Although closure of ductus arteriosus requires multiple intriguing cell signalling pathways, current treatment options merely act through cyclooxygenase inhibition. Expectedly, medical management of ductus arteriosus is quite far away from optimum and there is an ongoing debate on its efficiency and safety. The ideal therapeutic agent for patent ductus arteriosus should target vascular remodelling and support the arrested molecular steps that should completely eventuate during anatomical closure.

Platelet-rich plasma injection, which has been used as a treatment alternative for many musculoskeletal conditions, can be a promising solution in this context by compensating the relative platelet dysfunction in preterms and providing a convenient microenvironment for proper cellular communication for ductal closure.

First, by inducing hyaluronan synthase, platelet-rich plasma can induce mount formation in the intima, which is the significant defective milestone in preterms. Second, by providing platelet-derived growth factor, it can further stimulate platelet agregation and occlusion of the lumen. Finally, it can provide an increment in local vascular endothelial growth factor and transforming growth factor-β levels, which cannot be achieved because of insufficient intramural hypoxia. Migration of the vascular smooth muscles would further be triggered by transforming growth factor-β and vascular endothelial growth factor, aiding a major contribution to ductal closure.

Above and beyond all other considerations, opportunity of local application would render maximum effectiveness and minimum side effects.

In the United States, hypertrophic cardiomyopathy and coronary artery anomalies account for the leading two causes of sudden death in athletes. We present a case of a patient with an anomalous origin of the left main from the right coronary sinus with associated gene-confirmed hypertrophic cardiomyopathy. The patient underwent surgical repair with unroofing of the intramural portion of the left main coronary artery with a good result. We also review the reported cases in the medical literature describing this uncommon association between anomalous coronary artery origin and hypertrophic cardiomyopathy.

Atrial shunts are a common finding in both paediatric and adult populations. Recent developments in advanced imaging have widened the options for diagnosis and evaluation of such shunts. This paper reviews the various types of interatrial communications, discusses the features of clinical presentation in adults and children, and provides an overview of the clinical assessment including physical examination, electrocardiography, echocardiography, cardiac catheterisation, computed tomography, and magnetic resonance imaging. Focus will be placed on recent developments in magnetic resonance imaging that may improve the non-invasive evaluation of atrial shunts.

Introduction: Functionally univentricular hearts palliated with superior or total cavopulmonary connection result in circulations in series. The absence of a pre-pulmonary pump means that cardiac output is more difficult to adjust and control. Continuous monitoring of cardiac output is crucial during cardiac catheter interventions and can provide new insights into the complex physiology of these lesions. Materials and methods: The Icon® cardiac output monitor was used to study the changes in cardiac output during catheter interventions in 15 patients (median age: 6.1 years, range: 4.8–15.3 years; median weight: 18.5 kg, range: 15–63 kg) with cavopulmonary circulations. A total of 19 interventions were undertaken in these patients and the observed changes in cardiac output were recorded and analysed. Results: Cardiac output was increased with creation of stent fenestrations after total cavopulmonary connection (median increase of 22.2, range: 6.7%–28.6%) and also with drainage of significant pleural effusions (16.7% increase). Cardiac output was decreased with complete or partial occlusion of fenestrations (median decrease of 10.6, range: 7.1%–13.4%). There was a consistent increase in cardiac output with stenting of obstructive left pulmonary artery lesions (median increase of 7.7, range: 5%–14.3%, p = 0.007). Conclusions: Icon® provides a novel technique for the continuous, non-invasive monitoring of cardiac output. It provides a further adjunct for monitoring of physiologically complex patients during catheter interventions. These results are consistent with previously reported series involving manipulation of fenestrations. This is the first report identifying an increase in cardiac output with stenting of obstructive pulmonary arterial lesions.

Background: Assessment of right ventricular function is a key point in the follow-up of operated patients with tetralogy of Fallot. Cardiac magnetic resonance assessment of right ventricular function is considered the gold standard. However, this technique is expensive, has limited availability, and requires significant expertise to acquire and interpret the images. Myocardial performance index and isovolumic acceleration have recently been studied for the assessment of right ventricular function and are shown to be simple yet powerful tools for assessing patients with right ventricular dysfunction of various origins. Methods: In this study, the integrity of myocardial performance index and isovolumic acceleration obtained by tissue Doppler imaging echocardiography to quantify right ventricular function was assessed in 31 patients operated for tetralogy of Fallot. Myocardial performance index and isovolumic acceleration measurements were compared with the parameters derived by cardiac magnetic resonance imaging. Results: In this study, a significant correlation has not been detected between cardiac magnetic resonance-originated right ventricular ejection fraction, pulmonary regurgitation fraction and myocardial performance index, isovolumic acceleration obtained by tissue Doppler imaging echocardiography from the lateral tricuspid annulus of the right ventricle. Conclusion: We have concluded that when evaluated separately, myocardial performance index and isovolumic acceleration obtained from tissue Doppler imaging echocardiography can be used in the long-term follow-up of patients who have been operated for tetralogy of Fallot, but that they do not show correlation with cardiac magnetic resonance-originated right ventricle ejection fraction and pulmonary regurgitation fraction.

Introduction: Ischaemia-modified albumin, a novel biochemical marker for tissue ischaemia, was found to be associated with oxidative stress. The purpose of this study was to assess the role of ischaemia-modified albumin in the diagnosis of acute rheumatic fever and also to evaluate the ischaemia-modified albumin levels in children with heart valve disease. Methods: The study groups, aged 5–18 years, consisted of 128 individuals – 40 with acute rheumatic fever, 35 with congenital heart valve disease, 33 with chronic rheumatic heart disease, and 20 healthy control subjects. Results: The ischaemia-modified albumin, erythrocyte sedimentation rate, and C-reactive protein levels of the acute rheumatic fever group were significantly higher than those in the chronic rheumatic heart disease, congenital heart valve disease, and control groups, separately (p < 0.001). The ischaemia-modified albumin levels in both carditis and isolated arthritis subgroups of children with acute rheumatic fever were significantly higher than in the control group (p < 0.001, p < 0.01, respectively). However, there was no statistically significant difference between the chorea subgroup and control subjects. In addition, significant correlations were observed between ischaemia-modified albumin and acute phase reactants of patients with acute rheumatic fever (p < 0.001 for both erythrocyte sedimentation rate and C-reactive protein). The ischaemia-modified albumin levels of chronic rheumatic heart disease, congenital heart valve disease, and control subjects were similar. Conclusions: The increased level of ischaemia-modified albumin in children with acute rheumatic fever seems to be associated with inflammation. However, further studies are needed to provide stronger evidence.

Background: This study evaluated the effectiveness of long-term intensive lipid-lowering therapy in children and adolescents with familial hypercholesterolaemia. Methods: The charts of 89 children and adolescents with heterozygous familial hypercholesterolaemia among ∼1000 patients treated from 1974 to 2008 were reviewed. Familial hypercholesterolaemia was defined as low-density lipoprotein cholesterol level >90th percentile in individuals with a history of familial hypercholesterolaemia. Results: Of the 89 patients, 51% were male; the mean age at diagnosis was 8 ± 4 years, and the mean follow-up was 13 ± 8 years. Baseline and most recent low-density lipoprotein cholesterol levels (mg/dl) under treatment were 250 ± 50 and 142 ± 49, respectively, reduced 43% from baseline (p < 0.0001). At the most recent visit, 39 patients received statin monotherapy, mainly atorvastatin or rosuvastatin, and 50 (56%) patients received combination therapy, mainly vytorin or rosuvastain/ezetimibe, 15 patients were >30 years of age, and none developed symptomatic cardiovascular disease or needed revascularisation. Conclusions: Long-term statin-based therapy can reduce low-density lipoprotein cholesterol levels in most children and adolescents with heterozygous familial hypercholesterolaemia and decrease cardiovascular risk significantly.

Our aim is to screen miRNAs and genes related to tetralogy of Fallot and construct a co-expression network based on integrating miRNA and gene microarrays. We downloaded the gene expression profile GSE35490 (miRNA) and GSE35776 (mRNA) of tetralogy of Fallot from the Gene Expression Omnibus database, which includes eight normal and 15 disease samples from infants, and screened differentially expressed miRNAs and genes between normal and disease samples (cut-off: p < 0.05; FDR < 0.05; and log FC > 2 or log FC < −2); in addition, we downloaded human miRNA and their targets, which were collected in the miRNA targets prediction database TargetScan, and selected ones that also appeared in our differentially expressed miRNAs and their predicted targets (score >0.9) and then made a relationship of diff_miRNAs and diff_genes of our results. Finally, we uploaded all the diff_target genes into String, constructed a co-expression network regulated by diff_miRNAs, and performed functional analysis with the software DAVID. Comparing normal and disease lesion tissue, we got 32 and 875 differentially expressed miRNAs and genes, respectively, and found hsa-miR-124 with 34 diff_target genes and hsa-miR-138 with two diff_target genes. Then we constructed a co-expression network that contains 231 pairs of genes. Genes in the network were enriched into 14 function clusters, and the most significant one is protein localisation. We screened the tetralogy of Fallot-related hsa-miR-124 and hsa-miR-138 with their direct and indirect differentially expressed target genes, and found that protein localisation is the significant cause affecting tetralogy of Fallot. Our approach may provide the groundwork for a new therapy approach to treating tetralogy of Fallot.

Objectives: This publication aims to report the cases of four children with pseudoaneurysm of the mitral-aortic intervalvular fibrosa and carry out a review of the literature. Background: Pseudoaneurysm of the mitral-aortic intervalvular fibrosa is a very rare anomaly in children. It can be either congenital or acquired, namely, after bacterial endocarditis or cardiac trauma. This pathology does not usually cause specific symptoms but its outcome may be potentially fatal. Methods: We report the cases of four patients presenting with pseudoaneurysm of the mitral-aortic intervalvular fibrosa, referred for treatment in a paediatric cardiology clinic. Patient clinical notes were retrospectively reviewed for aetiology, clinical presentation, diagnostic work-up, surgical treatment, and follow-up. Literature on the subject was extensively reviewed. Results: In three patients, pseudoaneurysm of the mitral-aortic intervalvular fibrosa was acquired, being secondary to bacterial endocarditis in two cases and establishing after mitral surgery in another case. The remaining patient had a “congenital” aetiology – no other cause could be traced. The diagnosis was achieved by transthoracic echocardiography for all patients, and confirmed in all by trans-oesophageal echocardiography, to better define morphological details and to access flow into the aneurysmal formation. All patients were submitted to corrective cardiac surgery. Of the patients, three survived and were cured by surgery, staying asymptomatic, and one died after repeated interventions, for persistent endocarditis. Conclusions: Pseudoaneurysm of the mitral-aortic intervalvular fibrosa is a rare but potentially fatal anomaly. In our experience, surgical cure was achieved for the majority of the cases, except for a case for which infection could not be locally eradicated, leading to multiple reinterventions.

Objectives: This study sought to investigate the prevalence of atrial septal aneurysms in the paediatric population and to define coexisting abnormalities and their incidence. Background: Few papers refer to the prevalence of atrial septal aneurysms in childhood. Methods: We enrolled a total of 4522 children aged more than 12 months who underwent a transthoracic echocardiography. Atrial septal aneurysm was defined as a protrusion of the interatrial septum or part of it >15 mm beyond the plane of the atrial septum or phasic excursion of the interatrial septum during the cardiorespiratory cycle of at least 15 mm in total amplitude and a diameter of the base of the aneurysm of at least 15 mm. Results: Atrial septal aneurysms were found in 47 children (1.04%). They involved almost the entire septum in 14 patients (28.89%) and were limited to the fossa ovalis in 33 (71.11%). An atrial septal aneurysm was an isolated structural defect in 17 (35.56%). In 30 (64.44%) patients, it was associated with interatrial shunting – atrial septal defect and patent foramen ovale. At the echo follow-up after a year, no changes were recorded. Conclusions: Prevalence of atrial septal aneurysms is almost 1%. The most common abnormalities associated are interatrial shunts, that is, a patent foramen ovale and an atrial septal defect. From a medical point of view, it is suggested that no action is to be taken during childhood, as a child with an atrial septal aneurysm is not at increased risk compared with a child without one. Follow-up is scheduled on an individual basis.

Hypertension is a risk factor in many cardiovascular or cerebrovascular diseases. Adolescent hypertension may develop into adult hypertension. Examining the aetiologic factors of adolescent hypertension is crucial in its prevention and in managing its possible complications. The predominant view of aetiologic factors includes heredity, overweight/obesity, insulin resistance, gestational hypertension, diet, and intrauterine growth retardation. This article reported that children's academic grades in schools were positively correlated with adolescent blood pressure.

Objective: During the course of acute rheumatic fever, some electrocardiographic changes are seen. First-degree atrioventricular block is the most common electrocardiographic abnormality. Second- and third-degree atrioventricular block, ventricular tachycardia, and junctional acceleration are also seen. In the present study, the specificity of accelerated junctional rhythm to acute rheumatic fever was investigated. Methods: The study included patients with acute rheumatic fever (Group 1), healthy children who had suffered from recent group A β-haemolytic streptococcal upper respiratory tract infection but did not develop acute rheumatic fever (Group 2), and patients who had other diseases that may affect the joints and/or heart (Group 3). Results: Accelerated junctional rhythm was detected in 10 patients in Group 1, but in none of the patients from Group 2 or 3. Specificity of accelerated junctional rhythm for acute rheumatic fever was 100% and the positive predictive value was 100%. Conclusion: Accelerated junctional rhythm is specific to acute rheumatic fever. Although its frequency is low, it seems that it can be used in the differential diagnosis of acute rheumatic fever, especially in patients with isolated polyarthritis.

Purpose: The aim of this study was to compare associations between generic versus disease-specific functional health status assessments and patient and clinical characteristics for patients with severe congenital heart disease. Methods: This was a cross-sectional observational study involving 325 single ventricle patients, aged 10–18 years, after Fontan procedure. Enrolled patients underwent a medical history review, laboratory testing, and assessment of the functional health status by completion of the generic Child Report Child Health Questionnaire and the disease-specific Congenital Heart Adolescent and Teenage questionnaire. Correlated conceptually equivalent domains from both questionnaires were identified and their associations with patient and clinical variables were compared. Results: From the generic assessment, patients perceived marginally lower physical functioning (p = 0.05) but greater freedom from bodily pain compared with a normal population (p < 0.001). The equivalent physical functioning/limitations domain of the generic instrument, compared with the disease-specific instrument, had similar associations (higher multi-variable model R2) with medical history variables (R2 = 0.14 versus R2 = 0.12, respectively) and stronger associations with exercise testing variables (R2 = 0.22 versus R2 = 0.06). Similarly, the corresponding freedom from bodily pain/symptoms domains from both questionnaires showed a greater association for the generic instrument with medical history variables (R2 = 0.15 versus R2 = 0.09, respectively) and non-cardiac conditions (R2 = 0.13 versus R2 = 0.06). The associations of each questionnaire with echocardiographic results, cardiac magnetic resonance imaging results, and serum brain natriuretic peptide levels were uniformly weak (R2 range <0.01 to 0.04). Conclusions: Assessment of the physical functional health status using generic and disease-specific instruments yields few differences with regard to associations between conceptually similar domains and patient and clinical characteristics for adolescents after Fontan procedure.

We determined the relationship between aortic arch anatomy in tetralogy of Fallot with pulmonary stenosis and chromosomal or genetic abnormality, by performing analysis of 257 consecutive patients undergoing surgical repair from January, 2003 to March, 2011. Chromosomal or genetic abnormality was identified in 49 of the 257 (19%) patients. These included trisomy 21 (n = 14); chromosome 22q11.2 deletion (n = 16); other chromosomal abnormalities (n = 9); CHARGE (n = 2); Pierre Robin (n = 2); and Kabuki, Alagille, Holt–Oram, Kaufman McKusick, Goldenhar, and PHACE (n = 1 each). Aortic anatomy was classified as left arch with normal branching, right arch with mirror image branching, left arch with aberrant right subclavian artery, or right arch with aberrant left subclavian artery. Associated syndromes occurred in 33 of 203 (16%) patients with left arch and normal branching (odds ratio 1); three of 36 (8%) patients with right arch and mirror image branching (odds ratio 0.4, 95% confidence interval 0.1–1.6); seven of eight (88%) patients with left arch and aberrant right subclavian artery (odds ratio 36, 95% confidence interval 4–302); and six of 10 (60%) patients with right arch and aberrant left subclavian artery (odds ratio 8, 95% confidence interval 2–26). Syndromes were present in 13 of 18 (72%) patients with either right or left aberrant subclavian artery (odds ratio 15, 95% confidence interval 4–45). Syndromes in patients with an aberrant subclavian artery included trisomy 21 (n = 4); chromosome 22q11.2 deletion (n = 5); and Holt–Oram, PHACE, CHARGE, and chromosome 18p deletion (n = 1 each). Aberrant right or left subclavian artery in tetralogy of Fallot with pulmonary stenosis is associated with an increased incidence of chromosomal or genetic abnormality, whereas right aortic arch with mirror image branching is not. The assessment of aortic arch anatomy at prenatal diagnosis can assist counselling.

Purpose: The aim of this study was to investigate the frequency and gender distribution of variations in the aortic arch branching pattern using 64-slice computed tomograhic angiography. Materials and methods: A total of 1000 patients with a normal left-sided aortic arch who underwent computed tomographic angiography for various reasons were analysed retrospectively for the frequency of variation of aortic arch branching; the variations were categorised into seven types. Results: Of the 1000 patients, 79.2% had a normal aortic arch branching pattern – type 1 – and 20.8% had variations. The frequency of type 2 variation – brachiocephalic and left common carotid arteries arising from the aortic arch in a common trunk – was 14.1%, that of type 3 – left vertebral artery originating from the aortic arch – was 4.1%, that of type 4 – coexistence of type 2 and type 3 – was 1.2%, that of type 5 – aberrant right subclavian artery – was 0.6%, that of type 6 – coexistence of aberrant right subclavian artery and bicarotid trunk – was 0.7%, and that for type 7 – thyroidea ima artery arising from the aortic arch – was 0.1%. The incidences of the variations of aortic arch branching were similar among males and females (20% versus 22.1%). The incidence of an aberrant right subclavian artery – type 5 and type 6 – was higher among females compared with males (2.5% versus 0.5), whereas the frequencies of the other variations were either equal or similar in both genders. Conclusion: Recognition of variations of aortic arch branching is important because they may cause symptoms due to tracheoesophageal compression or complications during surgical or endovascular interventional procedures of the aorta and its branches.

Objectives: The aim of this study was to determine the timing of neonatal cardiac intervention in babies with antenatally diagnosed congenital heart disease and the impact on obstetric management. Methods: A retrospective review of all deliveries between January, 2008 and December, 2009 was conducted in a tertiary centre with foetal and paediatric cardiology, maternal–foetal medicine, and obstetric units. All live births with antenatally detected congenital heart disease were included. Data were collected from foetal, paediatric cardiology, and maternity databases and records. Induction, delivery mode, and timing of the first cardiac intervention in the neonate were studied. Results: 205 deliveries were included. Induction and elective Caesarean section rates were 51.2% (105/205) and 14.1% (29/205), respectively. The vaginal delivery rate was 56% (115/205). There was a non-significant trend towards a higher rate of vaginal delivery after spontaneous labour than after induction (75% versus 66%; p = 0.234). The rate of neonatal cardiac intervention during the initial stay was 59.5% (122/205); it was 18.5% (38/205) within 48 hours and 25.8% (53/205) within 72 hours. The median time to first intervention was 4 days (interquartile range 2–8). Babies with hypoplastic left heart syndrome (median 3, interquartile range 2–6), transposition of the great arteries (median 1, interquartile range 0–4.5), and arrhythmia (median 0.5, interquartile range 0–1) had a significantly earlier time to first intervention compared with those with other conditions (p = 0.001). Conclusion: Vaginal delivery can be achieved in women delivering babies with major congenital heart disease at a tertiary centre. Delivery in or near a tertiary centre is recommended for patients requiring early intervention, of which many can be identified in advance.

Objective: Placement of peritoneal drainage catheters intra-operatively has been shown to help prevent fluid overload in children recovering from surgery for two-ventricle heart disease. We aimed to determine whether this practice is also helpful in children recovering from Fontan palliation. Material and methods: A retrospective review was performed on children with single-ventricle anatomy undergoing Fontan palliation at our institution from 2007 to 2011. Variables in those with peritoneal drainage were compared with those without using t-tests, Mann–Whitney U-tests, chi-square tests, or analysis of variance for repeated measures as appropriate. Data were represented as mean with standard deviation unless otherwise noted. Results: A total of 43 children were reviewed, 21 (49%) with peritoneal drainage catheters. No complications from catheter placement occurred. The groups did not differ with regard to cardiopulmonary bypass duration, dominant ventricle, pre-operative haemodynamic data, fenestration use, and initial intensive care unit ventilation index. Central venous pressures, vasoactive medication use, and diuretic use during the first 48 hours were also not statistically different. At 48 hours, the median fluid balance was −9 (interquartile range : −50, +20) in those with peritoneal drainage and +77 cc/kg (interquartile range : +22, +96) in those without (p < 0.001), yet median duration of mechanical ventilation was 40 hours (range: 19–326) in those with peritoneal drainage and 23 hours (range: 9–92) in those without, p = 0.01. Conclusion: Patients with peritoneal drainage recovering from Fontan palliation achieved negative fluid balance as compared with those without peritoneal drainage, although this difference was associated with a longer duration of mechanical ventilation.

Introduction: A variety of patch materials have been used in the repair of intracardiac defects. We evaluated the short- and mid-term clinical and echocardiography results of glutaraldehyde-preserved bovine pericardium patches used to repair intracardiac defects in our clinic. Methods and results: This study examines the short- (up to 30 days post-operatively) and mid-term (up to 24 months post-operatively) results of 533 patients with intracardiac defects who underwent surgical correction with glutaraldehyde-preserved bovine pericardium patches between 2004 and 2010 at a university clinic. Short- and mid-term post-operative echocardiographic studies showed no evidence of calcification, thrombus, or aneurysmal dilatation on the patch. Vegetation developed in two (0.37%) of the 533 patients. Conclusion: These results that have been obtained from a group of large number of patients imply that the glutaraldehyde-preserved bovine pericardium patches may be preferable in the closure of cardiac defects because of their low complication rates and ease of use.

We report the case of a 2.5-year-old patient with single-ventricle physiology who underwent cardiac magnetic resonance study for cyanosis after Kawashima operation. Magnetic resonance imaging study showed a veno-venous collateral redirecting systemic venous flow, responsible for cyanosis.