Atrial Septation — Atrial Septum Embryology #2: Septum Secundum and Foramen Ovale

Atrial septation is not simply the construction of a wall between the right and left atria. During fetal development, the atrial septum must perform two apparently opposing functions: progressively separate the atrial chambers while preserving a controlled right-to-left interatrial pathway. This is accomplished through the coordinated development of the septum primum, the structure traditionally termed the septum secundum, the ostium secundum, and ultimately the foramen ovale.

The mature arrangement is therefore best understood as an overlapping, pressure-responsive valve rather than a simple hole within a single septal plate.

1. From Septum Primum to Ostium Secundum

The septum primum is the first major structure involved in partitioning the primitive atrium. It grows from the atrial roof toward the atrioventricular junction. Its leading edge contains a mesenchymal cap that ultimately participates in fusion with the atrioventricular cushion-derived mesenchyme and vestibular spine, thereby closing the primary interatrial communication, the ostium primum [1,2].

Complete closure at this stage would be incompatible with fetal circulation. Before the ostium primum is eliminated, perforations develop in the superior portion of the septum primum through localized tissue resorption. These perforations enlarge and coalesce to form the ostium secundum, also termed the foramen secundum [1].

The sequence is therefore carefully coordinated:

Ostium primum narrows → perforations develop in septum primum → ostium secundum forms → ostium primum closes.

Interatrial flow is maintained continuously throughout this transition.

The ostium secundum is an opening within the septum primum. It should not be considered synonymous with the definitive foramen ovale, which develops later through the spatial overlap between the septum primum and right-sided atrial structures.

2. Development of the Septum Secundum and the Right Atrial Infolding

Classical embryologic descriptions identify a second, thicker structure—the septum secundum—forming on the right atrial side of the septum primum and progressively overlapping the ostium secundum.

This model remains useful for understanding the geometry of the fetal flap valve. Modern developmental and definitive anatomy, however, requires an important qualification.

The superior and anterosuperior border of the oval fossa is not entirely a separate muscular septal plate. Much of this region is created by infolding of the right atrial wall, with extracardiac tissue interposed between the myocardial layers. Anderson and colleagues emphasized that the flap valve of the oval foramen and its inferior margin represent true septal structures, whereas much of the remaining apparent rim—particularly the anterosuperior rim—is formed by atrial-wall infolding rather than true interatrial septum [2].

Developmental studies similarly support formation of the superior roof of the secondary interatrial opening by late infolding of the atrial wall [1].

Thus, the traditional term septum secundum is useful embryologically, but the definitive anatomy is more accurately understood as a combination of septal tissue and right atrial infolding.

This distinction is clinically important because an apparent “septal rim” does not necessarily represent tissue that directly separates the right and left atrial cavities.

3. Formation of the Foramen Ovale

As the right-sided structure progressively overlaps the ostium secundum, the fetal interatrial communication becomes an oblique, tunnel-like pathway rather than a direct defect through a single plane.

Two structures are central:

• the relatively firm right-sided rim and atrial infolding surrounding the opening; and
• the thin septum primum on the left atrial side.

The residual inferior portion of the septum primum becomes the valve of the foramen ovale.

This distinction is fundamental:

The ostium secundum is an opening within the septum primum, whereas the foramen ovale is the functional pathway created by overlap between the septum primum and the right-sided rim of the oval fossa.

The anatomy therefore creates a valve capable of maintaining fetal interatrial flow without producing a permanently unrestricted atrial septal communication.

4. The Septum Primum as a Dynamic Flap Valve

The fetal foramen ovale should be considered a flap-valve system rather than a fixed opening.

The septum primum forms a mobile membrane on the left atrial side. Right-to-left forces can displace the flap away from the right-sided rim, creating an open passage from the right atrium to the left atrium. Conversely, a higher left atrial pressure pushes the flap toward the right-sided rim and narrows or closes the pathway.

Morphological examination of human fetal hearts has also demonstrated muscular components within the septum primum, suggesting that its behavior may not be entirely passive. In a morphological and histological study of 10 fetal hearts between 28 and 36 weeks of gestation, the septum primum showed structural features potentially capable of influencing its mobility and excursion toward the left atrium [3].

The major physiologic mechanism nevertheless remains the interaction among flap geometry, blood-flow direction, and the interatrial pressure relationship.

5. Fetal Flow Through the Foramen Ovale

During fetal life, oxygen exchange occurs in the placenta rather than the lungs. Pulmonary vascular resistance remains high, pulmonary blood flow is relatively limited, and the fetal circulation requires mechanisms that allow blood to bypass the pulmonary vascular bed.

Oxygenated placental blood reaches the right atrium through the inferior vena cava. Flow entering from the inferior vena cava is preferentially directed toward the region of the fossa ovalis. The eustachian valve, situated near the inferior vena caval entrance, contributes to this streaming toward the foramen ovale [4].

The resulting pathway is:

Inferior vena cava → right atrium → foramen ovale → left atrium → left ventricle → ascending aorta.

This preferential streaming allows relatively oxygen-rich blood to reach the left heart and subsequently the coronary and cerebral circulations.

The foramen ovale therefore functions as an integral component of fetal circulatory organization rather than merely as a residual opening between incompletely separated atria.

6. Why the Foramen Ovale Remains Patent Before Birth

Fetal patency results from the combined effects of atrial pressure conditions and directed venous flow.

Because pulmonary vascular resistance is high, pulmonary venous return to the left atrium is limited. At the same time, substantial systemic venous and placental return enters the right atrium. These conditions permit the septum primum to move toward the left atrium, opening the flap-valve pathway.

Inferior vena caval streaming further directs blood toward the opening [4].

Thus, fetal patency does not require absence or destruction of septal tissue. The normal septal components are present; their geometry is specifically arranged to allow physiologic right-to-left flow before birth while retaining the potential for rapid closure after birth.

This is an important conceptual distinction from a true secundum atrial septal defect.

7. Functional Closure After Birth

Birth abruptly changes the loading conditions of the atria.

With lung expansion:

• pulmonary vascular resistance falls;
• pulmonary blood flow increases;
• pulmonary venous return to the left atrium increases; and
• left atrial pressure rises.

Simultaneously, separation from the placental circulation changes systemic venous return and increases systemic vascular resistance.

The postnatal pressure relationship therefore favors the left atrium. The septum primum is pushed against the right-sided rim of the foramen ovale, producing functional closure of the flap valve [5].

Functional closure does not initially require tissue fusion. It represents pressure-dependent apposition of the two components.

Over time, fibrous adhesion may develop between the septum primum and the opposing atrial surface, producing anatomical closure. This fusion is variable rather than universal. Morphological and clinical reviews suggest that approximately one-quarter of adults retain the potential for communication because complete fusion does not occur [4,6].

Accordingly:

Functional closure = pressure-dependent apposition

Anatomical closure = subsequent tissue adhesion and fusion

The distinction explains why an apparently closed fetal communication can remain probe-patent or reopen transiently when the interatrial pressure gradient reverses.

8. The Fossa Ovalis in Postnatal Anatomy

After closure, the former fetal communication is represented by the fossa ovalis.

From the right atrial side, the fossa appears as a relatively thin floor surrounded by more prominent margins. The flap valve derived principally from the septum primum forms much of the floor of the fossa ovalis. The inferior margin also contains true septal components, whereas substantial portions of the superior and anterosuperior apparent rim represent atrial-wall infoldings [1,2].

This has direct procedural significance.

The true interatrial septum is considerably smaller than the broad area often described surgically as the “atrial septum.” Outside the floor and true septal components of the oval fossa, dissection or puncture may enter tissue planes created by atrial wall folds rather than passing directly from one atrial cavity to the other.

Understanding these relationships is important in:

• surgical closure of atrial septal defects;
• transseptal puncture;
• catheter-based device closure;
• echocardiographic interpretation; and
• cross-sectional imaging of interatrial communications.

Echocardiography remains central to defining atrial septal morphology, while CT can provide additional information regarding defect geometry, associated structures, and post-repair anatomy when required [7].

9. Patent Foramen Ovale versus Secundum Atrial Septal Defect

Embryology explains the fundamental difference between a patent foramen ovale (PFO) and a secundum atrial septal defect (ASD).

A PFO results when the septum primum and the opposing right-sided structure fail to fuse completely after birth. Both components are present, but a potential tunnel remains between them [5,6].

Therefore:

PFO = failure of postnatal fusion between overlapping structures.

A secundum ASD is different. It represents a true deficiency of tissue in the region of the oval fossa. Excessive resorption of septum primum, inadequate development of septal tissue, abnormal formation of the surrounding components, or combinations of these mechanisms may leave a persistent anatomical communication [1,8].

Therefore:

Secundum ASD = deficiency of atrial septal tissue.

A PFO is consequently a flap or tunnel that can open under appropriate pressure conditions, whereas a secundum ASD represents a persistent interatrial orifice.

This distinction has direct implications for imaging, hemodynamics, device selection, and surgical strategy.

10. Restrictive Interatrial Communications

The clinical importance of an atrial communication depends not only on whether it exists but also on its size, geometry, orientation, and pressure gradient.

A small opening, inadequate overlap, or unfavorable alignment of the flap-valve pathway can result in restrictive interatrial flow.

This becomes particularly important in congenital heart disease in which unrestricted atrial-level mixing or decompression is required. In such settings, the interatrial communication is not simply an anatomical finding; its effective orifice can become a critical determinant of systemic or pulmonary venous pressure and overall circulatory stability.

Thus, the developmental architecture of the foramen ovale remains clinically relevant well beyond normal fetal physiology.

11. Clinical and Surgical Implications

The fossa ovalis should be evaluated as a three-dimensional anatomical complex rather than as an isolated hole in the atrial septum.

For a secundum ASD, imaging should define:

• defect size and shape;
• superior and inferior rims;
• relationship to the SVC and IVC;
• relationship to the pulmonary venous orifices;
• relationship to the coronary sinus;
• proximity to the atrioventricular junction; and
• adequacy of tissue for device anchoring or surgical patch closure.

Echocardiography is the principal imaging modality, with CT providing complementary information in selected patients when spatial relationships or associated abnormalities require further characterization [7].

During surgical closure, these relationships determine exposure and the appropriate patch suture line. Particular attention is required inferiorly and posteroinferiorly, where the defect approaches the IVC, coronary sinus, and atrioventricular junction.

For transcatheter closure, adequate surrounding rims are needed to stabilize the device while avoiding interference with adjacent structures.

A PFO presents a different anatomical problem because tissue is generally present. The potential communication persists between overlapping septal components. Although most PFOs are clinically silent, transient elevation of right atrial pressure can open the flap and permit right-to-left passage. In selected settings, this creates a pathway for paradoxical systemic embolism or clinically important hypoxemia [9]. Percutaneous closure can eliminate this potential channel in appropriately selected patients.

12. Conceptual Summary

Formation of the foramen ovale is best understood as a sequence of septation, secondary perforation, overlap, flap-valve formation, fetal patency, and postnatal apposition.

The septum primum first grows toward the atrioventricular junction. Before closure of the ostium primum, perforations develop in its superior portion and coalesce to form the ostium secundum. Right-sided atrial tissue then overlaps this opening, producing the architecture traditionally described as the septum secundum and creating the oblique foramen ovale pathway [1,2].

The septum primum becomes the mobile valve.

During fetal life, right-to-left forces and preferential inferior vena caval streaming open the valve, allowing blood to bypass the pulmonary circulation. After birth, pulmonary vascular resistance falls, pulmonary venous return increases, and higher left atrial pressure pushes the septum primum against the right-sided rim, producing functional closure [4,5].

Subsequent fusion may permanently seal the pathway. When fusion remains incomplete, a PFO persists. When septal tissue itself is deficient, a secundum ASD results.

The distinction between these entities is therefore fundamentally developmental:

PFO is primarily a problem of fusion; secundum ASD is primarily a problem of tissue formation.

Understanding this developmental sequence provides the anatomical framework for interpreting fetal circulation, postnatal fossa ovalis anatomy, PFO, secundum ASD, restrictive atrial communications, and the surgical and interventional procedures performed across the atrial septum.

References

[1] Jensen B, Spicer DE, Sheppard M, Anderson RH. Development of the atrial septum in relation to postnatal anatomy and interatrial communications. Heart. 2016. doi:10.1136/heartjnl-2016-310660.

[2] Anderson RH, Webb S, Brown NA. Clinical anatomy of the atrial septum with reference to its developmental components. Clin Anat. 1999;12(5):362. doi:10.1002/(SICI)1098-2353(1999)12:5<362::AID-CA6>3.0.CO;2-F.

[3] Amaral HB, Zielinsky P, da Silveira AF, Costabeber I, Nicoloso LH, de Souza Filho OC, Salum M, Manica J, Zanettini J, Costabeber AM. Morphological basis for the study of the interatrial septum in the human fetus. Arq Bras Cardiol. 2007.

[4] Kronzon I. Patent foramen ovale: echocardiographic evaluation and clinical implications. Isr Med Assoc J. 2006.

[5] Meier B, Lock J. Contemporary management of patent foramen ovale. Circulation. 2003. doi:10.1161/01.CIR.0000046073.34261.C1.

[6] Ghosh AK, Jain A. Diagnosis and management of patent foramen ovale. Br J Hosp Med. 2015;76(7):C98. doi:10.12968/hmed.2015.76.7.C98.

[7] Johri AM, Rojas CA, El-Sherief A, Witzke C, Chitty DW, Palacios I, Passeri J, King ME, Abbara S. Imaging of atrial septal defects: echocardiography and CT correlation. Heart. 2011. doi:10.1136/hrt.2010.205732.

[8] 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.

[9] Kokkinidis D, Rios S, Avendaño R, Zaidi A, Faillace RT. Embryology, anatomy, and physiology. In: Patent Foramen Ovale Closure for Stroke, Myocardial Infarction, Peripheral Embolism, Migraine, and Hypoxemia. 2020. doi:10.1016/B978-0-12-816966-7.00001-4.