Atrial Isomerism Research Articles

Transhepatic approach for catheter interventions in infants and children with congenital heart disease

We report on our experience with transhepatic access for catheter interventions in six children (age range 2.5 months-9 years). Three had systemic venous anomalies, and one infant a femoral venous occlusion. In two further patients with bradyarrhythmia after a Fontan operation with an intraatrial Gore-Tex tunnel, transhepatic access was chosen to achieve a perpendicular orientation of the transseptal needle to the atrial baffle, allowing puncture of the Gore-Tex membrane. Two of the patients underwent ablation of an accessory pathway; in one an atrial septal defect was closed. A 2.5 month old baby after Norwood I operation, underwent balloon dilation of the pulmonary arteries. Two patients after prior Fontan surgery underwent DDDR pacemaker implantation. The size of the introducer sheath ranged from 4 F up to two 9 F introducers in the same vein for pacemaker insertion. At the end of the procedure, hemostasis was achieved by external compression. Transhepatic access could be established in all six patients (using a mirror image approach in children with left atrial isomerism) and the interventional procedures could be performed as planned. In one patient with implantation of a permanent pacemaker, a subcutaneous hematoma occurred, requiring blood transfusion. In selected pediatric patients, transhepatic access for catheter intervention can easily be achieved.

Holt-Oram Syndrome with Hemiazygous Continuation of Inferior Vena Cava

A rare and previously unreported combination of Holt-Oram syndrome, atrial septal defect, patent ductus arteriosus, isolated left atrial isomerism and inferior vena caval interruption with hemizygous continuation to the left superior vena cava is described.

Clarifying anatomical complexity: Diagnosing heterotaxy syndrome in the fetus

Heterotaxy syndrome, a disorder that involves abnormal lateralization of the abdominal viscera, thoracic organs and cardiac atria, remains one of the most challenging lesions in the field of pediatric cardiology both from a diagnostic and surgical strategy standpoint. Despite improved techniques, heterotaxy syndrome continues to be associated with high morbidity and mortality. Generally, heterotaxy syndrome can be categorized into two subtypes. Right atrial isomerism is associated with single ventricle, atrioventricular canal defect, pulmonary outflow obstruction, conotruncal abnormalities, bilateral superior vena cavae and total anomalous pulmonary venous connection. Left atrial isomerism can have similar intracardiac findings but also includes interruption of the inferior vena cava, ipsilateral pulmonary venous connection and complete heart block. Non-cardiac abnormalities such as splenic dysfunction, intestinal malrotation, and biliary atresia can be seen in both subtypes. Prenatal diagnosis of heterotaxy syndrome requires thorough knowledge of the typical findings as well as a systematic approach to the segmental anatomy. Accurate prenatal diagnosis is helpful to appropriately counsel families and for the perioperative management of these patients. However, the impact of prenatal diagnosis on long-term outcome remains to be seen.

Spectrum of Cardiovascular Disease, Accuracy of Diagnosis, and Outcome in Fetal Heterotaxy Syndrome

Because there is a paucity of information regarding the diagnosis and outcomes of fetal heterotaxy syndrome (HS), this study sought to determine the spectrum of cardiac pathology, accuracy of diagnosis, and outcome of fetal HS. All cases of fetal HS encountered in the investigators' institution over a 10-year period through 2002 were identified. Prenatal and postnatal echocardiograms and medical records were reviewed. Seventy-one fetuses were diagnosed with HS, including 48 with left atrial isomerism (LAI) and 23 with right atrial isomerism (RAI). For LAI and RAI, most intracardiac lesions, the pulmonary venous connections, and superior vena caval anatomy were correctly diagnosed in utero (93%, 86%, and 77% accuracy, respectively), whereas hepatic venous connections and inferior vena caval-atrial connections in RAI were difficult to define (65% and 56% accuracy, respectively). Of 32 continued and followed pregnancies with LAI, 22 are currently alive at 48 +/- 30 months. Heart block and associated major extracardiac pathology were significantly more common in nonsurvivors with fetal LAI (p = 0.007 and 0.024, respectively). Outcomes were even worse for prenatally diagnosed RAI: of 14 continued pregnancies, only 3 are currently alive. In conclusion, fetal HS is associated with a broad spectrum of cardiac pathology, which can be diagnosed accurately in utero. Fetal LAI is associated with a mortality of 31%, with heart block and extracardiac pathology as primary risk factors for perinatal mortality. The outcome of prenatally diagnosed RAI is poor.

Outcomes of 616 fetuses with sustained arrhythmia or structural cardiac defect

CARDIAC DEFECT BETTINA CUNEO, STEVEN AMBROSE, JUDE DUVAL, DON TAYLOR, XAVIER POMBAR, JAMES KELLER, The Heart Institute for Children, Oak Lawn, Illinois, Advocate Medical Group, Maternal Fetal Medicine, Oak Lawn, Illinois, Sherman Hospital, Maternal Fetal Medicine, Elgin, Illinois, Suburban Maternal Fetal Medicine, Maternal Fetal Medicine, Hoffman Estates, Illinois, Rush University Medical Center, Obstetrics and Gynecology, Chicago, Illinois, Lutheran General Hospital, Park Ridge, Illinois OBJECTIVE: This study’s purpose was examining outcomes of fetuses with abnormal cardiac rhythm or structural cardiac defects (SCD) diagnosed by fetal echocardiography. STUDY DESIGN: A retrospective cohort study of 616 fetuses referred to the Heart Institute for Children between 1996-2005 was conducted. SCD were classified as 4 chamber (4C), outflow tract (OT) defects, or other. Pregnancy outcome and associated chromosomal or noncardiac defects were ascertained by chart review. SCD were confirmed by echocardiography after birth. A logistic regression model was fitted including diagnosis, chromosomal or noncardiac abnormality, using the group with 4C and no chromosomal or non-cardiac malformation as referent. RESULTS: Sustained non-sinus arrhythmia was detected in 41 and SCD in 575. Of those with SCD, 298 had 4C abnormalities, 214 had OT defects, and 58 had other defects. Excluding patients in utero or awaiting surgery, overall mortality was 49%. Mortality was 12% for fetuses with arrhythmia (secondary to either long QT syndrome or left atrial isomerism with complete AV block); and 56% for fetuses with chromosome or noncardiac abnormalities. Combined mortality (in utero and postnatal) was highest for tricuspid valve dysplasia/Ebsteins malformation and hypoplastic left heart syndrome (70%), and lowest for L-transposition (7.6%). Those with 4C SCD and non-cardiac malformations had adjusted ORs for death of 2.9 (95% CI: 2.0-4.4) and 4.7 (95% 2.2-9.9) respectively. Mortality declined over time (p for trend !.001). CONCLUSION: Fetuses with 4 chamber structural cardiac anomalies, associated non-cardiac malformations or AV block associated with left atrial isomerism were at greatest risk of mortality. Over time, there was a significant decline in mortality.

Late Assessment After Biventricular Repair for Isomerism Heart

Although biventricular repair is theoretically ideal for the treatment of isomerism heart, the long-term outcome is unknown. We assessed the outcome of biventricular repair for atrial isomerism. From 1984 to 2002 in our surgical database, 10 of 67 patients with atrial isomerism received biventricular repair. The age at operation was 7.7 +/- 9.1 years. Preoperative ventricular volume was normal in all patients. Left ventricular ejection fraction was 62% +/- 8%. Intra-atrial rerouting was required in 8. The atrioventricular septal defect with double-outlet right ventricle was closed using comma-shaped intraventricular conduit in 8. Other procedures included pulmonary valvotomy and infundibulectomy in 2, transannular patch in 1 and right ventricle to pulmonary artery conduit in 1. There was one early death due to hemolytic phagocytic syndrome. The other 9 patients are in New York Heart Association class I at 12.7 +/- 5.3 years postoperatively. There was no atrial baffle stenosis except in 1 patient; it was successfully treated by stent placement 10 years after the operation. There was no incidence of left ventricular outflow obstruction. Mitral replacement (4 months postoperatively) or repair (15 years postoperatively) was done in 2 patients. The other 5 patients with atrioventricular septal defect showed trivial to mild regurgitation in the long-term period. Arrhythmia was observed in 5 (left 4, right 1). Catheter ablation was needed in a patient with atrial flutter. Three of 9 patients require diuretics or digitalization, or both. The long-term outcome of the biventricular repair for atrial isomerism was excellent. Late development of mitral regurgitation and arrhythmia could be managed adequately.

Pränatale Diagnose der rechtsatrialen Isomerie (Apslenie-Syndrom): ein Fallbericht

Right atrial isomerism (earlier known as asplenia) is a group of malformations including anomalies of the heart and the visceral organs. Complex defects of the heart are normally found, but these are non-specific. The suspected diagnosis can be confirmed most easily by focusing on a specific and segmental examination of the heart. We report on a fetus referred at 22 weeks in whom AV-septal defect was detected. Heart and stomach were on the left side, but the segmental approach allowed the detection of juxtaposed descending aorta and inferior vena cava as typical signs of right isomerism. The suspected malformation could be verified by the additional detection of infra-diaphragmatic total anomalous pulmonary venous drainage by using colour Doppler. Howell-Jolly bodies from fetal blood supported the diagnosis of asplenia. Autopsy after termination of pregnancy demonstrated the typical signs of right isomerism. The paper reviews the typical prenatal findings which lead to the detection of right isomerism in the fetus. Segmental approach should be performed in each fetus with an anomaly of the heart especially in the presence of complex defects.

Total anomalous pulmonary venous drainage with major aorto-pulmonary collaterals - a diagnostic dilemma

A term female newborn presented with right atrial isomerism and infra-diaphragmatic total anomalous pulmonary venous drainage associated with complex cardiac anatomy. The repair was performed utilizing circulatory arrest in deep hypothermia. However, in the post-operative period the patient could not be weaned off mechanical ventilation and underwent cardiac catheterisation. This revealed major aortopulmonary collaterals, which were occluded with coils. We review the literature with specific focus on the occurrence of this unusual combination and its implication in the management during the postoperative period.

Electrophysiologic patterns of fetal heart rate augmentation with terbutaline in complete AV block

Background: The beta-2 agonist terbutaline (terb) increases fetal heart rate (FHR) in fetuses with complete AV block (CAVB) due to either maternal Sjögren’s antibodies (SSA) or left atrial isomerism (LAI), but the electrophysiologic characteristics of the FHR augmentation have not been evaluated. We hypothesized that, reflecting the differing pathophysiology of LAI and SSA CAVB, the patterns of FHR acceleration in terb treated fetuses would differ between those with LAI and those with SSA.

Cited2is required both for heart morphogenesis and establishment of the left-right axis in mouse development

Establishment of the left-right axis is a fundamental process of vertebrate embryogenesis. Failure to develop left-right asymmetry leads to incorrect positioning and morphogenesis of numerous internal organs, and is proposed to underlie the etiology of several common cardiac malformations. The transcriptional modulator Cited2 is essential for embryonic development: Cited2-null embryos die during gestation with profound developmental abnormalities, including cardiac malformations, exencephaly and adrenal agenesis. Cited2 is also required for normal establishment of the left-right axis; we demonstrate that abnormal heart looping and right atrial and pulmonary isomerism are consistent features of the left-right-patterning defect. We show by gene expression analysis that Cited2 acts upstream of Nodal, Lefty2 and Pitx2 in the lateral mesoderm, and of Lefty1 in the presumptive floor plate. Although abnormal left-right patterning has a major impact on the cardiac phenotype in Cited2-null embryos, laterality defects are only observed in a proportion of these embryos. We have therefore used a combination of high-resolution imaging and three-dimensional (3D) modeling to systematically document the full spectrum of Cited2-associated cardiac defects. Previous studies have focused on the role of Cited2 in cardiac neural crest cell development, as Cited2 can bind the transcription factor Tfap2, and thus affect the expression of Erbb3 in neural crest cells. However, we have identified Cited2-associated cardiac defects that cannot be explained by laterality or neural crest abnormalities. In particular, muscular ventricular septal defects and reduced cell density in the atrioventricular (AV) endocardial cushions are evident in Cited2-null embryos. As we found that Cited2 expression tightly correlated with these sites, we believe that Cited2 plays a direct role in development of the AV canal and cardiac septa. We therefore propose that, in addition to the previously described reduction of cardiac neural crest cells, two other distinct mechanisms contribute to the spectrum of complex cardiac defects in Cited2-null mice; disruption of normal left-right patterning and direct loss of Cited2 expression in cardiac tissues.

Modified fenestration technique for the Kawashima operation in a young infant

Cases involving small infants undergoing the Kawashima operation for left atrial isomerism, single ventricle, and azygos continuation of the inferior vena cava are rare and challenging because of the risk associated with this particular circulation, which is similar to a total cavopulmonary shunt, except for the hepatic flow. Taking into account the recent encouraging report from Hannan and associates, we decided to perform a modified fenestrated Kawashima operation, preserving a limited antegrade flow, in a 51⁄2-month-old infant with severe cyanosis caused by progressive pulmonary stenosis.

Assessment of intracardiac anomalies in two adults with Ivemark's syndrome

Ivemark's syndrome consists of intracardiac anomalies, abnormal lobation of the lungs, and abdominal heterotaxy. A frequent intracardiac anomaly seen in Ivemark's syndrome is a common atrium, which is associated with left-to-right shunting. The increased blood flow and resistance within the pulmonary vasculature creates pulmonary hypertension and eventual reversal of the shunt physiology. In the absence of additional cyanotic malformations, survival into adulthood without prior surgical septation of the common atrium depends on the extent of pulmonary hypertension and intracardiac right-to-left shunting. We present two patients with a common atrium in the setting of Ivemark's syndrome who survived into adulthood without prior operation. Two-dimensional echocardiography assessed their intracardiac structures. One patient had right atrial isomerism manifested by asplenia and a common atrium, into which the hepatic veins drained directly, and the other patient had left atrial isomerism manifested by polysplenia, a common atrium, and a ventricular septal defect with a single atrioventricular valve. Neither patient had additional cyanotic malformations, including obstruction to pulmonary venous return, transposition of the great vessels, or pulmonic valve stenosis. The 2-dimensional echocardiogram guides the clinician to refer patients for surgical septation of the common atrium before the right-to-left shunt physiology predominates. The medical and surgical treatment of these patients is discussed.

P01.09: Evaluation of fetal condition using cardiovascular score in cases with complete atrioventricular block and heart defect

To find prognostic signs in fetal echocardiography to predict outcome in fetuses with complete heart block (CHB) and heart defect (CHD). 11 fetuses with CHB and CHD. Cardiovascular score (CVS) was used to evaluate fetal condition. The heart defects were: left atrial isomerism (LAI)—8 cases, dextrocardia/l-TGA-2, AVSD with Down syndrome-1. First echo was performed between 10 and 29 weeks' gestation (median 23 weeks). Fetal heart rate varied from 46 to 84 bpm. In 8 fetuses with LAI CVS varied from 1 to 6. In six with non-immunological hydrops (NIHF) CVS was below 4 and five of them died in utero. Beta-mimetics were administered in 5, without effect. Two fetuses with NIHF were delivered vaginally. In 1 pacemaker was implanted but he died 2 months later. In 1 case CHB was complicated by atrial flutter. The boy died in the 5th day of life. Two fetuses with l-TGA had higher CVS (6 and 7). Beta-mimetics increased their heart rate. In spite of this, neonatal condition was severe in both cases and both died—one after pacemaker implantation, the second before the operation. Condition of the fetus with AVSD and Down syndrome deteriorated in spite of beta-mimetics, CVS was 1. She died in the 3rd day of life. All fetuses with CHB and CHD died in utero or after delivery. All of them had signs of fetal circulatory failure and those with NIHF had CVS less than 4. CHB with CHD was lethal condition, what is necessary information when counseling parents, planning transplacental treatment and way of delivery. Beta-mimetics can increase FHR, but not always decrease signs of heart failure. CVS was easy and useful prognostic factor to predict outcome of fetuses with CHB.

P01.10: Left atrial isomerism with complete heart block and atrial flutter

P01.10: Left atrial isomerism with complete heart block and atrial flutter

Right atrial isomerism in four siblings.

Heterotaxy syndromes, right or left atrial isomerism, result from disruption of left-right axis determination and their manifestations include complicated heart defects. Recent studies in model organisms have revealed complex genetic pathways and several genes involved in this process. In affected humans, however, molecular studies have identified mutations in a small number of individuals, while in most the cause remains unknown. Furthermore, although family data suggest, autosomal recessive inheritance, such genes have not yet been identified. We have studied six members of a family, four children affected with right atrial isomerism (RAI) and their healthy parents, for disturbances of left-right axis development. The children, one female and three males who all had complicated heart defects, succumbed and had an autopsy. Their nonconsanguineous parents were examined by cardiac and abdominal ultrasound or MRI. In all four children the heart defects included single ventricle with dysplastic atrioventricular (AV) valve, total anomalous pulmonary venous drainage (TAPVD), and malposition of great arteries (MGA) with pulmonary stenosis (PS). All had asplenia; two also had dextrocardia and abdominal situs inversus. The diagnosis of RAI was made postnatally in the first child and prenatally in others. Two siblings had no surgery and died as a newborn, one with obstructed supracardiac TAPVD and the other with regurgitating AV valve. Two children underwent heart surgery. One had repair of obstructive infracardiac TAPVD but died in infancy. The other underwent both hemi-Fontan operation and heart transplantation but died at the age of 2 years. This is the first report describing four children with RAI in the same family. The occurrence of RAI in male and female siblings without any indication of left-right axis abnormalities in their parents suggests autosomal recessive inheritance of human isomerism.

Autoantibody-associated congenital heart block: the clinical perspective.

Congenital heart block (CHB) can occur in association with structural heart disease, such as atrioventricular septal defects, left atrial isomerism, and abnormalities of the great arteries, with tumors, such as mesotheliomas, or as an isolated defect. In 1928, Aylward reported the occurrence of CHB in two children whose mother "suffered from Mikulicz's disease." This curious clinical observation was further solidified by the 1970s, with reports of CHB in children whose mothers had autoimmune diseases and that the maternal sera contained antibodies to Ro ribonucleoproteins. It was subsequently reported that many mothers also had antibodies to La. Other abnormalities affecting the skin, liver, and blood elements were associated with anti-Ro/La antibodies in the maternal and fetal circulation, and are now grouped under the heading of neonatal lupus syndromes. Neonatal lupus was termed because the cutaneous lesions of the neonate resembled those seen in systemic lupus erythematosus.

Partial and total anomalous pulmonary venous connection in the fetus: two-dimensional and Doppler echocardiographic findings.

Prenatal diagnosis of total (TAPVC) or partial (PAPVC) anomalous pulmonary venous connection in isolation or associated with other cardiac disease is important for appropriate prenatal counseling and perinatal management. We sought to assess the echocardiographic clues to the fetal diagnosis of TAPVC and PAPVC in a cohort of affected fetuses. We retrospectively reviewed 29 fetal echocardiograms performed in 16 pregnancies with fetal TAPVC or PAPVC, systematically analyzing heart chamber size, presence of a confluence behind the left atrium or of a vertical vein, and Doppler flow patterns. Prenatal diagnosis was made at a mean gestational age of 27 +/- 7 weeks. TAPVC was found in 11 cases; five cases for each of supracardiac and infracardiac types and one mixed type. PAPVC was diagnosed in five fetuses, four of which had scimitar syndrome. Ten fetuses had an additional major cardiac defect, including hypoplastic left heart syndrome and right atrial isomerism. In three cases the prenatal diagnosis was only made at follow-up assessment. Among TAPVC cases, visualization of a confluence behind the left atrium (10/11) and a vertical vein (11/11) were the most consistent echocardiographic clues. Dextrocardia and a small right pulmonary artery suggested scimitar syndrome. The diagnosis was confirmed postnatally or at autopsy in 12 cases. In six fetuses with TAPVC and obstruction confirmed postnatally, continuous turbulent flow in the vertical vein and monophasic continuous flow in the pulmonary veins were demonstrated by color and spectral Doppler. Fetal echocardiography permits prenatal diagnosis of TAPVC or PAPVC. Spectral and color Doppler provide clues to the presence of an obstructed pulmonary venous pathway.

The fenestrated Kawashima operation for single ventricle with interrupted inferior vena cava

An 8-month-old boy with double outlet right ventricle with hypoplastic left ventricle, heterotaxy, left atrial isomerism, bilateral superior vena cavae without bridging vein, and interruption of the inferior vena cava with azygous continuation to the left superior cava underwent a bilateral bidirectional cavopulmonary anastomosis. A calibrated 3-mm connection between the right pulmonary artery and the common atrium was constructed with the proximal right superior vena cava to allow right to left shunting, analogous to a fenestration in a Fontan operation. We hypothesize that in small young patients undergoing the Kawashima operation a fenestration may improve postoperative hemodynamics.

Improving results of the modified Fontan operation in patients with heterotaxy syndrome

Background Historically the Fontan operation in patients with single ventricle heterotaxy syndrome and atrial isomerism has been associated with high mortality. We studied whether recent modifications of the surgical technique have improved outcome. Methods A retrospective review of 135 patients with heterotaxy syndrome who underwent a Fontan operation between 1981 and 2000 was performed. Results There were 93 patients with right isomerism and 42 with left isomerism. Anomalies of venous return included 25 patients with extracardiac pulmonary venous connection (19%) and 37 patients with an interrupted inferior vena cava (27%). Thirty-six patients (27%) had at least moderate atrioventricular valve regurgitation. The type of Fontan procedure included 17 patients with an atriopulmonary Fontan connection, 67 with a lateral tunnel modification, 19 with an intraatrial tube graft, 25 with an extracardiac tubegraft, and 7 with an intra-extra atrial tube graft. A fenestration was placed in 93 patients (78%). Early mortality was 19% before 1991, 3% since 1991, and no patient has died early since 1993. Ten-year survivals were 70% for Fontan operations before 1990 and 93% for Fontan operations after 1990. Thirty-two patients (23%) had prolonged pleural effusions. Risk factors for death included anomalous pulmonary venous connection ( p = 0.02) and higher preoperative pulmonary vascular resistance ( p = 0.002). Sixty-two patients (47%) had some form of early postoperative arrhythmia. At 10 years, freedom from late bradyarrhythmia and late tachyarrhythmia were 78% and 70%, respectively. Preoperative arrhythmias, older age at operation, and anatomic features were each independent predictors of late arrhythmia. Conclusions The Fontan operation can now be performed in patients with heterotaxy syndrome with excellent survival. However, morbidity in terms of postoperative arrhythmias and prolonged pleural effusions remains significant. Fontan staging, appropriate choice of Fontan modification, aggressive treatment of concomitant malformations, and use of a baffle fenestration contribute to improved outcome.

Fontan-type procedures: residual lesions and late interventions

Background. The purpose of this study was to determine the type and incidence of hemodynamic and electrophysiological abnormalities requiring surgical or catheter-based interventions in a single-center long-term experience. Methods. Eighty-eight patients with a follow-up of at least 5 years (mean follow-up, 9.6 ± 2.6 years) after Fontan-type procedures were included. All patients had undergone cardiac catheterization either as part of the regular postoperative protocol or because of symptomatic atrial tachycardia or increasing cyanosis. Results. Freedom from reoperation for up to 5 years was documented for 82% of patients and decreased to 76% after 8 years. Late reoperations included conversion of an atriopulmonary anastomosis to a total cavopulmonary anastomosis in 2 patients with atrial dysrhythmia and implantation of an extracardiac conduit in 1 patient with left atrial isomerism and intrapulmonary arteriovenous malformations after a Kawashima operation. Decline in sinus node function with symptomatic bradycardia required pacemaker therapy in 10 patients (11%). Transcatheter interventions included fenestration occlusion in 5 of the 11 patients with initial baffle fenestration. In 6 of 17 patients with aortopulmonary collaterals, coil occlusion was indicated to reduce future systemic ventricular volume load. Various systemic venous collaterals were documented in 11 patients and required coil occlusion in 2. One patient with symptomatic protein-losing enteropathy underwent transcatheter fenestration creation without sustained relief of symptoms. Freedom from transcatheter interventions decreased from 94% to 82% after 5 and 10 years, respectively. Conclusions. During long-term follow-up, reoperations are rare and mainly involve Fontan conversion to either a lateral-tunnel or extracardiac-conduit procedure. Detailed angiographic evaluation on a routine basis allows identification of the vascular sites of origin of aortopulmonary collateral vessels and systemic venous collaterals potentially developing during long-term follow-up. Transcatheter interventions including fenestration occlusion and occlusion of venous collaterals and aortopulmonary collaterals were performed to maintain and improve the Fontan circulation in clinically symptomatic and asymptomatic patients. During long-term follow-up after Fontan-type operations, a regular postoperative cardiac catheterization protocol is recommended.