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• W4243630221 abstract "HomeCirculationVol. 128, No. 8Circulation Editors’ Picks Free AccessResearch ArticlePDF/EPUBAboutView PDFView EPUBSections ToolsAdd to favoritesDownload citationsTrack citationsPermissions ShareShare onFacebookTwitterLinked InMendeleyReddit Jump toFree AccessResearch ArticlePDF/EPUBCirculation Editors’ PicksMost Read Articles on the Topic of Pediatric Cardiology The Editors The Editors Search for more papers by this author Originally published20 Aug 2013https://doi.org/10.1161/CIRCULATIONAHA.113.005113Circulation. 2013;128:e107–e117Childhood Air Pollutant Exposure and Carotid Artery Intima-Media Thickness in Young AdultsSummary—The atherogenic process has important determinants early in life. Childhood exposure to ozone may be a novel risk factor for carotid artery intima-media thickness in young adults. Exposure to ambient air pollutants increases risk for cardiovascular health outcomes in adults. Early life exposure to ozone has been associated with childhood lung function development. Systemic inflammation induced first in the lung may be propagated throughout the body to target other organ systems. Regulation of air pollutants and efforts that focus on limiting childhood exposures continue to be important public health goals to potentially reduce atherosclerotic burden and its consequences.Conclusions—Childhood exposure to O3 may be a novel risk factor for carotid artery intima-media thickness in a healthy population of college students. Regulation of air pollutants and efforts that focus on limiting childhood exposures continue to be important public health goals.1Parental Electrocardiographic Screening Identifies a High Degree of Inheritance for Congenital and Childhood Nonimmune Isolated Atrioventricular BlockSummary—The origin of congenital or childhood nonimmune isolated atrioventricular (AV) block remains unknown. Because familial clustering of progressive cardiac conduction defects of unknown causes, including congenital AV block, has been reported, we hypothesized that idiopathic AV block in the young may be a heritable disease. This hypothesis was tested in a nationwide (France) retrospective cohort of 141 idiopathic pediatric AV blocks. Screening ECGs from 130 parents (mean age 42.0±6.8 years, 57 couples) were compared with 130 matched healthy control subjects. Although a family history of sudden death or progressive cardiac conduction defect, respectively, was found in only 1.4% and 11.1% of parents, conduction abnormalities were more frequent in parents than in control subjects, found in 50.8% versus 4.6%, respectively (P<0.001), and estimated heritability for isolated conduction disturbances was 91% (standard error, 1.019; P=2.10−16). SCN5A mutation screening identified 2 mutations in 2 patients among 97 children. Thus, ECG screening in parents of children affected by idiopathic AV block revealed diffuse subclinical impairment of cardiac conduction, which provides strong evidence for a genetic origin in congenital and childhood nonimmune isolated AV block. Such an ECG screening may be helpful in clinical practice if other obvious causes have been ruled out. Heritability estimate confirmed a high contribution of genetic factors, which opens the field to further molecular studies.Conclusions—ECG screening in parents of children affected by idiopathic AV block revealed a high prevalence of conduction abnormalities. These results support the hypothesis of an inheritable trait in congenital and childhood nonimmune isolated AV block.2Outcomes of Restrictive Cardiomyopathy in Childhood and the Influence of Phenotype: A Report From the Pediatric Cardiomyopathy RegistrySummary—Restrictive cardiomyopathy is a rare form of cardiomyopathy in childhood with a few risk factors identified for death or transplantation. This analysis from the Pediatric Cardiomyopathy Registry identified 152 cases of restrictive cardiomyopathy among 3375 children with cardiomyopathy (4.5%), approximately one-third of whom had a mixed restrictive/hypertrophic phenotype. Survival did not differ between those with pure and mixed phenotypes, but transplant-free survival was inferior in the pure restrictive cardiomyopathy group. Overall outcomes were worse than for all other forms of cardiomyopathy in the Pediatric Cardiomyopathy Registry. Clinical and echocardiographic risk factors at presentation for worse outcome were identified and should aid the clinician in risk stratification.Conclusions—Transplant-free survival is poor for restrictive cardiomyopathy in childhood. Survival is independent of phenotype; however, the restrictive cardiomyopathy/hypertrophic cardiomyopathy phenotype has significantly better transplant-free survival.3Early Predictors of Survival to and After Heart Transplantation in Children With Dilated CardiomyopathySummary—Factors that affect outcome in pediatric heart diseases such as dilated cardiomyopathy are often difficult to define because of the rarity of disease. To study the potential importance of factors at presentation and at listing for heart transplantation in children with dilated cardiomyopathy on outcome, we analyzed data from 2 large pediatric registries: the Pediatric Cardiomyopathy Registry and the Pediatric Heart Transplant Study. In the merged data set, there were 261 children with dilated cardiomyopathy. Among the factors studied were age, duration of illness, sex, race, ventricular geometry, and the clinical or histological diagnosis of myocarditis at presentation. We found that death while waiting was associated with ventilator use and older age at listing. A shorter duration of illness was associated with a more urgent listing status (United Network for Organ Sharing status 1). Death after transplantation was associated black race and lower left ventricular end-diastolic dimension z score at presentation. We also found that death after transplantation was associated with the diagnosis of myocarditis at presentation (P<0.009). Death while waiting was not associated with the diagnosis of myocarditis, and 97% of children with myocarditis survived to transplantation. Furthermore, the most common cause of death after transplantation in the myocarditis group was acute rejection (17%). This is the first study to show that children with dilated cardiomyopathy and myocarditis have significantly higher posttransplantation mortality compared with children without myocarditis. This finding suggests that preexisting viral infection or inflammation could adversely affect heart allograft survival and has implications for the management of these children before and after heart transplantation in the future.Conclusions—Mechanical ventilator use and older age at listing predicted death while waiting, whereas nonwhite race, smaller left ventricular dimension, and myocarditis were associated with death after transplantation. Although 97% of children with clinically or biopsy-diagnosed myocarditis at presentation survived to transplantation, they had significantly higher posttransplantation mortality compared with children without myocarditis, raising the possibility that preexisting viral infection or inflammation adversely affects graft survival.4Relationship Between Arterial Partial Oxygen Pressure After Resuscitation From Cardiac Arrest and Mortality in ChildrenSummary—Postresuscitation care is an important component that affects outcome after cardiac arrest. Adult studies have suggested a relationship between exposure to hyperoxia and survival in this setting. We undertook a national retrospective cohort study that involved 1875 patients from all pediatric intensive care units in the United Kingdom and Ireland to investigate the relationship between arterial partial oxygen pressure (PaO2) after resuscitation from cardiac arrest and mortality. We found exposure to supranormal oxygen tension was common, with 33% of patients having PaO2>150 mm Hg on the first blood gas. We demonstrated a significant association between early postarrest hyperoxia and increased mortality after admission to the pediatric intensive care unit. A stronger association was also seen between the degree of hypoxia and mortality. Our data lend support for intervention studies to assess the safety and efficacy of using the lowest inspired oxygen concentration that maintains arterial oxyhemoglobin saturation of 94% to 96% in the postresuscitation period.Conclusions—Both severe hypoxia and, to a lesser extent, hyperoxia are associated with an increased risk of death after pediatric intensive care unit admission after cardiac arrest.5Maternal Use of Hydroxychloroquine Is Associated With a Reduced Risk of Recurrent Anti-SSA/Ro-Antibody–Associated Cardiac Manifestations of Neonatal LupusSummary—A recent case-control study suggested a benefit of hydroxychloroquine (HCQ) in lowering the risk of cardiac manifestations of neonatal lupus (cardiac-NL) in pregnancies of anti-SSA/Ro–positive patients with systemic lupus erythematosus. In this study, we examined whether HCQ reduces the ≈10-fold higher recurrence rate in cardiac-NL by identifying 257 pregnancies of anti-SSA/Ro–positive mothers (40 exposed and 217 unexposed to HCQ) after the birthof a child with cardiac-NL from 3 international databases. Exposure was defined as the sustained use of HCQ throughout pregnancy with initiation before 10 weeks of gestation. The recurrence rate of cardiac-NL in fetuses exposed to HCQ was 7.5% (3 of 40) compared with 21.2% (46 of 217) in the unexposed group (P=0.050). There were no deaths in the HCQ-exposed group, whereas the overall case fatality rate of the cardiac-NL fetuses in the unexposed group was 21.7%. In a multivariable analysis, HCQ use remained significantly associated with a decreased risk of cardiac-NL (odds ratio, 0.23; P=0.037). Similar results (odds ratio, 0.18; P=0.011) were obtained with propensity score analysis, an alternative approach to adjust for possible confounding by indication. Data obtained from this multinational historical cohort study suggest that HCQ use in a mother with anti-SSA/Ro antibodies and a previous child with cardiac-NL may reduce the riskof cardiac-NL recurrence in a subsequent offspring. Further prospective studies are needed to confirm these findings.Conclusions—Aggregate data from a multinational effort show that in mothers at high risk of having a child with cardiac-NL, the use of HCQ may protect against recurrence of disease in a subsequent pregnancy.6Costs and Benefits of Targeted Screening for Causes of Sudden Cardiac Death in Children and AdolescentsSummary—This article examines the cost-effectiveness of ECG screening in 2 asymptomatic pediatric populations for whom it has been recommended: school-aged children with attention-deficit/hyperactivity disorder for whom stimulants are being considered and adolescents participating in sports. The risk of sudden cardiac death in these pediatric patients is very low, even compared with groups of young adults themselves only several years out of their own childhood. However, several cardiac disorders are capable of presenting as sudden cardiac death in the pediatric community. If these disorders were diagnosed while the patient is asymptomatic, it is assumed that appropriate treatments and avoidance of stimulant medication and/or stressful athletic activity may mitigate that risk. Only a handful of the several disorders that have been linked to pediatric SCD are (1) typically asymptomatic in the school-aged child and adolescent, (2) identifiable on ECG, and (3) sufficiently prevalent to warrant targeted screening compared with rarer disorders. We developed decision analyses models for ECG screening for 3 disorders that meet these criteria and hence are considered potentially appropriate targets for ECG screening programs: hypertrophic cardiomyopathy, Wolff-Parkinson-White syndrome, and long-QT syndrome. However, our findings indicate that, even under the conditions that might be expected to favor screening used in our base case, estimates of the cost-effectiveness of screening for these diseases are relatively unfavorable, ranging from $91 000 (adolescent participating in sports) to $204 000 per life-year (child with attention-deficit/hyperactivity disorder).Conclusions—Results based on assumptions favoring sudden cardiac death screening indicated that its cost is high relative to its health benefits.7Does Initial Shunt Type for the Norwood Procedure Affect Echocardiographic Measures of Cardiac Size and Function During Infancy?: The Single Ventricle Reconstruction TrialSummary—Hypoplastic left heart syndrome is a common form of functional single-ventricle congenital heart disease and is associated with significant morbidity/mortality. A National Heart, Lung, and Blood Institute Pediatric Heart Network study, the Single Ventricle Reconstruction trial, randomized initial surgical Norwood palliation in 549 infants with hypoplastic left heart syndrome to either a right ventricle–pulmonary artery shunt or a modified Blalock-Taussig shunt to determine the optimal surgical approach. The primary result of the trial found better 1-year transplant-free survival in subjects who received a right ventricle–pulmonary artery shunt compared with those who had a modified Blalock-Taussig shunt. This study compared 2-dimensional echocardiographic indices to assess the effect of initial shunt type at 4 stages during the trial (at baseline preoperatively, early after the Norwood procedure, immediately before the second-stage surgical procedure, and at 14 months of age). We found that differences in neoaortic annular size and flow patterns between shunt types when the shunts are in place can likely be explained by the different physiologies created rather than by intrinsic differences in cardiac function. After the shunt was removed at the second-stage surgery, echocardiographic indices were similar between the 2 groups, including measures of right ventricular function, cardiac and vascular dimensions, neoaortic and tricuspid dimensions and valve function, and neoaortic flow patterns. This lack of shunt-related differences in echocardiographic indices of cardiac and vascular function in survivors of the Norwood procedure at 14 months suggests that the best initial surgical pathway for infants with hypoplastic left heart syndrome remains unclear and emphasizes the importance of longitudinal follow-up of this unique cohort.Conclusions—Indices of cardiac size and function after the Norwood procedure are similar for modified Blalock-Taussig shunt and right ventricle-pulmonary artery shunt by 14 months of age. Interstage differences between shunt types can likely be explained by the physiology created when the shunts are in place rather than by intrinsic differences in cardiac function.8Interleukin-1β Is Crucial for the Induction of Coronary Artery Inflammation in a Mouse Model of Kawasaki DiseaseSummary—Kawasaki disease (KD) is now recognized as the leading cause of acquired heart disease in children in the United States and developed world. The underlying cause of KD and the mechanisms leading to vessel inflammation, coronary artery lesions, and aneurysms, which are the hallmarks of KD, remain largely unknown. Standard therapy with intravenous immunoglobulin (IVIG) effectively reduces the incidence of coronary arterial lesions, but 10% to 20% of patients with KD fail to respond to IVIG and thus show a high prevalence of coronary lesions. There is no definitive treatment recommendation for patients who fail to respond to an initial course of IVIG treatment. Rescue treatment for IVIG resistance includes additional IVIG dose(s), steroids, anti–tumor necrosis factor monoclonal antibody, and cyclosporine A, but these approaches have shown mixed results, and the effectiveness of these therapies remains controversial. Development of an optimal alternative for IVIG-resistant KD patients is now an urgent matter. Using a well-established KD mouse model, we found that interleukin-1β is critically involved in the development of coronary arteritis and myocarditis in KD mice and that these lesions can be prevented by treatment with an interleukin-1 receptor antagonist. These observations provide mechanistic insights into the cellular and molecular understanding of the vasculitis and coronary arteritis in the KD mouse model and suggest that anti–interleukin-1β agents might prevent the development of coronary lesions in KD patients. Our findings provide justification for future prospective multicenter clinical trials to determine the efficacy of therapies designed to block interleukin-1β–dependent signaling in children with KD.Conclusions—Our results strongly suggest that caspase-1 and IL-1β play critical roles in the development of coronary lesions in this KD mouse model, blocked by IL-1 receptor antagonist. Therefore, anti–IL-1β treatment strategies may constitute an effective, more targeted treatment of KD to prevent coronary lesions.9Metabolic Syndrome in Adolescence: Can It Be Predicted From Natal and Parental Profile?The Prediction of Metabolic Syndrome in Adolescence (PREMA) StudySummary—The prevalence of metabolic syndrome in adolescence has gradually increased to approximately 10% in the United States and Western Europe. Because it is strongly associated with adult metabolic syndrome, subclinical atherosclerosis, and type 2 diabetes mellitus, the early detection of children at high risk may have potential clinical impact. After assessment of an overall urban population of 2361 white children and adolescents over a 10-year period, the present study showed that birth measurements and family history can be helpful for the practicing clinician in classifying children according to risk of metabolic syndrome in adolescence. The coexistence of low birth weight (<10th percentile) and small birth head circumference (<10th percentile) together with parental (in at least 1 parent) overweight or obesity was found to predict metabolic syndrome in adolescence with a sensitivity of 91% and a specificity of 98%. Thus, the coexistence of low birth weight, small head circumference, and parental history of overweight or obesity may be helpful in targeting children at risk for developing metabolic syndrome in adolescence who may benefit especially from early institution of heart-healthy behaviors.Conclusions—The coexistence of low birth weight, small head circumference, and parental history of overweight or obesity may be useful for detection of children at risk of developing metabolic syndrome in adolescence.10Prevalence of Cardiomyopathy in Italian Asymptomatic Children With Electrocardiographic T-Wave Inversion at Preparticipation ScreeningSummary—T-wave inversion (≥2 contiguous leads) on a 12-lead ECG is usually dismissed in children as a normal “juvenile pattern of repolarization.” However, T-wave inversion is a common ECG abnormality of inherited heart muscle diseases such as hypertrophic cardiomyopathy and arrhythmogenic right ventricular cardiomyopathy, which are leading causes of sudden cardiac death in young competitive athletes. These cardiomyopathies are genetically determined and show an age-dependent phenotypic expression. Because early disease manifestations usually occur after puberty, the persistence of T-wave inversion in the postpubertal age raises the problem of differential diagnosis between a developing heart muscle disease and a benign juvenile pattern of repolarization. The present study was designed to assess prospectively the prevalence, age relation, and underlying cardiomyopathy of T-wave inversion in a large, consecutive series of Italian children (2765) with a mean age of 13.9±2.2 years (range, 8–18 years) undergoing preparticipation screening. In this age group, T-wave inversion, localized predominantly in the right precordial leads, was documented in 5.7% of cases, significantly decreased with increasing age and pubertal development, and most important, reflected an underlying cardiomyopathy such as arrhythmogenic right ventricular cardiomyopathy and hypertrophic cardiomyopathy in 2.5% of cases. These results indicate that after complete pubertal development, T-wave inversion becomes significantly less common than traditionally believed, and its persistence may suggest an underlying heart muscle disease at risk of sudden cardiac death. As a corollary, demonstration of postpubertal persistence of T-wave inversion in children engaged in competitive sports activity justifies an echocardiographic investigation, which may lead to presymptomatic identification of early cardiomyopathy.Conclusions—The prevalence of T-wave inversion decreases significantly after puberty. Echocardiographic investigation of children with postpubertal persistence of T-wave inversion at preparticipation screening is warranted because it may lead to presymptomatic diagnosis of a cardiomyopathy that could lead to sudden cardiac death during sports.11A Randomized, Double-Blind, Placebo-Controlled, Dose-Ranging Study of Oral Sildenafil Citrate in Treatment-Naive Children With Pulmonary Arterial HypertensionSummary—Pulmonary arterial hypertension is an important cause of morbidity and mortality in children and adults. Currently, 8 drugs are approved for adult pulmonary arterial hypertension, yet no drugs are approved for children. Because of similar clinical characteristics and histopathology, treatment for children has been extrapolated from evidence-based adult guidelines. However, better information is required to provide optimal pediatric dosing and to ensure safety in children of all ages. The 16-week, randomized, double-blind, placebo-controlled Sildenafil in Treatment-Naive Children, Aged 1 to 17 Years, With Pulmonary Arterial Hypertension (STARTS-1) study evaluated the effects of sildenafil in childhood pulmonary arterial hypertension. Treatment-naive children with pulmonary arterial hypertension (n=234; aged 1–17 years; ≥8 kg) received low-, medium-, or high-dose sildenafil or placebo orally 3 times daily. Peak oxygen consumption, measured only in children who were able to reliably perform exercise testing (using cycle ergometry), was the primary end point. Hemodynamic parameters and World Health Organization functional class were assessed across all patients, including those unable to reliably perform exercise testing. Although the primary comparison of percent change in peak oxygen consumption for the 3 sildenafil groups combined was only marginally statistically significant, the improvements in exercise capacity, functional class, and hemodynamics with medium- and high-dose sildenafil suggest efficacy with these doses. Combined with interim data from the ongoing extension study, the overall profile favors the medium dose. Further investigation is warranted to determine optimal dosing based on age and body weight.Conclusions—Sixteen-week sildenafil monotherapy is well tolerated in pediatric pulmonary arterial hypertension. Percent change in PO2 for the 3 sildenafil doses combined was only marginally significant; however, PO2, functional class, and hemodynamic improvements with medium and high doses suggest efficacy with these doses. Combined with STARTS-2 data, the overall profile favors the medium dose. Further investigation is warranted to determine optimal dosing based on age and weight.12Survival in Childhood Pulmonary Arterial Hypertension: Insights From the Registry to Evaluate Early and Long-Term Pulmonary Arterial Hypertension Disease ManagementSummary—The importance of this study is the size of the cohort for such a rare disease. The Registry to Evaluate Early and Long-Term Pulmonary Arterial Hypertension Disease Management (REVEAL) pediatric cohort is the most comprehensive prospective database of group 1 childhood pulmonary arterial hypertension reported to date. The size of the study (n=216), number of referral sites (n=26), and geographical distribution make the observations generalizable to clinical US practice. Although descriptive, the information is potentially useful for clinicians because it is a mixed incidence and prevalence cohort collected over 3 years. We describe the characteristics and outcomes of the cohort, and we identify key predictors of survival in childhood pulmonary arterial hypertension.Conclusions—Using REVEAL, we identified key predictors of survival in childhood pulmonary arterial hypertension. Refining these prognostic parameters should help clinicians improve outcomes.13Impact of Cardiac Devices on the Quality of Life in Pediatric PatientsSummary—To date, there has been a paucity of data with regard to quality of life (QOL) in pediatric patients with implanted defibrillators and pacemakers. In this study, QOL was assessed using both general pediatric and cardiac-specific QOL measurement tools. It was demonstrated that defibrillators, as well as pacemakers, have significant effect on patient QOL, which is further modified by device type as well as other patient characteristics, such as congenital heart disease. Furthermore, specific psychological factors that correlate with improved or worsened QOL, as well as key differences in drivers of QOL between patients and their parents, were identified. These data should both raise awareness of this effect on QOL and help design patient-specific psychological management strategies to mitigate these deleterious effects.Conclusions—Patient QOL is significantly affected by the presence of cardiac rhythm devices. Whether these effects can be mitigated through the use of psychotherapy needs to be assessed.14Demographics, Trends, and Outcomes in Pediatric Acute Myocarditis in the United States, 2006 to 2011Summary—Pediatric acute myocarditis has a heterogeneous clinical presentation, and its accurate diagnosis is difficult. There is lack of sufficient evidence-based diagnostic and treatment guidelines for management of pediatric acute myocarditis. There is significant regional variability and temporal changes in treatments used for pediatric myocarditis during the past 5 years in the United States. Myocarditis continues to have significant morbidity and mortality, with a large percentage of patients requiring mechanical cardiovascular support.Conclusions—There is significant temporal and regional variation in the diagnostic modalities and management used for pediatric myocarditis, which continues to have high morbidity and mortality. Extracorporeal membrane oxygenation, ventricular assist device, and vasoactive medications are independently associated with increased mortality/transplantation.15Normal Values of Left Atrial Volume in Pediatric Age Group Using a Validated Allometric ModelSummary—Left atrial size is an important diagnostic and prognostic measure of severity of disease and outcomes. Normal standards for left atrial size in children are not yet established. Current standardization methods have not been validated and if used clinically will categorize children with normal left atrial size in the abnormal category. Allometric scaling allows for accurate correction of chamber size for changes in body size (body surface area [BSA]), age, and sex. We have used this science to derive validated allometric models for the left atrial volume (LAV). In our study, we derived and validated an allometric model for children with BSA ≤1 m2 and >1 m2. The allometric models were further validated in a prospective cohort of children with structurally normal hearts and BSA. Indexing chamber volumes using BSA to the exponent of 1 is physiologically incorrect, and this has been published previously for left ventricular volumes. Results of our analysis show that z scores for indexed LAV should be based on indexing LAV/BSA1.48 and LAV/BSA1.08 in children with BSA ≤1 m2 and >1 m2, respectively. Using the validated allometric model will allow for accurate diagnosis of left atrial enlargement that will be independent of patients’ body size, age, and sex. The z-score graphs provided will allow for referencing and allocation of z scores for measured LAV.Conclusions—This study demonstrates the fallacy of using “per-BSA1 standards” for normalization of LAV in pediatrics. LAV/BSA1.48 for children with BSA≤1 m2 and LAV/BSA1.08 for those with BSA>1 m2 is accurate and can be used to derive Z-scores.16Conduction Abnormalities in Pediatric Patients With Restrictive CardiomyopathySummary—The findings of this review of pediatric patients with restrictive cardiomyopathy reiterate the high-risk nature of this unique patient population secondary to its association with potential sudden cardiac death. Although tachyarrhythmias will continue to be a major concern in this disease process, the risk of associated life-threatening bradyarrhythmias should not be overlooked. Secondary to the proposed link to central conduction system disease, most notably progressive AV nodal disease, seen in this study, close surveillance with ECG and ambulatory monitoring is warranted. In this study, PR prolongation and a wider QRS complex were associated with an acute cardiac event. The effectiveness of prophylactic pacing in this population as a bridge to cardiac transplantation or potentially as a means to delay listing for cardiac transplantation in patients with preserved pulmonary vascular resistance must be evaluated.Conclusions—Pediatric patients with restrictive cardiomyopathy are at risk for acute high-grade heart block, and, in this cohort, bradycardic events represented a significant portion of all arrhythmic events. Aggressive ECG monitoring strategies looking for conduction system disease should be ongoing in all patients with restrictive cardiomyopathy. Implantation of a defibrillator/pacemaker should be considered as prophylactic management.17Outcomes of Children Following a First Hospitalization for Dilated CardiomyopathySummary—Dilated cardiomyopathy (DCM) in children is a heterogeneous disease with a variable clinical course. Whereas some patients with DCM c" @default.
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