Deficiency of the vestibular spine in atrioventricular septal defects in human fetuses with down syndrome

Data on the morphogenesis of atrioventricular septal defect (AVSD) in Down syndrome are lacking to support molecular studies on Down syndrome heart critical region. Therefore, we studied the development of complete AVSD in human embryos and fetuses with trisomy 21 using 3-dimensional graphic reconstructions and immunohistochemical markers. Eight trisomic hearts with AVSD and 10 normal hearts, ranging from 5 to 16 weeks' gestation, were examined. In AVSD, the muscular septum primum and venous valves develop normally, and the size and histology of the nonfused endocardial cushions also appear normal. However, the mass of extracardiac mesenchyme (vestibular spine), located at the dorsal mesocardium, is reduced and does not protrude ventrally along the right wall of the common pulmonary vein. As a result of this, the muscular septum primum and the right pulmonary ridge are seen as 2 separate septa that attach to the inferior endocardial cushion. Both the muscular septum primum and the superiorly fused venous valves (septum spurium) converge and are capped by a small rim of mesenchyme, which forms the roof of the persisting ostium primum and connects to cushions and the reduced vestibular spine. At 7 weeks, ventricular septation in AVSD is comparable to 5 to 6 weeks of normal cardiac development. At later stages, the septum spurium forms the anterosuperior limbus of the septum secundum and the mesenchymal cap becomes the bridging tendon that connects the bridging leaflets. Therefore, reduced expansion of the vestibular spine derived from the dorsal mesocardium appears to play an important role in the development of AVSD in Down syndrome.     

Electro‐vectorcardiographic demonstration of bifascicular block associated with ventricular preexcitation

Down syndrome occurs more frequently in the offsprings of older pregnant women and may be associated with atrioventricular septal defect. This refers to a broad spectrum of malformations characterized by a deficiency of the atrioventricular septum and abnormalities of the atrioventricular valves caused by an abnormal fusion of the superior and inferior endocardial cushions with the midportion of the atrial septum and the muscular portion of the ventricular septum.     

Development of the myocardium of the atrioventricular canal and the vestibular spine in the human heart

To establish the morphogenetic mechanisms underlying formation and separation of the atrioventricular connections, we studied the remodeling of the myocardium of the atrioventricular canal and the extracardiac mesenchymal tissue of the vestibular spine in human embryonic hearts from 4.5 to 10 weeks of development. Septation of the atrioventricular junction is brought about by downgrowth of the primary atrial septum, fusion of the endocardial cushions, and forward expansion of the vestibular spine between atrial septum and cushions. The vestibular spine subsequently myocardializes to form the ventral rim of the oval fossa. The connection of the atrioventricular canal with the atria expands evenly. In contrast, the expression patterns of creatine kinase M and GlN2, markers for the atrioventricular and interventricular junctions, respectively, show that the junction of the canal with the right ventricle forms by local growth in the inner curvature of the heart. Growth of the caudal portion of the muscular ventricular septum to make contact with the inferior endocardial cushion occurs only after the canal has expanded rightward. The atrioventricular node develops from that part of the canal myocardium that retains its continuity with the ventricular myocardium.     

Diagnosis of atrial septal defect using magnetic resonance imaging

We studied the morphological features of defects of the interatrial septum using magnetic resonance imaging (MRI) to determine the sizes of defects and other abnormalities. MR images were obtained in 28 patients with atrial septal defect, including five cases with complicated anomalies (two with Ebstein's anomaly, one pentalogy of Fallot, and one anomalous pulmonary vein connection and azygos continuation). Images were also obtained in the control subjects including seven normal volunteers and 142 patients with various acquired heart diseases. The diagnosis of atrial septal defect was established by cardiac catheterization, angiography and two-dimensional echocardiography prior to the MRI studies, and in 14 patients, the diagnosis was confirmed by surgery. The MRI unit had a superconducting magnet and operated at 0.25 or 0.50 Tesla. A spin echo pulse sequence was used with an echo time of 40 or 60 msec. At the beginning of this study, non-gated MRI images were obtained in the 28 controls and in three patients with atrial septal defect. Nongated MRI could not image the anatomical structure of the interatrial septa of 12 of the 28 controls, or any of the three patients with atrial septal defect. Nongated MRI was, therefore, inadequate for visualizing cardiac anatomy. Gated MRI images were obtained in 141 controls and in 25 patients with atrial septal defect. Gated MRI revealed the interatrial septum, interventricular septum, atrioventricular septum, mitral valve, tricuspid valve and other intracardiac structures in most subjects. In 17 control subjects (12%), however, there was a very faint signal from the central portion of the interatrial septum. In these instances, there was a gradual fading of the signal of the interatrial septum, so that they could be distinguished from the atrial septal defect. The sudden disappearance of the signal from the interatrial septum was observed by gated MRI in all 25 patients with atrial septal defect. The sizes of the defects by MRI coincided with the findings at surgery in all 14 patients. MRI showed right atrial dilatation, right ventricular hypertrophy and dilatation, and pulmonary artery dilatation in most of the patients having atrial septal defect. Complex anomalies associated with atrial septal defect were also clearly shown by MRI, such as displacement of the tricuspid leaflets in two patients with Ebstein's anomaly, and anomalous pulmonary venous connection and persistent left superior vena cava in one patient. These results indicated that gated MRI is a valuable noninvasive method of diagnosing atrial septal defect and complicating anomalies.     

Necessity for evaluation of anomalous pulmonary venous return before percutaneous closure of atrial septal defects--a case report

About 10%-15% of patients with an atrial septal defect will have some form of anomalous pulmonary venous connection. With the advent of percutaneous closure of atrial septal defects, it is imperative that presence of partial anomalous pulmonary venous return be excluded to prevent unnecessary percutaneous closure in patients who would ultimately require a surgical approach. The authors herein report a 29-year-old man who underwent percutaneous closure of 2 atrial septal defects but was later found to have his left upper pulmonary vein draining into the innominate vein via a vertical vein. He subsequently underwent surgical repair of the anomalous pulmonary vein.     

Echocardiographic assessment of atrioventricular canal defects

AV canal defects (AVCD) are caused by maldevelopment of the endocardial cushions and typically include a primum atrial septal defect (ASD), an inlet ventricular septal defect (VSD), and a common atrioventricular valve. The variations in deformities provide the basis for the many terms used in the anatomical classifications: partial, transitional, intermediate, and complete common AVCD (balanced or unbalanced). The balanced complete common AVCDs are classified as Rastelli A, B, C depending on the anomaly of the anterior bridging leaflet division and attachments. Unbalanced complete AVCDs occur when the common AV valve leads primarily into the RV or LV. Echocardiographic apical, subcostal, and parasternal views are the best views to image AV canal defects. These views can help determine the type of repair required for the various AV canal defects.     

Double outlet right ventricle with discordant atrioventricular connection. Clinical study

The clinical and anatomic findings were reviewed in 17 patients with double-outlet right ventricle and atrioventricular discordance. Ten cases had atrial situs solitus, seven with right-sided heart three with left-sided heart. Seven cases had atrial situs inversus, five with left-sided heart and two with right-sided heart. All cases presented ventricular septal defect, 13 subvalvar pulmonary stenosis, two tricuspid regurgitation and two complete atrioventricular block. The spatial relationship between the arterial valves are variable. Most cases in atrial situs solitus had a left-sided and anterior aorta and all patients in atrial situs inversus had a right-sided and anterior aorta. In this study we compared the anomalies found in our cases with double outlet right ventricle with those in 58 patients with corrected transposition. Absolute, relative and attributable risks were calculated for the presence of subvalvular pulmonary stenosis, ventricular septal defect, tricuspid regurgitation and atrioventricular block for each the two groups. We concluded that patients with double-outlet right ventricle are more prone to present ventricular septal defect and subvalvar pulmonary stenosis, while those with corrected transposition have a greater likelihood of presenting with tricuspid regurgitation and atrioventricular block. There is no typical clinical picture for the malformations. Symptoms depend upon the associated anomalies. The final diagnosis is best achieved by the echocardiographic and angiocardiographic studies, but electrocardiogram and chest radiograph may suggest the presence of a discordant atrioventricular connection.     

Echocardiographic Hypertrabeculated/Non-compacted Right Ventricle Accompanied by Atrial Septal Defect and Anomalous Pulmonary Vein Connection

Myocardial noncompaction (NC) is a disorder of the embryonic endomyocardial morphogenesis frequently associated with congenital cardiac abnormalities. NC predominantly affects the left ventricle (LV). Right ventricle (RV) NC may occur in association with LV involvement or in isolation. A 47-year-old woman was admitted for atrial septal defect closure. Transthoracic echocardiography revealed hypertrabeculation of the RV apex, consisting of multiple deep recesses with the entrance of blood flow in color Doppler imaging, suggestive of isolated RV hypertrabeculation/NC. The RV and right atrium (RA) were enlarged, and systolic pulmonary arterial pressure was slightly increased. Our patient''s associated abnormalities were atrial septal defect (superior sinus venosus type), anomalous connection of the right upper pulmonary vein to the junction of the superior vena cava and the RA, and large patent foramen ovale. Association between atrial septal defect and partial anomalous pulmonary vein connection and isolated hypertrabeculated/noncompacted RV should be considered by cardiologists.     

Partial anomalous pulmonary venous connection to the azygous vein with intact atrial septum.

A five-year-old girl with partial anomalous pulmonary venous connection to the azygous vein with intact atrial septum is reported. The clinical and roentgenographic features suggested the correct diagnosis. Surgical correction of this previously unreported defect was accomplished by creating an atrial septal defect and constructing a baffle to direct the blood flow from the azygous vein to the left atrium.     

Outcomes of left atrial isomerism over a 28-year period at a single institution

OBJECTIVES: We determined long-term outcomes in a large cohort with left atrial isomerism (LAI). BACKGROUND: Left atrial isomerism is associated with a complex spectrum of cardiac and noncardiac anomalies that may impact on outcomes. METHODS: The records of all patients with LAI, born between 1970 and 1998, and treated at one center were reviewed. Kaplan-Meier survival was estimated, and independent factors associated with time-related death were identified. RESULTS: There were 163 patients (63% women), and extracardiac anomalies were noted in 36%, including biliary atresia in 10%. Cardiac defects included interrupted inferior caval vein in 92%, anomalous pulmonary veins in 56%, atrioventricular septal defect in 49%, pulmonary atresia or stenosis in 28% and aortic coarctation in 16%, with congenital atrioventricular block in 7%. Of 22 patients with a normal heart, 18% died of extracardiac anomalies. Of 71 patients with hearts suitable for biventricular repair, 62 (87%) had surgery, with survival of 80% at one year, 71% at five years, 66% at 10 years and 63% after 15 years. Of 70 patients with unbalanced cardiac defects suitable for single-ventricle palliation, 47 (67%) had surgery, with survival of 73% at one year, 61% at five years, 53% at 10 years and 48% at 15 years (p < 0.001). Independent factors associated with time-related death included congenital atrioventricular block, aortic coarctation, single ventricle, biliary atresia and other gastrointestinal malformations. CONCLUSIONS: Both cardiac and noncardiac anomalies contribute to a high mortality with LAI. Cardiac transplantation may need to be a considered a primary option for selected high-risk patients.     

Implantation of drug-eluting stents for relief of obstructed infra-cardiac totally anomalous pulmonary venous connection in isomerism of the right atrial appendages

We describe an infant with severe obstruction of infra-cardiac totally anomalous pulmonary venous connection associated with right isomerism, atrioventricular septal defect, pulmonary atresia, and multiple aortopulmonary collateral arteries. Implantation of a stent into the obstructed descending vertical vein provided effective palliation, with a dramatic increase in saturations of oxygen obviating the need for urgent high-risk surgery.     

A case of anomalous pulmonary venous drainage from the entire left lung associated with complete heart block.

A 22-year-old female patient presenting complete atrioventricular block and giant P waves in electrocardiogram had anomalous pulmonary venous drainage from the entire left lung. There was normal drainage from the right lung and no associated atrial septal defect or other intracardiac abnormalities. After a permanent pacemaker was implanted, she manifested signs and symptoms of heart failure. Although the anomalous pulmonary vein was anastomosed to the left atrium, intractable heart failure continued. She died six months later after surgical intervention. Postmortem examination revealed diffuse interstitial fibrosis throughout the myocardium.     

Surgical experience with congenital heart disease in Down's syndrome

Children with Down's syndrome and congenital heart defects have multiple problems. The role of cardiac surgery in the management of these patients was investigated by reviewing the clinical data, hospital course and follow-up of 21 patients (9 males and 12 females, age range 1 month to 14 years) with Down's syndrome and congenital heart defects operated in our institute. Twelve (57%) of these were infants and nine (43%), older children. Five were in congestive cardiac failure, four were hypothyroid. The heart lesions ranked in incidence as follows: atrioventricular septal defect 7 (33.3%), tetralogy of Fallot 3 (14.3%), tetralogy of Fallot & atrioventricular septal defect both 2 (9.5%), double outlet right ventricle with pulmonary stenosis 1 (4.8%), patent ductus arteriosus 2 (9.5%), patent ductus arteriosus plus coarctation 1 (4.8%), ventricular septal defect 2 (9.5%), atrial septal defect plus ventricular septal defect 1 (4.8%), atrial septal defect plus patent ductus arteriosus plus right pulmonary artery stenosis 1 (4.8%) and transposition of great arteries with multiple ventricular septal defect 1 (4.8%). Four (19%) patients had palliative procedures while the rest (81%) underwent primary repair. All survived the operation. The post-operative period was complicated in 6 (28.5%), with respiratory infections in 3, pulmonary hypertensive crisis in 2 and complete heart block in 1. The early mortality was 0, while there were 2 (9.5%) late deaths. The number of hospitalisations was markedly reduced according to the parents. Follow-up showed near normal pulmonary artery pressure in 50 percent children with large shunts and a good developmental spurt was seen in 60 percent. From a purely surgical viewpoint, the prognosis for children with Down's syndrome and congenital heart disease is good.     

Origin of mesenchymal tissue in the septum primum: a structural and ultrastructural study

A structural, ultrastructural and histochemical study in chick embryos indicates that the septum primum mesenchymal tissue originate between 3 and 5 days of development and that their origin may be related to an activation of endocardial cells that cover the septum primum. By day 3, endocardial cells display migratory appendages, cell hypertrophy and an increase in secretory and mitotic activity. In later stages (day 4) hypertrophic endocardial cells undergoing division seem to delaminate and translocate toward the subendocardial space to give rise to free mesenchymal-type cells. These results suggest that the endocardium makes up the bulk of the septum primum mesenchymal tissue as has been demonstrated during mesenchymal tissue formation in the atrioventricular canal and outflow tract. Before and during mesenchymal tissue formation an accumulation of extracellular matrix components like proteoglycans can be visualized using tannic acid. These extracellular components might be related to the promotion of cellular events described during endocardial activation. The fusion of the septum primum with the atrioventricular (AV) endocardial cushions which would obliterate the foramen primum, occurs between mesenchymal tissues. Therefore, any alteration in the normal development of these mesenchymal tissues could be related to pathological cases of persistent atrial communications. Light microscopy preliminary observations of embryonic mouse heart indicate that septum primum mesenchymal tissue formation occurs similarly between mouse and chick embryos.     

Occlusion of azygos vein via direct percutaneous puncture of innominate vein following cavopulmonary anastomosis

A 2-year-10-month-old boy was diagnosed with a complex congenital heart disease: right atrial isomerism, left superior vena cava (LSVC), complete atrioventricular septal defect, secundum type atrial septal defect, transposition of the great arteries with pulmonary atresia, patent ductus arteriosus, absence of a right superior vena cava (RSVC), and dextrocardia. He had received a left Blalock-Taussig (BT) shunt at the age of 3 months and a left bidirectional Glenn shunt one year after BT shunt. Progressive cyanosis was noted after the second operation and cardiac catheterization showed a functional Glenn shunt with an engorged azygos vein, which was inadvertently skipped for ligation. Because of the absence of RSVC, transcatheter occlusion of the azygos vein was performed successfully via direct puncture of the innominate vein.     

Endocardial cushion defect associated with cor triatriatum sinistrum or supravalve mitral ring

Clinical and angiographic or autopsy data, or both, on three children with a subdivided left atrium (cor triatriatum) and an associated endocardial cushion defect are reviewed. (One child had ostium primum defect, and two had complete atrioventricular [A-V] canal.) A fourth patient demonstrates the difficulties in differentiating subdivided left atrium from supravalve mitral stenosis in the presence of an endocardial cushion defect. The clinical findings are greatly influenced by the endocardial cushion defect. A pressure gradient between the pulmonary wedge and (left or right) ventricular end-diastolic pressures in patients with an endocardial cushion defect indicates pulmonary venous obstruction and should alert one to the possibility of these combined lesions. The exact diagnosis is made with injections of angiographic contrast medium into the proximal and distal left atrial chambers, to document the respective relations of the pulmonary veins, left atrial appendage and A-V valves to these atrial chambers. All three patients with an endocardial cushion defect and a subdivided left atrium had an associated patent ductus arteriosus. The common association of subdivided left atrium with intracardiac, pulmonary venous and aortic anomalies is again demonstrated.     

Anatomical-embryological correlates in atrioventricular septal defect.

Recent embryological studies have supported the consideration that the ventricular septum is multifocal in origin. These data have also provided excellent correlation of the morphology of malformed hearts with their embryology. In particular, atrioventricular septal defect correlates accurately with these observations on ventricular septation. Many of the names given to atrioventricular septal defect (for example ostium primum, persistent atrioventricular canal, endocardial cushion defect) indicate attempts at correlating the anatomy with embryology. None of these has been very convincing. In the light of this uncertainty, this review considers briefly the anatomy of the malformation and its ontogeny, and presents a hypothesis of the development of atrioventricular septal defect. Although there is almost always a communication above the atrioventricular valves, the malformation lies in the ventricular, not the atrial septum. Hearts with inlet septal defect without interatrial communication represent one end of the spectrum of anomalies, and those with common atrioventricular orifice, in which Fallot's tetralogy or single outlet heart may be associated, mark the other end. The outflow tract malformations are not randomly associated, but are points in a huge range of cardiac malformations.     

Giant Chiari network mimics intracardiac tumor in a case of neurofibromatosis

Neurocutaneos syndromes are associated with cardiac or heart related extracardiac tumors, as well as atrial or ventricular septal defect, pulmonary stenosis, coarctation of aorta. Here we describe a case of neurofibromatosis with valvular pulmonary stenosis and giant Chiari network, which mimics a right atrial tumor originating from interatrial septum.