Neurodevelopmental Outcomes in Children With Congenital Heart Disease: Evaluation and Management

Over the past decade, new research has advanced scientific knowledge of neurodevelopmental trajectories, factors that increase neurodevelopmental risk, and neuroprotective strategies for individuals with congenital heart disease. In addition, best practices for evaluation and management of developmental delays and disorders in this high-risk patient population have been formulated based on literature review and expert consensus. This American Heart Association scientific statement serves as an update to the 2012 statement on the evaluation and management of neurodevelopmental outcomes in children with congenital heart disease. It includes revised risk categories for developmental delay or disorder and an updated list of factors that increase neurodevelopmental risk in individuals with congenital heart disease according to current evidence, including genetic predisposition, fetal and perinatal factors, surgical and perioperative factors, socioeconomic disadvantage, and parental psychological distress. It also includes an updated algorithm for referral, evaluation, and management of individuals at high risk. Risk stratification of individuals with congenital heart disease with the updated categories and risk factors will identify a large and growing population of survivors at high risk for developmental delay or disorder and associated impacts across the life span. Critical next steps must include efforts to prevent and mitigate developmental delays and disorders. The goal of this scientific statement is to inform health care professionals caring for patients with congenital heart disease and other key stakeholders about the current state of knowledge of neurodevelopmental outcomes for individuals with congenital heart disease and best practices for neuroprotection, risk stratification, evaluation, and management.

Over the last two decades advances in congenital heart surgery, pediatric cardiology, and pediatric intensive care have dramatically increased the survival of infants with critical congenital heart disease (CHD). Survivors often experience neurodevelopmental deficits and behavioral and emotional problems. These complications often have a profound impact on quality of life in this high-risk population. This review will focus on the most significant and innovative studies that have been published over the last 18 months that focus on predicting, evaluating, and managing neurodevelopmental outcomes in children with CHD. Recent reports demonstrate new potential predictors of worse neurodevelopmental outcome, including abnormal fetal cerebrovascular resistance, brain biomarkers, and abnormalities in electroencephalogram (EEG) during the perioperative period, and new stratification schemata. In addition, a new evidence-based scientific statement from the American Heart Association (AHA) and American Academy of Pediatrics (AAP) describing how to evaluate and manage neurodevelopmental outcomes in children and adolescents with CHD and novel interventions to improve neurodevelopmental outcomes will be reviewed. The literature reviewed reveals new intervention opportunities to improve neurodevelopmental outcome in the fetus (cerebrovascular resistance), during the perioperative period (brain biomarkers and EEG), and through the utilization of new stratification schemata. The new AHA/AAP guidelines on the evaluation and management of neurodevelopmental outcomes create the opportunity to identify and treat a significant population of survivors with neurodevelopmental deficits with novel interventions.

Several diseases show geographic clustering, giving insights into possible genetic and environmental causes. The pathogenesis of Congenital Heart Disease (CHD) remains largely unknown and analysis of geographic distribution of CHD cases lacks input from large, national-scale datasets. People with structural CHD were selected from the Australia and New Zealand CHD Registry. Of people known to be still living, from linkage with the National Death Index, addresses were geocoded and aggregated to standardised geographic regions with measures of the Australian population. Areas were described based on measures of their remoteness and driving time to hospitals. The relationship between the distribution of the CHD and Australian populations was compared with bivariate spatial correlation. Of 81,349 people with structural CHD in the Registry, 63,863 were still living and could be geocoded. Overall, most people lived in Major Cities, and within 1-hour drive from a hospital, with the proportion the same across the CHD population, the "complex CHD" population and the Australian population. Across the country, there was a strong positive correlation between the Australian population and the CHD population. There were only a small number of areas (6%) where the Australian and the CHD populations were proportionally different. Overall, there was clear evidence that the geographic distribution of the CHD population proportionally follows the general Australian population. This suggests that there is unlikely to be any spatial clusters that are driven by genetic or environmental causes.

The society for cardiovascular angiography and interventions (SCAI) think tank is a collaborative venture that brings together interventional cardiologists, administrative partners, and select members of the cardiovascular industry community for high-level field-wide discussions. The 2020 think tank was organized into four parallel sessions reflective of the field of interventional cardiology: (a) coronary intervention, (b) endovascular medicine, (c) structural heart disease, and (d) congenital heart disease (CHD). Each session was moderated by a senior content expert and co-moderated by a member of SCAI's emerging leader mentorship program. This document presents the proceedings to the wider cardiovascular community in order to enhance participation in this discussion, create additional dialogue from a broader base, and thereby aid SCAI and the industry community in developing specific action items to move these areas forward.

Several diseases (cancer, neurological) show geographic clustering, giving insights into possible genetic and environmental causes. The pathogenesis of Congenital Heart Disease (CHD) remains largely unknown and analysis of geographic distribution of CHD cases lacks input from large, national-scale datasets.People with structural CHD were selected from the Australia and New Zealand CHD Registry. Of people known to be still living, from linkage with the National Death Index, addresses were geocoded and aggregated to standardised geographic regions with measures of the Australian population. Areas were described based on measures of their remoteness and driving time to hospitals. The relationship between the distribution of the CHD and Australian populations was compared with bivariate spatial correlation.Of 81,349 people with structural CHD in the Registry, 63,863 were still living and could be geocoded. Overall, most people lived in Major Cities, and within 1-hour drive from a hospital, with the proportion the same across the CHD population, the “complex CHD” population and the Australian population. Across the country, there was a strong positive correlation between the Australian population and the CHD population. There were only a small number of areas (6%) where the Australian and the CHD populations were proportionally different.Overall, there was clear evidence that the geographic distribution of the CHD population proportionally follows the general Australian population. This suggests that there is unlikely to be any spatial clusters that are driven by genetic or environmental causes.Author SummaryPeople living with congenital heart disease have overgone many changes over recent decades. As surgical intervention has improved, people with congenital heart disease are living longer and a greater proportion are now adults. This is success brings new challenges surrounding their healthcare. What kinds of complications will older people with congenital heart disease face, how will our health services cope with the increasing demands, and how should we deploy health services? We aimed to answer some of these question by assessing where people with congenital heart disease lived in Australia, and how that distribution compares with the general Australian population. This research is made possible by the Australia and New Zealand Congenital Heart Disease Registry, which enables this analysis to be conducted at a national scale for the first time. Most of the congenital heart disease population was living in major cities, and within a 1-hour drive of a hospital. Overall, their geographic distribution was very similar to that of the Australia population. These results suggest that there are not any environmental factors that are causing congenital heart disease, or that people with congenital heart disease are choosing to live in different places, compared to the general Australian population.

BackgroundNeurodevelopmental disorder (ND) has emerged as a critical factor affecting the long-term quality of life among patients with congenital heart disease (CHD). The aim of this study was to provide a multi-omics perspective on the mechanisms of ND.MethodsWe analyzed the serum metabolome and gut microbiome of children with ND and non-ND (NND) in CHD populations.ResultsIn this prospective observational study, we identified associations between serum metabolites, gut microbial, and ND. Linolenic acid was most closely related to neurodevelopmental outcomes, showing positive correlations with multiple neurodevelopmental domains. Among the gut microbiota, the Escherichia genus was most strongly associated with neurodevelopmental outcomes, and negative correlations with neurodevelopmental domains.ConclusionThis multi-omics study reveals significant association between altered serum metabolites, gut microbiota dysbiosis, and neurodevelopmental outcomes in children with CHD. The microbes and metabolites identified here may contribute to addressing the challenge of ND in the CHD population. Based on our findings, therapeutic strategies to reduce the risk of ND could be developed, including targeted manipulation of the gut microbiota and metabolites.

Cardiac resynchronization therapy in paediatric and congenital heart disease patients

Effective medical and surgical management of pediatric congenital heart disease (CHD) to reduce long-term adverse neurodevelopmental outcomes is an important clinical objective in primary and specialty health care. We identify clinical predictors associated with an increased risk of 6 long-term neurodevelopmental outcomes in children with CHD compared to the general pediatric Medicaid population. South Carolina's retrospective, 15-year Medicaid data set (January 1, 1996-December 31, 2010) for 19,947 patients aged ≤ 17 years diagnosed with ≥ 1 CHD lesions (on the basis of International Classification of Diseases, Ninth Revision, Clinical Modification codes) were compared to 19,948 patients without CHD matched on age at entry into and duration in Medicaid using logistic and Cox proportional hazards regression. The CHD cohort was significantly less likely to have incident neurologic or psychiatric disorders, mental retardation, developmental delays, or inattention/hyperactivity (adjusted odds ratios [ORs] = 0.34, 0.56, 0.03, 0.01, 0.004, respectively) but was more likely to have incident seizures (OR = 2.00) compared to controls. Exposure to both cardiac and noncardiac surgical intervention was associated with a significantly increased risk of developing neurologic or psychiatric disorders, mental retardation, developmental delays, or inattention/hyperactivity (cardiac ORs = 1.66, 2.00, 1.67, 1.43, 1.76, respectively) (noncardiac ORs = 2.25, 1.59, 1.48, 1.29, 1.36, 2.46, respectively). Any documented hypoxemia was associated with a significantly increased risk of developing 5 of the neurodevelopmental conditions (neurologic OR = 4.52, psychiatric OR = 1.60, mental retardation OR = 2.90, developmental delay OR = 2.12, seizures OR = 4.23). Practitioners should maintain vigilant surveillance of all CHD patients, especially those exposed to surgical procedures or experiencing hypoxemia, to identify any neurodevelopmental issues early and address them promptly.

To investigate the impact of feeding mode on neurodevelopmental outcomes in children with congenital heart defects. A retrospective cohort study of 208 children with congenital heart disease (CHD), who had surgery from 1 January 2013 until 31 December 2016 at Texas Children's Hospital, Houston, TX, US. University Hospital, Developmental Outcome Clinic. Standardized cognitive scores were assessed with Capute Scales and motor development with Revised Gesell Developmental Schedules. We analyzed anthropometrics, mode of feeding, surgical complexity, syndrome, and gender as predictors of developmental outcomes at four time points: hospital discharge, and 6, 12, and 24 months of age. Mode of feeding is associated with neurodevelopmental outcome in children with CHD. Children on enteral feeding tubes had significantly lower developmental quotient (DQ) scores in cognition, communication, and motor function at 12 and 24 months compared to orally fed children. There were greater proportions of developmental delays (DQ<70) in enteral tube fed children at the 6, 12, and 24 months visits. Further, there was a strong association between presence of enteral feeding tube, syndrome, and developmental outcome. Greater surgical complexity, weight gain and ethnicity were not associated with the developmental outcomes. Our findings suggest that the presence of an enteral feeding tube following corrective congenital heart surgery are at increased risk of neurodevelopmental delays at 12 and 24 months.

Safety and efficacy of atrial antitachycardia pacing in congenital heart disease

Improving neurologic and quality-of-life outcomes in children with congenital heart disease: Past, present, and future

Background: Congenital heart disease (CHD) often requires intensive surgeries and care, especially in the early years of a CHD patient. However, it is not well understood how their health care utilization and costs vary as CHD patients transition into young adulthood. Objective: We aim to identify the utilization patterns of hospitalization by age among CHD patients 10-29 years old and to measure the associated costs as compared with the general population in California. Methods: We utilized the California State Inpatient Database (SID) and the Healthcare Cost and Utilization Project (HCUP) Cost-to-Charge Ratio Files 2005-2009. By merging the two datasets, we obtained data on about 97% of all hospital discharge records in California including principal and secondary diagnoses, principal and secondary procedures, admission and discharge status, basic patient demographics, total charges, imputed total costs, and length of stay (LOS). Hospital discharges of CHD patients were identified by one or more principal or secondary ICD-9 diagnosis codes of 745.xx, 746.xx, or 747.xx. Utilization and cost patterns were compared to the general population by 5-year age groups (10-14, 15-19, 20-24, and 25-29). We then conducted a multivariate linear regression with the CHD population to understand how age and other factors influence costs of hospitalization per stay. Results: The average hospitalization costs per stay among CHD patients remain 2-3 times as high as that of the general population across all age groups ($21-31k vs. $7k-12k). However, the total hospitalization costs of the CHD population monotonically decrease as patients with CHD age into adulthood: in 2005-2009, the total costs were $75m in the 10-14 group, $74m in the 15-19 group, $50m in the 20-24 group and $48m in the 25-29 group, which represented 3.8%, 1.7%, 0.8%, 0.7% of the total costs in the general population of the respective age group. The decline in total costs by age among the CHD population manifested in both decreasing numbers of hospitalizations and lower costs per stay. Other observed trends include increasing fraction of admissions from the emergency department (ED), decreasing fraction of surgery-related hospitalizations, and shorter LOS as CHD population age into adulthood. Regression results within the CHD population 10-29 years old (n=9680) suggest that costs per stay were positively associated with LOS (+$2674, p&lt;.001) and were negatively associated with being 25-29 years old (-$3240, p&lt;.001), being female (-$1935, p&lt;.001), having no surgeries (-$16758, p&lt;.001) or other procedures performed ($21396, p&lt;.001), and being admitted from the ED (-$3638, p&lt;.001). Conclusion: The CHD population incurs lower hospitalization costs as they age into young adulthood.

Introduction: Patients with congenital heart disease (CHD) frequently require implantable cardiac devices. Device infection or malfunction may necessitate lead extraction. Extraction may be challenging due to long lead dwell times, anatomic abnormalities, and prior cardiac surgery. Little is known about extraction outcomes in the CHD population. Methods and Results: This retrospective study included 41 CHD patients and 82 age and gender matched controls that underwent lead extractions at two centers between 2001-2014. Only patients with leads older than 12 months were included. There were 79 leads in CHD patients and 150 in controls. Patients with CHD had a mean age of 39±17 years at extraction and on average their leads had been implanted for 81±84 months, this was not significantly different from the control group. Eighty eight percent of CHD patients had 1 or more cardiac surgeries as compared to only 22% of controls (p&lt;0.001). The number of abandoned leads was also significantly different with 16 abandoned leads in the CHD group and 3 in controls (p&lt;0.001). There was no statistically significant difference in extraction techniques between the groups. Complete extraction was achieved in 94% of patients in both groups. There were no CHD group complications. Control group complications included 3 SVC lacerations requiring sternotomy (one was fatal), and 1 ventricular perforations with tamponade requiring sternotomy. None of these patients had a history of cardiac surgery. The average age of leads in patients with a complication was 15.3 years which was older than the mean lead age seen in the CHD and control populations which was 6.75 and 4.6 years respectively. Conclusions: Lead extraction can be safely performed in patients with CHD. Despite anatomic abnormalities and previous cardiac surgery, the outcome of lead extraction in patients with CHD is comparable to controls. Prior cardiac surgery may lower the risk for extraction complications.

The congenital heart disease (CHD) population is growing and aging. We aim to examine the impact by describing the temporal trend and causes of lifetime hospitalization burden among the CHD population. From the Danish National Patient Registry, 23 141 patients with CHD and their hospitalizations from 1977 to 2018 were identified, excluding patients with extracardiac malformation. Patients with CHD were categorized into major CHD and minor CHD, and each patient was matched with 10 controls by sex and year of birth. The rate of all-cause hospitalization increased over time from 28.3 to 36.4 hospitalizations per 100 person-years (PY) with rate difference (RD) per decade of 2.5 (95% CI, 2.0-3.1) hospitalizations per 100 PY for the patients with CHD, compared with the increase from 10.8 to 17.0 per 100 PY (RD per decade, 2.0 [95% CI, 1.8-2.2] per 100 PY) for the control group (RD for CHD versus control, P=0.08). The all-cause hospitalization rate remained constant for the major CHDs (RD per decade, -0.2 [95% CI, -1.2 to 0.9] per 100 PY) but increased for the minor CHDs (RD per decade, 5.2 [95% CI, 4.3-6.0] per 100 PY). For all patients with CHD, the cardiovascular hospitalization rate remained constant over time (RD per decade, 0.2 [95% CI, -0.3 to 0.6] per 100 PY) whereas the noncardiovascular hospitalization rate increased (RD per decade, 2.1 [95% CI, 1.6-2.7] per 100 PY). The length of all-cause hospital stays for all patients with CHD decreased from 2.7 (95% CI, 2.6-2.8) days per PY in 1977 to 1987 to 1.6 (95% CI, 1.6-1.7) days per PY in 2008 to 2018. Compared with previous decades, patients with CHD have an increasing hospitalization rate, similar to the general population, but a decreasing length of hospital stay. The increase in hospitalization rate was driven by noncardiovascular hospitalizations, with the patients with minor CHD being the key contributor to the increasing rate.

Toward Improved Neurodevelopmental Outcomes: The Role of Transfontanel Ultrasound Assessment of Cerebral Blood Flow in Infants Undergoing Cardiac Surgery