Fallot's Tetralogy

First described in 1888 by Etienne-Louis Arthur Fallot (1850-1911).¹ He was a French physician renowned for his painstaking physical examination.

Incidence 1 in 3,600 live births.

• It is the commonest congenital cardiac defect causing cyanosis.
• It is slightly more common in males than females.

• TOF may be associated with Di George syndrome, fetal alcohol syndrome, maternal phenylketonuria and fetal hydantoin syndrome.
• They are part of a range of lesions known as CATCH 22 (cardiac defects, abnormal facies, thymic hypoplasia, cleft palate, hypocalcemia) linked to deletions of a segment of chromosome band 22q11 (DiGeorge critical region).

The right ventricular outflow obstruction combined with large VSD causes blood to enter the aorta from both the right and left ventricles, so it is significantly deoxygenated, causing cyanosis.

• Severe cyanosis may present at birth in a patient with TOF and associated pulmonary atresia.
• Birth weight is low and growth is retarded.
• First presentation may include poor feeding, breathlessness and agitation.
• Dyspnoea on exertion (usually after prolonged crying) is common.
• Squatting to rest whilst exercising is characteristic of a right-to-left shunt and presents in an older child.
• Cyanosis occurs and indicates the need for surgical repair.
• Development and puberty may be delayed.
• Hypoxic spells are potentially lethal, unpredictable episodes that occur even in noncyanotic patients with TOF. These are known as "Tet spells" and consist of prolonged crying, intense cyanosis and decreased intensity of the murmur of pulmonic stenosis.
• The rare patient may remain marginally and imperceptibly cyanotic, or acyanotic and asymptomatic, into adult life.

In older children with long-standing cyanosis (without surgery) signs include:

• Cardiac:
  • Right ventricular predominance on palpation or possibly a bulging left hemithorax.
  • Systolic thrill at the lower left sternal border
  • Aortic ejection click
  • A patient without cyanosis has a long, loud, systolic murmur with a thrill along the RVOT
  • Single S2 - Pulmonary valve closure not heard
  • Systolic ejection murmur - varies in intensity inversely with the degree of RVOT obstruction
  • Cyanotic patients have greater obstruction and a softer murmur.
• General appearance:
  • Cyanosis and clubbing is variable
  • Asymmetric crying facies is caused by agenesis or hypoplasia of the depressor anguli oris muscle on one side of the mouth. Though it is an isolated finding in most cases, it may be associated with other congenital malformations.⁴
  • Scoliosis is common
• Ophthalmological:
  • Vessels in the retina appear engorged
• Gastrointestinal:
  • Haemoptysis

May rarely be diagnosed late, in adults.

• Where antenatal ultrasound is performed on high risk mothers e.g. elevated serum screening for Trisomy 21, the demonstration of a normal aortic root would make the presence of TOF unlikely.⁵
• AP chest X-ray shows normal heart size:
  • There may be a concavity in area of main pulmonary artery - silhouette compared to a boot or wooden shoe – 'coeur on sabot'
  • The lung fields are oligaemic and the aorta is usually large
• ECG shows right axis deviation with right ventricular hypertrophy:
  • Dominant R-wave in right praecordial chest leads
• Echocardiography and selective right ventriculography may demonstrate the abnormal anatomy.
• In children with congenital heart defects, plasma B-type natriuretic peptide (BNP) levels are closely correlated to ventricular function:
  • BNP plasma levels mirror the impairment of the loaded ventricles, rather than directly indicating the extent of ventricular pressure or volume work.
  • Normal BNP does not exclude pathology, but reflects the compensated status of the heart.⁶

Neonates

In severe form in neonates:

• Give O₂
• Keep warm
• Check blood glucose
• IV prostaglandin E₁ to keep ductus arteriosus open whilst waiting for surgery

Choice is between early palliative systemic-to-pulmonary artery shunt (usually a modified Blalock-Taussig shunt from subclavian to pulmonary artery, which can be used even in premature infants) or corrective open heart surgery.

• The Blalock-Taussig shunt is a relatively safe palliative procedure, requiring fewer resources and less expertise than corrective surgery.⁷

Infants

In less severe right ventricular outflow obstruction:
Surgery is usually performed at age 6-12 months.

• During intervening period need to prevent dehydration and iron deficiency.
• Hypercyanotic events are initially treated by placing infant on abdomen or on parents shoulder, in knee-chest position, which may, with calming abort the attack.
• Otherwise give O₂ and morphine +/- IV propranolol.
• Oral propranolol may reduce number and severity of attacks, but best to refer for surgery as soon as they start.
• Occasionally diaphragmatic paralysis may occur requiring ventilatory support and physical therapy, but usually function returns in 1-2 months

Adults

• Repair of tetralogy of Fallot and of pulmonary atresia with ventricular septal defect in adults is associated with a high early mortality.
• Elevated haemoglobin concentration is indicative of chronic cyanosis and predictive for early mortality.
• Surgical correction in this patient group should still be recommended because daily function considerably improves.⁸

This depends on the severity of the right ventricular outflow tract obstruction (RVOT):³

• Approximately 25% of untreated patients with TOF and RVOT obstruction die within the first year of life.
• 95% of patients die by 40 years.
• Delayed growth and development including puberty if untreated.

After surgical correction, many patients are usually without symptoms and can lead normal lives.⁹ However, some may have mild outflow obstruction and/or mild to moderate pulmonary insufficiency and in some cases moderate to marked heart enlargement.^10,11 Some children may show delayed neurodevelopment.^12,13 After 5-20 years following surgery, patients generally have reduced exercise capacity and cardiac output than healthy individuals.