Evaluation and Management of Chronic Heart Failure in Children and Adolescents With Congenital Heart Disease: A Scientific Statement From the American Heart Association.

With continued medical and surgical advancements, most children and adolescents with congenital heart disease are expected to survive to adulthood. Chronic heart failure is increasingly being recognized as a major contributor to ongoing morbidity and mortality in this population as it ages, and treatment strategies to prevent and treat heart failure in the pediatric population are needed. In addition to primary myocardial dysfunction, anatomical and pathophysiological abnormalities specific to various congenital heart disease lesions contribute to the development of heart failure and affect potential strategies commonly used to treat adult patients with heart failure. This scientific statement highlights the significant knowledge gaps in understanding the epidemiology, pathophysiology, staging, and outcomes of chronic heart failure in children and adolescents with congenital heart disease not amenable to catheter-based or surgical interventions. Efforts to harmonize the definitions, staging, follow-up, and approach to heart failure in children with congenital heart disease are critical to enable the conduct of rigorous scientific studies to advance our understanding of the actual burden of heart failure in this population and to allow the development of evidence-based heart failure therapies that can improve outcomes for this high-risk cohort.

Longitudinal Follow-Up of Children With HLHS and Association Between Norwood Shunt Type and Long-Term Outcomes: The SVR III Study.

OBJECTIVE: In the SVR trial (Single Ventricle Reconstruction), newborns with hypoplastic left heart syndrome were randomly assigned to receive a modified Blalock-Taussig-Thomas shunt (mBTTS) or a right ventricle-to-pulmonary artery shunt (RVPAS) at Norwood operation. Transplant-free survival was superior in the RVPAS group at 1 year, but no longer differed by treatment group at 6 years; both treatment groups had accumulated important morbidities. In the third follow-up of this cohort (SVRIII [Long-Term Outcomes of Children With Hypoplastic Left Heart Syndrome and the Impact of Norwood Shunt Type]), we measured longitudinal outcomes and their risk factors through 12 years of age. METHODS: Annual medical history was collected through record review and telephone interviews. Cardiac magnetic resonance imaging (CMR), echocardiogram, and cycle ergometry cardiopulmonary exercise tests were performed at 10 through 14 years of age among participants with Fontan physiology. Differences in transplant-free survival and complication rates (eg, arrhythmias or protein-losing enteropathy) were identified through 12 years of age. The primary study outcome was right ventricular ejection fraction (RVEF) by CMR, and primary analyses were according to shunt type received. Multivariable linear and Cox regression models were created for RVEF by CMR and post-Fontan transplant-free survival. RESULTS: Among 549 participants enrolled in SVR, 237 of 313 (76%; 60.7% male) transplant-free survivors (mBTTS, 105 of 147; RVPAS, 129 of 161; both, 3 of 5) participated in SVRIII. RVEF by CMR was similar in the shunt groups (RVPAS, 51±9.6 [n=90], and mBTTS, 52±7.4 [n=75]; P=0.43). The RVPAS and mBTTS groups did not differ in transplant-free survival by 12 years of age (163 of 277 [59%] versus 144 of 267 [54%], respectively; P=0.11), percentage predicted peak Vo2 for age and sex (74±18% [n=91] versus 72±18% [n=84]; P=0.71), or percentage predicted work rate for size and sex (65±20% versus 64±19%; P=0.65). The RVPAS versus mBTTS group had a higher cumulative incidence of protein-losing enteropathy (5% versus 2%; P=0.04) and of catheter interventions (14 versus 10 per 100 patient-years; P=0.01), but had similar rates of other complications. CONCLUSIONS: By 12 years after the Norwood operation, shunt type has minimal association with RVEF, peak Vo2, complication rates, and transplant-free survival. RVEF is preserved among the subgroup of survivors who underwent CMR assessment. Low transplant-free survival, poor exercise performance, and accruing morbidities highlight the need for innovative strategies to improve long-term outcomes in patients with hypoplastic left heart syndrome. REGISTRATION: URL: https://www. CLINICALTRIALS: gov; Unique identifier: NCT0245531.

Identifying novel data-driven subgroups in congenital heart disease using multi-modal measures of brain structure.

Individuals with congenital heart disease (CHD) have an increased risk of neurodevelopmental impairments. Given the hypothesized complexity linking genomics, atypical brain structure, cardiac diagnoses and their management, and neurodevelopmental outcomes, unsupervised methods may provide unique insight into neurodevelopmental variability in CHD. Using data from the Pediatric Cardiac Genomics Consortium Brain and Genes study, we identified data-driven subgroups of individuals with CHD from measures of brain structure. Using structural magnetic resonance imaging (MRI; N = 93; cortical thickness, cortical volume, and subcortical volume), we identified subgroups that differed primarily on cardiac anatomic lesion and language ability. In contrast, using diffusion MRI (N = 88; white matter connectivity strength), we identified subgroups that were characterized by differences in associations with rare genetic variants and visual-motor function. This work provides insight into the differential impacts of cardiac lesions and genomic variation on brain growth and architecture in patients with CHD, with potentially distinct effects on neurodevelopmental outcomes.

The Incidence and Relevance of Hematochezia in the Interstage Congenital Heart Population.

Necrotizing enterocolitis (NEC) increases morbidity and mortality for infants with single ventricle heart disease (SVHD). While hematochezia often proceeds NEC not all hematochezia progresses to NEC. We aimed to examine the incidence, risk-factors, and outcomes associated with hematochezia and NEC for infants with SVHD. A single-center cohort study including SVHD patients requiring Stage I palliation from 12/2010 to 12/2015 was performed. Demographic, clinical, and outcome measures during the interstage period were abstracted from medical records. We defined hematochezia as blood in the stool without alternative etiology and NEC as systemic or intestinal signs concurrent with hematochezia and/or the presence of radiographic pneumatosis. Clinical characteristics and outcome measures were compared between patients with/without hematochezia and with/without NEC. Of 135 patients, 59(44%) had hematochezia and 20(15%) developed NEC. Demographic and operative factors were similar between patients with and without hematochezia. Patients with NEC were more often premature (15% vs 0%, p = 0.04), have lower birth weight (3.0 ± 0.6 vs 3.3 ± 0.5 kg, p = 0.03), longer cardiopulmonary bypass time (median 131 vs. 90 min, p = 0.02) and more often underwent unplanned cardiac catheterization (20% vs 3%, p = 0.04). Patients with hematochezia had more line days (p < 0.0001) and longer post-Stage-I length of stay (p < 0.0001) than those without hematochezia, and those with NEC had more line days than those without NEC (p = 0.02). Hematochezia is frequent following Stage-I palliation, however only one third of these patients develop NEC. Non-NEC Hematochezia is associated with a similar increase in line and hospital days. Further research is needed to identify methods to avoid over treatment.

Development of the data registry for the Cardiac Neurodevelopmental Outcome Collaborative.

Children with congenital heart disease (CHD) can face neurodevelopmental, psychological, and behavioural difficulties beginning in infancy and continuing through adulthood. Despite overall improvements in medical care and a growing focus on neurodevelopmental screening and evaluation in recent years, neurodevelopmental disabilities, delays, and deficits remain a concern. The Cardiac Neurodevelopmental Outcome Collaborative was founded in 2016 with the goal of improving neurodevelopmental outcomes for individuals with CHD and pediatric heart disease. This paper describes the establishment of a centralised clinical data registry to standardize data collection across member institutions of the Cardiac Neurodevelopmental Outcome Collaborative. The goal of this registry is to foster collaboration for large, multi-centre research and quality improvement initiatives that will benefit individuals and families with CHD and improve their quality of life. We describe the components of the registry, initial research projects proposed using data from the registry, and lessons learned in the development of the registry.

Empirical evidence for effects of invasive American Bullfrogs on occurrence of native amphibians and emerging pathogens.

Invasive species and emerging infectious diseases are two of the greatest threats to biodiversity. American Bullfrogs (Rana [Lithobates] catesbeiana), which have been introduced to many parts of the world, are often linked with declines in native amphibians via predation and the spread of emerging pathogens such as amphibian chytrid fungus (Batrachochytrium dendrobatidis [Bd]) and ranaviruses. Although many studies have investigated the potential role of bullfrogs in the decline of native amphibians, analyses that account for shared habitat affinities and imperfect detection have found limited support for clear effects. Similarly, the role of bullfrogs in shaping the patch-level distribution of pathogens is unclear. We used eDNA methods to sample 233 sites in the southwestern USA and Sonora, Mexico (2016-2018) to estimate how the presence of bullfrogs affects the occurrence of four native amphibians, Bd, and ranaviruses. Based on two-species, dominant-subordinate occupancy models fitted in a Bayesian context, federally threatened Chiricahua Leopard Frogs (Rana chiricahuensis) and Western Tiger Salamanders (Ambystoma mavortium) were eight times (32% vs. 4%) and two times (36% vs. 18%), respectively, less likely to occur at sites where bullfrogs occurred. Evidence for the negative effects of bullfrogs on Lowland Leopard Frogs (Rana yavapaiensis) and Northern Leopard Frogs (Rana pipiens) was less clear, possibly because of smaller numbers of sites where these native species still occurred and because bullfrogs often occur at lower densities in streams, the primary habitat for Lowland Leopard Frogs. At the community level, Bd was most likely to occur where bullfrogs co-occurred with native amphibians, which could increase the risk to native species. Ranaviruses were estimated to occur at 33% of bullfrog-only sites, 10% of sites where bullfrogs and native amphibians co-occurred, and only 3% of sites where only native amphibians occurred. Of the 85 sites where we did not detect any of the five target amphibian species, we also did not detect Bd or ranaviruses; this suggests other hosts do not drive the distribution of these pathogens in our study area. Our results provide landscape-scale evidence that bullfrogs reduce the occurrence of native amphibians and increase the occurrence of pathogens, information that can clarify risks and aid the prioritization of conservation actions.

Quality of life after Ross procedure in children.

INTRODUCTION: Health-related quality of life in children who have undergone the Ross procedure has not been well characterised. The aim of this study was to characterise health-related quality of life in this cohort and compare to children with other CHD. METHOD: In this cross sectional, single-centre study, health-related quality of life was assessed in patients who underwent a non-neonatal Ross procedure using the Pediatric Quality of Life Inventory. Ross cohort scores were compared with healthy norms, patients with CHD requiring no surgical intervention or had curative surgery (Severity 2, S2) and patients who were surgically repaired with ≥1 surgical procedure and with significant residual lesion or need for additional surgery (Severity 3, S3). Associations between Pediatric Quality of Life Inventory score and patient factors were also examined. RESULTS: 68 patients completed surveys. Nearly one-sixth of patients had overall scores below the cut-off for at-risk status for impaired health-related quality of life. There was no difference in overall health-related quality of life score between the Ross cohort and healthy children (p = 0.56) and S2 cohort (p = 0.97). Health-related quality of life was significantly higher in the Ross cohort compared to S3 cohort (p = 0.02). This difference was driven by a higher psychosocial health-related quality of life in the Ross cohort as compared to S3 cohort (p = 0.007). Anxiety scores were significantly worse in the Ross cohort compared to both S2 (p = 0.001) and S3 (p = 0.0017), respectively. CONCLUSION: Children who have undergone a Ross procedure report health-related quality of life equivalent to CHD not requiring therapy and superior to CHD with residual lesions. Despite these reassuring results, providers should be aware of potential anxiety among Ross patients.

Neurocognitive function and health-related quality of life in adolescents and young adults with CHD with pulmonary valve dysfunction.

BACKGROUND: Neurocognitive impairment and quality of life are two important long-term challenges for patients with complex CHD. The impact of re-interventions during adolescence and young adulthood on neurocognition and quality of life is not well understood. METHODS: In this prospective longitudinal multi-institutional study, patients 13-30 years old with severe CHD referred for surgical or transcatheter pulmonary valve replacement were enrolled. Clinical characteristics were collected, and executive function and quality of life were assessed prior to the planned pulmonary re-intervention. These results were compared to normative data and were compared between treatment strategies. RESULTS: Among 68 patients enrolled from 2016 to 2020, a nearly equal proportion were referred for surgical and transcatheter pulmonary valve replacement (53% versus 47%). Tetralogy of Fallot was the most common diagnosis (59%) and pulmonary re-intervention indications included stenosis (25%), insufficiency (40%), and mixed disease (35%). There were no substantial differences between patients referred for surgical and transcatheter therapy. Executive functioning deficits were evident in 19-31% of patients and quality of life was universally lower compared to normative sample data. However, measures of executive function and quality of life did not differ between the surgical and transcatheter patients. CONCLUSION: In this patient group, impairments in neurocognitive function and quality of life are common and can be significant. Given similar baseline characteristics, comparing changes in neurocognitive outcomes and quality of life after surgical versus transcatheter pulmonary valve replacement will offer unique insights into how treatment approaches impact these important long-term patient outcomes.

The pediatric heart network's study on long-term outcomes of children with HLHS and the impact of Norwood Shunt type in the single ventricle reconstruction trial cohort (SVRIII): Design and adaptations.

BACKGROUND: The Single Ventricle Reconstruction (SVR) Trial was the first randomized clinical trial of a surgical approach for treatment of congenital heart disease. Infants with hypoplastic left heart syndrome (HLHS) and other single right ventricle (RV) anomalies were randomized to a modified Blalock Taussig Thomas shunt (mBTTS) or a right-ventricular-to-pulmonary-artery shunt (RVPAS) at the time of the Norwood procedure. The aim of the Long-term Outcomes of Children with HLHS and the Impact of Norwood Shunt Type (SVR III) study is to compare early adolescent outcomes including measures of cardiac function, transplant-free survival, and neurodevelopment, between those who received a mBTTS and those who received an RVPAS. METHODS: Transplant-free survivors of the SVR cohort were enrolled at 10 to 15 years of age for multifaceted in-person evaluation of cardiac function (cardiac magnetic resonance [CMR], echocardiogram and exercise test) and neurodevelopmental evaluation. Right ventricular ejection fraction measured by CMR served as the primary outcome. Development of arrhythmias, protein losing enteropathy, and other comorbidities were assessed through annual medical history interview. Through the course of SVR III, protocol modifications to engage SVR trial participants were designed to enhance recruitment and retention. CONCLUSIONS: Evaluation of long-term outcomes will provide important data to inform decisions about the shunt type placed at the Norwood operation and will improve the understanding of cardiovascular and neurodevelopmental outcomes for early adolescents with HLHS.

Facilitative interaction promotes occupancy of a desert amphibian across a climate gradient.

Biotic interactions and environmental factors influence a species' occurrence. Facilitative interactions have the potential to expand species occupancy and mitigate abiotic stress, but are often not considered. The Great Basin clade of the Columbia spotted frog (Rana luteiventris) is an aquatic amphibian found in the arid and semi-arid Great Basin, USA. Aquatic resources in this system are limited and likely to change under future climate scenarios. American beavers (Castor canadensis) are ecosystem engineers that impact the surrounding landscape by increasing water availability. Consequently, beaver-created habitat can facilitate the presence of other species by providing the aquatic resources required by many aquatic and riparian animals. Our objective was to understand patterns of co-occurrence between Columbia spotted frogs and beavers across environmental gradients in the Great Basin, USA. We used environmental DNA detections to quantify the co-occurrence of Columbia spotted frog and beaver using a two-species occupancy framework. At the lowest annual precipitation (202 mm), Columbia spotted frogs were 3× (95% CI 2.35, 3.96) more likely to occur with beavers than without; however, they were less likely to occur with beavers once precipitation was > 380 mm. Thus, beaver activity may increase aquatic resources for Columbia spotted frogs in the Great Basin that may mitigate changing precipitation patterns under climate change. Facilitative interactions likely extend to other aquatic species in arid systems and highlight an important consideration for ecologists when evaluating a species' response to climate change, and may promote the formation of refugia for species with strict abiotic tolerances and dispersal limitations.

Impact of tight glycemic control and hypoglycemia after pediatric cardiac surgery on neurodevelopmental outcomes at three years of age: Findings from a randomized clinical trial.

BACKGROUND: Studies examining the impact of randomization As per standard instruction, city is required for affiliations; however, this information is missing in affiliation 6. Please check if the provided city is correct and amend if necessary. to tight glycemic control (TGC) and resultant hypoglycemia on later neurodevelopmental outcomes have produced mixed results. Our study examined this association in children undergoing cardiac surgery. METHODS: Participants who were enrolled in the Safe Pediatric Euglycemia after Cardiac Surgery (SPECS) trial returned for neurodevelopmental (ND) follow-up between 30 to 42.5 months of age. ND outcomes were assessed using the Bayley Scales of Infant and Toddler Development, Third Edition. ND scores were compared between the TGC and standard care treatment groups and between patients with moderate to severe and no to mild hypoglycemia. As a secondary analysis, to increase sample size and power, we combined the three-year-old assessments with previously collected assessments done at < 30 months of age to further examine differences between groups longitudinally. RESULTS: Among the 269 participants who completed neurodevelopmental evaluation (in-person testing or questionnaires) at three years of age (follow-up rate, 31%), there were no statistically significant differences in ND outcomes according to treatment group or hypoglycemia status. In the combined analysis of all evaluations (from 9 to 42.5 months of age), we found no treatment group differences. However, in these longitudinal analyses, children who experienced moderate to severe hypoglycemia had lower scores on the Bayley-III cognitive and motor domains compared to children with no to mild hypoglycemia. CONCLUSIONS: For infants undergoing cardiac surgery, there was no impact of tight glycemic control on neurodevelopmental outcomes. Moderate to severe hypoglycemia was associated with worse ND outcomes in longitudinal analyses. TRIAL REGISTRATION: ClinicalTrials.gov NCT00443599. Registered: November 2016.

Rapid detection of amphibian chytrid fungus Batrachochytrium dendrobatidis using in situ DNA extraction and a handheld mobile thermocycler.

The amphibian chytrid fungus (Bd) has caused declines and some extinctions of amphibian populations worldwide. Early and accurate Bd detection is essential for management of susceptible anurans. We analyzed the effectiveness of in situ DNA extraction with a handheld mobile quantitative PCR (qPCR) thermocycler to detect Bd on frog skin swabs and in water samples using environmental DNA (eDNA). We collected duplicate eDNA samples and skin swabs from 3 Bd-positive Rana sierrae populations. We processed one set of samples using a field protocol (a handheld thermocycler) and the other half using a standard lab protocol. We detected Bd DNA in all R. sierrae swabbed using both the field and lab protocols. We also detected Bd DNA in eDNA samples at all sites, although the field and lab protocols failed to detect Bd eDNA at separate singular sites; results from the field and lab eDNA protocol did not match. The probability of detecting Bd DNA in the technical replicates was lower for the field protocol than the lab protocol, suggesting the field protocol has lower sensitivity and may not detect low quantities of DNA. Our results suggest that the field extraction protocol using a handheld qPCR platform is a promising tool for rapid detection of Bd in susceptible amphibian populations, yielding accurate results in less than 60 min. However, the applied field protocol may be prone to false negatives when analyzing low-quantity DNA samples such as eDNA water samples or frog swabs with low pathogen loads.

Trajectories in Neurodevelopmental, Health-Related Quality of Life, and Functional Status Outcomes by Socioeconomic Status and Maternal Education in Children with Single Ventricle Heart Disease.

Trajectories of neurodevelopment and quality of life were analyzed in children with hypoplastic left heart syndrome according to socioeconomic status (SES) and maternal education. Lower SES and less maternal education were associated with greater early delays in communication and problem-solving and progressive delays in problem-solving and fine motor skills over time.

Drivers of distributions and niches of North American cold-adapted amphibians: evaluating both climate and land use.

Species distribution estimates are often used to understand the niche of a species; however, these are often based solely on climatic predictors. When the influences of biotic factors are ignored, erroneous inferences about range and niche may be made. We aimed to integrate climate data with a unique set of available land cover and land use data for the six cold-adapted amphibians of North America (Ambystoma macrodactylum, Anaxyrus hemiophrys, Anaxyrus boreas, Pseudacris maculata, Rana sylvatica, Rana luteiventris) to determine the relative importance of climate and non-climate drivers through the use of ecological niche models for present-day range estimates. We compared climate-only, land use-only, and combination models of climate and land use, derived from two different model selection techniques, to determine which was most likely to drive current distributions of cold-adapted amphibian species. Land use layers included land cover type, human population, vegetation type, ecoregion, and the overall human footprint. The most supported models included both climate and land use, with climate and human footprint variables having the highest permutation importance and percent contribution. Models that incorporated climate and land use data performed best as measured with AIC and AUC, although qualitatively most underestimated the northern range edge, implying potential sampling bias or locations of reduced habitat quality for these species in the northern area of the ranges. There were small differences in overall combination models dependent on the method of model selection. The overall effect sizes of landscape factors within the combination models were small except for one landscape feature: human footprint, which incorporated multiple aspects of anthropogenic change on the landscape, including human population density, travel access, and agricultural impact. This aspect of the landscape was just as important as climate, and counter to what we expected, the association was mostly positive, with a negative response only occurring at very high levels. This highlights the importance of moving beyond climate only species range estimates as land cover, specifically human impact, may be driving the patterns of species' ranges.

An introduction to and review of cardiac neurodevelopment: the risks and recommended approaches.

PURPOSE OF REVIEW: To introduce the reader to the current understanding of the neurocognitive profile of congenital heart disease (CHD) survivors, the risk factors that may influence outcomes, and to the recommendations for cardiac neurodevelopmental care. RECENT FINDINGS: A growing body of literature has shown that survivors of CHD are at increased risk for neurodevelopmental impairments. Multiple elements influence each patient's risk, which likely begins in utero and extends to perioperative management, surgical considerations, and long-term clinical care. Additionally, sociodemographic factors may compound these risks. Serial developmental follow-up is recommended for children with critical CHD. SUMMARY: Though there are some clinical factors that increase risk, based on the high rate of developmental impairments for children with CHD, serial evaluations are recommended. Multidisciplinary and multicenter collaboration is ongoing and will facilitate moving this field forward to improve neurodevelopmental outcomes for children with CHD.

Low occurrence of ranavirus in the Prairie Pothole Region of Montana and North Dakota (USA) contrasts with prior surveys.

Ranaviruses are emerging pathogens that have caused mortality events in amphibians worldwide. Despite the negative effects of ranaviruses on amphibian populations, monitoring efforts are still lacking in many areas, including in the Prairie Pothole Region (PPR) of North America. Some PPR wetlands in Montana and North Dakota (USA) have been contaminated by energy-related saline wastewaters, and increased salinity has been linked to greater severity of ranavirus infections. In 2017, we tested tissues from larvae collected at 7 wetlands that ranged in salinity from 26 to 4103 mg Cl l-1. In 2019, we used environmental DNA (eDNA) to test for ranaviruses in 30 wetlands that ranged in salinity from 26 to 11754 mg Cl l-1. A previous study (2013-2014) found that ranavirus-infected amphibians were common across North Dakota, including in some wetlands near our study area. Overall, only 1 larva tested positive for ranavirus infection, and we did not detect ranavirus in any eDNA samples. There are several potential reasons why we found so little evidence of ranaviruses, including low larval sample sizes, mismatch between sampling and disease occurrence, larger pore size of our eDNA filters, temporal variation in outbreaks, low host abundance, or low occurrence or prevalence of ranaviruses in the wetlands we sampled. We suggest future monitoring efforts be conducted to better understand the occurrence and prevalence of ranaviruses within the PPR.

Utilisation of early intervention services in infants with congenital heart disease following open-heart surgery.

OBJECTIVE: To examine the use of early intervention services in infants with CHD after open-heart surgery and identify factors associated with receipt of services. STUDY DESIGN: Surveys were administered to caregivers of infants who underwent open-heart surgery before 1 year of age at a single institution between July, 2017 and July, 2018. Information regarding the infant's use of early intervention services and the caregiver's experience with the programme was obtained. Clinical data were retrieved from the medical record review. Logistic regression identified factors associated with receipt of services. RESULTS: The study included 158 eligible infants. Ninety-eight caregivers (62%) completed the surveys. Of those surveyed, 53.1% of infants were currently or previously enrolled in early intervention services. Infants most frequently received physical therapy (76.9%). The majority of caregivers found services to be moderately/very helpful (92.3%) and sufficient for their child (76.9%). In the univariate analysis, single-ventricle disease, known syndrome/genetic abnormality, extracardiac anomaly, and longer intensive care and hospital length of stay were associated with receipt of services. Single-ventricle disease (p = 0.004) and known syndrome/genetic abnormality (p < 0.0001) remained independently associated with receipt of services in the multivariable analysis. CONCLUSION: Amongst infants at risk for neurodevelopmental deficits, approximately half received services after open-heart surgery. Caregivers expressed satisfaction with the programme. While infants with single-ventricle disease and a known syndrome/genetic abnormality were more likely to receive early intervention services, many at-risk infants with CHD failed to receive services. Further research is needed to identify barriers to early intervention services and promote developmental outcomes.

The origins and development of the cardiac neurodevelopment outcome collaborative: creating innovative clinical, quality improvement, and research opportunities.

Compared to the general population, individuals with complex congenital heart disease are at increased risk for deficits in cognitive, neurodevelopmental, psychosocial, and physical functioning, resulting in a diminished health-related quality of life. These deficits have been well described over the past 25 years, but significant gaps remain in our understanding of the best practices to improve neurodevelopmental and psychosocial outcomes and health-related quality of life for individuals with paediatric and congenital heart disease. Innovative clinical, quality improvement, and research opportunities with collaboration across multiple disciplines and institutions were needed to address these gaps. The Cardiac Neurodevelopmental Outcome Collaborative was founded in 2016 with a described mission to determine and implement best practices of neurodevelopmental and psychosocial services for individuals and their families with paediatric and congenital heart disease through clinical, quality improvement, and research initiatives. The vision is to be a multi-centre, multi-national, multi-disciplinary group of healthcare professionals committed to working together and partnering with families to optimise neurodevelopmental outcomes for individuals with paediatric and congenital heart disease through clinical, quality, and research initiatives, intending to maximise quality of life for every individual across the lifespan. This manuscript describes the development and organisation of the Cardiac Neurodevelopmental Outcome Collaborative.

Variations in practice in cardiac neurodevelopmental follow-up programs.

Over the last two decades, heart centres have developed strategies to meet the neurodevelopmental needs of children with congenital heart disease. Since the publication of guidelines in 2012, cardiac neurodevelopmental follow-up programmes have become more widespread. Local neurodevelopmental programmes, however, have been developed independently in widely varying environments. We sought to characterise variation in structure and personnel in cardiac neurodevelopmental programmes. A 31-item survey was sent to all member institutions of the Cardiac Neurodevelopmental Outcome Collaborative. Multidisciplinary teams at each centre completed the survey. Responses were compiled in a descriptive fashion. Of the 29 invited centres, 23 responded to the survey (79%). Centres reported more anticipated neurodevelopment visits between birth and 5 years of age (median 5, range 2-8) than 5-18 years (median 2, range 0-10) with 53% of centres lacking any standard for routine neurodevelopment evaluations after 5 years of age. Estimated annual neurodevelopment clinic volume ranged from 85 to 428 visits with a median of 16% of visits involving children >5 years of age. Among responding centres, the Bayley Scales of Infant and Toddler Development and Wechsler Preschool and Primary Scale of Intelligence were the most routinely used tests. Neonatal clinical assessment was more common (64%) than routine neonatal brain imaging (23%) during hospitalisation. In response to clinical need and published guidelines, centres have established formal cardiac neurodevelopment follow-up programmes. Centres vary considerably in their approaches to routine screening and objective testing, with many centres currently focussing their resources on evaluating younger patients.

Transplant-Free Survival and Interventions at 6 Years in the SVR Trial.

BACKGROUND: In the SVR trial (Single Ventricle Reconstruction), 1-year transplant-free survival was better for the Norwood procedure with right ventricle-to-pulmonary artery shunt (RVPAS) compared with a modified Blalock-Taussig shunt in patients with hypoplastic left heart and related syndromes. At 6 years, we compared transplant-free survival and other outcomes between the groups. METHODS: Medical history was collected annually using medical record review, telephone interviews, and the death index. The cohort included 549 patients randomized and treated in the SVR trial. RESULTS: Transplant-free survival for the RVPAS versus modified Blalock-Taussig shunt groups did not differ at 6 years (64% versus 59%, P=0.25) or with all available follow-up of 7.1±1.6 years (log-rank P=0.13). The RVPAS versus modified Blalock-Taussig shunt treatment effect had nonproportional hazards (P=0.009); the hazard ratio (HR) for death or transplant favored the RVPAS before stage II surgery (HR, 0.66; 95% confidence interval, 0.48-0.92). The effect of shunt type on death or transplant was not statistically significant between stage II to Fontan surgery (HR, 1.36; 95% confidence interval, 0.86-2.17; P=0.17) or after the Fontan procedure (HR, 0.76; 95% confidence interval, 0.33-1.74; P=0.52). By 6 years, patients with RVPAS had a higher incidence of catheter interventions (0.38 versus 0.23/patient-year, P<0.001), primarily because of more interventions between the stage II and Fontan procedures (HR, 1.72; 95% confidence interval, 1.00-3.03). Complications did not differ by shunt type; by 6 years, 1 in 5 patients had had a thrombotic event, and 1 in 6 had had seizures. CONCLUSIONS: By 6 years, the hazards of death or transplant and catheter interventions were not different between the RVPAS versus modified Blalock-Taussig shunt groups. Children assigned to the RVPAS group had 5% higher transplant-free survival, but the difference did not reach statistical significance, and they required more catheter interventions. Both treatment groups have accrued important complications. CLINICAL TRIAL REGISTRATION: URL: https://www.clinicaltrials.gov. Unique identifier: NCT00115934.