Abstract-Deterioration in endothelial function and arterial stiffness are early events in the development of cardiovascular diseases. In adults, noninvasive measures of atherosclerosis have become established as valid and reliable tools for refining cardiovascular risk to target individuals who need early intervention. With limited pediatric data, the use of these techniques in children and adolescents largely has been reserved for research purposes. Therefore, this scientific statement was written to (1) review the current literature on the noninvasive assessment of atherosclerosis in children and adolescents, (2) make recommendations for the standardization of these tools for research, and (3) stimulate further research with a goal of developing valid and reliable techniques with normative data for noninvasive clinical evaluation of atherosclerosis in pediatric patients. Precise and reliable noninvasive tests for atherosclerosis in youth will improve our ability to estimate future risk for heart attack and stroke. Currently, large longitudinal studies of cardiovascular risk factors in youth, such as the Bogalusa and Muscatine studies, lack sufficient adult subjects experiencing hard outcomes, such as heart attack and stroke, to produce meaningful risk scores like those developed from Framingham data.

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Girls and women with Turner syndrome face a lifelong struggle with both congenital heart disease and acquired cardiovascular conditions. Bicuspid aortic valve is common, and many have left-sided heart obstructive disease of varying severity, from hypoplastic left-sided heart syndrome to minimal aortic stenosis or coarctation of the aorta. Significant enlargement of the thoracic aorta may progress to catastrophic aortic dissection and rupture. It is becoming increasingly apparent that a variety of other cardiovascular conditions, including early-onset hypertension, ischemic heart disease, and stroke, are the major factors reducing the life span of those with Turner syndrome. The presentations and management of cardiovascular conditions in Turner syndrome differ significantly from the general population. Therefore, an international working group reviewed the available evidence regarding the diagnosis and treatment of cardiovascular diseases in Turner syndrome. It is recognized that the suggestions for clinical practice stated here are only the beginning of a process that must also involve the establishment of quality indicators, structures and processes for implementation, and outcome studies.

Cardiovascular abnormalities are a major determining factor in the clinical picture and trajectory of patients with Williams syndrome. Advances in surgical techniques, medical therapeutic options, and periprocedural management hold promise for significant improvements in the cardiovascular outcomes of these patients.

CHS is associated with decreased in-hospital mortality in T18 and T13. These results suggest CHS may be beneficial in select cases.

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Aortopathy can be defined as aortic dilation, aneurysm, dissection, and tortuosity. Familial aortopathy may occur secondary to fibrillin-1 (FBN1) mutations in the setting of Marfan syndrome, or may occur as a result of other genetic defects with different, but occasionally overlapping, phenotypes. Because of the phenotypic overlap and genetic heterogeneity of disorders featuring aortopathy, we developed a next generation sequencing (NGS) assay and comparative genomic hybridization (CGH) array to detect mutations in 10 genes that cause thoracic aortic aneurysms (TAAs). Here, we report on the clinical and molecular findings in 175 individuals submitted for aortopathy panel testing at ARUP laboratories. Ten genes associated with heritable aortopathies were targeted using hybridization capture prior to sequencing. NGS results were analyzed, and variants were confirmed using Sanger sequencing. Array CGH was used to detect copy-number variation. Of 175 individuals, 18 had a pathogenic mutation and 32 had a variant of uncertain significance (VUS). Most pathogenic mutations (72%) were identified in FBN1. A novel large SMAD3 duplication and FBN1 deletion were identified. Over half who had TAAs or other aortic involvement tested negative for a mutation, suggesting that additional aortopathy genes exist. We anticipate that the clinical sensitivity of at least 10.3% will rise with VUS reclassification and as additional genes are identified and included in the panel. The aortopathy NGS panel aids in the timely molecular diagnosis of individuals with disorders featuring aortopathy and guides proper treatment.

Objective Patients with Williams syndrome (WS) undergoing cardiac surgery are at risk for major adverse cardiac events (MACE). Prevalence and risk factors for such events have not been well described. We sought to define frequency and risk of MACE in WS patients using a multicenter clinical registry. Methods We identified cardiac operations performed in WS patients using the Society of Thoracic Surgeons Congenital Heart Surgery Database (2000-2012). Operations were divided into 4 groups: isolated supravalvar aortic stenosis, complex left ventricular outflow tract (LVOT), isolated right ventricular outflow tract (RVOT), and combined LVOT/RVOT procedures. The proportion of patients with MACE (in-hospital mortality, cardiac arrest, or postoperative mechanical circulatory support) was described and association with preoperative factors examined. Results Of 447 index operations (87 centers), median (IQR) age and weight at surgery were 2.4 years (0.6-7.4) and 10.6 kg (6.5-21.5), respectively. Mortality occurred in 20 patients (5%). MACE occurred in 41 patients (9%), most commonly after combined LVOT/RVOT (18/87, 21%) and complex LVOT (12/131, 9%) procedures, but not after isolated RVOT procedures. Odds of MACE decreased with age (OR, 0.99; 95% CI, 0.98-0.99), weight (OR, 0.97; 95% CI, 0.93-0.99), but increased in the presence of any preoperative risk factor (OR, 2.08; 95% CI, 1.06-4.00), and in procedures involving coronary artery repair (OR, 5.37; 95% CI, 2.05-14.06). Conclusion In this multicenter analysis, MACE occurred in 9% of WS patients undergoing cardiac surgery. Demographic and operative characteristics were associated with risk. Further study is needed to elucidate mechanisms of MACE in this high-risk population.