Children with critical CHD are at risk for neurodevelopmental impairments, including delays in expressive and receptive language development. However, no study has synthesised the literature regarding language abilities in children with this condition.

We summarised the literature regarding expressive and receptive language in preschool children with critical CHD.

MEDLINE, Embase, Scopus, Child Development and Adolescent Studies, ERIC, PsycINFO, and CINAHL.

We included studies published between January, 1990 and 1 July, 2021, focused on children aged ≤5 years with critical CHD requiring a complex cardiac procedure at age <1 year. Language ability was documented using standardised, validated tools assessing both expressive and receptive language outcomes.

Data (study, patient and language characteristics, and results) were extracted by two reviewers.

Seventeen studies were included. Among children 2–5 years old with critical CHD, there were statistically significant deficits in overall (standardised mean difference: –0.46; 95 % confidence interval: –0.56, –0.35), expressive (standardised mean difference: –0.45;95 % confidence interval: –0.54, –0.37), and receptive (standardised mean difference: –0.32; 95 % confidence interval: –0.40, –0.23) language compared to normative data. Results reported as medians were similar to meta-analysis findings. Subgroup analysis showed that children with univentricular physiology had lower language scores than children with biventricular physiology.

Preschool children with critical CHD had statistically significantly lower language outcomes compared to expected population norms. Healthcare professionals should test early and often for language deficits, referring to individually tailored supports.

While there is evidence that cognitive impairment of children with congenital heart disease (CHD) may persist into adolescence, little is known about the spectrum of neurocognitive functioning of young adults with this disorder. The aim of this study was to assess neurocognitive functioning in a population of young adults with different types of CHD.

Cross-sectional cohort study in young adults with CHD and a group-matched healthy control group. We assessed neurocognitive and general intellectual functioning with a comprehensive battery of standardised neuropsychological tests. In addition to task-based assessments, questionnaire data of executive dysfunctions in everyday life were measured with the Behaviour Rating Inventory of Executive Function – Adult Version.

A total of 67 patients (55% men) with CHD and 55 healthy controls (51% men) were included for analysis. Mean age at assessment was 26.9 (3.68) and 26.0 (3.32) years, respectively. The CHD group performed poorer in the domains of Executive Functions, Memory, Attention & Speed, and general intellectual functioning. Patients with a CHD of severe complexity were more affected than patients with simple or moderate complexity. Behaviour Rating Inventory of Executive Function – Adult Version scores indicated that patients’ self-rated deficits in behaviour regulation in everyday life was higher compared with healthy controls.

Our findings indicate lower neurocognitive functioning in young adults with a CHD, particularly in those with severe defect complexity. In view of the potentially enhanced risk for cerebrovascular and neurodegenerative disease in this patient group as reported in the literature, systematic longitudinal monitoring of cognitive functioning is recommended.

Congenital atrioventricular block is diagnosed in uterine life, at birth, or early in life. Atrioventricular blocks can be life threatening immediately at birth so urgent pacemaker implantation techniques are requested. Reasons can be cardiac or non-cardiac, but regardless of the reason, operations are challenging. We aimed to present technical procedure and operative results of pacemaker implantation in neonates.

Between June 2014 and February 2021, 10 neonates who had congenital atrioventricular block underwent surgical operation to implant permanent epicardial pacemaker by using minimally invasive technique. Six of the patients were female and four of them were male. Mean age was 4.3 days (0–11), while three of them were operated on the day of birth. Mean weight was 2533 g (1200–3300).

Operations were achieved through subxiphoidal minimally skin incision. Epicardial 25 mm length dual leads were implanted on right ventricular surface and generators were fixed on the right (seven patients) or left (three patients) diaphragmatic surface by incising pleura. There were no complication, morbidity, and mortality related to surgery.

Few studies have characterised the surgical outcomes following epicardial permanent pacemaker implantation in neonates. The surgical approach is attractive and compelling among professionals so we aimed to present the techniques and results in patients who required permanent pacemaker implantation in the first month of life.

Patients with cyanotic heart disease are at an increased risk of developing thrombosis. Aspirin has been the mainstay of prophylactic anticoagulation for shunt-dependent patients with several reports of prevalent aspirin resistance, especially in neonates. We investigate the incidence of aspirin resistance and its relationship to thrombotic events and mortality in a cohort of infants with shunt-dependent physiology.

Aspirin resistance was assessed using the VerifyNow™ test on infants with single-ventricle physiology following shunt-dependent palliation operations. In-hospital thrombotic events and mortality data were collected. Statistical analysis was performed to evaluate the effect of aspirin resistance on in-hospital thrombotic events and mortality risk.

Forty-nine patients were included with 41 of these patients being neonates. Six patients (12%) were aspirin resistant. A birth weight < 2500 grams was a significant factor associated with aspirin resistance (p = 0.04). Following a dose increase or additional dose administration, all patients with initial aspirin resistance had a normal aspirin response. There was no statistically significant difference between aspirin resistance and non-resistance groups with respect to thrombotic events. However, a statistically significant incidence of in-hospital mortality in the presence of thrombotic events was observed amongst aspirin-resistant patients (p = 0.04) in this study.

Low birth weight was associated with a higher incidence of aspirin resistance. Inadequate initial dosing appears to be the primary reason for aspirin resistance. The presence of both thrombotic events and aspirin resistance was associated with significantly higher in-hospital mortality indicating that these patients warrant closer monitoring.

To determine the utility of screening electrocardiograms after severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection among children in detecting myocarditis related to coronavirus disease 2019 (COVID-19).

A retrospective chart review was performed at a large paediatric academic institution to identify patients with prior SARS-CoV-2 infection who received a screening electrocardiogram by their primary care providers and were subsequently referred for outpatient cardiology consultation due to an abnormal electrocardiogram. The outcomes were the results from their cardiology evaluations, including testing and final diagnoses.

Among 46 patients, during their preceding COVID-19 illness, the majority had mild symptoms, 4 were asymptomatic, and 1 had moderate symptoms. The median length of time from positive SARS-CoV-2 test to screening electrocardiogram was 22 days, and many electrocardiogram findings that prompted cardiology consultation were normal variants in asymptomatic adolescent athletes. Patients underwent frequent additional testing at their cardiology appointments: repeat electrocardiogram (72%), echocardiogram (59%), Holter monitor (11%), exercise stress test (7%), and cardiac MRI (2%). Five patients were incidentally diagnosed with CHD or structural cardiac abnormalities, and three patients had conduction abnormalities (pre-mature atrial contractions, pre-mature ventricular contractions, borderline prolonged QTc), although potentially incidental to COVID-19. No patients were diagnosed with myocarditis or ventricular dysfunction.

In a small cohort of children with prior COVID-19, who were primarily either asymptomatic or mildly symptomatic, subsequent screening electrocardiograms identified various potential abnormalities prompting cardiology consultation, but no patient was diagnosed with myocarditis. Larger multi-centre studies are necessary to confirm these results and to evaluate those with more severe disease.

A novel paediatric disease, multi-system inflammatory syndrome in children, has emerged during the 2019 coronavirus disease pandemic.

To describe the short-term evolution of cardiac complications and associated risk factors in patients with multi-system inflammatory syndrome in children.

Retrospective single-centre study of confirmed multi-system inflammatory syndrome in children treated from 29 March, 2020 to 1 September, 2020. Cardiac complications during the acute phase were defined as decreased systolic function, coronary artery abnormalities, pericardial effusion, or mitral and/or tricuspid valve regurgitation. Patients with or without cardiac complications were compared with chi-square, Fisher’s exact, and Wilcoxon rank sum.

Thirty-nine children with median (interquartile range) age 7.8 (3.6–12.7) years were included. Nineteen (49%) patients developed cardiac complications including systolic dysfunction (33%), valvular regurgitation (31%), coronary artery abnormalities (18%), and pericardial effusion (5%). At the time of the most recent follow-up, at a median (interquartile range) of 49 (26–61) days, cardiac complications resolved in 16/19 (84%) patients. Two patients had persistent mild systolic dysfunction and one patient had persistent coronary artery abnormality. Children with cardiac complications were more likely to have higher N-terminal B-type natriuretic peptide (p = 0.01), higher white blood cell count (p = 0.01), higher neutrophil count (p = 0.02), severe lymphopenia (p = 0.05), use of milrinone (p = 0.03), and intensive care requirement (p = 0.04).

Patients with multi-system inflammatory syndrome in children had a high rate of cardiac complications in the acute phase, with associated inflammatory markers. Although cardiac complications resolved in 84% of patients, further long-term studies are needed to assess if the cardiac abnormalities (transient or persistent) are associated with major cardiac events.

To explore the feasibility and superiority of applying the WeChat platform in a midterm follow-up of surgical repair for ventricular septal defects in infants.

Eighty-six infants with VSD who underwent surgical repair were divided into an outpatient follow-up group and a WeChat follow-up group. The clinical data, including complications, economic cost, time spent, loss to follow-up rate, and parents’ satisfaction at the 3-month and 1-year follow-ups, were recorded and analysed.

There was no significant difference in the incidence of post-operative complications between the two groups. Although the loss to follow-up rate in the WFU group was lower than that of the OFU group, the difference was not statistically significant. The economic cost and time spent in the 3 months and 1 year after discharge in the WFU group were significantly lower than those in the OFU group. One year after discharge, the PSQ-18 score of the WFU group was significantly higher than that of the OFU group.

Compared with outpatient follow-up, the WeChat platform at the midterm follow-up after surgical repair of VSDs in infants has the advantages of saving time and economic costs and improves parents’ satisfaction.

The objective of this study was to investigate changes in serum biomarkers of acute brain injury, including white matter and astrocyte injury during chronic foetal hypoxaemia. We have previously shown histopathological changes in myelination and neuronal density in fetuses with chronic foetal hypoxaemia at a level consistent with CHD.

Mid-gestation foetal sheep (110 ± 3 days gestation) were cannulated and attached to a pumpless, low-resistance oxygenator circuit, and incubated in a sterile fluid environment mimicking the intrauterine environment. Fetuses were maintained with an oxygen delivery of 20–25 ml/kg/min (normoxemia) or 14–16 ml/kg/min (hypoxaemia). Myelin Basic Protein and Glial Fibrillary Acidic Protein serum levels in the two groups were assessed by ELISA at baseline and at 7, 14, and 21 days of support.

Based on overlapping 95% confidence intervals, there were no statistically significant differences in either Myelin Basic Protein or Glial Fibrillary Acidic Protein serum levels between the normoxemic and hypoxemic groups, at any time point. No statistically significant correlations were observed between oxygen delivery and levels of Myelin Basic Protein and Glial Fibrillary Acidic Protein.

Chronic foetal hypoxaemia during mid-gestation is not associated with elevated serum levels of acute white matter (Myelin Basic Protein) or astrocyte injury (Glial Fibrillary Acidic Protein), in this model. In conjunction with our previously reported findings, our data support the hypothesis that the brain dysmaturity with impaired myelination found in fetuses with chronic hypoxaemia is caused by disruption of normal developmental pathways rather than by direct cellular injury.

To examine relationships amongst parental post-traumatic stress symptoms, parental post-traumatic growth, overprotective parenting, and child emotional/behavioural problems in families of children with critical CHD.

Sixty parents (15 fathers) of children aged 1–6 completed online questionnaires assessing parental post-traumatic stress symptoms and post-traumatic growth, overprotective parenting, and child emotional/behavioural problems. Bivariate correlations and mediational analyses were conducted to evaluate overprotective parenting as a mediator of the association between parental post-traumatic stress symptoms and child emotional/behavioural problems.

Parents reported significant post-traumatic stress symptoms, with over 18% meeting criteria for post–traumatic stress disorder and 70% meeting criteria in one or more clusters. Parental post-traumatic growth was positively correlated with intrusion (r = .32, p = .01) but it was not associated with other post-traumatic stress symptom clusters. Parental post-traumatic stress symptoms were positively associated with overprotective parenting (r = .37, p = .008) and total child emotional/behavioural problems (r = .29, p = .037). Overprotective parenting was positively associated with total child emotional/behavioural problems (r = .45, p = .001) and fully mediated the relationship between parental post-traumatic stress symptoms and child emotional/behavioural problems.

Overprotective parenting mediates the relationship between parental post-traumatic stress symptoms and child emotional and behavioural problems in families of children with CHD. Both parental post-traumatic stress symptoms and overprotective parenting may be modifiable risk factors for poor child outcomes. This study highlights the need for interventions to prevent or reduce parental post-traumatic stress symptoms and to promote effective parenting following a diagnosis of CHD.

In this study, we assessed the acute changes in biventricular longitudinal strain after atrial septal defect transcatheter closure and its relation to the device size.

Hundred atrial septal defect patients and 40 age-matched controls were included. Echocardiography and strain study were performed at baseline and 24 hours and 1 month after the intervention. The study group was divided into two subgroups; group 1: smaller devices were used (mean device size = 1.61 ± 0.05 cm, n = 74) and group 2: larger devices were used (mean device size = 2.95 ± 0.07 cm, n = 26).

At baseline, there was a significant difference between the study group and controls as regards right ventricular global longitudinal strain with significant hyperkinetic apex (p = 0.033, p = 0.020, respectively). There was a significant immediate reduction in right ventricular global longitudinal strain (from −24.43 ± 0.49% to −21.62 ± 0.47%, p < 0.001), which showed insignificant improvement after 1-month follow-up. While only left ventricular global longitudinal strain increased after 1 month. Within 24 hours of device closure, all the basal- and mid-lateral segments strains and apical right ventricular strains showed a significant reduction. There was a significant negative correlation between the indexed large device size and an immediate change in the right ventricular global longitudinal strain (r = −0.425, p = 0.034).

Significant right ventricular global longitudinal strain reduction starts as early as 24 hours after transcatheter closure, irrespective of the device size used. The rapid impact of closure was mainly on the biventricular basal and lateral segments and right ventricular apical ones, especially with the large sized atrial septal defect.

Transcatheter ventricular septal defect closure remains a complex procedure with potential complications like complete heart block and aortic regurgitation. The ideal device design for such intervention is still evolving.

To assess the safety, efficacy, and short-term outcome of ventricular septal defect closure using LifeTechTM multifunctional (KONAR-MFTM) VSD Occluder.

In a multicenre study, 44 patients with haemodynamically significant, restrictive ventricular septal defects underwent closure with the KONAR-MFTM device from April, 2019 to March, 2020. Clinical, echocardiographic, and angiographic data were collected and reviewed. Patients were followed up at 1, 3, 6, and 12 months.

The median age and weight were 8 (1.7–36) years and 20 (11–79) kg. Of 44 patients, 8 (18%) had a high muscular and 36 (82%) had a perimembranous defect, of which 6 had mild prolapse of the right coronary cusp. The median ventricular septal defect size was 8.8 (3.9–13.4) mm. A retrograde approach was adopted in 39 (88.6%) patients. Nine patients (20.5%) had a small residual leak and there was a slight increase in aortic regurgitation in one patient. One device, which embolised to pulmonary artery was retrieved, and the defect was closed with a larger device. At a median follow-up of 13 (5–18) months, the residual leak persisted in 1 (2.3%) patient. Mild aortic regurgitation in one patient remained unchanged. There were no major complications.

Percutaneous closure of ventricular septal defect using KONAR-MFTM device is safe and effective in short and midterm follow-up including selected patients with perimembranous defect and mild prolapse of the right coronary cusp.

Recent studies confirm the role of B vitamins deficiency and hyperhomocysteinaemia in the development of dysautonomia that has been considered to be the main factor in vasovagal syncope development. The aim of the study was to investigate serum pyridoxine, folate, cobalamin, and homocysteine levels in children presenting with vasovagal syncope and to analyse the correlation between them and main clinical parameters of syncope.

We studied 40 children, ages 8–17 years with a history of vasovagal syncope and 24 healthy volunteers. The serum pyridoxine, folate, cobalamin, and homocysteine levels were measured by a quantitative sandwich enzyme immunoassay technique using a commercial kit (Monobind, USA). Twenty-four-hour Holter monitoring and 24-hour ambulatory blood pressure monitoring were conducted for all participated patients.

Serum pyridoxine (9.42 ± 4.87, 16.11 ± 5.53 µg/L) and cobalamin (307.48 ± 95.50, 447.28 ± 108.85 ng/L) levels were reasonably low (p < 0.05) in patients with vasovagal syncope. Although there was no significant change in folate levels between syncope and healthy children (4.00 ± 1.34, 4.71 ± 1.73 µg/L; p = 0.20), we detected low folate-level association with longer duration of syncope (r = −0.42) and post syncope (r = −0.43) symptoms (p < 0.05). Finally, there was increased serum homocysteine level (13.55 ± 5.03, 7.81 ± 1.71 µmol/L; p < 0.05) in patients with vasovagal syncope. It was positively correlated with the average PQ interval (r = 0.35, p < 0.05) and average QTc interval (r = 0.49, p < 0.05).

The results suggested that pyridoxine, folate, cobalamin, and homocysteine may be involved in the pathogenesis of vasovagal syncope. This might provide a new approach for effective treatment of paediatric vasovagal syncope, requiring further study.

Paediatric cardiology fellows, tasked with studying a large and dynamic field, may benefit from a quick-access digital resource that reflects contemporary practice. The objective of this study was to evaluate the effectiveness of a paediatric cardiology handbook smartphone app in enhancing the accessibility of information such as guidelines and recommendations for paediatric cardiology fellows.

The Peds Cardiology Handbook app (iOS) was designed using XCode and Swift programming. A pre-app survey and download instructions were sent to the US paediatric cardiology fellows, followed by a post-app survey. Fellows were asked to rate the ease of rapid access to various types of information. Responses were compared pre- and post-app using McNemar’s test and Wilcoxon signed-rank test.

Two-hundred and thirty paediatric cardiology fellows were contacted; 23% (n = 53) completed both the pre- and post-app surveys and were included for analysis. After using the app, fellows found it easier to quickly access information in eight out of nine domains evaluated (p < 0.05). All fellows found the app easy to use (100%), most felt that the app was well-organised (98%), contained reliable information (92%), and was useful for finding quick answers to clinical questions (87%).

The Peds Cardiology Handbook iPhone app is a useful, reliable tool that provides quick access to high-yield information, including guidelines and references. Overall, paediatric cardiology fellows found it easier to rapidly access clinically relevant information after using the app. Future studies may be necessary to evaluate long-term use and impact on evidence-based practice.

Hypotension is an adverse event that may be related to systemic exposure of milrinone; however, the true exposure–safety relationship is unknown.

Using the Pediatric Trials Network multicentre repository, we identified children ≤17 years treated with milrinone. Hypotension was defined according to age, using the Pediatric Advanced Life Support guidelines. Clinically significant hypotension was defined as hypotension with concomitant lactate >3 mg/dl. A prior population pharmacokinetic model was used to simulate milrinone exposures to evaluate exposure–safety relationships.

We included 399 children with a median (quarter 1, quarter 3) age of 1 year (0,5) who received 428 intravenous doses of milrinone (median infusion rate 0.31 mcg/kg/min [0.29,0.5]). Median maximum plasma milrinone concentration was 110.7 ng/ml (48.4,206.2). Median lowest systolic and diastolic blood pressures were 74 mmHg (60,85) and 35 mmHg (25,42), respectively. At least 1 episode of hypotension occurred in 178 (45%) subjects; clinically significant hypotension occurred in 10 (2%). The maximum simulated milrinone plasma concentrations were higher in subjects with clinically significant hypotension (251 ng/ml [129,329]) versus with hypotension alone (86 ng/ml [44, 173]) versus without hypotension (122 ng/ml [57, 208], p = 0.002); however, this relationship was not retained on multivariable analysis (odds ratio 1.01; 95% confidence interval 0.998, 1.01).

We successfully leveraged a population pharmacokinetic model and electronic health record data to evaluate the relationship between simulated plasma concentration of milrinone and systemic hypotension occurrence, respectively, supporting the broader applicability of our novel, efficient, and cost-effective study design for examining drug exposure–response and –safety relationships.

Aortic valve repair in children is still a challenge. The aim of this study was to analyse the surgical results of children with aortic regurgitation who underwent single leaflet reconstruction using the Ozaki procedure in our medical centre.

A retrospective study was conducted of nine children with aortic regurgitation who received single leaflet reconstruction from May 2017 to September 2019. Paired t-tests and Wilcoxon signed rank tests were used to compare the data at different time points.

The median surgical age was 4.7 (3.5, 6.4) years. Eight patients were pre-operatively diagnosed with severe aortic regurgitation, while one had moderate regurgitation. The left ventricles were significantly enlarged, with an average z-score of 3.8. Single leaflet reconstruction was carried out using glutaraldehyde-treated autologous pericardium under the standard Ozaki procedure. The median follow-up was 22 (14, 33) months. There was no post-operative death or re-intervention. One patient had moderate or more aortic regurgitation during the follow-up. The average degree of aortic regurgitation was mild, and the average z-score of the left ventricle decreased to −0.2 in the last follow-up.

Single leaflet reconstruction using the Ozaki procedure was an effective surgical method for treating children with aortic regurgitation in our centre with satisfactory short-term results.

The aim of this retrospective cohort study was to determine the incidence, potential risk factors, characteristics, and outcomes of acute kidney injury in children following the arterial switch operation for transposition of the great arteries.

Retrospective review of children who underwent ASO between 2000 and 2020 in our tertiary children’s hospital in the Netherlands. Pre-and post-ASO serum creatinine levels were collected. Severe AKI was defined as 100% serum creatinine rise or estimated creatinine clearance <35 ml/min/1.73 m2 according to pRIFLE criteria. Logistic regression was used to adjust for confounders.

A total of 242 children were included. Fifty-seven (24%) children developed severe AKI after ASO. Four patients with severe AKI were treated with renal replacement therapy. Children with severe AKI had a longer duration of mechanical ventilation 4.5 (1.0–29) versus 3 (1.0–12) days (p = 0.001), longer PICU stay 7 (2–76) versus 5 (1–70) days, (p = 0.001), higher rate of myocardial infarction 5% versus 0.5% (p = 0.001), sepsis 24% versus 9% (p = 0.002), post-operative pulmonary hypertension 19% versus 6% (p = 0.002), post-operative bleeding 9% versus 3% (p = 0.044), longer time to sternal closure 3 (1–19) versus 2 (1–6) days, (p = 0.009), and a higher mortality rate 9.0% versus 0.5% (p = 0.001) compared to children without severe AKI. Sepsis was a risk factor for developing severe AKI.

In this single-centre cohort, 24% of our patients developed severe AKI after ASO, which is associated with increased morbidity, longer PICU stay, and higher mortality.

Coronavirus disease 2019 (COVID-19) is responsible for significant lung disease in adults. Despite mild manifestations in most children, multisystem inflammatory syndrome (MIS-C) associated with COVID-19 is well described in older children with cardiac manifestations. However, MIS-C-related cardiac manifestations are not as well described in younger children.

The study is a retrospective analysis of MIS-C patients under the age of 5 years admitted between May and November 2020 to a single centre. Included cases fulfilled the case definition of MIS-C according to Royal College of Pediatrics and Child Health criteria with laboratory, electrocardiogram, or echocardiographic evidence of cardiac disease. Collected data included patients’ demographics, laboratory results, echocardiographic findings, management, and outcomes.

Out of 16 MIS-C cases under 5 years of age, 10 (62.5%) had cardiac manifestations with a median age of 12 months, 9 (90%) were previously healthy. Cardiac manifestations included coronary arterial aneurysms or ectasia in five (50%) cases, two (20%) with isolated myopericarditis, coronary ectasia with myocarditis in two (20%), and supraventricular tachycardia in one (10%). Intravenous immunoglobulins were given in all cases with coronary involvement or myocarditis. The median duration of hospitalisation was 7 (6–14) days; two (20%) cases with cardiac disease were mechanically ventilated and mortality in MIS-C cases below 5 years was 12.5%. Normalisation of systolic function occurred in half of the affected cases within 1 week and reached 100% by 30 days of follow-up.

MIS-C associated with SARS-CoV-2 has a high possibility of serious associated cardiac manifestations in children under the age of 5 years with mortality and/or long-term morbidities such as coronary aneurysms even in previously healthy children.