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Childhood hypertrophic cardiomyopathy; Outcomes; Phenotype Miocardiopatía hipertrófica infantil; Resultados; Fenotipo Miocardiopatia hipertròfica infantil; Resultats; Fenotip 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. This work was supported by the British Heart Foundation (grant FS/16/72/32270) to Drs Norrish and Kaski. This work is (partly) funded by the National Institute for Health Research Great Ormond Street Hospital Biomedical Research Centre. Dr Norrish is supported by Great Ormond Street Hospital Children’s Charity. Drs Field and Kaski are supported by Max’s Foundation and Great Ormond Street Hospital Children’s Charity. Dr Kaski is supported by a Medical Research Council–National Institute for Health Research Clinical Academic Research Partnership award. This work was financially supported by the Foundation for Paediatric Research of Finland (Dr Ojala). Dr Fernandez has received speaker fees from Sanofi-Genzyme. Dr Kubus is supported by MH CZ – DRO, Motol University Hospital (00064203). All other authors have reported that they have no relationships relevant to the contents of this paper to disclose.

The number of potential pediatric heart transplant recipients continues to exceed the number of donors, and consequently the waitlist mortality remains significant. Despite this, around 40% of all donated organs are not used and are discarded. This document (62 authors from 53 institutions in 17 countries) evaluates factors responsible for discarding donor hearts and makes recommendations regarding donor heart acceptance. The aim of this statement is to ensure that no usable donor heart is discarded, waitlist mortality is reduced, and post-transplant survival is not adversely impacted.

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 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 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.

(1) Background: Post-transplant lymphoproliferative disease (PTLD) is a significant complication of solid organ transplantation (SOT). However, there is lack of consensus in PTLD management. Our aim was to establish a present benchmark for comparison between international centers and between various organ transplant systems and modalities, (2) Methods: A cross-sectional questionnaire of relevant PTLD practices in pediatric transplantation was sent to multidisciplinary teams from 17 European center members of ERN TransplantChild to evaluate the centers’ approach strategies for diagnosis and treatment and how current practices impact a cross-sectional series of PTLD cases, (3) Results: A total of 34 SOT programs from 13 European centers participated. The decision to start preemptive treatment and its guidance was based on both EBV viremia monitoring plus additional laboratory methods and clinical assessment (61%). Among treatment modalities the most common initial practice at diagnosis was to reduce the immunosuppression (61%). A total of 126 PTLD cases were reported during the period 2012–2016. According to their histopathological classification, monomorphic lesions were the most frequent (46%). Graft rejection after PTLD remission was 33%. Of the total cases diagnosed with PTLD, 88% survived, (4) Conclusions: There is still no consensus on prevention and treatment of PTLD, which implies the need to generate evidence. This might successively allow the development of clinical guidelines.

The current pandemic SARS-CoV-2 has required an unusual allocation of resources that can negatively impact chronically ill patients and high-complexity procedures. Across the European Reference Network on Pediatric Transplantation (ERN TransplantChild), we conducted a survey to investigate the impact of the COVID-19 outbreak on pediatric transplant activity and healthcare practices in both solid organ transplantation (SOT) and hematopoietic stem cell transplantation (HSCT). The replies of 30 professionals from 18 centers in Europe were collected. Twelve of 18 centers (67%) showed a reduction in their usual transplant activity. Additionally, outpatient visits have been modified and restricted to selected ones, and the use of telemedicine tools has increased. Additionally, a total of 14 COVID-19 pediatric transplanted patients were identified at the time of the survey, including eight transplant recipients and six candidates for transplantation. Only two moderate-severe cases were reported, both in HSCT setting. These survey results demonstrate the limitations in healthcare resources for pediatric transplantation patients during early stages of this pandemic. COVID-19 disease is a major worldwide challenge for the field of pediatric transplantation, where there will be a need for systematic data collection, encouraging regular discussions to address the long-term consequences for pediatric transplantation candidates, recipients, and their families. info:eu-repo/semantics/publishedVersion

To investigate the epidemiology of acute respiratory tract infections (ARIs) in children younger than 24 months old with hemodynamically significant congenital heart diseases. Primary aim: incidence of hospital admission due to ARI. Secondary aims: risk factors, etiologic agents, clinical outcomes, and usefulness of preventive measures.Prospective, multicenter, epidemiologic study conducted in 57 Spanish hospitals covering four 7-month seasons (2004-2008).A total of 2613 patients were eligible for the study. Three hundred fifty-four patients (13.5%) (95% confidence interval: 12.3-14.9) required a total of 453 hospital admissions. Clinical diagnoses: bronchiolitis (54.1%), upper respiratory tract infection (21%), pneumonia (19.9%), and others (17.4%). Median length of hospital stay: 7.0 days. No etiologic agent was identified in two-thirds of the patients. In the remaining patients either a single agent (26.8%) or polymicrobial infection (5%) was identified. Respiratory syncytial virus (RSV) was the agent that was most commonly found (3.8% specific hospitalization rate). Children receiving adequate RSV prophylaxis (90.5%) had a 58.2% (95% confidence interval: 37.6-78.3) reduction in RSV hospitalization. Risk factors for admission included malnourishment, infant age, male gender, chromosome alterations, wheezing, inadequate RSV prophylaxis fulfillment, and siblings11 years of age. Pediatric intensive care unit care was required in 21.8% of the admissions and 9 patients (0.34%) died.Hospital admission rate and severity of ARI remain as important issues in hemodynamically significant congenital heart disease patients. The strict fulfillment of prophylactic recommendations against RSV is the only protective factor that can be modulated to decrease the ARI hospital admission rate.

Resumen: Introducción: Se comparan las tasas de hospitalización por infección respiratoria aguda en niños con cardiopatías congénitas significativas sin síndrome de Down y en niños con síndrome de Down, con y sin cardiopatías, menores de 24 meses. Material y métodos: Estudio epidemiológico, multicéntrico (53 hospitales), observacional y prospectivo, de octubre de 2006 a abril de 2007. Se siguió a 1.085 pacientes; 806 sin síndrome de Down y con cardiopatía significativa y 279 con síndrome de Down: 135 con cardiopatía significativa, 38 con cardiopatías leves y 105 sin cardiopatía. Resultados: Ingresaron 147 (13,1%) pacientes (intervalo de confianza del 95%, 11,2–15,2%) por infecciones respiratorias. Las tasas en niños sin y con síndrome de Down fueron del 11 frente al 19,1%. Entre los últimos, el 26,3%, con cardiopatías no significativas; el 23%, con cardiopatías significativas, y el 11,4%, sin cardiopatía. El diagnóstico principal (59,4%) fue bronquiolitis. Se identificó algún germen en el 36,2%. La tasa de ingreso específica por virus respiratorio sincitial fue del 4,4%, con diferencias entre los niños sin y con síndrome de Down (el 3,2 frente al 7,8%) y entre los grupos con síndrome de Down con cardiopatías no significativas (15,8%), cardiopatías significativas (9,3%) y sin cardiopatía (3%). Había recibido profilaxis contra el virus respiratorio sincitial el 83,4 frente al 39,9% de los niños sin y con síndrome de Down. No hubo diferencias en el tiempo ni en la gravedad de las estancias. Conclusiones: Las hospitalizaciones por infecciones respiratorias y específicamente por virus respiratorio sincitial predominan en los niños con síndrome de Down, y entre ellos, en los que tienen cardiopatías leves y escasa inmunoprofilaxis frente al virus respiratorio sincitial. Abstract: Introduction: We compare hospitalisation rates for acute respiratory tract infection in children younger than 24 months with significant congenital heart disease without Down's syndrome with those with Down's syndrome with or without congenital heart disease. Material and methods: This was an epidemiological, multicentre (53 Spanish hospitals), observational and prospective study, from October 2006 to April 2007. A total of 1085 patients were followed-up, of which 806 did not have Down's syndrome and 279 with Down's syndrome: 135 with significant, 38 with non significant and 105 without congenital heart disease. Results: A total of 147 patients (13.1%; 95% CI, 11.2–15.2%) required hospitalisation due to respiratory infection. Rates in patients without and with Down's syndrome were 11% vs 19.1%. In the Down's group, 26.3% had no significant, a 23% had significant and 11.4% had no congenital heart disease. The main diagnosis was bronchiolitis (59.4%). An infectious agent was found in 36.2% cases. The specific admission rate due to respiratory syncytial virus was 4.4%, with differences in children without vs with Down's syndrome (3.2% vs 7.8%). In the Down's patients we found rates of 15.8%, 9.3% and 3% in the non-significant, significant and no congenital heart disease. Immunoprophylaxis against respiratory syncytial virus rates were 83.4% vs 39.9% in no Down's versus Down's syndrome patients. No differences were found in hospital stay or the severity. Conclusions: Hospital admission rates due to respiratory infection, and specifically respiratory syncytial virus, were higher in the Down's patients, particularly in the group with no significant congenital heart disease and low immunoprophylaxis against respiratory syncytial virus.

Presentamos nuestra experiencia en el estudio de las cardiopatias congenitas (CPC) y seguimiento posquirurgico de dos anos de duracion, con resonancia magnetica (RM) y angiorresonancia tridimensional (angio-RM 3D). Se evaluan principalmente los aspectos tecnicos de realizacion, administracion de contraste y de preparacion anestesica en los casos pediatricos. No se detectaron complicaciones tras la administracion de gadolinio, y solamente se observaron dos casos de eritema cutaneo difuso transitorio sin aumento de la temperatura corporal. La RM y mas concretamente la angio-RM con gadolinio permite realizar un adecuado diagnostico y seguimiento posquirurgico de las CPC, y evita el riesgo de las radiaciones ionizantes y del cateterismo cardiaco en muchos casos.

BACKGROUND: Infants with cyanotic congenital heart disease palliated with placement of a systemic-to-pulmonary-artery shunt are at risk for shunt thrombosis and death. We investigated whether the addition of clopidogrel to conventional therapy reduces mortality from any cause and morbidity related to the shunt. METHODS: In a multicenter, double-blind, event-driven trial, we randomly assigned infants 92 days of age or younger with cyanotic congenital heart disease and a systemic-to-pulmonary-artery shunt to receive clopidogrel at a dose of 0.2 mg per kilogram of body weight per day (467 infants) or placebo (439 infants), in addition to conventional therapy (including aspirin in 87.9% of infants). The primary efficacy end point was a composite of death or heart transplantation, shunt thrombosis, or performance of a cardiac procedure due to an event considered to be thrombotic in nature before 120 days of age. RESULTS: The rate of the composite primary end point did not differ significantly between the clopidogrel group (19.1%) and the placebo group (20.5%) (absolute risk difference, 1.4 percentage points; relative risk reduction with clopidogrel, 11.1%; 95% confidence interval, -19.2 to 33.6; P=0.43), nor did the rates of the three components of the composite primary end point. There was no significant benefit of clopidogrel treatment in any subgroup, including subgroups defined by shunt type. Clopidogrel recipients and placebo recipients had similar rates of overall bleeding (18.8% and 20.2%, respectively) and severe bleeding (4.1% and 3.4%, respectively). CONCLUSIONS: Clopidogrel therapy in infants with cyanotic congenital heart disease palliated with a systemic-to-pulmonary-artery shunt, most of whom received concomitant aspirin therapy, did not reduce either mortality from any cause or shunt-related morbidity. (Funded by Sanofi-Aventis and Bristol-Myers Squibb; ClinicalTrials.gov number, NCT00396877.).

Desmoplakin plays a vital role in cell adhesion, linking the transmembrane desmosomal complex to the cytoskeletal network. Clues to the biological significance of desmoplakin have emerged from the embryonic lethal phenotype of null mice and from naturally occurring human desmoplakin mutations, which cause cardiocutaneous phenotypes.In this study, we describe a child who presented with the unique constellation of bullous dermatosis, profound plantar keratoderma, alopecia totalis and cardiomyopathy leading to sudden cardiac death at the age of 9 years.This complex cardiocutaneous phenotype is associated with compound heterozygosity for two novel nonsense desmoplakin mutations. Histological examination of a plantar skin biopsy showed full thickness epidermal acantholysis with superimposed spongiosis, hyperorthokeratosis and focal parakeratosis. Immunohistochemistry and quantitative confocal microscopy showed abnormal tissue distribution and reduced levels of expression for plakoglobin, desmoplakin and connexin 43 at epidermal junctional sites.Interpretation of the changes in the context of the two mutations provides insight into the mechanism of clinical cell adhesion disease.Asimaki A, Syrris P, Ward D, Guereta LG, Saffitz JE, McKenna WJ. Unique epidermolytic bullous dermatosis with associated lethal cardiomyopathy related to novel desmoplakin mutations.J Cutan Pathol 2009; 36: 553-559. (C) 2008 Blackwell Munksgaard.

ObjectivesTo evaluate the rate of hospitalization for acute respiratory tract infection in children less than 24 months with haemodynamically significant congenital cardiac disease, and to describe associated risk factors, preventive measures, aetiology, and clinical course.Materials and methodsWe followed 760 subjects from October 2004 through April 2005 in an epidemiological, multicentric, observational, follow-up, prospective study involving 53 Spanish hospitals.ResultsOf our cohort, 79 patients (10.4%, 95% CI: 8.2%–12.6%) required a total of 105 admissions to hospital related to respiratory infections. The incidence rate was 21.4 new admissions per 1000 patients-months. Significant associated risk factors for hospitalization included, with odds ratios and 95% confidence intervals shown in parentheses: 22q11 deletion (8.2, 2.5–26.3), weight below the 10th centile (5.2, 1.6–17.4), previous respiratory disease (4.5, 2.3–8.6), incomplete immunoprophylaxis against respiratory syncytial virus (2.2, 1.2–3.9), trisomy 21 (2.1, 1.1–4.2), cardiopulmonary bypass (2.0, 1.1–3.4), and siblings aged less than 11 years old (1.7, 1.1–2.9). Bronchiolitis (51.4%), upper respiratory tract infections (25.7%), and pneumonia (20%) were the main diagnoses. An infectious agent was found in 37 cases (35.2%): respiratory syncytial virus in 25,Streptococcus pneumoniaein 5, and Haemophilus influenzae in 4. The odds ratio for hospitalization due to infection by the respiratory syncytial virus increases by 3.05 (95% CI: 2.14 to 4.35) in patients with incomplete prophylaxis. The median length of hospitalization was 7 days. In 18 patients (17.1%), the clinical course of respiratory infection was complicated and 2 died.ConclusionsHospital admissions for respiratory infection in young children with haemodynamically significant congenital cardiac disease are mainly associated with non-cardiac conditions, which may be genetic, malnutrition, or respiratory, and to cardiopulmonary bypass. Respiratory syncytial virus was the most commonly identified infectious agent. Incomplete immunoprophylaxis against the virus increased the risk of hospitalization.

The association between respiratory viruses and myocarditis has hardly ever been described. We report a case of acute myocarditis in an immunocompetent child associated with the presence of parainfluenza virus type 3 infection, in a context of recent influenza illness, confirmed by molecular and serological studies.

Sir,—Rosenthal et al recently documented the presence of an atrioventricular bypass tract after a modified Fontan operation in which the right atrial appendage was anastomosed to the right ventricular outflow tract.1Their patient developed persistent supraventricular tachycardia resulting from atrioventricular re-entry within the surgical right anastomosis, which was abolished by radiofrequency ablation. They also mentioned a previous report of ablation after the Fontan operation.2 Based on the evidence of these …