Significance of colonization by antibiotic-resistant organisms prior to congenital heart disease surgery in children from low- to middle-income countries sent by non-governmental organizations to Switzerland.

PURPOSE: Children with congenital heart disease (CHD) from low- to middle-income countries (LMIC) are suspected to have a high prevalence of antibiotic-resistant microorganisms (ARMOs) carriage, but data are currently lacking. Carriage of ARMOs could impact the post-operative course in pediatric intensive care unit (PICU). The aim of the study was to assess the prevalence of ARMOs carriage in children with CHD from LMIC and its impact on post-operative outcomes. METHODS: This was a retrospective monocentric study from 01/2019 to 12/2022. Included patients were children (0-18 years) from a LMIC admitted after CHD surgery and with AMRO screening performed the week before. Infections and post-operative evolution were compared based on ARMOs carriage status. FINDINGS: Among 224 surgeries (median age 38.5 months (IQR 22-85.5)), ARMOs carriage was evidenced in 95 cases (42.4%). Main organisms isolated were Extended Spectrum Beta-Lactamase (ESBL) producing E. coli (75/224) 33.5%)) and ESBL-K. pneumoniae (30/224) 13.4%)). Median mechanical ventilation duration was 1 day (IQR 0-1), PICU stay 3 days (IQR 2-4) and hospital stay 6.5 days (IQR 5-10). A total of 17 infectious episodes occurred in 15 patients, mostly consisting in hospital-acquired pneumonia (HAP) (12/17). Only two infections were caused by a colonizing ARMO. Occurrence of infections and patients' outcome were similar between ARMO carriers and non-carriers. Higher use of carbapenems (6 (6.3%) vs 1 (0.8%), p = 0.04) and a trend to a higher use of vancomycin (14 (13.7%) vs 9 (6.9%), p = 0.04) in case of ARMOs carriage. Applying current guidelines, negative swab screening could have led to sparing most of empirical vancomycin therapy (11/12) for HAP based on current guidelines. CONCLUSION: Prevalence of AMROs carriage is high in children from LMIC and has a limited impact on patients' outcome. However, ARMOs carriage leads to higher consumption of antibiotics. Screening may help saving use of broad-spectrum antibiotic in non-carrier patients.

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.

Neurometabolism and brain morphometry in an adolescent female with an extra-hepatic congenital portosystemic shunt.

Background: Chronic hepatic encephalopathy (CHE) has been reported both in patients with congenital porto-systemic shunts (CPSS) and chronic liver disease. CHE is difficult to recognize in children as there is no clear definition and its manifestations are highly variable. CHE is associated with variations in brain volumes and metabolites that have already been demonstrated using 1.5-3T MRI systems. However, the in-depth study of brain metabolism requires the high spectral resolution of high magnetic fields. Objectives and Methods: We analyzed the neurometabolic profile, brain volumes and T1 relaxation times of a child with a CPSS using high field proton magnetic resonance spectroscopy (1H MRS, 7T) combined with MRI and compared it to an age-matched control group. We also evaluated the impact of shunt closure on neurocognitive symptoms using adapted neuropsychological tests. Results: 7T MRS revealed a significant increase in glutamine compared to controls, a decrease in brain osmolytes, and a slight elevation in NAA concentrations. 7T MRI scans showed morphological abnormalities but no changes in the signal intensity of the globus pallidus. Neurocognitive testing revealed attention deficit disorder, language difficulties, and mild intellectual disability. Most of these areas improved after shunt closure. Conclusions: In this paediatric case of type B HE with normal fasting ammonia, neurometabolic profile was compatible with what has been previously shown in chronic liver disease, while also demonstrating an isolated glutamine peak. In addition, neurocognitive function partially improved after shunt closure, arguing strongly for shunt closure in both presymptomatic and symptomatic patients.

Corrigendum to "Expert management of congenital portosystemic shunts and their complications" [JHEP Reports 6 (2024)].

[This corrects the article DOI: 10.1016/j.jhepr.2023.100933.].

Application of a modified clinical classification for pulmonary arterial hypertension associated with congenital heart disease in children: emphasis on atrial septal defects and transposition of the great arteries. An analysis from the TOPP registry.

Aims: A proportion of patients with pulmonary arterial hypertension associated with congenital heart disease (PAH-CHD) do not fit in the current classification. We aimed to analyse the applicability of an adapted clinical classification of PAH-CHD to pediatric patients using the TOPP-1 registry (Tracking Outcomes and Practice in Pediatric Pulmonary Hypertension) and focus on atrial septal defects (ASD) and transposition of the great arteries (TGA). Methods and results: Hemodynamic and clinical data of all patients with PAH-CHD in the TOPP cohort were reviewed. Patients were classified according to predefined ABCDE categories (A: Eisenmenger syndrome, B: left-to-right shunt, C: coincidental defects, including all ASDs, D: corrected CHD, E: TGA), or as complex CHD (group 5), by 2 independent investigators. In case of disagreement, a third reviewer could either settle a final decision, or the patient was deemed not classifiable. Survival curves were calculated for each group and compared to idiopathic PAH patients of the registry. A total of 223 out of 531 patients in the registry had PAH-CHD, and 193 were categorized to the following groups: A 39(20%), B 27(14%), C 62(32%) including 43 ASDs, D 58(30%), E 7(4%), whereas 6 patients were categorized as group 5, and 10 patients were unable to be classified. No survival difference could be demonstrated between the groups. Conclusions: This modified classification seems to be more applicable to pediatric PAH-CHD patients than the previous classification, but some patients with PAH-CHD who never had a shunt remain unclassifiable. The role of ASD in pediatric PH should be reconsidered.

Expert management of congenital portosystemic shunts and their complications.

Congenital portosystemic shunts are often associated with systemic complications, the most challenging of which are liver nodules, pulmonary hypertension, endocrine abnormalities, and neurocognitive dysfunction. In the present paper, we offer expert clinical guidance on the management of liver nodules, pulmonary hypertension, and endocrine abnormalities, and we make recommendations regarding shunt closure and follow-up.

Infective Endocarditis Due to Kingella kingae.

Infective endocarditis due to Kingella kingae is a rare but serious invasive infection that occurs mostly in children. Recent advances in nucleic acid amplification testing as well as in cardiac imaging have enabled more accurate diagnosis. A good understanding of the epidemiology and virulence factors remains crucial to guide the therapeutic approach. Here, we synthesize the current state of knowledge on epidemiological features, pathophysiological insights, complications, and therapy regarding Kingella kingae endocarditis in children and adults. Finally, throughout this comprehensive review, knowledge gaps and areas for future research are also identified.

TBX20 loss-of-function variants in families with left ventricular non-compaction cardiomyopathy.

TBX20 encodes a cardiac transcription factor that is associated with atrial septal defects. Recent studies implicate loss-of-function TBX20 variants with left ventricular non-compaction cardiomyopathy (LVNC), although clinical and genetic data in families are limited. We report four families with TBX20 loss-of-function variants that segregate with LVNC. Genetic testing using genome or exome sequencing was performed in index cases, variants were validated with Sanger sequencing, and cascade genetic testing was performed in family members. A multi-exon deletion, small deletion, essential splice site variant and nonsense variant in TBX20 were found in four families. The index cases in two families were symptomatic children with identical congenital heart diseases and LVNC who developed different cardiomyopathy phenotypes with one developing heart failure requiring transplantation. In another family, the child index case had LVNC and congestive heart failure requiring heart transplantation. In the fourth family, the index case was a symptomatic adult with LVNC. In all families, the variants segregated in relatives with isolated LVNC, or with congenital heart disease or cardiomyopathy. Family members displayed a clinical spectrum from asymptomatic to severe presentations including heart failure. Our data strengthen TBX20 loss-of-function variants as a rare cause of LVNC and support TBX20 inclusion in genetic testing of LVNC.

Death by Neurologic Criteria in Children Undergoing Extracorporeal Cardiopulmonary Resuscitation: Retrospective Extracorporeal Life Support Organization Registry Study, 2017-2021.

OBJECTIVES: To determine factors associated with brain death in children treated with extracorporeal cardiopulmonary resuscitation (E-cardiopulmonary resuscitation). DESIGN: Retrospective database study. SETTINGS: Data reported to the Extracorporeal Life Support Organization (ELSO), 2017-2021. PATIENTS: Children supported with venoarterial extracorporeal membrane oxygenation (ECMO) for E-cardiopulmonary resuscitation. INTERVENTION: None. MEASUREMENTS AND MAIN RESULTS: Data from the ELSO Registry included patient characteristics, blood gas values, support therapies, and complications. The primary outcome was brain death (i.e., death by neurologic criteria [DNC]). There were 2,209 children (≥ 29 d to < 18 yr of age) included. The reason for ECMO discontinuation was DNC in 138 patients (6%), and other criteria for death occurred in 886 patients (40%). Recovery occurred in 1,109 patients (50%), and the remaining 76 patients (4%) underwent transplantation. Fine and Gray proportional subdistribution hazards' regression analyses were used to examine the association between variables of interest and DNC. Age greater than 1 year ( p < 0.001), arterial blood carbon dioxide tension (Pa co2 ) greater than 82 mm Hg ( p = 0.022), baseline lactate greater than 15 mmol/L ( p = 0.034), and lactate 24 hours after cannulation greater than 3.8 mmol/L ( p < 0.001) were independently associated with greater hazard of subsequent DNC. In contrast, the presence of cardiac disease was associated with a lower hazard of subsequent DNC (subdistribution hazard ratio 0.57 [95% CI, 0.39-0.83] p = 0.004). CONCLUSIONS: In children undergoing E-cardiopulmonary resuscitation, older age, pre-event hypercarbia, higher before and during ECMO lactate levels are associated with DNC. Given the association of DNC with hypercarbia following cardiac arrest, the role of Pa co2 management in E-cardiopulmonary resuscitation warrants further studies.

The burden of splice-disrupting variants in inherited heart disease and unexplained sudden cardiac death.

There is an incomplete understanding of the burden of splice-disrupting variants in definitively associated inherited heart disease genes and whether these genes can amplify from blood RNA to support functional confirmation of splicing outcomes. We performed burden testing of rare splice-disrupting variants in people with inherited heart disease and sudden unexplained death compared to 125,748 population controls. ClinGen definitively disease-associated inherited heart disease genes were amplified using RNA extracted from fresh blood, derived cardiomyocytes, and myectomy tissue. Variants were functionally assessed and classified for pathogenicity. We found 88 in silico-predicted splice-disrupting variants in 128 out of 1242 (10.3%) unrelated participants. There was an excess burden of splice-disrupting variants in PKP2 (5.9%), FLNC (2.7%), TTN (2.8%), MYBPC3 (8.2%) and MYH7 (1.3%), in distinct cardiomyopathy subtypes, and KCNQ1 (3.6%) in long QT syndrome. Blood RNA supported the amplification of 21 out of 31 definitive disease-associated inherited heart disease genes. Our functional studies confirmed altered splicing in six variants. Eleven variants of uncertain significance were reclassified as likely pathogenic based on functional studies and six were used for cascade genetic testing in 12 family members. Our study highlights that splice-disrupting variants are a significant cause of inherited heart disease, and that analysis of blood RNA confirms splicing outcomes and supports variant pathogenicity classification.

Dual-energy computed tomography to detect early pulmonary vascular changes in children with sickle cell disease: a pilot study.

Introduction: Pulmonary hypertension (PH) is a rare but fatal complication of sickle cell disease (SCD) that is possibly reversible if treated early. Dual-energy computed tomography (DECT) is a valuable tool for diagnosing PH. We attempted to determine if DECT can detect early signs of PH in children with SCD. Methods: This prospective observational pilot study was conducted at the Geneva University Hospitals and was approved by the local human ethics committee (CCER 2019-01975). A written informed consent was obtained from the patients and/or their legal guardian. Eight children (consisting of five girls and three boys) with homozygous SCD were included in the study. They underwent full cardiological workup using transthoracic echocardiography (TTE) and cardiopulmonary exercise test (CPET), as well as DECT. Results: The median age of the children was 11 years old (range 8-12). All patients exhibited a normal biventricular systo-diastolic function using the TTE. The median tricuspid regurgitant jet velocity value was 2.24 m/s (range 1.96-2.98). Four children were found to have signs of vasculopathy detected on DECT. Of them, two had abnormal screening test results. They both had an increased VE/VCO2 slope during CPET and an increased TVR of >2.5 m/s on TTE. Conclusion: DECT is capable of identifying early signs of pulmonary vascular disease in children with SCD. Further studies are needed to understand the correlation between DECT abnormalities and hemodynamic pulmonary circulation better.

Triple switch' aortic and pulmonary root inversion and modified Senning procedure for anatomically complex left transposition of the great arteries with inlet ventricular septal defect and pulmonary stenosis.

Left transposition of the great arteries with inlet ventricular septal defect and pulmonary stenosis is a relatively uncommon cardiac malformation. Two surgical treatments are available: double switch or physiological correction. The choice of surgical technique depends on the results of a discussion between the family and the surgeon. Choosing the appropriate technique is challenging because all options present various complications and benefits. We present a 'triple switch' aortic and pulmonary root inversion and modified Senning procedure for an anatomically complex left transposition of the great arteries with an inlet ventricular septal defect and pulmonary stenosis.

Pulmonary vascular disease as a complication of pediatric congenital heart diseases.

Congenital and acquired heart diseases can cause pulmonary hypertension (PH) in children, either by increasing pulmonary blood flow (PBF), left atrial pressure (LAp), and/or pulmonary vascular resistance (PVR). Pathophysiological process of pulmonary vascular disease (PVD) in different types of congenital heart diseases (CHDs) are reviewed hereafter. As with other types of PH, a rigorous diagnostic evaluation is mandatory to characterize the etiology of the PH, rule out other or additional causes of PH, and establish a risk profile. Cardiac catheterization remains the gold standard exam for PH diagnosis. Treatment of pulmonary arterial hypertension (PAH) associated with CHD (PAH-CHD) can then be started according to the recent guidelines recommendations, although most of the evidence is extrapolated from studies on other causes of PAH. PH in pediatric heart disease is often multifactorial, and sometimes unclassifiable, making the management of these patients complicated. The operability of patients with a prevalent left-to-right shunt and increase of PVR, the management of children with PH associated with left-sided heart disease, the challenges of pulmonary vascular disorders in children with univentricular heart physiology and the role of vasodilator therapy in failing Fontan patients are some of the hot topics discussed in this review.

Successful heart transplant in a child with congenital core myopathy and delayed-onset restrictive cardiomyopathy due to recessive mutations in the titin (TTN) gene.

BACKGROUND: Mutations in the TTN gene, encoding the muscle filament titin, are a major cause of inherited dilated cardiomyopathy. Early-onset skeletal muscle disorders due to recessive TTN mutations have recently been described, sometimes associated with cardiomyopathies. CASE DESCRIPTION: We report the case of a boy with congenital core myopathy due to compound heterozygosity for TTN variants. He presented in infancy with rapidly evolving restrictive cardiomyopathy, requiring heart transplantation at the age of 5 years with favorable long-term cardiac and neuromuscular outcome. CONCLUSION: Heart transplantation may have a role in selected patients with TTN-related congenital myopathy with disproportionally severe cardiac presentation compared to skeletal and respiratory muscle involvement.

Use of CO2-Derived Variables in Cardiac Intensive Care Unit: Pathophysiology and Clinical Implications.

Shock is a life-threatening condition, and its timely recognition is essential for adequate management. Pediatric patients with congenital heart disease admitted to a cardiac intensive care unit (CICU) after surgical corrections are particularly at risk of low cardiac output syndrome (LCOS) and shock. Blood lactate levels and venous oxygen saturation (ScVO2) are usually used as shock biomarkers to monitor the efficacy of resuscitation efforts, but they are plagued by some limitations. Carbon dioxide (CO2)-derived parameters, namely veno-arterial CO2 difference (ΔCCO2) and the VCO2/VO2 ratio, may represent a potentially valuable addition as sensitive biomarkers to assess tissue perfusion and cellular oxygenation and may represent a valuable addition in shock monitoring. These variables have been mostly studied in the adult population, with a strong association between ΔCCO2 or VCO2/VO2 ratio and mortality. In children, particularly in CICU, few studies looked at these parameters, while they reported promising results on the use of CO2-derived indices for patients' management after cardiac surgeries. This review focuses on the physiological and pathophysiological determinants of ΔCCO2 and VCO2/VO2 ratio while summarizing the actual state of knowledge on the use of CO2-derived indices as hemodynamical markers in CICU.

The Influence of Methods for Cardiac Output Determination on the Diagnosis of Precapillary Pulmonary Hypertension: A Mathematical Model.

Background: precapillary pulmonary hypertension (PH, PcPH) is now defined as a mean pulmonary artery pressure (mPAP) > 20 mmHg, a pulmonary artery wedge pressure (PAWP) ≤ 15 mmHg and a pulmonary vascular resistance (PVR) > 2 WU. For PVR calculation, the measurement of cardiac output (CO) is necessary. It is generally measured using thermodilution. However, recent data showed that the agreement with direct Fick method, historically the gold standard, is less than previously reported. We aimed to create a mathematical model that calculated the probability of being classified differently (PcPH or unclassified PH) if CO measured by direct Fick was used instead of thermodilution for any individual patients with a mPAP > 20 mmHg and a PAWP ≤ 15 mmHg. Methods: The model is based on Bland and Altman analysis with a normally distributed difference of cardiac output, fixed 1.96 standard deviation of bias, bias and physiological cardiac output limits. Results: Following a literature review of the studies comparing CO measured with direct Fick and thermodilution, we fixed the 1.96 standard deviation of bias at 2 L/min, bias at 0 L/min and physiological resting CO limits between 1.3 L/min and 10.2 L/min. Conclusions: This model can help the clinician to evaluate the potential benefit of measuring CO using direct Fick during the diagnostic work-up and its utility in confirming or ruling out a diagnosis of PcPH in any given patient with a mPAP > 20 mmHg and a PAWP ≤ 15 mmHg.

Early and Late Postoperative Tachyarrhythmias in Children and Young Adults Undergoing Congenital Heart Disease Surgery.

The population of patients with congenital heart disease is constantly growing with an increasing number of individuals reaching adulthood. A significant proportion of these children and young adults will suffer from tachyarrhythmias due to the abnormal anatomy, the hemodynamic burden, or as a sequela of surgical treatment. Depending on the underlying mechanism, arrhythmias may arise in the early postoperative period (hours to days after surgery) or in the late postoperative period (usually years after surgery). A good understanding of the electrophysiological characteristics and pathophysiological mechanisms is therefore crucial to guide the therapeutic approach. Here, we synthesize the current state of knowledge on epidemiological features, risk factors, pathophysiological insights, electrophysiological features, and therapy regarding tachyarrhythmias in children and young adults undergoing reparative surgery for congenital heart disease. The evolution and latest data on treatment options, including pharmacological therapy, ablation procedures, device therapy decision, and thromboprophylaxis, are summarized. Finally, throughout this comprehensive review, knowledge gaps and areas for future research are also identified.