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The pharyngeal arches are a series of bulges found on the lateral surface of the head of vertebrate embryos. In humans, and other amniotes, there are five pharyngeal arches and traditionally these have been labelled from cranial to caudal—1, 2, 3, 4 and 6. This numbering is odd—there is no '5'. Two reasons have been given for this. One is that during development, a 'fifth' arch forms transiently but is not fully realised. The second is that this numbering fits with the evolutionary history of the pharyngeal arches. Recent studies, however, have shown that neither of these justifications have basis. The traditional labelling is problematic as it causes confusion to those trying to understand the development of the pharyngeal arches. In particular, it creates difficulties in the field of congenital cardiac malformations, where it is common to find congenital cardiac lesions interpreted on the basis of persistence of the postulated arteries of the fifth arch. To resolve these problems and to take account of the recent studies that have clarified pharyngeal arch development, we propose a new terminology for the pharyngeal arches. In this revised scheme, the pharyngeal arches are to be labelled as follows—the first, most cranial, the mandibular (M), the second, the hyoid (H), the third, the carotid (C), the fourth, the aortic (A) and the last, most caudal, the pulmonary (P). [ABSTRACT FROM AUTHOR]

Aims: Evidence is emerging that, in the setting of isomerism, the atrial and bronchial arrangement are not always concordant, nor are these patterns always harmonious with the arrangement of the abdominal organs. We aimed to evaluate the concordance between these features in a cohort of patients with cardiac malformations in the setting of known isomerism, seeking to determine whether it was feasible to assess complexity on this basis, in this regard taking note of the potential value of bronchial as opposed to appendage morphology. Methods and Results: We studied 78 patients known to have isomerism of the bronchuses, 43 with right and 35 with left isomerism. Appendage anatomy could be determined in 49 cases (63%), all but one of these being concordant with bronchial anatomy. When assessing abdominal features, in only 59 cases (76%) was splenic morphology in keeping with the thoracic findings. As expected, right isomerism was associated with greater complexity of cardiac malformations, with an odds ratio of 6.53, with confidence intervals from 2.2-19.3 (p < 0.001). The odds were slightly decreased with thoraco-abdominal disharmony, when lesions shown to carry higher risk were then found in the setting of left isomerism. Conclusion: Harmony is excellent between bronchial and appendage isomerism, but less so with the arrangement of the abdominal organs. Right isomerism in our cohort, was indicative of a sixfold increase in intracardiac complexity. When discordance was found between the systems, however, the cardiac anomalies were less typical of the anticipated findings for right vs. left isomerism of the appendages. [ABSTRACT FROM AUTHOR]

Background and Aim: To review the anatomical details, diagnostic challenges, associated cardiovascular anomalies, and techniques and outcomes of management, including re‐interventions, for the rare instances of transposition physiology with concordant ventriculo‐arterial connections. Methods: We reviewed clinical and necropsy studies on diagnosis and surgical treatment of individuals with transposition physiology and concordant ventriculo‐arterial connections, analyzing also individuals with comparable flow patterns in the setting of isomerism. Results: Among reported cases, just over two‐thirds were diagnosed during surgery, after initial palliation, or after necropsy. Of the patients, four‐fifths presented in infancy with either cyanosis or congestive cardiac failure, with complex associated cardiac malformations. Nearly half had ventricular septal defects, and one‐fifth had abnormalities of the tricuspid valve, including hypoplasia of the morphologically right ventricle. A small minority had common atrioventricular junctions We included cases reported with isomerism when the flow patterns were comparable, although the atrioventricular connections are mixed in this setting. Management mostly involved construction of intraatrial baffles, along with correction of coexisting anomalies, either together or multistaged. Overall mortality was 25%, with one‐fifth of patients requiring pacemakers for surgically‐induced heart block. The majority of survivors were in good functional state. Conclusions: The flow patterns produced by discordant atrioventricular and concordant ventriculo‐arterial connections remain an important, albeit rare, indication for atrial redirection or hemi‐Mustard's procedure with bidirectional Glenn. The procedure recruits the morphologically left ventricle in the systemic circuit, producing good long‐term functional results. The approach can also be used for those with isomeric atrial appendages and comparable hemodynamic circuits. [ABSTRACT FROM AUTHOR]

In the last issue, two case reports separately present examples of the extremely rare and complex congenital heart diseases that show concordant atrioventricular connections to the L-looped ventricles in the presence of situs solitus. Both cases highlight that the relationship between the two ventricles within the ventricular mass is not always harmonious with the given atrioventricular connection. Such disharmony between the connections and relationships requires careful assessment of the three basic facets of cardiac building blocks, namely their morphology, the relationship of their component parts, and their connections with the adjacent segments. 3D imaging and printing can now facilitate an otherwise difficult diagnosis in such complex situations. Rotation of either the 3D images or the models permit accurate assessment of the ventricular topologic pattern by creating the right ventricular en-face septal view, thus facilitating placement of the observer's hands. As we now emphasize, an alternative approach, which might prove more attractive to imagers, is to rotate the ventricular mass to provide the ventricular apical view, thus permitting determination of the ventricular relationship without using the hands. [ABSTRACT FROM AUTHOR]

Background and Aim: We showed in our anatomical review, ventricular septal defects existing as multiple entities can be considered in terms of three major subsets. We address here the diagnostic challenges, associated anomalies, the role and techniques of surgical instead of interventional closure, and the outcomes, including reinterventions, for each subset. Methods: We reviewed 80 published investigations, noting radiographic findings, and the results of clinical imaging elucidating the location, number, size of septal defects, associated anomalies, and the effect of severe pulmonary hypertension. Results: Overall, perioperative mortality for treatment of residual multiple defects has been cited to be between 0% and 14.2%, with morbidity estimated between 6% and 13%. Perioperative mortality is twice as high for perimembranous compared to muscular defects, with the need for reoperation being over four times higher. Perventricular hybrid approaches are useful for the closure of high anterior or apical defects. Overall, the results have been unsatisfactory. Pooled data reveals incidences between 2.8% and 45% for device‐related adverse events. Currently, however, outcomes cannot be assessed on the basis of the different anatomical subsets. Conclusions: We have addressed the approaches, and the results, of therapeutic treatment in terms of coexisting discrete defects, the Swiss‐cheese septum, and the arrangement in which a solitary apical muscular defect gives the impression of multiple defects when viewed from the right ventricular aspect. Treatment should vary according to the specific combination of defects. [ABSTRACT FROM AUTHOR]

Background: Over the course of time, new developments associated with the embryogenesis of the murine heart have served to clarify the developmental processes observed in the human heart. This evidence allows for the creation of a developmental framework for many congenital cardiac defects. Aims: We aim to solidify the framework related to the categorization of both solitary and multiple ventricular septal defects. Materials and Methods: Mice having genetic perturbation of the Furin enzyme have demonstrated perimembranous and juxta‐arterial ventricular septal defects, permitting the inference to be made that these defects can co‐exist with defects occurring within the apical muscular septum. Results: Basis of developmental evidence, furthermore, all interventricular communications can be placed into one of three groups, namely those which are perimembranous, juxta‐arterial, and muscular. All of the defects are described based on their borders as seen from the morphologically right ventricle. Our focus here will be on those defects within the muscular ventricular septum, recognizing that such defects can co‐exist with those that are perimembranous. We discuss the differentiation of multiple discrete defects from those referred to as the "Swiss cheese" variant. Conclusions: As we show, appropriate surgical management requires an understanding of the specific terminology, as the surgical approach may differ depending on the combination of the individual defects. Data from the Society for Thoracic Surgeons revealed that both mortality and morbidity were increased in the setting of multiple as opposed to solitary ventricular septal defects. [ABSTRACT FROM AUTHOR]

Open in new tab Download slide Open in new tab Download slide OBJECTIVES Ventricular septal defects can be classified according to their borders or according to the fashion in which they open to the right ventricle, so-called geography. As yet, there is no consensus as to how they should be classified. In an attempt to achieve agreement, the International Society for Nomenclature of Congenital and Paediatric Heart Disease, in 2018, proposed a system incorporating both approaches. We have assessed the subjectivity of their suggested terms hoping to determine their suitability in the desired universal system for classification. METHODS We examined 212 specimens held in the archive of Birmingham Women's and Children's Hospital. Each defect was described by 3 independent examiners on the basis of borders and their relationship to the landmarks of the right ventricle. The interobserver agreement was then calculated using Fleiss' method. RESULTS Calculations to assess interobserver agreement showed that the examiners were more likely to agree on the borders of the defects than their so-called geography (κ  = 0.804 vs κ  = 0.518). The landmarks of the right ventricle proved to be highly variable such that the application of 'geographic' terms to hearts with perimembranous defects proved particularly challenging. CONCLUSIONS Interobserver agreement is lower when using terms based on 'geography' as opposed to borders. Whilst providing important morphological detail, the terms based on right ventricular landmarks are highly subjective. They should not be prioritized in a universal system of classification. Instead, the defects can be classified simply by using 'perimembranous', 'muscular', or 'doubly committed and juxta-arterial' as first-order terms. [ABSTRACT FROM AUTHOR]

Palliation of patients with hypoplastic left heart syndrome remains challenging. Although coronary ischemia can be catastrophic, the prevalence and pathologies of anomalies of the coronary arteries remains unknown. We reviewed 119 specimens with the features of hypoplastic left heart syndrome, focusing our attention on the aortic root and the coronary arteries. We found 36 (30%) specimens with the combination of mitral and aortic atresia, 26 (22%) with mitral and aortic stenosis, and 57 (48%) with mitral stenosis combined with aortic atresia. In 29 specimens (24%), the coronary arteries were not located in the center of any sinuses, while in 24 specimens (21%) at least 1 coronary artery was located very proximal to a raphe or commissure, with potential for obstruction. The specimens with combined stenosis were more likely to have eccentric positions of the coronary arteries (11 specimens, 42%), compared to the 3 specimens with combined atresia (9%, P = 0.009). The specimens with combined stenosis were also more likely to have positioning at risk for obstruction (9 specimens, 35%), compared to those with combined atresia (3 specimens, 9%, P = 0.05). Coronary arterial fistulous communications were found in 11 specimens (9%), significantly more frequently in specimens with mitral stenosis and aortic atresia (9 specimens, 16%, P = 0.041). The origins of the coronary arteries in patients with hypoplastic left heart syndrome place them at potential risk for ischemia, with fistulous communications being a particular risk in those with mitral stenosis combined with aortic atresia. [ABSTRACT FROM AUTHOR]

The article focuses on the study to define variations in aortic override, coronary arterial patterns and ventricular septal defects in tetralogy of Fallot. Tetralogy of Fallot is characterized by anterocephalad deviation of the outlet septum, along with abnormal septoparietal trabeculations, which lead to subpulmonary infundibular stenosis. Archives of retained hearts are an important resource to understand congenital heart defects and their morphological variability.

Computed tomography has an established role in the evaluation of a variety of cardiac disorders, including congenital heart diseases. The current generation of high-speed scanners produces volumetric data at low doses of radiation. The interpretation of cardiac anatomy, however, is generally limited to multiplanar assessment of two-dimensional images. The volume rendering technique provides an excellent three-dimensional demonstration of external morphology but offers little information about the intracardiac anatomy. The alternative approach of virtual cardiac dissection, which is a modification of volume rendering, on the other hand, provides crucial insights regarding the intracardiac anatomy. At present, virtual cardiac dissection requires expensive software packages. These software packages are not available in all countries, thus limiting its use in routine clinical care. We present here the details of a newly developed technique that permits virtual cardiac dissection using a personal computer and open-source software. Our technique involves no additional cost and can be achieved in the comfort of the office or operating room of the cardiologist, radiologist, or cardiac surgeon. This enhanced three-dimensional visualization of intracardiac anatomy will surely improve the understanding of the morphological details of both normal and malformed hearts. In addition, by permitting assessment in projections with which modern-day cardiologists and cardiac surgeons are conversant, it is likely to improve clinical decision-making. We illustrate here its potential utility in the morphologic assessment of the atrial septum and its deficiencies, along with malformations of the ventricular outflow tracts, including common arterial trunk. [ABSTRACT FROM AUTHOR]

The pulmonary dominant variant of the common arterial trunk has always been reported to be associated with aortic coarctation, or interruption of the aortic arch, along with a duct-dependent systemic circulation. This mandates a complex surgical repair with attendant high surgical mortality. We report a 23-day-old baby with a pulmonary dominant trunk with mild aortic hypoplasia but with an arch free of coarctation or interruption, who underwent successful surgical repair. In the preoperative evaluation of a common arterial trunk, pulmonary dominance may not necessarily denote an adverse risk factor when the aorta is only mildly hypoplastic. [ABSTRACT FROM AUTHOR]

The rapid changes that have taken place in recent years in relation to techniques used to image the fetal heart have emphasized the need to have a detailed knowledge ofnormal cardiac anatomy. Without such knowledge, it is difficult, if not impossible, to recognize the multiple facets of congenital cardiac disease. From the inception of fetal echocardiographic screening, the importance of basic knowledge of cardiac anatomy has been well recognized. The current machines used for imaging, however, now make it possible potentially to recognize features not appreciated at the start of the specialty. So as to match the advances made in imaging, we have now revisited our understanding of normal cardiac anatomy in the mid-gestational fetus. This was made possible by our dissection of 10 fetal hearts, followed by production of addition histological sections that mimic the standard ultrasound views. The fetuses ranged in gestational age from between 20 and 28 weeks. We then correlated the obtained anatomic images with the corresponding ultrasonic images used in the standard fetal screening scan. We also interrogated the anatomic sections so as to clarify ongoing controversies regarding detailed features of the normal cardiac anatomy. We have been able to show that the views now obtained using current technology reveal many details of anatomy not always appreciated at earlier times. Knowledge of these features should now permit diagnosis of most congenital cardiac malformations. The anatomic-echocardiographic correlations additionally provide a valuable resource for both the understanding and teaching of fetal echocardiography. [ABSTRACT FROM AUTHOR]

Background: Chronic pulmonary regurgitation often leads to myocardial dysfunction and heart failure. It is not fully known why secondary hypertrophy cannot fully protect against the increase in wall stress brought about by the increased end-diastolic volume in ventricular dilation. It has been assumed that mural architecture is not deranged in this situation, but we hypothesised that there might be a change in the pattern of orientation of the aggregations of cardiomyocytes, which would contribute to contractile impairment. Methods: We created pulmonary valvular regurgitation by open chest, surgical suturing of its leaflets in seven piglets, performing sham operations in seven control animals. Using cardiovascular magnetic resonance imaging after 12 weeks of recovery, we demonstrated significantly increased right ventricular volumes in the test group. After sacrifice, diffusion tensor imaging of their hearts permitted measurement of the orientation of the cardiomyocytes. Results: The helical angles in the right ventricle approached a more circumferential orientation in the setting of right ventricular RV dilation (p = 0.007), with an increased proportion of surface-parallel cardiomyocytes. In contrast, this proportion decreased in the left ventricle. Also in the left ventricle a higher proportion of E3 angles with a value around zero was found, and conversely a lower proportion of angles was found with a numerical higher value. In the dilated right ventricle the proportion of E3 angles around -90° is increased, while the proportion around 90° is decreased. Conclusion: Contrary to traditional views, there is a change in the orientation of both the left ventricular and right ventricular cardiomyocytes subsequent to right ventricular dilation. This will change their direction of contraction and hinder the achievement of normalisation of cardiomyocytic strain, affecting overall contractility. We suggest that the aetiology of the cardiac failure induced by right vetricular dilation may be partly explained by morphological changes in the myocardium itself. [ABSTRACT FROM AUTHOR]

The most complex combinations of congenital cardiac malformations are found in the setting of bodily isomerism. The question remains, however, as to whether evidence of cardiac isomerism is always to be found in the setting of bodily isomerism, also known as "heterotaxy." We have previously shown that, when assessed on the basis of the extent of the pectinate muscles relative to the atrioventricular junctions, there is always isomerism of the atrial appendages in this setting. Doubt has been remained, however, as to whether these cardiac features can accurately be recognized during life. We have now encountered two patients showing features of the left and right bodily isomerism. Examinations of these patients made using computed tomography show that all features of isomerism, no matter how complex, can now be visualized during life. The images currently presented show, furthermore, that the features of the so-called "heterotaxy" can be seen during life, not only within the heart but also in all the thoracic and abdominal organs, albeit that the isomeric features are confined to the thoracic organs. Based on the images presented, we argue that if each system of organs is analyzed and described in independent fashion; then it is possible for clinicians to exclude any suggestion of ambiguity and to provide accurate descriptions of the overall arrangement. We further discuss the appropriate terminology to describe the entity we prefer to call isomerism, along with the indications and usefulness of computed tomography in revealing the anatomic features of the congenitally malformed heart. [ABSTRACT FROM AUTHOR]

Background: Heterozygous human NKX2-5 homeodomain (DNA-binding domain) missense mutations are highly penetrant for varied congenital heart defects, including progressive atrioventricular (AV) block requiring pacemaker implantation. We recently replicated this genetic defect in a murine knockin model, in which we demonstrated highly penetrant, pleiotropic cardiac anomalies. In this study, we examined postnatal AV conduction in the knockin mice. Methods and Results: A murine knockin model (Arg52Gly, Nkx2-5(+/R52G)) in a 129/Sv background was analyzed by histopathology, surface, and telemetry ECG, and in vivo electrophysiology studies, comparing with control Nkx2-5(+/+) mice at diverse postnatal stages, ranging from postnatal day 1 (P1) to 17 months. PR prolongation (first degree AV block) was present at 4 weeks, 7 months, and 17 months of age, but not at P1 in the mutant mice. Advanced AV block was also occasionally demonstrated in the mutant mice. Electrophysiology studies showed that AV nodal function and right ventricular effective refractory period were impaired in the mutant mice, whereas sinus nodal function was not affected. AV nodal size was significantly smaller in the mutant mice than their controls at 4 weeks of age, corresponding to the presence of PR prolongation, but not P1, suggesting, at least in part, that the conduction abnormalities are the result of a morphologically atrophic AV node. Conclusions: The highly penetrant and progressive AV block phenotype seen in human heterozygous missense mutations in NKX2-5 homeodomain was replicated in mice by knocking in a comparable missense mutation. [ABSTRACT FROM AUTHOR]

Aims Anomalies of the arterial valves, principally bicuspid aortic valve (BAV), are the most common congenital anomalies. The cellular mechanisms that underlie arterial valve development are poorly understood. While it is known that the valve leaflets derive from the outflow cushions, which are populated by cells derived from the endothelium and neural crest cells (NCCs), the mechanism by which these cushions are sculpted to form the leaflets of the arterial valves remains unresolved. We set out to investigate how NCCs participate in arterial valve formation, reasoning that disrupting NCC within the developing outflow cushions would result in arterial valve anomalies, in the process elucidating the normal mechanism of arterial valve leaflet formation. Methods and results By disrupting Rho kinase signalling specifically in NCC using transgenic mice and primary cultures, we show that NCC condensation within the cardiac jelly is required for correct positioning of the outflow cushions. Moreover, we show that this process is essential for normal patterning of the arterial valve leaflets with disruption leading to a spectrum of valve leaflet patterning anomalies, abnormal positioning of the orifices of the coronary arteries, and abnormalities of the arterial wall. Conclusion NCCs are required at earlier stages of arterial valve development than previously recognized, playing essential roles in positioning the cushions, and patterning the valve leaflets. Abnormalities in the process of NCC condensation at early stages of outflow cushion formation may provide a common mechanism underlying BAV, and also explain the link with arterial wall anomalies and outflow malalignment defects. [ABSTRACT FROM PUBLISHER]

Controversy still exists in the categorization of holes between the ventricles, although they are the most common congenital cardiac malformation. Advanced imaging techniques such as three-dimensional echocardiography and computed tomographic angiography offer superb anatomical details of these defects. In this review, we have sought to collate the features highlighted in different categorizations and identify their similarities, but also emphasize their differences. We hope that an analysis of this type, now achievable during life, using advanced imaging, might lead to the appearance of a unified system for diagnosis and description of holes between the ventricles. [ABSTRACT FROM AUTHOR]

The article discusses the phenotypic features of cardiac segments and shows how this approach helps in categorising the arrangements in all patients with congenitally malformed hearts. It discusses the basic approach to categorisation and the importance of sequential segmental analysis. The starting point for subsequential analysis is the establishment of the arrangement of the atrial chambers. The most common atrial arrangement is the usual arrangement, also called situs solitus while the second arrangement is often called situs inversus. In these two arrangements, the appendages show lateralization, with the morphologically right appendage in one side and the morphologically left appendage to the other. Arrangements of union or non-union of the atrial and ventricular chambers are noted.

Tetralogy of Fallot is a congenital cardiac malformation that consists of an interventricular communication, also known as a ventricular septal defect, obstruction of the right ventricular outflow tract, override of the ventricular septum by the aortic root, and right ventricular hypertrophy. This combination of lesions occurs in 3 of every 10,000 live births, and accounts for 7-10% of all congenital cardiac malformations. Patients nowadays usually present as neonates, with cyanosis of varying intensity based on the degree of obstruction to flow of blood to the lungs. The aetiology is multifactorial, but reported associations include untreated maternal diabetes, phenylketonuria, and intake of retinoic acid. Associated chromosomal anomalies can include trisomies 21, 18, and 13, but recent experience points to the much more frequent association of microdeletions of chromosome 22. The risk of recurrence in families is 3%. Useful diagnostic tests are the chest radiograph, electrocardiogram, and echocardiogram. The echocardiogram establishes the definitive diagnosis, and usually provides sufficient information for planning of treatment, which is surgical. Approximately half of patients are now diagnosed antenatally. Differential diagnosis includes primary pulmonary causes of cyanosis, along with other cyanotic heart lesions, such as critical pulmonary stenosis and transposed arterial trunks. Neonates who present with ductal-dependent flow to the lungs will receive prostaglandins to maintain ductal patency until surgical intervention is performed. Initial intervention may be palliative, such as surgical creation of a systemic-to-pulmonary arterial shunt, but the trend in centres of excellence is increasingly towards neonatal complete repair. Centres that undertake neonatal palliation will perform the complete repair at the age of 4 to 6 months. Follow-up in patients born 30 years ago shows a rate of survival greater than 85%. Chronic issues that now face such adults include pulmonary regurgitation, recurrence of pulmonary stenosis, and ventricular arrhythmias. As the strategies for surgical and medical management have progressed, the morbidity and mortality of those born with tetralogy of Fallot in the current era is expected to be significantly improved. [ABSTRACT FROM AUTHOR]

Background: In patients with congenital cardiac malformations, accurate diagnosis is critical in diagnosis and management. The multiplanar review mode (MPR) allows the operator to cut three-dimensional (3D) echocardiographic data sets in infinite planes, and to review the moving image in three simultaneous orthogonal planes. We sought to describe the clinical utility of MPR of 3D echocardiography for analysis of congenitally malformed hearts. Methods: Cross-sectional and 3D MPR echocardiography was performed in 300 patients with congenitally malformed hearts. Results: Analysis in multiplanar mode was possible in all patients. New, clinically important information, which altered management or changed the principal diagnosis, was obtained in 32 (11%) cases. This determined suitability for biventricular repair in 11 patients, clarified the morphology of atrioventricular valves in 7, helped in assessment of aortic, mitral, or prosthetic valvar disease in 13, and identified a vascular ring in the other patient. Conclusions: 3D MPR is feasible in the setting of the congenitally malformed heart, permitting focused and in-depth analysis. This substantially improves the understanding of functional morphology, above the information derived from cross-sectional echocardiography. We recommend the use of the 3D format with MPR for patients with complex congenital cardiac disease. [Copyright &y& Elsevier]

Background: A serious complication after surgical closure of ventricular septal defect (VSD) is complete heart block. In this retrospective study, we reviewed the incidence of complete heart block after surgical closure of a VSD at Great Ormond Street Hospital from 1976 to 2001 to identify any particular anatomic features that still predisposed patients to surgically-induced complete heart block and to provide anatomic guidelines to avoid this in future. Methods: Data were extracted from our local database for patients having (1) isolated VSD or VSD in the setting of (2) tetralogy of Fallot with pulmonary stenosis or (3) tetralogy of Fallot with pulmonary atresia; (4) absent pulmonary valve syndrome; (5 and 6) coarctation or interruption of the aortic arch; and (7) subaortic fibrous shelf. We carefully reviewed the operative notes from all patients with postoperative complete heart block to discover any predisposing anatomical reasons to explain the complication. Results: Two thousand seventy-nine patients had a VSD closure. Permanent complete heart block developed in 7 of 996 patients (0.7%) with an isolated defect and in 1 of 847 patients (0.1%) with tetralogy of Fallot. Four more patients had postoperative complete heart block. Conclusions: Instances of iatrogenic complete heart block continue to occur after surgical VSD closure, either because of unexpected biological variations or because of unawareness of the disposition of the atrioventricular conduction axis in particular circumstances. This report emphasizes the latter aspect in details and suggests a risk of iatrogenic complete heart block of less than 1%. [Copyright &y& Elsevier]

Objective: The splotch (Sp2H) mutation disrupts the Pax3 gene and is lethal in homozygotes. The aim of the present study was to investigate the cause of lethality. Methods and results: Using the splotch (Sp2H) mouse mutant, we demonstrated that approximately 60% of Sp2H homozygotes die in utero at 13.5–14.5 days of gestation. All these embryos have cardiac malformations involving partial or complete failure of septation of the outflow tract. Although the cause of death in utero is unknown, the dying embryos are edematous, their superior caval veins are over-expanded, and the fetal liver is enlarged and engorged with blood, all signs of cardiac failure. The remaining Sp2H homozygotes die around the time of birth, and these embryos have grossly normal hearts. All Sp2H homozygotes have neural tube defects, either spina bifida, exencephaly, or both. Although these defects clearly do not cause death in utero, they are very likely responsible for the perinatal death of homozygotes that survive to late gestation. There is no correlation between the presence or absence of a cardiac defect and the type of neural tube defect. On the other hand, there is a striking correlation between presence of a cardiac defect and reduction or absence of dorsal root ganglia, which are derivatives of the neural crest. Conclusions: In this paper, we show that the lethality has a biphasic pattern, and the data strongly suggests that mid-gestation lethality is due to cardiac defects and not the associated neural tube defects. This finding supports the idea that ‘conotruncal’ cardiac defects involving the ventricular outflow tracts develop as a result of failure of the ‘cardiac’ neural crest to colonise the developing heart in the mid-gestation embryo, and that the resulting heart defects are solely responsible for the observed mortality. [ABSTRACT FROM PUBLISHER]

Anderson * Biosciences Institute, Newcastle University, London, UK Received 24 September 2020; accepted 18 October 2020 Keywords: Hypoplastic left ventricle Definitions Pulmonary veins I read with great interest the impressive "guidelines" relating to hypoplastic left heart syndrome [1]. Only cases with mitral atresia and aortic stenosis and ventricular septal defect now survive in the guidelines. In his letter, Professor Anderson questioned our decision to include mitral atresia with aortic stenosis and ventricular septal defect in the Guidelines as part of the hypoplastic left heart syndrome anatomic discussion. [Extracted from the article]

The author presents his comments on the article s published in the 2013 issue of the journal including "An unusual example of isolated double- orifice tricuspid valve" by S. Spare and colleagues and "Double-outlet left atrium: Ventriculo-atrial malalignment defect" by S. Shetkar. He states that dual orifices in the setting of tricuspid atresia is caused by overriding and straddling of a left atrioventricular valve and the atrioventricular junctions Differentiation permits describing valves.

Unguarded tricuspid orifice is a congenital cardiac malformation characterized by absence of the tricuspid valvar leaflets in the setting of a normal atrioventricular junction and obligatory severe tricuspid regurgitation. A neonate with such a lesion presented with severe cardiac failure. The right atrium and ventricle were grossly dilated, and there were small muscular ventricular septal defects. We plicated the right-sided structures to create space for adequate expansion of the lungs and left ventricular filling, proceeding to staged conversion to the Fontan circulation. Our experience shows that neonates with cardiac failure due to dilated right-sided structures can be stabilized by surgical plication. [Copyright &y& Elsevier]

The article discusses the cardiac anatomy in phylums such as reptiles and crocodilians which are being encountered in humans with congenitally malformed heart. It states that one of the malformations found in humans with congenital cardiac disease is persistence bilaterally of right and left aortic arches that are both arising from a solitary intrapericardial aortic trunk of various phylums.