Organisation of paediatric echocardiography laboratories and governance of echocardiography services and training in Europe: current status, disparities, and potential solutions. A survey from the Association for European Paediatric and Congenital Cardiology (AEPC) imaging working group.

BACKGROUND: There is limited data on the organisation of paediatric echocardiography laboratories in Europe. METHODS: A structured and approved questionnaire was circulated across all 95 Association for European Paediatric and Congenital Cardiology affiliated centres. The aims were to evaluate: (1) facilities in paediatric echocardiography laboratories across Europe, (2) accredited laboratories, (3) medical/paramedical staff employed, (4) time for echocardiographic studies and reporting, and (5) training, teaching, quality improvement, and research programs. RESULTS: Respondents from forty-three centres (45%) in 22 countries completed the survey. Thirty-six centres (84%) have a dedicated paediatric echocardiography laboratory, only five (12%) of which reported they were European Association of Cardiovascular Imaging accredited. The median number of echocardiography rooms was three (range 1-12), and echocardiography machines was four (range 1-12). Only half of all the centres have dedicated imaging physiologists and/or nursing staff, while the majority (79%) have specialist imaging cardiologist(s). The median (range) duration of time for a new examination was 45 (20-60) minutes, and for repeat examination was 20 (5-30) minutes. More than half of respondents (58%) have dedicated time for reporting. An organised training program was present in most centres (78%), 44% undertake quality assurance, and 79% perform research. Guidelines for performing echocardiography were available in 32 centres (74%). CONCLUSION: Facilities, staffing levels, study times, standards in teaching/training, and quality assurance vary widely across paediatric echocardiography laboratories in Europe. Greater support and investment to facilitate improvements in staffing levels, equipment, and governance would potentially improve European paediatric echocardiography laboratories.

Prenatal vs postnatal diagnosis of 22q11.2 deletion syndrome: cardiac and noncardiac outcomes through 1 year of age.

BACKGROUND: The 22q11.2 deletion syndrome is the most common microdeletion syndrome and is frequently associated with congenital heart disease. Prenatal diagnosis of 22q11.2 deletion syndrome is increasingly offered. It is unknown whether there is a clinical benefit to prenatal detection as compared with postnatal diagnosis. OBJECTIVE: This study aimed to determine differences in perinatal and infant outcomes between patients with prenatal and postnatal diagnosis of 22q11.2 deletion syndrome. STUDY DESIGN: This was a retrospective cohort study across multiple international centers (30 sites, 4 continents) from 2006 to 2019. Participants were fetuses, neonates, or infants with a genetic diagnosis of 22q11.2 deletion syndrome by 1 year of age with or without congenital heart disease; those with prenatal diagnosis or suspicion (suggestive ultrasound findings and/or high-risk cell-free fetal DNA screen for 22q11.2 deletion syndrome with postnatal confirmation) were compared with those with postnatal diagnosis. Perinatal management, cardiac and noncardiac morbidity, and mortality by 1 year were assessed. Outcomes were adjusted for presence of critical congenital heart disease, gestational age at birth, and site. RESULTS: A total of 625 fetuses, neonates, or infants with 22q11.2 deletion syndrome (53.4% male) were included: 259 fetuses were prenatally diagnosed (156 [60.2%] were live-born) and 122 neonates were prenatally suspected with postnatal confirmation, whereas 244 infants were postnatally diagnosed. In the live-born cohort (n=522), 1-year mortality was 5.9%, which did not differ between groups but differed by the presence of critical congenital heart disease (hazard ratio, 4.18; 95% confidence interval, 1.56-11.18; P<.001) and gestational age at birth (hazard ratio, 0.78 per week; 95% confidence interval, 0.69-0.89; P<.001). Adjusting for critical congenital heart disease and gestational age at birth, the prenatal cohort was less likely to deliver at a local community hospital (5.1% vs 38.2%; odds ratio, 0.11; 95% confidence interval, 0.06-0.23; P<.001), experience neonatal cardiac decompensation (1.3% vs 5.0%; odds ratio, 0.11; 95% confidence interval, 0.03-0.49; P=.004), or have failure to thrive by 1 year (43.4% vs 50.3%; odds ratio, 0.58; 95% confidence interval, 0.36-0.91; P=.019). CONCLUSION: Prenatal detection of 22q11.2 deletion syndrome was associated with improved delivery management and less cardiac and noncardiac morbidity, but not mortality, compared with postnatal detection.

Management of prenatally detected vascular rings: a United Kingdom national survey.

OBJECTIVE: To investigate UK variability in prenatal and postnatal management strategy of right aortic arch and double aortic arch (RAA/DAA). METHODS: Online surveys were sent to senior physicians (consultants) of the National Fetal Cardiology Working Group regarding prenatal diagnosis, counselling, and perinatal management of antenatally diagnosed RAA/DAA and to the British Congenital Cardiovascular Association regarding postnatal management strategies. RESULTS: There were 28 prenatal and 90 postnatal surveys completed. Prenatally, there was consensus for potential associated chromosomal/genetic anomalies, but there was variation in the risk quoted. Confidence in defining aortic arch morphology was reported by 43% (12/28) of fetal cardiologists. There was variation in what was felt to be possible symptoms/signs of a compressive vascular ring, postnatal investigation, postnatal management, follow-up duration of asymptomatic patients, and indications for surgical intervention. CONCLUSION: This study has highlighted important areas for future research: improving accuracy of prenatal diagnosis, clarification of potential symptoms, optimal investigation strategies, and indications for surgery.

Phenolic furanochromene hydrazone derivatives: Synthesis, antioxidant activity, ferroptosis inhibition, DNA cleavage and DNA molecular docking studies.

Twenty-four phenolic furanochromene hydrazone derivatives were designed and synthesized in order to evaluate structure-activity relationships in a series of antioxidant-related assays. The derivatives have varying substitution patterns on the phenol ring, with some compounds having one, two or three hydroxy groups, and others containing one hydroxy group in combination with methoxy, methyl, bromo, iodo and/or nitro groups. Antioxidant activity was determined using the DPPH free radical scavenging and CUPRAC assays. Compounds containing ortho-dihydroxy and para-dihydroxy patterns had the highest free radical scavenging activity, with IC50 values ranging from 5.0 to 28 µM. Similarly, derivatives with ortho-dihydroxy and para-dihydroxy patterns, together with a 4-hydroxy-3,5­dimethoxy pattern, displayed strong copper (II) ion reducing capacity, using Trolox as a standard. Trolox equivalent antioxidant capacity (TEAC) coefficients for these derivatives ranged from 1.75 to 3.97. As further evidence of antioxidant potential, greater than half of the derivatives reversed erastin-induced ferroptosis in HaCaT cells. In addition, twenty-three of the derivatives were effective at cleaving supercoiled plasmid DNA in the presence of copper (II) ions at 1 mM, with the 3,4­dihydroxy derivative showing cleavage to both the linear and open circular forms at 3.9 uM. The interaction of the phenolic furanochromene derivatives with DNA was confirmed by molecular docking studies, which revealed that all the derivatives bind favorably in the minor groove of DNA.

Diazoxide-induced pulmonary hypertension in hyperinsulinaemic hypoglycaemia: Recommendations from a multicentre study in the United Kingdom.

OBJECTIVE: Diazoxide is first-line treatment for hyperinsulinaemic hypoglycaemia (HH) but diazoxide-induced pulmonary hypertension (PH) can occur. We aim to characterize the incidence and risk factors of diazoxide-induced PH in a large HH cohort to provide recommendations for anticipating and preventing PH in diazoxide-treated patients with HH. DESIGN AND PATIENTS: Retrospective cohort study involving four UK regional HH centres; review of case notes of HH patients on diazoxide. MEASUREMENTS: The diagnosis of PH was based on clinical and echocardiography evidence. Patient and treatment-related risk factors were analysed for association. RESULTS: Thirteen (6 men) of 177 HH diazoxide-treated patients developed PH, an incidence of 7%. In the PH group, HH was diagnosed at median (range) of 9 (1,180) days, with diazoxide commenced 4 (0,76) days from diagnosis and reaching a maximum dose of 7 (2.5,20) mg/kg/d. The majority (8 of 13 patients) developed PH within 2 weeks of diazoxide. Complete diazoxide withdrawal, but not dose reduction, led to PH resolution at 41 (3,959) days. In three patients, PH continued beyond 12 months. Risk factors for the development of PH included the presence of congenital heart disease (CHD) (P = .008), and total fluid volume exceeding 130 mL/kg/d in the immediate 24 hours preceding diazoxide (P = .019). CONCLUSION: Pulmonary hypertension can occur in 7% of diazoxide-treated HH patients. Risk factors include the presence of congenital heart disease and fluid overload. Recommendations include echocardiography and fluid restriction to 130 mL/kg/d prior to diazoxide treatment and immediate discontinuation of diazoxide if PH develops.

Dilated cardiomyopathy in a national paediatric population.

Dilated cardiomyopathy is the most common form of childhood cardiomyopathy and is known to result in significant morbidity and mortality. This study aims to review the aetiology and associated outcomes of DCM. The median age at diagnosis was 6 months (0-42 months); n = 23 (43.3%) were idiopathic; n = 11 (20.9%) secondary to a viral infection; n = 12 (22.6%) genetic disorders and n = 7 (13.2%) as a result of vitamin D deficiency. There was a significant correlation between aetiology and mortality, r = 0.85, with a lower survival rate in idiopathic and genetic cohorts. Males were significantly less likely to survive to 1 year of age, p = 0.035. The age at diagnosis did not alter survival to 1 year and the predicted survival beyond 1 year was 84.3% (95% CI, 71.3 to 94.5%). Severely impaired left ventricular fractional shortening at presentation (< 15%) was an independent predictor of death, p = 0.002, (95% CI, 11.2 to 14.2%).Conclusion: Paediatric DCM is a heterogeneous disease resulting in significant morbidity. The aetiology alters the age of presentation. Identification of a specific cause is a useful for risk stratification and prognostication. The first year after diagnosis is a critical time period reflected by the significant morbidity and mortality. What is Known: •Paediatric dilated cardiomyopathy (DCM) is the commonest of the childhood cardiomyopathies, with significant associated morbidity and mortality. •DCM is most commonly idiopathic. What is New: •Identifying the aetiology of DCM in the paediatric population aids risk stratification and prognostication. •The first year after diagnosis of DCM is associated with significant mortality.

Ventricular Dysfunction, Interdependence, and Mechanical Dispersion in Newborn Infants with Congenital Diaphragmatic Hernia.

BACKGROUND: Congenital diaphragmatic hernia (CDH) is an important cause of mortality and morbidity in the neonatal period. Pulmonary hypertension and pulmonary hypoplasia are key pathological findings. Cardiac function may also be an important determinant of disease severity, prognostic indicator, and therapeutic target in CDH. OBJECTIVE: The aim of this study was to assess ventricular mechanics and synchrony in infants with CDH and controls using speckle tracking echocardiography (STE). METHODS: Retrospective analysis was performed of echocardiograms obtained in the first 48 h of life in 27 infants with CDH and 20 controls. STE-derived longitudinal strain (LS) was measured in the right and left ventricles (RV, LV). Circumferential strain (CS) and radial strain (RS) were additionally measured in the LV. Mechanical dispersion (MD), a measure of synchrony, was assessed by calculation of the standard deviation of time to peak systolic strain in six ventricular segments. RESULTS: RV LS and LV LS, LV CS, and LV RS were significantly reduced in CDH compared to controls. In the LV free wall, LS and RS were significantly reduced in CDH. LV LS correlated significantly with RV LS in CDH cases (r2 = 0.37, p = 0.002), but not controls (r2 = 0.19, p = 0.06). LV LS also correlated with LV MD in CDH (r2 = 0.25, p = 0.01) but not controls (r2 = 0.02, p = 0.54). CONCLUSIONS: Global impairment of RV and LV systolic function are present in newborn infants with CDH and are associated with primary left ventricular dysfunction, ventricular interdependence, and MD.

Surgical Approach for Hypoplastic Mirror Circumflex Aortic Arch.

Surgical approach for the mirror-form of circumflex aortic arch with a long-segment hypoplasia is described. Instead of "uncrossing" the arch, posterior aortic translocation of the aorta is required for the mirror-form. These surgical strategies addressed all the associated patho-mechanisms: (1) relief of vascular ring, (2) removal of posterior arch compression on the trachea, and (3) correction of any arch obstruction. Posterior tracheobronchopexy was further required to address severe underlying tracheobronchomalacia.

Early Postnatal Ventricular Dysfunction Is Associated with Disease Severity in Patients with Congenital Diaphragmatic Hernia.

OBJECTIVE: To assess patterns of postnatal ventricular function and their relationship to prenatal and postnatal markers of disease severity in infants with congenital diaphragmatic hernia (CDH). STUDY DESIGN: In this observational case-control study of cardiac function in infants with CDH in the first 5 days of life, systolic and diastolic function in the right ventricle (RV) and left ventricle (LV) were assessed using speckle tracking echocardiography-derived global strain and tissue Doppler imaging. Correlation between cardiac function and prenatal observed:expected total fetal lung volume (TFLV), oxygenation index (OI), duration of intubation, and hospital length of stay were assessed. RESULTS: All measures of systolic and diastolic function were significantly reduced in the CDH group (n = 25) compared with controls (n = 20) at <48 hours, and were improved by 72-120 hours. LV global systolic longitudinal strain (GLS) correlated with prenatal TFLV (R2 = 0.32; P = .03), OI (R2 = 0.35; P < .001), duration of intubation (R2 = 0.24; P = .04), and length of stay (R2 = 0.4; P = .006). Mean (SD) LV GLS at <48 hours was significantly lower in infants with CDH who did not survive and/or required ECMO compared with those who did not: -11.5 (5.3)% vs -16.9 (5.3)% (P = .02). CONCLUSIONS: RV and LV function are impaired in the transitional period in infants with CDH. Early LV systolic function correlates with prenatal and postnatal markers of clinical disease severity and may be an important determinant of disease severity and therapeutic target in CDH. These findings support regular assessment of cardiac function in CDH and investigational trials of targeted cardiovascular therapies.

EDUCATIONAL SERIES IN CONGENITAL HEART DISEASE: Prenatal diagnosis of congenital heart disease.

This review article will guide the reader through the background of prenatal screening for congenital heart disease. The reader will be given insight into the normal screening views, common abnormalities, risk stratification of lesions and also recent advances in prenatal cardiology.

Fetal aortic valve stenosis: a critique of case selection criteria for fetal intervention.

OBJECTIVE: Selection of fetuses with aortic stenosis (AS) for prenatal intervention has been influenced by published scoring systems. This study aimed to test these scoring systems by retrospective application to consecutive cases of fetal AS. METHODS: Retrospective analysis of the echocardiographic findings of 31 consecutive fetuses with AS evaluated at a tertiary fetal cardiology centre. Published 'eHLHS' scores and threshold scores were applied to the group and compared to postnatal management, in terms of biventricular repair versus single ventricle palliation. RESULTS: Thirty-one fetuses were identified with AS, and eHLHS was identified in 17 at the initial echocardiogram. No fetus with a full eHLHS score (3/3 or 4/4) achieved a biventricular repair. Three fetuses had a favourable threshold score (≥4), one of whom had a successful biventricular outcome. Seven fetuses had an unfavourable threshold score (<4) and underwent a univentricular pathway. CONCLUSION: The eHLHS score is a reliable predictor for the progression to HLHS at term. The score identifies those who would achieve a biventricular repair postnatally without prenatal intervention. A minority of fetuses with favourable threshold scores may achieve a biventricular repair postnatally without prenatal intervention, but eHLHS and an unfavourable threshold score (<4) predict a single ventricle pathway postnatally.

Deaths in children with epilepsies: a UK-wide study.

PURPOSE: This UK-wide review of deaths in children with epilepsies was undertaken to ascertain any demographic, clinical, organisational, or management factors associated with the deaths, and to determine the extent to which any of these may have deviated from nationally agreed best practice. METHOD: Paediatricians across the UK were asked to notify any deaths in children with epilepsies over a 10-month period. Hospital and community case notes were reviewed by pairs of case assessors using a structured assessment tool combining holistic and criterion-based approaches. RESULTS: Of 46 deaths notified, case notes were obtained on 33. The majority of children had associated developmental impairments. The majority (24), died of an associated co-morbidity rather than of epilepsy. Seven died of convulsive status epilepticus and seven as sudden unexpected deaths in epilepsy. Twenty four percent of deaths were judged to be preventable; potentially modifiable factors included fragmentation of care, support for families, and recognition of and response to acute illness in the child, including the appropriate management of prolonged seizures. CONCLUSIONS: Although this audit has demonstrated significant improvements in quality of care when compared with the last national audit of epilepsy deaths in 2002, further improvement is still required.

Atrioventricular block during fetal life.

Congenital complete atrioventricular (AV) block occurs in approximately 1 in 20,000 live births and is known to result in significant mortality and morbidity both during fetal life and postnatally. Complete AV block can occur as a result of an immune or a non-immune mediated process. Immune mediated AV block is a multifactorial disease, but is associated with the trans-placental passage of maternal autoantibodies (anti-Ro/SSA and/or anti-La/SSB). These autoantibodies attach to and subsequently damage the cardiomyocytes and conduction tissue in susceptible fetuses. In this report, we examine the evidence in reference to means of assessment, pathophysiology, and potential prenatal therapy of atrioventricular block.

A review of the quality of care following prolonged seizures in 1-18 year olds with epilepsies.

PURPOSE: To review the quality of care of children and young people with epilepsies who, following a prolonged seizure, received high-dependency or intensive care. To identify and learn from clinical, organisational, management or personal issues that contributed to these admissions, in order to inform practice and improve clinical services for children across the UK. METHOD: Notifications were collected from consultant paediatricians in England, Wales, Scotland and Northern Ireland over a 10-month period. For all eligible cases a clinical questionnaire was sent to the notifying clinician. A sample of these cases were selected for a detailed case note review. Case notes were reviewed by paediatrician-nurse pairs using a purpose-built assessment tool derived from national guidelines. RESULTS: Data were collected from 135 clinical questionnaires, and 36 sets of case notes were reviewed. Findings were compared to national standards of care and emerging themes identified. There was evidence of good epilepsy management in many cases. In some cases there was evidence of a lack of clear emergency care plans, of delays in administration of emergency medication, and of deviation from established national guidelines. CONCLUSION: The findings of this review suggest there have been improvements in the care of children and young people with epilepsies presenting with prolonged seizures compared to previous studies. Nevertheless, further improvements are needed, particularly in communication with families and prompt administration of emergency medication.

Prenatal screening for structural congenital heart disease.

Congenital heart defects can be diagnosed during fetal life using echocardiography. Prenatal diagnosis allows full investigation of affected fetuses for coexisting abnormalities, and gives time for parents to be informed about the prognosis of the fetus and treatments that might be required. In a minority of cases, where the natural history suggests an unfavourable outcome, prenatal diagnosis provides an opportunity for fetal cardiac intervention. For some cardiac lesions, notably hypoplastic left heart syndrome, transposition of the great arteries, and coarctation of the aorta, prenatal diagnosis has been shown to reduce postnatal morbidity and mortality. Some costs of care, notably the transport of critically ill infants, are reduced by prenatal diagnosis. Prenatal screening programmes typically recommend detailed assessment of fetuses judged to be at high risk of congenital heart disease. However, most cases of congenital heart disease arise in the low-risk population, and detection of affected fetuses in this setting depends on recognizing abnormalities of the heart during the midtrimester scan. Evidence supports the use of structured training interventions and feedback to those undertaking sonographic examinations, to improve the prenatal detection of congenital heart disease.

An outbreak of Candida albicans folliculitis masquerading as Malassezia folliculitis in a prison population.

Several inmates from a non-air-conditioned prison were sent to the University of Texas Medical Branch dermatology clinic for unexplained eruptions not responding to various treatments. They were initially diagnosed with Malassezia folliculitis based on clinical examination and histological findings. The patients' cultures from skin scrapings, however, revealed Candida albicans confirmed by growth on Mycosel agar and further by the germ tube production method. Five cases were brought to the clinic, but at least 30 other inmates were reported to have similar cutaneous eruptions. Given that these patients were generally immunocompetent, this is a rare finding. Factors favoring pseudohyphal growth for these patients included use of topical steroids and/or systemic antibiotics and hot and humid climate. All patients' folliculitis resolved with fluconazole and/or antifungal cream with no further complications.