Synonyms: Fallot's tetralogy, TOF

There are four characteristic abnormalities in tetralogy of Fallot (TOF):

• Right ventricular outflow tract (RVOT) obstruction
• Ventricular septal defect (VSD) – usually large and just below the aortic valve
• Aortic root overrides a VSD
• Right ventricular hypertrophy

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

Epidemiology

There is an incidence of 1 in 3,600 live births.¹

• It is the most common congenital cardiac defect causing cyanosis.
• Males and females are affected equally.

Aetiology

• 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).

Presentation

The right ventricular outflow obstruction combined with large ventricular septal defect (VSD) causes blood to enter the aorta from both the right and left ventricles, so it is significantly deoxygenated, causing cyanosis.²

• Severe cyanosis may present at birth in a patient with TOF and associated pulmonary atresia.
• Birthweight 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 longstanding 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 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 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.³
  • Scoliosis is common.
• Ophthalmological:
  • Vessels in the retina appear engorged.
• Gastrointestinal:
  • Haemoptysis.

May rarely be diagnosed late, in adults.

Investigations

• 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.⁴
• AP chest X-ray 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.¹
• 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.⁵

Management

When severely obstructed pulmonary blood flow is diagnosed in a fetus, perinatal management can be planned better to facilitate early prostaglandin therapy to maintain ductal patency.¹

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

The 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.⁶

Infants

In less severe right ventricular outflow obstruction:
Surgery is usually performed at age 3-6 months. 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 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 +/- IV 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 and of pulmonary atresia with ventricular septal defect (VSD) 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.⁷

Pregnancy

Pregnancy-associated risks depend on their postoperative haemodynamic state:¹

• The risk is low/similar to that of the general population, for patients with good underlying haemodynamics.
• However, if patients have substantial residual obstruction across the right ventricular outflow tract (RVOT), severe pulmonary regurgitation, tricuspid regurgitation, and right and left ventricular dysfunction, the increased volume load of pregnancy may lead to right heart failure and arrhythmias.

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.^8,9
• Aortic root dilation.
• Sustained ventricular tachycardia.
• Some children may show delayed neurodevelopment.^10,11
• Sudden death.

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

Prognosis

This depends on the severity of the right ventricular outflow tract obstruction (RVOT):²

• 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.¹²

Historical note

TOF was first described by Niels Stenson in 1671, but the description of a large outlet ventricular septal defect (VSD) 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. The term 'tetralogy of Fallot' is attributed to Canadian Maude Abbott in 1924.

Document references

1. Apitz C, Webb GD, Redington AN; Tetralogy of Fallot. Lancet. 2009 Oct 24;374(9699):1462-71. Epub 2009 Aug 14. [abstract]
2. Spektor M, Pflieger K; Tetralogy of Fallot, eMedicine, Dec 2009
3. Rioja-Mazza D, Lieber E, Kamath V, et al; Asymmetric crying facies: a possible marker for congenital malformations. J Matern Fetal Neonatal Med. 2005 Oct;18(4):275-7. [abstract]
4. Tongsong T, Sittiwangkul R, Chanprapaph P, et al; Prenatal sonographic diagnosis of tetralogy of fallot. J Clin Ultrasound. 2005 Oct;33(8):427-31. [abstract]
5. Koch A, Zink S, Singer H; B-type natriuretic peptide in paediatric patients with congenital heart disease. Eur Heart J. 2006 Apr;27(7):861-6. Epub 2006 Feb 8. [abstract]
6. Rana JS, Ahmad KA, Shamim AS, et al; Blalock-Taussig shunt: experience from the developing world. Heart Lung Circ. 2002;11(3):152-6. [abstract]
7. Horer J, Friebe J, Schreiber C, et al; Correction of tetralogy of Fallot and of pulmonary atresia with ventricular septal defect in adults. Ann Thorac Surg. 2005 Dec;80(6):2285-91. [abstract]
8. Therrien J, Marx GR, Gatzoulis MA; Late problems in tetralogy of Fallot--recognition, management, and prevention. Cardiol Clin. 2002 Aug;20(3):395-404. [abstract]
9. van den Berg J, Hop WC, Strengers JL, et al; Clinical condition at mid-to-late follow-up after transatrial-transpulmonary repair of tetralogy of Fallot. J Thorac Cardiovasc Surg. 2007 Feb;133(2):470-7. [abstract]
10. Hovels-Gurich HH, Konrad K, Skorzenski D, et al; Long-term neurodevelopmental outcome and exercise capacity after corrective surgery for tetralogy of Fallot or ventricular septal defect in infancy. Ann Thorac Surg. 2006 Mar;81(3):958-66. [abstract]
11. Hovels-Gurich HH, Bauer SB, Schnitker R, et al; Long-term outcome of speech and language in children after corrective surgery for cyanotic or acyanotic cardiac defects in infancy. Eur J Paediatr Neurol. 2008 Jan 21. [abstract]
12. Walker WT, Temple IK, Gnanapragasam JP, et al; Quality of life after repair of tetralogy of Fallot. Cardiol Young. 2002 Dec;12(6):549-53. [abstract]

Internet and further reading

• British Heart Foundation
• Ramaswamy P, Pfleiger K; Tetralogy of Fallot with Absent Pulmonary Valve. eMedicine, July 2006.

Acknowledgements