Parameters of cardiopulmonary exercise testing were recently identified as strong predictors of mortality in adults with congenital heart disease. We hypothesized that combinations of cardiopulmonary ...exercise testing parameters may provide optimal prognostic information on midterm survival in this population.
A total of 1375 consecutive adult patients with congenital heart disease (age, 33±13 years) underwent cardiopulmonary exercise testing at a single center over a period of 10 years. Peak oxygen consumption (peak V(O(2))), ventilation per unit of carbon dioxide production (V(E)/V(O(2)) slope), and heart rate reserve were measured. During a median follow-up of 5.8 years, 117 patients died. Peak V(O(2)), heart rate reserve, and V(E)/V(O(2)) slope were related to midterm survival in adult patients with congenital heart disease. Risk of death increased with lower peak V(O(2)) and heart rate reserve. A higher V(E)/V(O(2)) slope was also related to increased risk of death in noncyanotic patients, whereas the V(E)/V(O(2)) slope was not predictive of mortality in cyanotic patients. The combination of peak V(O(2)) and heart rate reserve provided the greatest predictive information after adjustment for clinical parameters such as negative chronotropic agents, age, and presence of cyanosis. However, the incremental value of these exercise parameters was reduced in patients with peak respiratory exchange ratio <1.0.
Cardiopulmonary exercise testing provides strong prognostic information in adult patients with congenital heart disease. Prognostication should be approached differently, depending on the presence of cyanosis, use of rate-lowering medications, and achieved level of exercise. We provide 5-year survival prospects based on cardiopulmonary exercise testing parameters in this growing population.
Turner syndrome is a rare condition in women that is associated with either complete or partial loss of one X chromosome, often in mosaic karyotypes. Turner syndrome is associated with short stature, ...delayed puberty, ovarian dysgenesis, hypergonadotropic hypogonadism, infertility, congenital malformations of the heart, endocrine disorders such as type 1 and type 2 diabetes mellitus, osteoporosis and autoimmune disorders. Morbidity and mortality are increased in women with Turner syndrome compared with the general population and the involvement of multiple organs through all stages of life necessitates a multidisciplinary approach to care. Despite an often conspicuous phenotype, the diagnostic delay can be substantial and the average age at diagnosis is around 15 years of age. However, numerous important clinical advances have been achieved, covering all specialty fields involved in the care of girls and women with Turner syndrome. Here, we present an updated Review of Turner syndrome, covering advances in genetic and genomic mechanisms of disease, associated disorders and multidisciplinary approaches to patient management, including growth hormone therapy and hormone replacement therapy.
Neurodevelopmental impairment is common in children with congenital heart disease (CHD), but postnatal variables explain only 30% of the variance in outcomes. To explore whether the antecedents for ...neurodevelopmental disabilities might begin in utero, we analyzed whether fetal brain volume predicted subsequent neurodevelopmental outcome in children with CHD.
Fetuses with isolated CHD and sociodemographically comparable healthy control fetuses underwent fetal brain magnetic resonance imaging and 2-year neurodevelopmental evaluation with the Bayley Scales of Infant and Toddler Development, Third Edition (Bayley-III) and the Adaptive Behavior Assessment System, Third Edition (ABAS-3). Hierarchical regression evaluated potential predictors of Bayley-III and ABAS-3 outcomes in the CHD group, including fetal total brain volume adjusted for gestational age and sex, sociodemographic characteristics, birth measures, and medical history.
The CHD group (n=52) had lower Bayley-III cognitive, language, and motor scores than the control group (n=26), but fetal brain volumes were similar. Within the CHD group, larger fetal total brain volume correlated with higher Bayley-III cognitive, language, and motor scores and ABAS-3 adaptive functioning scores (
=0.32-0.47; all
<0.05), but this was not noted in the control group. Fetal brain volume predicted 10% to 21% of the variance in neurodevelopmental outcome measures in univariate analyses. Multivariable models that also included social class and postnatal factors explained 18% to 45% of the variance in outcome, depending on developmental domain. Moreover, in final multivariable models, fetal brain volume was the most consistent predictor of neurodevelopmental outcome across domains.
Small fetal brain volume is a strong independent predictor of 2-year neurodevelopmental outcomes and may be an important imaging biomarker of future neurodevelopmental risk in CHD. Future studies are needed to support this hypothesis. Our findings support inclusion of fetal brain volume in risk stratification models and as a possible outcome in fetal neuroprotective intervention studies.
Pulmonary arterial hypertension (PAH) is commonly associated with congenital heart disease (CHD) and relates to type of the underlying cardiac defects and repair history. Large systemic to pulmonary ...shunts may develop PAH if untreated or repaired late. PAH, when present, markedly increases morbidity and mortality in patients with CHD. Significant progress has been made for patients with Eisenmenger syndrome in pathophysiology, prognostication and disease-targeting therapy (DTT), which needs to be applied to routine patient care. Patients with PAH-CHD and systemic to pulmonary shunting may benefit from late defect closure if pulmonary vascular resistance (PVR) is still normal or near normal. Patients with PAH and coincidental defects, or previous repair of CHD should be managed as those with idiopathic PAH. Patients with a Fontan circulation, despite not strictly fulfilling criteria for PAH, may have elevated PVR; recent evidence suggests that they may also benefit from DTT, but more data are required before general recommendations can be made. CHD-PAH is a lifelong, progressive disease; patients should receive tertiary care and benefit from a proactive DTT approach. Novel biomarkers and genetic advances may identify patients with CHD who should be referred for late defect closure and/or patients at high risk of developing PAH despite early closure in childhood. Ongoing vigilance for PAH and further controlled studies are clearly warranted in CHD.
Despite the overall improvement in life expectancy of patients living with congenital heart disease (congenital HD), disparities in morbidity and mortality remain throughout the lifespan. ...Longstanding systemic inequities, disparities in the social determinants of health, and the inability to obtain quality lifelong care contribute to poorer outcomes. To work toward health equity in populations with congenital HD, we must recognize the existence and strategize the elimination of inequities in overall congenital HD morbidity and mortality, disparate health care access, and overall quality of health services in the context of varying social determinants of health, systemic inequities, and structural racism. This requires critically examining multilevel contributions that continue to facilitate health inequities in the natural history and consequences of congenital HD. In this scientific statement, we focus on population, systemic, institutional, and individual-level contributions to health inequities from prenatal to adult congenital HD care. We review opportunities and strategies for improvement in lifelong congenital HD care based on current public health and scientific evidence, surgical data, experiences from other patient populations, and recognition of implicit bias and microaggressions. Furthermore, we review directions and goals for both quantitative and qualitative research approaches to understanding and mitigating health inequities in congenital HD care. Finally, we assess ways to improve the diversity of the congenital HD workforce as well as ethical guidance on addressing social determinants of health in the context of clinical care and research.
Noonan syndrome is a pleomorphic genetic disorder, in which a high percentage of affected individuals have cardiovascular involvement, most prevalently various forms of congenital heart disease ...(i.e., pulmonary valve stenosis, septal defects, left-sided lesions, and complex forms with multiple anomalies). Care includes attentiveness to several comorbidities, some directly impacting cardiac management (bleeding diatheses and lymphatic anomalies). More than 50% of patients with Noonan syndrome harbor PTPN11 pathogenic variation, which results in hyperactivation of RAS/mitogen-activated protein kinase signaling. Several other disease genes with similar biological effects have been uncovered for NS and phenotypically related disorders, collectively called the RASopathies. Molecular diagnosis with gene resequencing panels is now widely available, but phenotype variability and in some cases, subtlety, continues to make identification of Noonan syndrome difficult. Until genetic testing becomes universal for patients with congenital heart disease, alertness to Noonan syndrome's broad clinical presentations remains crucial. Genotype-phenotype associations for Noonan syndrome enable better prognostication for affected patients when a molecular diagnosis is established. We still lack Noonan syndrome-specific treatment; however, newly developed anticancer RAS pathway inhibitors could fill that gap if safety and efficacy can be established for indications such as pulmonary valve stenosis.
Congenital heart disease (CHD) is one of the most common birth defects. Studies in animal models and humans have indicated a genetic etiology for CHD. About 400 genes have been implicated in CHD, ...encompassing transcription factors, cell signaling molecules, and structural proteins that are important for heart development. Recent studies have shown genes encoding chromatin modifiers, cilia related proteins, and cilia-transduced cell signaling pathways play important roles in CHD pathogenesis. Elucidating the genetic etiology of CHD will help improve diagnosis and the development of new therapies to improve patient outcomes.
Background Despite advances in pediatric health care over recent decades, it is not clear whether survival in children with congenital heart disease (CHD) is still increasing. Methods and Results We ...identified all patients with CHD using nationwide Swedish health registries for 1980 to 2017. We examined the survival trends in children with CHD; we investigated the mortality risk in patients with CHD compared with matched controls without CHD from the general population using Cox proportional regression models and Kaplan-Meier survival analysis. Among 64 396 patients with CHD and 639 012 matched controls without CHD, 3845 (6.0%) and 2235 (0.3%) died, respectively. The mean study follow-up (SD) was 11.4 (6.3) years in patients with CHD. The mortality risk was 17.7 (95% CI, 16.8-18.6) times higher in children with CHD compared with controls. The highest mortality risk was found during the first 4 years of life in patients with CHD (hazard ratio HR, 19.6; 95% CI, 18.5-20.7). When stratified by lesion group, patients with non-conotruncal defects had the highest risk (HR, 97.2; 95% CI, 80.4-117.4). Survival increased substantially according to birth decades, but with no improvement after the turn of the century where survivorship reached 97% in children with CHD born in 2010 to 2017. Conclusions Survival in children with CHD has increased substantially since the 1980s; however, no significant improvement has been observed this century. Currently, >97% of children with CHD can be expected to reach adulthood highlighting the need of life-time management.
22q11.2 deletion syndrome (22q11.2 DS) is the most common microdeletion syndrome and is underdiagnosed in diverse populations. This syndrome has a variable phenotype and affects multiple systems, ...making early recognition imperative. In this study, individuals from diverse populations with 22q11.2 DS were evaluated clinically and by facial analysis technology. Clinical information from 106 individuals and images from 101 were collected from individuals with 22q11.2 DS from 11 countries; average age was 11.7 and 47% were male. Individuals were grouped into categories of African descent (African), Asian, and Latin American. We found that the phenotype of 22q11.2 DS varied across population groups. Only two findings, congenital heart disease and learning problems, were found in greater than 50% of participants. When comparing the clinical features of 22q11.2 DS in each population, the proportion of individuals within each clinical category was statistically different except for learning problems and ear anomalies (P < 0.05). However, when Africans were removed from analysis, six additional clinical features were found to be independent of ethnicity (P ≥ 0.05). Using facial analysis technology, we compared 156 Caucasians, Africans, Asians, and Latin American individuals with 22q11.2 DS with 156 age and gender matched controls and found that sensitivity and specificity were greater than 96% for all populations. In summary, we present the varied findings from global populations with 22q11.2 DS and demonstrate how facial analysis technology can assist clinicians in making accurate 22q11.2 DS diagnoses. This work will assist in earlier detection and in increasing recognition of 22q11.2 DS throughout the world.
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