The GDF3 gene plays a fundamental role in embryonic morphogenesis. Recent studies have indicated that GDF3 plays a previously unrecognised role in cardiovascular system development. Non-syndromic CHDs might be a clinically isolated manifestation of GDF3 mutations. The purpose of the present study was to identify potential pathological mutations in the GDF3 gene in Chinese children with non-syndromic CHDs, and to gain insight into the aetiology of non-syndromic CHDs.

A total of 200 non-syndromic CHDs patients and 202 normal control patients were sampled. There were two exons of the human GDF3 gene amplified using polymerase chain reaction. The polymerase chain reaction products were purified and directly sequenced.

One missense mutation (c.C635T, p.Ser212 Leu, phenotype: isolated muscular ventricular septal defect) was found that has not been reported previously.

To the best of our knowledge, this is the first study to investigate the role of the GDF3 gene in non-syndromic CHDs. Our results expand the spectrum of mutations associated with CHDs and first suggest the potentially disease-related GDF3 gene variant in the pathogenesis of CHDs.

To test the hypothesis that myocardial scars after repair of tetralogy of Fallot are related to impaired cardiac function and adverse clinical outcome.

A total of 53 patients were retrospectively analysed after repair of tetralogy of Fallot. The median patient age was 20 years (range 2–48).

Cardiac MRI with a 1.5 T magnet included cine sequences to obtain volumes and function, phase-sensitive inversion recovery delayed enhancement imaging to detect myocardial scars, and flow measurements to determine pulmonary regurgitation fraction. In addition, clinical parameters were obtained.

An overall 83% of patients were in NYHA class I. All patients with the exception of 2 (96%) had pulmonary insufficiency. Mean ejection fraction and end-diastolic volume index were 46% and 128 ml/m2 for the right ventricle and 54% and 82 ml/m2 for the left ventricle, respectively. Excluding enhancement of the septal insertion and prosthetic patches, delayed enhancement was seen in 11/53 cases (21%). Delayed enhancement of the right ventricle was detected in 6/53 patients (11%) and of the left ventricle in 5/53 patients (9%). The patient group with delayed enhancement was significantly older (p=0.003), had later repair (p=0.007), and higher left ventricular myocardial mass index (p=0.009) compared with the group without delayed enhancement.

This study reveals that scarring is common in patients after surgical repair of tetralogy of Fallot and is associated with older age and late repair. However, there was no difference in right ventricular function, NYHA class, or occurrence of clinically relevant arrhythmias between patients with and those without myocardial scars.

Acute rheumatic fever is an autoimmune, inflammatory, and multi-systemic disease secondary to pharyngitis and is caused by group A streptococcus. In developing countries, acute rheumatic fever is the most common cause of acquired heart disease. Gelsolin is a calcium-dependent, multi-functional actin-regulatory protein circulating in the plasma of healthy human beings. The correlation between blood gelsolin levels and inflammatory conditions suggests the potential benefit of gelsolin as a prognostic marker. The aim of the present study was to appraise the association of gelsolin and acute rheumatic carditis in childhood.

Plasma gelsolin levels were measured and echocardiographic examinations were performed in patients (n=37) with acute rheumatic carditis and compared with those of age- and gender-matched healthy controls (n=24).

The plasma gelsolin levels in children with acute rheumatic carditis were significantly lower compared with controls (197±218 versus 322±255 mg/L, p=0.039). There was a significant correlation among gelsolin levels and the grade of mitral regurgitation (p=0.030), left ventricular end-diastolic diameter (p=0.017), and left ventricular end-systolic diameter (p=0.028) at diagnosis.

Levels of the gelsolin plasma isoform were decreased in patients with acute rheumatic carditis compared with healthy controls. Gelsolin may be used as a biochemical marker for acute rheumatic carditis.

Arrhythmias are common in patients admitted to the paediatric intensive care unit. We sought to identify the rates of occurrence and types of arrhythmias, and determine whether an arrhythmia was associated with illness severity and paediatric intensive care unit length of stay.

This is a prospective, observational study of all patients admitted to the paediatric intensive care unit at the Children’s Hospital at Montefiore from March to June 2012. Patients with cardiac disease or admitted for the treatment of primary arrhythmias were excluded. Clinical and laboratory data were collected and telemetry was reviewed daily. Tachyarrhythmias were identified as supraventricular tachycardia, ventricular tachycardia, and arrhythmias causing haemodynamic compromise or for which an intervention was performed.

A total of 278 patients met the inclusion criteria and were analysed. There were 97 incidences of arrhythmia in 53 patients (19%) and six tachyarrhythmias (2%). The most common types of arrhythmias were junctional rhythm (38%), premature atrial contractions (24%), and premature ventricular contractions (22%). Tachyarrhythmias included three supraventricular tachycardia (50%) and three ventricular tachycardia (50%). Of the six tachyarrhythmias, four were related to placement or migration of central venous lines and two occurred during aminophylline infusion. Patients with an arrhythmia had longer duration of mechanical ventilation and paediatric intensive care unit stay (p<0.001). In multivariate analysis, central venous lines (odds ratio 3.1; 95% confidence interval 1.3–7.2, p=0.009) and aminophylline use (odds ratio 5.1; 95% confidence interval 1.7–14.9, p=0.003) were independent predictors for arrhythmias.

Arrhythmias were common in paediatric intensive care unit patients (19%), although tachyarrhythmias occurred rarely (2%). Central venous lines and use of aminophylline were identified as two clinical factors that may be associated with development of an arrhythmia.

Aortic coarctation in older children most frequently represents cases of re-coarctation following previous transcatheter or surgical therapy or missed cases of native coarctation.

We describe three cases of adolescents – two girls and one boy – with aortic coarctation, operated between January, 2012 and December, 2013. Computed tomography angiography was performed as an essential diagnostic procedure.

Hypertension was detected, and weaker arterial pulses in the lower limbs were noted in all cases. All operations were performed via left posterolateral thoracotomy. Aortic coarctation was treated surgically, with left subclavian-lower descending thoracic aorta bypass grafting. Postoperative course was uneventful in all cases. No residual brachial-ankle pressure gradient was observed, and all patients have remained in good condition after the operation.

Surgical treatment of aortic coarctation in adolescent patients can be achieved by resection with end-to-end anastomosis, interposition of a graft or bypass graft across the area of coarctation when the distance to be bridged is too long for end-to-end repair.

The extra-anatomic subclavian-descending aortic bypass grafting provides good results in adolescent patients, particularly in those with complex coarctation.

Children with functionally univentricular circulations have chronic volume loading of the systemic ventricle, potentially affecting ventricular function. Medications including angiotensin-converting enzyme inhibitors and β-blockers are used to treat ventricular dysfunction, despite limited evidence of their efficacy in this population.

To determine the effects of angiotensin-converting enzyme inhibitors on elevated filling pressures in children with single ventricle physiology.

We performed a single-centre, retrospective review of patients with single ventricle physiology who underwent multiple cardiac catheterisations between 1991 and 2013. Study population comprised of patients who commenced or had optimised dosing of angiotensin-converting enzyme inhibitors between assessments in response to high ventricular filling pressures. Patients undergoing interventions influencing loading conditions between assessments were excluded.

A total of 17 patients were identified, with dominant morphologic right ventricle in eight patients (47.1%). Among them, 11 (64.7%) were pre-Fontan and six (35.3%) were post-Fontan completion. Median inter-assessment interval was 9.4 months (range 7.3–19.1). There was a reduction in end-diastolic pressure from 13 to 10 mmHg (p=0.002), mean pulmonary artery pressure from 16 to 13 mmHg (p=0.049), and mean atrial pressure from 12 to 9 mmHg (p=0.001). There was one cardiac transplant, and there were no patient deaths at median follow-up after 31 months.

We observed a reduction in ventricular end-diastolic pressure, pulmonary artery pressure, and mean atrial pressure following treatment with angiotensin-converting enzyme inhibitors in patients with single ventricle physiology. Our study provides insights into the potential impact of anti-heart failure therapy in single ventricle circulations and calls for larger, controlled studies to assess for a therapeutic response.

Dilated cardiomyopathy is a leading cause of cardiac death in children. Approximately 30% of children die or need cardiac transplantation in the first year after establishing the diagnosis. New strategies are needed to improve the outcome in this high-risk patient population.

We present our experience in 38 patients below the age of three years, who were diagnosed with dilated cardiomyopathy and who were treated at our institution between 2006 and 2012. The treatment strategy involved institution of β-blockers and angiotensin-converting enzyme inhibitors as soon as feasible. In selected cases, pulmonary artery banding or intracoronary autologous bone marrow-derived cell therapy was performed. The median age at presentation was six months (range 1–26 months). The median follow-up age was 16 months (range 2–80 months). Kaplan–Meier analysis of survival after dilated cardiomyopathy diagnosis revealed a one-year survival of 97% and a five-year survival of 86%. The rate of freedom from death or heart transplantation was 82% at one year and 69% at five years. Surviving patients who were free of transplantation, at the follow-up at 25 months (3–80 months), showed a significant improvement in left ventricular ejection fraction (from 19±11 to 46±16%) and left ventricular end-diastolic diameter (z-score from 4.6±2.4 to 1.4±1.6). In addition, the levels of B-type natriuretic peptide improved significantly (from 3330±3840 to 171±825 pg/ml).

Our data suggest that the clinical approach described here may result in a markedly improved medium-term outcome in young children with dilated cardiomyopathy. Further studies are required to evaluate whether these approaches reduce end-points such as transplantation or death.

Neonates with severe pulmonary valve stenosis tend to remain oxygen dependent, despite resolution of the transpulmonary gradient. Alpha 2 blockers – phentolamine – and angiotensin-converting enzyme inhibitors – captopril – were reported to improve oxygen saturation.

To describe the role of phentolamine and captopril in the treatment of these patients.

In a retrospective cohort study, 28 neonates with severe pulmonary valve stenosis underwent balloon valvuloplasty. Among them, 20 remained oxygen or prostaglandin dependent after intervention, and were treated with phentolamine or captopril. Oxygen saturation was monitored before and after intervention and following treatment with these medications. Mean duration of hospitalisation was recorded.

Mean age and weight were 25.2 days and 3.1 kg, respectively. Before balloon dilation, 18/20 (90%) neonates were on prostaglandin, whereas after the procedure only 6/18 patients required it. All 20 patients required oxygen after the procedure, and nine patients (45%) were started on phentolamine. Among them, one patient with severe infundibular stenosis did not respond favourably, and 11 patients (55%) were started on captopril. After starting phentolamine or captopril treatment, prostaglandin could be discontinued after a mean time of 15.86 hours. Within <2 days, there was an increase in mean oxygen saturation from 76.6 to 93.0%.

Phentolamine and captopril seem to have therapeutic roles in neonates with severe pulmonary valve stenosis who remain oxygen dependent after balloon dilation. Both drugs led to vasodilation of the pulmonary and systemic vascularisation and facilitated inflow to the right ventricle. Right-to-left shunt across a patent foramen ovale or atrial septal defect decreased and saturation improved, leading to a significant reduction in the length of hospitalisation.

We have lately documented the importance of N-terminal pro-brain natriuretic peptide in aiding the diagnosis of Kawasaki disease.

We sought to investigate the potential value of N-terminal pro-brain natriuretic peptide pertaining to the prediction of coronary artery dilatation (Z-score>2.5) and/or of resistance to intravenous immunoglobulin therapy. We hypothesised that increased serum N-terminal pro-brain natriuretic peptide level correlates with increased coronary artery dilatation and/or resistance to intravenous immunoglobulin.

We carried out a prospective study involving newly diagnosed patients treated with 2 g/kg intravenous immunoglobulin within 5–10 days of onset of fever. Echocardiography was performed in all patients at onset, then weekly for 3 weeks, then at month 2, and month 3. Coronary arteries were measured at each visit, and coronary artery Z-score was calculated. All the patients had N-terminal pro-brain natriuretic peptide serum level measured at onset, and the Z-score calculated.

There were 109 patients enrolled at 6.58±2.82 days of fever, age 3.79±2.92 years. High N-terminal pro-brain natriuretic peptide level was associated with coronary artery dilatation at onset in 22.2 versus 5.6% for normal N-terminal pro-brain natriuretic peptide levels (odds ratio 4.8 [95% confidence interval 1.05–22.4]; p=0.031). This was predictive of cumulative coronary artery dilatation for the first 3 months (p=0.04–0.02), but not during convalescence at 2–3 months (odds ratio 1.28 [95% confidence interval 0.23–7.3]; p=non-significant). Elevated N-terminal pro-brain natriuretic peptide levels did not predict intravenous immunoglobulin resistance, 15.3 versus 13.5% (p=1).

Elevated N-terminal pro-brain natriuretic peptide level correlates with acute coronary artery dilatation in treated Kawasaki disease, but not with intravenous immunoglobulin resistance.

Cardiovascular events and complications are the leading cause of mortality and morbidity in patients with sickle cell disease. Cardiac abnormalities occur frequently and at an early stage in sickle cell anaemia patients, despite being more evident in adulthood. Sickle cell anaemia patients are increasingly able to reach adulthood owing to improved healthcare, and may, therefore, suffer the consequences of chronic cardiac injury. Thus, the study of cardiac abnormalities is essential in children

The aim of this study was to determine the echocardiographic changes in left ventricular function in children suffering from sickle cell disease in Mumbai, Western India.

The study comprised of 48 cases of sickle cell anaemia and 30 non-anaemic controls with normal haemoglobin and electrophoresis pattern. M-mode, two-dimensional, and Doppler echocardiographic measurements of patients and controls were performed according to the criteria of the American Echocardiography Society.

On Doppler study, the A wave height was increased and the E/A ratio was decreased, whereas the deceleration and isovolumetric relaxation times were prolonged, which is typically seen in slowed or impaired myocardial relaxation (p<0.001). Although chamber dilatations were present, echocardiographic parameters showed no statistically significant correlation with severity of anaemia and age among the sickle cell patients.

We conclude that the increased left ventricular stiffness, compared with controls, might be due to fibrosis related to ischaemia caused by SS disease in addition to wall hypertrophy.

Recent efforts have focused on optimising interstage outcomes, including growth, for infants following the Norwood operation. The impact of the site of interstage care remains unclear, and it has been hypothesised that care at the surgical site may be beneficial due to greater access to resources such as nutritional support. This study evaluated the relationship between site of interstage care and weight gain in a large multicentre cohort.

Infants enrolled in the National Paediatric Cardiology Quality Improvement Collaborative (2008–2013) surviving up to Stage 2 were included. Change in weight-for-age z-score between Norwood discharge and Stage 2 admission was compared in those receiving care at the surgical versus non-surgical site.

Of the 487 interstage survivors, 60% received all care at the surgical site, and 40% received care at a non-surgical site. There was no significant difference between groups in change in weight-for-age z-score: +0.36±0.96 for the surgical site group versus +0.46±1.02 for the non-surgical site group, p=0.3. Results were unchanged in multivariable analysis adjusting for differences in important baseline characteristics, duration of interstage, and home surveillance strategy. The proportion of all patients with weight-for-age z-score <−2 decreased from 40% at Norwood discharge to 29% at Stage 2, with no significant difference in change between the two groups (p=0.1).

The site of interstage care was not associated with weight gain during the interstage period. Nearly one-third of patients overall had a weight-for-age z-score <−2 at Stage 2. Further study is required to identify methods to optimise weight gain in these patients.

Aortic arch obstruction can be evaluated by catheter peak-to-peak gradient or by Doppler peak instantaneous pressure gradient. Previous studies have shown moderate correlation in discrete coarctation, but few have assessed correlation in patients with more complex aortic reconstruction.

We carried out retrospective comparison of cardiac catheterisations and pre- and post-catheterisation echocardiograms in 60 patients with native/recurrent coarctation or aortic reconstruction. Aortic arch obstruction was defined as peak-to-peak gradient ⩾25 mmHg in patients with native/recurrent coarctation and ⩾10 mmHg in aortic reconstruction.

Diastolic continuation of flow was not associated with aortic arch obstruction in either group. Doppler peak instantaneous pressure gradient, with and without the expanded Bernoulli equation, weakly correlated with peak-to-peak gradient even in patients with a normal cardiac index (r=0.36, p=0.016, and r=0.49, p=0.001, respectively). Receiver operating characteristic curve analysis identified an area under the curve of 0.61 for patients with all types of obstruction, with a cut-off point of 45 mmHg correctly classifying 64% of patients with arch obstruction (sensitivity 39%, specificity 89%). In patients with aortic arch reconstruction who had a cardiac index ⩾3 L/min/m2, a cut-off point of 23 mmHg correctly classified 69% of patients (71% sensitivity, 50% specificity) with an area under the curve of 0.82.

The non-invasive assessment of aortic obstruction remains challenging. The greatest correlation of Doppler indices was noted in patients with aortic reconstruction and a normal cardiac index.

To quantify myocardial blood flow in infants and children with mild or moderate aortic stenosis using adenosine-infusion cardiac magnetic resonance.

It is unclear whether asymptomatic children with mild/moderate aortic stenosis have myocardial abnormalities. In addition, cardiac magnetic resonance-determined normative myocardial blood flow data in children have not been reported.

We studied 31 infants and children with either haemodynamically normal hearts (n=20, controls) or mild/moderate aortic stenosis (n=11). The left ventricular myocardium was divided into six segments, and the change in average segmental signal intensity during contrast transit was used to quantify absolute flow (ml/g/minute) at rest and during adenosine infusion by deconvolution of the tissue curves with the arterial input of contrast.

In all the cases, adenosine was well tolerated without complications. The mean pressure gradient between the left ventricle and the ascending aorta was higher in the aortic stenosis group compared with controls (24 versus 3 mmHg, p<0.001). Left ventricular wall mass was slightly higher in the aortic stenosis group compared with controls (65 versus 50 g/m2, p<0.05). After adenosine treatment, both the absolute increase in myocardial blood flow (p<0.0001) and the hyperaemic flow significantly decreased (p<0.001) in children with mild/moderate aortic stenosis compared with controls.

Abnormal myocardial blood flow in children with mild/moderate aortic stenosis may be an important therapeutic target.

The aim of this study was to evaluate whether the use of therapeutic hypothermia in patients receiving extracorporeal membrane oxygenation after paediatric cardiac surgery is associated with increased complication rates.

We undertook a retrospective study to compare the complication rates and clinical course of children after cardiac surgery in two groups – extracorporeal membrane oxygenation without therapeutic hypothermia (group 1) and extracorporeal membrane oxygenation with therapeutic hypothermia (group 2). Therapeutic hypothermia was performed via the extracorporeal membrane oxygenation circuit heater–cooler device.

A total of 96 patients were included in this study (59 in group 1 and 37 in group 2). Complications were comparable between group 1 and group 2, except that more patients with therapeutic hypothermia had hypertension while on extracorporeal membrane oxygenation. Therapeutic hypothermia was not independently associated with in-hospital mortality (adjusted odds ratio 1.16, 95% CI: 0.33–4.03; p=0.82).

Therapeutic hypothermia can be safely provided to children on extracorporeal membrane oxygenation after cardiac surgery without an increase in complication rates.