.04). This is the first application of TAG analysis to CAA caused by KD, and demonstrates significantly different TAG values in aneurysmal versus normal arteries. Lack of correlation between TAG and CAA geometry suggests that TAG may provide hemodynamic information not available from anatomy alone. TAG represents a possible extension to standard CTA for KD patients who may improve thrombotic risk stratification and aid in clinical decision making.

Predicting Coronary Artery Aneurysms in Kawasaki Disease at a North American Center: An Assessment of Baseline z Scores.

BACKGROUND: Accurate risk prediction of coronary artery aneurysms (CAAs) in North American children with Kawasaki disease remains a clinical challenge. We sought to determine the predictive utility of baseline coronary dimensions adjusted for body surface area (z scores) for future CAAs in Kawasaki disease and explored the extent to which addition of established Japanese risk scores to baseline coronary artery z scores improved discrimination for CAA development. METHODS AND RESULTS: We explored the relationships of CAA with baseline z scores; with Kobayashi, Sano, Egami, and Harada risk scores; and with the combination of baseline z scores and risk scores. We defined CAA as a maximum z score (zMax) ≥2.5 of the left anterior descending or right coronary artery at 4 to 8 weeks of illness. Of 261 patients, 77 patients (29%) had a baseline zMax ≥2.0. CAAs occurred in 15 patients (6%). CAAs were strongly associated with baseline zMax ≥2.0 versus <2.0 (12 [16%] versus 3 [2%], respectively, P<0.001). Baseline zMax ≥2.0 had a C statistic of 0.77, good sensitivity (80%), and excellent negative predictive value (98%). None of the risk scores alone had adequate discrimination. When high-risk status per the Japanese risk scores was added to models containing baseline zMax ≥2.0, none were significantly better than baseline zMax ≥2.0 alone. CONCLUSIONS: In a North American center, baseline zMax ≥2.0 in children with Kawasaki disease demonstrated high predictive utility for later development of CAA. Future studies should validate the utility of our findings.

Eficacia y seguridad de la inmunoglobulina intravenosa en el tratamiento inicial de pacientes con enfermedad de kawasaki en la fase aguda / Efficacy and safety of intravenous immunoglobulin in the initial treatment of patients with acute phase kawasaki disease

INTRODUCCÇÃO: Antecedentes: El presente informe expone la evaluación de la inmunoglobulina intravenosa como primera línea de tratamiento de pacientes con diagnóstico de enfermedad de Kawasaki debut y activa con alteraciones de las arterias carótidas. Aspectos Generales: La enfermedad de Kawasaki (EK), previamente conocida como síndrome linfo-mucocutâneo, es una de las vasculitis más comunes de la infancia. Es una condición médica tipicamente auto-limitada, con fiebre y manifestaciones de inflamaciónaguda de una duración promedio de 12 dias sin tratamiento. Tecnología Sanitaria de Interés: La inmunoglobulina es un producto biológico que se deriva del plasma de donantes humanos y es usada en el tratamiento de múltiples condiciones médicas, incluyendo los estados de inmunodeficiencia primaria y secundaria, y una variedad de enfermedades inflamatorias. METODOLOGÍA: Estregia de Búsqueda: Se realizó una búsqueda de la literatura con respecto a la eficacia y seguridad de la inmunoglobulina intravenosa para el tratamiento de primera línea de los pacientes con enfermedad de Kawasaki activa y anormalidades de las arterias coronarias. Esta búsqueda se realizó utilkizando los meta-buscadores: Translating Research into Practice (TRIPDATABASE), National Lbrary of Medicine (Pubmed-Medline) y Health Systems Evidence. RESULTADOS: Sinopsis de la Evidencia: Se realizó la busqueda bibliográfica y de evidencia científica para el sustento del uso de IGIV como tratamiento de primera línea en pacientes con enfermedad de Kawasakicon anormalidades de las arterias carótidas. CONCLUSIONES: No se identificaron estudios que hayan comparado los efectos del tratamiento con IGIV con los de Aspirina en pacientes con EK en fase aguda. En su lugar, se ha evaluado los efectos de la adición de IGIV a la apirina, en varios ensayos clínicos aleatorizados y controlados; pero la evidencia es insuficientes y no concluyente respecto ao beneficio que ofrece la aspirina al tratamiento con IGIV. El Instituto de Evaluación de Tecnologías Sanitarias -IETSI, aprueba por el periodo de 2 años a partir de la fecha de publicación del presente dictamen preliminar, el uso de IGIV para el tratamiento de pacientes pediátricos con EK en fase aguda con o sin anormalidades de las arterias carótidas, ya que se ha demostrado su eficacia en la reducción de anormalidades de las arterias carótidas y consecuentemente disminución de la morbimortalidad en la fase aguda y a largo plazo.

Predictors of in-hospital mortality in coronary artery dissection: Findings from the National Inpatient Sample 2009-2010.

BACKGROUND: The pathophysiology of coronary artery dissection (CD) remains poorly under-stood and little is known about the factors predicting mortality in these patients. We aimed to study the epidemiology of CD and predictors of mortality in these patients. METHODS: All patients diagnosed with CD in the Nationwide Inpatient Sample 2009-2010 database using International Classification of Diseases ninth revision 414.12 were included in the study. Chronic conditions included in the analysis were diabetes mellitus, hypertension, hyperlipidemia, coronary artery disease (CAD), obesity, alcohol use, smoking, heart failure and ventricular arrhythmias. Non-cardiovascular conditions were connective tissue disorders, fibromuscular dysplasia, Ehlers-Danlos syndrome, Marfan's syndrome, sarcoidosis, Crohn's disease, polycystic kidney disease, rheumatoid arthritis, vasculitis including giant cell arteritis, polyarteritis nodosa and Takayasu's disease, cocaine use, early or premature labor. RESULTS: The prevalence of CD in the United States was 0.02% (n = 11,255), based on the hospital admissions reviewed in the database. The mean age was 63.25 years with women (64.62 years) being older than men (62.25 years) (p < 0.001). In-hospital mortality rate was 4.2%, with women (5.5%) having higher mortality than men (3.2%) (p = 0.009). Ventricular arrhythmias (OR 5.86, p < 0.001) predicted higher mortality, while hyperlipidemia (OR 0.26, p < 0.001) and CAD (OR 0.31, p = 0.001) predicted lower mortality in multivariate analysis. CONCLUSIONS: Our study demonstrated that CD was more prevalent in men but women had higher mortality than men. Age, heart failure and ventricular arrhythmias were independent predictors of increased mortality but hyperlipidemia CAD predicted lower mortality in patients with CD.