Fallot's tetralogy

Synonyms: tetralogy of Fallot, TOF

What is Fallot's tetralogy?

Fallot's tetralogy (TOF) is the most common form of cyanotic congenital heart disease in children who survive beyond their first month.

The original definition consists of four main anatomical features: a large ventricular septal defect (anterior malaligned), overriding aorta, right ventricular outflow obstruction and right ventricular hypertrophy.¹ However, the two key abnormalities are:

• A large ventricular septal defect, which allows the pressures in the two ventricles to become equal.

• Right ventricular outflow obstruction.

There is also right-sided aortic arch in around 20% of cases and atrial septal defect in 8-10% - pentalogy of Fallot. There are many anatomical variations.

How common is Fallot's tetralogy? (Epidemiology)

There is an incidence of 1 in 3,600 live births and it accounts for between 7-10% of congenital defects.²

TOF is a well-recognised feature of the 22q11 microdeletion syndrome and trisomy 21 (Down'ssyndrome).³ TOF may be associated with DiGeorge's 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, hypocalcaemia) linked to deletions of a segment of chromosome band 22q11 (DiGeorge's critical region).⁴

Fallot's tetralogy symptoms (presentation)²

Fetal ultrasound screening and echocardiography have led to an increase in prenatal diagnosis.⁵

Most cases of TOF in the UK are now either diagnosed antenatally, present with low oxygen saturations post-delivery or are diagnosed following assessment for a heart murmur. Therefore, many babies with TOF are now diagnosed while they are still pink with no clinical cyanosis ('pink Fallot'). Very occasionally TOF may be unrecognised and presents with cyanotic episodes or clubbing.

Therefore, only a minority of patients with TOF will present with the following clinical features:

• Severe cyanosis may present at birth in a patient with TOF and associated pulmonary atresia.

• Birthweight is low and growth is restricted.

• 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 non-cyanotic 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 the now rare situation, an older child or adult with long-standing cyanosis (without surgery) may present with the following signs:

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 right ventricular outflow tract (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 are variable.

• Scoliosis is common.

Ophthalmological

• Vessels in the retina appear engorged.

Respiratory

• Haemoptysis.

Investigations

• Where antenatal ultrasound is performed on high-risk mothers (eg, elevated serum screening for trisomy 21), the demonstration of a normal aortic root would make the presence of TOF unlikely.⁶

• AP CXR shows normal heart size:
  

  • There may be a concavity in the area of main pulmonary artery - a silhouette compared with a boot or wooden shoe - 'coeur en 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 precordial chest leads.

• Transthoracic cross-sectional echocardiography provides a comprehensive description of the intracardiac anatomy. ⁷

• Pre-operative assessment with MRI scanning and CT angiography is essential to assess the level of right ventricle outflow obstruction and the state of the pulmonary arteries.⁸

Fallot's tetralogy treatment and management²

Neonates

In the severe form in neonates, immediate treatment includes oxygen, keeping the baby warm, investigations for other causes of neonatal collapse, such as infection and hypoglycaemia, and intravenous prostaglandin E1 to keep the ductus arteriosus open whilst waiting for surgery.

Infants with tetralogy of Fallot usually have operative correction in the first year of life. If possible, elective repair after the first few months of life is associated with better outcomes.⁹ Those who become symptomatically cyanotic as neonates may need earlier intervention. The options are primary repair, or staged repair. The latter involves an initial palliative procedure (which may be a transcatheter balloon valvuloplasty or stent insertion), followed by a complete repair. Research suggests primary repair may be associated with lower overall costs and fewer re-interventions, but this area remains controversial.¹⁰ An individualised surgical strategy (based on type of defect and size) is recommended.¹¹

Infants

In less severe right ventricular outflow obstruction: surgery may be performed at age 3-6 months. There have also been reports of good outcomes with later repairs (23-163 months).¹² However, some units advocate surgery at diagnosis, even within the first few days of life.

• During the intervening period there is a need to prevent dehydration and iron deficiency.

• Hypercyanotic events ('tet spells') are initially treated by placing the infant on the abdomen or on a parent's shoulder, in knee-chest position, which may, with calming, abort the attack.

• Otherwise give O₂ and morphine +/- intravenous propranolol.

• Oral propranolol may reduce the number and severity of attacks, but it is 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 TOF in adults is no longer associated with a high early mortality.A 2020 series of 45 patients aged >15 years (median age 21 years) reported 2% immediate postoperative mortality and excellent early and mid-term results.¹³

• Elevated haemoglobin concentration is indicative of chronic cyanosis and predictive for early mortality.

Fallot's tetralogy and pregnancy¹⁴

Women who have had their tetralogy repaired may want to consider pregnancy. Pregnancy is well tolerated with only 8% having cardiac complications. There is an increased risk of ventricular arrhythmia and heart failure among this group and risk may be assessed with markers such as NT-proBNP.¹⁵ There may be growth restriction and an increased risk of congenital heart disease in the fetus compared to the general population.

Vaginal delivery is the recommended mode of delivery for most women.

Complications

• Early postoperative course may be complicated by a low cardiac output syndrome despite an apparently adequate repair.

• Residual pulmonary incompetence.¹⁶

• Aortic root dilation.

• Sustained ventricular tachycardia.

• Some children may show delayed neurodevelopment.¹⁷

• Sudden death.

After 5-20 years following surgery, patients generally have reduced exercise capacity and cardiac output compared with that of healthy individuals.

Prognosis

If left untreated, TOF has a survival rate of 11% at 20 years and 3% at 40 years.¹⁸ Untreated TOF also causes delayed growth and development, including delayed puberty.

Current surgical treatment produces much improved 30-year survival rates between 68.5-90.5%.¹⁹ However residual problems (such as right ventricular outflow tract obstruction and pulmonary regurgitation) are common. They may require further interventions.

Historical note

TOF was first described by Niels Stenson in 1671, but the description of a large outlet ventricular septal defect together with subpulmonary and pulmonary valve stenosis, and its resulting physiology, was first demonstrated by William Hunter and then refined by Étienne-Louis Fallot in 1888.