Jonathan M. Parsons

Cardiac tumours in children

Cardiac tumours are benign or malignant neoplasms arising primarily in the inner lining, muscle layer, or the surrounding pericardium of the heart. They can be primary or metastatic. Primary cardiac tumours are rare in paediatric practice with a prevalence of 0.0017 to 0.28 in autopsy series. In contrast, the incidence of cardiac tumours during foetal life has been reported to be approximately 0.14%. The vast majority of primary cardiac tumours in children are benign, whilst approximately 10% are malignant. Secondary malignant tumours are 10–20 times more prevalent than primary malignant tumours. Rhabdomyoma is the most common cardiac tumour during foetal life and childhood. It accounts for more than 60% of all primary cardiac tumours. The frequency and type of cardiac tumours in adults differ from those in children with 75% being benign and 25% being malignant. Myxomas are the most common primary tumours in adults constituting 40% of benign tumours. Sarcomas make up 75% of malignant cardiac masses. Echocardiography, Computing Tomography (CT) and Magnetic Resonance Imaging (MRI) of the heart are the main non-invasive diagnostic tools. Cardiac catheterisation is seldom necessary. Tumour biopsy with histological assessment remains the gold standard for confirmation of the diagnosis. Surgical resection of primary cardiac tumours should be considered to relieve symptoms and mechanical obstruction to blood flow. The outcome of surgical resection in symptomatic, non-myxomatous benign cardiac tumours is favourable. Patients with primary cardiac malignancies may benefit from palliative surgery but this approach should not be recommended for patients with metastatic cardiac tumours. Surgery, chemotherapy and radiotherapy may prolong survival. The prognosis for malignant primary cardiac tumours is generally extremely poor.

Transcatheter occlusion of the arterial duct with Cook detachable coils: early experience.

OBJECTIVE: To assess the effectiveness of modified, controlled release Gianturco coils for transcatheter occlusion of the arterial duct. DESIGN: Prospective study, approved by local medical ethics committee. SETTING: Tertiary paediatric cardiac centre. PATIENTS: 43 patients with left to right shunting through the arterial duct, two of whom had a residual leak after surgical ligation and three had residual shunting after previous Rashkind umbrella implantation. INTERVENTION: Transcatheter delivery of one or more coils to the arterial duct. MAIN OUTCOME MEASURES: Complete occlusion of the arterial duct, based on intention to treat and judged by Doppler echocardiography. Absence of flow disturbance in the branch pulmonary arteries and the descending aorta following the procedure. Assessment of cost of the disposable items used. RESULTS: At a median follow up period of three months complete duct occlusion was achieved in 37 (86%) of the 43 patients. No flow disturbance in the branch pulmonary arteries or the descending aorta was detected in any patient. The median cost of disposable items used during the procedure was 342 pounds. CONCLUSIONS: The Cook detachable coil is an effective and financially attractive alternative to the Rashkind umbrella for closure of the arterial duct.

Laser valvotomy with balloon valvoplasty for pulmonary atresia with intact ventricular septum: five years' experience.

OBJECTIVE: To assess immediate and medium term results of transcatheter laser valvotomy with balloon valvoplasty in selected infants with pulmonary atresia and intact ventricular septum. DESIGN: Prospective study. SETTING: Tertiary cardiac unit. PATIENTS: All infants with pulmonary atresia and intact septum with no more than minor tricuspid valve hypoplasia referred between November 1990 and June 1995. Laser valvotomy was attempted in nine infants of median age 4-5 days and median weight 3.6 kg. INTERVENTION: The pulmonary valve was perforated using a 0.018 inch fibreoptic guidewire attached to a NdYag laser and introduced through a catheter positioned beneath the valve. After perforation the valve was dilated with progressively larger balloons. MAIN OUTCOME MEASURES: Successful laser valvotomy and balloon dilatation, complications, pulse oximetry, right ventricular outflow velocities, and need for surgical treatment. RESULTS: Valvotomy was successful in all but one case, the failure being due to laser breakdown. After perforation the valve was dilated to 6-8 mm diameter. Prostaglandin E was withdrawn immediately in six of the eight duct dependent infants, and 28 and 49 days later in two. No patient required an aortopulmonary shunt. Two patients had repeat valvoplasty at 20 days and three months of age, respectively; one required infundibular resection and closure of the atrial septum at age four and one is awaiting similar treatment. CONCLUSIONS: Laser valvotomy with balloon valvoplasty is safe and effective treatment for selected patients with pulmonary atresia and intact ventricular septum and should be considered as first line treatment in place of surgical valvotomy.

Genome-wide association study identifies loci on 12q24 and 13q32 associated with Tetralogy of Fallot

We conducted a genome-wide association study to search for risk alleles associated with Tetralogy of Fallot (TOF), using a northern European discovery set of 835 cases and 5159 controls. A region on chromosome 12q24 was associated (P = 1.4 × 10−7) and replicated convincingly (P = 3.9 × 10−5) in 798 cases and 2931 controls [per allele odds ratio (OR) = 1.27 in replication cohort, P = 7.7 × 10−11 in combined populations]. Single nucleotide polymorphisms in the glypican 5 gene on chromosome 13q32 were also associated (P = 1.7 × 10−7) and replicated convincingly (P = 1.2 × 10−5) in 789 cases and 2927 controls (per allele OR = 1.31 in replication cohort, P = 3.03 × 10−11 in combined populations). Four additional regions on chromosomes 10, 15 and 16 showed suggestive association accompanied by nominal replication. This study, the first genome-wide association study of a congenital heart malformation phenotype, provides evidence that common genetic variation influences the risk of TOF.

Right ventricular outflow stent implantation: an alternative to palliative surgical relief of infundibular pulmonary stenosis.

OBJECTIVE: Preliminary assessment of the use of stents for palliative relief of right ventricular infundibular stenosis as an alternative to palliative surgical ventricular outflow enlargement. DESIGN: Descriptive clinical study. PATIENTS: Four patients with right ventricular outflow obstruction, aged between 2 and 15 years. One had had previous palliative surgery for pulmonary atresia, one had hypoplastic pulmonary arteries after palliative surgery for tetralogy of Fallot, one had multiple congenital abnormalities, and one had hypertrophic cardiomyopathy. SETTING: Tertiary paediatric cardiac centre. METHODS: After initial echocardiographic diagnosis the extent of right ventricular outflow obstruction was assessed by angiography. Balloon expandable stainless steel stents (Johnson & Johnson) were deployed in the right ventricular infundibulum. MAIN OUTCOME MEASURES: Improvement in right ventricular outflow assessed by ventriculography and change in right ventricular/ left ventricular pressure ratio, change in systemic oxygen saturation, freedom from arrhythmias, and sustained improvement in echocardiographic indices of obstruction. RESULTS: Mean right to left ventricular pressure ratio fell from 0.95 to 0.35 in the three patients with intact ventricular septum. Oxygen saturation increased from 76% to 91% in the patient with tetralogy. No arrhythmias were detected. Improvement was maintained at mean follow up of 9.7 months in three cases, but one patient required stent enlargement 17 months later because of neoendothelial proliferation within the stent. CONCLUSION: Stent implantation provides an effective alternative to palliative surgical enlargement of the right ventricular infundibulum. Neoendothelial proliferation causes reduction in lumen in some cases, but this may respond to redilatation.

Exploring health‐related experiences of children and young people with congenital heart disease

Objective  To determine the health‐related experiences of children with congenital heart disease.

Systematic survey of variants in TBX1 in non-syndromic tetralogy of Fallot identifies a novel 57 base pair deletion that reduces transcriptional activity but finds no evidence for association with common variants

Background Tetralogy of Fallot (TOF) is common in individuals with hemizygous deletions of chromosome 22q11.2 that remove the cardiac transcription factor TBX1. Objective To assess the contribution of common and rare TBX1 genetic variants to TOF. Design Rare TBX1 variants were sought by resequencing coding exons and splice-site boundaries. Common TBX1 variants were investigated by genotyping 20 haplotype-tagging SNPs capturing all the common variations present at the locus. Association analysis was performed using the program UNPHASED. Patients TBX1 exons were sequenced in 93 patients with non-syndromic TOF. Single nucleotide polymorphism analysis was performed in 356 patients with TOF, their parents and healthy controls. Results Three novel variants not present in 1000 chromosomes from healthy ethnically matched controls were identified. One of these variants, an in-frame 57 base-pair deletion in the third exon which removed 19 evolutionarily conserved residues, decreased transcriptional activity by 40% in a dual luciferase assay (p=0.008). Protein expression studies demonstrated that this mutation affected TBX1 protein stability. After correction for multiple comparisons, no significant associations between common genetic variants and TOF susceptibility were found. Conclusion This study demonstrates that rare TBX1 variants with functional consequences are present in a small proportion of non-syndromic TOF.

The development of a new measure of quality of life for children with congenital cardiac disease.

The purpose of the study was to develop a questionnaire measuring health-related R1 quality of life for children and adolescents with congenital heart disease, the ConQol, that would have both clinical and research applications. We describe here the process of construction of a questionnaire, the piloting and the development of a weighted scoring system, and data on the psychometric performance of the measure in a sample of 640 children and young people recruited via 6 regional centres for paediatric cardiology from across the United Kingdom. The ConQol has two versions, one designed for children aged from 8 to 11 years, and the other for young people aged from 12 to 16 years. Initial findings suggest that it is a valid and reliable instrument, is acceptable to respondents, and is simple to administer in both a research and clinical context.

The views of parents concerning the planning of services for rehabilitation of families of children with congenital cardiac disease

BACKGROUND AND PURPOSE Although much previous research has focused on the medical aspects of congenital cardiac disease, there is a growing body of research which suggests that families may need help and support with the wider issues associated with the medical condition. We have previously ascertained from young people with congenital cardiac disease their views on this subject. The purpose of this study was to obtain the views of their parents about the need for, and shape of, services for rehabilitation. METHODS This was a qualitative study using semi-structured interviews. We interviewed 17 parents in their own home. Interviews were tape-recorded and transcribed. RESULTS Parents would welcome more help and support from health professionals to enable them to manage more effectively the condition with their children. Particular areas of concern relate to the information they receive about the condition; communication between themselves and health professionals; establishing safe levels of activity; and managing the condition at school. CONCLUSIONS This is a small study of the experiences and views of parents, which provides some important information on ways in which health professionals could address the current lack of services for rehabilitation.

Residual and recurrent shunts after implantation of Cook detachable duct occlusion coils

Objective To assess the presence and outcome of Doppler detectable shunts following implantation of the Cook detachable PDA coil. Design Prospective study. Setting Tertiary paediatric cardiac centre. Patients 76 consecutive patients undergoing coil implantation (80 procedures). Main outcome measures Detection and colour Doppler echocardiographic appearance of residual or recurrent shunts, the timing of the appearance of recurrent shunts, and the time taken for spontaneous resolution of these shunts. Results Immediate occlusion was achieved in 52 patients. At one month 63 patients had complete occlusion and after three months the duct was completely occluded in 67 patients. In 27 cases small residual shunts were detected on echocardiography 10 minutes after the completion of the implantation procedure; 15 of these had resolved by 24 hours and 20 had resolved by three months. Recurrent shunts were detected after apparent initial complete occlusion in 11 cases 24 hours after coil implantation and in two cases one month after the procedure. Six recurrent shunts resolved on later follow up. Residual shunts appeared as single jets after implantation of a single coil, but up to three separate jets were detected after implantation of multiple coils. Conclusions Spontaneous resolution of small residual shunts occurs in most patients. The recurrence of small shunts after apparent complete occlusion suggests that recanalisation of the duct may occur in a small percentage of patients up to one month after occlusion. Residual shunts may take the form of multiple residual jets that may require implantation of further coils to achieve complete duct occlusion.