Anatomical and Clinical Features of Tetralogy of Fallot

Core Anatomical Components

Tetralogy of Fallot is defined by four classic anatomic components: right‑ventricular outflow tract (RVOT) obstruction (subpulmonary infundibular stenosis), a ventricular septal defect (VSD), an overriding aorta, and right‑ventricular hypertrophy. 1, 2, 3, 4
Subpulmonary infundibular stenosis is the primary obstructive lesion of the RVOT, and the pulmonary valve is frequently small and stenotic. 1, 5
RVOT obstruction may be present at multiple levels—including infundibular, valvular, and supravalvular sites. 1
The VSD in Tetralogy of Fallot is typically a single, large, subaortic, malalignment defect that results from anterosuperior deviation of the conal (outlet) septum. 1, 5, 2, 3, 4
The aorta overrides the VSD by less than 50 % of its diameter, reflecting a biventricular origin; this override is a direct consequence of the malaligned conal septum. 1, 2, 3, 4
Right‑ventricular hypertrophy develops as a secondary response to chronic pressure overload caused by RVOT obstruction. 1, 2, 3, 4

The fundamental embryologic defect is an antero‑cephalad (anterosuperior) deviation of the developing conal septum, which creates the malalignment VSD, produces the overriding aorta, and generates RVOT obstruction, thereby unifying the four components as a single developmental malformation. 2, 3, 4

Pulmonary‑artery abnormalities frequently accompany Tetralogy of Fallot and include hypoplasia of the pulmonary trunk or branch pulmonary arteries, stenosis at any level, and occasional unilateral absence of a pulmonary artery (most often left‑sided). 1, 5
Approximately 25 % of individuals with Tetralogy of Fallot have a right aortic arch. 1, 5
Additional cardiac anomalies may be present, such as a secundum atrial septal defect, atrioventricular septal defect (particularly in patients with Down syndrome), and coronary‑artery anomalies—most commonly involving the left anterior descending artery. 1, 5

The clinical severity of Tetralogy of Fallot exists on a morphological spectrum:
- “Pink tetralogy” – mild pulmonary obstruction with minimal cyanosis, often diagnosed in adulthood.
- Classic Tetralogy – moderate obstruction with cyanosis developing in infancy.
- Severe Tetralogy – severe RVOT obstruction with profound cyanosis and reliance on aortopulmonary collaterals.
- Most extreme form – pulmonary atresia with VSD (considered a distinct entity).