Deficiency of the Wnt receptor Ryk causes multiple cardiac and outflow tract defects.

Ryk is a member of the receptor tyrosine kinase (RTK) family of proteins that control and regulate cellular processes. It is distinguished by binding Wnt ligands and having no detectable intrinsic protein tyrosine kinase activity suggesting Ryk is a pseudokinase. Here, we show an essential role for Ryk in directing morphogenetic events required for normal cardiac development through the examination of Ryk-deficient mice. We employed vascular corrosion casting, vascular perfusion with contrast dye, and immunohistochemistry to characterize cardiovascular and pharyngeal defects in Ryk-/- embryos. Ryk-/- mice exhibit a variety of malformations of the heart and outflow tract that resemble human congenital heart defects. This included stenosis and interruption of the aortic arch, ventriculoarterial malalignment, ventricular septal defects and abnormal pharyngeal arch artery remodelling. This study therefore defines a key intersection between a subset of growth factor receptors involved in planar cell polarity signalling, the Wnt family and mammalian cardiovascular development.

Anatomy of functionally single ventricle.

Hearts that have previously been called univentricular hearts, or single ventricles, can be described as having a univentricular atrioventricular connection. Most such hearts have two ventricular chambers, albeit one is small and incomplete-lacking an inlet component. The atriums of these hearts connect only to one of these ventricular chambers, which is usually the larger and dominant ventricle. Other hearts, with biventricular atrioventricular connections, may have hypoplasia of one ventricle, making it impossible to restore a biventricular circulation and such hearts are functionally univentricular. The term "functionally single ventricle" (or functionally univentricular heart) encompasses both these categories of malformation.

Anatomy of discordant atrioventricular connections.

The term discordant atrioventricular connections refers to the situation in which the ventricles are connected inappropriately to the atrial chambers. In most instances, the connections of the great arteries are also abnormal, with the aorta and the pulmonary trunk arising from morphologically inappropriate ventricles. This combination results in the presence of so-called congenitally corrected transposition. Double-outlet right ventricle is occasionally present, while concordant ventriculoarterial connections may be seen rarely. Most such hearts have a range of additional abnormalities, including ventricular septal defects; outflow tract obstruction, usually of the morphologically left ventricle; anomalies of the morphologically tricuspid valve; and a highly abnormal location of the specialized atrioventricular conduction axis. Some examples exhibit bizarre abnormalities of ventricular relationships and topology, including criss-cross atrioventricular connections and superoinferior ventricular relations. In describing the anatomy of these malformations, it is important to use a step-by-step segmental approach to the documentation of the connections and associated defects in each case and to avoid potentially confusing shorthand terms.

Aortic translocation, Senning procedure and right ventricular outflow tract augmentation for congenitally corrected transposition, ventricular septal defect and pulmonary stenosis.

The management of congenitally corrected transposition of the great arteries and associated lesions is frequently challenging. Significant pulmonary stenosis is a contraindication to the conventional double-switch. Instead repair may be accomplished by the Rastelli-Senning procedure, using an extracardiac conduit to achieve continuity between the morphological left ventricle and the pulmonary arteries. This however can be accompanied by conduit and intra-ventricular baffle-related problems that can necessitate surgical re-intervention and lead to late mortality. We describe the use of aortic translocation, Senning procedure and reconstruction of the right ventricular outflow tract using autologous tissue and valved homograft to facilitate anatomical correction in congenitally corrected transposition. The advantages of this technique in this group of patients and the implications for conduction tissue are discussed.

Angiographic diagnosis, prevalence and outcomes for left ventricular noncompaction in children with congenital cardiac disease.

Little is known about the implications of left ventricular noncompaction in children with additional congenital cardiac malformations. With this in mind, we conducted a retrospective review of every left ventricular angiogram performed in a single tertiary referral centre for paediatric cardiology, in Melbourne, Australia, between 1994 and 2000 in children with congenital heart disease, looking specifically for patients with angiographic evidence of noncompaction of the left ventricle. The outcome of patients identified as having noncompaction was compared with that of patients from the same population, stratified by their primary congenital cardiac malformation. Of 1515 children undergoing left ventricular angiography, 31, with 13 being male, were found to have angiographic evidence of left ventricular noncompaction, giving a prevalence of 2% (95% CI: 1.3%-2.8%). Of 69 (22%) children with a functionally single left ventricle, 15 fulfilled the criterions for noncompaction, compared to 16 of 1446 (1.1%) children with a balanced ventricular arrangement (p is less than 0.0001). The presence of noncompaction and a functionally single left ventricle were each associated with a doubling of mortality, the effect being cumulative. Of surviving patients with left ventricular noncompaction, 19% (4%-34%) have left ventricular dysfunction at their latest follow-up. We suggest that the important late sequels of noncompaction justify careful scrutiny for this entity in children with congenital cardiac disease.

The diverse cardiac morphology seen in hearts with isomerism of the atrial appendages with reference to the disposition of the specialised conduction system.

Congenital cardiac malformations which include isomerism of the atrial appendages are amongst the most challenging of problems for diagnosis and also for medical and surgical management. The nomenclature for pathological description is controversial, but difficulties can be overcome by the use of a segmental approach. Such an approach sets out the morphology and the topology of the chambers of the heart, together with the types and modes of the atrioventricular, ventriculo-arterial, and venous connections. We have applied this method to a study of 35 hearts known to have isomerism of the atrial appendages. We have already published accounts of 27 of these cases, but these were reviewed for this study in the light of our increased awareness of the implications of isomerism, and 8 new cases were added. After examining, or re-examining, the morphology of every heart in detail, we grouped them together according to their ventricular topology and modes of atrioventricular connection. Then we studied the course of the specialised conduction system, by the use of the light microscope, first in each individual case, and then together in their groups. We conclude that the pathways for atrioventricular conduction in hearts with isomerism of the atrial appendages are conditioned both by ventricular topology, and by the atrioventricular connections. Based on our experience, we have been able to establish guidelines that direct the clinician to the likely location of the conduction tissues.

Concordant ventriculoarterial connections with parallel arterial trunks in the setting of isomerism of the right atrial appendages.

We describe an autopsied specimen, from an infant who died in 1967, in which concordant ventriculoarterial connections coexisted with parallel arterial trunks, usually described as "anatomically corrected malposition." Based on their shape, the extent of the pectinate muscles, and the absence of a coronary sinus, we diagnosed isomeric right atrial appendages. Despite this, the arrangement of the remaining thoracic and abdominal organs, as well as the patterns of venous drainage, was almost completely mirror imaged.

The nomenclature, definition and classification of discordant atrioventricular connections.

During the process of creation of a bidirectional crossmap between the system emerging, on the one hand, from the initiative sponsored by the Congenital Heart Committees of the European Association for Cardio-Thoracic Surgery and the Society of Thoracic Surgeons, and on the other hand, from that formulated by the Coding Committee of the European Association for Pediatric Cardiology, the Nomenclature Working Group has successfully created the International Paediatric and Congenital Cardiac Code. As would be expected, during the process of crossmapping it became clear that, for most lesions, the European Pediatric Cardiac Code was more complete in its description of the diagnoses, while the International Congenital Heart Surgery Nomenclature and Database Project was more complete in its description of the procedures. This process of crossmapping exemplifies the efforts of the Nomenclature Working Group to create a comprehensive and all-inclusive international system for the naming of paediatric and congenital cardiac disease, the International Pediatric and Congenital Cardiac Code. Although names and classification for paediatric and congenital cardiac disease will continue to evolve over time, we are now closer than ever to reaching uniform international agreement and standardization. The International Paediatric and Congenital Cardiac Code can be downloaded from the Internet, free of charge, at www.ipccc. net.

Pulmonary atresia with ventricular septal defects and major aortopulmonary collateral arteries: unifocalization brings no long-term benefits.

OBJECTIVES: We sought to evaluate the contribution of unifocalization procedures in the management of patients with pulmonary atresia, ventricular septal defect, and major aortopulmonary collateral arteries. METHODS: From 1975 through 1995, 82 consecutive patients were entered in a multistage approach and had 189 sternotomies and thoracotomies to perform 119 shunts, 130 major aortopulmonary collateral artery transplantations, and 76 major aortopulmonary collateral artery ligations. The serial angiographies and the follow-up of these patients were reviewed. RESULTS: The concurrent follow-up rate was 80%. The hospital mortality of the preliminary procedures was 4% (7/189). Fifty-three (65%) patients had a complete repair. The hospital mortality of the repair was 8% (4/53), and 9 late deaths occurred after repair, all of which were cardiac related. The overall survival of all patients to the age of 30 years was 58% +/- 7%. Survival 12 years after complete repair was 51% +/- 14%. On angiography, central shunts promoted growth of central pulmonary arteries in all cases (29 patients). Sixty unifocalized major aortopulmonary collateral arteries were identified in 31 patients. After a mean of 3.2 +/- 4 years, 26 thrombosed, and 12 presented with a stenosis of greater than 50%. Serial measurements of 29 major aortopulmonary collateral arteries showed no signs of growth (P = .25). CONCLUSION: Long-term survival into adulthood of patients with pulmonary atresia, ventricular septal defect, and major aortopulmonary collateral arteries has been achieved with a multistage approach. However, late survival depends exclusively on the growth of the native pulmonary circulation. The few unifocalized major aortopulmonary collateral arteries that did not thrombose failed to grow.

Reconstruction of left main coronary artery with subclavian artery free graft in an infant.

We report the case of a 3-month-old infant with anomalous origin of the left coronary artery from the pulmonary artery (ALCAPA) with absent left main coronary artery (LMCA). She underwent repair by reimplantation technique with the construction of a short LMCA using two opposite flaps. Two months later she was re-admitted in cardiac failure. Occlusion of the reconstructed LMCA was found by angiogram. At reoperation the right subclavian artery was used as a free interposition graft to reconstruct the LMCA. The post-operative course was uneventful. At 8 months she was asymptomatic and LMCA patency was demonstrated by angiogram.

New approach to multiple ventricular septal defect closure with intraoperative echocardiography and double patches sandwiching the septum.

OBJECTIVE: This was an evaluation of a new approach to the management of multiple muscular ventricular septal defects. The defects were located with epicardial echocardiography, then transfixed with a guide wire inserted directly through the right ventricular free wall. They were closed with a custom-made multilayered double-patch device under cardioplegic arrest through a standard right atriotomy. METHODS: This was a retrospective study of 14 consecutive patients. RESULTS: The median age and body weight at repair were 40 days (range 1 week-8 years, 3 months) and 4.1 kg (2.8-24 kg), respectively. Five patients (36%) had undergone at least one previous sternotomy; 11 patients (78%) had associated cardiac lesions. Closure of the multiple septal defects was successful in 12 patients (85%). Failure to localize all defects led to pulmonary artery banding in 2 patients. One patient had the residual septal defect closed with a percutaneous device 6 months later, and in the second patient the residual defect was closed with a conventional approach 11 months afterward. Two patients had permanent pacemaker insertion. In 279 patient-months of follow-up, there was 1 cardiac arrest on day 1 and no early or late deaths; all children but one are free of cardiac medications, and no significant residual left-to-right shunts were demonstrated in any patient. CONCLUSION: The reported management of multiple ventricular septal defects has been successful in this series, even in neonates and infants with complex associated cardiac lesions. It appears safe, simple, and effective.

Successful stenting for Budd-Chiari syndrome after pediatric liver transplantation: a case series and review of the literature.

Hepatic venous outflow obstruction, known as Budd-Chiari syndrome, is a rare but serious complication of orthotopic liver transplantation and may lead to graft loss. Our aim was to describe a single center experience of percutaneous interventional management of hepatic outflow obstruction post liver transplantation in children. Three children with post-transplant hepatic venous outflow obstruction were treated successfully with percutaneous stent placement. This resulted in long-term resolution of symptoms and was superior to balloon angioplasty both in our series and in cases reported in the literature. Stenting may be the treatment of choice for hepatic venous obstruction after pediatric liver transplantation, particularly if there is a recurrence of stenosis after balloon dilatation.

The epidemiology of childhood cardiomyopathy in Australia.

BACKGROUND: The incidence and age distribution of primary cardiomyopathy in children are not well defined. We undertook a population-based, retrospective cohort study in Australia to document the epidemiology of childhood cardiomyopathy. METHODS: We analyzed all cases of primary cardiomyopathy in children who presented between 1987 and 1996 and who were younger than 10 years of age. Children were recruited from multiple sources, and cases of cardiomyopathy were classified according to World Health Organization guidelines. RESULTS: Over the 10-year period, 314 new cases of primary cardiomyopathy were identified, for an annual incidence of 1.24 per 100,000 children younger than 10 years of age (95 percent confidence interval, 1.11 to 1.38). Dilated cardiomyopathy made up 58.6 percent of cases, hypertrophic cardiomyopathy 25.5 percent, restrictive cardiomyopathy 2.5 percent, and left ventricular noncompaction 9.2 percent of cases. The incidence of all types of cardiomyopathy except restrictive declined rapidly after infancy. In 11 cases (3.5 percent), sudden death was the first symptom. There was a male predominance among children with hypertrophic and unclassified cardiomyopathy. Indigenous children had a higher incidence of dilated cardiomyopathy than nonindigenous children (relative risk, 2.67; 95 percent confidence interval, 1.42 to 4.63) and a higher rate of death as the presenting symptom (16.7 percent vs. 2.6 percent, P=0.02). Lymphocytic myocarditis was present in 25 of 62 children with dilated cardiomyopathy (40.3 percent) who underwent cardiac histologic examination within two months after presentation. CONCLUSIONS: Lymphocytic myocarditis and left ventricular noncompaction are important causes of childhood cardiomyopathy in Australia. The timing and severity of presentation in children with cardiomyopathy are related to the type of cardiomyopathy, as well as to genetic and ethnic factors.

Corrosive behaviour of Amplatzer devices in experimental and biological environments.

PURPOSE: Nitinol, a nickel-titanium alloy, is a valuable material in the construction of interventional endoluminal devices because of its biocompatibility, super elasticity, high resiliency and shape memory. The possibility of nickel toxicity has been raised with devices constructed of Nitinol. Our investigation examines the long-term corrosive behavior of this alloy in experimental and biological environments. METHODS: We performed three levels of study. Microscopic examination was made of 64 devices of various sizes, randomly selected from 240 Amplatzer Septal Occluders that had been exposed to saline solution at 37 degrees C for fourteen months. All samples were studied by electron microscopy ranging from 50 to 5000 times magnification. We also studied microscopically 3 Amplatzer devices explanted 18-36 months after implantation in dogs, and 2 Amplatzer Septal Occluders removed from patients 18 months (cardiac transplant) and 19 months (died of causes unrelated to device placement) after implantation, which were examined grossly and by electron microscopy up to 5000 times magnification. We then measured the levels of nickel in the blood using inductive plasma mass spectroscopy in 19 patients with implanted Amplatzer devices, making measurements before and 6 months after implantation. RESULTS: Electron microscopy showed an intact titanium oxide layer with no evidence of corrosion in vitro and in vivo. One explanted device in direct contact with the platinum leads of a pacemaker for eighteen months showed minor pitting of the titanium oxide layer believed to be galvanic in nature. No wire fractures were found in vitro after cycle testing with 400 million cycles, nor in devices taken from the animals and humans. Biochemical studies showed no significant elevation of levels of nickel levels after implantation. CONCLUSION: Nitinol wire of Amplatzer septal occlusion devices is resistant to corrosion when exposed to physiologic saline solution, and in experimental animals as well as humans. A device in contact with a platinum pacemaker electrode developed minimal pitting of the titanium oxide layer, believed to be galvanic in nature and of no structural or clinical significance. There is no increase of concentrations of nickel in the blood of patients who have received Amplatzer nitinol devices. These favorable testing results reveal that nickel-titanium is an inert, corrosion resistant alloy.

T wave alternans threshold late after repair of tetralogy of Fallot.

INTRODUCTION: Sustained microvolt-level T wave alternans (TWA) is a marker of increased risk for malignant ventricular arrhythmia. There is a significant risk of arrhythmia and sudden death after repair of congenital heart disease. The aim of this study was to determine the prevalence and characteristics of TWA after repair of tetralogy of Fallot (TOF). METHODS AND RESULTS: TWA was evaluated during bicycle exercise in 49 subjects who had consecutively undergone transatrial-transpulmonary repair. Median values for age, age at repair, and follow-up duration were 14.9 years (11.5-20.8), 1.6 years (0.2-4.9), and 11.6 years (9.4-17.2), respectively. All patients were in New York Heart Association functional class I and were asymptomatic. Median QRS duration was 120 msec (80-150). Sustained TWA was detected in 7 (23%) of 31 subjects with adequate tests. In these 7 subjects, median onset heart rate (HR) was 120 (98-155). Median HR threshold as a percentage of predicted maximum HR (220 - age) was 58% (48-77). Sustained TWA prevalence was not significantly different compared with normal subjects (7/31 vs 9/83; P = 0.1). Onset HR in the TOF group was significantly lower [mean (SD) of 122 (20) vs 139 (12), P < 0.05]. In the TOF group with sustained TWA, the TWA occurred in 4 of 7 at <60% predicted maximum HR versus 1 of 9 normal subjects (P < 0.05); 3 of 7 had onset HR <120 versus 0 of 9 normal subjects (P < 0.03). There was no significant difference in age, gender, transannular patch use, restrictive right ventricular physiology, QRS duration, QTc, QT/QRS dispersion, or nonsustained ventricular tachycardia in subjects with or those without sustained TWA. CONCLUSION: The onset HR for sustained TWA is significantly lower after repair of TOF. Further study is required to determine whether this represents an increased risk for arrhythmia in this patient group.

Innocent murmurs: the perception of the parents versus that of the child.

Innocent murmurs in childhood are common, and often they do not reflect cardiac disease. We have performed a prospective review, by means of a questionnaire, to clarify the parental perception of the innocent murmur identified in their child. Whenever possible, depending on age, we also sought the input of the child. Of a cohort of 63 infants and children with innocent murmurs, a response was obtained from 40 parents and 8 children to an initial questionnaire, with 26 parents replying to a second questionnaire a year later. No parent reported any symptoms in their children, or had imposed any restrictions. Of the parents, however three sets considered regular review was necessary. We conclude that the diagnosis of an innocent murmur by a paediatric cardiologist, aided by investigations including cross-sectional echocardiography, and an opportunity for explanation and reassurance, led to the child being treated normally.