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Abstract: Neural crest cells (NCCs) are physically responsible for craniofacial skeleton formation, pharyngeal arch artery remodeling and cardiac outflow tract septation during vertebrate development. Cdc42 (cell division cycle 42) is a Rho family small GTP-binding protein that works as a molecular switch to regulate cytoskeleton remodeling and the establishment of cell polarity. To investigate the role of Cdc42 in NCCs during embryonic development, we deleted Cdc42 in NCCs by crossing Cdc42 flox mice with Wnt1-cre mice. We found that the inactivation of Cdc42 in NCCs caused embryonic lethality with craniofacial deformities and cardiovascular developmental defects. Specifically, Cdc42 NCC knockout embryos showed fully penetrant cleft lips and short snouts. Alcian Blue and Alizarin Red staining of the cranium exhibited an unfused nasal capsule and palatine in the mutant embryos. India ink intracardiac injection analysis displayed a spectrum of cardiovascular developmental defects, including persistent truncus arteriosus, hypomorphic pulmonary arteries, interrupted aortic arches, and right-sided aortic arches. To explore the underlying mechanisms of Cdc42 in the formation of the great blood vessels, we generated Wnt1Cre-Cdc42-Rosa26 reporter mice. By beta-galactosidase staining, a subpopulation of Cdc42-null NCCs was observed halting in their migration midway from the pharyngeal arches to the conotruncal cushions. Phalloidin staining revealed dispersed, shorter and disoriented stress fibers in Cdc42-null NCCs. Finally, we demonstrated that the inactivation of Cdc42 in NCCs impaired bone morphogenetic protein 2 (BMP2)-induced NCC cytoskeleton remodeling and migration. In summary, our results demonstrate that Cdc42 plays an essential role in NCC migration, and inactivation of Cdc42 in NCCs impairs craniofacial and cardiovascular development in mice. [Copyright &y& Elsevier]

The coincident occurrence of tricuspid atresia and aortopulmonary window (APW) is exceedingly rare, with one previous case reported in the literature. We present a patient with tricuspid atresia, pulmonary atresia, and APW. Postnatal echocardiograms demonstrated no visible pulmonary valve, and additional defects including a bicuspid aortic valve, right aortic arch and anomalous coronary arteries raised suspicion for tricuspid atresia with persistent truncus arteriosus. However, fetal echocardiography and direct visualization of the anatomy confirmed the alternate diagnosis. The patient underwent successful palliation consisting of APW repair, atrial septectomy and a 3.5 mm modified Blalock-Taussig shunt, followed by a bidirectional cavopulmonary connection. [ABSTRACT FROM AUTHOR]

Introduction: To report our experience in fetuses prenatally diagnosed with common arterial trunk (CAT) and to evaluate the postnatal outcomes. Material and Methods: This was a retrospective study conducted at Asan Medical Center, Seoul, Korea, between 2003 and 2012. Maternal medical and fetal echocardiographic records regarding fetuses were prenatally diagnosed with CAT were reviewed. Postnatal outcomes of survivors were also assessed during the mean follow-up of 36 months. Results: Of the 17 fetuses that were prenatally diagnosed with CAT and had a final diagnosis by postnatal echocardiography or autopsy, 12 were confirmed to have CAT and 5 were incorrectly diagnosed with CAT. Of the latter, 3 had pulmonary atresia and 2 had aortic atresia. The diagnostic accuracy was 71%. The median gestational age at prenatal diagnosis of confirmed CAT was 24.4 weeks (range 21.1-34.3). The truncal valve was prenatally thickened in 8 fetuses. All but 1 of the 12 confirmed CAT cases had associated heart and/or extracardiac anomalies. Of the 8 liveborn cases of postnatally confirmed CAT, 2 died before or after surgery respectively. The remaining 6 remained alive after successful corrective surgery. Conclusion: Prenatal diagnosis of CAT can be difficult in some cases and other diseases should be excluded before diagnosing CAT. Isolated CAT can be repaired by postnatal corrective surgery with a good outcome. Copyright © 2013 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

Objective: To evaluate the long-term results of patients in Kuwait who were operated for persistent truncus arteriosus (PTA). Subjects and Methods: The following data were collected for retrospective analysis from 24 medical records of consecutive patients with PTA in Kuwait between August 1993 and August 2009: demographics, morphology, management and outcome. Major associated abnormalities included interrupted aortic arch in 1 patient and abnormal coronary artery anatomy in 2. Results: Of the 24 patients, 16 underwent total intracardiac repair. The age at operation ranged from 15 days to 5 years (mean 166.19 ± 438.63 days) and weight ranged from 2.5 to 15 kg (mean 4.3 ± 3.01 kg). The right ventricle to pulmonary artery continuity was established with aortic homograft in 11, pulmonary homograft in 4 and by implantation of a Contegra conduit in 1 patient. Four patients had moderate truncal valve regurgitation requiring concomitant truncal valve repair. After a mean follow-up period of 81.81 ± 61.58 months (range 3-166) there was no death. Eight of the 16 (50%) patients underwent redo homograft operations. One patient who had concomitant truncal valve repair subsequently underwent aortic valve replacement. Conclusion: The data showed that complete repair of PTA in the neonatal and early infancy period was the treatment with the best potential for survival. The homograft remained one of the conduits of choice to establish continuity between the right ventricle and the pulmonary artery in spite of the high incidence of conduit redo operations. Copyright © 2011 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

Patent ductus arteriosus (PDA) complicates the clinical course of preterm infants. Nonsteroidal anti-inflammatory drugs, especially Indomethacin and Ibuprofen, have been widely used for both prevention and treatment of PDA. Short-term efficacy of Indomethacin or Ibuprofen is equivalent, while Ibuprofen results show a higher safety profile. Ibuprofen is associated with fewer clinical gastrointestinal and renal side effects with respect to Indomethacin even if subclinical potential effects are reported. When administered as prophylaxis, Ibuprofen has no effects on prevention of intraventricular haemorrhage unlike Indomethacin. Considering the potential adverse effects of both these drugs, a careful monitoring during and after the treatment period is highly recommended. [ABSTRACT FROM AUTHOR]

Abstract: Objective: Establishing a new continuity between the right ventricle and the pulmonary artery is the mainstay of repair for persistent truncus arteriosus. We used the Tran Viet–Neveux technique without a Lecomte maneuver to construct the connection without a conduit. Here, we retrospectively review the mid-term surgical results to examine the effectiveness of this approach. Methods: A cylindrical segment incorporating both pulmonary artery branches was sleeve-resected from the truncal artery. The cylindrical segment was cut in the middle and two truncal arterial flaps were combined to form the posterior floor of the new pulmonary arterial trunk. The edge of the floor was attached directly to the superior margin of an oblique incision made in the left-anterior wall of the right ventricle. A polytetrafluoroethylene monocusp was attached to the lower half margin of the right ventricular incision. A large glutaraldehyde-treated pericardial patch was used to form the anterior hood of the new right ventricular outflow tract. Both great arteries were located in a normal spiral configuration. Results: Ten babies (range: 3 days to 9 months of age) underwent this procedure. The Collett–Edwards classification of persistent truncus arteriosus was type I in five cases and type II in five others. There was one hospital death due to severe respiratory distress. During follow-up (36–60 months, median 54 months), only one re-operation was required to enlarge a left branch pulmonary artery stenosis. Follow-up echocardiography showed pulmonary regurgitation (mild two, moderate seven, and severe one) and mild flow acceleration in the left pulmonary artery branch and right ventricle–pulmonary artery connection in one case. Conclusion: This simple modification for surgical correction of persistent truncus arteriosus may be an effective alternative that overcomes conduit-related problems. [Copyright &y& Elsevier]

Abstract: Congenital heart defects (CHDs) occur in 0.5–1% of live births, yet the underlying genetic etiology remains mostly unknown. Recently, a new source of myocardial cells, namely the second heart field (SHF), was discovered in the splanchnic mesoderm. Abnormal development of the SHF leads to a spectrum of outflow tract defects, such as persistent truncus arteriosus and tetralogy of Fallot. Intracellular Ca2+ signaling is known to be essential for many aspects of heart biology including heart development, but its role in the SHF is uncertain. Here, we analyzed mice deficient for genes encoding inositol 1,4,5-trisphosphate receptors (IP3Rs), which are intracellular Ca2+ release channels on the endo/sarcoplasmic reticulum that mediate Ca2+ mobilization. Mouse embryos that are double mutant for IP3R type 1 and type 3 (IP 3 R1 −/− IP 3 R3 −/− ) show hypoplasia of the outflow tract and the right ventricle, reduced expression of specific molecular markers and enhanced apoptosis of mesodermal cells in the SHF. Gene expression analyses suggest that IP3R-mediated Ca2+ signaling may involve, at least in part, the Mef2C–Smyd1 pathway, a transcriptional cascade essential for the SHF. These data reveal that IP3R type 1 and type 3 may play a redundant role in the development of the SHF. [Copyright &y& Elsevier]

Abstract: Anomalies of conotruncal septation are rare in dogs and uncommon in humans. Congenital conotruncal defects most commonly reported in veterinary medicine include aorto-pulmonary window and persistent truncus arteriosus. We report a case of an anomalous vessel connecting the ascending aorta to the right pulmonary artery causing left-to-right shunting, left-sided volume overload, and pulmonary overcirculation. Transesophageal echocardiography, cardiac catheterization, and contrast-enhanced computed tomography assisted in the diagnosis and facilitated the surgical correction of the anomalous vessel. The authors hypothesize this defect represents an unusual anomalous vessel connecting the ascending aorta to the right pulmonary artery. [Copyright &y& Elsevier]

Objective: Postoperative atrial fibrillation is the most common complication after cardiac surgery. A variety of postoperative atrial fibrillation risk factors have been reported, but study results have been inconsistent or contradictory, particularly in patients with preexisting atrial fibrillation. The incidence of postoperative atrial fibrillation was evaluated in a group of 10,390 patients undergoing cardiac surgery among a comprehensive range of risk factors to identify reliable predictors of postoperative atrial fibrillation. Methods: This 20-year retrospective study examined the relationship between postoperative atrial fibrillation and demographic factors, preoperative health conditions and medications, operative procedures, and postoperative complications. Multivariate logistic regression models were used to evaluate potential predictors of postoperative atrial fibrillation. Results: Increasing age, mitral valve surgery (odds ratio = 1.91), left ventricular aneurysm repair (odds ratio = 1.57), aortic valve surgery (odds ratio = 1.52), race (Caucasian) (odds ratio = 1.51), use of cardioplegia (odds ratio = 1.36), use of an intraaortic balloon pump (odds ratio = 1.28), previous congestive heart failure (odds ratio = 1.28), and hypertension (odds ratio = 1.15) were significantly associated with postoperative atrial fibrillation. The non-linear relationship between age and postoperative atrial fibrillation revealed the acceleration of postoperative atrial fibrillation risk in patients aged 55 years or more. In patients undergoing coronary artery bypass grafting, increasing age and previous congestive heart failure were the only factors associated with a higher risk of postoperative atrial fibrillation. There was no trend in incidence of postoperative atrial fibrillation over time. No protective factors against postoperative atrial fibrillation were detected, including commonly prescribed categories of medications. Conclusions: The persistence of the problem of postoperative atrial fibrillation and the modest predictability using common risk factors suggest that limited progress has been made in understanding its cause and treatment. [Copyright &y& Elsevier]

Abstract: Objective: This study aims to analyse long-term results after correction of truncus arteriosus in all patients operated in one institution over 28 years. Methods: Between 1981 and 2009, 83 patients, median age 54 days, underwent repair of truncus arteriosus. Interrupted aortic arch was present in 14 (17%), severe truncal valve insufficiency in 10 (12%) and non-confluent pulmonary arteries in five (6%) patients. Repair with reconstruction of the right ventricular to pulmonary artery continuity was performed using a valved conduit in 80, and other methods in three patients. At the same time, correction of interrupted aortic arch was done in 14 and truncal valve repair in eight patients. Survivors were repeatedly examined echocardiographically for assessment of residual heart lesions. Results: The early mortality was 19 (23%). Out of 35 patients operated between 1981 and 1996, 17 (46%) died, and out of 48 patients operated between 1997 and 2009, two (4%) died. Operation before 1997 (p =0.001) and aortic cross-clamping time >90min (p =0.009) were found to be risk factors of death. Eight (10%) patients died late, a median of 68 days after surgery. Fifty-seven (69%) patients were followed for 10.9±6.7 years. Three (4%) patients were lost. Twenty-five (30%) patients are alive with their original conduit 7.5±5.2 years after correction. Twenty-eight patients required 41 re-operations for conduit dysfunction with first replacement at mean 5.8±4.1 (range 0.1–14.1 years) years after correction. Nine (11%) patients required 12 truncal valve replacements. Eleven (13%) patients required balloon dilatation or stent for conduit obstruction, pulmonary branch stenosis, aortic arch obstruction or stenosis of vena cava. Recent clinical examination was undertaken in 53 (64%) patients and 49 (59% or 77% of early survivors) are in good/very good condition. Conclusions: Truncus arteriosus remains a challenging heart disease. With growing experience, the early mortality decreased to 4%, but numerous re-interventions for conduit obstruction, pulmonary branch stenosis and truncal valve insufficiency are required. Surgery before 1997 and prolonged cross-clamping were risk factors of death. Pulmonary homografts had the best re-intervention-free survival. Statistically, however, the difference between conduits was not significant. Dysplastic valve and truncal valve insufficiency represent risk factors presenting the need for truncal valve replacement. [Copyright &y& Elsevier]

The unilateral absence of a proximal pulmonary artery (UAPPA) is rare and is most frequently accompanied by cardiovascular anomalies such as tetralogy of Fallot or septal defects. We report a patient with truncus arteriosus with UAPPA in which we performed a two-stage surgical repair. During the first palliative operation, a right modified Blalock-Taussig shunt was constructed to develop the hypoplastic right pulmonary artery. At 10 months, the patient underwent patch closure of a ventricular septal defect with integration of both pulmonary arteries, and reconstruction of the right ventricular outflow tract using a conduit. Four years postoperatively, he continues to do well. [ABSTRACT FROM AUTHOR]

Congenital heart diseases (CHD) occur in nearly 1% of all live births and are the major cause of infant mortality and morbidity. Although an improved understanding of the genetic causes of CHD would provide insight into the underlying pathobiology, the genetic etiology of most CHD remains unknown. Here we show that mutations in the gene encoding the transcription factor GATA6 cause CHD characteristic of a severe form of cardiac outflow tract (OFT) defect, namely persistent truncus arteriosus (PTA). Two different GATA6 mutations were identified by systematic genetic analysis using DNA from patients with PTA. Genes encoding the neurovascular guiding molecule semaphorin 3C (SEMA3C) and its receptor plexin AZ (PLXNA2) appear to be regulated directly by GATA6, and both GATA6 mutant proteins failed to transactivate these genes. Transgenic analysis further suggests that, in the developing heart, the expression of SEMA3C in the OFT/subpulmonary myocardium and PLXNA2 in the cardiac neural crest contributing to the OFT is dependent on GATA transcription factors. Together, our data implicate mutations in GATA6 as genetic causes of CHD involving OFT development, as a result of the disruption of the direct regulation of semaphorin-plexin signaling. [ABSTRACT FROM AUTHOR]

This article present a case report involving a three-week-old lamb with persistent truncus arteriosus (PTA), a serious cardiac malformation. PTA was characterized by the presence of a common arterial trunk originating from the right ventricle and overriding a ventricular septal defect. A rupture of the PTA with subsequent cardiac tamponade was the cause of the lamb's death. Histologic examination identified a dissecting aneurysm with elastic fiber fragmentation in the wall of the PTA.

The tricuspid atresia associated with persistent truncus arteriosus is a rare anomaly. A case is presented of one male patient of three months age in which was detected a cardiac murmur. The diagnosis was made by echocardiography and confirmed by cardiac catheterization. The first step of the palliation was done with disconnection of the trunk of the pulmonary artery combined with a systemic- to- pulmonary shunt of 4 mm. The patient died 24 hours later for persistent metabolic acidosis. [ABSTRACT FROM AUTHOR]

Abstract: A 5-month-old male domestic cat presented with a history of rapid, heavy breathing and cyanosis after exercise. Physical examination showed an abnormal respiratory pattern with an increased rate and stress-induced cyanosis. Auscultation revealed tachycardia and a grade 5/6 systolic murmur best heard over the left base. Radiographs showed evidence of right atrial and ventricular enlargement with distended pulmonary vessels and an enlarged ascending aorta. An echocardiographic examination revealed a dilated right atrium, eccentric right ventricular hypertrophy and an overriding aorta associated with a large ventricular septal defect (VSD). The pulmonary trunk could not be identified by echocardiography. Doppler and saline contrast studies showed large right-to-left shunting through the VSD. These findings were compatible with persistent truncus arteriosus, which was confirmed at necropsy. [Copyright &y& Elsevier]

Abstract: Morphogenesis of the cardiac arterial pole is dependent on addition of myocardium and smooth muscle from the secondary heart field and septation by cardiac neural crest cells. Cardiac neural crest ablation results in persistent truncus arteriosus and failure of addition of myocardium from the secondary heart field leading to malalignment of the arterial pole with the ventricles. Previously, we have shown that elevated FGF signaling after neural crest ablation causes depressed Ca2+ transients in the primary heart tube. We hypothesized that neural crest ablation results in elevated FGF8 signaling in the caudal pharynx that disrupts secondary heart field development. In this study, we show that FGF8 signaling is elevated in the caudal pharynx after cardiac neural crest ablation. In addition, treatment of cardiac neural crest-ablated embryos with FGF8b blocking antibody or an FGF receptor blocker rescues secondary heart field myocardial development in a time- and dose-dependent manner. Interestingly, reduction of FGF8 signaling in normal embryos disrupts myocardial secondary heart field development, resulting in arterial pole malalignment. These results indicate that the secondary heart field myocardium is particularly sensitive to FGF8 signaling for normal conotruncal development, and further, that cardiac neural crest cells modulate FGF8 signaling in the caudal pharynx. [Copyright &y& Elsevier]

GATA transcription factors play critical roles in restricting cell lineage differentiation during development. Here, we show that conditional inactivation of GATA-6 in VSMCs results in perinatal mortality from a spectrum of cardiovascular defects, including interrupted aortic arch and persistent truncus arteriosus. Inactivation of GATA-6 in neural crest recapitulates these abnormalities, demonstrating a cell-autonomous requirement for GATA-6 in neural crest-derived SMCs. Surprisingly, the observed defects do not result from impaired SMC differentiation but rather are associated with severely attenuated expression of semaphorin 3C, a signaling molecule critical for both neuronal and vascular patterning. Thus, the primary function of GATA-6 during cardiovascular development is to regulate morphogenetic patterning of the cardiac outflow tract and aortic arch. These findings provide new insights into the conserved functions of the GATA-4, -5, and -6 subfamily members and identify GATA-6 and GATA-6-regulated genes as candidates involved in the pathogenesis of congenital heart disease. [ABSTRACT FROM AUTHOR]

Abstract: Previous studies have demonstrated that TGFβ induces a smooth muscle fate in primary neural crest cells in culture. By crossing a conditional allele of the type II TGFβ receptor with the neural crest-specific Wnt1cre transgene, we have addressed the in vivo requirement for TGFβ signaling in smooth muscle specification and differentiation. We find that elimination of the TGFβ receptor does not alter neural crest cell specification to a smooth muscle fate in the cranial or cardiac domains, and that a smooth muscle fate is not realized by trunk neural crest cells in either control or mutant embryos. Instead, mutant embryos exhibit with complete penetrance two very specific and mechanistically distinct cardiovascular malformations—persistent truncus arteriosus (PTA) and interrupted aortic arch (IAA-B). Pharyngeal organ defects such as those seen in models of DiGeorge syndrome were not observed, arguing against an early perturbation of the cardiac neural crest cell lineage. We infer that TGFβ is an essential morphogenic signal for the neural crest cell lineage in specific aspects of cardiovascular development, although one that is not required for smooth muscle differentiation. [Copyright &y& Elsevier]

Abstract:: Objective: The aim of our study was to analyse experience with repair of truncus arteriosus with interrupted aortic arch. Methods: Between 1993 and 2004, eight consecutive patients underwent repair of truncus arteriosus with interrupted aortic arch. The median age was 6.5 days (range 1–85 days) and median weight was 3.2kg (range 2.6–4.8 kg). Five patients had type A and 3 patients had type B aortic arch interruption. The repair was performed in deep hypothermia with circulatory arrest in 4 patients and isolated selective low-flow perfusion of the head and the heart in the last 4 patients. The repair consisted in aortic arch reconstruction by direct anastomosis between descending and ascending aorta, closure of ventricular septal defect and reconstruction of the right ventricular to pulmonary artery continuity using a valved conduit. Results: One (12.5%) patient died from sepsis and hepato-renal failure 18 days after surgery. Seven (87.5%) patients were followed up for 2.0–11.7 years (median 2.6 years). No patient died after the discharge from hospital. In 4 patients 1–3 reinterventions were required 0.6–10.0 years after repair. Reoperations were performed for conduit obstruction in 2 patients, aortic regurgitation in 2 patients, right pulmonary artery stenosis in 2 patients and airway obstruction in 1 patient. In 2 patients concommitant aortic valve and conduit replacement was required. Balloon angioplasty for aortic arch obstruction was necessary in 1 patient, and for bilateral pulmonary branch stenosis in 1 patient. Five (28.6%) surviving patients are in NYHA class I and 2 (71.4%) patients are in NYHA class II. Conclusions: Primary repair of persistent truncus arteriosus with interrupted aortic arch can be done with low mortality and good mid-term results. Aortic arch reconstruction in isolated low-flow perfusion of the head and the heart influences favourably the postoperative recovery. The main postoperative problems are associated with conduit obstruction and aortic insufficiency. [Copyright &y& Elsevier]

Truncus arteriosus (TA) was diagnosed in a 6-year-old neutered female domestic short-haired cat by two-dimensional and M-mode echocardiography, colour flow imaging and spectral Doppler examinations. The lesion was characterized by a single large artery originating from the right ventricle. A single ascending aorta and a single pulmonary trunk arose from the common arterial trunk. The residual pulmonary trunk immediately split into left and right branches. The lesion was identified as a type I (TA). This case is of interest because it is the first reported echo-Doppler description of such a malformation in felines, and because of the age of the cat at the time of diagnosis. [ABSTRACT FROM AUTHOR]

Unlabelled: A variety of cardiac defects, encompassing truncus arteriosus, tetralogy of Fallot, pulmonary atresia with ventricular septal defect and interrupted aortic arch, are generally summarised as conotruncal malformations. Patients with these cardiac defects were frequently found to have a common microdeletion on chromosome 22, the so-called monosomy 22q11.2. The aim of our study was to determine whether the laterality of the aortic arch or the presence of subclavian artery anomalies (SAA) represent markers for monosomy 22q11.2 in these patients. 170 patients with these cardiac anomalies were recruited at presentation in the paediatric cardiology units of two tertiary referral centres from 1994 until 2003. Of the 170 children and young adults, 33 had interrupted aortic arch, 35 tetralogy of Fallot, 31 truncus arteriosus communis and 71 pulmonary atresia with ventricular septal defect. All were screened for monosomy 22q11.2 and the results were correlated with the laterality of the aortic arch and the presence of SAA contralateral to the aortic arch (aberrant origin from the descending aorta, isolation, distal ductal origin from the pulmonary artery and cervical origin of the right subclavian artery). Monosomy 22q11.2 was present in 59/170 patients (35%). A left aortic arch (LAA) was found in 118 (69%), a right aortic arch (RAA) in 52 (31%) patients. Almost 50% of the patients with RAA (46%), but only 30% of the patients with LAA had monosomy 22q11.2 ( P=0.054). A total of 47 patients (28%) had an anomaly of the subclavian artery, 81% of whom had monosomy 22q11.2. This deletion was found in decreasing percentage in patients with LAA+SAA (85%) >RAA+SAA (75%) >RAA without SAA (28%) >LAA without SAA (13%).Conclusion: In patients with conotruncal malformations, anomalies of the subclavian arteries are the most important anatomical marker for the presence of monosomy 22q11.2, independent of the laterality of the aortic arch. Therefore, we recommend cytogenetic testing for this microdeletion in all patients with subclavian artery anomalies and conotruncal malformations. [ABSTRACT FROM AUTHOR]

Different techniques are used in fetal cardiology, and their accuracy has been demonstrated on several occasions. Color Doppler US has proved to be a reliable and valuable tool in the diagnosis of fetal cardiac abnormalities. Magnetic resonance imaging (MRI) of the fetal heart has, so far, played no role in prenatal diagnostics. We report on a truncus arteriosus communis diagnosed prenatally during a screening ultrasound at 22 weeks of gestation. In addition to real-time ultrasound and color Doppler echocardiography, fetal MRI was performed. Fetal echocardiography arose suspicion of a type I common trunk. Fetal MR showed solely a widened vessel coursing retrocardially and additionally an inhomogeneous fluid distribution of the lung not shown on prenatal US. After termination of pregnancy at 23 weeks of gestation, MR fetography and autopsy were performed, and both found a type II common trunk. MR autopsy of the heart was very reliable in this case and could be an alternative when fetal pathology is not available for different reasons. Postmortem MRI was also able to demonstrate the inhomogeneous fluid distribution in the lung, which was confirmed by autopsy. Fetal and postmortem MR was reliable in the detection of an inhomogeneous fluid distribution in the lung not shown on prenatal US, providing a relevant additional finding to US. Therefore, MRI should be used more often in fetal cardiology, although it still must be further developed. [ABSTRACT FROM AUTHOR]

A sub-population of the neural crest is known to play a crucial role in development of the cardiac outflow tract. Studies in avians have mapped the complete migratory pathways taken by 'cardiac' neural crest cells en route from the neural tube to the developing heart. A cardiac neural crest lineage is also known to exist in mammals, although detailed information on its axial level of origin and migratory pattern are lacking. We used focal cell labelling and orthotopic grafting, followed by whole embryo culture, to determine the spatio-temporal migratory pattern of cardiac neural crest in mouse embryos. Axial levels between the post-otic hindbrain and somite 4 contributed neural crest cells to the heart, with the neural tube opposite somite 2 being the most prolific source. Emigration of cardiac neural crest from the neural tube began at the 7-somite stage, with cells migrating in pathways dorsolateral to the somite, medial to the somite, and between somites. Subsequently, cardiac neural crest cells migrated through the peri-aortic mesenchyme, lateral to the pharynx, through pharyngeal arches 3, 4 and 6, and into the aortic sac. Colonisation of the outflow tract mesenchyme was detected at the 32-somite stage. Embryos homozygous for the Sp2H mutation show delayed onset of cardiac neural crest emigration, although the pathways of subsequent migration resembled wild type. The number of neural crest cells along the cardiac migratory pathway was significantly reduced in Sp2H/Sp2H embryos. To resolve current controversy over the cell autonomy of the splotch cardiac neural crest defect, we performed reciprocal grafts of premigratory neural crest between wild type and splotch embryos. Sp2H/Sp2H cells migrated normally in the +/+ environment, and +/+ cells migrated normally in the Sp2H/Sp2H environment. In contrast, retarded migration along. [ABSTRACT FROM AUTHOR]

A Simmentaler × Braunvieh calf had been anorexic during its first 36 hours of life, had a loud heart murmur and was suspected to have pneumonia. In the light of the results of radiographic and echocardiographic examinations, right heart catheterization and angiography, a diagnosis of persistent truncus arteriosus and patent foramen ovale was made. The diagnosis was confirmed on postmortem examination. [ABSTRACT FROM AUTHOR]

Mouse embryos lacking the retinoic acid (RA) receptors RARα1 and RARβ suffer from a failure to properly septate (divide) the early outflow tract of the heart into distinct aortic and pulmonary channels, a phenotype termed persistent truncus arteriosus. This phenotype is associated with a failure in the development of the cardiac neural crest cell lineage, which normally forms the aorticopulmonary septum. In this study, we examined the fate of the neural crest lineage in RARα1/RARβ mutant embryos by crossing with the Wnt1-cre and conditional R26R alleles, which together constitute a genetic lineage marker for the neural crest. We find that the number, migration, and terminal fate of the cardiac neural crest is normal in mutant embryos; however, the specific function of these cells in forming the aorticopulmonary septum is impaired. We furthermore show that the neural crest cells themselves do not utilize retinoid receptors and do not respond to RA during this process, but rather that the phenotype is cell non-autonomous for the neural crest cell lineage. This suggests that an alternative tissue in the vicinity of the outflow tract of the heart responds directly to RA, and thereby induces or permits the neural crest cell lineage to initiate aorticopulmonary septation. [Copyright &y& Elsevier]

The developmental background of common arterial trunk still remains to be elucidated. In this anomaly both the coronary, systemic and pulmonary circulation arise from a common arterial stem with a common orifice. The contribution of the embryonic ectomesenchymal neural crest seems to be essential for a normal separation of the aorta, pulmonary trunk and the adjoining myocardium lined outflow tract. Experimental neural crest ablation studies in chicken have proved that there is a role for neural crest cells. Several molecular biological studies, however, have shown that we are not solely dealing with the influence of neural crest. Many genes and gene cascades have been manipulated in mice and have shown that e.g. the endothelin cascade, Foxc1 and Foxc2, and more recently Sema3C and neuropilin-1 are factors, that if disturbed, can lead to common arterial trunk often in combination with aortic arch anomalies such as interruption type B. In humans common arterial trunk is one of the characteristics of the 22q11 deletion syndrome. In the mouse several of these genes, located on the syntenic chromosome 16 have been studied for this effect, but most result in an embryolethal phenotype. Neural crest tracing studies in both chicken–quail chimeras and transgenic neural crest reporter mice have revealed that there is a difference in neural crest contribution to the aortic and pulmonary truncal wall. The orifice of the common arterial trunk reflects this finding in that the often abnormally high positioned coronary orifices reside in the aortic part of the orifice. Combining current data the common denominator for common arterial trunk seems to be a defective interaction of neural crest, endothelial cells and the surrounding mesenchyme. Disturbances of genes in any of the three cell types can lead to the malformation. [Copyright &y& Elsevier]

Unlabelled: This retrospective study was designed to evaluate serum levels of intact parathyroid hormone and calcium in patients with conotruncal heart defects with or without microdeletion 22q11.2 in order to investigate a correlation between various types of conotruncal heart defect and hypoparathyroidism. A total of 67 patients with truncus arteriosus, tetralogy of Fallot, pulmonary atresia and ventricular septal defect, interrupted aortic arch or vascular ring were included of whom 28 had a 22q11.2 deletion (Group I) and 39 did not (Group II). In two patients of Group I and in one patient of Group II, parathyroid hormone level was decreased with normal serum calcium levels. No patient of Group II showed hypocalcaemia. In Group I, complete hypoparathyroidism with low parathyroid hormone and hypocalcaemia occurred in seven patients; 5 patients had bilateral anomalies of the right and the left 4th aortic arch derivates. In addition to an interrupted aortic arch type B or a high aortic arch, the contralateral subclavian artery arose cervically, high thoracically or anomalously from the descending aorta. Two patients had unilateral anomalies of the 4th aortic arch system: The origin of the right subclavian artery was cervical or from the descending aorta.Conclusion: Hypoparathyroidism occurred in 7 of our 28 patients with conotruncal heart defect and monosomy 22q11.2 and was associated with an extended regression of the 4th aortic arch development on both sides of the aortic arch system. [ABSTRACT FROM AUTHOR]