N-terminal pro-brain natriuretic peptide has an established role in the diagnosis and prognosis of heart failure. In Fontan patients, this peptide is often increased, but its diagnostic value in this particular non-physiologic, univentricular circulation is unclear. We investigated whether N-terminal pro-brain natriuretic peptide represents ventricular function or other key variables in Fontan patients.

Ninety-five consecutive Fontan patients ≥10 years old who attended the outpatient clinic of the Center for Congenital Heart Diseases in 2012–2013 were included. Time since Fontan completion was 16 ± 9 years. Median N-terminal pro-brain natriuretic peptide was 114 (61–264) ng/l and was higher than gender-and age-dependent normal values in 54% of the patients. Peptide Z-scores were higher in patients in NYHA class III/IV compared to those in class I/II, but did not correlate with ventricular function assessed by MRI and echocardiography, nor with peak exercise capacity. Instead, peptide Z-scores significantly correlated with follow-up duration after Fontan completion (p < 0.001), right ventricular morphology (p = 0.004), indexed ventricular mass (p = 0.001), and inferior caval vein diameter (p < 0.001) (adjusted R2 = 0.615).

N-terminal pro-brain natriuretic peptide levels in Fontan patients correlate with functional class, but do not necessarily indicate ventricular dysfunction. Increased peptide levels were associated with a longer existence of the Fontan circulation, morphologic ventricular characteristics, and signs of increased systemic venous congestion. Since the latter are known to be key determinants of the performance of the Fontan circulation, these findings suggest increase in N-terminal pro-brain natriuretic peptide levels to indicate attrition of the Fontan circulation, independent of ventricular function.

Liver dysfunction, associated with morbidity and mortality, is common in patients with CHD. We investigate risk factors for and outcomes of hyperbilirubinaemia in neonates and infants after cardiac surgery.

In a retrospective analysis of neonates and infants undergoing cardiac surgery at our institution between January 2013 and December 2017, we identified those with post-operative conjugated hyperbilirubinaemia. We tested various demographic and surgical risk factors, and use of post-operative interventions, for an association with conjugated hyperbilirubinaemia. We also tested hyperbilirubinaemia for association with post-operative mortality and prolonged length of stay.

We identified 242 post-operative admissions, of which 45 (19%) had conjugated hyperbilirubinaemia. The average conjugated bilirubin level in this group was 2.0 mg/dl versus 0.3 mg/dl for peers without hyperbilirubinaemia. The post-operative use of both extracorporeal membrane oxygenation (OR 4.97, 95% CI 1.89–13.5, p = 0.001) and total parenteral nutrition (OR 2.98, 95% CI 1.34–7.17, p = 0.010) was associated with conjugated hyperbilirubinaemia. No demographic variable analysed was found to be a risk factor. Hyperbilirubinaemia was associated with higher odds of mortality (OR 3.74, 95% CI 2.69–13.8, p = 0.005) and prolonged length of stay (OR 2.87, 95% CI 2.02–7.97, p = 0.005), which were independent of other risk factors.

We identified the post-operative use of total parenteral nutrition and extracorporeal membrane oxygenation as risk factors for hyperbilirubinaemia. These patients were more likely to experience morbidity and mortality than control peers. As such, bilirubin may be marker for elevated risk of poor post-operative outcomes and should be more frequently measured after cardiac surgery.

Thrombocytopenia is a risk factor for patent ductus arteriosus. Immature and mature platelets exhibit distinct haemostatic properties; however, whether platelet maturity plays a role in postnatal, ductus arteriosus closure is unknown.

In this observational study, counts of immature and mature platelets (=total platelet count − immature platelet count) were assessed on days 1, 3, and 7 of life in very low birth weight infants (<1500 g birth weight). We performed echocardiographic screening for haemodynamically significant patent ductus arteriosus on day 7.

Counts of mature platelets did not differ on day 1 in infants with (n = 24) and without (n = 45) haemodynamically significant patent ductus arteriosus, while infants with significant patent ductus arteriosus exhibited lower counts of mature platelet on postnatal days 3 and 7. Relative counts of immature platelets (fraction, in %) were higher in infants with patent ductus arteriosus on day 7 but not on days 1 and 3. Receiver operating characteristic curve analysis unraveled associations between both lower mature platelet counts and higher immature platelet fraction (percentage) values on days 3 and 7, with haemodynamically significant ductus arteriosus. Logistic regression analysis revealed that mature platelet counts, but not immature platelet fraction values, were independent predictors of haemodynamically significant patent ductus arteriosus.

During the first week of postnatal life, lower counts of mature platelets and higher immature platelet fraction values are associated with haemodynamically significant patent ductus arteriosus. Lower counts of mature platelet were found to be independent predictors of haemodynamically significant patent ductus arteriosus.

A certain degree of pulmonary stenosis after total correction of tetralogy of Fallot has been considered acceptable. But the long-term outcomes are not well understood. We observed the natural course of immediate pulmonary stenosis and investigated related factors for progression.

Fifty-two patients with acceptable pulmonary stenosis immediately after operation were enrolled. Acceptable pulmonary stenosis was defined as peak pressure gradient between 15 and 45 mmHg by Doppler echocardiography. Latent class linear mixed model was used to differentiate patients with progressed pulmonary stenosis, and the factors related to progression were analysed.

Pulmonary stenosis progressed in 14 patients (27%). Between the progression group and no progression group, there were no significant differences in operative age, sex, and the use of the transannular patch technique. However, immediate gradient was higher in the progression group (32.1 mmHg versus 25.7 mmHg, p = 0.009), and the cut-off value was 26.8 mmHg (sensitivity = 65.3%, specificity = 65.8%). Main stenosis at the sub-valve was observed more frequently in the progression group (85.7% versus 52.6%, p = 0.027). Despite no difference in the preoperative pulmonary valve z value, the last follow-up pulmonary valve z value was significantly lower in the progression group (−1.15 versus 0.35, p = 0.002).

Pulmonary stenosis immediately after tetralogy of Fallot total correction might progress in patients with immediate pulmonary stenosis higher than ≥26.8 mmHg and the main site was sub-valve area.

Fascicular tachycardia is a common form of sustained idiopathic left ventricular tachycardia. This study aimed to achieve successful results with catheter ablation procedures performed through three-dimensional electroanatomic mapping using near-zero fluoroscopy in fascicular tachycardia patients.

In this study, we included 33 consecutive children with fascicular tachycardia, for whom we performed a transcatheter radiofrequency ablation procedure using the EnSite® system. Activation mapping was performed in all patients during tachycardia, and the earliest presystolic purkinje potentials were the target site for radiofrequency lesions.

Twenty-five patients were male, and eight were female. The mean weight of the patients was 39.6 ± 10.4 kg, and the mean age was 13.6 ± 2.5 years. The mean procedure time was 121.3 ± 44.3 minutes. The mean follow-up period was 18.4 ± 6.5 months. No fluoroscopy was needed in 30 patients. The mean fluoroscopy time in the remaining patients was 166.6 ± 80 seconds. All of the patients had left posterior fascicular tachycardia except for one who had left anterior fascicular tachycardia. The acute success rate was perfect (100%). No patients developed left bundle branch block or complete atrioventricular block. Recurrence developed in one patient.

We suggest that radiofrequency ablations via an electroanatomic mapping system are quite safe and effective, with high success rates in paediatric patients with fascicular tachycardia. This method has the advantage of avoiding ionising radiation exposure for both the patient and operator, thus reducing the lifetime risk of malignancy in the paediatric population.

Pulmonary vascular disease resulting from CHDs may be the most preventable cause of pulmonary artery hypertension worldwide. Many children in developing countries still do not have access to early closure of clinically significant defects, and the long-term outcomes after corrective surgery remain unclear. Focused on long-term results after isolated ventricular septal defect repair, our review sought to determine the most effective medical therapy for the pre-operative management of elevated left-to-right shunts in patients with an isolated ventricular septal defect.

We identified articles specific to the surgical repair of isolated ventricular septal defects. Specific parameters included the pathophysiology and pre-operative medical management of pulmonary over-circulation and outcomes.

Studies most commonly focused on histologic changes to the pulmonary vasculature and levels of thromboxanes, prostaglandins, nitric oxide, endothelin, and matrix metalloproteinases. Only 2/44 studies mentioned targeted pharmacologic management to any of these systems related to ventricular septal defect repair; no study offered evidence-based guidelines to manage pulmonary over-circulation with ventricular septal defects. Most studies with long-term data indicated a measurable frequency of pulmonary artery hypertension or diminished exercise capacity late after ventricular septal defect repair.

Long-term pulmonary vascular and respiratory changes can occur in children after ventricular septal defect repair. Research should be directed at providing an evidenced-based approach to the medical management of infants and children with ventricular septal defects (and naturally all CHDs) to minimise consequences of pulmonary artery hypertension, particularly as defect repair may occur late in underprivileged societies.

Registry-based trials have emerged as a potentially cost-saving study methodology. Early estimates of cost savings, however, conflated the benefits associated with registry utilisation and those associated with other aspects of pragmatic trial designs, which might not all be as broadly applicable. In this study, we sought to build a practical tool that investigators could use across disciplines to estimate the ranges of potential cost differences associated with implementing registry-based trials versus standard clinical trials.

We built simulation Markov models to compare unique costs associated with data acquisition, cleaning, and linkage under a registry-based trial design versus a standard clinical trial. We conducted one-way, two-way, and probabilistic sensitivity analyses, varying study characteristics over broad ranges, to determine thresholds at which investigators might optimally select each trial design.

Registry-based trials were more cost effective than standard clinical trials 98.6% of the time. Data-related cost savings ranged from $4300 to $600,000 with variation in study characteristics. Cost differences were most reactive to the number of patients in a study, the number of data elements per patient available in a registry, and the speed with which research coordinators could manually abstract data. Registry incorporation resulted in cost savings when as few as 3768 independent data elements were available and when manual data abstraction took as little as 3.4 seconds per data field.

Registries offer important resources for investigators. When available, their broad incorporation may help the scientific community reduce the costs of clinical investigation. We offer here a practical tool for investigators to assess potential costs savings.

Lower respiratory tract infections caused by respiratory syncytial virus can be severe during infancy, which requires admission to the hospital. These infections may be more severe especially in patients with congenital heart disease. Passive immunisation with palivizumab, a monoclonal antibody, is recommended in high-risk infants. We tried to determine the compliance rates, factors affecting compliance, and also other microorganisms responsible for lower respiratory tract infections after palivizumab prophylaxis in these patients.

We evaluated patients’ compliance to prophylaxis with palivizumab in two consecutive respiratory syncytial virus seasons from pharmacy records. We also investigated factors affecting compliance and the frequency of hospitalisations for lower respiratory tract infections. We investigated the causative microorganisms detected in hospitalised patients.

In this study, 86.7% of the desired number of injections was achieved in 176 patients in two seasons. Out of these, 117 patients (66.4%) received all the doses they were prescribed. Although not statistically significant, compliance to prophylaxis was higher in male patients, cyanotic patients, those who started under 1 year old, and who lived in the city centre. Human metapneumovirus, parainfluenza type 3, and bocavirus were detected in the hospitalised patients.

Patients with congenital heart disease can survive the period of infancy with less problem by making palivizumab prophylaxis more effective, and awareness about non- respiratory syncytial virus factors may be a guide for the development of new treatments.

There are little data about renal follow-up of neonates after cardiovascular surgery and no guidelines for long-term renal follow-up. Our objectives were to assess renal function follow-up practice after neonatal cardiac surgery, evaluate factors that predict follow-up serum creatinine measurements including acute kidney injury following surgery, and evaluate the estimated glomerular filtration rate during follow-up using routinely collected laboratory values.

Two-centre retrospective cohort study of children 5–7 years of age with a history of neonatal cardiac surgery. Univariable and multivariable analyses were performed to determine factors associated with post-discharge creatinine measurements. Glomerular filtration rate was estimated for each creatinine using a height-independent equation.

Seventeen of 55 children (30%) did not have any creatinine measured following discharge after surgery until the end of study follow-up, which occurred at a median time of 6 years after discharge. Of the 38 children who had the kidney function checked, 15 (40%) had all of their creatinine drawn only in the context of a hospitalisation or emergency department visit. Acute kidney injury following surgery did not predict the presence of follow-up creatinine measurements.

A large proportion of neonates undergoing congenital heart repair did not have a follow-up creatinine measured in the first years following surgery. In those that did have a creatinine measured, there did not appear to be any identified pattern of follow-up. A follow-up system for children who are discharged from cardiac surgery is needed to identify children with or at risk of chronic kidney disease.

Pulmonary vasodilators improve the functional capacity of some patients with pulmonary arterial hypertension. However, pulmonary vasodilators frequently fail to improve unequivocal endpoints of efficacy in patients with lower pulmonary arterial pressures who have been palliated with a Fontan procedure.

Haemodynamic measurements and the results of acute vasodilator testing in a subset of patients were reviewed to determine whether some patients acutely respond more favourably to sildenafil and might be candidates for precision care with a phosphodiesterase V inhibitor long term.

Heart catheterisation was performed in 11 patients with a Fontan procedure. Haemodynamic measurements were performed before and after treatment with intravenous sildenafil (mean 0.14, range 0.05–0.20 mg/kg). Results (mean ± standard deviation) were compared by paired and unpaired t-tests to identify statistically significant changes.

Sildenafil was acutely associated with changes in mean pulmonary arterial pressure, transpulmonary gradient, indexed blood flow, and indexed vascular resistance. Changes in mean pulmonary arterial pressure were greater for patients with a mean pulmonary arterial pressure greater than 14 mmHg compared to patients with a lower mean pulmonary arterial pressure. Changes in transpulmonary gradient were greater for patients with a transpulmonary gradient greater than 5 mmHg compared to patients with a lower transpulmonary gradient.

Sildenafil acutely decreases mean pulmonary arterial pressure and transpulmonary gradient and causes greater acute changes in patients with higher mean pulmonary arterial pressures and transpulmonary gradients. Haemodynamic measurements and vasodilator testing might help to guide precision care following Fontan palliation.

Giant coronary aneurysms are the most severe complications of Kawasaki disease. There are few reports of outcomes from China. Most previous studies were based only on absolute aneurysmal dimensions. The aim of the present study was to catalog the outcomes of Kawasaki disease with giant coronary aneurysms in southwest China based on absolute dimensions and the z-score adjusted for body surface area.

All patients diagnosed with giant coronary aneurysms (z-score ≥ 10 or absolute dimension ≥ 8 mm) between December, 2002 and December, 2018 were included. We retrospectively analysed patient characteristics and clinical data from 38 patients with giant coronary aneurysms. Over a median follow-up period of 30.5 months (range from 1.7 months to 22.3 years), including patients in chronic phase who had been diagnosed prior to 2002, eight patients had myocardial infarction, including two deaths and one patient with coronary artery bypass grafting. The 1-, 2-, and 5-year event-free rates were 0.63, 0.63, and 0.53 for thrombosis, respectively, and 0.86, 0.81, and 0.81 for major adverse cardiac events, respectively. The 1-, 2-, and 5-year regression-free rates were 0.94, 0.85, and 0.67, respectively. A total of 73.7% of patients remained active.

In the early stages of Kawasaki disease, patients with giant coronary aneurysms often experience major cardiovascular events; however, they are also likely to have normalisation of the coronary internal luminal diameter. With long-term anticoagulation, close cardiologic monitoring, and prompt thrombolytic therapy, most patients can achieve disease-free periods.

The use of statins in children, although not frequent, is recommended in specific clinical contexts, namely, familial hypercholesterolaemia, conditions carrying a moderate-high cardiovascular risk and sub-optimal cholesterol levels after implementation of lifestyle modifications. The aim of this study is to characterise children with dyslipidaemia managed with statins, followed at a tertiary referral centre in central Portugal.

The authors carried out a retrospective and descriptive study made up of 66 patients (50% males, mean age of therapy onset 11.9 years) followed up at the Cardiovascular Clinic of a tertiary referral centre between January, 2012, and May, 2018. Clinical, analytical, and echocardiographic parameters were analysed. About 60.6% had clinical and/or molecular diagnosis of familial hypercholesterolaemia. On average, each patient had three cardiovascular risk factors, obesity (31%) being most prevalent, followed by arterial hypertension (14%). Statin therapy showed a statistically significant reduction in the lipid profile, particularly in the total cholesterol (23%) and low-density lipoprotein cholesterol (30%) levels, as well as in the carotid intima-media thickness (p = 0.015). Hepatic and muscle integrity markers were within normal range.

Statins are safe and efficient in the management of children with hypercholesterolaemia. Our study showed that apart from its lipid-lowering properties, it also reduced significantly the carotid intima-media thickness and, implicitly, the cardiovascular risk of these patients.

Monitoring for acute allograft rejection improves outcomes after cardiac transplantation. Endomyocardial biopsy is the gold standard test defining rejection, but carries risk and has limitations. Cardiac magnetic resonance T2 mapping may be able to predict rejection in adults, but has not been studied in children. Our aim was to evaluate T2 mapping in identifying paediatric cardiac transplant patients with acute rejection.

Eleven paediatric transplant patients presenting 18 times were prospectively enrolled for non-contrast cardiac magnetic resonance at 1.5 T followed by endomyocardial biopsy. Imaging included volumetry, flow, and T2 mapping. Regions of interest were manually selected on the T2 maps using the middle-third technique in the left ventricular septal and lateral wall in a short-axis and four-chamber slice. Mean and maximum T2 values were compared with Student’s t-tests analysis.

Five cases of acute rejection were identified in three patients, including two cases of grade 2R on biopsy and three cases of negative biopsy treated for clinical symptoms attributed to rejection (new arrhythmia, decreased exercise capacity). A monotonic trend between increasing T2 values and higher biopsy grades was observed: grade 0R T2 53.4 ± 3 ms, grade 1R T2 54.5 ms ± 3 ms, grade 2R T2 61.3 ± 1 ms. The five rejection cases had significantly higher mean T2 values compared to cases without rejection (58.3 ± 4 ms versus 53 ± 2 ms, p = 0.001).

Cardiac magnetic resonance with quantitative T2 mapping may offer a non-invasive method for screening paediatric cardiac transplant patients for acute allograft rejection. More data are needed to understand the relationship between T2 and rejection in children.

Neonates undergoing surgery for congenital heart disease are vulnerable to adverse events. Conventional quality improvement processes centring on mortality and significant morbidity leave a gap in the identification of systematic processes that, though not directly linked to an error, may still contribute to adverse outcomes. Implementation of a multidisciplinary “flight path” process for surgical patients may be used to identify modifiable threats and errors and generate action items, which may lead to quality improvement.

A retrospective review of our neonatal “flight path” initiative was performed. Within 72 hours of a cardiac surgery, a meeting of the multidisciplinary patient care team occurs. A “flight path” is generated, graphically illustrating the patient’s hospital course. Threats, errors, or unintended consequences are identified. Action items are generated, and a working group is formed to address the items. A patient’s flight path is updated weekly until discharge. The errors and action items are logged into a database, which is analysed quarterly to identify trends.

Thirty one patients underwent flight path review over a 1-year period; 22.5% (N = 7) of patients had an error-free “flight.” Eleven action items were generated – four from identified errors and seven from identified threats. Nine action items were completed.

Flight path reviews of congenital cardiac patients can be generated with few resources and aid in the detection of quality improvement opportunities. The regular multidisciplinary meetings that occur as a part of the flight path review process can promote inter-professional teamwork.