Paediatric heart transplantation in Australia comes of age: 21 years of experience in a national centre.

BACKGROUND: Heart transplantation (HT) is established therapy for end-stage heart failure in children with cardiomyopathy or congenital heart disease. AIMS: This review summarises experience at a national referral centre since the first local transplant. METHODS: Medical records of children referred for HT between 1 April 1988 and 1 January 2010 were retrospectively reviewed. All patients listed for HT were included. Survival analysis was used to summarise wait-list time to death/transplant, and separately, time to death in HT patients. RESULTS: One hundred and thirty-nine children were accepted on to the HT waiting list during the study (median age 7.7 (interquartile range (IQR) 2.5, 13.6) years), of whom 93 underwent HT (median age 10.9 (IQR 4.4, 14.6) years). Wait-list mortality was 32% (45 of 139 patients), lowest among children aged >10 years at listing (P < 0.001). Median time to HT was 69 days (range 29-146). Survival post-transplantation was 90% (95% confidence interval 82-95) at 1 year, 82% (72-89%) at 5 years and 68% (50-80%) at 10 years. Increasing case complexity over the study period included pre- and post-transplant circulatory support, management of pulmonary hypertension and introduction of ABO-incompatible HT for infants. Post-transplant survival did not vary according to age, pre-transplant diagnosis or use of pre-transplant circulatory support (all P > 0.05). CONCLUSIONS: Results of paediatric HT in Australia are comparable with international results, despite limitations of geographic isolation, small population and low organ donation rate. Increasing case complexity has not impacted on post-transplant survival.

An investigation of bupropion substitution for the interoceptive stimulus effects of nicotine.

Although the exact mechanism that makes bupropion hydrochloride (Zyban) effective as a smoking cessation aid has not been fully elucidated, studies have found that bupropion and nicotine share behavioural and neurophysiological properties suggesting that bupropion might serve as a substitute for nicotine. In fact, bupropion prompts nicotine-appropriate responding in operant and Pavlovian drug discrimination studies with rats. A majority of the literature examining this substitution pattern has been done with an operant paradigm. The present research extended this literature by further characterising the behavioural and neuropharmacological properties underlying the substitution for a nicotine conditioned stimulus (CS). Examination of the dose-effect function and temporal dynamics of this substitution pattern showed that bupropion (20 mg/kg) produced conditioned responding similar to nicotine (0.4 mg base/kg) (ED(50) = 9.9 mg/kg) at 15 and 30 min after injection and partially substituted 5 and 60 min post-injection. Bupropion produced a pattern of conditioned responding similar to nicotine during a 60-min extinction test. Additionally, it has been hypothesised that bupropion and nicotine have an overlapping dopaminergic mechanism. We tested the effects of bupropion pretreatment, the nicotine dose-effect function and the ability of dopamine antagonist to block the substitution of bupropion for nicotine. Pretreatment with doses of bupropion that did not substitute for the nicotine stimulus (5 and 10 mg/kg) did not affect nicotine-conditioned responding; pretreatment with 20 mg/kg attenuated nicotine-evoked responding. Pretreatment with the dopamine antagonists SCH-23390 and eticlopride blocked the substitution. Finally, S,S-hydroxybupropion, the major metabolite of bupropion in humans, did not substitute for the nicotine CS.

Initial results of primary device closure of large muscular ventricular septal defects in early infancy using perventricular access.

OBJECTIVES: To report our experience with the use of the Amplatzer muscular ventricular septal defect (VSD) occluder, using direct right ventricle free wall puncture for primary closure of muscular VSDs in infants. BACKGROUND: Young infants with heart failure due to large or multiple muscular VSDs often require intervention at a stage when percutaneous device closure is impractical due to delivery system limitations. There are considerable benefits to avoiding bypass in these infants. METHODS: Patients with suitable muscular VSDs, considered too small for transvenous closure, underwent periventricular muscular VSD closure under transesophageal echo (TEE) guidance. RESULTS: Eight infants underwent the procedure. The median age was 14 weeks (2-41) with median weight of 4 kg (3-6.6). Four patients had additional VSDs and one patient had previous repair of coarctation. One patient had dextrocardia and severe left ventricular impairment due to an associated cardiomyopathy. The median VSD size was 8 mm (range, 4-10 mm). A single device (6-12 mm) was deployed in each patient, the size chosen being 1-2 mm larger than the TEE measurement. Two patients had subsequent pulmonary artery banding, with absorbable bands, because of moderate residual shunting through additional VSDs. The latest echo study at a median of 7.2 weeks (0.5-66) post device implantation revealed no patients with a hemodynamically significant shunt. CONCLUSION: Perventricular muscular VSD closure can be safely and effectively undertaken in small infants with suitable muscular defects, and this strategy can avoid the need for bypass.

Nicotine serves as a feature-positive modulator of Pavlovian appetitive conditioning in rats.

The present experiments examined whether a nicotine state could set the occasion for a pairing between visual cues and a rewarding outcome in rats. Following nicotine administration, presentation of a conditional stimulus (CS; light-on) was followed by brief access to a sucrose solution. When saline was administered, the same CS was presented but was not followed by any consequence. In Experiment 1, two groups assessed whether rats could acquire this Pavlovian feature-positive discrimination via different training procedures. An anticipatory food-seeking conditioned response (CR) developed during the CS on nicotine sessions but not on saline sessions in both groups. In Experiment 2, centrally acting antagonists of nicotinic acetylcholine and opiate receptors (mecamylamine and naloxone, respectively) dose-dependently blocked nicotine's control of the CR, whereas the peripherally acting nicotinic antagonist hexamethonium had no effect. Increasing or decreasing the interval between nicotine administration and testing also attenuated the CR. These results are consistent with the hypothesis that nicotine can occasion appetitive Pavlovian relations via its action at central nervous system cholinergic receptors.

Long term somatic growth after repair of tetralogy of Fallot: evidence for restoration of genetic growth potential.

OBJECTIVE: To compare actual with predicted long term growth after early repair of tetralogy of Fallot (TOF). DESIGN: Serial preoperative and postoperative anthropometric data were converted with z scores. The presence of restrictive physiology was assessed by echocardiography. PATIENTS: 45 otherwise healthy patients who underwent repair at median age 1.6 years (range 0.2-4.9) were studied. Predicted height was determined from mid-parental height corrected for sex. RESULTS: Mean (SD) weight and height z scores at the time of surgery were significantly depressed (-1.04 (0.82) and -0.93 (0.95), respectively; p < 0.0001 for both). At latest follow up at a median age of 14.2 years (range 11-20.5), mean weight and height z scores were 0.16 (1.1) and -0.05 (0.81) (p = 0.32 and p = 0.41, respectively). The improvement between surgical and late weight and height z scores was significant (p < 0.0001 for each comparison). Catch up growth was largely complete within two years. Age at correction, duration of follow up, and prior surgical procedures were unrelated to growth. Mean current height z scores were similar to those predicted by mid-parental height. Patients with restrictive right ventricular physiology (n = 24) had a significantly greater late z score for weight (0.49 v -0.34; p = 0.01), with a similar trend for height. Low birth weight patients experienced comparable catch up growth but remained shorter than patients with normal birth weight (mean height z score -0.64 v 0.06; p = 0.03). CONCLUSIONS: Early repair of TOF results in significant acceleration of weight and height, with normalisation of long term growth and fulfilment of genetic growth potential.

Prospective comparison of costs and short term health outcomes of surgical versus device closure of atrial septal defect in children.

OBJECTIVE: To compare surgical and device closure of isolated secundum atrial septal defect (ASD) in terms of hospital costs, clinical outcome, and impact on the patient and family. DESIGN: Prospective, observational study. SETTING: Paediatric tertiary referral centre. PATIENTS: Consecutive local children with a secundum ASD, admitted between 1 May 1999 and 1 May 2001. METHODS: Parents completed a standardised questionnaire at recruitment (on admission), at discharge, and one month after the procedure. Clinical and hospital generated cost data were collated at discharge. RESULTS: 62 children were included in the analysis: 19 who underwent surgical repair and 43 who underwent device closure with the Amplatzer septal occluder. Median procedure times and hospital stay were significantly longer for surgical patients (170 (147 to 180) v 92 (70 to 115) minutes and 88 (78 to 112) v 29 (28 to 30) hours, respectively; p < 0.01). There was no difference in the complication rate. No device patients required intensive care or blood products. The median values for postoperative pain score, analgesia use, and convalescence time were greater for surgical patients. The median cost of each procedure was similar, but higher nursing and laboratory costs contributed to a slightly greater total cost for surgical repair (Aus$12 969 ($11 569 to $14 215) v Aus$11 845 ($10 669 to $12 555), p = 0.03). CONCLUSIONS: Device closure of ASD involves a shorter hospital stay, causes less discomfort and familial disturbance, and carries less cost than surgical closure. However, there should be guarded acceptance of this technique until long term data are available.

Clinical, electrocardiographic, and histologic correlations in children with dilated cardiomyopathy.

OBJECTIVE: To determine whether presenting electrocardiography is related to histologic findings and clinical outcomes in children with dilated cardiomyopathy. BACKGROUND: Lymphocytic myocarditis is an important cause of childhood dilated cardiomyopathy, the outcome of which is unclear. The results of non-invasive investigations are often used to infer the presence or absence of lymphocytic myocarditis. METHODS: Thirty-four children, presenting acutely with dilated cardiomyopathy, underwent both early electrocardiography and endomyocardial biopsy. The parameters examined included heart rate, PR, QRS, and corrected QT intervals, R-wave voltages in Leads V(1) and V(6), S-wave voltages in Leads V(1) and V(6), and sum of SV(1) and RV(6). We expressed measurements as Z scores, based on published normal values for age and gender. RESULTS: A total of 15 patients had lymphocytic myocarditis on endomyocardial biopsy (Group I), and 19 had non-specific histologic findings (Group II). We did not distinguish the 2 groups by age, time to endomyocardial biopsy, or duration of follow-up. Group I patients had significantly smaller R-wave Z scores in Leads V(1) and V(6), and combined S in V(1) and R in V(6) Z scores (p < 0.02 for each). The positive and negative predictive values of an R-wave amplitude in V(6) < 5th percentile were 75% and 65%, respectively, for the diagnosis of lymphocytic myocarditis. An R-wave amplitude in V(6) > 95th percentile had a positive and negative predictive value of 80% and 63%, respectively, for the diagnosis of idiopathic dilated cardiomyopathy. Survival and freedom from late cardiac dysfunction were more common among Group I patients compared with Group II (p

T wave alternans threshold in normal children.

INTRODUCTION: Sustained microvolt-level T wave alternans (TWA) during exercise is a predictor of ventricular arrhythmia propensity in adult populations. TWA occurs in normal adults, but it is rare at < 70% of predicted maximum heart rate. An onset heart rate < or = 110 is believed to be significant. The aim of this study was to examine the feasibility of performing the test in children and to determine the normal heart rate threshold for sustained TWA in children. METHODS AND RESULTS: Alternans was evaluated during bicycle exercise in 100 normal volunteers aged 8 to 17 years. Adequate resting data were obtained in 76 of 100 children and was negative in all. Exercise data from 16 of 100 was excluded due to excessive noise. Median maximum heart rate was 192 (range 140 to 214). Sustained alternans was absent in 75 (89%) of 84. In the nine children with sustained alternans, median onset heart rate was 138 (range 120 to 158), and 7 of 9 had an onset heart rate > or = 135. Median heart rate threshold as a percentage of predicted maximum heart rate (220 - age) was 67% (range 58% to 76%). Only 1 subject (1.2%) had an onset heart rate < 60% of predicted maximum. There was no significant difference between age, gender, endurance, maximum heart rate, QRS duration, QT interval, or QTc in those with and those without sustained TWA. CONCLUSION: Noninvasive assessment of TWA is feasible at > or = 8 years of age. Sustained TWA was present in 11% of normal children, but was absent at heart rates below 120 and rare (1.2%) below 60% of predicted maximum heart rate.

Successful occlusion of a coronary arteriovenous fistula using an Amplatzer duct occluder.

In an 11-year old boy with a large coronary arteriovenous fistula between the left coronary artery and the right atrium, we achieved successful closure using a 10-8 Amplatzer Duct Occluder introduced from the right internal jugular vein. Angiography 6 weeks later showed complete occlusion of the fistula, with normal opacification of the left coronary arterial system. This technique may be used as an alternative to coils and surgery in selected patients.

Interventional pediatric cardiology: device closures.

Surgical treatment of various septal defects has been long established. With the advances in transcatheter therapy dilatation techniques for valular stenosis and vascular obstruction have become established procedures. Closure of septal defects in the catheterization laboratory has also been introduced; some of these have come into regular use in current practice. In 1967, Porstmann et al reported the use of Ivalon plug to close patent ductus arteriosus (PDA). Since then, several devices have been used including Rashkind PDA occluder (not being used now), Gianturco coils, detachable coils (for small PDA), CardioSEAL and other umbrella devices and Amplatzer PDA occluder. Closure rates vary from 95-98% in most series, however, some of these devices are very expensive, more so, when compared to the cost of surgical ligation of PDA. Catheter closure of secundum atrial septal defect (ASD) has also been done by various devices like clamshell device, Sideris Buttoned device, ASDOS device, Amplatzer device and cardioSEAL. So far no device has been accepted as ideal for every case, however, Amplatzer device has been used most extensively. Issues such as completeness of endothelialisation, incidence of late arrhythmias, endocarditis remain uncertain. However, in a select population of ASD cases with a central secundum defect, device closure is being used increasingly. Device closure of ventricular septal defect remains challenging and controversial and is probably available to a small group of children with defects that are difficult to close surgically and involve higher risk.

New interventional therapeutic approach for dual drainage of the scimitar vein.

A patient with scimitar syndrome and dual drainage of a right-sided scimitar vein into the inferior vena cava and the left atrium underwent coil occlusion of the right aortopulmonary collateral artery and device occlusion of the lower scimitar vein drainage, leaving it flowing solely into the left atrium.

Interventional pediatric cardiology: device closures.

Surgical treatment of various septal defects has been long established. With the advances in transcatheter therapy dilatation techniques for valvular stenosis and vascular obstruction have become established procedures. Closure of septal defects in the catheterization laboratory has also been introduced; some of these have come into regular use in current practice. In 1967, Porstmann et al reported the use of Ivalon plug to close patent ductus arteriosus (PDA). Since then, several devices have been used including Rashkind PDA ocluder (not being used now), Gianturco coils, detachable coils (for small PDA), CardioSEAL and other umbrella devices and Amplatzer PDA occluder. Closure rates vary from 95-98% in most series, however, some of these devices are very expensive, more so, when compared to the cost of surgical ligation of PDA. Catheter closure of secundum atrial septal defect (ASD) has also been done by various devices like clamshell device, Sideris Buttoned device, ASDOS device, Amplatzer device and cardioSEAL. So far no device has been accepted as ideal for every case, however, Amplatzer device has been used most extensively. Issues such as completeness of endothelialisation, incidence of late arrhythmias, endocarditis remain uncertain. However, in select population of ASD cases with a central secundum defect, device closure is being used increasingly. Device closure of ventricular septal defect remains challenging and controversial and is probably available to a small group of children with defects that are difficult to close surgically and involve higher risk.

The diagnosis of innocent murmurs in childhood.

Innocent murmurs are common in childhood. They require accurate diagnosis to avoid unnecessary anxiety and/or restrictions. With this in mind, we studied prospectively children diagnosed by a paediatric cardiologist as having innocent murmurs to review the necessity of investigations in excluding organic abnormalities. We included 63 children in the study. The majority had the so-called Still's, or musical/vibratory murmur. None had abnormal investigations, suggesting that such investigations are largely superfluous for the purpose of diagnosis in those patients with innocent murmurs seen by a paediatric cardiologist. They are often done, nonetheless, as part of the assessment and/or expectations of the parent or the referring physician.

Pulmonary vascular resistance and reactivity in children with end-stage cardiomyopathy.

Pulmonary vascular resistance (PVR) and reactivity were compared in 63 children with end-stage cardiomyopathy (CM) referred for cardiac transplantation. Diagnostic category of CM was the sole determinant of PVR. Compared with other patients, children with restrictive CM were younger at diagnosis and had a significantly higher pulmonary vascular resistance index (PVRI). Children with a baseline PVRI of up to 11.8 units per meter squared (U.m(2)) who showed reactivity underwent successful orthotopic cardiac transplantation.

Congenital Heart Surgery Nomenclature and Database Project: corrected (discordant) transposition of the great arteries (and related malformations).

The extant nomenclature for congenitally corrected transposition of the great arteries is reviewed for the purpose of establishing a unified reporting system. The subject was debated and reviewed by members of the STS-Congenital Heart Surgery Database Committee and representatives from the European Association for Cardiothoracic Surgery. All efforts were made to include all relevant nomenclature categories using synonyms where appropriate. Congenitally corrected transposition of the great arteries is a complex cardiac lesion that is associated with ventricular septal defect, left ventricular outflow tract obstruction, and tricuspid valve abnormalities. Nomenclature for this lesion has been variable and confusing. Herein we attempt to clarify the terminology, with an emphasis on identification of synonymous and nonsynonymous appellations. A comprehensive database set is presented that is based on a hierarchical scheme. Data are entered at various levels of complexity and detail that can be determined by the clinician. These data can lay the foundation for comprehensive risk stratification analyses. A minimum database set is also presented that will allow for data sharing and would lend itself to basic interpretation of trends. Outcome tables relating diagnoses, procedures, and various risk factors are presented.

Infective endocarditis on an occluder closing an atrial septal defect.

Closure of atrial septal defects be means of intravenous catheterisation has been undertaken using a variety of devices as an alternative to surgical closure. We describe the first case, to the best of our knowledge, of infective endocarditis complicating a successful transcatheter closure. This highlights the potential risk of this procedure, and emphasises the need for appropriate antibiotic prophylaxis until complete endothelialization of the device has occurred.

The long QT syndrome and seizures in childhood.

Children with the long QT syndrome (LQTS) are prone to life threatening ventricular arrhythmias. These arrhythmias may result in syncope and seizures that are often attributed incorrectly to a seizure disorder or to common fainting. The untreated mortality for symptomatic children with the LQTS is high but is improved significantly with therapy. Paediatricians should be aware of the presentations of the syndrome. Recommendations for screening for the syndrome are given.