Tetralogy of Fallot

Tetralogy of Fallot (TOF) is the overall most common cyanotic congenital heart condition with many cases presenting after the newborn period. It has been classically characterised by the combination of ventricular septal defect (VSD), right ventricular outflow tract obstruction (RVOTO), overriding aorta, and a late right ventricular hypertrophy.

Epidemiology

This anomaly accounts for 5 to 10% of all congenital heart disease and has an estimated prevalence of 1 in 2000 births ¹⁰.

Associations

• cardiovascular associations
  • right-sided aortic arch: seen in ~25% of cases
  • pulmonary hypoplasia +/- atresia: particularly important in determining treatment ⁸, when there is pulmonary atresia it is sometimes termed pseudotruncus arteriosus ⁹
  • atrial septal defect (ASD) or patent ductus arteriosus (PDA) (termed pentalogy of Fallot)
  • coronary artery anomalies: seen in 3% of cases ⁶
  • persistent left-sided superior vena cava
• extra-cardiovascular associations: may be present in ~15% of cases ¹⁰
  • congenital lobar emphysema
  • DiGeorge syndrome
  • fetal rubella syndrome
  • prune belly syndrome
  • tracheo-oesophageal fistula ¹²
  • VACTERL association ¹²

Clinical presentation

The presentation relies on the degree of right ventricular outflow tract obstruction (RVOTO). Typically this is significant, resulting in cyanosis evident in the neonatal period, as a consequence of the right to left shunt across the VSD. In cases where outflow obstruction is minimal, cyanosis may be unapparent (pink tetralogy) resulting in delayed presentation, even into adulthood, although this is rare.

Pathology

Tetralogy of Fallot is classically characterised by four features which are:

1. ventricular septal defect (VSD)
   • may be multiple in ~5% of cases ⁶
2. right ventricular outflow tract obstruction (RVOTO) due to
   • infundibular stenosis, or
   • hypoplastic pulmonary valve annulus, or
   • bicuspid pulmonary valve, and/or
   • hypoplasia of pulmonary artery
3. overriding aorta
4. right ventricular hypertrophy: only develops after birth

The right ventricular hypertrophy is a result of the VSD and right ventricular outlet obstruction, both contributing to elevated resistance to right heart emptying ⁶.

Genetics

In ~15% of cases, it is associated with a deletion on chromosome 22q11 ¹³.

Radiographic features

Plain radiograph

Chest radiographs may classically show a "boot-shaped" heart with an upturned cardiac apex due to right ventricular hypertrophy and concave pulmonary arterial segment. Most infants with TOF, however, may not show this finding ².

Pulmonary oligaemia occurs due to decreased pulmonary arterial flow. RightA right-sided aortic arch is seen in 25%.

Echocardiography

Echocardiography allows direct visualisation of the abnormal anatomy and remains the primary modality for the diagnosis of tetralogy of Fallot. It has limitations on assessing associated extracardiac anomalies (e.g. peripheral pulmonary stenosis and atresia). Salient features which may be assessed during a standard sequence of transthoracic echocardiographic views include ¹⁶;

• parasternal long axis view
  • left and right ventricular size/function
  • degree of aortic override
    • override of aortic root over the VSD should be less than half of the aortic diameter ¹⁷
  • analysis of the ventricular septal defect
    • magnitude and direction of shunting across the VSD with spectral and color flow Doppler
  • confirmation of aorto-mitral continuity
    • absence of the fibrous continuity between the aortic and mitral valves is inconsistent with tetralogy of fallot, and may be suggestive of double outlet right ventricle (DORV) ¹⁸
• parasternal short axis view
  • location of the VSD
  • anatomy of the right ventricular outflow tract
    • dilation of the RVOT may be observed
    • dynamic obstruction of the RVOT may be noted, resulting from incursion of the infundibulum into the outflow tract
    • continuous wave Doppler through the RVOT may demonstrate a late-peaking, high velocity envelope is consistent with dynamic obstruction
    • right ventricular systolic pressure (RVSP) may also be quantified using the velocity of the tricuspid regurgitant jet, if visualized
  • pulmonic valve
    • leaflet number and degree of mobility
    • dimensions of the annulus
    • spectral Doppler interrogation for the presence and grading of associated pulmonic regurgitation or stenosis
  • presence or absence of associated coronary artery anomalies
• apical 4 chamber view
  • assess right and left ventricular size and function
    • right ventricular hypertrophy may be assessed by measurement of the free wall of the RV

CT

MDCT is useful in demonstrating the complex cardiovascular morphology of tetralogy of Fallot, especially the anatomy of the pulmonary and coronary arteries as well as identification of major aortopulmonary collateral vessels (MAPCAs). MDCT can be used to evaluate post-surgical changes (e.g. patency of palliative shunts) and complications.

MRI

MRI has the great advantage of providing both exquisite anatomical details and functional information without ionising radiation. The detailed assessment of the pulmonary artery is of particular importance because repair of the cardiac defects without addressing pulmonary artery hypoplasia/stenosis has a poor outcome ⁸.

The main pulmonary artery or right pulmonary artery diameter should be compared to that of the ascending aorta. A ratio of <0.3 usually signifies that primary repair would be unsuccessful, and a bridging shunt operation may be of benefit ⁸.

Assessment of coronary artery origin is also essential to surgical planning.

Treatment and prognosis

Approximately 90% of untreated tetralogy of Fallot patients succumb by the age of 10 years ⁶. Over the years many surgical approaches were performed until the current primary repair was developed. Shunts are nowadays only performed as a palliative procedure in inoperable cases or to bridge patients until the repair can be carried out, typically in the setting of pulmonary arterial hypoplasia ⁸.

Shunt operations included ⁶:

• shunts: designed to reduce cyanosis
• Pott shunt
• Waterston shunt
• Blalock-Taussig shunt: still performed in selected cases

Primary repair is now the preferred treatment and is usually performed at the time of diagnosis.

Common post-surgical complications include ⁶:

• conduction abnormalities
  • right bundle branch block (RBBB): 80-90% of cases
  • bifascicular block: 15% of cases
  • premature ventricular contractions (PVC): ~50% of cases
  • sustained ventricular tachycardias (VT): ~5% of cases
  • atrial arrhythmias: common
• valvular dysfunction
  • tricuspid regurgitation
  • pulmonary regurgitation

Prognosis is largely dependent on how soon the defect is diagnosed and corrected, with the best outcome seen in patients repaired before the age of 5 ⁶. Overall there is a 90-95% survival rate at 10 years of age, however, residual right ventricular dysfunction is common. Up to 10% of patients require re-operation within 20 years ⁶.

History and etymology

It is named after Étienne-Louis Arthur Fallot (1850-1911), a French physician, who described the tetralogy of defects in 1888 ¹⁴.

Differential diagnosis

Findings on a chest radiograph are commonly non-specific, and other cyanotic congenital heart diseases should be considered.Other conditions involving an outflow tract overriding a VSD are ¹⁵:

• pulmonary atresia with VSD: considered an extreme form of tetralogy of Fallot, the PA is obstructed with anterograde flow. The ductus arteriosus is tortuous with retrograde flow in the pulmonary arteries. Surgery and prognosis is related to the anatomy of the pulmonary arteries: type 1 features a simple diaphragm at the pulmonary annulus, type 2 has no pulmonary trunk but the pulmonary arteries are preserved, type 3 is type 2 with atretic pulmonary arteries, type 4 does not feature any pulmonary arteries but a systemic-pulmonary vascularisation by major aortopulmonary collateral arteries (MAPCAs).
• absent pulmonary valve syndrome: aortic root is overriding but not enlarged. PA trunk is, conversely, very large with to-and-fro flow due to both stenosis and insufficiency. Ductus arteriosus is classically absent or atretic.
• common arterial trunk: pulmonary is arising from the overriding vessel, the common valve often regurgitates.
• double outlet right ventricle: mimics transposition of the great vessels, combined with a ventricular septal defect