Neurocognitive Dysfunction and Smaller Brain Volumes in Adolescents and Adults With a Fontan Circulation.

BACKGROUND: Neurocognitive outcomes beyond childhood in people with a Fontan circulation are not well defined. This study aimed to investigate neurocognitive functioning in adolescents and adults with a Fontan circulation and associations with structural brain injury, brain volumetry, and postnatal clinical factors. METHODS: In a binational study, participants with a Fontan circulation without a preexisting major neurological disability were prospectively recruited from the Australia and New Zealand Fontan Registry. Neurocognitive function was assessed by using Cogstate software in 107 participants with a Fontan circulation and compared with control groups with transposition of the great arteries (n=50) and a normal circulation (n=41). Brain MRI with volumetric analysis was performed in the participants with a Fontan circulation and compared with healthy control data from the ABIDE I and II (Autism Brain Imaging Data Exchange) and PING (Pediatric Imaging, Neurocognition, and Genetics) data repositories. Clinical data were retrospectively collected. RESULTS: Of the participants with a Fontan circulation who had a neurocognitive assessment, 55% were male and the mean age was 22.6 years (SD 7.8). Participants with a Fontan circulation performed worse in several areas of neurocognitive function compared with those with transposition of the great arteries and healthy controls (P<0.05). Clinical factors associated with worse neurocognitive outcomes included more inpatient days during childhood, younger age at Fontan surgery, and longer time since Fontan procedure (P<0.05). Adults with a Fontan circulation had more marked neurocognitive dysfunction than adolescents with a Fontan circulation in 2 domains (psychomotor function, P=0.01 and working memory, P=0.02). Structural brain injury was present in the entire Fontan cohort; the presence of white matter injury was associated with worse paired associate learning (P<0.001), but neither the presence nor severity of infarct, subcortical gray matter injury, and microhemorrhage was associated with neurocognitive outcomes. Compared with healthy controls, people with a Fontan circulation had smaller global brain volumes (P<0.001 in all regions) and smaller regional brain volumes in most cerebral cortical regions (P<0.05). Smaller global brain volumes were associated with worse neurocognitive functioning in several domains (P<0.05). A significant positive association was also identified between global brain volumes and resting oxygen saturations (P≤0.04). CONCLUSIONS: Neurocognitive impairment is common in adolescents and adults with a Fontan circulation and is associated with smaller gray and white matter brain volume. Understanding modifiable factors that contribute to brain injury to optimize neurocognitive function is paramount.

Ex vivo cardiovascular magnetic resonance diffusion weighted imaging in congenital heart disease, an insight into the microstructures of tetralogy of Fallot, biventricular and univentricular systemic right ventricle.

PURPOSE: Common types of congenital heart disease exhibit a variety of structural and functional variations which may be accompanied by changes in the myocardial microstructure. We aimed to compare myocardial architecture from magnetic resonance diffusion tensor imaging (DTI) in preserved pathology specimens. MATERIALS AND METHODS: Pathology specimens (n = 24) formalin-fixed for 40.8 ± 7.9 years comprised tetralogy of Fallot (TOF, n = 10), dextro-transposition of great arteries (D-TGA, n = 8) five with ventricular septal defect (VSD), systemic right ventricle (n = 4), situs inversus totalis (SIT, n = 1) and levo-TGA (L-TGA, n = 1). Specimens were imaged using a custom spin-echo sequence and segmented automatically according to tissue volume fraction. In each specimen T1, T2, fractional anisotropy, mean diffusivity, helix angle (HA) and sheet angle (E2A) were quantified. Pathologies were compared according to their HA gradient, HA asymmetry and E2A mean value in each myocardial segment (anterior, posterior, septal and lateral walls). RESULTS: TOF and D-TGA with VSD had decreased helix angle gradient by - 0.34°/% and remained symmetric in the septum in comparison to D-TGA without VSD. Helix angle range was decreased by 45°. It was associated with a decreased HA gradient in the right ventricular (RV) wall, i.e. predominant circumferential myocytes. The sheet angle in the septum of TOF was opposing those of the left ventricular (LV) free wall. Univentricular systemic RV had the lowest HA gradient (- 0.43°/%) and the highest HA asymmetry (75%). HA in SIT was linear, asymmetric, and reversed with a sign change at about 70% of the depth at mid-ventricle. In L-TGA with VSD, HA was asymmetric (90%) and its gradients were decreased in the septum, anterior and lateral wall. CONCLUSION: The organization of the myocytes as determined by DTI differs between TOF, D-TGA, L-TGA, systemic RV and SIT specimens. These differences in cardiac structure may further enlighten our understanding of cardiac function in these diverse congenital heart diseases.

Pulse oximetry screening in a midwifery-led maternity setting with high antenatal detection of congenital heart disease.

AIM: To assess local and individual factors that should be considered in the design of a pulse oximetry screening strategy in New Zealand's midwifery-led maternity setting. METHODS: An intervention study was conducted over 2 years. Three hospitals and four primary maternity units participated in the study. Post-ductal saturation levels were measured on well infants with a gestation of ≥35 weeks. Infant activity and age (hours) at the time of the test were recorded. RESULTS: Screening was performed on 16 644 of 27 172 (61%) eligible infants. The age at which the screening algorithm was initiated varied significantly among centres. The probability of achieving a pass result (saturations ≥95%) in the context of no underlying pathology ranged from .94 for an unsettled infant screened <4 hours of age to .99 (P < .001) when the test was performed after 24 hours on a settled infant. Forty-eight (0.3%) infants failed to reach saturation targets: 37 had significant pathology of which three had cardiac disease. CONCLUSION: Screening practices were influenced by the setting in which it was undertaken. Infant activity and age at the time of testing can influence saturation levels. Screening is associated with the identification of significant non-cardiac pathology.

Newborn pulse oximetry screening in the context of a high antenatal detection rate of critical congenital heart disease.

AIM: Assess the potential additional benefit from pulse oximetry screening in the early detection of critical congenital heart disease in a country with a well-developed antenatal ultrasound screening programme. METHODS: Live-born infants, pregnancy terminations and stillbirths from 20 weeks' gestational age, between 2013 and 2015, with critical cardiac defects defined as primary or secondary targets of pulse oximetry screening were identified. Critical defects were those resulting in the death of a fetus or an infant in the first 28 days after birth, or a defect requiring intervention in the first 28 days. RESULTS: Two hundred and sixty-eight infants and Fetuses were identified. Antenatal detection rates improved from 69% to 77% over the study period. An associated co-morbidity improved antenatal detection rates. Twenty-seven live-born infants were diagnosed after discharge: 15 aortic arch obstruction (AAO); 10 d-loop transposition of the great arteries (d-TGA), and two total anomalous pulmonary venous drainage (TAPVD). Of these, five with AAO, nine with d-TGA and likely both with TAPVD could potentially have been detected with oximetry screening. CONCLUSION: The antenatal detection of critical cardiac anomalies continues to improve in New Zealand. Despite high antenatal detection rates for most lesions, universal postnatal oximetry screening has the potential to improve early detection.

CSANZ Position Statement on COVID-19 From the Paediatric and Congenital Council✰.

At the time of writing (25 May 2020), there have been nearly 4.4 million infections and 300,000 deaths worldwide related to COVID-19, an infection caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Australia (currently 6,900 infections and 98 deaths) and New Zealand (1,500 infections and 21 deaths) have thus far been less affected than other regions. Risk factors for more severe disease include older age and pre-existing cardiovascular disease. The purposes of this document from the Paediatric and Congenital Council of the Cardiac Society of Australia and New Zealand (CSANZ) are to: 1) To review the mechanisms for cardiac involvement in COVID-19, specifically as they may impact patients with childhood and adult congenital heart disease (CHD); 2) To review the impact of SARS-CoV-2 infection in the paediatric population; 3) To review available data on the risks related to COVID-19 for childhood heart disease and adult CHD; 4) To provide guidance for childhood heart disease and adult CHD units in our Australasian region to re-organise services during the pandemic, so as to protect a highly specialised workforce and yet continue to provide an essential service; and 5) To review risk reduction strategies for acquiring COVID-19 for patients with childhood heart disease or adult CHD. Eleven (11) recommendations relevant to the care of children with heart disease and adults with CHD to mitigate the impact of COVID-19 are highlighted through the document.

Management of People With a Fontan Circulation: a Cardiac Society of Australia and New Zealand Position statement.

The Fontan circulation describes the circulatory state resulting from an operation in congenital heart disease where systemic venous return is directed to the lungs without an intervening active pumping chamber. As survival increases, so too does recognition of the potential health challenges. This document aims to allow clinicians, people with a Fontan circulation, and their families to benefit from consensus agreement about management of the person with a Fontan circulation. The document was crafted with input from a multidisciplinary group of health care providers as well as individuals with a Fontan circulation and families. It is hoped that the shared common vision of long-term wellbeing will continue to drive improvements in care and quality of life in this patient population and eventually translate into improved survival. KEYPOINTS.

Antenatal Detection of Treatable Critical Congenital Heart Disease Is Associated with Lower Morbidity and Mortality.

OBJECTIVE: To establish the impact that timing of diagnosis and place of birth have on neonatal outcomes in those with readily treatable critical congenital heart disease. STUDY DESIGN: This was a population-based study with a complete national cohort of live-born infants with transposition of the great arteries and aortic arch obstruction in New Zealand between 2006 and 2014. Timing of diagnosis, place of birth, survival to surgery, in-hospital events, and neonatal mortality were reviewed. Live births with a gestation of ≥35 weeks and without associated major extracardiac anomalies were included for analysis. RESULTS: A total of 166 live-born infants with transposition of the great arteries and 87 with aortic arch obstruction were included. Antenatal detection increased from 32% in the first 3 years to 47% in the last 3 years (P = .05). During the same period, neonatal mortality decreased from 9% to 1% (P = .02). No deaths occurred after surgical intervention. An antenatal diagnosis was associated with decreased mortality (1/97 [1%] vs 11/156 [7%]; P = .03) and birth outside the surgical center was associated with increased risk of mortality (11/147 [7%] vs 1/106 [1%]; P = .02). Those with an antenatal diagnosis required fewer hours of mechanical ventilation (P = .02) and had shorter durations of hospital stay (P = .05) compared with those diagnosed >48 hours after birth. CONCLUSIONS: The mortality risk for transposition of the great arteries and critical aortic arch obstruction is greatest before cardiac surgery. Improved antenatal detection allowing delivery at a surgical center is associated with reduced mortality.

The New Zealand Norwood Procedure Experience: 22-Year Cumulative Review.

BACKGROUND: Babies born with a functional single ventricle heart and systemic outflow tract obstruction may require a Norwood (NW) procedure as the first of three staged procedures to obtain a Fontan circulation. This procedure and the following treatment pathway are associated with significant mortality. Risk factors for the Norwood procedure and the subsequent pathway are not necessarily the same. To identify these factors within New Zealand, the collective experience with the Norwood procedure was examined. METHODS: Charts from 133 New Zealand children undergoing Norwood procedure from 1992 to 2014 were examined. Deaths were assigned as "early" (30-day or in-hospital) or "late" (based on timeframe from the Norwood procedure). Cardiac anatomic, patient demographic and surgery related variables were examined. Important risk factors were identified using univariate and multivariate analysis. Kaplan-Meier survival curves were calculated. RESULTS: Survival following the Norwood procedure was 83%. Overall survival was 67% at six months, 65% at one year, and 63% at five years. Size of the ascending aorta appeared as an important risk factor with "early" death while New Zealand deprivation index and low birth weight appeared more important for "late" death. These factors each impacted overall survival. CONCLUSIONS: The Norwood procedure and subsequent medical treatment carries significant mortality in New Zealand. Cardiac anatomical factors affect survival of the immediate Norwood procedure whereas social factors weigh more significantly on longer term survival. Nevertheless, both anatomical and social factors carry real survival risk.

Redefining expectations of long-term survival after the Fontan procedure: twenty-five years of follow-up from the entire population of Australia and New Zealand.

BACKGROUND: The life expectancy of patients undergoing a Fontan procedure is unknown. METHODS AND RESULTS: Follow-up of all 1006 survivors of the 1089 patients who underwent a Fontan procedure in Australia and New Zealand was obtained from a binational population-based registry including all pediatric and adult cardiac centers. There were 203 atriopulmonary connections (AP; 1975-1995), 271 lateral tunnels (1988-2006), and 532 extracardiac conduits (1997-2010). The proportion with hypoplastic left heart syndrome increased from 1/173 (1%) before 1990 to 80/500 (16%) after 2000. Survival at 10 years was 89% (84%-93%) for AP and 97% (95% confidence interval [CI], 94%-99%) for lateral tunnels and extracardiac conduits. The longest survival estimate was 76% (95% CI, 67%-82%) at 25 years for AP. AP independently predicted worse survival compared with extracardiac conduits (hazard ratio, 6.2; P<0.001; 95% CI, 2.4-16.0). Freedom from failure (death, transplantation, takedown, conversion to extracardiac conduits, New York Heart Association III/IV, or protein-losing enteropathy/plastic bronchitis) 20 years after Fontan was 70% (95% CI, 63%-76%). Hypoplastic left heart syndrome was the primary predictor of Fontan failure (hazard ratio, 3.8; P<0.001; 95% CI, 2.0-7.1). Ten-year freedom from failure was 79% (95% CI, 61%-89%) for hypoplastic left heart syndrome versus 92% (95% CI, 87%-95%) for other morphologies. CONCLUSIONS: The long-term survival of the Australia and New Zealand Fontan population is excellent. Patients with an AP Fontan experience survival of 76% at 25 years. Technical modifications have further improved survival. Patients with hypoplastic left heart syndrome are at higher risk of failure. Large, comprehensive registries such as this will further improve our understanding of late outcomes after the Fontan procedure.

Dilated cardiomyopathy in children: Review of all presentations to a children's hospital over a 5-year period and the impact of family cardiac screening.

AIM: This study aims to report the aetiology and outcome of dilated cardiomyopathy (DCM) in children from New Zealand and to assess the outcome of protocolised family cardiac investigation introduced in 2007. METHODS: Retrospective review of all patients with DCM, aged <15 years, presenting to the children's hospital between 01/01/2007 and 01/03/2012. Oncology patients were excluded. Family screening results were assessed. RESULTS: Thirty-five patients were identified. Median age 1 year: 26/35 (74%) <5 years. Ethnicity: New Zealand European 14/35 (40%), Maori 11/35 (31%), Pacific Island 5/35 (14%) and other 5/35(14%). Excluding the four cases with biopsy-proven myocarditis, family cardiac screening was documented in 15/31 (48%). Of these, 7/15 (47%) had a positive family screen. Six previously undiagnosed DCM cases were found in these families. Five of the seven familial DCM cases had evidence of viral infection at presentation. Final aetiology: Myocarditis, 15/35 (43%), with Parvovirus being the commonest virus identified 10/15(67%). Familial, seven (20%), Idiopathic, seven (20%), Others, six (17%). Overall outcome was death 10/35(28%), ongoing dysfunction 16/35 (46%) and normalisation in 9/35 (26%). The median time to death from diagnosis was 1.5 months (3 days to 3 years). Death occurred in 4/7 with familial DCM (57%) compared with 6/28 (21%) among the others (ns). Recovery occurred in 0/7 with familial DCM versus 4/4 with biopsy proven myocarditis (P < 0.05). CONCLUSIONS: Almost half of families screened had evidence of familial DCM, and these children carried a worse prognosis. Maori and Pacific Island children seem to be over-represented. Family investigation led to the identification of many pre-symptomatic individuals even when viral aetiology was suspected initially.

Mitral valve geometry in paediatric rheumatic mitral regurgitation.

Rheumatic mitral valve disease is associated with valvulitis and valvular regurgitation; however, the effect of the rheumatic process on the mitral valve geometry and function is not well understood. To assess mitral valve annulus remodelling in rheumatic mitral valve disease, 16 subjects aged 6-15 years with rheumatic mitral valve regurgitation [MR] [6 mild or moderate (Group 1), 10 severe (Group 2)] and 7 age- and body size-matched normal controls with adequate trans-thoracic echocardiograms were recruited. None of the patients had undergone surgical intervention and none had more than mild aortic regurgitation. None of the patients had mitral stenosis. 3D mitral valve geometry was assessed using a Tomtec system. The non-planar angle was increased in all subjects during early (control 147° ± 10, Group 1 168° ± 9, Group 2 166° ± 10; p < 0.05) and late systole (control 149° ± 12, Group 1 162° ± 10, Group 2 164° ± 6; p < 0.05), indicating loss of saddle shape. 2D annular area increased in Group 2 (control 397 ± 48 mm(2)/m(2) vs Group 2 739 ± 207, p < 0.05) with no significant change in annular perimeter indicating leaflet effacement. Mitral valve area correlated with left ventricular size (p < 0.001, r (2) = 0.74). There was no significant change in valve area and perimeter between early and late systole. Remodelling of the mitral valve apparatus in childhood rheumatic heart disease results in abnormal annular geometry. The mitral valve loses its saddle shape regardless of the severity of MR. This may be a consequence of inflammation on the fibrous trigones and surrounding annulus. In contrast, annular area enlargement occurs as a result of leaflet effacement and relates to MR severity and LV size.

Emergency arterial switch: Rescue therapy for life-threatening hypoxemia in infants with transposition of great arteries with intact intraventricular septum.

OBJECTIVE: A small percentage of infants with d-loop transposition of the great arteries with intact intraventricular septum have life-threatening refractory hypoxemia often due to coexistent persistent pulmonary hypertension of the newborn. In this case series we describe the outcomes of a "rescue" emergency arterial switch operation (ASO). METHODS: We undertook a retrospective medical record analysis of infants with d-loop transposition of the great arteries with intact intraventricular septum who underwent an ASO in New Zealand from January 1, 1996, to April 30, 2017. Data were compared for those who received an emergency ASO and those with a nonemergency ASO for descriptive purposes. An emergency ASO was defined as one that was undertaken for life-threatening refractory hypoxemia when the only alternative stabilization strategy was preoperative extracorporeal life support. Primary outcome measures were 30-day postoperative mortality and abnormal neurodevelopmental outcome in the survivors. Secondary outcomes were low cardiac output, arrhythmia, renal dysfunction, postoperative seizures, and length of stay. Other known risk factors for morbidity and mortality were also assessed. RESULTS: Two hundred seventy-two infants underwent an ASO with 25 (9%) who received an emergency ASO. No infants received preoperative extracorporeal life support. The emergency group had greater 30-day postoperative mortality (8.0% vs 0.4%; P = .01) with no difference in abnormal neurodevelopmental outcome among the survivors (17.4% vs 13.8%; P = .35). The emergency group had more therapies for low cardiac output syndrome, more postoperative seizures, and a longer length of stay. CONCLUSIONS: An emergency ASO is a definitive rescue therapy that can be undertaken with acceptable mortality and neurodevelopmental outcome with consideration of the preoperative clinical state.

High burden of rheumatic heart disease confirmed by echocardiography among Pacific adults living in New Zealand.

BACKGROUND: Despite numerous echocardiographic screening studies of children in high incidence acute rheumatic fever (ARF)/rheumatic heart disease (RHD) communities, little is known about the prevalence of RHD in adults in these populations.We sought to determine the prevalence of RHD in an urban area of South Auckland, New Zealand, where previous studies had shown the prevalence of RHD in children to be around 2%. METHODS: A cross-sectional screening study was conducted between 2014 and 2016. Echocardiography clinics were conducted at an urban Pacific-led primary healthcare clinic in New Zealand. Eligible persons aged 16-40 years were recruited according to a stratified randomised approach. Echocardiograms were performed with a standardised image acquisition protocol and reported by cardiologists. RESULTS: There were 465 individuals who underwent echocardiograms. The overall prevalence of RHD (define and borderline) was 56 per 1000 (95% CI 36 to 78 per 1000). Definite RHD was found in 10 individuals (4 of whom were already under cardiology review at a hospital clinic) with a prevalence of 22 per 1000 (95% CI 9 to 36 per 1000). Non-rheumatic cardiac abnormalities were found in 29 individuals. CONCLUSIONS: There is a high burden of both rheumatic and non-rheumatic cardiac abnormalities in this population. Rates described in New Zealand are as high as lower-middle-income countries in Africa. Addressing knowledge gaps regarding the natural history of RHD detected by echocardiography in adults is a priority issue for the international RHD community.

Factors influencing the choice-of-care pathway and survival in the fetus with hypoplastic left heart syndrome in New Zealand: a population-based cohort study.

OBJECTIVES: To better understand the relative influence of fetal and maternal factors in determining the choice-of-care pathway (CCP) and outcome in the fetus with hypoplastic left heart syndrome (HLHS). DESIGN: A retrospective, population-based study of fetuses with HLHS from a national dataset with near-complete case ascertainment from 20 weeks' gestation. Fetal cardiac and non-cardiac factors were recorded from the patient record and maternal factors from the national maternity dataset. The primary endpoint was a prenatal decision for active treatment after birth (intention-to-treat). Factors associated with a delayed diagnosis (≥24 weeks' gestation) were also reviewed. Secondary endpoints included proceeding to surgical treatment, and 30-day postoperative mortality in liveborns with an intention-to-treat. SETTING: New Zealand population-wide. PARTICIPANTS: Fetuses with a prenatal diagnosis of HLHS between 2006 and 2015. RESULTS: Of 105 fetuses, the CCP was intention-to-treat in 43 (41%), and pregnancy termination or comfort care in 62 (59%). Factors associated with intention-to-treat by multivariable analysis included a delay in diagnosis (OR: 7.8, 95% CI: 3.0 to 20.6, p<0.001) and domicile in the maternal fetal medicine (MFM) region with the most widely dispersed population (OR: 5.3, 95% CI: 1.4 to 20.3, p=0.02). Delay in diagnosis was associated with Maori maternal ethnicity compared with European (OR: 12.9, 95% CI: 3.1 to 54, p<0.001) and greater distance from the MFM centre (OR: 3.1, 95% CI: 1.2 to 8.2, p=0.02). In those with a prenatal intention-to-treat, a decision not to proceed to surgery was associated with maternal ethnicity other than European (p=0.005) and the presence of major non-cardiac anomalies (p=0.01). Thirty-day postoperative mortality occurred in 5/32 (16%) and was more frequent when there were major non-cardiac anomalies (p=0.02). CONCLUSIONS: Factors associated with the prenatal CCP relate to healthcare access. Anatomic characteristics impact treatment decisions after birth and early postoperative mortality. The association of ethnicity with delayed prenatal diagnosis and postnatal decision-making suggests systemic inequity and requires further investigation.

From fetus to neonate: A review of cardiovascular modeling in early life.

Computational modeling has well-established utility in the study of cardiovascular hemodynamics, with applications in medical research and, increasingly, in clinical settings to improve the diagnosis and treatment of cardiovascular diseases. Most cardiovascular models developed to date have been of the adult circulatory system; however, the perinatal period is unique as cardiovascular physiology undergoes drastic changes from the fetal circulation, during the birth transition, and into neonatal life. There may also be further complications in this period: for example, preterm birth (defined as birth before 37 completed weeks of gestation) carries risks of short-term cardiovascular instability and is associated with increased lifetime cardiovascular risk. Here, we review computational models of the cardiovascular system in early life, their applications to date and potential improvements and enhancements of these models. We propose a roadmap for developing an open-source cardiovascular model that spans the fetal, perinatal, and postnatal periods. This article is categorized under: Cardiovascular Diseases > Computational Models Cardiovascular Diseases > Biomedical Engineering Congenital Diseases > Computational Models.

Longitudinal cohort study investigating neurodevelopmental and socioemotional outcomes in school-entry aged children after open heart surgery in Australia and New Zealand: the NITRIC follow-up study protocol.

INTRODUCTION: Despite growing awareness of neurodevelopmental impairments in children with congenital heart disease (CHD), there is a lack of large, longitudinal, population-based cohorts. Little is known about the contemporary neurodevelopmental profile and the emergence of specific impairments in children with CHD entering school. The performance of standardised screening tools to predict neurodevelopmental outcomes at school age in this high-risk population remains poorly understood. The NITric oxide during cardiopulmonary bypass to improve Recovery in Infants with Congenital heart defects (NITRIC) trial randomised 1371 children <2 years of age, investigating the effect of gaseous nitric oxide applied into the cardiopulmonary bypass oxygenator during heart surgery. The NITRIC follow-up study will follow this cohort annually until 5 years of age to assess outcomes related to cognition and socioemotional behaviour at school entry, identify risk factors for adverse outcomes and evaluate the performance of screening tools. METHODS AND ANALYSIS: Approximately 1150 children from the NITRIC trial across five sites in Australia and New Zealand will be eligible. Follow-up assessments will occur in two stages: (1) annual online screening of global neurodevelopment, socioemotional and executive functioning, health-related quality of life and parenting stress at ages 2-5 years; and (2) face-to-face assessment at age 5 years assessing intellectual ability, attention, memory and processing speed; fine motor skills; language and communication; and socioemotional outcomes. Cognitive and socioemotional outcomes and trajectories of neurodevelopment will be described and demographic, clinical, genetic and environmental predictors of these outcomes will be explored. ETHICS AND DISSEMINATION: Ethical approval has been obtained from the Children's Health Queensland (HREC/20/QCHQ/70626) and New Zealand Health and Disability (21/NTA/83) Research Ethics Committees. The findings will inform the development of clinical decision tools and improve preventative and intervention strategies in children with CHD. Dissemination of the outcomes of the study is expected via publications in peer-reviewed journals, presentation at conferences, via social media, podcast presentations and medical education resources, and through CHD family partners. TRIAL REGISTRATION NUMBER: The trial was prospectively registered with the Australian New Zealand Clinical Trials Registry as 'Gene Expression to Predict Long-Term Neurodevelopmental Outcome in Infants from the NITric oxide during cardiopulmonary bypass to improve Recovery in Infants with Congenital heart defects (NITRIC) Study - A Multicentre Prospective Trial'. TRIAL REGISTRATION: ACTRN12621000904875.

COVID Vaccine-Associated Myocarditis in Adolescent Siblings: Does It Run in the Family?

The development of myocarditis after receiving messenger RNA vaccination against COVID-19 is well documented, particularly in adolescent and young adult males. We report a case of vaccine-associated myocarditis in adolescent brothers following their second dose of the BNT162b2 mRNA vaccine (Pfizer-BioNTech, Mainz, Germany). This report illustrates the need to better understand the mechanisms leading to myocarditis after mRNA vaccination.

A diffusion MRI study of brain white matter microstructure in adolescents and adults with a Fontan circulation: Investigating associations with resting and peak exercise oxygen saturations and cognition.

INTRODUCTION: Adolescents and adults with a Fontan circulation are at risk of cognitive dysfunction; Attention and processing speed are notable areas of concern. Underlying mechanisms and brain alterations associated with worse long-term cognitive outcomes are not well determined. This study investigated brain white matter microstructure in adolescents and adults with a Fontan circulation and associations with resting and peak exercise oxygen saturations (SaO2), predicted maximal oxygen uptake during exercise (% pred VO2), and attention and processing speed. METHODS: Ninety-two participants with a Fontan circulation (aged 13-49 years, ≥5 years post-Fontan completion) had diffusion MRI. Averaged tract-wise diffusion tensor imaging (DTI) metrics were generated for 34 white matter tracts of interest. Resting and peak exercise SaO2 and % pred VO2 were measured during cardiopulmonary exercise testing (CPET; N = 81). Attention and processing speed were assessed using Cogstate (N = 67 and 70, respectively). Linear regression analyses adjusted for age, sex, and intracranial volume were performed to investigate associations between i) tract-specific DTI metrics and CPET variables, and ii) tract-specific DTI metrics and attention and processing speed z-scores. RESULTS: Forty-nine participants were male (53%), mean age was 23.1 years (standard deviation (SD) = 7.8 years). Mean resting and peak exercise SaO2 were 93.1% (SD = 3.6) and 90.1% (SD = 4.7), respectively. Mean attention and processing speed z-scores were -0.63 (SD = 1.07) and -0.72 (SD = 1.44), respectively. Resting SaO2 were positively associated with mean fractional anisotropy (FA) of the left corticospinal tract (CST) and right superior longitudinal fasciculus I (SLF-I) and negatively associated with mean diffusivity (MD) and radial diffusivity (RD) of the right SLF-I (p ≤ 0.01). Peak exercise SaO2 were positively associated with mean FA of the left CST and were negatively associated with mean RD of the left CST, MD of the left frontopontine tract, MD, RD and axial diffusivity (AD) of the right SLF-I, RD of the left SLF-II, MD, RD and AD of the right SLF-II, and MD and RD of the right SLF-III (p ≤ 0.01). Percent predicted VO2 was positively associated with FA of the left uncinate fasciculus (p < 0.01). Negative associations were identified between mean FA of the right arcuate fasciculus, right SLF-II and right SLF-III and processing speed (p ≤ 0.01). No significant associations were identified between DTI-based metrics and attention. CONCLUSION: Chronic hypoxemia may have long-term detrimental impact on white matter microstructure in people living with a Fontan circulation. Paradoxical associations between processing speed and tract-specific DTI metrics could be suggestive of compensatory white matter remodeling. Longitudinal investigations focused on the mechanisms and trajectory of altered white matter microstructure and associated cognitive dysfunction in people with a Fontan circulation are required to better understand causal associations.

Echocardiography for latent rheumatic heart disease in first degree relatives of children with acute rheumatic fever: Implications for active case finding in family members.

BACKGROUND: Individuals with Acute Rheumatic Fever (ARF) often report a family history of ARF or Rheumatic Heart Disease (RHD) however the degree of familial susceptibility to RHD is poorly defined. This study aimed to determine RHD prevalence among first degree relatives of ARF patients using echocardiography. METHODS: Children with ARF were recruited from Auckland, New Zealand. Parents and siblings ≥ 4years were offered echocardiography. Echocardiograms were reported according to World Heart Federation 2012 criteria. RHD prevalence in first degree relatives was compared to previously established population rates in the region. FINDINGS: In total, 70 index cases with ARF were recruited. Echocardiography was performed in 94 parents and 132 siblings. There were 3 siblings with definite RHD and 9 with borderline RHD. There were 4 parents with definite RHD. Overall prevalence of RHD (definite and borderline) in siblings was 90/1,000 (95% CI 45-143/1,000) compared to 36/1,000 (95% CI 30-42/1,000) in New Zealand children from high ARF incidence populations (p 0.001). Prevalence of definite RHD in parents was 42/1,000 (95% CI 7-87/1,000) compared to 22/1,000 (95% CI 9-36/1,000) in adults from a high ARF incidence New Zealand population (p 0.249). INTERPRETATION: RHD prevalence in siblings and parents of ARF cases is significantly greater than in comparable background populations. The contribution of hereditary versus environmental risk factors remains uncertain. We recommend targeted echocardiographic case-finding among siblings and parents of ARF/RHD cases in order to detect previously unrecognized latent RHD.