To determine the efficacy and safety of endotracheal instillation of iloprost as a rescue therapy for persistent pulmonary hypertension of the newborn.

Neonates diagnosed with persistent pulmonary hypertension who were unresponsive to standard treatment protocol applied for persistent pulmonary hypertension in our unit, and who were being followed up with mechanical ventilation, were included in the study. Iloprost was instilled endotracheally as a rescue treatment. Systolic pulmonary artery pressure, oxygen saturation index, mean airway pressure, fraction of inspired oxygen, preductal and postductal venous oxygen saturation, heart rate, and blood pressure were recorded before and after 30 minutes of endotracheal iloprost instillation. Adverse events after endotracheal iloprost were recorded.

Twenty neonates were included. The median gestational age and birth weight were found to be 37 (30.5-38) weeks and 2975 (2125-3437.5) grams, respectively. When compared to the period before endotracheal iloprost instillation, systolic pulmonary artery pressure, oxygen saturation index, mean airway pressure, and fraction of inspired oxygen values significantly decreased (p < 0.001, p < 0.001, p = 0.021, p = 0.001, respectively), whereas preductal and postductal oxygen saturation values significantly increased 30 minutes after the endotracheal iloprost instillation (p = 0.002, p < 0.001, respectively). There were no significant differences in heart rate and blood pressure values before and after the iloprost administration. No adverse events were observed.

Endotracheal instillation of iloprost was found to be an effective and safe therapy for persistent pulmonary hypertension unresponsive to conventional treatment.

Salih myopathy, characterised by both congenital myopathy and fatal dilated cardiomyopathy, is an inherited muscle disorder that affects skeletal and cardiac muscles. TTN has been identified as the main cause of this myopathy, the enormous size of this gene poses a formidable challenge to molecular genetic diagnostics.

In the present study, whole-exome sequencing, cardiac MRI, and metabolic parameter assessment were performed to investigate the genetic causes of Salih myopathy in a consanguineous Iranian family who presented with titinopathy involving both skeletal and heart muscles in an autosomal recessive inheritance pattern.

Two missense variants of TTN gene (NM_001267550.2), namely c.61280A>C (p. Gln20427Pro) and c.54970G>A (p. Gly18324Ser), were detected and segregations were confirmed by polymerase chain reaction-based Sanger sequencing.

The compound heterozygous variants, c.61280A>C, (p. Gln20427Pro) and c.54970G>A, (p. Gly18324Ser) in the TTN gene appear to be the cause of Salih myopathy and dilated cardiomyopathy in the family presented. Whole-exome sequencing is an effective molecular diagnostic tool to identify the causative genetic variants of large genes such as TTN.

Cardiopulmonary resuscitation (CPR) in the shunted single-ventricle population is associated with poor outcomes. Interposed abdominal compression-cardiopulmonary resuscitation, or IAC-CPR, is an adjunct to standard CPR in which pressure is applied to the abdomen during the recoil phase of chest compressions.

A lumped parameter model that represents heart chambers and blood vessels as resistors and capacitors was used to simulate blood flow in both Blalock-Taussig-Thomas and Sano circulations. For standard CPR, a prescribed external pressure waveform was applied to the heart chambers and great vessels to simulate chest compressions. IAC-CPR was modelled by adding phasic compression pressure to the abdominal aorta. Differential equations for the model were solved by a Runge-Kutta method.

In the Blalock-Taussig-Thomas model, mean pulmonary blood flow during IAC-CPR was 30% higher than during standard CPR; cardiac output increased 21%, diastolic blood pressure 16%, systolic blood pressure 8%, coronary perfusion pressure 17%, and coronary blood flow 17%. In the Sano model, pulmonary blood flow during IAC-CPR increased 150%, whereas cardiac output was improved by 13%, diastolic blood pressure 18%, systolic blood pressure 8%, coronary perfusion pressure 15%, and coronary blood flow 14%.

In this model, IAC-CPR confers significant advantage over standard CPR with respect to pulmonary blood flow, cardiac output, blood pressure, coronary perfusion pressure, and coronary blood flow. These results support the notion that single-ventricle paediatric patients may benefit from adjunctive resuscitation techniques, and underscores the need for an in-vivo trial of IAC-CPR in children.

Acute rheumatic fever in childhood continues to cause serious morbidity despite all developments. The objective of this study was to evaluate the clinical and laboratory characteristics of patients with acute rheumatic fever and to determine the frequency of subclinical carditis and the side effects of the drugs used in the treatment.

The data of patients hospitalised between 2008 and 2018 with the diagnosis of acute rheumatic fever were included in the study. The relationship of gender and age with the frequency of major symptoms and the distribution of the drugs used in the treatment and their side effects were evaluated.

Medical records of 102 patients with complete data were reviewed. 56.9% of the patients were male and the mean age was 10.7 ± 1.9 years. The most common distribution of complaints found were arthritis (51%), arthralgia (25.5%) and fever (16.7%). 10.8% of all patients (n = 11) were diagnosed subclinical carditis via echocardiographic evaluation. The frequency of carditis was higher in female patients with a borderline statistical significance (p = 0.05). However, there was no statistically significant difference between gender and arthritis (p = 0.22) and carditis (p > 0.05). Anti-congestive therapy was required in 22% and inotropic treatment was needed in 6.1% cases. Toxic hepatitis developed in four cases during the acetylsalicylic acid treatment.

In a 10-year period, detection of subclinical carditis in 10.8% cases supported that echocardiography should be performed as a standard method for the diagnosis of acute rheumatic fever. Patients should be followed closely in terms of hepatic toxicity due to acetylsalicylic acid used in the treatment.

Prenatal maternal stress is associated with adverse offspring outcomes, which may be mediated by maternal stress hormones. However, evidence supporting the association between maternal stress and cortisol levels in high-risk pregnancies is limited. This study aims to determine the relationship between self-reported maternal mental distress and maternal salivary cortisol levels in pregnancies complicated by foetal CHD compared with healthy pregnancies.

We recruited women with pregnancies complicated by foetal CHD and healthy pregnancies. Maternal saliva was collected between 22 and 40 gestational weeks. Standardized questionnaires measuring stress, depression, and anxiety were completed by patients. Generalized estimating equation was used to evaluate associations between maternal mental distress scales and cortisol levels.

We studied 165 women (55 CHD, 110 controls) and collected 504 cortisol samples (160 CHD, 344 controls). Women carrying CHD foetuses had higher stress, anxiety, and depression scores compared to women carrying healthy foetuses. However, maternal cortisol levels did not significantly differ in CHD and controls. Cortisol levels were higher in women carrying foetuses with functionally single-ventricle versus two-ventricle CHD. In both CHD and controls, there was no significant association between maternal stress, depression or anxiety scores and cortisol levels.

Our data suggest that self-reported maternal stress, anxiety, and depression are not associated with maternal salivary cortisol levels in CHD and healthy pregnancies. The impact of maternal mental distress on foetal health may be through other mediating pathways other than maternal cortisol concentrations.

The diagnosis of hypertension in adolescents aged ≥13 and <16 years is based on the percentile according to age, gender, and height in the European Society of Hypertension guidelines guideline; whereas, the American Academy of Pediatrics guideline uses blood pressure above 130/80 mmHg as a single criterion. Therefore, this study aimed to evaluate the compatibility of these two guidelines in adolescents aged ≥13 and <16 years.

This study was designed by retrospectively screening the records of 395 adolescents with both office and 24-hour ambulatory blood pressure measurements. Each blood pressure measurement was classified according to both the ESGH2016 and AAP2017 guidelines. Patients were divided into three subgroups according to body mass index. Cohen’s kappa analysis was used to evaluate the agreement between the two guidelines.

The majority of adolescents were normotensive according to both guidelines, 55.9% by ESHG2016 and 43.1% by AAP2017. For the whole group, the frequency of hypertension was 32.4% with ESHG2016 and 34.4% with AAP2017; while, in obese patients, hypertension frequencies were 38.8% and 43.3%, respectively. The diagnosis of hypertension was demonstrated with the two guidelines, and there was significant agreement at a substantial level, both for the obese subgroup and the whole study group (kappa value = 0.738 and 0.785, respectively). The frequency of white-coat hypertension was higher with the AAP2017 guideline (28.1% versus 16.2%, p < 0.001).

With our experience in this single-centre study, it seems that both the AAP2017 and the ESHG2016 guidelines can be used in the diagnosis of hypertension in adolescents.

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.

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.

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.

Caring for infants after the first-stage palliative surgery for single-ventricle heart disease bring challenges beyond the usual parenting responsibilities. Current studies fail to capture the nuances of caregivers’ experiences during the most critical “interstage” period between the first and second surgery.

To explore the perceptions of caregivers about their experiences while transitioning to caregiver roles, including the successes and challenges associated with caregiving during the interstage period.

Constructivist Grounded Theory methodology guided the collection and analysis of data from in person or telephonic interviews with caregivers after their infants underwent the first-stage palliative surgery for single-ventricle heart disease, and were sent to home for 2–4 months before returning for their second surgery. Symbolic interactionism informed data analyses and interpretation.

Our sample included 14 parents, who were interviewed 1–2 times between November, 2019 and July, 2020. Most patients were mothers (71%), Latinx (64%), with household incomes <$30K (42%). Data analysis led to the development of a Grounded Theory called Developing a Sense of Self-Reliance with three categories: (1) Owning caregiving responsibilities despite grave fears, (2) Figuring out how “to make it work” in the interstage period, and (3) Gaining a sense of self-reliance.

Parents transitioned to caregiver roles by developing a sense of self-reliance and, in the process, gained self-confidence and decision-making skills. Our study responded to the key research priority from the AHA Scientific Statement to address the knowledge gap in home monitoring for interstage infants through qualitative research design.

Approximate Entropy is an extensively enforced metric to evaluate chaotic responses and irregularities of RR intervals sourced from an eletrocardiogram. However, to estimate their responses, it has one major problem – the accurate determination of tolerances and embedding dimensions. So, we aimed to overt this potential hazard by calculating numerous alternatives to detect their optimality in malnourished children.

We evaluated 70 subjects split equally: malnourished children and controls. To estimate autonomic modulation, the heart rate was measured lacking any physical, sensory or pharmacologic stimuli. In the time series attained, Approximate Entropy was computed for tolerance (0.1→0.5 in intervals of 0.1) and embedding dimension (1→5 in intervals of 1) and the statistical significances between the groups by their Cohen’s ds and Hedges’s gs were totalled.

The uppermost value of statistical significance accomplished for the effect sizes for any of the combinations was −0.2897 (Cohen’s ds) and −0.2865 (Hedges’s gs). This was achieved with embedding dimension = 5 and tolerance = 0.3.

Approximate Entropy was able to identify a reduction in chaotic response via malnourished children. The best values of embedding dimension and tolerance of the Approximate Entropy to identify malnourished children were, respectively, embedding dimension = 5 and embedding tolerance = 0.3. Nevertheless, Approximate Entropy is still an unreliable mathematical marker to regulate this.

Tetralogy of Fallot is a common CHD. Studies have shown a close link between heart failure and myocardial fibrosis. Interleukin-6 has been suggested to be a post-independent factor of heart failure. This study aimed to explore the relationship between IL-6 and myocardial fibrosis during cardiopulmonary bypass.

We downloaded the expression profile dataset GSE132176 from Gene Expression Omnibus. After normalising the raw data, Gene Set Enrichment Analysis and differential gene expression analysis were performed using R. Further, a weighted gene correlation network analysis and a protein–protein interaction network analysis were used to identify HUB genes. Finally, we downloaded single-cell expression data for HUB genes using PanglaoDB.

There were 119 differentially expressed genes in right atrium tissues comparing the post-CPB group with the pre-CPB group. IL-6 was found to be significantly up-regulated in the post-CPB group. Six genes (JUN, FOS, ATF3, EGR1, IL-6, and PTGS2) were identified as HUB genes by a weighted gene correlation network analysis and a protein–protein interaction network analysis. Gene Set Enrichment Analysis showed that IL-6 affects the myocardium during CPB mainly through the JAK/STAT signalling pathway. Finally, we used PanglaoDB data to analyse the single-cell expression of the HUB genes.

Our findings suggest that high expression of IL-6 and the activation of the JAK/STAT signalling pathway during CPB maybe the potential mechanism of myocardial fibrosis. We speculate that the high expression of IL-6 might be an important factor leading to heart failure after ToF surgery. We expect that these findings will provide a basis for the development of targeted drugs.

Acute kidney injury is a risk factor for chronic kidney disease and mortality after congenital heart surgery under cardiopulmonary bypass. The neutrophil–lymphocyte ratio is an inexpensive and easy to measure biomarker for predicting outcomes in children with congenital heart disease undergoing surgical correction.

To identify children at high risk of acute kidney injury after tetralogy of Fallot repair using the neutrophil–lymphocyte ratio.

This single-centre retrospective analysis included consecutive patients aged < 18 years who underwent tetralogy of Fallot repair between January 2014 and December 2018. The pre-operative neutrophil–lymphocyte ratio was measured using the last pre-operative complete blood count test. We used the Acute Kidney Injury Network definition.

A total of 116 patients were included, of whom 39 (33.6%) presented with acute kidney injury: 20 (51.3%) had grade I acute kidney injury, nine had grade II acute kidney injury (23.1%), and 10 (25.6%) had grade III acute kidney injury. A high pre-operative neutrophil–lymphocyte ratio was associated with grade III acute kidney injury in the post-operative period (p = 0.04). Patients with acute kidney injury had longer mechanical ventilation time (p = 0.023), intensive care unit stay (p < 0.001), and hospital length of stay (p = 0.002).

Our results suggest that the pre-operative neutrophil–lymphocyte ratio can be used to identify patients at risk of developing grade III acute kidney injury after tetralogy of Fallot repair.

The pathophysiology of idiopathic chest pain remains unclear. Studies evaluating pain pressure thresholds in other idiopathic pain syndromes have revealed pain sensitivity in both affected and unaffected areas. The present study aimed to evaluate thoracic and extrathoracic pain pressure thresholds and their correlation with patients’ pain characteristics and quality of life.

This cross-sectional, single-blind, controlled study included children and adolescents with idiopathic chest pain. The patients’ pain characteristics, including their symptom duration, type of pain, mean pain intensity, mean duration of painful periods, pain frequency, and Pediatric Quality of Life Inventory Child Version scores, were assessed by a paediatric cardiologist via a face-to-face interview. Pain pressure thresholds were measured using an algometer by an algologist who was blinded to the study groups.

There was a statistically significant difference in pain pressure thresholds in the trapezius; supraspinatus; thoracic 2, 4, and 10 areas; deltoid; and tibia between the patient and healthy control groups. In the patient group, while there was a positive correlation between the mean all-region pain pressure thresholds and age (p = 0.047, r = 0.235), there was no correlation between pain pressure thresholds and symptom duration, pain intensity, and quality of life.

The present study is the first step towards investigating probable pain sensitivity mechanisms in children and adolescents with idiopathic chest pain. We noted lower thoracic and extrathoracic pain pressure thresholds in children and adolescents with idiopathic chest pain than in healthy controls.