Cause of Atrial Septal Defect (ASD)
Atrial septal defects are congenital cardiovascular malformations resulting from abnormal embryologic development of the atrial septum, with specific subtypes arising from distinct developmental failures during cardiac septation. 1
Embryologic Basis by ASD Subtype
The cause of ASD varies by anatomic subtype, each reflecting a different developmental abnormality:
Secundum ASD (Most Common: 60-80% of cases)
- Results from deficiency of septum primum, though deficiency of septum secundum may also contribute 1
- Represents failure of normal fossa ovalis development during cardiac septation 1
- Accounts for the majority of ASDs presenting in adults 2
Primum ASD (15-20% of cases)
- Arises as a variant of atrioventricular septal defect with specific developmental characteristics 1
- Caused by failure of endocardial cushion fusion, resulting in an interatrial communication just above the atrioventricular valve 1
- Associated with varying degrees of malformation of the left-sided component of the common atrioventricular valve 1
Sinus Venosus Defect (5-10% of cases)
- Results from abnormal development where the vena cava and/or pulmonary veins override the atrial septum or septum secundum 1
- Produces an interatrial or anomalous venoatrial communication 1
- Approximately 90% are associated with partial anomalous pulmonary venous drainage, most commonly involving right pulmonary veins draining into the superior vena cava or right atrium 3
Patent Foramen Ovale
- Represents failure of normal postnatal closure rather than a true septal deficiency 1
- Characterized by no deficiency of septum primum and a normal limbus with no deficiency of septum secundum 1
Unroofed Coronary Sinus (<1% of cases)
- Results from failure of normal coronary sinus roof development, creating direct communication between the left atrium and coronary sinus 1
Genetic and Familial Factors
While most ASDs are sporadic, genetic factors play a role in some cases:
- Familial ASDs may occur with mutations in myocardial transcription factors including NKX2.5, GATA4, and TBX6 4
- These genetic mutations may be associated with conduction disorders such as AV block in addition to the structural defect 4
- ASDs can occur as part of genetic syndromes or in association with other congenital heart defects 1
Risk Factors for Development
The European Heart Journal identifies several factors associated with ASD development:
- Gender is a definite risk factor, with female predominance noted in most ASD series 1
- Pregnancy is listed as a possible contributing factor 1
- The exact pathophysiological mechanisms linking these demographic factors to ASD development remain incompletely understood 1
Clinical Implications of Etiology
Understanding the embryologic cause is critical because:
- Each ASD subtype has characteristic associated cardiac malformations that must be identified during evaluation 5
- Sinus venosus defects have higher incidence of pulmonary arterial hypertension (16%) compared to ostium secundum defects (4%) 1
- Surgical approach and repair technique vary according to the specific developmental abnormality present 5