Tetralog Fallot

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Tetralogy of FallotHighlights

SummaryOverview

BasicsDefinition

Epidemiology AetiologyPathophysiologyClassification

PreventionScreeningSecondary

DiagnosisHistory & examinationTestsDifferentialStep-by-step

CriteriaGuidelinesCase history

TreatmentDetailsStep-by-stepEmergingGuidelines

Follow UpRecommendationsComplicationsPrognosis

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History & examKey factors

hypercyanotic episodes

harsh systolic ejection murmur

cyanosis

tachypnoea

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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 detailsTreatment 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

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infective endocarditis prophylaxisTreatment 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 andcephalad 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.

DefinitionTetralogy 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]

EpidemiologyCongenital heart defects are relatively common overall. During the early1980s, an epidemiological study designed to estimate the prevalence of congenital heart disease (CHD) in the northeastern US showed theprevalence rate of CHD to be 3.7 per 1000 live births. There was a slight, butnot statistically significant, male predominance and no ethnicdifference. [2] However, a subsequent study (1999-2001) estimated theprevalence 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 incidencemay be as high as 9 per 1000 live births, with an overall increase if a first-degree relative has CHD. [4] Acyanotic defects include atrial septal defects,isolated ventricular septal defects, and coarctation of the aorta. Cyanoticdefects include TOF, total anomalous pulmonary venous return, transposition

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of great vessels, tricuspid atresia, persistent truncus arteriosus, andhypoplastic left-heart syndrome. TOF is the most common cyanoticcongenital 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 1000live births. [2] [3]

A prevalence of 3.01 per 10,000 live births was noted in a survey of TOFpatients 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 correctivesurgery. [5] However, in Malta, the birth prevalence for TOF between 1980and 1994 was 0.64 per 1000 live births, prompting speculation of a geneticpredisposition towards the condition. [6]

AetiologyLittle is known about the exact aetiology of TOF. There is most likely to beinterplay between genetic and environmental factors, but this has not beenfully defined. One study of pregnant women with a first-degree relative withcongenital heart disease (CHD) found 178 per 6640 (2.7%) pregnancies withCHD. [4] There is a well-accepted association between certain genetic defects andCHD. Patients with trisomy 21, 18, or 13 have a higher incidence of TOF thaninfants without trisomy. [7] A retrospective analysis in patients with apparentlynon-syndromic TOF found 10 out of 21 patients to have deletions of chromosome 22q11 (DiGeorge's and associated syndromes), suggesting aregion on this chromosome may harbour a TOF susceptibility gene. [8] In anearlier study comparing patients who had TOF with and without chromosome22q11 deletion, every patient with TOF and 22q11 deletion was found to havean additional conotruncal anomaly. [9] Alagille's syndrome, a syndrome withcardiovascular phenotypes ranging from mild pulmonary stenosis to TOF withsevere pulmonary obstruction, has been found to be due to mutations in theJagged1 gene. [10] Additionally, mutations in Jagged1 have been associatedwith 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 significantrole in some cases of CHD. [13] Maternal diabetes, maternalphenylketonuria, [14] and maternal ingestion of retinoic acids [15] or trimethadione [16] have all been associated with an increased risk of CHD.

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AetiologyLittle is known about the exact aetiology of TOF. There is most likely to beinterplay between genetic and environmental factors, but this has not beenfully defined. One study of pregnant women with a first-degree relative with

congenital heart disease (CHD) found 178 per 6640 (2.7%) pregnancies withCHD. [4] There is a well-accepted association between certain genetic defects andCHD. Patients with trisomy 21, 18, or 13 have a higher incidence of TOF thaninfants without trisomy. [7] A retrospective analysis in patients with apparentlynon-syndromic TOF found 10 out of 21 patients to have deletions of chromosome 22q11 (DiGeorge's and associated syndromes), suggesting aregion on this chromosome may harbour a TOF susceptibility gene. [8] In anearlier study comparing patients who had TOF with and without chromosome22q11 deletion, every patient with TOF and 22q11 deletion was found to havean additional conotruncal anomaly. [9] Alagille's syndrome, a syndrome withcardiovascular phenotypes ranging from mild pulmonary stenosis to TOF withsevere pulmonary obstruction, has been found to be due to mutations in theJagged1 gene. [10] Additionally, mutations in Jagged1 have been associatedwith 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 significantrole in some cases of CHD. [13] Maternal diabetes, maternalphenylketonuria, [14] and maternal ingestion of retinoic acids [15] or trimethadione [16] have all been associated with an increased risk of CHD.

PathophysiologyIn TOF, the pathophysiology and management are dictated by 3 specificanatomical 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.

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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.

Additional VSDs may be present and should be looked for as these may complicate the postoperative

course.

Hypercyanotic spells, or tet spells, are episodes of severe cyanosisassociated with hyperpnoea. They result from an increase in right ventricular

outflow tract obstruction causing a decrease in the pulmonary blood flow andan increase in right-to-left shunting across the VSD. The exact aetiology of hypercyanotic spells is unclear, but they are thought to be initiated byincreases in the right ventricular infundibular contractility. Hypercyanoticspells may be self-limited; however, if sustained, they can result in brainischaemia or death. [17]

ClassificationVariants of TOFThere is no standard classification for TOF, but many experts would use thefollowing 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.

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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 pulseoximetry to screen infants for structural heart disease, but its sensitivity as a

screening test has not been fully established. [18] All children with certainsyndromes such as trisomy 21 should be screened for CHD. A screeningfetal echocardiogram may be indicated in a pregnant mother who has hadother children with CHD or has CHD herself.Secondary preventionImmunisation 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 first-

degree 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 & examinationKey diagnostic factors hide 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.

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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 appearsseverely cyanotic at birth.

tachypnoea (common)

May have significant tachypnoea with severe pulmonary obstruction.Other diagnostic factors hide allshock (uncommon)

Infants with severe pulmonary obstruction or a hypercyanotic spell may present with severe

cyanosis and acidosis due to tissue hypoxia.Risk factors hide all

Weaktrisomy 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]

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Diagnostic tests1st tests to order hide allTest

pulse oximetry

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

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.

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 consider hide allTest

cardiac catheterisation

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

hypercyanotic spells.

Performed if definition of the coronary artery anatomy is not possible by echocardiogram.

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Differential diagnosis

ConditionDifferentiatingsigns/symptoms Differentiating tests

Other cyanotic congenital cardiacabnormalities

Includes single

ventricle lesions

such as hypoplastic

left heart syndrome

or tricuspid atresia.

Other possibilities

include D-

transposition,

pulmonary atresia,

anomalous

pulmonary venous

connection, truncus

arteriosus, or

Ebstein's anomaly.

These may all be

difficult todifferentiate

clinically from a

cyanotic newborn

with TOF. Most are

not specifically

associated with

other syndromes,

although this can

vary.

No change in PaO2 with hyperoxia test.

Echocardiogram can define anatomy to class

In some cases, a cardiac catheterisation may

define anatomy and physiology.

Pulmonary stenosis Usually presents in

an asymptomatic

patient with a

systolic ejection

murmur on

Echocardiogram will show presence or absen

TOF with pulmonary obstruction to different

stenosis alone.

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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.

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 VSDand may result in

pulmonary over-

circulation and heart

failure. This is

uncommon with

TOF, as the

Echocardiogram will show presence or absen

obstructive lesion to determine whether this i

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pulmonary

obstruction prevents

over-circulation.

Double outlet right ventricle withnormally related great vessels andpulmonary stenosis

Cannot bedifferentiated from

TOF on physical

examination alone.

Echocardiogram will show presence or absenand degree of aorta over-ride of the VSD to d

double outlet right ventricle.

Primary pulmonary disease On examination,

infant may be

tachypnoeic and

desaturated,

potentially requiringmechanical

ventilation.

Cardiovascular

examination is

usually normal.

Hyper-oxygenation test should show increase

administration of 100% FiO2.

CXR will show normal cardiac silhouette wi

Echocardiogram will show normal intracardi

Step-by-step diagnostic approachPatients typically present with cyanosis and/or a murmur. Echocardiographyis the definitive investigation for diagnosis of TOF and should be ordered inany newborn with a suspected diagnosis of congenital heart disease.

HistoryCertain 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 isusually noted. The degree of cyanosis may vary and can be subtle, and someclinicians advocate routine screening of all neonates with pulse oximetry. [18] Some infants may not present at birth but rather may present later withincreasing cyanosis, murmur, or hypercyanotic (tet) spells. Hypercyanoticspells may present as episodic, increasing cyanosis in a baby with TOF. Thebaby is typically crying and breathing deeply and rapidly, but may not be in

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significant respiratory distress. The typical murmur of TOF may disappear during the spell. This presentation is potentially life-threatening and requiresrapid intervention.

TOF with severe pulmonary obstruction is a more severe presentation and

may present in a newborn who appears severely cyanotic at birth. Infantswith severe pulmonary obstruction or a hypercyanotic spell may present withsevere cyanosis and acidosis due to tissue hypoxia.

Physical examinationCan vary significantly depending on the degree of pulmonary obstruction. Theinfant with mild obstruction is typically comfortable, and cyanosis may bedifficult to discover on physical examination. With moderate obstruction thecyanosis is likely to be apparent on examination and the infant is typically

comfortable. With severe obstruction the baby may have significanttachypnoea and cyanosis.

The cardiac examination typically finds an increased right ventricular (parasternal) impulse. S1 is normal and S2 is single. There is typically a 3/6harsh systolic ejection murmur, heard best at the left sternal border. Themurmur on examination represents blood flow across the pulmonary outflowand not the ventricular septal defect. The intensity of the murmur depends onthe degree of pulmonary stenosis and decreases with severe stenosis.

InvestigationsTransthoracic 2-dimensional and Doppler echocardiography is the preferredtechnique for defining the anatomical diagnosis. In the vast majority of casesno further testing is needed pre-operatively. Sedation may be judiciouslyused if the child is not co-operative with the examination.

Pre-ductal and post-ductal (right arm and either leg) pulse oximetry should beordered if there is any suspicion of a congenital cardiac malformation. [19] Ahyper-oxygenation test can be used to determine whether hypoxaemia isfrom a pulmonary or a cardiac lesion.ECG will often show evidence of right ventricular hypertrophy and may showright axis deviation beyond normal limits for age. View imageCXR is classically described as a boot-shaped heart, but most patients do nothave this finding. The presence of a right aortic arch may be noted in asubset of patients, particularly those with 22q11 deletion. [9]

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Cardiac catheterisation is usually unnecessary in diagnosing TOF and mayinduce hypercyanotic spells. [17] If there is significant concern for coronaryartery anomalies that cannot be defined echocardiographically, thencatheterisation 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 byuncomplicated spontaneous vaginal delivery is noted to have cyanosis of theoral mucosa. The baby otherwise appears comfortable. On examination,respiratory rate is 40 and pulse oximetry is 80%. A right ventricular lift ispalpated, 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 byuncomplicated spontaneous vaginal delivery is noted to have a murmur onexamination. The baby otherwise appears well. On examination, respiratoryrate 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 isheard at the left upper sternal border.

Other presentationsCyanosis occurs if severe right ventricular outflow tract obstruction forcesblood returning to the right side of the heart to be shunted right to left acrossthe ventricular septal defect (VSD) and out to the systemic circulation, by-

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passing the lungs. Hypercyanotic spells may present as episodic, increasingcyanosis in a baby with TOF. The baby is typically crying and breathingdeeply and rapidly, but may not be in significant respiratory distress. Thetypical murmur of TOF may disappear during the spell. This presentation ispotentially life-threatening and requires rapid intervention. Alternatively, a

baby may be severely cyanotic at birth.Treatment Options

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Patient group

Treatment

line Treatment hide all

hypercyanotic spells 1st 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, andbicarbonate 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 bearranged.

Primary Options

esmolol : 100-500 micrograms/kg intravenous bolus

initially, followed by 50-500 micrograms/kg/min

infusion

More

OR

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Patient group

Treatment

line Treatment hide all

hypercyanotic spells 1st 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, andbicarbonate 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 bearranged.

Primary Options

esmolol : 100-500 micrograms/kg intravenous bolus

initially, followed by 50-500 micrograms/kg/min

infusion

More

OR

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Patient group

Treatment

line Treatment hide all

hypercyanotic spells 1st 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 ca lm the child as needed, andbicarbonate 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 bearranged.

Primary Options

esmolol : 100-500 micrograms/kg intravenous bolus

initially, followed by 50-500 micrograms/kg/min

infusion

More

OR

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Patient group

Treatment

line Treatment hide all

hypercyanotic spells 1st 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, andbicarbonate 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 bearranged.

Primary Options

esmolol : 100-500 micrograms/kg intravenous bolus

initially, followed by 50-500 micrograms/kg/min

infusion

More

OR

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Patient group

Treatment

line Treatment hide all

hypercyanotic spells 1st manoeuvres to increase systemic venous return Infant should be kept calm and manoeu vres t ried to

increase the amount of blood exiting th e 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, andbicarbonate 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 bearranged.

Primary Options

esmolol : 100-500 micrograms/kg intravenous bolus

initially, followed by 50-500 micrograms/kg/min

infusion

More

OR

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Patient group

Treatment

line Treatment hide all

hypercyanotic spells 1st 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, andbicarbonate 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 bearranged.

Primary Options

esmolol : 100-500 micrograms/kg intravenous bolus

initially, followed by 50-500 micrograms/kg/min

infusion

More

OR

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Patient group

Treatment

line Treatment hide all

hypercyanotic spells 1st manoeuvres to increase systemic venous return Infant should be kept calm and manoeuvres tried to

increase the amount of blood exiting the right

ventricle th rough the pulmonary vasculature instead

of to the a orta. 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, andbicarbonate 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 bearranged.

Primary Options

esmolol : 100-500 micrograms/kg intravenous bolus

initially, followed by 50-500 micrograms/kg/min

infusion

More

OR

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Patient group

Treatment

line Treatment hide all

hypercyanotic spells 1st 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, andbicarbonate 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 bearranged.

Primary Options

esmolol : 100-500 micrograms/kg intravenous bolus

initially, followed by 50-500 micrograms/kg/min

infusion

More

OR

7/27/2019 Tetralog Fallot

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Patient group

Treatment

line Treatment hide all

hypercyanotic spells 1st 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, andbicarbonate 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 bearranged.

Primary Options

esmolol : 100-500 micrograms/kg intravenous bolus

initially, followed by 50-500 micrograms/kg/min

infusion

More

OR

7/27/2019 Tetralog Fallot

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Patient group

Treatment

line Treatment hide all

hypercyanotic spells 1st 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, andbicarbonate 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 bearranged.

Primary Options

esmolol : 100-500 micrograms/kg intravenous bolus

initially, followed by 50-500 micrograms/kg/min

infusion

More

OR

7/27/2019 Tetralog Fallot

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Patient group

Treatment

line Treatment hide all

hypercyanotic spells 1st 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, andbicarbonate 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 bearranged.

Primary Options

esmolol : 100-500 micrograms/kg intravenous bolus

initially, followed by 50-500 micrograms/kg/min

infusion

More

OR

7/27/2019 Tetralog Fallot

27/35

Patient group

Treatment

line Treatment hide all

hypercyanotic spells 1st 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 ins tead

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, andbicarbonate 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 bearranged.

Primary Options

esmolol : 100-500 micrograms/kg intravenous bolus

initially, followed by 50-500 micrograms/kg/min

infusion

More

OR

7/27/2019 Tetralog Fallot

28/35

Patient group

Treatment

line Treatment hide a ll

hypercyanotic spells 1st manoeuvres to increase system ic ve nous return Infant should be kept calm and manoeuvres tried to

increase the amount of blo od exiting the right

ventricle through the pulm onary vasculature instead

of to the aorta. Infant should be held in the parent's arms and

positione d with the knees to the chest.

adjunct

[?]

supportive care Supportive medical therapy may include

volume/bl ood administration as needed, intravenous

morphine to calm the child as needed, andbicarbonate to reverse acidosis as needed. Oxygen

should be given, but care should be taken not to

increase the infant's stimulation.

2nd beta-bl ocker 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 bearranged.

Primary Options

esmolol : 100-500 micrograms/kg intravenous bolus

initially, followed by 50-500 micrograms/kg/min

infusion

More

OR

7/27/2019 Tetralog Fallot

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Last

Treatment approach All pre-operative patients with TOF need careful follow-up with their primaryphysician and a paediatric cardiologist. Attention to their weight gain is

mandatory. Progression of cyanosis should be noted. Parents should becounselled to alert their physicians should they notice the onset of hypercyanotic spells, as these would be an indication for urgent surgicalintervention.

Management of hypercyanotic (tet) spells An infant with TOF and hypercyanotic spells is a medical emergency becausea 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 thepulmonary vasculature instead of to the aorta. Often the best place for theinfant is in the mother's arms. Initially, the infant should be positioned with theknees 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'sstimulation. 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 profoundcyanosis may benefit from prostaglandins (e.g., alprostadil) to maintain thepatency 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 interventionwill be needed in the neonatal period.

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If all medical therapies fail and the infant remains severely cyanotic, anemergency Blalock-Taussig shunt (a small GORE-TEX tube placed from asystemic 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 anindication for urgent surgical repair, [23] but propranolol may be used untilsurgery can be arranged.

Surgical managementThe definitive treatment for TOF is complete surgical repair. Over the last 10to 15 years, there has been a trend towards neonatal repair of both cyanoticand 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 firstyear of life and has a very low morbidity and mortality. [24] [25] Patients with TOF with severe pulmonary stenosis may undergo completeneonatal repair at some institutions or alternatively may undergo a Blalock-Taussig shunt in the newborn period before complete repair. [22] [25] Excellent results with complete repair in the neonatal period have beenreported, [26] with one cohort reporting a 5-year survival rate of 93% inpatients 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 tobe a significant amount of postoperative pulmonary regurgitation. There is anincreasing awareness of the need to monitor patients for progressive dilationof the right ventricle secondary to long-standing pulmonary regurgitation, andthe need for pulmonary valve replacement in this setting. Typically MRImeasurements are used to quantify the pulmonary regurgitation and rightventricular size. One group has suggested that valve replacement before theright ventricular diastolic volume reaches 160 mL/m^2 allows for

normalisation of right ventricular volumes. [27] Another group found that nopatient with a right ventricular volume >170 mL/m^2 had normalisation of their right ventricular volumes after valve replacement. [28] While there is noconsensus on the exact criteria for the timing of replacement of thepulmonary 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:

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o Right ventricular end-diastolic volume index 160 mL/m^2 (Z score >5)

o Right ventricular end-systolic volume index 70 mL/m^2

o Left ventricular end-diastolic volume index 65 mL/m^2

o Right ventricular ejection fraction 45%

o Right ventricular outflow tract aneurysm

o 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,