Risk Model Development and Validation for Prediction of Coronary Artery Aneurysms in Kawasaki Disease in a North American Population.

Background Accurate prediction of coronary artery aneurysms ( CAAs ) in patients with Kawasaki disease remains challenging in North American cohorts. We sought to develop and validate a risk model for CAA prediction. Methods and Results A binary outcome of CAA was defined as left anterior descending or right coronary artery Z score ≥2.5 at 2 to 8 weeks after fever onset in a development cohort (n=903) and a validation cohort (n=185) of patients with Kawasaki disease. Associations of baseline clinical, laboratory, and echocardiographic variables with later CAA were assessed in the development cohort using logistic regression. Discrimination (c statistic) and calibration (Hosmer-Lemeshow) of the final model were evaluated. A practical risk score assigning points to each variable in the final model was created based on model coefficients from the development cohort. Predictors of CAAs at 2 to 8 weeks were baseline Z score of left anterior descending or right coronary artery ≥2.0, age <6 months, Asian race, and C-reactive protein ≥13 mg/ dL (c=0.82 in the development cohort, c=0.93 in the validation cohort). The CAA risk score assigned 2 points for baseline Z score of left anterior descending or right coronary artery ≥2.0 and 1 point for each of the other variables, with creation of low- (0-1), moderate- (2), and high- (3-5) risk groups. The odds of CAA s were 16-fold greater in the high- versus the low-risk groups in the development cohort (odds ratio, 16.4; 95% CI , 9.71-27.7 [ P<0.001]), and >40-fold greater in the validation cohort (odds ratio, 44.0; 95% CI, 10.8-180 [ P<0.001]). Conclusions Our risk model for CAA in Kawasaki disease consisting of baseline demographic, laboratory, and echocardiographic variables had excellent predictive utility and should undergo prospective testing

Treatment Intensification in Patients With Kawasaki Disease and Coronary Aneurysm at Diagnosis.

BackgroundCoronary artery aneurysms (CAA) are a serious complication of Kawasaki disease. Treatment with intravenous immunoglobulin (IVIg) within 10 days of fever onset reduces the risk of CAA from 25% to <5%. Corticosteroids and infliximab are often used in high-risk patients or those with CAA at diagnosis, but there are no data on their longer-term impact on CAA.MethodsRetrospective multicenter study including children who had CAA with a z score ≥2.5 and <10 at time of diagnosis and who received primary therapy with IVIg alone or in combination with either corticosteroids or infliximab within 10 days of onset of fever.ResultsOf 121 children, with a median age of 2.8 (range 0.1-15.5) years, 30 (25%) received primary therapy with corticosteroids and IVIg, 58 (48%) received primary therapy with infliximab and IVIg, and 33 (27%) received primary therapy with IVIg only. Median coronary z scores at the time of diagnosis did not differ among treatment groups (P = .39). Primary treatment intensification with either corticosteroids or infliximab were independent protective factors against progression of coronary size on follow-up (coefficient: -1.31 [95% confidence interval: -2.33 to -0.29]; coefficient: -1.07 [95% confidence interval: -1.95 to -0.19], respectively).ConclusionsAmong a high-risk group of patients with Kawasaki disease with CAA on baseline echocardiography, those treated with corticosteroids or infliximab in addition to IVIg had less progression in CAA size compared with those treated with IVIg alone. Prospective randomized trials are needed to determine the best adjunctive treatment of patients who present with CAA

Temporal Trends in Pulse Pressure and Mean Arterial Pressure During the Rise of Pediatric Obesity in US Children

Background: Somatic growth in childhood is accompanied by substantial remodeling of the aorta. Obesity is associated with increased aortic stiffness and flow and may interfere with aortic remodeling during growth. Wide pulse pressure (PP) indicates mismatch between aortic impedance and pulsatile flow and increases risk for future systolic hypertension and cardiovascular disease (CVD). We hypothesized that the rise of pediatric obesity would be associated with a temporal trend to higher PP. Methods and Results: We analyzed demographic, anthropometric, and blood pressure (BP) data for 8‐ to 17‐year‐old children (N=16 457) from the cross‐sectional National Health and Nutrition Examination Surveys (NHANES) for 1976 through 2008. Multivariable adjusted survey regression was used to examine temporal trends in PP and mean arterial pressure (MAP) and the relation to obesity. Across this period, unadjusted PP was higher (0.29 mm Hg/y, 95% CI 0.26 to 0.33 mm Hg/y; P<0.0001), while MAP was lower (−0.24 mm Hg/y, 95% CI −0.27 to −0.20 mm Hg/y; P<0.0001) across examinations. Adjusting for body mass index partially attenuated the temporal trend for PP by 32% (P<0.0001). Obesity amplified the relation between taller height and higher PP (from 0.23 [95% CI 0.19 to 0.28] to 0.27 [95% CI 0.21 to 0.34] mm Hg/cm height in boys and from 0.08 [95% CI 0.04 to 0.13] to 0.22 [95% CI 0.13 to 0.31] mm Hg/cm height in girls; P<0.01 for both). Conclusions: PP has increased during the rise of pediatric obesity. Higher PP may indicate mismatch between aortic diameter, wall stiffness, and flow in obese children during a period of rapid somatic growth when the aorta is already under considerable remodeling stress

Gene-expression patterns reveal underlying biological processes in Kawasaki disease

Analysis of patterns of gene expression in peripheral blood from children with Kawasaki disease revealed dynamic and variable gene expression programs involving neutrophil activation and apoptosis

Development and Utility of Quality Metrics for Ambulatory Pediatric Cardiology in Kawasaki Disease.

The Adult Congenital and Pediatric Cardiology (ACPC) Section of the American College of Cardiology sought to develop quality indicators/metrics for ambulatory pediatric cardiology practice. The objective of this study was to report the creation of metrics for patients with Kawasaki disease. Over a period of 5 months, 12 pediatric cardiologists developed 24 quality metrics based on the most relevant statements, guidelines, and research studies pertaining to Kawasaki disease. Of the 24 metrics, the 8 metrics deemed the most important, feasible, and valid were sent on to the ACPC for consideration. Seven of the 8 metrics were approved using the RAND method by an expert panel. All 7 metrics approved by the ACPC council were accepted by ACPC membership after an "open comments" process. They have been disseminated to the pediatric cardiology community for implementation by the ACPC Quality Network

Lowy, Michael, The Marxism of Che Guevara : Philosophy, Economics, and Revolutionary Warfare, New York and London, Monthly Review Press, 1973, 127 p.

BACKGROUND: Infants with cyanotic congenital heart disease palliated with placement of a systemic-to-pulmonary-artery shunt are at risk for shunt thrombosis and death. We investigated whether the addition of clopidogrel to conventional therapy reduces mortality from any cause and morbidity related to the shunt. METHODS: In a multicenter, double-blind, event-driven trial, we randomly assigned infants 92 days of age or younger with cyanotic congenital heart disease and a systemic-to-pulmonary-artery shunt to receive clopidogrel at a dose of 0.2 mg per kilogram of body weight per day (467 infants) or placebo (439 infants), in addition to conventional therapy (including aspirin in 87.9% of infants). The primary efficacy end point was a composite of death or heart transplantation, shunt thrombosis, or performance of a cardiac procedure due to an event considered to be thrombotic in nature before 120 days of age. RESULTS: The rate of the composite primary end point did not differ significantly between the clopidogrel group (19.1%) and the placebo group (20.5%) (absolute risk difference, 1.4 percentage points; relative risk reduction with clopidogrel, 11.1%; 95% confidence interval, -19.2 to 33.6; P=0.43), nor did the rates of the three components of the composite primary end point. There was no significant benefit of clopidogrel treatment in any subgroup, including subgroups defined by shunt type. Clopidogrel recipients and placebo recipients had similar rates of overall bleeding (18.8% and 20.2%, respectively) and severe bleeding (4.1% and 3.4%, respectively). CONCLUSIONS: Clopidogrel therapy in infants with cyanotic congenital heart disease palliated with a systemic-to-pulmonary-artery shunt, most of whom received concomitant aspirin therapy, did not reduce either mortality from any cause or shunt-related morbidity. (Funded by Sanofi-Aventis and Bristol-Myers Squibb; ClinicalTrials.gov number, NCT00396877.)

The impact of socio-economic status on health related quality of life for children and adolescents with heart disease

Background: Socioeconomic status (SES) is known to influence children’s health-related quality of life. Many SES indicators assess distinct dimensions of a family’s position rather than measuring the same underlying construct. Many researchers, however, see SES indicators as interchangeable. The primary aim of this study was to determine which measure of SES had the strongest impact on health-related quality of life. Methods: This is a secondary analysis of the Pediatric Cardiac Quality of Life Inventory Validation Study. The SES variables were family income, Hollingshead Index (occupational prestige), and highest parent educational attainment level. Health-related quality of life was measured using the Pediatric Cardiac Quality of Life Inventory. Correlations tested the relationship among the three SES indicators. Regression-based modeling was used to calculate the strength of the association between SES measures and the Pediatric Cardiac Quality of Life Inventory. Results: The correlations among the SES measures were moderately high, with the correlation between the Hollingshead Index and parental education being r = 0.62 (95% CI = 0.56-0.65). There were equally high correlations between family income and the Hollingshead (r = 0.61, 95% CI = 0.57-0.65) and a slightly lower correlation between family income and parental education (r = 0.55, 95% CI = 0.52-0.59). Family income had the highest explanatory value compared to the Hollingshead Index or parental educational attainment, while controlling for sex, race, current cardiac status, and original diagnosis, accounting for 4-5% of the variation in patient and parent Pediatric Cardiac Quality of Life Inventory Total score, respectively, compared to the other SES measures. Conclusion: Family income as an SES measure demonstrated the greatest fidelity with respect to health-related quality of life as measured by the Pediatric Cardiac Quality of Life Inventory across respondent groups and explained more of the variation compared to the Hollingshead Index or highest parental educational attainment