The morphogenesis of most types of human congenital cardiac malformations is still obscure. The reasons for this are, first, the paucity of data from human embryos and fetuses and, second, the paucity of appropriate animal models. During the past few years, we have tested several chemicals for their teratogenic potential, hoping to find, particularly in the chick, substances that could be used for the development of models for specific cardiac malformations. We have now discovered that suramin, an antitrypanosomal drug, can induce a special type of congenital cardiac defect in which the two atrial appendages are positioned to the left of the great arteries. This situation resembles the situation found in humans and classified as left juxtaposition of the atrial appendages. In the present study, we have analysed the pathomorphological features of a series of our chicken hearts to assess precisely how accurately these cardiac malformations in the chick correspond to the situation seen in the human. We found that the cases observed in the chick did, indeed, have many features in common with the human cases described in the literature. This suggests that we have developed an animal model for human left juxtaposition. Our model could be used for two kinds of embryological studies: first, documentation of the morphogenesis of left juxtaposition; and second, studies on the mechanisms driving the normal positional changes between the atriums and outflow tract of the embryonic heart during the late phase of cardiac looping. The fact that left juxtaposition of the atrial appendages can be induced by suramin might help to elucidate the molecular mechanisms underlying this type of congenital cardiac malformation. Furthermore, the fact that suramin is used for the chemotherapy of frequent tropical diseases, such as African trypanosomiasis and onchocerciasis, poses the question as to whether this drug might play a role in the aetiology of left juxtaposition in some human populations.

Coronary arterial involvement is rare in Takayasu’s arteritis. We describe successful coronary arterial bypass grafting in a 15 year teenager with Takayasu’s arteritis and unstable angina because of stenosis of the main stem of the left coronary artery.

The previous reviews in this section of our Supplement1,2 have summarized the anatomic components of the ventriculo-arterial junctions, and then assessed the echocardiographic approach to the ventriculo-arterial junction or junctions as seen in the morphologically right ventricle. In this complementary review, we discuss the echocardiographic assessment of the comparable components found in the morphologically left ventricle, specifically the outflow tract and the arterial root. We will address the echocardiographic anatomy of the aortic valvar complex, and we will review the causes of congenital arterial valvar stenosis, using the aortic valve as our example. We will also review the various lesions that, in the outflow of the morphologically left ventricle, can produce subvalvar and supravalvar stenosis. We will then consider the salient features of the left ventricular outflow tract in patients with discordant ventriculo-arterial connections, and double outlet ventricles. To conclude the review, we will briefly address some rarer anomalies that involve the left ventricular outflow tract, showing how the transesophageal echocardiogram is used to assist the surgeon preparing for repair. The essence of the approach will be to consider the malformations as seen at valvar, subvalvar, or supravalvar levels,1 but we should not lose sight of the fact that aortic coarctation or interruption, hypoplasia of the left heart, and malformations of the mitral valve are all part of the spectrum of lesions associated with obstruction to the left ventricular outflow tract. These additional malformations, however, are beyond the scope of this review.

To determine the long-term results in patients with critical aortic stenosis who survive initial intervention, and to identify factors which predict prognosis, we studied patients who underwent intervention between 1979 and 1992 for critical aortic stenosis treated within the first three months of life. Patients with a hypoplastic left ventricle or mitral stenosis who were not considered for a biventricular repair were excluded. Follow-up examination included cross-sectional and Doppler echocardiography. All initial and subsequent patient data were reviewed. Of the 64 patients with critical aortic stenosis, 41 (64%) survived more than one month after initial intervention (surgical valvotomy in 39, balloon valvoplasty in two). These survivors constitute the study group. Mild or moderate residual aortic stenosis or regurgitation without further intervention was found in 28 patients at a median duration of 3.1 years (range 0.2–15.0 years). A poor result with re-intervention (n=6) or death (n=7) occurred in 13 patients. The diameter of the aortic valve at presentation was smaller (p<0.02) in patients with a poor result (median 5.5; range 5–15 mm), than in those with a satisfactory result (median 8.0; range 5–10 mm). Significant residual aortic stenosis was present from the time of initial intervention in nine of the 13 patients (69%) with a poor result. No difference was found in the incidence of a duct-dependent systemic circulation, associated cardiac lesions, mechanical ventilation, acidosis or the use of inotropes preoperatively between patients with a satisfactory or a poor late outcome. Of patients with critical aortic stenosis, 64% survived for more than a month after initial intervention. A small aortic valvar diameter at presentation ( 6 mm) and residual stenosis after initial intervention were important determinants of long-term prognosis.

We present two interesting cases of isolated left subclavian artery from the pulmonary artery with symptoms of upper airway obstruction. The first patient had tetralogy of Fallot, pulmonary artery sling, bilateral superior caval veins, and left bronchial isomerism, suggesting heterotaxy syndrome. The second patient had a right aortic arch, isolated left subclavian artery, and bilateral arterial ducts. These two cases are interesting because of their rarity and uncommon presentation.

Congenital anomalies of the tricuspid valve, and/or its supporting apparatus, leading to severe tricuspid regurgitation are rare. Although well tolerated in early childhood, long-standing and progressive volume loading of the right heart leads to symptoms of decreased exercise tolerance, and may predispose to arrhythmias in the long term. We report three cases of severe tricuspid regurgitation related to anomalies of the cords supporting the antero-superior leaflet of the tricuspid valve. Shortened cords leading to tethering of the leaflet were seen in two cases, and hypoplasia of the leaflet in the other. In all cases, the regurgitant jet was directed posteriorly towards the coronary sinus and atrial septum. Surgical repair was possible in one case, while it proved necessary to replace the valve in a second. The third child is asymptomatic and under regular review.

Diffuse endocardial thickening in dilated hearts has been considered as a distinct pathological entity, usually being termed endocardial fibroelastosis. It is common in infants and children and rare in adults. Current opinion holds that the endocardial thickening is a non-specific reaction to stress in the ventricular wall. Our personal observations point to the most severe forms occurring in young infants. To determine the frequency and severity of endocardial fibroelastosis in children with dilated cardiomyopathy, we studied 21 necropsy hearts, both grossly and microscopically. Ages of the patients ranged from two to 175 months (mean 46.5, median 23 months). Using a graduated eyepiece, we measured the endocardial thickness in samples from three sites in the left ventricle and one from the right ventricle. The values were compared to those obtained from similar measurements of the endocardium in hearts from four children presenting with tetralogy of Fallot. All the dilated hearts presented some degree of endocardial thickening. The gross detection of fibroelastosis depended on the degree of thickening. There was a negative but linear correlation between age and the mean endocardial thickness (r=0.70; p>0.001). Our findings support the concept that endocardial cells have greater replicative and secretory potentials in young patients, and that endocardial fibroelastosis is a secondary phenomenon in dilated hearts.

We describe the importance of angiographic identification of collateral venous channels by balloon occlusion venography after bidirectional cavopulmonary connections. Use of the balloon occlusion technique is essential for identification of these vessels, as they can easily be missed by standard venous angiography, with possible clinical consequences for postoperative management.

Catheter ablation of an accessory atrioventricular pathway using 500 kHz radiofrequency current was attempted in 53 children and young adolescents less than 16 years of age (mean 9.3±4.1 years) who were referred for treatment of symptomatic supraventricular tachycardia. Thirty children had the Wolff-Parkinson-White syndrome and 23 had tachyarrhythmias related to an accessory pathway conducting only in retrograde fashion. Of the latter, seven were found to have the permanent form of junctional reciprocating tachycardia, which had resulted in depressed left ventricular function in four. Ablation of left-sided accessory pathways was usually attempted utilizing an arterial approach to the annulus of the mitral valve, while the venous route to the atrial aspect of the tricuspid valvar annulus was chosen for right-sided accessory connections. To reduce invasiveness and the duration of the procedure, a technique with a solitary catheter was attempted in 20 children with the Wolff-Parkinson-White syndrome, regardless of the anatomical site of the accessory pathway. Ablation of 54 of 56 accessory connections was achieved in 51 patients (96% success) with a median of six applications of radiofrequency current. The sessions were completed within 3.4±2.2 hours, with a median exposure to radiation of 31.1 minutes. During a 10-month period of follow- up, no patient required antiarrhythmic medication, and 51 children (96%) were completely free of any symptoms related to arrhythmias. Left ventricular function returned to normal in the four children with tachycardia-induced cardiomyopathy. Except for a patient with an arterial thrombotic occlusion, no serious complications were encountered. Catheter ablation using radiofrequency current is a highly effective and safe curative approach for treating young patients with supraventricular tachycardias mediated by accessory pathways. The use of fewer catheters of smaller size is feasible and advisable in this cohort of patients.

Calcifying fibrous tumour is a rare benign fibrous lesion. It is paucicellular, with fibroblasts, dense collagenisation, psammomatous and dystrophic calcification, and patchy lymphoplasmacytic infiltrates. Calcifying fibrous tumour was first described in subcutaneous and deep soft tissues, and has been reported all over the body. However, calcifying fibrous tumour originating from the heart is extremely rare. This article describes the case of a giant calcifying fibrous tumour arising from the right ventricle in a child, where the tumour was totally resected and no recurrence was observed during a 4-year follow-up period.

We describe a rare instance of isolated pulmonary regurgitation caused by a dysplastic pulmonary valve which was detected prenatally. Fetal echocardiography demonstrated severe pulmonary regurgitation, and progressive cardiomegaly because of right ventricular volume overload. After birth, conservative therapy was successful in alleviating the pulmonary vascular resistance, and the pulmonary regurgitation gradually decreased.

Aim: The use of β-blocker therapy in asymptomatic patients with hypertrophic cardiomyopathy is controversial. This study evaluates the effect of lifestyle changes and high-dose β-blocker therapy on their exercise capacity. Methods and results: A total of 29 consecutive newly diagnosed asymptomatic patients with familial hypertrophic cardiomyopathy, median age 15 years (range 7–25), were recruited. In all, 16 patients with risk factors for sudden death were treated with propranolol if no contraindications, or equivalent doses of metoprolol; 13 with no risk factors were randomised to metoprolol or no active treatment. Thus, there were three treatment groups, non-selective β-blockade (n=10, propranolol 4.0–11.6 mg/kg/day), selective β-blockade (n=9, metoprolol 2.7–5.9 mg/kg/day), and randomised controls (n=10). All were given recommendations for lifestyle modifications, and reduced energetic exercise significantly (p=0.002). Before study entry, and after 1 year, all underwent bicycle exercise tests with a ramp protocol. There were no differences in exercise capacity between the groups at entry, or follow-up, when median exercise capacity in the groups were virtually identical (2.4, 2.3, and 2.3 watt/kg and 55, 55, and 55 watt/(height in metre)2 in control, selective, and non-selective groups, respectively. Maximum heart rate decreased in the selective (−29%, p=0.04) and non-selective (−24%, p=0.002) groups. No patient developed a pathological blood-pressure response to exercise because of β-blocker therapy. Boys were more frequently risk-factor positive than girls (75% versus 33%, p=0.048) and had higher physical activity scores than girls at study-entry (p=0.011). Conclusions: Neither selective nor non-selective β-blockade causes significant reductions in exercise capacity in patients with hypertrophic cardiomyopathy above that induced by lifestyle changes.

Approximately, 1.7 million individuals in the United States have been infected with SARS-CoV-2, the virus responsible for the novel coronavirus disease-2019 (COVID-19). This has disproportionately impacted adults, but many children have been infected and hospitalised as well. To date, there is not much information published addressing the cardiac workup and monitoring of children with COVID-19. Here, we share the approach to the cardiac workup and monitoring utilised at a large congenital heart centre in New York City, the epicentre of the COVID-19 pandemic in the United States.

We evaluated the concentrations of brain natriuretic peptide in the plasma as a marker of systolic ventricular function before and after maximal exercise in 15 surgically palliated patients with functionally univentricular hearts, with apparently good ventricular function. Of the patients, 6 with median age of 14.6 years, and a range from 12.5 to 17.9 years, had been palliated by construction of a total cavopulmonary connection, while the other 9 patients, with a median age of 32.1 years, and a range from 15.6 to 54.2 years, had undergone the classical Fontan procedure. We used 8 healthy individuals, with a median age of 13.9 years, and a range from 12.8 to 14.2 years, as a control group for the measurements of brain natriuretic peptide. The values of the peptide were significantly higher in those with the classical Fontan procedure, both before, when the median value was 131.8 nanogram per litre, with a range from 0.5 to 296.4, and after maximal exercise, when the median value was 108.1, with a range from 0.1 to 235.9. The comparable values in those with a total cavopulmonary connection were a median of 12.8, and a range from 0.5 to 39.1 before, and a median of 9.7, with a range from 2.7 to 26.2 after maximal exercise. The median value for the control group was 13.1, with a range from 2.6 to 38.7 before exercise (p = 0.016), and a median of 24.1, with a range from 5.8 to 66.7 after maximal exercise (p = 0.03), respectively. In the control subjects, the level of the peptide increased by a median of 9.7 nanograms per litre, with a range from 1.2 to 28.0 after maximal exercise (p = 0.008). The level was unchanged after maximal exercise in those with classical Fontan procedures and total cavopulmonary connections, with a difference between levels before and after exercise of a median of 5.9 nanogram per litre, and a range from −23.7 to 31.0 (p = 0.96), and a median of −1.0 nanogram per litre, with a range from −12.0 to 3.9 (p > 0.99), respectively. We conclude that maximal exercise did not increase the level of brain natriuretic peptide level in those patients with the classical Fontan procedure, nor those with a total cavopulmonary connection, findings which may indicate that systolic ventricular dysfunction is not the major cause of the decreased working capacity observed in patients with well functioning palliated functionally univentricular hearts.