Tetralogy of Fallot

Highlights
Summary Overview

Basics
Definition Epidemiology Aetiology Pathophysiology Classification

Prevention
Screening Secondary

Diagnosis
History & examination Tests Differential Step-by-step Criteria Guidelines Case history

Treatment
Details Step-by-step Emerging Guidelines

Follow Up
Recommendations Complications Prognosis

Resources
References Images Patient leaflets Credits Email Print Feedback Share Add to Portfolio Bookmark Add notes

History & exam

Key factors
hypercyanotic episodes harsh systolic ejection murmur cyanosis tachypnoea

Other diagnostic factors

shock History & exam details

Diagnostic tests
1st tests to order
pulse oximetry echocardiogram ECG CXR hyper-oxygenation test

Tests to consider
cardiac catheterisation Diagnostic tests details

Treatment details
Acute
hypercyanotic spells manoeuvres to increase systemic venous return supportive care beta-blocker supportive care phenylephrine supportive care infant with non-remitting severe cyanosis surgical shunt extracorporeal membrane oxygenation (ECMO) neonate with profound cyanosis and severely limited pulmonary blood flow alprostadil supportive care

Ongoing
all patients complete surgical repair monitoring with possible pulmonary valve replacement

infective endocarditis prophylaxis Treatment details

Summary
Ventricular septal defect with over-riding aorta and right ventricular (RV) outflow tract obstruction and resulting RV hypertrophy. The common embryological cause for this constellation of findings is anterior and cephalad deviation of the muscular outlet of the ventricular septum. Usually presents in the neonatal period with a murmur, cyanosis, or both. Diagnosed by echocardiography. Treatment is by surgical repair. This usually consists of complete intracardiac repair typically during the neonatal or infant period. Occasionally, an aortopulmonary shunt is used palliatively before complete repair. The most common long-term complications of complete repair are progressive pulmonary regurgitation and RV failure, atrial arrhythmias, and ventricular arrhythmias.

Definition
Tetralogy of Fallot (TOF) is a congenital cardiac malformation. The key morphological abnormality is anterior and cephalad deviation of the muscular outlet of the ventricular septum, which causes the 4 classic findings: (1) a mal-alignment ventricular septal defect (VSD), (2) aorta over-riding the VSD, (3) right ventricular outflow tract obstruction, (4) secondary concentric right ventricular hypertrophy. This was classically described by Dr. Etienne-Louis Arthur Fallot, a pathologist, who described it in 1888 and coined the term 'la maladie bleue' (blue-baby syndrome). The cyanosis associated with this condition is due to right-to-left shunting of de-oxygenated blood at the level of the VSD. Historically, children with TOF presented with cyanosis that was progressive and life-limiting; untreated children with TOF would typically squat down, which would lead to increased pulmonary blood flow. [1]

Epidemiology
Congenital heart defects are relatively common overall. During the early 1980s, an epidemiological study designed to estimate the prevalence of congenital heart disease (CHD) in the northeastern US showed the prevalence rate of CHD to be 3.7 per 1000 live births. There was a slight, but not statistically significant, male predominance and no ethnic difference. [2]However, a subsequent study (1999-2001) estimated the prevalence of CHD to be 1.62 per 1000 live births. [3] Types of congenital heart defects vary and may be classified as cyanotic or acyanotic. If all types of defects are included, estimates of overall incidence may be as high as 9 per 1000 live births, with an overall increase if a firstdegree relative has CHD. [4] Acyanotic defects include atrial septal defects, isolated ventricular septal defects, and coarctation of the aorta. Cyanotic defects include TOF, total anomalous pulmonary venous return, transposition

of great vessels, tricuspid atresia, persistent truncus arteriosus, and hypoplastic left-heart syndrome. TOF is the most common cyanotic congenital heart defect and is estimated to account for 4% to 9% of congenital heart defects overall, or in the range of 0.262 to 0.392 per 1000 live births. [2] [3] A prevalence of 3.01 per 10,000 live births was noted in a survey of TOF patients born in western Denmark between 1984 and 1992. Of these, 26% of infants died, 54% in the first year of life and 75% before receiving corrective surgery. [5] However, in Malta, the birth prevalence for TOF between 1980 and 1994 was 0.64 per 1000 live births, prompting speculation of a genetic predisposition towards the condition. [6]

Aetiology
Little is known about the exact aetiology of TOF. There is most likely to be interplay between genetic and environmental factors, but this has not been fully defined. One study of pregnant women with a first-degree relative with congenital heart disease (CHD) found 178 per 6640 (2.7%) pregnancies with CHD. [4] There is a well-accepted association between certain genetic defects and CHD. Patients with trisomy 21, 18, or 13 have a higher incidence of TOF than infants without trisomy. [7] A retrospective analysis in patients with apparently non-syndromic TOF found 10 out of 21 patients to have deletions of chromosome 22q11 (DiGeorge's and associated syndromes), suggesting a region on this chromosome may harbour a TOF susceptibility gene. [8] In an earlier study comparing patients who had TOF with and without chromosome 22q11 deletion, every patient with TOF and 22q11 deletion was found to have an additional conotruncal anomaly. [9] Alagille's syndrome, a syndrome with cardiovascular phenotypes ranging from mild pulmonary stenosis to TOF with severe pulmonary obstruction, has been found to be due to mutations in the Jagged1 gene. [10] Additionally, mutations in Jagged1 have been associated with non-syndromic forms of TOF. [11] A prospective study looking for mutations in NKX2.5 in patients with known TOF found approximately 4% of patients with non-syndromic TOF to have a mutation in NKX2.5. [12] Increasing evidence suggests environmental factors may play a significant role in some cases of CHD. [13] Maternal diabetes, maternal phenylketonuria, [14] and maternal ingestion of retinoic acids [15] or trimethadione [16] have all been associated with an increased risk of CHD.

Aetiology
Little is known about the exact aetiology of TOF. There is most likely to be interplay between genetic and environmental factors, but this has not been fully defined. One study of pregnant women with a first-degree relative with congenital heart disease (CHD) found 178 per 6640 (2.7%) pregnancies with CHD. [4] There is a well-accepted association between certain genetic defects and CHD. Patients with trisomy 21, 18, or 13 have a higher incidence of TOF than infants without trisomy. [7] A retrospective analysis in patients with apparently non-syndromic TOF found 10 out of 21 patients to have deletions of chromosome 22q11 (DiGeorge's and associated syndromes), suggesting a region on this chromosome may harbour a TOF susceptibility gene. [8] In an earlier study comparing patients who had TOF with and without chromosome 22q11 deletion, every patient with TOF and 22q11 deletion was found to have an additional conotruncal anomaly. [9] Alagille's syndrome, a syndrome with cardiovascular phenotypes ranging from mild pulmonary stenosis to TOF with severe pulmonary obstruction, has been found to be due to mutations in the Jagged1 gene. [10] Additionally, mutations in Jagged1 have been associated with non-syndromic forms of TOF. [11] A prospective study looking for mutations in NKX2.5 in patients with known TOF found approximately 4% of patients with non-syndromic TOF to have a mutation in NKX2.5. [12] Increasing evidence suggests environmental factors may play a significant role in some cases of CHD. [13] Maternal diabetes, maternal phenylketonuria, [14] and maternal ingestion of retinoic acids [15] or trimethadione [16] have all been associated with an increased risk of CHD.

Pathophysiology
In TOF, the pathophysiology and management are dictated by 3 specific anatomical factors: 1. Degree of right ventricular outflow tract obstruction
Typically occurs at multiple levels, including below the pulmonary valve (subvalvar or infundibular stenosis), at the level of the valve (valvar pulmonary stenosis), and above the valve (supravalvar stenosis). The degree of pulmonary obstruction determines whether the infant is cyanotic or acyanotic by affecting the amount of blood that shunts right to left at the ventricular septal defect (VSD). TOF with mild pulmonary obstruction is typically not a cyanotic lesion. There is no significant restriction to the flow of blood into the pulmonary arteries and therefore the infant is well saturated.

TOF and significant pulmonary obstruction result in a cyanotic infant. This is because blood in the right ventricle has a higher resistance to overcome in order to enter the pulmonary circulation. Blood is shunted from the right ventricle to the aorta through the VSD and into the systemic circulation without being oxygenated in the pulmonary circulation.

2. Pulmonary artery anatomy

Pulmonary artery anatomy can dramatically affect the physiology. Pulmonary atresia with VSD (TOF with pulmonary atresia) and absent pulmonary valve syndrome (TOF with absent pulmonary valve) are very different physiologically and are considered different disease processes from TOF. For that reason, they are not discussed here.

3. Non-restrictive, mal-alignment VSD

Anterior mal-alignment VSD in TOF is nearly always non-restrictive. With a large, non-restrictive VSD, the pressure in the right ventricle and left ventricle equalises. In this case, the VSD does not determine the degree of shunting. The degree of shunting in TOF is therefore due to the relative resistance to flow of the pulmonary versus systemic circulations. course. Additional VSDs may be present and should be looked for as these may complicate the postoperative

Hypercyanotic spells, or tet spells, are episodes of severe cyanosis associated with hyperpnoea. They result from an increase in right ventricular outflow tract obstruction causing a decrease in the pulmonary blood flow and an increase in right-to-left shunting across the VSD. The exact aetiology of hypercyanotic spells is unclear, but they are thought to be initiated by increases in the right ventricular infundibular contractility. Hypercyanotic spells may be self-limited; however, if sustained, they can result in brain ischaemia or death. [17]

Classification
Variants of TOF There is no standard classification for TOF, but many experts would use the following classification:
1. Cyanotic TOF (also know as blue tet): infants with TOF and moderate to severe pulmonary obstruction are cyanotic at birth due to right-to-left shunting of de-oxygenated blood from the right ventricle across the ventricular septal defect (VSD) to the body.

2.

Acyanotic TOF (also know as pink tet): infants with TOF and mild pulmonary obstruction are commonly acyanotic because there is little or no right-to-left shunting of blood at the ventricular level. These patients still undergo complete intracardiac repair.

3.

Pulmonary atresia/VSD: sometimes referred to as TOF with pulmonary atresia and is anatomically and physiologically very different. It is often associated with malformation of the central pulmonary arteries.

4.

Absent pulmonary valve syndrome: sometimes referred to as TOF with absent pulmonary valve. It is often associated with tracheobronchial compression and malformation.

Screening
Asymptomatic newborns are not screened for congenital heart disease (CHD). There is some discussion of the use of routine neonatal pulse oximetry to screen infants for structural heart disease, but its sensitivity as a screening test has not been fully established. [18] All children with certain syndromes such as trisomy 21 should be screened for CHD. A screening fetal echocardiogram may be indicated in a pregnant mother who has had other children with CHD or has CHD herself.

Secondary prevention
Immunisation against respiratory syncytial virus is indicated during the appropriate season. Infective endocarditis prophylaxis before dental procedures or for procedures on the respiratory tract or infected skin, skin structures, or musculoskeletal tissue is required for unrepaired cyanotic CHD, including palliative shunts and repaired CHD with residual defects at or adjacent to the site of a prosthetic patch or device. [30] Patients with TOF should have pre-conception counselling. Women with repaired TOF should be evaluated by a cardiologist before pregnancy. The risk of having an offspring with CHD increases 10-fold with an affected firstdegree relative. [43] A screening fetal echocardiogram may be indicated in a pregnant mother who has had other children with CHD or has CHD herself. There are no clear guidelines

History & examination

Key diagnostic factorshide all
hypercyanotic episodes (common)

Hypercyanotic (tet) spells may present as episodic, increasing cyanosis in a baby with TOF. The baby is typically crying and breathing deeply and rapidly, but may not be in significant respiratory distress.

The typical murmur of TOF may disappear during the spell. This presentation is potentially life-threatening and requires rapid intervention. Can occur in both cyanotic and acyanotic infants with TOF.

harsh systolic ejection murmur (common)

Loudest at the left sternal border represents the blood flow across the narrowed right ventricular outflow tract.

cyanosis (common)

Usually noted; however, the degree of cyanosis may vary and can be subtle. TOF with severe pulmonary obstruction is a more severe presentation and may present in a newborn who appears severely cyanotic at birth.

tachypnoea (common)

May have significant tachypnoea with severe pulmonary obstruction. Other diagnostic factorshide all shock (uncommon)

Infants with severe pulmonary obstruction or a hypercyanotic spell may present with severe cyanosis and acidosis due to tissue hypoxia. factorshide all

Risk

Weak trisomy 21, 18, or 13

There is a well-accepted association between certain genetic defects and congenital heart disease. Patients with trisomy 21, 18, or 13 have a higher incidence of TOF than infants without trisomy. [7]

chromosome 22q11 deletions (DiGeorge's syndrome)

A retrospective analysis in patients with apparently non-syndromic TOF found 10 out of 21 patients to have deletions of chromosome 22q11 (DiGeorge's and associated syndromes), suggesting a region on this chromosome may harbour a TOF susceptibility gene. [8]

Jagged1 gene mutations (Alagille's syndrome)

Alagille's syndrome, a syndrome with cardiovascular phenotypes ranging from mild pulmonary stenosis to TOF with severe pulmonary obstruction, has been found to be due to mutations in the Jagged1 gene. [10]Additionally, mutations in Jagged1 have been associated with non-syndromic forms of TOF. [11]

mutation in NKX2.5 gene

A prospective study looking for mutations in NKX2.5 in patients with known TOF found approximately 4% of patients with non-syndromic TOF to have a mutation in NKX2.5. [12]

environmental factors

Increasing evidence suggests environmental factors, such as maternal diabetes and phenylketonuria and maternal ingestion of retinoic acids and trimethadione, may play a significant causative role in certain cases of congenital heart disease. [14] [15] [16]

family history of congenital heart disease

Believed to contribute to the recurrence of congenital heart disease in a family, but it cannot be clearly explained by mendelian genetics or complete penetrance. [4]

Diagnostic tests
1st tests to orderhide all
Test

pulse oximetry baby is hypoxaemic. echocardiogram Should be ordered in any newborn with a suspected diagnosis of congenital heart disease. Echocardiography is definitive investigation for diagnosis of TOF.

May be normal in TOF with mild pulmonary stenosis. However, in TOF with moderate to severe pulmonary steno

ECG RVH may be difficult to interpret in a neonate. View image In an older child RVH is more likely to be seen.

CXR Normal cardiac silhouette does not rule out cyanotic heart disease. hyper-oxygenation test Used to determine whether hypoxaemia is from a pulmonary or a cardiac lesion.

PaO2 on room air should be checked, 100% FiO2 given for at least 10 minutes, and then PaO2 re-checked. If th increases by >25 mmHg and to >100 mmHg, the hypoxaemia is likely to be caused by a pulmonary problem. In acyanotic patients this test may yield false-negative results.

Tests to considerhide all

Test

cardiac catheterisation hypercyanotic spells. Performed if definition of the coronary artery anatomy is not possible by echocardiogram.

Not routinely done for diagnostic evaluation of TOF because stimulation of the infundibular muscle may precipita

Differential diagnosis
Condition Differentiating signs/symptoms Differentiating tests

Other cyanotic congenital cardiac abnormalities

Includes single ventricle lesions such as hypoplastic left heart syndrome or tricuspid atresia. Other possibilities include Dtransposition, pulmonary atresia, anomalous pulmonary venous connection, truncus arteriosus, or Ebstein's anomaly.

No change in PaO2 with hyperoxia test.

Echocardiogram can define anatomy to classify

In some cases, a cardiac catheterisation may b define anatomy and physiology.

These may all be difficult to differentiate clinically from a cyanotic newborn with TOF. Most are not specifically associated with other syndromes, although this can vary.

Pulmonary stenosis

Usually presents in an asymptomatic patient with a systolic ejection murmur on

Echocardiogram will show presence or absenc stenosis alone.

TOF with pulmonary obstruction to differentiate

examination. Difficult to differentiate clinically from TOF. [21] Ventricular septal defect (VSD)

At birth, an infant with simple VSD is fully saturated with regurgitant murmur on examination.

Echocardiogram will show presence or absenc obstructive lesion to determine whether this is

Intensity of murmur depends on size of VSD and flow across the VSD. A small VSD has a louder murmur because the gradient between the right and left ventricles is higher. A large VSD has a soft murmur because pressures are equalised between the right and left ventricles.

As pulmonary vascular resistance drops, more blood shunts from left to right across the VSD and may result in pulmonary overcirculation and heart failure. This is uncommon with TOF, as the

pulmonary obstruction prevents over-circulation.

Double outlet right ventricle with normally related great vessels and pulmonary stenosis

Cannot be differentiated from TOF on physical examination alone.

Echocardiogram will show presence or absenc double outlet right ventricle.

and degree of aorta over-ride of the VSD to dif

Primary pulmonary disease

On examination, infant may be tachypnoeic and desaturated, potentially requiring mechanical ventilation.

Hyper-oxygenation test should show increase i administration of 100% FiO2.

CXR will show normal cardiac silhouette with in Echocardiogram will show normal intracardiac

Cardiovascular examination is usually normal.

Step-by-step diagnostic approach

Patients typically present with cyanosis and/or a murmur. Echocardiography is the definitive investigation for diagnosis of TOF and should be ordered in any newborn with a suspected diagnosis of congenital heart disease.

History
Certain genetic syndromes are associated with an increased incidence of TOF, such as DiGeorge and Down's syndromes. There may be a history of abnormality on fetal echocardiogram that suggests cardiac pathology. A typical infant presents in the newborn nursery with a murmur. Cyanosis is usually noted. The degree of cyanosis may vary and can be subtle, and some clinicians advocate routine screening of all neonates with pulse oximetry. [18] Some infants may not present at birth but rather may present later with increasing cyanosis, murmur, or hypercyanotic (tet) spells. Hypercyanotic spells may present as episodic, increasing cyanosis in a baby with TOF. The baby is typically crying and breathing deeply and rapidly, but may not be in

significant respiratory distress. The typical murmur of TOF may disappear during the spell. This presentation is potentially life-threatening and requires rapid intervention. TOF with severe pulmonary obstruction is a more severe presentation and may present in a newborn who appears severely cyanotic at birth. Infants with severe pulmonary obstruction or a hypercyanotic spell may present with severe cyanosis and acidosis due to tissue hypoxia.

Physical examination
Can vary significantly depending on the degree of pulmonary obstruction. The infant with mild obstruction is typically comfortable, and cyanosis may be difficult to discover on physical examination. With moderate obstruction the cyanosis is likely to be apparent on examination and the infant is typically comfortable. With severe obstruction the baby may have significant tachypnoea and cyanosis. The cardiac examination typically finds an increased right ventricular (parasternal) impulse. S1 is normal and S2 is single. There is typically a 3/6 harsh systolic ejection murmur, heard best at the left sternal border. The murmur on examination represents blood flow across the pulmonary outflow and not the ventricular septal defect. The intensity of the murmur depends on the degree of pulmonary stenosis and decreases with severe stenosis.

Investigations
Transthoracic 2-dimensional and Doppler echocardiography is the preferred technique for defining the anatomical diagnosis. In the vast majority of cases no further testing is needed pre-operatively. Sedation may be judiciously used if the child is not co-operative with the examination. Pre-ductal and post-ductal (right arm and either leg) pulse oximetry should be ordered if there is any suspicion of a congenital cardiac malformation. [19] A hyper-oxygenation test can be used to determine whether hypoxaemia is from a pulmonary or a cardiac lesion. ECG will often show evidence of right ventricular hypertrophy and may show right axis deviation beyond normal limits for age. View image CXR is classically described as a boot-shaped heart, but most patients do not have this finding. The presence of a right aortic arch may be noted in a subset of patients, particularly those with 22q11 deletion. [9]

Cardiac catheterisation is usually unnecessary in diagnosing TOF and may induce hypercyanotic spells. [17] If there is significant concern for coronary artery anomalies that cannot be defined echocardiographically, then catheterisation may be indicated. Anomalies in the distribution or course of the coronary arteries may be present in approximately one third of patients with TOF. [20]

Diagnostic criteria
Echocardiogram findings of TOF
Anterior and cephalad deviation of the muscular outlet of the ventricular septum resulting in: Mal-alignment ventricular septal defect Over-riding of the aorta Multi-level right ventricular outflow tract obstruction Right ventricular hypertrophy.

Case history #1
A 1-day-old infant in the general care nursery born at full term by uncomplicated spontaneous vaginal delivery is noted to have cyanosis of the oral mucosa. The baby otherwise appears comfortable. On examination, respiratory rate is 40 and pulse oximetry is 80%. A right ventricular lift is palpated, S1 is normal, S2 is single, and a harsh 3/6 systolic ejection murmur is heard at the left upper sternal border.

Case history #2
A 1-day-old infant in the general care nursery born at full term by uncomplicated spontaneous vaginal delivery is noted to have a murmur on examination. The baby otherwise appears well. On examination, respiratory rate is 40 and pulse oximetry is 96%. Precordium is normoactive. With auscultation, S1 is normal, S2 is single, and a 2/6 systolic ejection murmur is heard at the left upper sternal border.

Other presentations
Cyanosis occurs if severe right ventricular outflow tract obstruction forces blood returning to the right side of the heart to be shunted right to left across the ventricular septal defect (VSD) and out to the systemic circulation, by-

passing the lungs. Hypercyanotic spells may present as episodic, increasing cyanosis in a baby with TOF. The baby is typically crying and breathing deeply and rapidly, but may not be in significant respiratory distress. The typical murmur of TOF may disappear during the spell. This presentation is potentially life-threatening and requires rapid intervention. Alternatively, a baby may be severely cyanotic at birth.

Treatment Options

Treatment Patient group hypercyanotic spells line 1st Treatmenthide all

manoeuvres to increase systemic venous return

Infant should be kept calm and manoeuvres tried to increase the amount of blood exiting the right ventricle through the pulmonary vasculature instead of to the aorta.

Infant should be held in the parent's arms and positioned with the knees to the chest.

adjunct [?]

supportive care

Supportive medical therapy may include volume/blood administration as needed, intravenous morphine to calm the child as needed, and bicarbonate to reverse acidosis as needed. Oxygen should be given, but care should be taken not to increase the infant's stimulation.

2nd

beta-blocker

Thought to help resolve hypercyanotic spells, but the mechanism of action is not completely clear. It is believed that it helps to decrease the infundibular obstruction by decreasing the heart rate, prolonging diastolic filling, and decreasing contractility. [17]

May be initiated in patients with TOF with pulmonary stenosis if manoeuvres such as knee-to-chest positioning or fluid bolus have not resolved the hypercyanotic spell.

Propranolol has been used in the past in the outpatient setting of an infant with spells to delay surgery. An infant with a single spell is considered an indication for urgent surgical repair, [23] but propranolol may be used until surgery can be arranged. Primary Options esmolol : 100-500 micrograms/kg intravenous bolus initially, followed by 50-500 micrograms/kg/min infusion More OR

Treatment Patient group hypercyanotic spells line 1st Treatmenthide all

manoeuvres to increase systemic venous return

Infant should be kept calm and manoeuvres tried to increase the amount of blood exiting the right ventricle through the pulmonary vasculature instead of to the aorta.

Infant should be held in the parent's arms and positioned with the knees to the chest.

adjunct [?]

supportive care

Supportive medical therapy may include volume/blood administration as needed, intravenous morphine to calm the child as needed, and bicarbonate to reverse acidosis as needed. Oxygen should be given, but care should be taken not to increase the infant's stimulation.

2nd

beta-blocker

Thought to help resolve hypercyanotic spells, but the mechanism of action is not completely clear. It is believed that it helps to decrease the infundibular obstruction by decreasing the heart rate, prolonging diastolic filling, and decreasing contractility. [17]

May be initiated in patients with TOF with pulmonary stenosis if manoeuvres such as knee-to-chest positioning or fluid bolus have not resolved the hypercyanotic spell.

Propranolol has been used in the past in the outpatient setting of an infant with spells to delay surgery. An infant with a single spell is considered an indication for urgent surgical repair, [23] but propranolol may be used until surgery can be arranged. Primary Options esmolol : 100-500 micrograms/kg intravenous bolus initially, followed by 50-500 micrograms/kg/min infusion More OR

Treatment Patient group hypercyanotic spells line 1st Treatmenthide all

manoeuvres to increase systemic venous return

Infant should be kept calm and manoeuvres tried to increase the amount of blood exiting the right ventricle through the pulmonary vasculature instead of to the aorta.

Infant should be held in the parent's arms and positioned with the knees to the chest.

adjunct [?]

supportive care

Supportive medical therapy may include volume/blood administration as needed, intravenous morphine to calm the child as needed, and bicarbonate to reverse acidosis as needed. Oxygen should be given, but care should be taken not to increase the infant's stimulation.

2nd

beta-blocker

Thought to help resolve hypercyanotic spells, but the mechanism of action is not completely clear. It is believed that it helps to decrease the infundibular obstruction by decreasing the heart rate, prolonging diastolic filling, and decreasing contractility. [17]

May be initiated in patients with TOF with pulmonary stenosis if manoeuvres such as knee-to-chest positioning or fluid bolus have not resolved the hypercyanotic spell.

Propranolol has been used in the past in the outpatient setting of an infant with spells to delay surgery. An infant with a single spell is considered an indication for urgent surgical repair, [23] but propranolol may be used until surgery can be arranged. Primary Options esmolol : 100-500 micrograms/kg intravenous bolus initially, followed by 50-500 micrograms/kg/min infusion More OR

Treatment Patient group hypercyanotic spells line 1st Treatmenthide all

manoeuvres to increase systemic venous return

Infant should be kept calm and manoeuvres tried to increase the amount of blood exiting the right ventricle through the pulmonary vasculature instead of to the aorta.

Infant should be held in the parent's arms and positioned with the knees to the chest.

adjunct [?]

supportive care

Supportive medical therapy may include volume/blood administration as needed, intravenous morphine to calm the child as needed, and bicarbonate to reverse acidosis as needed. Oxygen should be given, but care should be taken not to increase the infant's stimulation.

2nd

beta-blocker

Thought to help resolve hypercyanotic spells, but the mechanism of action is not completely clear. It is believed that it helps to decrease the infundibular obstruction by decreasing the heart rate, prolonging diastolic filling, and decreasing contractility. [17]

May be initiated in patients with TOF with pulmonary stenosis if manoeuvres such as knee-to-chest positioning or fluid bolus have not resolved the hypercyanotic spell.

Propranolol has been used in the past in the outpatient setting of an infant with spells to delay surgery. An infant with a single spell is considered an indication for urgent surgical repair, [23] but propranolol may be used until surgery can be arranged. Primary Options esmolol : 100-500 micrograms/kg intravenous bolus initially, followed by 50-500 micrograms/kg/min infusion More OR

Treatment Patient group hypercyanotic spells line 1st Treatmenthide all

manoeuvres to increase systemic venous return

Infant should be kept calm and manoeuvres tried to increase the amount of blood exiting the right ventricle through the pulmonary vasculature instead of to the aorta.

Infant should be held in the parent's arms and positioned with the knees to the chest.

adjunct [?]

supportive care

Supportive medical therapy may include volume/blood administration as needed, intravenous morphine to calm the child as needed, and bicarbonate to reverse acidosis as needed. Oxygen should be given, but care should be taken not to increase the infant's stimulation.

2nd

beta-blocker

Thought to help resolve hypercyanotic spells, but the mechanism of action is not completely clear. It is believed that it helps to decrease the infundibular obstruction by decreasing the heart rate, prolonging diastolic filling, and decreasing contractility. [17]

May be initiated in patients with TOF with pulmonary stenosis if manoeuvres such as knee-to-chest positioning or fluid bolus have not resolved the hypercyanotic spell.

Propranolol has been used in the past in the outpatient setting of an infant with spells to delay surgery. An infant with a single spell is considered an indication for urgent surgical repair, [23] but propranolol may be used until surgery can be arranged. Primary Options esmolol : 100-500 micrograms/kg intravenous bolus initially, followed by 50-500 micrograms/kg/min infusion More OR

Treatment Patient group hypercyanotic spells line 1st Treatmenthide all

manoeuvres to increase systemic venous return

Infant should be kept calm and manoeuvres tried to increase the amount of blood exiting the right ventricle through the pulmonary vasculature instead of to the aorta.

Infant should be held in the parent's arms and positioned with the knees to the chest.

adjunct [?]

supportive care

Supportive medical therapy may include volume/blood administration as needed, intravenous morphine to calm the child as needed, and bicarbonate to reverse acidosis as needed. Oxygen should be given, but care should be taken not to increase the infant's stimulation.

2nd

beta-blocker

Thought to help resolve hypercyanotic spells, but the mechanism of action is not completely clear. It is believed that it helps to decrease the infundibular obstruction by decreasing the heart rate, prolonging diastolic filling, and decreasing contractility. [17]

May be initiated in patients with TOF with pulmonary stenosis if manoeuvres such as knee-to-chest positioning or fluid bolus have not resolved the hypercyanotic spell.

Propranolol has been used in the past in the outpatient setting of an infant with spells to delay surgery. An infant with a single spell is considered an indication for urgent surgical repair, [23] but propranolol may be used until surgery can be arranged. Primary Options esmolol : 100-500 micrograms/kg intravenous bolus initially, followed by 50-500 micrograms/kg/min infusion More OR

Treatment Patient group hypercyanotic spells line 1st Treatmenthide all

manoeuvres to increase systemic venous return

Infant should be kept calm and manoeuvres tried to increase the amount of blood exiting the right ventricle through the pulmonary vasculature instead of to the aorta.

Infant should be held in the parent's arms and positioned with the knees to the chest.

adjunct [?]

supportive care

Supportive medical therapy may include volume/blood administration as needed, intravenous morphine to calm the child as needed, and bicarbonate to reverse acidosis as needed. Oxygen should be given, but care should be taken not to increase the infant's stimulation.

2nd

beta-blocker

Thought to help resolve hypercyanotic spells, but the mechanism of action is not completely clear. It is believed that it helps to decrease the infundibular obstruction by decreasing the heart rate, prolonging diastolic filling, and decreasing contractility. [17]

May be initiated in patients with TOF with pulmonary stenosis if manoeuvres such as knee-to-chest positioning or fluid bolus have not resolved the hypercyanotic spell.

Propranolol has been used in the past in the outpatient setting of an infant with spells to delay surgery. An infant with a single spell is considered an indication for urgent surgical repair, [23] but propranolol may be used until surgery can be arranged. Primary Options esmolol : 100-500 micrograms/kg intravenous bolus initially, followed by 50-500 micrograms/kg/min infusion More OR

Treatment Patient group hypercyanotic spells line 1st Treatmenthide all

manoeuvres to increase systemic venous return

Infant should be kept calm and manoeuvres tried to increase the amount of blood exiting the right ventricle through the pulmonary vasculature instead of to the aorta.

Infant should be held in the parent's arms and positioned with the knees to the chest.

adjunct [?]

supportive care

Supportive medical therapy may include volume/blood administration as needed, intravenous morphine to calm the child as needed, and bicarbonate to reverse acidosis as needed. Oxygen should be given, but care should be taken not to increase the infant's stimulation.

2nd

beta-blocker

Thought to help resolve hypercyanotic spells, but the mechanism of action is not completely clear. It is believed that it helps to decrease the infundibular obstruction by decreasing the heart rate, prolonging diastolic filling, and decreasing contractility. [17]

May be initiated in patients with TOF with pulmonary stenosis if manoeuvres such as knee-to-chest positioning or fluid bolus have not resolved the hypercyanotic spell.

Propranolol has been used in the past in the outpatient setting of an infant with spells to delay surgery. An infant with a single spell is considered an indication for urgent surgical repair, [23] but propranolol may be used until surgery can be arranged. Primary Options esmolol : 100-500 micrograms/kg intravenous bolus initially, followed by 50-500 micrograms/kg/min infusion More OR

Treatment Patient group hypercyanotic spells line 1st Treatmenthide all

manoeuvres to increase systemic venous return

Infant should be kept calm and manoeuvres tried to increase the amount of blood exiting the right ventricle through the pulmonary vasculature instead of to the aorta.

Infant should be held in the parent's arms and positioned with the knees to the chest.

adjunct [?]

supportive care

Supportive medical therapy may include volume/blood administration as needed, intravenous morphine to calm the child as needed, and bicarbonate to reverse acidosis as needed. Oxygen should be given, but care should be taken not to increase the infant's stimulation.

2nd

beta-blocker

Thought to help resolve hypercyanotic spells, but the mechanism of action is not completely clear. It is believed that it helps to decrease the infundibular obstruction by decreasing the heart rate, prolonging diastolic filling, and decreasing contractility. [17]

May be initiated in patients with TOF with pulmonary stenosis if manoeuvres such as knee-to-chest positioning or fluid bolus have not resolved the hypercyanotic spell.

Propranolol has been used in the past in the outpatient setting of an infant with spells to delay surgery. An infant with a single spell is considered an indication for urgent surgical repair, [23] but propranolol may be used until surgery can be arranged. Primary Options esmolol : 100-500 micrograms/kg intravenous bolus initially, followed by 50-500 micrograms/kg/min infusion More OR

Treatment Patient group hypercyanotic spells line 1st Treatmenthide all

manoeuvres to increase systemic venous return

Infant should be kept calm and manoeuvres tried to increase the amount of blood exiting the right ventricle through the pulmonary vasculature instead of to the aorta.

Infant should be held in the parent's arms and positioned with the knees to the chest.

adjunct [?]

supportive care

Supportive medical therapy may include volume/blood administration as needed, intravenous morphine to calm the child as needed, and bicarbonate to reverse acidosis as needed. Oxygen should be given, but care should be taken not to increase the infant's stimulation.

2nd

beta-blocker

Thought to help resolve hypercyanotic spells, but the mechanism of action is not completely clear. It is believed that it helps to decrease the infundibular obstruction by decreasing the heart rate, prolonging diastolic filling, and decreasing contractility. [17]

May be initiated in patients with TOF with pulmonary stenosis if manoeuvres such as knee-to-chest positioning or fluid bolus have not resolved the hypercyanotic spell.

Propranolol has been used in the past in the outpatient setting of an infant with spells to delay surgery. An infant with a single spell is considered an indication for urgent surgical repair, [23] but propranolol may be used until surgery can be arranged. Primary Options esmolol : 100-500 micrograms/kg intravenous bolus initially, followed by 50-500 micrograms/kg/min infusion More OR

Treatment Patient group hypercyanotic spells line 1st Treatmenthide all

manoeuvres to increase systemic venous return

Infant should be kept calm and manoeuvres tried to increase the amount of blood exiting the right ventricle through the pulmonary vasculature instead of to the aorta.

Infant should be held in the parent's arms and positioned with the knees to the chest.

adjunct [?]

supportive care

Supportive medical therapy may include volume/blood administration as needed, intravenous morphine to calm the child as needed, and bicarbonate to reverse acidosis as needed. Oxygen should be given, but care should be taken not to increase the infant's stimulation.

2nd

beta-blocker

Thought to help resolve hypercyanotic spells, but the mechanism of action is not completely clear. It is believed that it helps to decrease the infundibular obstruction by decreasing the heart rate, prolonging diastolic filling, and decreasing contractility. [17]

May be initiated in patients with TOF with pulmonary stenosis if manoeuvres such as knee-to-chest positioning or fluid bolus have not resolved the hypercyanotic spell.

Propranolol has been used in the past in the outpatient setting of an infant with spells to delay surgery. An infant with a single spell is considered an indication for urgent surgical repair, [23] but propranolol may be used until surgery can be arranged. Primary Options esmolol : 100-500 micrograms/kg intravenous bolus initially, followed by 50-500 micrograms/kg/min infusion More OR

Treatment Patient group hypercyanotic spells line 1st Treatmenthide all

manoeuvres to increase systemic venous return

Infant should be kept calm and manoeuvres tried to increase the amount of blood exiting the right ventricle through the pulmonary vasculature instead of to the aorta.

Infant should be held in the parent's arms and positioned with the knees to the chest.

adjunct [?]

supportive care

Supportive medical therapy may include volume/blood administration as needed, intravenous morphine to calm the child as needed, and bicarbonate to reverse acidosis as needed. Oxygen should be given, but care should be taken not to increase the infant's stimulation.

2nd

beta-blocker

Thought to help resolve hypercyanotic spells, but the mechanism of action is not completely clear. It is believed that it helps to decrease the infundibular obstruction by decreasing the heart rate, prolonging diastolic filling, and decreasing contractility. [17]

May be initiated in patients with TOF with pulmonary stenosis if manoeuvres such as knee-to-chest positioning or fluid bolus have not resolved the hypercyanotic spell.

Propranolol has been used in the past in the outpatient setting of an infant with spells to delay surgery. An infant with a single spell is considered an indication for urgent surgical repair, [23] but propranolol may be used until surgery can be arranged. Primary Options esmolol : 100-500 micrograms/kg intravenous bolus initially, followed by 50-500 micrograms/kg/min infusion More OR

Treatment Patient group hypercyanotic spells line 1st Treatmenthide all

manoeuvres to increase systemic venous return

Infant should be kept calm and manoeuvres tried to increase the amount of blood exiting the right ventricle through the pulmonary vasculature instead of to the aorta.

Infant should be held in the parent's arms and positioned with the knees to the chest.

adjunct [?]

supportive care

Supportive medical therapy may include volume/blood administration as needed, intravenous morphine to calm the child as needed, and bicarbonate to reverse acidosis as needed. Oxygen should be given, but care should be taken not to increase the infant's stimulation.

2nd

beta-blocker

Thought to help resolve hypercyanotic spells, but the mechanism of action is not completely clear. It is believed that it helps to decrease the infundibular obstruction by decreasing the heart rate, prolonging diastolic filling, and decreasing contractility. [17]

May be initiated in patients with TOF with pulmonary stenosis if manoeuvres such as knee-to-chest positioning or fluid bolus have not resolved the hypercyanotic spell.

Propranolol has been used in the past in the outpatient setting of an infant with spells to delay surgery. An infant with a single spell is considered an indication for urgent surgical repair, [23] but propranolol may be used until surgery can be arranged. Primary Options esmolol : 100-500 micrograms/kg intravenous bolus initially, followed by 50-500 micrograms/kg/min infusion More OR

Last

Treatment approach
All pre-operative patients with TOF need careful follow-up with their primary physician and a paediatric cardiologist. Attention to their weight gain is mandatory. Progression of cyanosis should be noted. Parents should be counselled to alert their physicians should they notice the onset of hypercyanotic spells, as these would be an indication for urgent surgical intervention.

Management of hypercyanotic (tet) spells

An infant with TOF and hypercyanotic spells is a medical emergency because a prolonged hypercyanotic spell can result in brain ischaemia and death. [17] Management of a hypercyanotic spell consists of calming the child and manoeuvres to increase the amount of blood exiting the right ventricle to the pulmonary vasculature instead of to the aorta. Often the best place for the infant is in the mother's arms. Initially, the infant should be positioned with the knees to the chest as this will increase venous return to the heart (preload) and systemic afterload. Oxygen should be given, but care should be taken not to increase the infant's stimulation. If the infant is still profoundly cyanotic, acidosis will result. If these measures are not successful, medical therapy includes:
Adjunctive supportive measures such as volume repletion, reversal of acidosis, or morphine Beta-blockers to relax the contracted infundibulum and to allow more time for right ventricular filling, improving pulmonary blood flow Phenylephrine as a final medical option to increase systemic venous resistance and force more blood to the lungs.

Neonates with severely limited pulmonary blood flow causing profound cyanosis may benefit from prostaglandins (e.g., alprostadil) to maintain the patency of the ductus arteriosus. This provides an alternative source of pulmonary blood flow while the infant awaits surgical intervention. If prostaglandins are needed to maintain ductal patency, surgical intervention will be needed in the neonatal period.

If all medical therapies fail and the infant remains severely cyanotic, an emergency Blalock-Taussig shunt (a small GORE-TEX tube placed from a systemic artery to the pulmonary arteries to increase pulmonary blood flow) or extra-corporeal membrane oxygenation may be necessary. [22] Propranolol has been used in the past in the outpatient setting of an infant with spells to delay surgery. An infant with a single spell is considered an indication for urgent surgical repair, [23]but propranolol may be used until surgery can be arranged.

Surgical management
The definitive treatment for TOF is complete surgical repair. Over the last 10 to 15 years, there has been a trend towards neonatal repair of both cyanotic and acyanotic infants with TOF, but this is often determined by their pulmonary anatomy. [23] In acyanotic patients without spells, repair is usually undertaken in the first year of life and has a very low morbidity and mortality. [24] [25] Patients with TOF with severe pulmonary stenosis may undergo complete neonatal repair at some institutions or alternatively may undergo a BlalockTaussig shunt in the newborn period before complete repair. [22] [25] Excellent results with complete repair in the neonatal period have been reported, [26] with one cohort reporting a 5-year survival rate of 93% in patients with TOF who underwent complete repair as a neonate. [23] Patients who undergo repair in childhood should be counselled about the possible need for future surgical or transcatheter interventions. In particular, if relief of pulmonary obstruction requires a transannular patch, there is likely to be a significant amount of postoperative pulmonary regurgitation. There is an increasing awareness of the need to monitor patients for progressive dilation of the right ventricle secondary to long-standing pulmonary regurgitation, and the need for pulmonary valve replacement in this setting. Typically MRI measurements are used to quantify the pulmonary regurgitation and right ventricular size. One group has suggested that valve replacement before the right ventricular diastolic volume reaches 160 mL/m^2 allows for normalisation of right ventricular volumes. [27] Another group found that no patient with a right ventricular volume >170 mL/m^2 had normalisation of their right ventricular volumes after valve replacement. [28] While there is no consensus on the exact criteria for the timing of replacement of the pulmonary valve, one review suggests using the following criteria:[29]
Repaired TOF or similar physiology with moderate or severe pulmonary regurgitation (regurgitation fraction 25% measured by cardiovascular magnetic resonance imaging) and 2 or more of the following criteria:

o o o o o o

Right ventricular end-diastolic volume index 160 mL/m^2 (Z score >5) Right ventricular end-systolic volume index 70 mL/m^2 Left ventricular end-diastolic volume index 65 mL/m^2 Right ventricular ejection fraction 45% Right ventricular outflow tract aneurysm Clinical criteria: exercise intolerance, symptoms and signs of heart failure, cardiac medications, syncope, or sustained ventricular tachycardia.

Other haemodynamically significant lesions such as moderate or severe tricuspid regurgitation, residual atrial or ventricular septal defects, and severe aortic regurgitation may trigger referral for surgery in patients with moderate or severe pulmonary regurgitation. In the absence of the 6 criteria above, pulmonary valve replacement should be considered on a case-by-case basis.

Due to a higher risk of adverse clinical outcomes in patients who underwent TOF repair at age 3 years, pulmonary valve replacement may be indicated sooner and in the presence of less severe right ventricular dilation and dysfunction.

Infective endocarditis prophylaxis

This is recommended pre-operatively and should be used for 6 months after repair. Those patients who have residual defects at the site or adjacent to the site of a prosthetic patch or prosthetic device should continue to receive lifelong infective endocarditis prophylaxis whenever undergoing an invasive procedure (e.g., dental procedures, or procedures on the respiratory tract or infected skin, skin structures, or musculoskeletal tissue). [30]

Emerging treatments
Percutaneous pulmonary valve In the complete surgical repair of TOF, there is dilation or reconstruction of the stenotic portion of the right ventricular outflow tract (RVOT). The repair of the RVOT depends on the anatomy of the pulmonary valve and artery, and infants frequently develop progressive pulmonary regurgitation (as in the case with transannular patch augmentation or progressive pulmonary obstruction) as they grow. It is not uncommon for TOF patients to need pulmonary valve replacement throughout their lives, necessitating multiple by-pass surgeries. In the last decade, advancements have been made in the development of a transcatheter valved stent, and outcomes of 58 patients

undergoing percutaneous pulmonary valve implantation in Europe have recently been reported. [31] In this series, there were 3 major procedural complications and 7 minor complications with no mortality. [31]

Monitoring
Patients with surgically corrected TOF should be routinely assessed by a paediatric cardiologist. Joint guidelines from the American College of Cardiology and American Heart Association recommend that adult patients with repaired TOF should have at least annual follow-up with a cardiologist who has expertise in adults with congenital heart disease (CHD). They further advise that echocardiographic examinations and/or MRIs performed on these patients be performed by staff with expertise in adult CHD. [41] Guidelines from the European Society of Cardiology also suggest that adults with TOF be followed by cardiologists with expertise in congenital heart disease. [42] Echocardiograms to evaluate right ventricular (RV) function and the progression of pulmonary stenosis or regurgitation should be performed every 1 to 5 years. The timing is patient specific, and patients with significant progressive RV dilation, pulmonary stenosis or regurgitation, or symptoms may require at least yearly scans. Cardiac MRI or CT is an additional tool increasingly used to evaluate RV volume and function. MRI allows for accurate 3-dimensional measurements of RV volumes and is increasingly being used to determine timing of surgical pulmonary valve replacement. [42]

Patient Instructions
Patients should be aware that corrective repair does not mean a cure and further surgical intervention may be required. Patients need to be informed that having CHD increases the risk of their own children having CHD, and that pre-conception genetic testing and fetal echocardiography may be indicated.

Complications
Complicationhide all

cyanotic spells see our comprehensive coverage of Assessment of cyanosis in the newborn Hypercyanotic spells present with dyspnoea and severe cyanosis.

They result from contraction of the infundibular musculature creating increased right ventricular outflow tract obstruction and increased shunting of de-oxygenated blood from the right ventricle across the ventricular septal defect (VSD) to the systemic circulation. Treatment of hypercyanotic spells is targeted towards relaxing the pulmonary obstruction and increasing systemic vascular resistance to increase the blood flow through the pulmonary circulation. paradoxical emboli Preoperatively, patients with TOF have a VSD, which allows communication of venous blood in the right heart with the systemic circulation. Normally, a thrombus in the venous circulation that embolises will be trapped in the pulmonary vasculature. However, the VSD provides communication such that a thrombus can paradoxically cross the VSD and lodge in an arterial bed, causing ischaemia. Patients with known communication between the right and left cardiac chambers should have precautions taken when using intravenous catheters, as an air bubble in the intravenous tubing can embolise to the systemic circulation, causing end-organ ischaemia. Prophylactic anticoagulation is not commonly given to patients with TOF. However, the possibility of venous thrombi should be carefully considered and treated aggressively if identified. progressive pulmonary regurgitation and right ventricular failure see our comprehensive coverage of Pulmonary regurgitation A single-centre study of 100 consecutive adult patients with TOF repaired in childhood who underwent cardiac MRI found poor right ventricular and left ventricular systolic function to be independent risk factors for impaired clinical status. [40] ventricular arrhythmias see our comprehensive coverage of Non-sustained ventricular tachycardias While short-term results of surgical repair are good, the long-term results are limited by the development of arrhythmias. A retrospective analysis of 66 patients undergoing surgical repair of TOF between 1960 and 1993 found 28% to have no ventricular arrhythmias, 51% to have minor ventricular arrhythmias, 10.5% to have non-sustained ventricular tachycardia, and 9% to have sustained ventricular tachycardia or ventricular fibrillation. [37] Serial ECGs have been performed to monitor the width of the QRS complex as an arrhythmogenic risk factor. [38]If the QRS complex is noted to widen, further electrophysiological evaluation may be necessary. Some experts recommend periodic Holter monitors to screen for arrhythmia. Exercise testing is used by some clinicians. atrial arrhythmias In the past decade, atrial arrhythmias have been increasingly recognised as a common long-term morbidity in

repaired TOF. A retrospective study of adults with TOF repaired in childhood found that one third of patients had documented atrial arrhythmias, including sinus node dysfunction, atrial fibrillation, atrial flutter, and supraventricular tachycardia. [39] sudden cardiac death see our comprehensive coverage of Cardiac arrest Sudden cardiac death from ventricular tachycardia or ventricular fibrillation is the most common cardiac cause of death in patients with repaired TOF. [33] It is believed to be associated with progressive right ventricular failure. Ten years after surgery, the risk of sudden cardiac death increased from 0.06% per year to 0.2% per year. [34] A retrospective analysis of patients undergoing surgical repair in 1 state in the US between 1958 and 1996 found that 11 out of 445 patients with repaired TOF died of sudden cardiac death. [35] A retrospective study of 793 adult patients who underwent surgical repair for TOF in childhood at 6 different institutions found moderate to severe pulmonary regurgitation in 100% of patients who died of sudden cardiac death. [36] congestive heart failure see our comprehensive coverage of Congestive heart failure, acute exacerbation Some patients with minimal pulmonary stenosis may have symptoms of heart failure. Furosemide is the most commonly used diuretic for symptoms of congestive heart disease. Care should be taken, as over-diuresis may precipitate hypercyanotic spells. CHF is not a commonly recognised long-term complication of surgically repaired TOF. A single-centre study of 100 adults with TOF surgically repaired in childhood found 48% to be in New York Heart Association (NYHA) class I, 40% in class II, and 12% in class III. [40]

Prognosis
Historically, the survival for untreated TOF was quite poor. In a report of 1000 patients with congenital heart disease, the average life expectancy for TOF was 12 years. [32] Current surgical outcomes are excellent with recent cohorts following complete repair showing survival rates of 100% at 1 month, 93% at 1 year, and 93% at 5 years. Freedom from reoperation rates were 100% at 1 month, 89% at 1 year, and 58% at 5 years. [23] Once the patient has undergone complete surgical repair, the prognosis and long-term outcome are related to anatomy and type of surgical repair, as well as any associated conditions. One study of survivors of the first year after surgical repair showed actuarial survival rates of 97% at 10 years, 94% at 20 years, 89% at 30 years, and 85% at 36 years. [33] Common long-term complications are related to arrhythmias, progressive pulmonary outflow obstruction, and progressive pulmonary regurgitation resulting in right ventricular failure. Reasons for re-operation are based on progressive pulmonary obstruction and pulmonary regurgitation.