Atrial Septation — Atrial Septum Embryology #1: Septum Primum
Atrial septation is a coordinated developmental process that progressively partitions the initially common atrium while preserving the interatrial communication required for fetal circulation. The septum primum, or primary atrial septum, is the first major septal structure to appear. It grows toward the atrioventricular junction, initially leaving the foramen primum, then develops perforations that coalesce to form the foramen secundum. Its inferior margin subsequently becomes incorporated into the developing atrioventricular septal complex, closing the foramen primum without interrupting interatrial flow [1].
The septum primum later forms the mobile flap component of the fetal foramen ovale and contributes substantially to the floor, or valve, of the postnatal oval fossa. Understanding this sequence provides the developmental framework for interpreting the normal atrial septum, patent foramen ovale (PFO), secundum atrial septal defect (ASD), and the atrial component of atrioventricular septal defects.
1. The Initially Common Atrium
Early in cardiac development, the atrial component of the heart is not divided into definitive right and left chambers. Septation occurs while systemic and pulmonary venous connections are simultaneously undergoing substantial remodeling.
The first prominent partition is the septum primum, a thin crescentic structure arising from the atrial roof. It extends inferiorly between the developing systemic and pulmonary venous components toward the atrioventricular junction [1].
Because the leading edge of the septum primum does not initially reach the inferior atrial structures, an opening remains between it and the developing atrioventricular mesenchyme. This opening is the foramen primum, traditionally termed the ostium primum.
The foramen primum is therefore not an abnormal defect. It is a normal, transient component of atrial development that permits interatrial blood flow while septation progresses.
A fundamental principle is that normal atrial septation does not proceed by simply closing one opening. Instead, a new pathway develops before the preceding pathway disappears, ensuring continuous interatrial communication.
2. Formation of the Septum Primum
The septum primum grows inferiorly from the atrial roof toward the atrioventricular junction. Its free inferior margin is initially crescent shaped, producing the foramen primum beneath it.
The initial relationship can be conceptualized as:
Atrial roof → septum primum → foramen primum → atrioventricular mesenchymal structures
As the septum primum enlarges, the foramen primum progressively narrows.
The tissue participating in eventual closure of this opening is more complex than the simplified concept of a septal sheet merely “fusing with the endocardial cushions.” The leading edge of the septum primum carries a mesenchymal cap, which becomes incorporated into a central mesenchymal complex together with the atrioventricular cushions and the vestibular spine, also termed the dorsal mesenchymal protrusion in contemporary developmental descriptions [1,2].
Experimental developmental studies demonstrate that these multiple mesenchymal primordia participate in formation of the atrioventricular septal structures. Their fusion contributes to closure of the foramen primum and completion of the inferior component of atrial septation [2].
This developmental complexity is particularly important when interpreting atrioventricular septal defects, because these lesions cannot be explained simply as persistence of a normal embryologic “ostium primum.”
3. The Foramen Primum
During the early phase of septum primum development, the foramen primum provides the principal pathway between the developing right and left atrial compartments.
Progressive growth of the septum primum decreases the size of this communication. If the foramen primum were simply to close without development of another opening, the atria would become completely separated prematurely.
Normal development therefore requires temporal overlap between the disappearance of the foramen primum and creation of a new interatrial pathway.
This principle explains one of the most characteristic features of atrial septation: formation of the foramen secundum begins while the foramen primum is still present [1].
4. Formation of the Foramen Secundum
As the septum primum continues its inferior growth and the foramen primum narrows, multiple perforations develop within the superior portion of the septum primum.
These fenestrations enlarge and coalesce, producing the foramen secundum, or ostium secundum [1].
The developmental sequence is therefore:
Septum primum growth → narrowing of the foramen primum → perforation of the superior septum primum → coalescence of perforations → formation of the foramen secundum
The timing is physiologically critical. Interatrial communication is transferred from an opening beneath the free edge of the septum primum to an opening within the septum primum itself.
Thus, the foramen secundum should be understood as a deliberately created developmental pathway rather than a residual failure of atrial septation.
The continuous availability of an interatrial pathway permits right-to-left fetal shunting to persist as atrial architecture becomes increasingly partitioned.
5. Closure of the Foramen Primum
The foramen primum closes when the inferior septum primum and its mesenchymal cap become incorporated into the atrioventricular septal complex.
Morphologic studies emphasize that closure involves interaction among several structures: the mesenchymal cap of the septum primum, atrioventricular cushion tissue, and vestibular-spine-derived mesenchyme [1–3].
The atrial septum should therefore not be viewed as an isolated sheet developing independently from the atrioventricular junction. Its inferior development is closely integrated with formation of the atrioventricular septal structures.
By the time the foramen primum has disappeared, the foramen secundum maintains communication between the atrial chambers. Consequently, effective interatrial continuity is preserved throughout this transition.
This is the key sequence depicted by the developmental illustrations:
Foramen primum open → foramen primum narrowing with septum primum fenestration → foramen primum closure with an established foramen secundum.
6. From the Foramen Secundum to the Foramen Ovale
The foramen secundum and foramen ovale are related but are not synonymous structures.
The foramen secundum is an opening created within the septum primum. The fetal foramen ovale subsequently develops through the three-dimensional relationship between the septum primum and structures forming on its right atrial side.
Traditional descriptions refer to the latter structure as the septum secundum. Contemporary morphologic studies provide a more nuanced interpretation. Much of the superior and anterosuperior margin of the oval fossa is not a second true septal sheet but an infolding of the atrial wall [1,3].
The resulting fetal pathway is therefore an oblique rather than a simple circular opening.
Blood entering from the right atrial side passes beneath the muscular superior rim and then between that rim and the septum primum before entering the left atrium. The septum primum forms the mobile flap valve of this pathway [3].
This three-dimensional arrangement is central to understanding both fetal flow and postnatal atrial septal anatomy.
7. Septum Primum as the Flap Valve
As development progresses, the thin septum primum becomes positioned on the left atrial side of the fetal interatrial pathway.
It functions as the flap valve of the foramen ovale, permitting preferential right-to-left flow while limiting reverse movement of blood.
The septum primum should not necessarily be considered a completely passive membrane. Histologic examination of human fetal hearts has demonstrated myocardial fibers within both primary and secondary septal components. In a morphologic study of ten fetal hearts between 28 and 36 weeks of gestation, septum primum mobility and excursion toward the left atrium were examined in relation to the dimensions of the foramen ovale. The findings support the concept that the septum primum may have active structural characteristics that influence its motion and fetal interatrial flow [4].
The physiologic significance of this observation remains primarily morphologic rather than established through comparative clinical studies, but it reinforces the concept that the fetal atrial septum is a dynamic structure.
8. Fetal Interatrial Flow
During fetal life, pulmonary vascular resistance is high and pulmonary blood flow is relatively limited. The interatrial pathway allows blood entering the right atrium to reach the left atrium and subsequently the systemic circulation without passing through the pulmonary circulation.
The architecture of the foramen ovale facilitates this physiology.
The relatively firm muscular margins define the pathway, whereas the thin septum primum provides a mobile valve. Right-to-left pressure and flow displace the septum primum toward the left atrium, allowing interatrial passage.
Thus, fetal atrial septation achieves two apparently competing objectives:
- Progressive structural separation of the right and left atrial chambers.
- Preservation of a controlled communication between them.
The septum primum is central to both functions.
9. Transition at Birth
At birth, expansion of the lungs produces a marked fall in pulmonary vascular resistance and an increase in pulmonary blood flow. Pulmonary venous return to the left atrium increases, raising left atrial pressure relative to right atrial pressure.
The pressure reversal pushes the septum primum against the right-sided muscular rim of the foramen ovale, producing functional closure of the fetal interatrial pathway.
Subsequent adhesion and fusion between the flap valve and its surrounding rim may produce permanent anatomic closure.
The thin septum primum then forms the principal component of the valve or floor of the fossa ovalis, whereas the surrounding rims have different developmental origins. In particular, the anterosuperior rim is largely an infolding of the atrial wall rather than a true interatrial septum [3,5].
This distinction has considerable practical importance because the entire apparent medial right atrial wall should not be regarded as true septal tissue.
10. Patent Foramen Ovale
When postnatal fusion between the septum primum flap and the surrounding muscular rim remains incomplete, a patent foramen ovale persists.
A PFO is not primarily a deficiency of septal tissue. Instead, it is a potential tunnel-like passage between the free edge of the overlapping flap valve and its muscular rim [5,6].
The distinction is anatomically important:
PFO = separation between normally developed overlapping structures
whereas
secundum ASD = deficiency of tissue within the region of the true atrial septum
[5].
A PFO may therefore remain functionally closed when left atrial pressure exceeds right atrial pressure but permit transient or persistent right-to-left passage when the pressure relationship changes.
11. Secundum Atrial Septal Defect
A true secundum ASD, more precisely termed an oval-fossa defect in morphologic descriptions, is located within the confines of the true atrial septum [5].
Abnormal formation, excessive fenestration, or inadequate development of the septum primum can contribute to deficiency of the flap-valve tissue. The resulting communication differs fundamentally from a PFO because there is an actual absence or deficiency of septal tissue rather than incomplete fusion of overlapping components [5,7].
This developmental distinction helps explain the different morphology encountered during echocardiographic, catheter-based, and surgical assessment.
For transcatheter closure, the dimensions and quality of the surrounding rims determine device stability and relationships with adjacent structures. During surgical closure, understanding which portions represent true septum and which represent atrial-wall folds is similarly important.
12. Relationship to Atrioventricular Septal Defects
The inferior atrial septal region has historically generated considerable confusion because a primum defect was sometimes interpreted simply as persistence of the embryonic foramen primum.
Developmental and morphologic evidence indicates a more complex mechanism.
Formation of the atrioventricular septal structures requires coordinated contribution from the mesenchymal cap of the septum primum, atrioventricular cushions, vestibular-spine-derived mesenchyme, and adjacent myocardial tissues [2].
Abnormal formation or fusion within this complex can contribute to the spectrum of atrioventricular septal defects.
Importantly, the communication commonly called an ostium primum ASD lies outside the boundaries of the true oval-fossa atrial septum and should therefore be understood as part of an atrioventricular septal malformation rather than simply as a secundum-type defect located inferiorly [5].
13. Surgical Anatomy Derived from Embryology
Embryology explains why the mature atrial septum is not a uniform partition.
From the right atrial perspective, the floor of the fossa ovalis represents the thin flap-valve component derived predominantly from the septum primum. The surrounding margins are heterogeneous: the inferior portion contains true septal structures derived from mesenchymal and myocardial components, whereas much of the superior and anterosuperior rim is an infolding of the atrial wall [3,5].
This distinction matters during congenital heart surgery.
Incision or excision through the thin floor of the fossa ovalis provides direct intracardiac access between the atria. By contrast, dissection through some apparent “septal” rims can potentially enter extracardiac tissue because these structures are folds rather than true septal partitions [3].
Inferiorly, the relationship to the atrioventricular junction, coronary sinus, triangle of Koch, and conduction tissues becomes increasingly important. The developmental integration of septal and atrioventricular structures provides the anatomical basis for these close surgical relationships.
14. Key Concept
Septum primum development is best understood as sequential remodeling that preserves interatrial communication while progressively constructing the atrial septum.
The septum primum grows from the atrial roof toward the atrioventricular junction, leaving the foramen primum. As this communication narrows, superior perforations coalesce to form the foramen secundum. The septum primum and its mesenchymal cap then become incorporated with atrioventricular cushion and vestibular-spine-derived tissues, eliminating the foramen primum while the foramen secundum maintains interatrial flow [1–3].
The septum primum subsequently becomes the mobile flap valve of the fetal foramen ovale. After birth, increased left atrial pressure apposes this flap to the surrounding muscular rim, and subsequent fusion may permanently close the fetal pathway.
This developmental sequence is the foundation for distinguishing a normal foramen ovale, PFO, true secundum ASD, and the atrial component of atrioventricular septal defects. Most of the evidence defining these relationships derives from developmental morphology, histology, imaging correlation, and anatomical review rather than comparative clinical studies [1–7].
References
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[2] Webb S, Brown NA, Anderson RH. Formation of the atrioventricular septal structures in the normal mouse. Circulation Research. 1998. doi:10.1161/01.RES.82.6.645.
[3] Anderson RH, Webb S, Brown NA. Clinical anatomy of the atrial septum with reference to its developmental components. Clinical Anatomy. 1999. doi:10.1002/(SICI)1098-2353(1999)12:5<362::AID-CA6>3.0.CO;2-F.
[4] Amaral HB, Zielinsky P, Silveira AF, Costabeber I, Nicoloso LH, Souza Filho OC, et al. Bases morfolĂłgicas para o estudo do septo interatrial no feto humano. Arquivos Brasileiros de Cardiologia. 2007. doi:10.1590/S0066-782X2007000500010.
[5] Naqvi N, McCarthy KP, Ho SY. Anatomy of the atrial septum and interatrial communications. Journal of Thoracic Disease. 2018. doi:10.21037/jtd.2018.02.18.
[6] Asrress KN, Marciniak M, Marciniak A, Rajani R, Clapp B. Patent foramen ovale: the current state of play. Heart. 2015. doi:10.1136/heartjnl-2015-307639.
[7] Johri AM, Rojas CA, El-Sherief A, Witzke CF, Chitty DW, Palacios IF, et al. Imaging of atrial septal defects: echocardiography and CT correlation. Heart. 2011. doi:10.1136/hrt.2010.205732.