Background: Surgical closure of ventricular septal defects has been performed for many years, and is considered as the gold standard for treatment. It remains associated with morbidity and mortality. Transcatheter techniques have been developed in the last 10 years as a possible alternative to conventional surgery. Methods: The procedure is performed under general anaesthesia, and with continuous fluoroscopic and transesophageal echocardiographic guidance. Devices of the Amplatzer family, two in particular, have achieved a large popularity in clinical practice, and are currently the devices most commonly used to close muscular and perimembranous ventricular septal defect percutaneously. Results: Data from literature show that successful closure of muscular defects is obtained in around 96% of patients, with a rate of major complication of around 2%. Pooling data from the literature shows that successful closure of perimembranous defects is also obtained in 96% of patients, again with major acute complications in around 2%. The major problem is the occurrence of complete atrioventricular block, reported in 1.7% of subjects. Acquired defects can occur as residual leaks after surgical closure, or as consequence of myocardial infarction. There are very few data concerning percutaneous closure of postoperative residual defects. As for the surgical approach, in patients with post-myocardial defects the success rate of percutaneous closure is around 88%, with a mortality of 22%. Conclusions: Nowadays, in experienced hands, percutaneous closure is a safe and effective procedure. In selected patients, closure of congenital or acquired muscular and perimembranous ventricular septal defects can be considered a real alternative to the standard surgical approach, with the advantage of a significantly reduced rate of mortality and complications.

Objectives: This study was designed to assess the frequency and types of genetic variants in CFC1 in children with laterality disorders associated with cardiovascular involvement. Background: Laterality syndromes are estimated to comprise 3% of neonates with congenital cardiac disease. Genetic predisposition in some cases of laterality defects has been suggested by associated chromosomal anomalies and familial aggregation, often within consanguineous families, suggesting autosomal recessive inheritance. Mice with induced homozygous mutations in cfc1, and heterozygous CFC1 mutations in humans, have been associated with laterality defects. Methods: Direct sequence analysis of the coding sequence of CFC1 was performed in 42 subjects with laterality defects and congenital cardiac disease. Results: We identified 3 synonymous coding variants, 3 non-synonymous coding variants (N21H, R47Q, and R78W), and 2 intronic variants in CFC1. The N21H variant was observed in 3 of 19 affected Caucasians, and the R47Q variant in another 2. Neither polymorphism was observed in Caucasian controls. Furthermore, all subjects with the N21H polymorphism had double outlet right ventricle. Transmission of both the N21H and R47Q polymorphisms from unaffected parents was demonstrated, and all three non-synonymous variants had significant allele frequencies in unaffected African-American subjects, suggesting that other factors must also contribute to laterality defects. Conclusions: Three non-synonymous variants in CFC1 were identified, the N21H variant being associated with laterality defects in Caucasians, but not fully penetrant. One or more of these non-synonymous missense variants may act as a susceptibility allele in conjunction with other genes, and/or environmental factors, to cause laterality defects.

Introduction: The first step in diagnosing congenital cardiac malformations is to assess the arrangement of the atrial appendages. In patients with abnormal lateralization of the organs of the body, the arrangement of atrial appendages is neither normal, nor a mirror image of normal. There are 2 categories of abnormal arrangement based on the morphology of the atrial appendices, namely right isomerism and left isomerism, and in almost all instances these are found in the setting of so-called heterotaxy syndromes. Objective: To evaluate the various congenital cardiac malformations those are associated with abnormalities of lateralization, and to discuss the diagnostic tools, therapeutic options, and outcome for these patients. Patients and methods: We studied 134 patients, who had been admitted to our department of paediatric cardiology with known abnormalities of lateralization and congenital cardiac defects between 1990 and 2003. The data relating to each patient was evaluated retrospectively. The arrangement of the atrial appendages was established echocardiographically, and/or angiographically, and/or on the basis of morphologic investigations during the operation. These studies showed that 43 (32.1%) of the patients had right isomerism, and 88 (65.7%) had left isomerism. In 2 (1.5%), there was mirror-imaged arrangement, while in the final patient (0.07%), we were unable to determine sidedness with certainty. The median age at diagnosis was 0.66 years, and the females outnumbered the males in a ratio of 3 to 1. Patients in the 2 isomeric groups were compared with regard to age, cardiac defects, diagnostic tools and outcomes. Results: The difference in mean ages of the two groups of patients was statistically significant, those with right isomerism being 1.0 minus or plus 1.5 years, as opposed to those with left isomerism being 3.3 minus or plus 4.7 years (P is less than 0.005). Of the patients with right isomerism, 32 (74.4%) had left-sided, and 11 (25.6%) right-sided hearts, whereas in those with left isomerism, the hearts were left-sided in 65 (73.9%), and right-sided in 21 (23.9%), with 2 (2.2%) positioned in the midline. Extracardiac totally anomalous pulmonary venous connection was more common in those with right isomerism, being found in 13 patients (30.2%) as opposed to 5 patients (5.7%) with left isomerism. In only 8 of those with right isomerism did we find two perforate atrioventricular valves (18.6%), this arrangement being found in 34 (38.6%) of those with left isomerism. Pulmonary atresia and stenosis were present in 40 (93.0%) of those with right isomerism, but also in 41 (46.6%) of the patients with left isomerism. Angiographic and echocardiographic investigations were concordant in about three-quarters of patients with both right and left isomerism. All patients with extracardiac totally anomalous pulmonary venous connection died. Overall, 22 of the patients with right isomerism died (51.2%), as opposed to 20 (22.7%) of those with left isomerism. Conclusion: Our experience confirms that patients with right isomerism have more complex cardiac defects than those with left isomerism. Overall, the presence of isomerism carries a poor prognosis, the more so for right isomerism, with this related to the complex cardiac abnormalities. In our cohort, extracardiac totally anomalous pulmonary venous connection with pulmonary arterial obstruction was always a fatal combination. The mapping of cardiac and abdominal morphologies is still essential for proper diagnosis of these syndromes, especially in fetal life.

We report our initial experience in using the Amplatzer® vascular plug for closure of coronary arterial fistulas. The self-expanding, cylindrical, device is made from Nitinol wire mesh, and is available from 4 to 16 millimetres in diameter. We have now used the device to close fistulas in 3 patients, aged from 3 to 14 years, who presented with ratios of pulmonary-to-systemic flow from 1.5 to 3. In 2 patients, fistulas arising from the proximal right and left coronary arteries, with maximal diameters of 9 and 10 millimetres, respectively, had their narrowest diameter, of 6 millimetres, proximal to the entrance into the right atrium via a saccular aneurysm. The third fistula, with a maximal diameter of 16 millimetres, and with its origin from the circumflex coronary artery, entered the right atrium with nearly unrestricted flow, its narrowest diameter being 8 millimetres. For interventional closure, we chose plugs twice the diameter of the narrowest segment of the fistula, thus using 2 devices of 12 millimetres and one of 16 millimetres diameter. An arteriovenous loop was established through the fistula by snaring an exchange guide wire. Using a 7 or 8 French guide catheter inserted through the femoral vein, all plugs were placed at the narrowest segment of the fistula, leading to immediate complete closure of 2 fistulas. The third patient, with a fistula of the circumflex coronary artery, who received the largest plug initially had residual flow, but the fistula was found to be completely occluded at 12 months follow-up examination. We have demonstrated, therefore, safe and effective usage of the new vascular plug for transcatheter closure of moderate- to large-sized coronary arterial fistulas. The plug offers an alternative to cardiac surgery, or occlusion using coils.

We treated prospectively 14 patients with Eisenmenger's syndrome, with a mean age of 10 years, ranging from 3 to 18 years. Treatment continued for 12 months, and demonstrated a lasting symptomatic improvement, but no improvement in terms of mean saturation of oxygen over 24 hours. Exercise capacity, as judged by peak uptake of oxygen, worsened in the six patients able to perform a treadmill test. The symptomatic benefit from dual blockage of endothelin receptors in these patients may be due to mechanisms other than selective pulmonary vasodilatation alone.

Background: Nicotinamide adenine dinucleotide phosphate oxidase of the vascular cell membrane is an important source of reactive oxygen species. The aim of our study was to evaluate the possible influence of the p22phox C242T gene polymorphism on blood pressure and some markers of oxidative stress in children with tetralogy of Fallot. Methods: After surgical repair in early life, we recruited 38 children, aged 11.7 plus or minus 3.2 years, including 185 healthy individuals as controls for the purposes of establishing frequencies of alleles and genotypes. From this latter group, we matched a sub-sample of 53 healthy caucasian children, aged 11.0 plus or minus 1.0 years, in order to compare enzymic activities. Results: The children with tetralogy of Fallot showed significantly lower values of low-molecular-weight protein tyrosine phosphatase, particularly in carriers of CC genotype for the p22phox gene, with values of 145.2 plus or minus 77.4 μmol/g Hb/h, compared to controls, at 344.4 plus or minus 100.4 μmol/g Hb/h (p less than 0.001). Methemoglobin reductase activity in the patients with tetralogy was also lower in those with the CC genotype, at 9.8 plus or minus 3.2 μmol/g Hb−1 min−1 compared to 24.2 plus or minus 11.8 μmol/g Hb−1 min−1 as measured in the controls (p less than 0.01). Lower systolic (p less than 0.05) and diastolic (p less than 0.01) blood pressures were also observed in the patients with tetralogy of Fallot. Conclusions: Patients with tetralogy of Fallot having the CC genotype may be at a higher state of oxidative stress than T allele carriers, a finding which could have prognostic implications. Long term follow-up of these patients, however, may be necessary in order to draw definite conclusions.

Objective: To evaluate the role of transoesophageal echocardiography and problems related to safety during the surgical repair of congenital cardiac malformations in children. Methods: We examined the transoesophageal recordings made in 350 children with congenital cardiac diseases, aged from 2 months to 17 years and 9 months, with a median age of 2.7 years, tracings having been taken both before and after cardiopulmonary bypass. All patients had been scanned by transthoracic echocardiography before the operative procedures. Results: Preoperative transoesophageal echocardiography added additional findings, or changed the diagnoses made using transthoracic echocardiography, in 33 cases (9.4%), among which the findings had therapeutic significance in 23 cases (6.6%) that altered the planned surgical procedures. Residual problems or sequels were detected by postoperative transoesophageal echocardiography in 57 cases (16.3%), with 13 patients (3.7%) requiring instant intervention or return to bypass for modifications of the surgical procedures. We encountered no severe complications due to the performance of transoesophageal echocardiography. Mild complications occurred in only 2 patients (0.6%). Conclusions: Transoesophageal echocardiography is a useful tool with which to determine the strategies for treatment in the perioperative period, and to improve the quality of surgical procedures in children with congenital cardiac diseases. Complications were few, but still deserved careful attention to detail.

Background: Stenting for aortic coarctation has been shown to be effective in the short term. The safety and longer term efficacy of transcatheter therapy, however, must be well established if the technique is to be widely accepted as an alternative to surgery. In order to determine the frequency, spectrum, and outcome of injury to the aortic wall caused by angioplasty or stenting of aortic coarctation, the nomenclature of mural injury in these patients must be adapted to the conditions of transcatheter therapy. Methods and Results: Between 1989 and July 2005, we inserted stents in 153 patients with aortic coarctation, their median age being 15.8 years. Prior aortic interventions had been performed in 98 patients, and preexisting aneurysms were observed in 19. Stenting resulted in a significant reduction of the gradient across the site of coarctation, from a median of 30 millimetres of mercury to zero (p less than 0.001), with a residual gradient within the aortic arch of 20 millimetres of mercury or more in 5% of patients. Acute injuries to the aortic wall, other than therapeutic tears, were observed in 3 patients (2%), none of whom required surgery. At median follow-up of 2.5 years, this being more than 5 years in 30 patients, 4 patients had died, albeit none from complications relating to stenting or catheterization. Acute injuries to the aortic wall did not progress, and new aneurysms were observed in 6% of patients subsequent to follow-up imaging. Stent fractures, and jailed or partially covered brachiocephalic vessels, were observed in 12, and 49, patients, respectively, but did not result in haemodynamic or embolic complications. Conclusions: Stenting for aortic coarctation results in consistent relief of the gradient, and few serious complications in the short and intermediate term. Serious injuries to the aortic wall are uncommon in our experience, and can be minimized with a focus on technical measures, such as pre-dilation before stenting.

Objective: To emphasize the formation of fibrous aneurysmal structures in the setting of muscular ventricular septal defects Methods: Among patients with muscular ventricular septal defects followed in our institute, we described six who were diagnosed with formation of fibrous aneurysms. Of the patients, one was female and others were male. The age at diagnosis ranged from eight days to 16 years. In one, the defect opened between the ventricular inlets, but in the others the defects occupied the middle part of the apical trabecular septum. Results: The sizes of defects at initial echocardiographic evaluation ranged from 2.9 to 8 millimetres. The period of follow up for four patients was from 5 months to 7 years, one patient could not be followed up, and the other had already been diagnosed when first seen in our Institution. In our second and third patients, no aneurysm was seen during the initial echocardiographic evaluation, and it was recognized during follow-up. In these two patients, sequential echocardiographic examinations showed that the formation of the aneurysm made the defect smaller, with it almost closing in one. Conclusion: Although seen most frequently in the setting of perimembranous defects, fibrous aneurysms can also form adjacent to, and reduce the size of, muscular ventricular septal defects.

Pulmonary venous stenosis has been a challenge to paediatric cardiologists and surgeons. In spite of significant improvements in the management and outcome of various congenital cardiac problems, the prognosis of this condition continues to be dismal. Acquired stenosis of the pulmonary veins has been described in the adult population, especially after radiofrequency ablation for atrial arrhythmias. The outcome of this condition has generally been described to be favourable in the long term. Acquisition of pulmonary venous stenosis in childhood has a very different outcome, and is not a very well recognised entity, with symptoms and signs which are non-specific. We present 7 infants who, when first assessed, had normal pulmonary veins, but who subsequently acquired stenoses of the veins, with very significant resultant morbidity and mortality.

The ownership of mobile telephones is now almost universal amongst the teenage population of the United Kingdom. Such telephones are a potential source of electromagnetic interference to medical equipment. We describe a case of troublesome interference with an electrocardiogram recording in a teenage patient whose mobile telephone was left switched on during a visit to hospital. This is likely to be a common reason for poor quality electrocardiographic recordings.

An eight-month-old girl with hypoplastic left heart syndrome, who underwent a modified Norwood operation at the age of two days, and a Hemifontan operation at five months of age, had severely impaired ventricular function and new electrocardiographic changes. Coronary angiography demonstrated a small adherent thrombus in the non-coronary sinus of Valsalva of the native aortic root, which may be the cause of unexplained ventricular dysfunction.