Atrial Septation — Atrial Septum Embryology #1–2: Septum Primum, Septum Secundum, and the Foramen Ovale

Atrial septation is a coordinated developmental process that partitions the primitive atrium while preserving the right-to-left interatrial pathway required for fetal circulation. The mature atrial septal region is not simply produced by fusion of two independent septal sheets. Rather, it develops through interaction among the septum primum, atrioventricular cushion-associated tissues, mesenchymal cap, dorsal/mediastinal mesenchymal protrusion, and right atrial wall infolding. The septum primum ultimately forms the floor and valve of the oval foramen, whereas mesenchymal tissues contribute importantly to closure of the primary atrial communication and formation of the definitive septal base and rim [1,2].

This developmental sequence explains both normal fetal physiology and the anatomical differences among patent foramen ovale (PFO), secundum atrial septal defect (ASD), primum defect, sinus venosus defect, and coronary sinus defect.

1. The Developmental Objective of Atrial Septation

During early cardiac development, the atrial component initially functions as a relatively common chamber. Progressive separation into right and left atrial pathways is necessary, but complete septation cannot occur before birth because the fetal circulation depends on continued passage of blood from the right atrium to the left atrium.

Atrial septation therefore proceeds through a sequence of overlapping communications:

1. The ostium primum initially permits interatrial flow beneath the developing septum primum.
2. As the ostium primum narrows, perforations develop within the superior portion of the septum primum and coalesce to form the ostium secundum.
3. Right-sided muscular and infolded atrial structures overlap the septum primum, converting the interatrial pathway into the oblique foramen ovale.
4. The septum primum becomes the mobile flap valve of the foramen ovale.
5. After birth, reversal of the interatrial pressure relationship produces functional closure.

Thus, atrial septation is not simply progressive obliteration of an opening. It is a controlled transfer of the interatrial pathway from the ostium primum to the ostium secundum and subsequently to the flap-valved foramen ovale.

2. Septum Primum and the Ostium Primum

The septum primum is the first major structure to partition the primitive atrium. It develops as a relatively thin, crescentic sheet and extends from the superior atrial region toward the atrioventricular junction.

Its free inferior margin initially remains separated from the atrioventricular cushion-associated mesenchyme. The resulting communication is the ostium primum, historically also termed the foramen primum. This opening is a normal developmental structure rather than a congenital defect.

As the septum primum grows toward the atrioventricular junction, its inferior margin interacts with the mesenchymal cap, atrioventricular cushion tissue, and dorsal or mediastinal mesenchymal protrusion. Fusion and subsequent muscularization of these tissues contribute to closure of the primary opening and formation of the ventral or inferior portion of the definitive atrial septal complex [1,2].

This modern interpretation is more accurate than the simplified statement that the septum primum merely “fuses with the endocardial cushions.” Multiple mesenchymal components participate in closing the primary interatrial communication and establishing the definitive septal base.

3. Formation of the Ostium Secundum

Closure of the ostium primum cannot precede establishment of another interatrial pathway because fetal right-to-left flow must be maintained.

As the ostium primum becomes progressively smaller, multiple perforations appear in the superior portion of the septum primum. These fenestrations, classically attributed to localized tissue resorption and programmed cell death, enlarge and coalesce to form the ostium secundum [3].

The sequence is therefore physiologically coordinated:

Ostium primum narrows → superior septum primum becomes fenestrated → fenestrations coalesce → ostium secundum develops → ostium primum closes.

The ostium secundum is consequently a normal embryologic communication. It should not be equated with a postnatal secundum ASD. A secundum ASD represents deficient tissue within the region of the oval fossa, whereas the developmental ostium secundum is a necessary stage in formation of the normal fetal interatrial pathway.

4. Formation of the Definitive Septal Base

The inferior portion of atrial septation depends substantially on mesenchymal structures.

The mesenchymal cap on the leading edge of the septum primum interacts with atrioventricular cushion tissue and the dorsal mesenchymal protrusion. These components fuse and subsequently undergo remodeling and muscularization. The resulting tissue contributes to the definitive septal base and separates the inferior atrial structures from the atrioventricular junction [1,2].

This developmental concept has important clinical implications. Defects near the atrioventricular junction cannot be understood simply as persistence of an embryonic opening in the same manner as a PFO. In particular, primum defects belong to the atrioventricular septal defect spectrum and reflect abnormal formation of the atrioventricular junction and associated cushion- and mesenchyme-derived structures.

Thus, the location of an interatrial communication provides information about the developmental process that failed.

5. The “Septum Secundum” and the Right-Sided Rim

After development of the ostium secundum, a thicker structure appears on the right side of the septum primum and progressively overlaps the secondary opening. In traditional embryologic terminology, this structure is called the septum secundum.

Modern anatomical studies have refined this concept. Much of the superior rim traditionally described as the septum secundum is better interpreted as a muscular infolding of the atrial wall, rather than as a second independent septal sheet equivalent to the septum primum [4,5].

This distinction is particularly relevant to surgical and interventional anatomy because not all structures surrounding the fossa ovalis consist of true septal tissue.

The central thin component—the floor of the fossa ovalis—is predominantly derived from the septum primum. In contrast, portions of the superior and posterior apparent “rim” may represent folded atrial walls with extracardiac tissue between their layers [4].

The mature atrial septum should therefore be understood three-dimensionally rather than as two flat membranes fused together.

6. Formation of the Foramen Ovale

As the right-sided superior rim overlaps the ostium secundum, the interatrial communication becomes an oblique tunnel rather than a direct hole between the atria.

This configuration creates the foramen ovale.

Its essential components are:

• the right-sided muscular or infolded rim surrounding the opening;
• the thin septum primum forming the floor of the oval fossa;
• the inferior portion of the septum primum functioning as the valve of the foramen ovale.

The relationship between these structures converts the interatrial pathway into a pressure-sensitive flap valve [1,4].

This architecture is central to fetal physiology. The septum primum is sufficiently mobile to move away from the surrounding rim when right atrial pressure and directed venous flow favor right-to-left passage, but it can oppose the rim when the pressure gradient reverses.

7. Fetal Function of the Foramen Ovale

The fetal circulation requires blood to bypass the nonventilated lungs. The foramen ovale provides one of the major pathways through which this occurs.

Relatively oxygenated venous return reaching the right atrium from the inferior vena cava is preferentially directed toward the oval foramen. The flap valve formed by the septum primum opens toward the left atrium, permitting blood to follow the pathway:

Right atrium → foramen ovale → left atrium → left ventricle → ascending aorta

The foramen ovale is therefore not simply an opening. It is a dynamic unidirectional valve-like structure that favors right-to-left fetal flow [4,6].

Its function depends on both anatomy and hemodynamics. Adequate overlap between the septum primum and surrounding rim is required to create the flap-valve mechanism, while the fetal interatrial pressure relationship maintains patency.

Premature restriction of this communication may have major consequences in congenital heart disease when systemic or pulmonary blood flow depends on effective atrial-level mixing.

8. Postnatal Functional and Anatomical Closure

Birth rapidly alters the pressure relationship across the atrial septum.

Lung expansion decreases pulmonary vascular resistance and markedly increases pulmonary blood flow and pulmonary venous return. Left atrial pressure consequently rises relative to right atrial pressure. The septum primum is pressed against the surrounding rim, producing functional closure of the foramen ovale [6,7].

Functional closure does not necessarily imply immediate anatomical fusion.

Over time, adhesion and fibrous fusion may develop between the septum primum and the surrounding tissue. When fusion is complete, the fetal tunnel disappears and the septum primum becomes incorporated into the floor of the fossa ovalis.

When fusion remains incomplete, the overlapping septal tissues persist as a potential channel: a patent foramen ovale.

9. Patent Foramen Ovale

A PFO is fundamentally different from a true ASD.

In a PFO, the necessary septal components are present, but the valve of the foramen ovale has failed to fuse completely with the surrounding rim. The result is a tunnel-like potential communication between overlapping tissues, rather than absence of septal tissue [4,6].

Under normal circumstances, higher left atrial pressure may keep the flap functionally closed. Transient increases in right atrial pressure, however, can reopen the channel and permit right-to-left flow.

This physiology explains the potential for paradoxical embolization. PFO has also been associated with cryptogenic stroke, migraine, and decompression illness in selected adult populations, although the strength of causal relationships and indications for closure vary by clinical context [6,9].

The developmental distinction matters therapeutically: PFO closure addresses persistence of a fetal flap-valve tunnel rather than reconstruction of missing atrial septal tissue.

10. Secundum Atrial Septal Defect

A secundum ASD represents a true deficiency of tissue in the region of the oval fossa.

Developmental mechanisms may include excessive resorption of septum primum tissue, inadequate formation of the valve of the oval foramen, deficient development of surrounding rims, or combinations of these processes [4,7].

Unlike a PFO, a secundum ASD is therefore an anatomically persistent opening rather than a potentially closed tunnel between overlapping structures.

The morphology of the surrounding rims is critical for management. Echocardiography defines defect size, shunt physiology, right-sided chamber volume loading, and relationships to adjacent structures. Cross-sectional imaging, particularly CT in selected patients, can further delineate septal morphology, pulmonary venous anatomy, associated anomalies, and postoperative anatomy [7].

Appropriately selected secundum ASDs may be suitable for transcatheter device closure when adequate rims are present. Defects with unfavorable morphology, inadequate rims, very large size, or associated lesions may require surgical closure [8].

11. Primum, Sinus Venosus, and Coronary Sinus Defects

Not every communication appearing to involve the atrial septum is a defect of the true septal tissue.

Primum Defect

A primum defect lies adjacent to the atrioventricular junction and belongs to the atrioventricular septal defect spectrum. Its development reflects abnormal formation and fusion of cushion- and mesenchyme-associated structures rather than persistence of the normal fetal foramen ovale [1,2,8].

Its surgical significance extends beyond closure of an atrial communication because the atrioventricular junction and valve morphology are intrinsically involved.

Sinus Venosus Defect

Sinus venosus defects occur outside the central true atrial septum and involve abnormal relationships between systemic venous and pulmonary venous structures. They are frequently associated with anomalous pulmonary venous connection [4,8].

Their anatomy is therefore fundamentally different from that of a secundum ASD, and treatment generally requires surgical or specialized transcatheter reconstruction of the abnormal venous pathway rather than simply closing a central septal hole.

Coronary Sinus Defect

Coronary sinus defects similarly represent abnormal development of structures outside the floor of the fossa ovalis, typically involving deficient partitioning between the coronary sinus and left atrium [4].

These distinctions emphasize that the term “atrial septal defect” encompasses anatomically and developmentally different lesions.

12. Surgical and Clinical Relevance

For congenital heart surgeons and interventional cardiologists, atrial septal embryology provides a framework for interpreting the tissue encountered around an interatrial communication.

The fossa ovalis represents the central true septal region, with its thin floor derived largely from the septum primum. The apparent rims surrounding it are heterogeneous structures and should not all be regarded as equivalent true septal tissue [4,5].

This distinction becomes important during:

• surgical or device closure of secundum ASD;
• atrial septectomy or enlargement of an atrial communication;
• repair of primum defects;
• repair of sinus venosus defects and rerouting of anomalous pulmonary veins;
• procedures involving the venae cavae, coronary sinus, or atrioventricular junction.

The operative strategy must therefore be based on the developmental and three-dimensional anatomy of the defect, not simply its appearance as an opening between the atria.

Key Concept

Atrial septation is a process of progressive partitioning combined with preservation of fetal interatrial flow.

The septum primum initially grows toward the atrioventricular mesenchyme while leaving the ostium primum. Before that communication closes, superior fenestrations coalesce to create the ostium secundum. Mesenchymal cap, atrioventricular cushion, and dorsal mesenchymal tissues participate in closure of the primary opening and formation of the definitive septal base. A right-sided muscular infolding then overlaps the septum primum, creating the flap-valved foramen ovale. The septum primum becomes its floor and mobile valve. After birth, increased left atrial pressure produces functional closure, followed variably by anatomical fusion.

Failure at different stages produces different lesions: PFO reflects incomplete fusion of overlapping tissues; secundum ASD reflects deficient tissue in the oval-fossa region; primum defects involve the atrioventricular septal complex; and sinus venosus or coronary sinus defects arise outside the true atrial septum [1,4,8].

References

[1] Anderson RH, Spicer DE, Brown NA, Mohun TJ. The Development of Septation in the Four-Chambered Heart. Anat Rec (Hoboken). 2014. doi:10.1002/ar.22949.

[2] Jensen B, Wang T, Moorman AFM. Evolution and Development of the Atrial Septum. Anat Rec (Hoboken). 2018. doi:10.1002/ar.23914.

[3] Morse D, Rogers CS, McCann P. Atrial septation in the chick and rat: a review. J Submicrosc Cytol. 1984.

[4] Naqvi N, McCarthy KP, Ho SY. Anatomy of the atrial septum and interatrial communications. J Thorac Dis. 2018. doi:10.21037/jtd.2018.02.18.

[5] Anderson RH, Brown NA, Mohun TJ. Insights regarding the normal and abnormal formation of the atrial and ventricular septal structures. Clin Anat. 2016. doi:10.1002/ca.22627.

[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 C, Chitty DW, Palacios IF, Passeri JJ, King ME, Abbara S. Imaging of atrial septal defects: echocardiography and CT correlation. Heart. 2011. doi:10.1136/hrt.2010.205732.

[8] Webb G, Gatzoulis MA. Atrial septal defects in the adult: recent progress and overview. Circulation. 2006. doi:10.1161/CIRCULATIONAHA.105.592055.

[9] Romano V, Gallinoro CM, Mottola R, Serio A, Di Meglio F, Castaldo C, Sirico F, Nurzynska D. Patent Foramen Ovale—A Not So Innocuous Septal Atrial Defect in Adults. J Cardiovasc Dev Dis. 2021. doi:10.3390/jcdd8060060.