Clarifying the morphology of the ostium primum defect

Abstract

The 'ostium primum' defect is still frequently considered to be the consequence of deficient atrial septation, although the key feature is a common atrioventricular junction. The bridging leaflets of the common atrioventricular valve, which are joined to each other, are depressed distal to the atrioventricular junction, and fused to the crest of the muscular ventricular septum, which is bowed in the concave direction towards the ventricular apex. As a result, shunting across the defect occurs between the atrial chambers. These observations suggest that the basic deficiency in the 'ostium primum' defect is best understood as a product of defective atrioventricular septation, rather than an atrial septal defect. We have now encountered four examples of 'ostium primum' defects in mouse embryos that support this view. These were identified from a large number of mouse embryo hearts collected from a normal, outbred mouse colony and analysed by episcopic microscopy as part of an ongoing study of normal mouse cardiac development. The abnormal hearts were identified from embryos collected at embryonic days 15.5, 16.5 and 18.5 (two cases). We have analysed the features of the abnormal hearts, and compared the findings with those obtained in the large number of normally developed embryos. Our data show that the key feature of normal atrioventricular septation is the ventral growth through the right pulmonary ridge of a protrusion from the dorsal pharyngeal mesenchyme, confirming previous findings. This protrusion, known as the vestibular spine, or the dorsal mesenchymal protrusion, reinforces the closure of the primary atrial foramen, and muscularises along with the mesenchymal cap of the primary atrial septum to form the ventro-caudal buttress of the oval foramen, identified by some as the 'canal septum'. Detailed analysis of the four abnormal hearts suggests that in each case there has been failure of growth of the vestibular spine, with the result that the common atrioventricular junction found earlier during normal development now persists during cardiac development. Failure of separation of the common junction also accounts for the trifoliate arrangement of the left atrioventricular valve in the abnormal hearts. Analysis of the episcopic datasets also permits recognition of the location of the atrioventricular conduction axis. Comparison of the location of this tract in the normal and abnormal hearts shows that there is no separate formation of a ventricular component of the 'canal septum' as part of normal development. We conclude that it is abnormal formation of the primary atrial septum that is the cause of so-called 'secundum' atrial septal defects, whereas it is the failure to produce a second contribution to atrial septation (via growth of the vestibular spine) that results in the 'ostium primum' defect.

Development of the atrial septum in relation to postnatal anatomy and interatrial communications

“…Coronary sinus defects result from a fenestration between the cavities of the coronary sinus and the left atrium, producing the capacity for left-to-right atrial shunting through the mouth of the sinus (figure 3C) 14. The so-called ‘ostium primum’ defect is an atrioventricular, rather than atrial, septal defect15 with the essential phenotypical feature of a common atrioventricular junction. Shunting across the defect is confined at atrial level because the bridging leaflets of the common atrioventricular valve are firmly attached to the scooped-out crest of the muscular ventricular septum, thus producing dual orifices within the common atrioventricular junction (figure 3D).…”

Wilhelm His Junior and his bundle

“…To our minds, this ignores the initial description by His Senior. Our own preference is to describe it as the vestibular spine [7]. It could be argued that the structure is deserving of description as the protuberance of His.…”

“…His Senior named this protrusion the "spina vestibuli". We now know that this entity, along with a mesenchymal cap carried on the leading edge of the primary atrial septum, is muscularized to form the buttress that binds the atrial septum itself to the insulating tissues of the atrioventricular junctions [7]. The atrioventricular node is formed within this buttress.…”

Probing chromatin landscape reveals roles of endocardial TBX20 in septation

“…OFT and atrioventricular cushions were malformed. Mutant hearts had ventricular septal defects (VSDs) and ostium primum type atrial septal defects (ASDs) ( Figure 1C), which are considered a type of atrioventricular septal defect (AVSD) (12). Additionally, the dorsal mesenchymal protrusion (DMP), a second heart fieldderived structure that normally appears as a protrusion at the right pulmonary ridge (13), appeared to be lacking in the mutant hearts ( Figure 1C).…”