The influence of somatic maturity on the relationship between the triglyceride/high-density lipoprotein ratio and vascular health in children and adolescents with dyslipidemia.

INTRODUCTION: Both the triglyceride to HDL cholesterol (TG/HDL) ratio and timing of pubertal maturation have been identified as independent contributors to the development of atherosclerosis. OBJECTIVE: The purpose of our study was to determine the relationship between the TG/HDL ratio and measures of vascular health in children and adolescents with dyslipidemia stratified by somatic maturity. We hypothesized that somatic maturity would have a significant interaction with TG/HDL ratio and vascular health. METHODS: This was a longitudinal analysis of 120 children and adolescents (age 8-14 years) with dyslipidemia recruited from a pediatric preventive cardiology clinic. At baseline and each follow-up visit, a non-fasting serum lipid panel was collected and vascular health (carotid artery intima--media thickness, pulse wave velocity, augmentation index) was assessed. Peak height velocity (PHV) was calculated at each visit, and participants were stratified into groups by maturity offset (pre-PHV, mid-PHV, post-PHV). A mixed model design permitted baseline and follow-up visits to be classified as discrete data points. RESULTS: Of the n = 235 data points (pre-PHV = 23%, mid-PHV = 19%, and post-PHV = 58%), we identified no significant interaction between TG/HDL ratio, maturity offset, and measures of vascular structure or function. There was also no significant relationship found between TG/HDL and maturity group. Within the mid-pubertal group, there was weak relationship found between TG/HDL and augmentation index. CONCLUSION: Despite the well-described relationship between early pubertal maturation and development of cardiovascular risk factors in adulthood, we found that vascular damage resulting from an elevated TG/HDL ratio is not independently associated with somatic maturity.

COVID-19 Positive Versus Negative Complete Kawasaki Disease: A Study from the International Kawasaki Disease Registry.

To determine clinical differences for children with complete Kawasaki disease (KD) with and without evidence of preceding SARS-CoV-2 infection. From January 2020, contemporaneous patients with complete KD criteria were classified as either SARS-CoV-2 positive (KDCOVID+; confirmed household exposure, positive PCR and/or serology) or SARS-CoV-2 negative (KDCOVID-; negative testing and no exposure) and compared. Of 744 patients in the International Kawasaki Disease Registry, 52 were KDCOVID- and 61 were KDCOVID+. KDCOVID+ patients were older (median 5.5 vs. 3.7 years; p < 0.001), and all additionally met diagnostic criteria for multisystem inflammatory syndrome in children (MIS-C). They were more likely to have abdominal pain (60% vs. 35%; p = 0.008) and headache (38% vs. 10%; p < 0.001) and had significantly higher CRP, troponin, and BUN/creatinine, and lower hemoglobin, platelets, and lymphocytes. KDCOVID+ patients were more likely to have shock (41% vs. 6%; p < 0.001), ICU admission (62% vs. 10%; p < 0.001), lower left ventricular ejection fraction (mean lowest LVEF 53% vs. 60%; p < 0.001), and to have received inotropic support (60% vs. 10%; p < 0.001). Both groups received IVIG (2 doses in 22% vs. 18%; p = 0.63), but KDCOVID+ were more likely to have received steroids (85% vs. 35%; p < 0.001) and anakinra (60% vs. 10%; p = 0.002). KDCOVID- patients were more likely to have medium/large coronary artery aneurysms (CAA, 12% vs. 0%; p = 0.01). KDCOVID+ patients differ from KDCOVID-, have more severe disease, and greater evidence of myocardial involvement and cardiovascular dysfunction rather than CAA. These patients may be a distinct KD phenotype in the presence of a prevalent specific trigger.

Cardiac Biomarkers Aid in Differentiation of Kawasaki Disease from Multisystem Inflammatory Syndrome in Children Associated with COVID-19.

Kawasaki disease (KD) and Multisystem Inflammatory Syndrome in Children (MIS-C) associated with COVID-19 show clinical overlap and both lack definitive diagnostic testing, making differentiation challenging. We sought to determine how cardiac biomarkers might differentiate KD from MIS-C. The International Kawasaki Disease Registry enrolled contemporaneous KD and MIS-C pediatric patients from 42 sites from January 2020 through June 2022. The study population included 118 KD patients who met American Heart Association KD criteria and compared them to 946 MIS-C patients who met 2020 Centers for Disease Control and Prevention case definition. All included patients had at least one measurement of amino-terminal prohormone brain natriuretic peptide (NTproBNP) or cardiac troponin I (TnI), and echocardiography. Regression analyses were used to determine associations between cardiac biomarker levels, diagnosis, and cardiac involvement. Higher NTproBNP (≥ 1500 ng/L) and TnI (≥ 20 ng/L) at presentation were associated with MIS-C versus KD with specificity of 77 and 89%, respectively. Higher biomarker levels were associated with shock and intensive care unit admission; higher NTproBNP was associated with longer hospital length of stay. Lower left ventricular ejection fraction, more pronounced for MIS-C, was also associated with higher biomarker levels. Coronary artery involvement was not associated with either biomarker. Higher NTproBNP and TnI levels are suggestive of MIS-C versus KD and may be clinically useful in their differentiation. Consideration might be given to their inclusion in the routine evaluation of both conditions.

Variation in Pharmacologic Management of Patients with Kawasaki Disease with Coronary Artery Aneurysms.

OBJECTIVE: To evaluate practice variation in pharmacologic management in the International Kawasaki Disease Registry (IKDR). STUDY DESIGN: Practice variation in intravenous immunoglobulin (IVIG) therapy, anti-inflammatory agents, statins, beta-blockers, antiplatelet therapy, and anticoagulation was described. RESULTS: We included 1627 patients from 30 IKDR centers with maximum coronary artery aneurysm (CAA) z scores 2.5-4.99 in 848, 5.0-9.99 in 349, and ≥10.0 (large/giant) in 430 patients. All centers reported IVIG and acetylsalicylic acid (ASA) as primary therapy and use of additional IVIG or steroids as needed. In 23 out of 30 centers, (77%) infliximab was also used; 11 of these 23 centers reported using it in <10% of their patients, and 3 centers used it in >20% of patients. Nonsteroidal anti-inflammatory agents were used in >10% of patients in only nine centers. Beta-blocker (8.8%, all patients) and abciximab (3.6%, all patients) were mainly prescribed in patients with large/giant CAAs. Statins (2.7%, all patients) were mostly used in one center and only in patients with large/giant CAAs. ASA was the primary antiplatelet modality for 99% of patients, used in all centers. Clopidogrel (18%, all patients) was used in 24 centers, 11 of which used it in >50% of their patients with large/giant CAAs. CONCLUSIONS: In the IKDR, IVIG and ASA therapy as primary therapy is universal with common use of a second dose of IVIG for persistent fever. There is practice variation among centers for adjunctive therapies and anticoagulation strategies, likely reflecting ongoing knowledge gaps. Randomized controlled trials nested in a high-quality collaborative registry may be an efficient strategy to reduce practice variation.

Cardiorespiratory Fitness in Youth: An Important Marker of Health: A Scientific Statement From the American Heart Association.

Cardiorespiratory fitness (CRF) refers to the capacity of the circulatory and respiratory systems to supply oxygen to skeletal muscle mitochondria for energy production needed during physical activity. CRF is an important marker of physical and mental health and academic achievement in youth. However, only 40% of US youth are currently believed to have healthy CRF. In this statement, we review the physiological principles that determine CRF, the tools that are available to assess CRF, the modifiable and nonmodifiable factors influencing CRF, the association of CRF with markers of health in otherwise healthy youth, and the temporal trends in CRF both in the United States and internationally. Development of a cost-effective CRF measurement process that could readily be incorporated into office visits and in field settings to screen all youth periodically could help identify those at increased risk.

Comparison Between Currently Recommended Long-Term Medical Management of Coronary Artery Aneurysms After Kawasaki Disease and Actual Reported Management in the Last Two Decades.

In the 2017 American Heart Association (AHA) Kawasaki disease (KD) guidelines, risk levels (RLs) for long-term management are defined by both maximal and current coronary artery (CA) dimensions normalized as z-scores. We sought to determine the degree to which current recommended practice differs from past actual practice, highlighting areas for knowledge translation efforts. The International KD Registry (IKDR) included 1651 patients with CA aneurysms (z-score > 2.5) from 1999 to 2016. Patients were classified by AHA RL using maximum CA z-score (RL 3 = small, RL 4 = medium, RL 5 = large/giant) and subcategorized based on decreases over time. Medical management provided was compared to recommendations. Low-dose acetylsalicylic acid (ASA) use ranged from 86 (RL 3.1) to 95% (RL 5.1) for RLs where use was "indicated." Dual antiplatelet therapy (ASA + clopidogrel) use ranged from 16% for RL 5.2 to 9% for RL 5.4. Recommended anticoagulation (warfarin or low molecular weight heparin) use was 65% for RL 5.1, while 12% were on triple therapy (anticoagulation + dual antiplatelet). Optional statin use ranged from 2 to 8% depending on RL. Optional beta-blocker use was 2-25% for RL 5, and 0-5% for RLs 3 and 4 where it is not recommended. Generally, past practice was consistent with the latest AHA guidelines, taking into account the flexible wording of recommendations based on the limited evidence, as well as unmeasured patient-specific factors. In addition to strengthening the overall evidence base, knowledge translation efforts may be needed to address variation in thromboprophylaxis management.

Statin Safety and Associated Adverse Events: A Scientific Statement From the American Heart Association.

One in 4 Americans >40 years of age takes a statin to reduce the risk of myocardial infarction, ischemic stroke, and other complications of atherosclerotic disease. The most effective statins produce a mean reduction in low-density lipoprotein cholesterol of 55% to 60% at the maximum dosage, and 6 of the 7 marketed statins are available in generic form, which makes them affordable for most patients. Primarily using data from randomized controlled trials, supplemented with observational data where necessary, this scientific statement provides a comprehensive review of statin safety and tolerability. The review covers the general patient population, as well as demographic subgroups, including the elderly, children, pregnant women, East Asians, and patients with specific conditions such as chronic disease of the kidney and liver, human immunodeficiency viral infection, and organ transplants. The risk of statin-induced serious muscle injury, including rhabdomyolysis, is <0.1%, and the risk of serious hepatotoxicity is ≈0.001%. The risk of statin-induced newly diagnosed diabetes mellitus is ≈0.2% per year of treatment, depending on the underlying risk of diabetes mellitus in the population studied. In patients with cerebrovascular disease, statins possibly increase the risk of hemorrhagic stroke; however, they clearly produce a greater reduction in the risk of atherothrombotic stroke and thus total stroke, as well as other cardiovascular events. There is no convincing evidence for a causal relationship between statins and cancer, cataracts, cognitive dysfunction, peripheral neuropathy, erectile dysfunction, or tendonitis. In US clinical practices, roughly 10% of patients stop taking a statin because of subjective complaints, most commonly muscle symptoms without raised creatine kinase. In contrast, in randomized clinical trials, the difference in the incidence of muscle symptoms without significantly raised creatinine kinase in statin-treated compared with placebo-treated participants is <1%, and it is even smaller (0.1%) for patients who discontinued treatment because of such muscle symptoms. This suggests that muscle symptoms are usually not caused by pharmacological effects of the statin. Restarting statin therapy in these patients can be challenging, but it is important, especially in patients at high risk of cardiovascular events, for whom prevention of these events is a priority. Overall, in patients for whom statin treatment is recommended by current guidelines, the benefits greatly outweigh the risks.

Valve Replacement in Children with Single Ventricle Physiology.

Severe atrioventricular valve (AVV) or semilunar valve (SLV) regurgitation in the setting of a single ventricle physiology may proceed to valve replacement if repair strategies fail. Outcome data for these children are limited. We present transplant-free survival of a case series of children with single ventricle physiology undergoing either atrioventricular replacement (AVVR) or semilunar valve replacement (SLVR) from a multi-institutional, US-based registry (Pediatric Cardiac Care Consortium-PCCC). Outcomes were derived from PCCC and by linkage with the National Death Index (NDI) and Organ Procurement Transplant Network (OPTN). Fifty children with single ventricle physiology were identified to have received either AVVR (n = 38) or SLVR (n = 12). There were 17 in-hospital deaths including 8 intraoperative deaths (all intraoperative deaths were among children requiring AVVR). The in-hospital mortality was 42% and 8% for AVVR and SLVR, respectively. Among the 33 children surviving to hospital discharge, follow-up was available in 15 (46%). Death or cardiac transplant after hospital discharge occurred in 10-death in 4 (all among those requiring AVVR), cardiac transplant in 6 (2 following AVVR, 4 following SLVR). Valve replacement in children with single ventricle physiology, especially AVVR, is associated with poor outcomes. Alternative palliation strategies should be considered in children with single ventricle physiology with significant AVV or SLV regurgitations.

Modifiable Clinical Correlates of Vascular Health in Children and Adolescents with Dyslipidemia.

Atherosclerosis promoting cardiovascular disease risk factors (CVDrf) are highly prevalent among youth in the U.S. Determining which standard modifiable clinical measures (SMCMs) has the greatest impact on vascular structure and function is valuable for the health care provider to help identify children at highest risk. The aim of this study was to determine modifiable outpatient clinical predictors of vascular health in youth with CVDrf. Children and adolescents with CVDrf (n = 120, 13.1 ± 1.9 years, 49% female) were recruited from a pediatric preventive cardiology clinic. The SMCMs included BMI z-score, waist-to-height ratio (WTHR), lipid panel, hemoglobin A1c, blood pressure (BP), presence of tobacco smoke exposure, and presence of hypertriglyceridemic waist (HTW) phenotype (triglycerides ≥ 110 mg/dL and waist circumference ≥ 90 percentile). Vascular function and structure were measured with pulse wave velocity (PWV), central systolic BP (CSP), augmentation index (AIx), and carotid artery intima-media thickness (cIMT). Sex and height specific z-scores for PWV, CSP, and cIMT were used. Multiple linear regression with backwards selection identified SMCMs which strongly predicted vascular function and structure. Among SMCMs, WTHR and HTW were the most frequent predictors of vascular function (PWV: R2 = 0.32; CSP: R2 = 0.35; AIx R2 = 0.13). Other predictors of vascular function included hemoglobin A1C, BP, and BMI z-score. Systolic BP and LDL cholesterol were predictors of vascular structure (cIMT: R2 = 0.14). The strongest predictors of vascular health in youth with CVDrf were related to measures of central obesity. Targeting these SMCM in lieu of vascular testing in outpatient clinic setting may be practical to identify children and adolescents at greatest risk for CVD.

Lipoprotein (a): Examination of Cardiovascular Risk in a Pediatric Referral Population.

Atherosclerotic cardiovascular disease (CVD), a leading cause of death globally, has origins in childhood. Major risk factors include family history of premature CVD, dyslipidemia, diabetes mellitus, and hypertension. Lipoprotein (a) [Lp(a)], an inherited lipoprotein, is associated with premature CVD, but its impact on cardiovascular health during childhood is less understood. The objective of the study was to examine the relationship between Lp(a), family history of premature CVD, dyslipidemia, and vascular function and structure in a high-risk pediatric population. This is a single-center, cross-sectional study of 257 children referred to a preventive cardiology clinic. The independent variable, Lp(a), separated children into high-Lp(a) [Lp(a) ≥ 30 mg/dL] and normal-Lp(a) groups [Lp(a) < 30 mg/dL]. Dependent variables included family history of premature CVD; dyslipidemia, defined as low-density lipoprotein cholesterol > 130 mg/dL, high-density lipoprotein cholesterol (HDL-C) < 45 mg/dL, triglycerides (TG) > 100 mg/dL; and vascular changes suggesting early atherosclerosis, as measured by carotid-femoral pulse wave velocity (PWV) and carotid artery intima-media thickness (CIMT). Of the 257 children, 110 (42.8%) had high Lp(a) and 147 (57.2%) had normal Lp(a). There was a higher prevalence of African-American children in the high-Lp(a) group (19.3%) compared to the normal-Lp(a) group (2.1%) (p < 0.001). High Lp(a) was associated with positive family history of premature CVD (p = 0.03), higher-than-optimal HDL-C (p = 0.02), and lower TG (p < 0.001). There was no difference in PWV or CIMT between groups. High Lp(a) in children is associated with family history of premature CVD and is prevalent in African-American children. In children with high Lp(a), promotion of intensive lifestyle modifications is prudent to decrease premature CVD-related morbidity.

Utility of arterial stiffness assessment in children.

Atherosclerotic cardiovascular disease is a leading cause of death and disability worldwide, and the atherosclerotic process begins in childhood. Prevention or containment of risk factors that accelerate atherosclerosis can delay the development of atherosclerotic cardiovascular disease. Although current recommendations are to periodically screen for commonly prevailing risk factors for atherosclerosis in children, a single test that could quantify the cumulative effect of all risk factors on the vasculature, thus assessing arterial health, would be helpful in further stratifying risk. Measurement of pulse wave velocity and assessment of augmentation index - measures of arterial stiffness - are easy-to-use, non-invasive methods of examining arterial health. Various studies have assessed pulse wave velocity and augmentation index in children with commonly occurring conditions including obesity, hypertension, insulin resistance, diabetes mellitus, dyslipidaemia, physical inactivity, chronic kidney disease, CHD and acquired heart diseases, and in children who were born premature or small for gestational age. This article summarises pulse wave velocity and augmentation index assessments and the effects of commonly prevailing chronic conditions on arterial health in children. In addition, currently available reference values for pulse wave velocity and augmentation index in healthy children are included. Further research to establish widely applicable normative values and the effect of lifestyle and pharmacological interventions on arterial health in children is needed.

Cardiovascular Consequences of Childhood Secondhand Tobacco Smoke Exposure: Prevailing Evidence, Burden, and Racial and Socioeconomic Disparities: A Scientific Statement From the American Heart Association.

BACKGROUND: Although public health programs have led to a substantial decrease in the prevalence of tobacco smoking, the adverse health effects of tobacco smoke exposure are by no means a thing of the past. In the United States, 4 of 10 school-aged children and 1 of 3 adolescents are involuntarily exposed to secondhand tobacco smoke (SHS), with children of minority ethnic backgrounds and those living in low-socioeconomic-status households being disproportionately affected (68% and 43%, respectively). Children are particularly vulnerable, with little control over home and social environment, and lack the understanding, agency, and ability to avoid SHS exposure on their own volition; they also have physiological or behavioral characteristics that render them especially susceptible to effects of SHS. Side-stream smoke (the smoke emanating from the burning end of the cigarette), a major component of SHS, contains a higher concentration of some toxins than mainstream smoke (inhaled by the smoker directly), making SHS potentially as dangerous as or even more dangerous than direct smoking. Compelling animal and human evidence shows that SHS exposure during childhood is detrimental to arterial function and structure, resulting in premature atherosclerosis and its cardiovascular consequences. Childhood SHS exposure is also related to impaired cardiac autonomic function and changes in heart rate variability. In addition, childhood SHS exposure is associated with clustering of cardiometabolic risk factors such as obesity, dyslipidemia, and insulin resistance. Individualized interventions to reduce childhood exposure to SHS are shown to be at least modestly effective, as are broader-based policy initiatives such as community smoking bans and increased taxation. PURPOSE: The purpose of this statement is to summarize the available evidence on the cardiovascular health consequences of childhood SHS exposure; this will support ongoing efforts to further reduce and eliminate SHS exposure in this vulnerable population. This statement reviews relevant data from epidemiological studies, laboratory-based experiments, and controlled behavioral trials concerning SHS and cardiovascular disease risk in children. Information on the effects of SHS exposure on the cardiovascular system in animal and pediatric studies, including vascular disruption and platelet activation, oxidation and inflammation, endothelial dysfunction, increased vascular stiffness, changes in vascular structure, and autonomic dysfunction, is examined. CONCLUSIONS: The epidemiological, observational, and experimental evidence accumulated to date demonstrates the detrimental cardiovascular consequences of SHS exposure in children. IMPLICATIONS: Increased awareness of the adverse, lifetime cardiovascular consequences of childhood SHS may facilitate the development of innovative individual, family-centered, and community health interventions to reduce and ideally eliminate SHS exposure in the vulnerable pediatric population. This evidence calls for a robust public health policy that embraces zero tolerance of childhood SHS exposure.

Major Depressive Disorder and Bipolar Disorder Predispose Youth to Accelerated Atherosclerosis and Early Cardiovascular Disease: A Scientific Statement From the American Heart Association.

In the 2011 "Expert Panel on Integrated Guidelines for Cardiovascular Health and Risk Reduction in Children and Adolescents," several medical conditions among youth were identified that predispose to accelerated atherosclerosis and early cardiovascular disease (CVD), and risk stratification and management strategies for youth with these conditions were elaborated. Major depressive disorder (MDD) and bipolar disorder (BD) among youth satisfy the criteria set for, and therefore merit inclusion among, Expert Panel tier II moderate-risk conditions. The combined prevalence of MDD and BD among adolescents in the United States is ≈10%, at least 10 times greater than the prevalence of the existing moderate-risk conditions combined. The high prevalence of MDD and BD underscores the importance of positioning these diseases alongside other pediatric diseases previously identified as moderate risk for CVD. The overall objective of this statement is to increase awareness and recognition of MDD and BD among youth as moderate-risk conditions for early CVD. To achieve this objective, the primary specific aims of this statement are to (1) summarize evidence that MDD and BD are tier II moderate-risk conditions associated with accelerated atherosclerosis and early CVD and (2) position MDD and BD as tier II moderate-risk conditions that require the application of risk stratification and management strategies in accordance with Expert Panel recommendations. In this scientific statement, there is an integration of the various factors that putatively underlie the association of MDD and BD with CVD, including pathophysiological mechanisms, traditional CVD risk factors, behavioral and environmental factors, and psychiatric medications.

Impact of Variability in Echocardiographic Interpretation on Assessment of Adequacy of Repair Following Congenital Heart Surgery: A Pilot Study.

Technical Performance Score (TPS) is based largely on the presence and magnitude of residual lesions on postoperative echocardiograms; this score correlates with outcomes following repair of congenital heart defects. We evaluated reader variability for echocardiographic components of TPS for complete repair of tetralogy of Fallot (TOF) and arterial switch operation (ASO) in two centers and measured its effect on TPS. Postoperative echocardiograms were evaluated in 67 children (39 TOF and 28 ASO). Two readers (one per center) interpreted each echocardiogram. Reader variability in image quality assessments and measurements was compared using weighted kappa (κ), percent agreement, and intra-class correlation. TPS class (1 optimal-no residua, 2 adequate-minor residua, 3 inadequate-major residua) was assigned for each echocardiographic review by an independent investigator. The effect of reader interpretation variability on TPS classification was measured. There was strong agreement for TPS between the two readers (κ = 0.88). The readers were concordant for TPS classes for 57 children (85%) and discordant for classes 2 (minor residua) versus 3 (major residua) in six (9%). Coronary arteries and branch pulmonary arteries were frequently suboptimally visualized. Although inter-reader agreement for TPS was strong, inter-reader variation in echocardiographic interpretations had a small, but important effect on TPS for TOF and ASO, particularly for the distinction between minor and major residua. Further studies of generalizability and reproducibility of TPS and refinement of scoring modules may be needed before it can be used as a tool to assess pediatric cardiac surgical performance and outcomes.

Vitamin D, Low-Grade Inflammation and Cardiovascular Risk in Young Children: A Pilot Study.

Vitamin D has anti-inflammatory properties, and deficiency is prevalent in children. There is a paucity of data regarding vitamin D status and its correlation with low-grade inflammation and vasculature. We prospectively enrolled 25 children, 9-11 years old (13 male); 21 obese. Eight atherosclerosis-promoting risk factors were scored as categorical variables with the following thresholds defining abnormality: body mass index Z score ≥ 1.5; systolic blood pressure ≥ 95th percentile (for age, sex, and height); triglyceride ≥ 100 mg/dL; low-density lipoprotein cholesterol (LDL-C) ≥ 110 mg/dL; high-density lipoprotein cholesterol ≤ 45 mg/dL; hemoglobin A1C (HBA1C) ≥ 5.5; 25-hydroxyvitamin D [25(OH) D] ≤ 30 ng/mL, and tobacco smoke exposure. High-sensitivity C-reactive protein (hsCRP) was measured to assess low-grade inflammation and classified as low- (<1 mg/L), average- (1-3 mg/L), and high-risk (>3 to <10 mg/L) groups. The proportion of children within each hsCRP group who had above threshold risk factors was calculated. Carotid artery ultrasound was performed to measure carotid artery intima-media thickness (CIMT). Median (range) for 25(OH) D was 24 (17-45) ng/mL. Eighteen were either 25 (OH) D deficient (<20 ng/mL) or insufficient (20-30 ng/mL), and seven were sufficient (>30 ng/mL). hsCRP was 1.7 (0.2-9.1) mg/L, with 11 being <1.0 mg/L, 8 between 1.0-3.0 and 6 > 3.0 to < 10.0 mg/L. Risk factor score was 3.9 ± 1.7 out of eight. 25(OH) D levels did not correlate with hsCRP or CIMT. While vitamin D deficiency, inflammation, and risk factors coexist at a very young age, causative mechanisms remain unclear.

Survival After Single-Stage Repair of Truncus Arteriosus and Associated Defects.

BACKGROUND: The goal of this study was to describe in-hospital and long-term mortality after single-stage repair of truncus arteriosus communis (TAC) and explore factors associated with these outcomes. METHODS: This was a cohort study of consecutive patients undergoing single-stage TAC repair between 1982 and 2011 reported to the Pediatric Cardiac Care Consortium registry. In-hospital mortality was obtained for the entire cohort from registry records. Long-term mortality was obtained for patients with available identifiers by matching with the National Death Index through 2020. Kaplan-Meier survival estimates were created for up to 30 years after discharge. Cox regression models estimated hazard ratios for the associations with potential risk factors. RESULTS: A total of 647 patients (51% male) underwent single-stage TAC repair at a median age of 18 days; 53% had type I TAC, 13% had interrupted aortic arch, and 10% underwent concomitant truncal valve surgery. Of these, 486 (75%) patients survived to hospital discharge. After discharge, 215 patients had identifiers for tracking long-term outcomes; 30-year survival was 78%. Concomitant truncal valve surgery at the index procedure was associated with increased in-hospital and 30-year mortality. Concomitant interrupted aortic arch repair was not associated with increased in-hospital or 30-year mortality. CONCLUSIONS: Concomitant truncal valve surgery but not interrupted aortic arch was associated with higher in-hospital and long-term mortality. Careful consideration of the need and timing for truncal valve intervention may improve TAC outcomes.

SLCO1B1 Genetic Variation Influence on Atorvastatin Systemic Exposure in Pediatric Hypercholesterolemia.

This clinical study examined the influence of SLCO1B1 c.521T>C (rs4149056) on plasma atorvastatin concentrations in pediatric hypercholesterolemia. The participants (8-21 years), including heterozygous (c.521T/C, n = 13), homozygous (c.521C/C, n = 2) and controls (c.521T/T, n = 13), completed a single-oral-dose pharmacokinetic study. Similar to in adults, the atorvastatin (AVA) area-under-concentration-time curve from 0 to 24 h (AUC0-24) was 1.7-fold and 2.8-fold higher in participants with c.521T/C and c.521C/C compared to the c.521T/T participants, respectively. The inter-individual variability in AVA exposure within these genotype groups ranged from 2.3 to 4.8-fold, indicating that additional factors contribute to the inter-individual variability in the AVA dose-exposure relationship. A multivariate model reinforced the SLCO1B1 c.521T>C variant as the central factor contributing to AVA systemic exposure in this pediatric cohort, accounting for ~65% of the variability in AVA AUC0-24. Furthermore, lower AVA lactone concentrations in participants with increased body mass index contributed to higher exposure within the c.521T/T and c.521T/C genotype groups. Collectively, these factors contributing to higher systemic exposure could increase the risk of toxicity and should be accounted for when individualizing the dosing of atorvastatin in eligible pediatric patients.

Berry syndrome: a possible genetic link.

Berry syndrome comprises a rare combination of heart defects that includes aortopulmonary window, interrupted aortic arch, intact ventricular septum, and aortic origin of the right pulmonary artery. We report the case of a neonate confirmed to have Berry syndrome by transthoracic echocardiogram and computed tomography (CT). This neonate had the additional finding of an aberrant right subclavian artery arising from the descending aorta. A single-stage repair was successfully performed when the infant was 7 days of age. Genetic testing showed a 102-kb deletion within chromosome band 9p24.2; this deletion has not been previously linked to congenital heart defects. Berry syndrome can be diagnosed accurately by transthoracic echocardiogram and CT. There may be an underlying genetic etiology, and this possibility warrants further investigation.

Toward a Roadmap for Best Practices in Pediatric Preventive Cardiology: A Science Advisory From the American Heart Association.

Cardiovascular disease risk factors are highly prevalent among youth in the United States and Canada. Pediatric preventive cardiology programs have independently developed and proliferated to address cardiovascular risk factors in youth, but there is a general lack of clarity on best practices to optimize and sustain desired outcomes. We conducted surveys of pediatric cardiology division directors and pediatric preventive cardiology clinicians across the United States and Canada to describe the current landscape and perspectives on future directions for the field. We summarize the data and conclude with a call to action for various audiences who seek to improve cardiovascular health in youth, reduce the burden of premature cardiovascular disease, and increase healthy longevity. We call on heart centers, hospitals, payers, and policymakers to invest resources in the important work of pediatric preventive cardiology programs. We urge professional societies to advocate for pediatric preventive cardiology and provide opportunities for training and cross-pollination across programs. We encourage researchers to close evidence gaps. Last, we invite pediatric preventive cardiology clinicians to collaborate and innovate to advance the practice of pediatric preventive cardiology.