Synonyms: tetralogy of Fallot, TOF
Fallot's tetralogy (TOF) is one of the most common forms of cyanotic congenital heart disease.
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.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.
TOF is a well-recognised feature of the 22q11 microdeletion syndrome and trisomy 21 (Down's syndrome).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).
Fetal screening and echocardiography have led to an increase in prenatal diagnosis.
Most cases of TOF in the UK are now either diagnosed antenatally, present with low oxygen saturations 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 with long-standing cyanosis (without surgery) may present with the following signs:
- 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.
- Cyanosis and clubbing are variable.
- Scoliosis is common.
- Vessels in the retina appear engorged.
- 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.
- 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.[2, 5]
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.
Full surgical repair within the first year of life, either primary repair or after a palliative procedure, is the mainstay of treatment.For patients older than 3 months, primary repair has been advocated regardless of symptoms. Primary repair can also be performed safely in most symptomatic 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.
Although primary repair is now the mainstay of surgical treatment, initial palliative surgical procedures may be required:
- A modified Blalock-Taussig shunt from subclavian to pulmonary artery can be used, even in premature infants. The Blalock-Taussig shunt is a relatively safe palliative procedure, requiring fewer resources and less expertise than corrective surgery.
- However, primary RVOT stenting is now increasingly replacing the modified Blalock-Taussig operation.
In less severe right ventricular outflow obstruction: surgery may be performed at age 3-6 months. 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 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.
- Repair of TOF 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.
Pregnancy-associated risks depend on their postoperative haemodynamic state:
- 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 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.
- Early postoperative course may be complicated by a low cardiac output syndrome despite an apparently adequate repair.
- Residual pulmonary incompetence.
- Aortic root dilation.
- Sustained ventricular tachycardia.
- Some children may show delayed neurodevelopment.
- Sudden death.
After 5-20 years following surgery, patients generally have reduced exercise capacity and cardiac output compared with that of healthy individuals.
This depends on the severity of the RVOT. If left untreated, TOF carries a 33% mortality in the first year of life and a 50% mortality in the first three years of life.Untreated TOF also causes delayed growth and development, including delayed puberty.
Surgical pulmonary valve replacement is associated with low rates of early and late mortality and significant decreases in right ventricular volumes, but no change in the right ventricular ejection fracture or QRS duration.
Although right ventricular dysfunction is present in postoperative TOF patients, the right ventricular function is not related to quality of life after surgical repair of TOF.
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.
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