To study the interaction between hemodynamics and morphology in abnormal development of the heart, it is essential to have an animal model with specific and reproducible cardiac malformations. A standardized method was developed for inducing such an anomaly in the chick embryo. For this purpose, all-trans retinoic acid, dissolved in 2% dimethylsulphoxide, was applied on the vitelline membrane of the embryo in concentrations of 1.0 μgm and 0.3 μgm. A total of 207 embryos, staged according to Hamburger and Hamilton, were treated at stages 10 (33 hours of incubation) and 15 (50–55 hours of incubation). Three control groups consisted of embryos solely treated with dimethylsulphoxide, sham operated chicks, and untreated embryos, respectively. The embryos were sacrificed on the 9th, 10th and 11th days of incubation and hearts were examined by microdissection. Additional histologic studies were undertaken in 110 cases. Embryos treated with retinoic acid at both stages of development showed a high percentage of lesions falling within the general spectrum of double outlet right ventricle. The abnormality varied from merely a rightward shift of the aorta to cases with an additional subaortic ventricular septal defect, which, in combination with the rightward positioned aorta, was classified as a double outlet right ventricle. Histologic examination showed the presence of muscular tissue between the leaflets of the aortic and mitral valves. No other types of cardiac malformations were seen. Our results, with respect to timing, resemble data from studies made of hearts after surgical ablation of neural crest at comparable stages. Both method and timing of treatment with retinoic acid are important factors for the induction of specific and reproducible cardiac anomalies. This chick model allows for further detailed study of development of double outlet right ventricle, as well as the assessment of early detectable hemodynamic changes.

We have investigated the spatial distribution of the α and β isoforms of myosin heavy chain in the force-producing ventricular myocardium, the ventricular conduction system and the atrioventricular junctional region of five neonatal human hearts–three born prior to and two at term. The results can be summarized as follows: 1) the force-producing myocardium: in each heart, the β isoform was found to be the predominating isoform, β-negative cells never being observed. Considerable amounts of the α isoform were observed only in those hearts that were obtained from patients dying within the first two weeks of postnatal life. This transient expression is probably correlated with the postnatal increase in levels of circulating thyroid hormone. 2) the ventricular conduction system: in addition to the expression of the β isoform, a strong expression of the α isoform was detected in all the components of the ventricular conduction system in the two full-term hearts. In the preterm hearts, however, this strong expression was mainly restricted to the atrioventricular node and the penetrating atrioventricular bundle. The level of expression of the α isoform in the conduction system of the neonatal hearts, therefore, might reflect the state of maturity of this system at the time of birth. 3) the atrioventricular junctional region: in each heart examined, structures were detected that resembled immunohistochemically and morphologically the atrioventricular node. Although the expression of the isoforms of myosin heavy chain in the conduction system, and in these comparable structures, cannot, as yet, be interpreted with regard to function, these resemblances, coupled with the same developmental background for these structures (they all develop from the so-called “primary ring”) suggest functional affinities during this stage of cardiac development.

Since February 1990, we have attempted nonsurgical occlusion of persistent patency of the arterial duct using the Rashkind double-disk occluding device, of either 12 or 17 mm diameter. Results are presented from 31 patients (23 female and eight male, ages 15 months to 16 years). M-Mode, cross-sectional, Doppler and color Doppler echocardiographic studies were made prior to closure, in the following 24 hours, and six months later. Left ventricular diastolic dimension and shortening fraction, systolic intervals, and left atrium/aortic ratio were evaluated by M-Mode echo. We examined carefully the location of the device relative to the left pulmonary artery and descending aorta, also checking for disturbed flows and residual shunts. These studies showed a clear tendency for the left ventricular diameter to decrease, and revealed a significant normalization of the left atrium/aortic ratio. Successful closure of the duct was achieved in 27 cases. Follow-up studies six months later showed residual shunting in four cases. In one patient, a second device was implanted with an excellent result. At the immediate follow-up, turbulences were noted in the area of the device (nine cases) and in the left pulmonary artery (seven cases). Distortion of the anatomic orientation of the left pulmonary artery was observed in three cases in which we discovered 20 mm Hg systolic gradients. In our opinion, echocardiography is the best technique with which to follow-up these patients. The high sensitivity of color Doppler echocardiography revealed minimal distortion of the left pulmonary artery, probably generated by regional anatomic adjustment to the insertion of the device.

Sinus venosus defects are relatively uncommon forms of interatrial communication in which one of the caval veins has a biatrial connection, and partial anomalous pulmonary venous connections are the rule. The variety related to the inferior caval vein is much the rarer of the two forms, and here the defect is posterior and inferiorly placed. To determine whether an inferior sinus venosus defect could be identified preoperatively, we reviewed retrospectively the available echocardiograms and cineangiograms of the five patients with an inferior sinus venosus defect who underwent surgical repair between January 1983 and December 1991. A cross-sectional echocardiogram had been performed preoperatively in four of these patients, but the correct diagnosis had been made in only one case. Retrospective study, however, showed that the extent of the true atrial septum and the nature of the junction of the inferior caval vein with the atriums could be evaluated from the subcostal position in three of these four patients. Each of the three had an interatrial communication located posteriorly and inferiorly adjacent to the atrial connection of the inferior caval vein, along with abnormally connected right pulmonary veins. The oval fossa was intact and the coronary sinus was normal in all. Cardiac catheterization had been performed in three of the five patients. Anomalous return of right pulmonary veins was noted in each, and the posterior and inferior location of the interatrial communication was evident in two. An interatrial communication adjacent to the atrial connection of the inferior caval vein, along with anomalous connection of the right-sided pulmonary veins, are the diagnostic features of the inferior variety of sinus venosus defects. These features can be demonstrated by cross-sectional echocardiography from the subcostal position.

To assess the prevalence and role of the arterial duct in hearts with incomplete development of the aorticopulmonary septum, 110 autopsy specimens, comprising 100 examples of common arterial trunk and 10 cases with aorticopulmonary window, were studied. In addition to intracardiac malformations, these specimens were analyzed to determine the side of the aortic arch, the presence and location of any interruption of the arch, the presence of any anomaly of origin and course of the subclavian arteries, and the status of the arterial duct. The arterial duct was present in 33 cases, absent in 63 cases and undetermined in four cases with common arterial trunk. The duct provided an essential pathway for flow in the 20 cases with interrupted aortic arch, and in two cases with interruption of the proximal portion of the left pulmonary artery. The presence of the duct in 11 cases, in functional terms, was not essential. In the 10 hearts with aorticopulmonary window, the duct was present in eight. It was an obligatory part of the circulatory pathways in three cases where the aortic arch was interrupted. The prevalence of non-obligatory ducts was 71% in hearts with aorticopulmonary window compared to 15% in hearts with common arterial trunk. The prevalence of the duct in cases with aorticopulmonary window suggests this lesion is a later developmental defect. The functional role of an arterial duct in these hearts should be properly assessed in the clinical situation.

After an initial attempt to close arterial ducts by the transcatheter insertion of an umbrella device had left significant residual patency, further attempts at closure were made in 14 patients by the insertion of an additional umbrella device. The ages of the patients ranged from four to 11 years. Overall, 17 attempts were made to insert additional devices at intervals of between six to 26 months after the insertion of the first umbrella. Successful insertion of a device was achieved in two patients only at a third attempt. One patient required the insertion of a third umbrella to achieve complete occlusion of the patent duct. Complete closure of the residual patency was achieved in 13 of the 14 patients. The remaining patient has been scheduled for insertion of a third umbrella.

A 21-day-old girl presented with congestive heart failure of acute onset and Doppler evidence of mitral regurgitation, which subsequently proved fatal. Necropsy revealed an anomalous arcade lesion of the mitral valve. The tendinous cords of the tricuspid valve were also abnormal, a finding, to the best of our knowledge, not reported before.

Worldwide figures suggest that two percent of appropriate referrals for neonatal extracorporeal membrane oxygenation turn out to have previously covert congenital heart disease. This is despite the fact that expert cardiological evaluation is routine prior to cannulation. The experience in the United Kingdom includes such a case which is reported here. The implications for the role of pediatric cardiologists in such a service are considered.

We studied 11 patients with pulmonary atresia and intact ventricular septum who died at ages ranging from one day to three years. All but two neonates died after surgery. Pre-surgical catheterization with left and right cineventriculography was performed in nine patients, and quantitative parameters were calculated. By histologic examination of transverse transmural sections, the incidence and extent of myocardial ischemia or infarction were determined, as well as the percentage area per field occupied by vessels, myocytes orientated longitudinally or transversely, interstitial space, and disarrayed fibers. Comparable sections were obtained from six normal neonates to constitute a control group. Myocardial ischemia or infarction were frequent complications. Morphometric analysis demonstrated a significant difference between the control group and the patients with regard to the percentage of myocytes (longitudinal and transverse), the percentage of area occupied by myocardial disarray, and the presence of fibrosis. The highest values for the proportion of disarray were seen in those patients with small right ventricles. The percentage of myocytes varied, but the highest degree of disarray always correlated with the lowest percentage of myocytes. The highest percentage value of left ventricular disarray was associated with the lowest ratio of left ventricular mass to end diastolic volume (inadequate hypertrophy). The lowest indices of contractility and left ventricular pump function were associated with myocytes less than 55% of normal. A linear correlation was found between the percentage area of fibrosis and the ratio of systolic pressure to end systolic volume in the left ventricle, arid between fibrosis and ejection fraction. Values for fibrosis exceeding 15% were associated with decreased functional indices. Disarray, therefore, seems to express a primary inability of myocardium to respond to anomalous overload with adequate hypertrophy and/or hyperplasia.

The objective of this study was to review the echocardiographic findings and autopsy correlates of pulmonary atresia with an intact ventricular septum when diagnosed during fetal life. All cases with this lesion (nearly 60) seen in the Perinatal Cardiology unit of Guy's Hospital since 1983 are part of this study. More than half of the cases were detected within the last two years, and all bar three were referred because of suspicion of a cardiac malformation detected on routine obstetric scanning. The cases were divided into two distinct groups. On the one hand were those with dilatation of the chambers of the right heart. These had a uniformly poor prognosis. Severe regurgitation of the tricuspid valve was a characteristic feature. On the other hand were the cases with cavitary hypoplasia due to mural overgrowth. Direct measurements of pressure in one such case revealed suprasystemic values in the right ventricle. Although contemplated, fetal intervention proved impossible. Autopsy revealed cases with either valvar or infundibular atresia. In most cases diagnosed prior to 24 weeks of gestation, mothers opted for termination of pregnancy. All cases with dilatation of the right ventricle died. Of pregnancies which continued, only 30% of children are still alive, all but one being less than two years of age at present. The use of cross-sectional and Doppler echocardiography permits the accurate diagnosis of pulmonary atresia with an intact ventricular septum during fetal life. Autopsied cases showed strong correlation with the echocardiographic findings. The poor prognosis in most cases warrants consideration in the future of intervention during fetal life.

A retrospective study was undertaken of patients with hypoplastic right ventricles, either with pulmonary atresia and intact ventricular septum or critical pulmonary valvar stenosis, and duct-dependent pulmonary blood flow who were investigated at the Royal Brompton Hospital between January 1976 and December 1990. The diagnosis was made on the basis of at least one diagnostic method (cross-sectional echocardiography, cardiac catheterization and angiography, or autopsy). Of the patients, 56 (82%) were found to have an imperforate pulmonary valve or infundibulum (pulmonary atresia), while 12(18%) had critical pulmonary valvar stenosis. The ratio of the diameters of the tricuspid and mitral valvar orifices was measured angiographically during diastole, and the right ventricle was analyzed according to the presence or overgrowth of the inlet, apical trabecular and outlet components. A correlation was made between the severity of the disease and the outcome. The overall mortality was 53% when those not undergoing any surgery were excluded, and significant differences were found between the group dying and those who survived. The incremental risk factors for death were a ratio between the diameter of the tricuspid and mitral valves of less than 0.6; the presence of fistulous communications with the coronary arteries; and obliteration of the apical trabecular component of the right ventricle. There was no significant difference between the group with pulmonary valvar atresia and the group with critical stenosis of the pulmonary valve.

In order to examine right ventricular diastolic function after complete correction of pulmonary atresia with intact ventricular septum and critical pulmonary valvar stenosis, we undertook a prospective analysis of seven patients who had previously undergone successful repair. Comparison was with age and sex-matched controls. The relationship between antegrade pulmonary arterial diastolic flow and other indices of right ventricular dysfunction were compared. The ratio of the velocity of early rapid filling to that of atrial systolic flow was no different from normal, but the deceleration of early rapid filling showed significant shortening with inspiration in patients, but not in control subjects. All patients, but none of the controls, demonstrated significant antegrade diastolic pulmonary arterial flow during late diastole. Despite “normal” ratios ofvelocity of early rapid filling to systolic atrial flow, patients after complete correction of pulmonary atresia with intact ventricular septum and critical pulmonary stenosis have abnormal right ventricular diastolic function typical of a restrictive physiology. This presumably reflects incomplete adaptation due to the presence of endomyocardial fibrosis.

We describe a new method of transvenous laser or radiofrequency perforation of the pulmonary valve with subsequent balloon pulmonary valvoplasty. The technique obviates the need for arterial catheterisation and considerably shortens the time needed for the procedure. Uncomplicated and successful relief of pulmonary valvar atresia was achieved in both patients attempted, although one ultimately required a Blalock-Taussig shunt because of increasing muscular obstruction of the right ventricular outflow tract.

Between February 1986 and December 1991, 41 patients with pulmonary atresia and intact ventricular septum were treated in our institution following a multistage protocol of management. In all cases, the first step was to construct a right modified Blalock-Taussig shunt during the neonatal period regardless of the right ventricular anatomy. Then, in patients with well-developed right ventricles possessing all three components, we proceeded to early surgical repair. In contrast, in patients with right ventricles having obliteration of some components, yet deemed to be recoverable, the next step was to provide palliative relief of obstruction in the right ventricular outflow tract followed, if possible, by subsequent repair. Fontan's operation was performed in patients with right ventricles considered unsuitable from the outset to support the pulmonary circulation. Only one patient died following the initial shunt procedure (mortality of 2.43%). The subsequent program of treatment has now been concluded in 22 patients. In all those deemed to have favorable native anatomy (10 cases), the subsequent complete repair was successful. Among the 24 patients who required palliation of the outflow tract, five died while total repair was subsequently performed in eight. Fontan's operation was performed without mortality in five patients with small right ventricles, although one patient died while waiting for surgery. In all, 89 procedures were performed with an overall mortality of 14%.

Review of an institutional experience of 81 patients admitted to the Royal Liverpool Children's Hospital between January 1958 and December 1990 with a diagnosis of pulmonary atresia and intact ventricular septum revealed that successful definitive repair was achieved in about one-third of those who underwent surgical treatment. A three-stage protocol, consisting of a systemic-pulmonary anastomosis followed by right ventricular decompression on cardiopulmonary bypass and subsequent separation of the systemic and pulmonary circulations, facilitated a biventricular correction but rarely led to a successful Fontan procedure. Both functional class and probability of survival improved after each stage of management.