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Kawasaki disease (KD) is a common childhood vasculitis associated with coronary artery aneurysms (CAA). However, there is limited published data on other cardiovascular events diagnosed during acute KD hospitalizations. Our objectives were to determine the incidence of cardiovascular events during acute KD hospitalizations, stratified by age at admission, CAA status, and pediatric intensive care unit (PICU) admission status. We identified all children (0–18 year) hospitalized with a new KD diagnosis in Ontario, between 1995 and 2018, through validated algorithms using population health administrative databases. We excluded children previously diagnosed with KD and non-Ontario residents. We evaluated for cardiovascular events that occurred during the acute KD hospitalizations, defined by administrative coding. Among 4597 children hospitalized with KD, 3307 (71.9%) were aged 0–4 years, median length of stay was 3 days (IQR 2–4), 113 children (2.5%) had PICU admissions, and 119 (2.6%) were diagnosed with CAA. During acute hospitalization, 75 children were diagnosed with myocarditis or pericarditis (1.6%), 47 with arrhythmias (1.0%), 25 with heart failure (0.5%), and ≤ 5 with acute MI (≤ 0.1%). Seven children underwent cardiovascular procedures (0.2%). Older children (10–18 years), children with CAA, and children admitted to the PICU were more likely to experience cardiovascular events, compared with children aged 0–4 years, without CAA or non-PICU admissions, respectively. The frequency of non-CAA cardiovascular events during acute KD hospitalizations did not change significantly between 1995 and 2018. During acute KD hospitalizations, older children, children with CAA, and PICU admissions are at higher risk of cardiovascular complications, justifying closer monitoring of these high-risk individuals. [ABSTRACT FROM AUTHOR]

Background: Cardiomyopathy is a clinically and genetically heterogeneous heart condition that can lead to heart failure and sudden cardiac death in childhood. While it has a strong genetic basis, the genetic aetiology for over 50% of cardiomyopathy cases remains unknown., Methods: In this study, we analyse the characteristics of tandem repeats from genome sequence data of unrelated individuals diagnosed with cardiomyopathy from Canada and the United Kingdom (n = 1216) and compare them to those found in the general population. We perform burden analysis to identify genomic and epigenomic features that are impacted by rare tandem repeat expansions (TREs), and enrichment analysis to identify functional pathways that are involved in the TRE-associated genes in cardiomyopathy. We use Oxford Nanopore targeted long-read sequencing to validate repeat size and methylation status of one of the most recurrent TREs. We also compare the TRE-associated genes to those that are dysregulated in the heart tissues of individuals with cardiomyopathy., Findings: We demonstrate that tandem repeats that are rarely expanded in the general population are predominantly expanded in cardiomyopathy. We find that rare TREs are disproportionately present in constrained genes near transcriptional start sites, have high GC content, and frequently overlap active enhancer H3K27ac marks, where expansion-related DNA methylation may reduce gene expression. We demonstrate the gene silencing effect of expanded CGG tandem repeats in DIP2B through promoter hypermethylation. We show that the enhancer-associated loci are found in genes that are highly expressed in human cardiomyocytes and are differentially expressed in the left ventricle of the heart in individuals with cardiomyopathy., Interpretation: Our findings highlight the underrecognized contribution of rare tandem repeat expansions to the risk of cardiomyopathy and suggest that rare TREs contribute to ∼4% of cardiomyopathy risk., Funding: Government of Ontario (RKCY), The Canadian Institutes of Health Research PJT 175329 (RKCY), The Azrieli Foundation (RKCY), SickKids Catalyst Scholar in Genetics (RKCY), The University of Toronto McLaughlin Centre (RKCY, SM), Ted Rogers Centre for Heart Research (SM), Data Sciences Institute at the University of Toronto (SM), The Canadian Institutes of Health Research PJT 175034 (SM), The Canadian Institutes of Health Research ENP 161429 under the frame of ERA PerMed (SM, RL), Heart and Stroke Foundation of Ontario & Robert M Freedom Chair in Cardiovascular Science (SM), Bitove Family Professorship of Adult Congenital Heart Disease (EO), Canada Foundation for Innovation (SWS, JR), Canada Research Chair (PS), Genome Canada (PS, JR), The Canadian Institutes of Health Research (PS)., Competing Interests: Declaration of interests SM holds the Heart and Stroke Foundation of Canada/Robert M Freedom Chair in Cardiovascular Science and serves on the Advisory Board for Bristol Myers Squibb and Tenaya Therapeutics. EO holds the Bitove Family Professorship of Adult Congenital Heart Disease. SWS is on the Scientific Advisory Committees of Population Bio, Inc. and Deep Genomics and serves as a Highly Cited Academic Advisor for the King Abdulaziz University. SWS and RY hold patent entitled “Genome-wide Detection of DNA Repeats Expanded in Disease” (WO2021119840A1). PM is a Senior Medical Director at Maternal Newborn Child Youth Strategic Clinical Network (Alberta Health Services) and was supported for attending Clinical Microbiology and Infectious Diseases, Long COVID and ENRICH meetings. TJM received support from CIHR, PSI and SickKids Foundation, CAMH and GSK. ES received support from COVID-19 Immune Task Force, Children's Hospital Foundation and CIHR, and is on the American Academy of Allergy, Asthma, and Immunology Credentials Committee. JR is supported by Canada Foundation for Innovation and received support for attending Ultima Biosciences and 10x Genomics meetings. Illumina, Inc. provided sequencing reagents for the CHILD cohort study. CHILD cohort study was supported by CIHR, AllerGen NCE, Alberta Health, Public Health Agency of Canada and Women's and Children's Health Research. Other authors declare that they have no competing interests., (Copyright © 2024 The Author(s). Published by Elsevier B.V. All rights reserved.)

Objective: Kawasaki disease (KD) is a childhood vasculitis with conflicting reported North American trends in incidence and patient characteristics., Objectives: (1) determine KD incidence between 1995 and 2017; (2) compare patient characteristics by era and age group; (3) determine complication and cardiovascular follow-up rates., Methods: We used population-based health administrative data to identify children (0-18 yr) hospitalized with KD in Ontario, Canada between 1995 and 2017. We excluded children with prior KD diagnosis or incomplete records. We determined the annualized incidence and follow-up trends., Results: KD was diagnosed in 4,346 children between 1995 and 2017. Annual KD incidence was 22.0 (<5 yr), 6.1 (5-9 yr), and 0.6 (10-18 yr) per 100,000 children. KD incidence increased significantly for all age groups, including from 18.4 to 25.0 cases per 100,000 children <5 yr. Ninety-day mortality occurred in ≤5 children (≤0.1%). Coronary artery aneurysm (CAA) occurred in 106 children (2.4%, 95% confidence interval 2.0-2.9) during admission and 151 (3.5%, 95% confidence interval 3.0-4.1) during 11-year median follow-up. Children 10-18 yr had longer hospitalizations (4.3 vs. 3.5 days, p = 0.003) and more CAA (7.4% vs. 3.4%, p = 0.007). By 1-year post-diagnosis, 3970 (91.3%) and 2576 (59.3%) children had echocardiography and cardiology follow-up, respectively., Conclusions: KD incidence is increasing in Ontario, with greater healthcare utilization from hospitalizations and subsequent follow-up., Impact: 4346 children were hospitalized for Kawasaki disease over 22 years in Ontario, and Kawasaki disease incidence increased significantly for all age groups, males and females. Older children (10-18 years) had longer hospital length of stay, more PICU admissions and more frequent coronary artery aneurysms. Nearly all children with Kawasaki disease had follow-up echocardiography within 1 year., (© 2021. The Author(s), under exclusive licence to the International Pediatric Research Foundation, Inc.)

Background: Transposition of the great arteries (TGA) may present as a life-threatening neonatal malformation. Although prenatal detection facilitates the perinatal management, the impact on outcome is controversial., Methods: This study reviewed the differences in prenatal diagnosis of TGA from 2009 to 2014 among the 5 geographic areas in Ontario and compared the management, morbidity, and mortality among neonates with a prenatal (prenatal cohort; n = 70) vs a postnatal (postnatal cohort; n = 76) anomaly diagnosis. Cases were identified from prospective databases of the provincial cardiac tertiary centres and the coroner's office., Results: Prenatal TGA detection rates varied significantly among areas (median: 50%; range: 14% to 72%; P = 0.03). Compared with the postnatal cohort, time from birth to tertiary care admission (1.4 vs 10.4 hours, P < 0.001), prostaglandin therapy (0.1 vs 5.3 hours; P < 0.001), balloon atrial septostomy (5.3 vs 14.9 hours; P <0.001), and arterial switch operation (6 vs 9 days, P = 0.002) was significantly shorter in the prenatal cohort. Although other preoperative variables-including the need of ventilation and mechanical support, morbidity score, and lowest pH and preductal oxygen saturations-were comparable, a prenatal diagnosis was associated with improved 1-year survival (odds ratio: 0.108; 95% confidence interval, 0.013-0.88; P = 0.0184)., Conclusions: Prenatal diagnosis of TGA significantly shortened time intervals from birth to neonatal care and surgery and was associated with improved survival. The prenatal detection rate of TGA in Ontario was low (50% or less) outside of Metropolitan Toronto, suggesting the need for new strategies to further improve intraprovincial detection rates., (Copyright © 2020 Canadian Cardiovascular Society. Published by Elsevier Inc. All rights reserved.)