Echocardiographic scores for biventricular repair risk prediction of congenital heart disease with borderline left ventricle: a review.

The aim of this review is to highlight the strengths and limitations of major echocardiographic biventricular repair (BVR) prediction models for borderline left ventricle (LV) in complex congenital heart disease (CHD). A systematic search in the National Library of Medicine for Medical Subject Headings and free text terms including echocardiography, CHD, and scores, was performed. The search was refined by adding keywords for critical aortic stenosis (AS), borderline LV, complex left ventricular outflow tract (LVOT) obstruction, hypoplastic left heart syndrome/complex (HLHS/HLHC), and unbalanced atrio-ventricular septal defects (uAVSD). Fifteen studies were selected for the final analysis. We outlined what echocardiographic scores for different types of complex CHD with diminutive LV are available. Scores for CHD with LVOT obstruction including critical AS, HLHS/HLHC, and aortic arch hypoplasia have been validated and implemented by several studies. Scores for uAVSD with right ventricle (RV) dominance have also been established and implemented, the first being the atrioventricular valve index (AVVI). In addition to AVII, both LV/RV inflow angle and LV inflow index have all been validated for the prediction of BVR. We conclude with a discussion of limitations in the development and validation of each of these scores, including retrospective design during score development, heterogeneity in echocardiographic parameters evaluated, variability in the definition of outcomes, differences in adopted surgical and Interventional strategies, and institutional differences. Furthermore, scores developed in the past two decades may have little clinical relevance now. In summary, we provide a review of echocardiographic scores for BVR in complex CHD with a diminutive LV that may serve as a guide for use in modern clinical practice.

Neonatal sepsis and cardiovascular dysfunction I: mechanisms and pathophysiology.

The highest incidence of sepsis across all age groups occurs in neonates leading to substantial mortality and morbidity. Cardiovascular dysfunction frequently complicates neonatal sepsis including biventricular systolic and/or diastolic dysfunction, vasoregulatory failure, and pulmonary arterial hypertension. The haemodynamic response in neonatal sepsis can be hyperdynamic or hypodynamic and the underlying pathophysiological mechanisms are heterogeneous. The diagnosis and definition of both neonatal sepsis and cardiovascular dysfunction complicating neonatal sepsis are challenging and not consensus-based. Future developments in neonatal sepsis management will be facilitated by common definitions and datasets especially in neonatal cardiovascular optimisation. IMPACT: Cardiovascular dysfunction is common in neonatal sepsis but there is no consensus-based definition, making calculating the incidence and designing clinical trials challenging. Neonatal cardiovascular dysfunction is related to the inflammatory response, which can directly target myocyte function and systemic haemodynamics.

Severe Restriction of a VSD and Development of Pulmonary Atresia in a Patient with Transposition of the Great Arteries: Fetal Diagnosis.

Pulmonary atresia with an intact ventricular septum typically occurs in patients with concordant atrioventricular and ventriculoarterial connections. When it does occur in patients with discordant connections, it is most frequently seen in association with congenitally corrected transposition. We present a rare case of transposition of the great arteries with a ventricular septal defect (VSD) detected in fetal life which evolved throughout pregnancy resulting in the development of pulmonary atresia and severe restriction of the VSD.

Nicolaides-Baraitser syndrome in a patient with hypertrophic cardiomyopathy and SMARCA2 gene deletion.

Nicolaides-Baraitser syndrome is a rare, neuro-developmental disorder caused by heterozygous pathogenic variants in the SMARCA2 gene, involved with chromatin regulation. Cardinal features include intellectual disability, short stature, microcephaly, triangular facies, sparse hair, brachydactyly, prominent interphalangeal joints and seizures. Genetic testing demonstrated a loss within SMARCA2 at 9p24.3 inclusive of basepairs 2094861_2141830 (hg19) in our patient. This case highlights a child with Nicolaides-Baraiter syndrome, a SMARCA2 gene deletion and a novel association of hypertrophic obstructive cardiomyopathy.

Early predictors of epilepsy and subsequent relapse in children with acute disseminated encephalomyelitis.

OBJECTIVE: To identify predictors of epilepsy and clinical relapses in children presenting with acute disseminated encephalomyelitis (ADEM). METHODS: Children presenting with ADEM between 2005 and 2017 and tested clinically for MOG-Ab were identified from three tertiary paediatric neurology centres in the United Kingdom. Patients were followed up for a median of 6 years (range, 1-16 years). RESULTS: A total of 74 children were studied (38 females; median age at first presentation: 4.5 years (range, 1.4-16 years)). MOG-Ab was positive in 50/74 (67.6%) of cases, and 27 (54%) of MOG-Ab positive children presented with a neurological relapse over time. MOG-Ab was more frequently positive in the relapsing group than in the monophasic group (27/31 vs 23/43; odds ratio 5.9 (95% CI: 1.8-19.7); p = 0.002). 16/74 (22%) children had seizures during the acute presentation with ADEM and 12/74 (16.2%) patients were diagnosed with post-ADEM epilepsy. The diagnosis of post-ADEM epilepsy was more frequently observed in children with relapsing disease than monophasic disease (10/31 vs 2/43; odds ratio 9.8 (95% confidence interval (CI): 2.0-48.7); p = 0.003), in children who had positive intrathecal oligoclonal bands than those with negative bands (4/7 vs 4/30; odds ratio 8.7 (95% CI: 1.4-54.0); p = 0.027) and in children who had positive MOG-Ab than negative MOG-Ab cases (11/12 vs 39/62; odds ratio 6.5 (95% CI:0.8-53.6); p = 0.051). CONCLUSION: A higher relapse rate and a greater risk of post-ADEM epilepsy in children with MOG-Ab-associated disease may indicate a chronic disease with immune-mediated seizures in these children.

Decision-Making in the Catheter Laboratory: The Most Important Variable in Successful Outcomes.

Increasingly the importance of how and why we make decisions in the medical arena has been questioned. Traditionally the aeronautical and business worlds have shed a light on this complex area of human decision-making. In this review we reflect on what we already know about the complexity of decision-making in addition to directing particular focus on the challenges to decision-making in the high-intensity environment of the pediatric cardiac catheterization laboratory. We propose that the most critical factor in outcomes for children in the catheterization lab may not be technical failures but rather human factors and the lack of preparation and robust shared decision-making process between the catheterization team. Key technical factors involved in the decision-making process include understanding the anatomy, the indications and objective to be achieved, equipment availability, procedural flow, having a back-up plan and post-procedural care plan. Increased awareness, pre-catheterization planning, use of standardized clinical assessment and management plans and artificial intelligence may provide solutions to pitfalls in decision-making. Further research and efforts should be directed towards studying the impact of human factors in the cardiac catheterization laboratory as well as the broader medical environment.

Paediatric multiple sclerosis: a new era in diagnosis and treatment.

Multiple sclerosis is a chronic immune-mediated demyelinating disease of the central nervous system. The diagnosis of multiple sclerosis in children, as in adults, requires evidence of dissemination of inflammatory activity in more than one location in the central nervous system (dissemination in space) and recurrent disease over time (dissemination in time). The identification of myelin oligodendrocyte glycoprotein antibodies (MOG-Ab) and aquaporin-A antibodies (AQP4-Ab), and the subsequent discovery of their pathogenic mechanisms, have led to a shift in the classification of relapsing demyelinating syndromes. This is reflected in the 2017 revised criteria for the diagnosis of multiple sclerosis, which emphasizes the exclusion of multiple sclerosis mimics and aims to enable earlier diagnosis and thus treatment initiation. The long-term efficacy of individual therapies initiated in children with multiple sclerosis is hard to evaluate, owing to the small numbers of patients who have the disease, the relatively high number of patients who switch therapy, and the need for long follow-up studies. Nevertheless, an improvement in prognosis with a globally reduced annual relapse rate in children with multiple sclerosis is now observed compared with the pretreatment era, indicating a possible long-term effect of therapies. Given the higher relapse rate in children compared with adults, and the impact multiple sclerosis has on cognition in the developing brain, there is a question whether rapid escalation or potent agents should be used in children, while the short- and long-term safety profiles of these drugs are being established. With the results of the first randomized controlled trial of fingolimod versus interferon-ß1a in paediatric multiple sclerosis published in 2018 and several clinical trials underway, there is hope for further progress in the field of paediatric multiple sclerosis. WHAT THIS PAPER ADDS: Early and accurate diagnosis of multiple sclerosis is crucial. The discovery of antibody-mediated demyelination has changed the diagnosis and management of relapsing demyelination syndromes. Traditional escalation therapy is being challenged by induction therapy.

ESCLEROSIS MÚLTIPLE PEDIÁTRICA: UNA NUEVA ERA EN EL DIAGNÓSTICO Y TRATAMIENTO: La esclerosis múltiple es una enfermedad desmielinizante crónica mediada por el sistema inmunitario del sistema nervioso central. El diagnóstico de esclerosis múltiple en niños, como en adultos, requiere evidencia de diseminación de actividad inflamatoria en más de un lugar en el sistema nervioso central (diseminación en el espacio) y enfermedad recurrente a lo largo del tiempo (diseminación en el tiempo). La identificación de los anticuerpos de la glicoproteína oligodendrocítica de la mielina (MOG-Ab) y los anticuerpos de la acuaporina-A (AQP4-Ab), y el posterior descubrimiento de sus mecanismos patógenos, han conducido a un cambio en la clasificación de los síndromes desmielinizantes recurrentes. Esto se refleja en los criterios revisados ​​de 2017 para el diagnóstico de esclerosis múltiple, que enfatiza la exclusión de los imitadores de la esclerosis múltiple y tiene como objetivo permitir un diagnóstico más temprano y, por lo tanto, el inicio del tratamiento. La eficacia a largo plazo de las terapias individuales iniciadas en niños con esclerosis múltiple es difícil de evaluar, debido a la pequeña cantidad de pacientes que tienen la enfermedad, la cantidad relativamente alta de pacientes que cambian de terapia y la necesidad de estudios de seguimiento prolongados. Sin embargo, ahora se observa una mejora en el pronóstico con una tasa de recaída anual globalmente reducida en niños con esclerosis múltiple en comparación con la era anterior al tratamiento previo, lo que indica un posible efecto a largo plazo de las terapias. Debido a la mayor tasa de recaída en niños en comparación con los adultos, y el impacto que tiene la esclerosis múltiple en la cognición en el cerebro en desarrollo, existe la duda de si se deben usar agentes de aumento rápido o potentes en niños, mientras que los perfiles de seguridad a corto y largo plazo de estos medicamentos se están estableciendo. Con los resultados del primer ensayo controlado aleatorio de fingolimod versus interferón-ß1a en esclerosis múltiple pediátrica publicado en 2018 y varios ensayos clínicos en curso, existe la esperanza de un mayor progreso en el campo de la esclerosis múltiple pediátrica.

ESCLEROSE MÚLTIPLA PEDIÁTRICA: UMA NOVA ERA NO DIAGNÓSTICO E TRATAMENTO: A esclerose múltipla é uma doença desmielinizante imunomediada crônica do sistema nervoso central. O diagnóstico de esclerose múltipla em crianças, como em adultos, exige evidência de disseminação da atividade inflamatória em mais de um local no sistema nervoso central (disseminação no espaço) e doença recorrente ao longo do tempo (disseminação no tempo). A identificação de anticorpos anti-glicoproteína de mielina do oligodendrócito (MOG-Ab) e anticorpos anti-aquaporina A (AQP4-Ab), e a subsequente descoberta de seus mecanismos patogênicos, levaram a uma mudança na classificação das síndromes desmielinizantes recidivantes. Isso se reflete nos critérios revisados de 2017 para o diagnóstico de esclerose múltipla, que enfatizam a exclusão de transtornos que mimetizam esclerose múltipla e visam permitir o diagnóstico precoce e, portanto, o início do tratamento. É difícil avaliar a eficácia a longo prazo de terapias individuais iniciadas em crianças com esclerose múltipla, devido ao pequeno número de pacientes que têm a doença, o número relativamente alto de pacientes que trocam de terapia e a necessidade de estudos de acompanhamento a longo prazo. No entanto, uma melhora no prognóstico com uma taxa de recaída anual globalmente reduzida em crianças com esclerose múltipla é agora observada em comparação com a era pré-tratamento, indicando um possível efeito a longo prazo das terapias. Dada a maior taxa de recaída em crianças em comparação com adultos, e o impacto da esclerose múltipla na cognição no cérebro em desenvolvimento, há uma questão se a escalada rápida ou agentes potentes devem ser usados em crianças, enquanto os perfis de segurança de curto e longo prazo destas drogas estão sendo estabelecidos. Com os resultados do primeiro estudo controlado randomizado de fingolimode versus interferon-ß1a na esclerose múltipla pediátrica publicado em 2018 e vários ensaios clínicos em andamento, há esperança de mais progressos no campo da esclerose múltipla pediátrica.

Myelin oligodendrocyte glycoprotein and aquaporin-4 antibodies are highly specific in children with acquired demyelinating syndromes.

AIM: Our objectives were to evaluate the utility of measuring myelin oligodendrocyte glycoprotein (MOG) and aquaporin-4 (AQP4) antibodies (Ab) in clinical practice and describe their associated neurological phenotypes in children. METHOD: Between 2012 and 2017, 371 children with suspected acquired demyelinating syndromes (ADS) seen in three tertiary centres were tested for MOG-Ab and AQP4-Ab. Medical notes were retrospectively reviewed, and clinical and demographic data compiled. Clinical phenotyping was performed blinded to the antibody results. RESULTS: After review, 237 of the 371 were diagnosed with ADS. Of these, 76 out of 237 (32.1%) were MOG-Ab positive and 14 out of 237 (5.9%) were AQP4-Ab positive. None were positive for both autoantibodies. All 134 patients with non-ADS were negative for MOG-Ab. MOG-Ab were identified in 45 out of 70 (64.3%) patients presenting with acute disseminated encephalomyelitis (ADEM) and in 24 out of 25 patients with relapsing ADEM. Thirty-six out of 75 (48%) MOG-Ab positive patients relapsed. Of the 33 children with neuromyelitis optic spectrum disorder, 14 were AQP4-Ab positive, 13 were MOG-Ab positive, and 6 were seronegative. Of the children with longitudinal samples, 8 out of 13 AQP4-Ab remained positive during the disease course compared to 35 out of 43 MOG-Ab (13/16 monophasic and 22/27 relapsing). INTERPRETATION: Myelin oligodendrocyte glycoprotein antibodies were identified in a third of children with ADS. Almost half of the MOG-Ab positive children relapsed and the majority of them remained antibody positive over 4-years follow-up. WHAT THIS PAPER ADDS: Myelin oligodendrocyte glycoprotein antibodies (MOG-Ab) are highly specific for acquired demyelinating syndromes (ADS). Myelin oligodendrocyte glycoprotein antibodies are not identified in children with peripheral demyelination or genetic leukodystrophies/hypomyelination. Up to 48% of MOG-Ab ADS paediatric patients relapse, higher than previously thought. Seroconversion to MOG-Ab negative status is infrequent; patients may test MOG-Ab positive at follow-up sampling even when asymptomatic. Myelin oligodendrocyte glycoprotein antibodies status should only be used in conjunction with the clinical information to guide maintenance therapy.

Complex Decision Making in the Pediatric Catheterization Laboratory: Catheterizer, Know Thyself and the Data.

Optimal outcomes are as much influenced by critical decision making pathways as by the technical skill of the operator. The complexity and potential cognitive traps underlying critical decision making has long been recognized in the aviation and business communities, however, remains a largely subconscious, unexamined discipline amongst congenital cardiac interventionalists. Challenges to making good decisions in the catheterization laboratory include heuristics, biases, and cognitive traps. In this paper we discuss some of the more common decision making challenges encountered and we address potential solutions to such decision making with particular focus towards standardization.

Decision Making in Paediatric Cardiology. Are We Prone to Heuristics, Biases and Traps?

Hidden traps in decision making have been long recognised in the behavioural economics community. Yet we spend very limited, if any time, analysing our decision-making processes in medicine and paediatric cardiology. Systems 1 and 2 thought processes differentiate between rapid emotional thoughts and slow deliberate rational thoughts. For fairly clear cut medical decisions, in-depth analysis may not be needed, but in our field of paediatric cardiology it is not uncommon for challenging cases and occasionally 'simple' cases to generate significant debate and uncertainty as to the best decision. Although morbidity and mortality meetings frequently highlight poor outcomes for our patients, they often neglect to analyse the process of thought which underlined those decisions taken. This article attempts to review commonly acknowledged traps in decision making in the behavioural economics world to ascertain whether these heuristics translate to decision making in the paediatric cardiology environment. We also discuss potential individual and collective solutions to pitfalls in decision making.

Prospective Analysis of Decision Making During Joint Cardiology Cardiothoracic Conference in Treatment of 107 Consecutive Children with Congenital Heart Disease.

The complexity and potential biases involved in decision making have long been recognised and examined in both the aviation and business industries. More recently, the medical community have started to explore this concept and its particular importance in our field. Paediatric cardiology is a rapidly expanding field and for many of the conditions we treat, there is limited evidence available to support our decision-making. Variability exists within decision-making in paediatric cardiology and this may influence outcomes. There are no validated tools available to support and examine consistent decision-making for various treatment strategies in children with congenital heart disease in a multidisciplinary cardiology and cardiothoracic institution. Our primary objective was to analyse the complexity of decision-making for children with cardiac conditions in the context of our joint cardiology and cardiothoracic conference (JCC). Two paediatric cardiologists acted as investigators by observing the weekly joint cardiology-cardiothoracic surgery conference and prospectively evaluating the degree of complexity of decision-making in the management of 107 sequential children with congenital heart disease discussed. Additionally, the group consensus on the same patients was prospectively assessed to compare this to the independent observers. Of 107 consecutive children discussed at our JCC conference 32 (27%) went on to receive surgical intervention, 20 (17%) underwent catheterisation and 65 (56%) received medical treatment. There were 53 (50%) cases rated as simple by one senior observer, while 54 (50%) were rated as complex to some degree. There was high inter-observer agreement with a Krippendorff's alpha of ≥ 0.8 between 2 observers and between 2 observers and the group consensus as a whole for grading of the complexity of decision-making. Different decisions were occasionally made on patients with the same data set. Discussions revisiting the same patient, in complex cases, resulted in different management decisions being reached in this series. Anchoring of decision-making was witnessed in certain cases. Potential application of decision making algorithms is discussed in making decisions in paediatric cardiology patients. Decision-making in our institution's joint cardiology-cardiothoracic conference proved to be complex in approximately half of our patients. Inconsistency in decision-making for patients with the same diagnosis, and different decisions made for the same complex patient at different time points confounds the reliability of the decision-making process. These novel data highlight the absence of evidence-based medicine for many decisions, occasional lack of consistency and the impact of anchoring, heuristics and other biases in complex cases. Validated decision-making algorithms may assist in providing consistency to decision-making in this setting.

Neoadjuvant chemoradiotherapy followed by liver transplantation for unresectable cholangiocarcinoma: a single-centre national experience.

BACKGROUND: Unresectable cholangiocarcinoma (CCA) has a dismal prognosis. Initial studies of orthotopic liver transplantation (OLT) alone for CCA yielded disappointing outcomes. The Mayo Clinic demonstrated long-term survival using neoadjuvant chemoradiotherapy followed by OLT in selected patients with unresectable CCA. This study reports the Irish National Liver Transplant Programme experience of neoadjuvant therapy and OLT for unresectable CCA. MATERIALS AND METHODS: Twenty-seven patients with CCA were selected for neoadjuvant chemoradiotherapy in a single centre from October 2004 to September 2011. Patients were given brachytherapy, external beam radiotherapy and 5-fluorouracil (5-Fu), followed by liver transplantation if progression free (20 patients). RESULTS: Twenty progression-free patients after neoadjuvant therapy underwent OLT. Hospital mortality was 20%. Of the 16 patients who left hospital, survival rates were 94% and 61% at 1 and 4 years. Seven patients developed recurrent disease and died at intervals of 10-58 months after OLT, whereas 9 are disease free with a median follow-up of 37 months (18-76). Predictors of disease recurrence were a tumour in explant specimen and high CA 19.9 levels. DISCUSSION: In selected patients with unresectable CCA, long-term survival can be achieved using neoadjuvant chemoradiotherapy and OLT although short-term mortality is high. Prospective international registries may aid patient selection and refinement of neoadjuvant regimens.

Natural history and outcomes in paediatric RASopathy-associated hypertrophic cardiomyopathy.

AIMS: This study aimed to describe the natural history and predictors of all-cause mortality and sudden cardiac death (SCD)/equivalent events in children with a RASopathy syndrome and hypertrophic cardiomyopathy (HCM). METHODS AND RESULTS: This is a retrospective cohort study from 14 paediatric cardiology centres in the United Kingdom and Ireland. We included children <18 years with HCM and a clinical and/or genetic diagnosis of a RASopathy syndrome [Noonan syndrome (NS), NS with multiple lentigines (NSML), Costello syndrome (CS), cardiofaciocutaneous syndrome (CFCS), and NS with loose anagen hair (NS-LAH)]. One hundred forty-nine patients were recruited [111 (74.5%) NS, 12 (8.05%) NSML, 6 (4.03%) CS, 6 (4.03%) CFCS, 11 (7.4%) Noonan-like syndrome, and 3 (2%) NS-LAH]. NSML patients had higher left ventricular outflow tract (LVOT) gradient values [60 (36-80) mmHg, P = 0.004]. Over a median follow-up of 197.5 [inter-quartile range (IQR) 93.58-370] months, 23 patients (15.43%) died at a median age of 24.1 (IQR 5.6-175.9) months. Survival was 96.45% [95% confidence interval (CI) 91.69-98.51], 90.42% (95% CI 84.04-94.33), and 84.12% (95% CI 75.42-89.94) at 1, 5, and 10 years, respectively, but this varied by RASopathy syndrome. RASopathy syndrome, symptoms at baseline, congestive cardiac failure (CCF), non-sustained ventricular tachycardia (NSVT), and maximal left ventricular wall thickness were identified as predictors of all-cause mortality on univariate analysis, and CCF, NSVT, and LVOT gradient were predictors for SCD or equivalent event. CONCLUSIONS: These findings highlight a distinct category of patients with Noonan-like syndrome with a milder HCM phenotype but significantly worse survival and identify potential predictors of adverse outcome in patients with RASopathy-related HCM.

Isolated left ventricular apical hypoplasia: Systematic review and analysis of the 37 cases reported so far.

BACKGROUND: Isolated left ventricular apical hypoplasia (ILVAH), also known as truncated left ventricle (LV), is a very unusual cardiomyopathy. It is characterised by a truncated, spherical, and non-apex forming LV. The true apex is occupied by the right ventricle. Due to the rarity of the disease, just a few case reports and limited case series have been published in the field. AIM: To analysing the so far 37 reported ILVAH cases worldwide. METHODS: The electronic databases PubMed and Scopus were investigated from their establishment up to December 13, 2022. RESULTS: The majority of cases reported occurred in males (52.7%). Mean age at diagnosis was 26.1 ± 19.6 years. More than a third of the patients were asymptomatic (35.1%). The most usual clinical presentation was breathlessness (40.5%). The most commonly detected electrocardiogram changes were T wave abnormalities (29.7%) and right axis deviation with poor R wave progression (24.3%). Atrial fibrillation/flutter was detected in 24.3%. Echocardiography was performed in 97.3% of cases and cardiac MRI in 91.9% of cases. Ejection fraction was reduced in more than a half of patients (56.7%). An associated congenital heart disease was found in 16.2%. Heart failure therapy was administered in 35.1% of patients. The outcome was favorable in the vast majority of patients, with just one death. CONCLUSION: ILVAH is a multifaceted entity with a so far unpredictable course, ranging from benign until the elderly to sudden death during adolescence.

Protocol for a prospective cohort study exploring the gut microbiota of infants with congenital heart disease undergoing cardiopulmonary bypass (the GuMiBear study).

INTRODUCTION: The gut microbiota develops from birth and matures significantly during the first 24 months of life, playing a major role in infant health and development. The composition of the gut microbiota is influenced by several factors including mode of delivery, gestational age, feed type and treatment with antibiotics. Alterations in the pattern of gut microbiota development and composition can be associated with illness and compromised health outcomes.Infants diagnosed with 'congenital heart disease' (CHD) often require surgery involving cardiopulmonary bypass (CPB) early in life. The impact of this type of surgery on the integrity of the gut microbiome is poorly understood. In addition, these infants are at significant risk of developing the potentially devastating intestinal condition necrotising enterocolitis. METHODS AND ANALYSIS: This study will employ a prospective cohort study methodology to investigate the gut microbiota and urine metabolome of infants with CHD undergoing surgery involving CPB. Stool and urine samples, demographic and clinical data will be collected from eligible infants based at the National Centre for Paediatric Cardiac Surgery in Ireland. Shotgun metagenome sequencing will be performed on stool samples and urine metabolomic analysis will identify metabolic biomarkers. The impact of the underlying diagnosis, surgery involving CPB, and the influence of environmental factors will be explored. Data from healthy age-matched infants from the INFANTMET study will serve as a control for this study. ETHICS AND DISSEMINATION: This study has received full ethical approval from the Clinical Research Ethics Committee of Children's Health Ireland, GEN/826/20.

Sudden cardiac death in childhood RASopathy-associated hypertrophic cardiomyopathy: Validation of the HCM risk-kids model and predictors of events.

BACKGROUND: RASopathies account for nearly 20% of cases of childhood hypertrophic cardiomyopathy (HCM). Sudden cardiac death (SCD) occurs in patients with RASopathy-associated HCM, but the risk factors for SCD have not been systematically evaluated. AIM: To validate the HCM Risk-Kids SCD risk prediction model in children with RASopathy-associated HCM and investigate potential specific SCD predictors in this population. METHODS: Validation of HCM Risk-Kids was performed in a retrospective cohort of 169 patients with a RASopathy-associated HCM from 15 international paediatric cardiology centres. Multiple imputation by chained equations was used for missing values related to the HCM Risk-Kids parameters. RESULTS: Eleven patients (6.5%) experienced a SCD or equivalent event at a median age of 12.5 months (IQR 7.7-28.64). The calculated SCD/equivalent event incidence was 0.78 (95% CI 0.43-1.41) per 100 patient years. Six patients (54.54%) with an event were in the low-risk category according to the HCM Risk-Kids model. Harrell's C index was 0.60, with a sensitivity of 9.09%, specificity of 63.92%, positive predictive value of 1.72%, and negative predictive value of 91%; with a poor distinction between the different risk groups. Unexplained syncope (HR 42.17, 95% CI 10.49-169.56, p < 0.001) and non-sustained ventricular tachycardia (HR 5.48, 95% CI 1.58-19.03, p < 0.007) were predictors of SCD on univariate analysis. CONCLUSION: Unexplained syncope and the presence of NSVT emerge as predictors for SCD in children with RASopathy-associated HCM. The HCM Risk-Kids model may not be appropriate to use in this population, but larger multicentre collaborative studies are required to investigate this further.

Post-transplant lymphoproliferative disorder presenting as supraglottitis following pediatric heart transplantation treated with EBV-specific cytotoxic T-lymphocytes.

We present the case of a 4 year-old boy post heart transplantation who presented with signs and symptoms of critical airway obstruction and was initially diagnosed with infective supraglottitis. Following re-presentation and biopsy, this was confirmed as post-transplant lymphoproliferative disorder (PTLD) in an unusual site; laryngeal PTLD is rare. The patient failed standard therapy and ultimately was successfully treated with EBV-specific cytotoxic T lymphocytes (CTL). This case describes a rare presentation of PTLD which required a novel treatment approach including elective tracheostomy prior to CTL therapy. The treatment was successful and the patient was decannulated prior to discharge following 4 negative biopsies, the most recent 6 months following treatment completion. The case also highlights the importance of extra-vigilance in the post-transplant population and of a collaborative approach between multiple specialties across two separate countries including the transplant center and the referral center.

Should We Be Screening for Ischaemic Heart Disease Earlier in Childhood?

Ischaemic heart disease is the most common cause of death in males and the second in the female gender. Yet we often only focus on identification and treatment of this foremost cause of death in adulthood. The review asks the question what form of coronary disease do we encounter in childhood, what predisposing factors give rise to atherosclerosis and what strategies in childhood could we employ to detect and reduce atherosclerosis development in later life.

Clinical Features and Natural History of Preadolescent Nonsyndromic Hypertrophic Cardiomyopathy.

BACKGROUND: Up to one-half of childhood sarcomeric hypertrophic cardiomyopathy (HCM) presents before the age of 12 years, but this patient group has not been systematically characterized. OBJECTIVES: The aim of this study was to describe the clinical presentation and natural history of patients presenting with nonsyndromic HCM before the age of 12 years. METHODS: Data from the International Paediatric Hypertrophic Cardiomyopathy Consortium on 639 children diagnosed with HCM younger than 12 years were collected and compared with those from 568 children diagnosed between 12 and 16 years. RESULTS: At baseline, 339 patients (53.6%) had family histories of HCM, 132 (20.9%) had heart failure symptoms, and 250 (39.2%) were prescribed cardiac medications. The median maximal left ventricular wall thickness z-score was 8.7 (IQR: 5.3-14.4), and 145 patients (27.2%) had left ventricular outflow tract obstruction. Over a median follow-up period of 5.6 years (IQR: 2.3-10.0 years), 42 patients (6.6%) died, 21 (3.3%) underwent cardiac transplantation, and 69 (10.8%) had life-threatening arrhythmic events. Compared with those presenting after 12 years, a higher proportion of younger patients underwent myectomy (10.5% vs 7.2%; P = 0.045), but fewer received primary prevention implantable cardioverter-defibrillators (18.9% vs 30.1%; P = 0.041). The incidence of mortality or life-threatening arrhythmic events did not differ, but events occurred at a younger age. CONCLUSIONS: Early-onset childhood HCM is associated with a comparable symptom burden and cardiac phenotype as in patients presenting later in childhood. Long-term outcomes including mortality did not differ by age of presentation, but patients presenting at younger than 12 years experienced adverse events at younger ages.

Relationship Between Maximal Left Ventricular Wall Thickness and Sudden Cardiac Death in Childhood Onset Hypertrophic Cardiomyopathy.

BACKGROUND: Maximal left ventricular wall thickness (MLVWT) is a risk factor for sudden cardiac death (SCD) in hypertrophic cardiomyopathy (HCM). In adults, the severity of left ventricular hypertrophy has a nonlinear relationship with SCD, but it is not known whether the same complex relationship is seen in childhood. The aim of this study was to describe the relationship between left ventricular hypertrophy and SCD risk in a large international pediatric HCM cohort. METHODS: The study cohort comprised 1075 children (mean age, 10.2 years [±4.4]) diagnosed with HCM (1-16 years) from the International Paediatric Hypertrophic Cardiomyopathy Consortium. Anonymized, noninvasive clinical data were collected from baseline evaluation and follow-up, and 5-year estimated SCD risk was calculated (HCM Risk-Kids). RESULTS: MLVWT Z score was <10 in 598 (58.1%), ≥10 to <20 in 334 (31.1%), and ≥20 in 143 (13.3%). Higher MLVWT Z scores were associated with heart failure symptoms, unexplained syncope, left ventricular outflow tract obstruction, left atrial dilatation, and nonsustained ventricular tachycardia. One hundred twenty-two patients (71.3%) with MLVWT Z score ≥20 had coexisting risk factors for SCD. Over a median follow-up of 4.9 years (interquartile range, 2.3-9.3), 115 (10.7%) had an SCD event. Freedom from SCD event at 5 years for those with MLVWT Z scores <10, ≥10 to <20, and ≥20 was 95.6%, 87.4%, and 86.0, respectively. The estimated SCD risk at 5 years had a nonlinear, inverted U-shaped relationship with MLVWT Z score, peaking at Z score +23. The presence of coexisting risk factors had a summative effect on risk. CONCLUSIONS: In children with HCM, an inverted U-shaped relationship exists between left ventricular hypertrophy and estimated SCD risk. The presence of additional risk factors has a summative effect on risk. While MLVWT is important for risk stratification, it should not be used either as a binary variable or in isolation to guide implantable cardioverter defibrillator implantation decisions in children with HCM.