Geetha Raghuveer

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.

“Vascular Age” Is Advanced in Children With Atherosclerosis-Promoting Risk Factors

Background—Obesity and familial dyslipidemia in children are associated with accelerated atherosclerosis by pathological examination. We sought to determine whether these children had increased carotid artery intima-media thickness (CIMT), a measure of subclinical atherosclerosis similar to 45-year-old adults. Adult CIMT percentile tables were used for comparison because normative CIMT data for children are limited. Methods and Results—Seventy children, ages 6 to 19 years, with obesity- and atherosclerosis-promoting risk factors such as dyslipidemia, hypertension, insulin resistance, and tobacco smoke exposure, or with familial dyslipidemia, underwent carotid artery ultrasound. Advanced “vascular age” (VA) was defined as having maximum CIMT that was ≥25th percentile for race- and sex-matched 45-year-old adults. Mean age was 13.0±3.3 years. Forty (57%) of 70 children had body mass index ≥95th percentile for age and sex. Maximum CIMT for obese children was 0.53±0.05 mm and for familial dyslipidemic children was 0.52±0.04 mm. Advanced VA was seen in 30 (75%) of obese children and 22 (73%) of familial dyslipidemic children. Thirty (75%) of obese children had >3 mutable atherosclerosis-promoting risk factors; these children had a nonsignificantly higher maximum CIMT compared with obese children with ≤3 risk factors (0.54±0.06 mm versus 0.52±0.03 mm, P=0.07). Obese children with high fasting triglyceride levels were more likely to have advanced VA. Conclusions—VA is advanced and comparable in obese children with atherosclerosis-promoting risk factors and in children with familial dyslipidemia. Advanced VA is prevalent in obese children with high fasting triglyceride levels.

Repair of “Simple” Total Anomalous Pulmonary Venous Connection: A Review From the Pediatric Cardiac Care Consortium

BACKGROUND Outcomes for repair of total anomalous pulmonary venous connection (TAPVC) from individual institutions suggest a significant improvement in mortality over the past several decades. The purpose of this study is to review the outcomes after repair of TAPVC from a large multiinstitutional registry. METHODS A retrospective review of the multiinstitutional database, the Pediatric Cardiac Care Consortium (PCCC), was used to identify patients with the diagnosis of TAPVC who underwent complete correction between 1982 and 2007. Data reviewed included age, decade of primary operation, anatomic type, presentation, and in-hospital mortality. RESULTS Of the 118,084 surgical procedures submitted to the PCCC, 2,191 (1.9%) consisted of primary surgical correction of TAPVC. Sixty-one percent of the cohort was male, with 6.8% reported as premature. Overall in-hospital surgical mortality for simple TAPVC was 13%. Mortality was 20% from 1982 to 1989, 16% from 1990 to 1999, and 8% from 2000 to 2007. Obstruction to the anomalous pulmonary venous connection occurred in 29%, with a mortality of 26%. CONCLUSIONS Surgical outcomes from repair of congenital cardiac anomalies have significantly improved over the past several decades. Multiinstitutional large databases are needed to confirm results published from single-institution experiences. Although improvements in surgical repair of TAPVC have occurred over the past three decades, specific subtypes still experience significant mortality.

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.

Vitamin D deficiency is associated with atherosclerosis-promoting risk factor clustering but not vascular damage in children

Summary Background Vitamin D has been associated with multiple cardiometabolic risk factors in children but there is a paucity of studies examining its correlation to vascular function and structure. Our objective was to determine whether there is a correlation between vitamin D, cardiometabolic risk, vascular distensibility and carotid artery intima-media thickness (CIMT) in high-risk children. Material/Methods This was a cross-sectional, cohort study that compared vitamin D to cardiometabolic risk factors, carotid artery distensibility, and CIMT in 74 children with multiple, modifiable atherosclerosis-promoting risk factors. Vitamin D was used as a continuous variable and also categorized as deficient (<20 ng/mL) or sufficient (≥20 ng/mL). Seven modifiable atherosclerosis-promoting risk factors were analyzed – body mass index, systolic blood pressure, total cholesterol, triglyceride, high density lipoprotein cholesterol, fasting insulin, & tobacco smoke exposure history. Results For the entire cohort, vitamin D was 26.1±9.4 ng/mL (6–63 ng/mL); and the levels were deficient in 20%. The number of modifiable atherosclerosis promoting risk factors per child was 3.3±1.6. Distensibility index was 2.62±0.87% per 10 mmHg, CIMT 0.54±0.06 mm. There was an inverse correlation between vitamin D and risk factor score (r=−0.27, p=0.02); this remained significant after adjusting for age, sex, and race. There was no association between vitamin D levels and distensibility index or CIMT. Conclusions Even though vitamin D levels were inversely correlated with cardiometabolic risk factor score in high-risk children, there are no demonstrable vascular functional or structural effects.

Societal solutions to childhood origins of coronary artery disease

Childhood obesity and associated risks result in premature cardiovascular damage and disease with a consequent, large burden to society. There are causes for childhood obesity that are rooted in the socioeconomic milieu. Interventions that are population-based, and aimed towards prevention as opposed to treatment, are likely to be most effective in curtailing childhood obesity. Reforms to federal and state managed social welfare programs provide a compelling opportunity to affect the course and consequences of childhood obesity.

Impact of SLCO1B1 Genotype on Pediatric Simvastatin Acid Pharmacokinetics

This study investigated the impact of allelic variation in SLCO1B1, a gene encoding for the liver‐specific solute carrier organic anion transporter family member 1B1 protein (SLCO1B1), on simvastatin and simvastatin acid (SVA) systemic exposure in children and adolescents. Participants (8–20 years old) with at least 1 variant SLCO1B1 c.521T>C allele (521TC, n = 15; 521CC, n = 2) and 2 wild‐type alleles (521TT, n = 15) completed a single oral dose pharmacokinetic study. At equivalent doses, SVA exposure was 6.3‐ and 2.5‐fold greater in 521CC and TC genotypes relative to 521TT (Cmax, 2.1 ± 0.2 vs 1.0 ± 0.5 vs 0.4 ± 0.3 ng/mL; P < .0001; and AUC, 12.1 ± 0.3 vs 4.5 ± 2.5 vs 1.9 ± 1.8 ng·h/mL; P < .0001). The impact of the SLCO1B1 c.521 genotype was more pronounced in children, although considerable interindividual variability in SVA exposure was observed within genotype groups. In addition, SVA systemic exposure was negligible in 25% of pediatric participants. Further investigation of the ontogeny and genetic variation of SVA formation and SLCO1B1‐mediated hepatic uptake is necessary to better understand the variability in SVA exposure in children and its clinical consequences.

RESPIRATORY DISTRESS SECONDARY TO A PULMONARY ARTERY SLING

Anomalous origin of the left pulmonary artery (LPA) from the right pulmonary artery (RPA), or pulmonary artery (PA) sling, is a rare anomaly presenting with respiratory distress and requiring surgical correction. A 6-week old male infant with Trisomy 21 and a small to moderate-sized perimembranous

OUTCOMES FOLLOWING PROLONGED EXTRA CORPOREAL MEMBRANE OXYGENATION SUPPORT IN CHILDREN WITH CARDIAC DISEASE: EXTRACORPOREAL LIFE SUPPORT ORGANIZATION REGISTRY STUDY

Optimal timing for discontinuation of Extra Corporeal Membrane Oxygenation (ECMO) in children with cardiac insufficiency unable to wean from ECMO is ill defined. Outcomes following prolonged ECMO support (≥14 days) for cardiac insufficiency in children <18 years of age were examined. We reviewed