Objective: To assess haemodynamic patterns in head-up tilt testing on 400 paediatric cases with unexplained syncope. Methods: Medical records of 520 children who underwent head-up tilt testing in the preceding year were retrospectively evaluated, and 400 children, 264 (66%) girls and 136 (34%) boys, aged 12.6±2.6 years (median 13; range 5–18), with unexplained syncope were enrolled in the study. Age, sex, baseline heart rate, baseline blood pressure, frequency of symptoms, and/or fainting attacks were recorded. The test protocol consisted of 25 minutes of supine resting followed by 20 minutes of 70° upright positioning. Subjects were divided into nine groups according to their differing haemodynamic patterns. Results: There were no statistically significant differences between the groups with regard to age, gender, baseline blood pressure, and frequency of syncope (p>0.05). The response was compatible with orthostatic intolerance in 28 cases (7.0%), postural orthostatic tachycardia syndrome in 24 cases (6.0%), asymptomatic postural orthostatic tachycardia syndrome in 26 cases (6.5%), orthostatic hypotension in seven cases (1.7%), vasovagal syncope in 38 cases (9.5%), and negative in 274 cases (69.2%). Vasovagal syncope response patterns were of type 3 in nine cases (2.2%), type 2A in 10 cases (2.5%), type 2B in two cases (0.5%), and type 1 (mixed) in 17 cases (4.25%). Conclusions: In the 400 paediatric cases with unexplained syncope, nine different haemodynamic response patterns to head-up tilt testing were discerned. Children with orthostatic intolerance syndromes are increasingly referred to hospitals because of difficulty in daily activities. Therefore, there is need for further clinical trials in these patient groups.

Foetal echocardiography has progressed to be able to diagnose many forms of CHD and to assess the prognosis of cardiac lesions based on their anatomy and presentation in utero. This article outlines a straightforward method for the rapid evaluation of foetus that may have congestive heart failure with or without hydrops and for the differentiation of the pre-hydropic state from normal. The presence of signs of foetal heart failure, such as cardiomegaly or valvular regurgitation, gives clues to the aetiology of hydrops. The assessment of the prognosis of hydrops foetalis can be difficult but can be aided by the use of the cardiovascular profile score. Once identified, the neurohumoral effects of foetal heart failure can be ameliorated using transplacental digoxin if the hydrops has not progressed.

Cardiovascular complications are among the leading causes of morbidity and mortality among survivors of childhood cancer, after cancer relapse and secondary malignancies. Although advances in cancer treatment have improved the 5-year survival rates, the same treatments, such as anthracyclines, that cure cancer also increase the risk for adverse cardiovascular effects. Anthracycline-related cardiotoxicity in survivors of childhood cancer is progressive and can take years to develop, initially presenting as sub-clinical cardiac abnormalities that, if left undetected or untreated, can lead to heart failure, myocardial infarction, or other clinical cardiac dysfunction. A higher cumulative dose of anthracycline is associated with cardiotoxicity in children; however, sub-clinical cardiac abnormalities are evident at lower doses with longer follow-up, suggesting that there is no “safe” dose of anthracycline. Other risk factors include female sex, younger age at diagnosis, black race, trisomy 21, longer time since treatment, and the presence of pre-existing cardiovascular disease and co-morbidities. Cardioprotective strategies during treatment are limited in children. Enalapril provides only temporary cardioprotection, whereas continuous anthracycline infusion extends none. On the other hand, dexrazoxane successfully prevents or reduces anthracycline-related cardiotoxicity in children with cancer, without increased risks for recurrence of primary or second malignancies or reductions in anti-tumour efficacy. With more childhood cancer survivors now reaching adulthood, it is vital to understand the adverse effects of cancer treatment on the cardiovascular system and their long-term consequences to identify and establish optimal prevention and management strategies that balance oncologic efficacy with long-term safety.

Introduction: Subclinical hypothyroidism or mild thyroid failure is a common problem in patients without known thyroid disease. Methods: Demographic and analytical data were collected in 309, of which 181 were male and 128 were female, congenital heart disease (CHD) patients. CHD patients with thyroid-stimulating hormone above 5.5 mIU/L were also followed up from an analytical point of view to determine changes in serum glucose, cholesterol, N-terminal pro b-type natriuretic peptide, and C-reactive protein concentrations. Results: Of the CHD patients, 35 (11.3%) showed thyroid-stimulating hormone concentration above 5.5 mIU/L. Of them, 27 were followed up during 2.4±1.2 years – 10 were under thyroid hormone replacement treatment, and 17 were not. Of the 27 patients (25.9%), 7 with subclinical hypothyroidism had positive anti-thyroid peroxidase, and 3 of them (42.8%) with positive anti-thyroid peroxidase had Down syndrome. Down syndrome and hypoxaemic CHD patients showed higher thyroid-stimulating hormone concentrations than the rest of the congenital patients (p<0.001). No significant differences were observed in serum thyroxine, creatinine, uric acid, lipids, C-reactive protein, or N-terminal pro b-type natriuretic peptide concentrations before and after the follow-up in those CHD patients with thyroid-stimulating hormone above 5.5 mIU/L whether or not they received levothyroxine therapy. Conclusions: CHD patients with subclinical hypothyroidism showed no significant changes in serum thyroxine, cholesterol, C-reactive protein, or N-terminal pro b-type natriuretic peptide concentrations whether or not they were treated with thyroid hormone replacement therapy.

Antibiotic prophylaxis in congenital cardiac disease has long been a topic of debate. Although there is little dispute around antibiotic cover for surgical procedures and catheter interventions where foreign material is being inserted, there are little data specific to non-device-placement procedures such as atrial septostomy or balloon valvotomy. We sought to assess the effect of routine prophylaxis on post-interventional infections via a retrospective pseudo-randomised analysis, and an online survey on paediatric interventional cardiologists in the United Kingdom and United States.

Objective: By employing the widely used and accepted methodologies of case-mix complexity adjustment in congenital cardiac surgery, we tried to evaluate our performance and use the ABC scores for a case complexity selection that may have different outcomes in various centres. Methods: We analysed outcomes of cardiac surgical procedures – with or without cardiopulmonary bypass – performed in our institution between January, 2008 and December, 2011. Data were collected from the European Association for Cardio-Thoracic Surgery database. Together with prospective collection of these data, the data of all patients sent abroad to foreign cardiosurgical centres were recorded. Results: During the period of study, 634 operations were performed; among them, 60% were performed in Croatia and 40% in foreign cardiosurgical centres. The number of operations performed in Croatia showed a linear increase: 55, 78, 121, and 126 operations performed in the years 2008, 2009, 2010, and 2011, respectively. Early mortality rates were 1.82%, 5.41%, 3.64%, and 3.48% in 2008, 2009, 2010, and 2011, respectively. The increase in the number of operations was followed by a satisfactory low average mortality rate of 3.85%. The mean ABC score complexity for operations performed in Croatia was 5.77. We determined a linear correlation between ABC score and early mortality, especially for the more complex operations. Conclusion: The use of standardised risk scores allows selection of complex cardiac diseases, which may have very different outcomes in various centres. In our case, those with higher ABC scores were correctly identified and referred for treatment abroad. In this way, we allowed gradual progress of the cardiosurgical model in Croatia and maintained an enviably low mortality rate.

Background: To study the feasibility and complications associated with the use of ductal occluders for closure of perimembranous ventricular septal defects. Methods: A total of 126 patients, ranging from 1 to 41 years of age (median – 8 years), underwent closure of ventricular septal defects from August 2010 to April 2013. Small- and moderate-sized defects were closed using first-generation Patent ductus arteriosus occluders or Amplatzer Duct Occluder-II. Patients were followed up for the development of complications such as heart block, aortic regurgitation, and tricuspid regurgitation. Results: Patent ductus arteriosus occluders were used in 81 patients, and the Amplatzer Duct Occluder-II device in 45 patients. The devices were successfully deployed in 99.2% of the cases. One patient had embolisation of an Amplatzer Duct Occluder-II device soon after deployment. There was one case of transient complete heart block (0.8%) needing temporary pacing, and two cases of isoarrhythmic atrioventricular dissociation (1.6%). One patient developed late-onset complete heart block 15 months after the procedure and underwent permanent pacemaker implantation. There were no instances of new-onset aortic regurgitation. New-onset mild tricuspid regurgitation was seen in two patients. Of the patients, three had small residual shunts on follow-up, without haemolysis. Conclusions: Duct occluders can be used to effectively close small- and moderate-sized ventricular septal defects. The incidence of complete heart block and valvular regurgitations are much less than reported with other devices, and they are cost-effective.

Background: Percutaneous closure of patent ductus arteriosus has become the treatment of choice in many centres. In patients with large ducts and pulmonary hypertension, transcatheter closure has been achieved with success using the Amplatzer Duct Occluder or even the Amplatzer Muscular Ventricular Septal Defect Occluder. Materials and methods: We present a series of 17 patients with large and hypertensive ductus arteriosus who were treated with an Amplatzer Septal Occluder. The group had 11 female patients (64.7%) and a mean age of 18.6±12.1 years. Results: The haemodynamic and anatomical data are as follows: pulmonary artery systolic pressure 71.3±31.8 mmHg, pulmonary to systemic flow ratio 3.14±1.36, ductal diameter at the pulmonary end 12.5±3.8 mm, and at the aortic end 20.2±7.7 mm; 14 cases (82.3%) had type A ducts. In 11 patients, we began the procedure using a different device – six with duct occluder and five with ventricular septal occluder – and it was changed because of device embolisation in six (35.3%). All septal occluders were delivered successfully. Residual shunt was moderate in six patients (35.3%), mild in eight (47%), trivial in two (11.8%), and no shunt in one (5.9%). Pulmonary systolic pressure decreased to 48.9±10.8 mmHg after occlusion (p=0.0015). Follow-up in 15 patients (88.2%) for 28.4±14.4 months showed complete closure in all cases but one, and continuous decrease of the pulmonary systolic pressure to 31.4±10.5 mmHg. No complications at follow-up have been reported. Conclusions: The Amplatzer Septal Occluder is a good alternative to percutaneously treat large and hypertensive ductus arteriosus.

Stress echocardiography in paediatrics is used to evaluate pre- and post-operative coronary artery conditions, as well as to gain haemodynamic information for a variety of diagnoses, although evidence regarding sensitivity, specificity, and predictive value is lacking. This review will consider the available literature with a focus on anomalous aortic origin of the coronary arteries and discuss a practical approach to test selection and use.

Geleophysic dysplasia is an extremely rare acromelic skeletal dysplasia resembling lysosomal storage disease. It is characterised by characteristic facial phenotype, short stature, micromelia, joint contracture, and early cardiac valvular involvement. It has been described worldwide in <40 patients. Herein, we describe the cardiac features in three Saudi sisters with proved autosomal recessive geleophysic dysplasia who showed different levels of severity of their cardiac involvement.

Purpose: To explore the use of three-dimensional patient-specific cardiovascular models using rapid prototyping techniques (fused deposition modelling) to improve surgical planning in patients with complex congenital heart disease. Description: Rapid prototyping techniques are used to print accurate three-dimensional replicas of patients' cardiovascular anatomy based on magnetic resonance images using computer-aided design systems. Models are printed using a translucent polylactic acid polymer. Evaluation: As a proof of concept, a model of the heart of a 1.5-year-old boy with transposition of the great arteries, ventricular septal defect and pulmonary stenosis was constructed to help planning the surgical correction. The cardiac model allowed the surgeon to evaluate the location and dimensions of the ventricular septal defect as well as its relationship with the aorta and pulmonary artery. Conclusions: Cardiovascular models constructed by rapid prototyping techniques are extremely helpful for planning corrective surgery in patients with complex congenital malformations. Therefore they may potentially reduce operative time and morbi-mortality.

Heart transplantation offers excellent survival benefit to children with end-stage heart failure. With its success, the number of potential recipients continues to exceed the number of available donors. Developing strategies to safely increase donor utilisation is crucial to decreasing wait-list mortality. A new paediatric heart allocation policy is set to be implemented with the goal of prioritising the most urgent listed candidates. Owing to excellent outcomes of ABO-incompatible heart transplantation, the sickest infants will soon receive priority for heart offers irrespective of blood group. Allosensitisation poses unique challenges within the paediatric population; ongoing multi-centre studies are poised to refine our understanding of key risk factors and optimal treatment strategies. Biomarkers for acute cellular rejection, such as donor-specific cell-free DNA, and cardiac allograft vasculopathy, such as VEGF-A, may lead to a decreased need for invasive screening. Ultimately, well-designed and executed randomised control trials of post-transplant immunosuppression are required to improve long-term outcomes after paediatric heart transplantation.

Background: Coronary artery lesions in Kawasaki disease invasively assessed by coronary angiography. Evaluation of myocardial perfusion by single-photon emission computed tomography may identify the haemodynamic significance of coronary lesions. Objective: To evaluate diagnostic accuracy of dipyridamole stress technetium-99 m tetrofosmin, single-photon emission computed tomography as a possible alternative to invasive coronary angiography for detection and follow-up of myocardial ischaemia in patients with Kawasaki disease, and pre- and post-coronary bypass grafting. Patients and methods: Coronary angiography and single-photon emission computed tomography were performed on 21 patients who were classified into three groups – group I (stenosis), group II (giant aneurysms), and group III (small aneurysms). Of the 21 patients, 16 (groups I and II) patients with myocardial perfusion defects, who underwent coronary bypass grafting, were followed up with single-photon emission computed tomography. Result: In group I, all patients had significant coronary stenosis and 100% of them had perfusion defects in the anterior and septal walls. In group II, all patients had giant aneurysms and 83% of them had inferior and inferolateral perfusion defects. In group III, all patients had small aneurysms and 100% of them had normal perfusion. Pre-coronary bypass grafting myocardial ischaemic defects disappeared in all patients after surgery. Sensitivity, specificity, and accuracy of single-photon emission computed tomography were 94, 100, and 95%, respectively. Conclusion: Technetium-99 m tetrofosmin single-photon emission computed tomography can be applied as an accurate non-invasive diagnostic technique for detecting myocardial perfusion defects with coronary artery lesions, and to show improved or even normalised perfusion of the myocardium in patients after surgical revascularisation.

An infant presented with features suggestive of an anomalous left coronary artery was found to have normal origins of both coronary arteries. Echocardiography during episodes of ischaemia showed marked aortic regurgitation with retrograde coronary flow. The left coronary leaflet was mildly hypoplastic. Surgical re-suspension of this leaflet prevented aortic regurgitation and the patient had no further symptoms and recovered cardiac function.

Objectives: Insulin-like growth factor-1 may serve some regulatory function in the immune system. Rheumatic mitral stenosis is related to autoimmune heart valve damage after streptococcal infection. The aim of this study was to assess the level of insulin-like growth factor-1 and its correlation with the Wilkins score in patients with rheumatic mitral stenosis. Methods: A total of 65 patients with rheumatic mitral stenosis and 62 age- and sex-matched control subjects were enrolled in this study. All subjects underwent transthoracic echocardiography. The mitral valve area and Wilkins score were evaluated for all patients. Biochemical parameters and serum insulin-like growth factor-1 levels were measured. Results: Demographic data were similar in the rheumatic mitral stenosis and control groups. The mean mitral valve area was 1.6±0.4 cm2 in the rheumatic mitral stenosis group. The level of insulin-like growth factor-1 was significantly higher in the rheumatic mitral stenosis group than in the control group (104 (55.6–267) versus 79.1 (23.0–244.0) ng/ml; p=0.039). There was a significant moderate positive correlation between insulin-like growth factor-1 and thickening of leaflets score of Wilkins (r=0.541, p<0.001). Conclusions: The present study demonstrated that serum insulin-like growth factor-1 levels were significantly higher in the rheumatic mitral stenosis group compared with control subjects and that insulin-like growth factor-1 level was also correlated with the Wilkins score. It can be suggested that there may be a link between insulin-like growth factor-1 level and immune pathogenesis of rheumatic mitral stenosis.

Objective: Symptomatic neonates with Ebstein’s anomaly pose significant challenge. Within this cohort, neonates with associated anatomical pulmonary atresia have higher mortality. We review our experience with this difficult subset. Methods: A total of 32 consecutive symptomatic neonates with Ebstein’s anomaly underwent surgical intervention between 1994 and 2013. Of them, 20 neonates (62%, 20/32) had associated pulmonary atresia. Patients’ weights ranged from 1.9 to 3.4 kg. All patients without pulmonary atresia had two-ventricle repair. Of the 20 neonates, 16 (80%, 16/20) with Ebstein’s anomaly and pulmonary atresia had two-ventricle repair and 4 had single-ventricle palliation, of which 2 underwent Starnes’ palliation and 2 Blalock–Taussig shunts. Six recent patients with Ebstein’s anomaly and pulmonary atresia had right ventricle to pulmonary artery valved conduit as part of their two-ventricle repair. Results: Overall early mortality was 28% (9/32). For those without pulmonary atresia, mortality was 8.3% (1/12). For the entire cohort of neonates with Ebstein’s anomaly and pulmonary atresia, mortality was 40% (8/20; p=0.05). Mortality for neonates with Ebstein’s anomaly and pulmonary atresia having two-ventricle repair was 44% (7/16). Mortality for neonates with Ebstein’s anomaly and pulmonary atresia having two-ventricle repair utilising right ventricle to pulmonary artery conduit was 16% (1/6). For those having one-ventricle repair, the mortality was 25% (1/4). Conclusions: Surgical management of neonates with Ebstein’s anomaly remains challenging. For neonates with Ebstein’s anomaly and anatomical pulmonary atresia, single-ventricle palliation is associated with lower early mortality compared with two-ventricle repair. This outcome advantage is negated by inclusion of right ventricle to pulmonary artery conduit as part of the two-ventricle repair.

Background: Coarctation of the aorta is a very common congenital heart malformation. It is frequently associated with other abnormalities. Echocardiography is the diagnostic modality for congenital heart disease. The carotid-subclavian artery index and the isthmus/descending aorta index were proposed for establishing the diagnosis of coarctation of the aorta. Objectives: The objectives were to evaluate such indexes and to look for other echocardiographic predictors of coarctation of the aorta. Method Echocardiography was reviewed for infants with coarctation of the aorta, as well as a control group, using the Echo PAC Dimension. Standard measurements were obtained from different sites of the aortic arch. Results: A total of 31 infants 3 months or less with coarctation of the aorta and 50 infants with no coarctation of the aorta were reviewed. Abnormal aortic valve was present in 65% of those with coarctation of the aorta. The diameters of the proximal and the distal transverse aortic arch were smaller in the coarctation of the aorta group. The distance between the aortic arch branches was longer in the coarctation of the aorta group. Apart from the ratio between distance 2 and the ascending aorta, other ratios/indexes were smaller in the coarctation of the aorta group than in the control group. Conclusion: The presence of abnormal aortic valve, a carotid subclavian index <1.1, I/AAo ratio <0.53, and DTA/AAo ratio <0.6 suggest the presence of coarctation of the aorta. Neonates with large patent ductus arteriosus and any of these findings need close observation until the patent ductus arteriosus closes. If the arch is difficult to assess by two-dimensional echocardiography, the patient may need further imaging to rule out coarctation of the aorta.