Ventricular septal defects are the commonest congenital cardiac malformations. They can exist in isolation, but are also found as integral components of other cardiac anomalies, such as tetralogy of Fallot, double outlet right ventricle, or common arterial trunk. As yet, there is no agreement on how best to classify such defects, nor even on the curved surface that is taken to represent the defect. Based on our previous pathological and clinical experiences, we have reviewed the history of classification of holes between the ventricles. We proposed that the defects are best defined as representing the area of deficient ventricular septation. This then permits the recognition of clinically significant variants according to the anatomic borders, and the way the curved surface representing the area of deficient septation opens into the morphologically right ventricle. Clinical manifestation depends on the size of the defect, and on the relationship between systemic and pulmonary vascular resistances. Symptoms include failure to thrive, along with the manifestations of the increase in flow of blood to the lungs. Diagnosis can be made by physical examination, but is confirmed by echocardiographic interrogation, which delineates the precise anatomy, and also provides the physiologic information required for optimal clinical decision-making. Cardiac catheterization offers additional information regarding hemodynamics, particularly if there is a concern regarding an increase in pulmonary vascular resistance. Hemodynamic assessment is rarely necessary to make decisions regarding management, although it can be helpful if assessing symptomatic adults with hemodynamically restrictive defects. In infants with defects producing large shunts, surgical closure is now recommended in most instances as soon as symptoms manifest. Only in rare cases is palliative banding of the pulmonary trunk now recommended. Closure with devices inserted on catheters is now the preferred approach for many patients with muscular defects, often using a hybrid procedure. Therapeutic closure should now be anticipated with virtually zero mortality, and with excellent anticipated long-term survival. Ventricular septal defects are best defined as representing the borders of the area of deficient ventricular septation. An approach on this basis permits recognition of the clinically significant phenotypic variants.

The Drosophila scribble gene regulates apical-basal polarity and is implicated in control of cellular architecture and cell growth control. Mutations in mammalian Scrib ( circletail ; Crc mutant) also result in abnormalities suggestive of roles in planar cell polarity regulation. We show that Crc mutants develop heart malformations and cardiomyopathy attributable to abnormalities in cardiomyocyte organization within the early heart tube. N-Cadherin is lost from the cardiomyocyte cell membrane and cell–cell adhesion is disrupted. This results in abnormalities in heart looping and formation of both the trabeculae and compact myocardium, which ultimately results in cardiac misalignment defects and ventricular noncompaction. Thus, these late abnormalities arise from defects occurring at the earliest stages of heart development. Mislocalization of Vangl2 in Crc/Crc cardiomyocytes suggests Scrib is acting in the planar cell polarity pathway in this tissue. Moreover, double heterozygosity for mutations in both Scrib and Vangl2 can cause cardiac defects similar to those found in homozygous mutants for each gene but without other major defects. We propose that heterozygosity for mutations in different genes in the planar cell polarity pathway may be an important mechanism for congenital heart defects and cardiomyopathy in humans.

Aims: The anatomic substrates for atrioventricular nodal re-entry remain enigmatic, but require knowledge of the normal arrangement of the inputs and exist from the atrioventricular node. This knowledge is crucial to understand the phenomenon of atrioventricular nodal re-entry. Methods and results: We studied 20 human hearts with serial sections covering the entirety of the triangle of Koch and the cavotricuspid isthmus. We determined the location of the atrioventricular conduction axis and the connections between the specialized cardiomyocytes of the conduction axis and the adjacent working atrial myocardium. The atrioventricular node was found at the apex of the triangle of Koch, with entry of the conduction axis to the central fibrous body providing the criterion for distinction of the bundle of His. We found marked variation in the inferior extensions of the node, the shape of the node, the presence or absence of a connecting bridge within the myocardium of the cavotricuspid isthmus, the connections between the compact node and the myocardium of the atrial septum, the presence of transitional cardiomyocytes, and the ‘last’ connection between the working atrial myocardium and the conduction axis before it became the bundle of His. Conclusion: The observed variations of the inferior extensions, combined with the arrangement of the ‘last’ connections between the atrial myocardium and the conduction axis prior to its insulation as the bundle of His, provide compelling evidence to support the concept for atrioventricular nodal re-entry as advanced by Katritsis and Becker.

The heart is a remarkably complex organ. Teaching its details to medical students and clinical trainees can be very difficult. Despite the complexity, accurate recognition of these details is a pre‐requisite for the subsequent understanding of clinical cardiologists and cardiac surgeons. A recent publication promoted the benefits of virtual reconstructions in facilitating the initial understanding achieved by medical students. If such teaching is to achieve its greatest value, the datasets used to provide the virtual images should themselves be anatomically accurate. They should also take note of a basic rule of human anatomy, namely that components of all organs should be described as they are normally situated within the body. It is almost universal at present for textbooks of anatomy to illustrate the heart as if removed from the body and positioned on its apex, the so‐called Valentine situation. In the years prior to the emergence of interventional techniques to treat cardiac diseases, this approach was of limited significance. Nowadays, therapeutic interventions are commonplace worldwide. Advances in three‐dimensional imaging technology, furthermore, now mean that the separate components of the heart can readily be segmented, and then shown in attitudinally appropriate fashion. In this review, we demonstrate how such virtual dissection of computed tomographic datasets in attitudinally appropriate fashion reveals the true details of cardiac anatomy. The virtual approach to teaching the arrangement of the cardiac components has much to commend it. If it is to be used, nonetheless, the anatomical details on which the reconstructions are based must be accurate. Clin. Anat. 32:288–309, 2019. © 2019 The Authors. Clinical Anatomy published by Wiley Periodicals, Inc. on behalf of American Association of Clinical Anatomists.

The past decades have seen immense progress in the understanding of cardiac development. Appreciation of precise details of cardiac anatomy, however, has yet to be fully translated into the more general understanding of the changing structure of the developing heart, particularly with regard to formation of the septal structures. In this review, using images obtained with episcopic microscopy together with scanning electron microscopy, we show that the newly acquired information concerning the anatomic changes occurring during separation of the cardiac chambers in the mouse is able to provide a basis for understanding the morphogenesis of septal defects in the human heart. It is now established that as part of the changes seen when the heart tube changes from a short linear structure to the looped arrangement presaging formation of the ventricles, new material is added at both its venous and arterial poles. The details of these early changes, however, are beyond the scope of our current review. It is during E10.5 in the mouse that the first anatomic features of septation are seen, with formation of the primary atrial septum. This muscular structure grows toward the cushions formed within the atrioventricular canal, carrying on its leading edge a mesenchymal cap. Its cranial attachment breaks down to form the secondary foramen by the time the mesenchymal cap has used with the atrioventricular endocardial cushions, the latter fusion obliterating the primary foramen. Then the cap, along with a mesenchymal protrusion that grows from the mediastinal mesenchyme, muscularizes to form the base of the definitive atrial septum, the primary septum itself forming the floor of the oval foramen. The cranial margin of the foramen is a fold between the attachments of the pulmonary veins to the left atrium and the roof of the right atrium. The apical muscular ventricular septum develops concomitant with the ballooning of the apical components from the inlet and outlet of the ventricular loop. Its apical part is initially trabeculated. The membranous part of the septum is derived from the rightward margins of the atrioventricular cushions, with the muscularizing proximal outflow cushions fusing with the muscular septum and becoming the subpulmonary infundibulum as the aorta is committed to the left ventricle. Perturbations of these processes explain well the phenotypic variants of deficient atrial and ventricular septation. Anat Rec, 297:1414–1429, 2014.

Heart development is topographically complex and requires visualization to understand its progression. No comprehensive 3-dimensional primer of human cardiac development is currently available. We prepared detailed reconstructions of 12 hearts between 3.5 and 8 weeks post fertilization, using Amira® 3D-reconstruction and Cinema4D®-remodeling software. The models were visualized as calibrated interactive 3D-PDFs. We describe the developmental appearance and subsequent remodeling of 70 different structures incrementally, using sequential segmental analysis. Pictorial timelines of structures highlight age-dependent events, while graphs visualize growth and spiraling of the wall of the heart tube. The basic cardiac layout is established between 3.5 and 4.5 weeks. Septation at the venous pole is completed at 6 weeks. Between 5.5 and 6.5 weeks, as the outflow tract becomes incorporated in the ventricles, the spiraling course of its subaortic and subpulmonary channels is transferred to the intrapericardial arterial trunks. The remodeling of the interventricular foramen is complete at 7 weeks.