Received: 15 August 2018 | Revised: 30 November 2018 | Accepted: 24 December 2018

DOI: 10.1111/pan.13569

EDUCATIONAL REVIEW

Tetralogy of Fallot: Everything you wanted to know but were

afraid to ask

Lisa Wise‐Faberowski1 | Ritu Asija2 | Doff B. McElhinney3

1
Department of Anesthesiology, Stanford
University, Palo Alto, California Summary
2
Department of Pediatrics, Stanford Tetralogy of Fallot (TOF) has four anatomic features: right ventricular hypertrophy
University, Palo Alto, California
(RVH), ventriculoseptal defect (VSD), overriding aorta and right ventricular outflow
3
Department of Surgery, Stanford
University, Palo Alto, California tract obstruction (RVOT) with an occurrence of 3.9 /10,000 births. The pathophysio-
logic effects in TOF are largely determined by the degree of RVOT and not the
Correspondence
Lisa Wise‐Faberowski, Department of VSD. Intra‐operative anesthetic management is also dependent on the degree of
Anesthesiology, Stanford University, Palo RVOT obstruction and influenced by the extent of surgical RVOT repair.
Alto, CA.
Email: Lwf1212@stanford.edu
KEYWORDS
Section Editor: Philip Arnold cardiac, children, congenital heart disease, infants, neonates, surgery

1 | INTRODUCTION Nonsyndromic TOF can be associated with various genetic defects,

Tetralogy of Fallot (TOF) is the most common form of congenital cyan-
otic heart disease, occurring in approximately 4 to 5 per 100 000 live
births, and represents 7%‐10% of all congenital heart defects.1,2
Although TOF is often thought of in terms of the tetrad of anomalies
—pulmonary stenosis, ventricular septal defect (VSD), aorta overriding
the ventricular septum, and right ventricular hypertrophy—it has been
proposed that all of these features are the result of anterior malalign-
ment of the infundibular septum with the muscular septum.
are several variants of TOF as well, which manifest other abnormal
features and are discussed in the following review.
Today, most patients with TOF undergo complete repair in early
infancy or early childhood with >90% survival. Children who have
undergone palliative procedures often suffer from failure to thrive
and erythrocytosis. Left untreated, patients with TOF have a 50%, 5‐
10 year survival, with mortality related to hypoxemia, endocarditis,
brain abscesses, or cerebral vascular accident. Longevity beyond the
fourth decade of life in unrepaired or palliated TOF is rare.5,6
2 | MAIN ARTICLE
2.1 | Genetics
Tetralogy of Fallot (TOF) occurs equally in males and females. Inheri-
tance is typically sporadic, not familial, and rarely associated with
7
other anomalies. However, TOF can be nonsyndromic or syndromic.
including transcription mutations in genes such as NKX2.5 in 4%,8
and rarely TBX1 or ZFPM2,9 or polymorphisms in genes such as
MTHFR.10 Syndromes associated with TOF include Down syndrome
(trisomy 21),11 Alagille syndrome (JAG 1 mutation),12 DiGeorge or
velocardiofacial (22q11 deletion), and others.13 DiGeorge syndrome
occurs in 13% of TOF patients. Other malformation associations in
which TOF can occur with extracardiac manifestations include VAC-
3,4
There TERL association (vertebral and cardiac defects, anal atresia, trachea‐
esophageal fistula, renal and limb abnormalities) and CHARGE asso-
ciation (coloboma of the eye, heart defects, choanal atresia, genito‐
urinary or ear abnormalities).
2.2 | Anatomy
The exact embryologic process leading to TOF or its variants is
unknown. It is believed that faulty partitioning of the conotruncus
during septation and incomplete rotation resulting in two unequally
sized vessels (larger aorta and smaller pulmonary artery) results in a
conal septum that deviates far anteriorly. Thus, it is the anterior and
cephalad deviation of the infundibular septum that gives rise to the
four anatomic features that characterizes TOF.3,4
The VSD in TOF, for the most part, is single, large/unrestrictive,
subaortic, and malaligned. The distinction from double‐outlet right
ventricle (DORV) or DORV with Taussig‐Bing anomaly (subpulmonic
VSD) must be recognized. DORV is a condition with greater than

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476 | WISE‐FABEROWSKI
50% override of the aorta over the right ventricle and absence of
aortic/mitral valve continuity. Most commonly, the VSD in TOF is
perimembranous, but in some, can extend into the muscular septum,
and rarely there are multiple additional muscular defects.5
The aorta is displaced to the right and overrides the malaligned
VSD. Thus, it receives blood flow from both ventricles depending on
the degree of right ventricular outflow tract obstruction. The degree
of aortic override can vary. A right aortic arch with mirror image
branching is seen in 25% of TOF patients. Aberrant origins of the
subclavian arteries (right subclavian from the descending aorta and
left subclavian from the pulmonary artery) can also be seen.3,4 Aortic
arch and branching anomalies are more common in patients with a
chromosome 22q11 deletion, but are usually not associated with a
13
vascular ring in the setting of TOF. Coronary abnormalities can be
seen in 5%‐12% of TOF patients. Most common is a left anterior
descending artery originates from right coronary artery and crosses
the RV infundibular surface. Various other coronary anomalies can
be seen, but are less common.14 Knowledge of an aberrant left coro-
nary artery from the right coronary artery plays an important part in
the surgical approach. In these patients, a Rastelli procedure (RV to
PA conduit) is preferred as opposed to a transventricular repair.15–17
Right ventricle outflow obstruction can occur at multiple levels:
subvalvar, valvar, and/or supravalvar. Subvalvar obstruction can result
from hypertrophy of the muscular bands in the subpulmonic region
and/or from the anterior and cephalad deviation of the VSD. Valvar
obstruction can be the result of a hypoplastic annulus and/or a
bicuspid or stenotic pulmonary valve. Supravalvular narrowing of the
main pulmonary artery (sinotubular ridge), stenotic proximal branch
pulmonary arteries (left pulmonary artery at the ductal insertion),
and/or hypoplastic branch pulmonary arteries can also occur.3,4
Various other anomalies can occur in conjunction with TOF,
including atrial septal defect, anomalous pulmonary venous drainage,
a left superior vena cava and/or an interrupted inferior vena cava,
and others. Beyond this typical set of features, TOF can include
other anatomic variants such as, pulmonary atresia (PA), complete
atrioventricular (AV) canal, and absent pulmonary valve.
2.2.1 | Tetralogy of Fallot with Pulmonary Atresia
Tetralogy of Fallot with pulmonary atresia (PA) is also referred to as
PA with ventricular septal defect (PA/VSD). As with TOF, anterior
malalignment of the VSD and aortic override are present, but the
pulmonary artery architecture and intrinsic structure can have vari-
able presentation. The central pulmonary arteries can be confluent,
with normally arborizing intraparenchymal branches, with all flow
supplied by a patent ductus arteriosus. At the other end of the spec-
trum, the central pulmonary arteries can be absent entirely, with all
pulmonary blood flow supplied by major aortopulmonary collateral
arteries (MAPCAs), which can arise not just from the aorta but also
from other systemic arteries. In between these extremes, there are
many variations, including discontinuity of the central pulmonary
arteries with one lung supplied by a ductus, hypoplastic central pul-
monary arteries that arborize to all lung segments which are also
ET AL.
supplied by MAPCAs, and central pulmonary arteries that are conflu-
ent but connect to some but not all lung segments.3–5
2.2.2 | Tetralogy of Fallot with Absent Pulmonary
Valve
Tetralogy of Fallot with absent pulmonary valve syndrome is charac-
terized by dysgenesis of the pulmonary valve, annular stenosis, and
pulmonary insufficiency. In TOF with absent pulmonary valve the
main and branch pulmonary arteries are massively enlarged with
abnormal central, segmental and subsegmental branching patterns.
Airway compression and trachea/bronchomalacia are common to this
variant of TOF.3–5 Patients usually present early in the neonatal per-
iod, some within days, in respiratory distress. Intubation, prone posi-
tioning, and PEEP are often indicated in addition to early surgical
repair. Despite adequate surgical repair, many of these children con-
tinue to have residual pulmonary difficulties, which include tracheo‐
and bronchomalacia and bronchospasm.18
2.2.3 | Tetralogy of Fallot with Complete
Atrioventricular (AV) canal
Tetralogy of Fallot with a complete AV canal defect is commonly
associated with Down syndrome, and is a relatively uncommon vari-
ant of TOF.11 The combination of TOF and complete AV canal is a
more challenging anomaly. In these patients, the tricuspid valve is
often abnormal and regurgitant. The coexistence of tricuspid and
pulmonary valve abnormalities with this lesion and resultant free pul-
monary and tricuspid insufficiency after transannular patch repair
can predispose to both right ventricular volume and pressure over-
load and their consequences.
2.3 | Pathophysiology of TOF
The pathophysiology of TOF is not usually dependent on the size of
the VSD, as it is usually large and unrestrictive, although in some
cases tricuspid valve tissue can cause VSD obstruction. There is typ-
ically little flow across the unrestrictive VSD in utero, as right and
left ventricular pressures are equal. Postnatally, the direction of
blood flow is determined by the path of the least resistance, and
thus is primarily dependent on the degree of right ventricular out-
flow obstruction. Symptoms of congestive heart failure, as a result
of pulmonary overcirculation, can be seen in patients with a large
VSD and minimal obstruction to pulmonary blood flow. The left to
right flow allows for a fully saturated circulation, hence the label
“pink tet.”3–5 With moderate obstruction, a balanced circulation is
present, usually with bidirectional flow across the VSD Though
patients are mildly desaturated, with oxygen saturation ~85%‐90%,
congestive heart failure and pulmonary hypertension are absent. Sig-
nificant hypoxemia, with saturations <80% as a result of a large
right to left shunt, can be seen in patients with severe subpulmonic
obstruction. Chronic cyanosis can result in clubbing and erythro-
cythemia.
WISE‐FABEROWSKI ET AL.
Subpulmonic stenosis has fixed and variable/dynamic component
and in situations of agitation or irritability, promotes an unbalanced
circulation, with predominant right to left flow across the VSD. This
type of episode is often described as a hypercyanotic spell or a “tet
spell.” In these circumstances, cyanosis can be profound and lead to
syncope. While these “spells” are temporary, they can increase in
frequency with progressive obstruction. The exact mechanism is the-
oretical and the etiology remains unclear, but it has been suggested
that increased infundibular contractility in the presence of hyper-
trophic infundibular muscle or muscle bundles, stimulation of right
ventricular mechanoreceptors, peripheral vasodilation, tachycardia,
and hyperventilation contribute to the constellation of a “tet spell.”3–5
Treatment for “tet spells” can include supplementation with oxygen,
sedation, volume administration, and the knee‐to‐chest position. In
extreme cases, phenylephrine, 5 to 20 μg/kg may be considered.
Patients with a history of tet spells are sometimes treated with beta‐
blocking agents in an effort to prevent the cascade of events.
2.4 | Diagnosis
Prenatal ultrasound has been useful in early diagnosis of TOF and in
offering prompt postdelivery treatment in cases with duct‐dependent
pulmonary blood flow. The physical findings of a murmur and cyano-
sis in a neonate are not specific to TOF. The presence or absence of
a murmur and the quality of the murmur is dependent on the degree
of outflow tract obstruction and not on the presence/size of the
VSD. An absent murmur can indicate either the absence of obstruc-
tion or the presence of severe obstruction, in which there is little
flow. Physical signs such as a right ventricular heave, a systolic thrill,
or prominent pulses (due to diastolic runoff from a patent ductus
arteriosus or MAPCAs) may or may not always be present. Textbook
findings of a “boot‐shaped” heart on chest x‐ray and right ventricular
hypertrophy with right axis deviation on electrocardiogram can be
useful. However, in the current era, confirmation of the anatomy
with postnatal echocardiography is the gold standard for diagnosis
of TOF and associated anomalies.3–5
Echocardiography can be useful in determining the location,
extension, and number of VSDs in addition to valve attachments (tri-
cuspid and aortic) in relation to the VSD. In addition, the size, func-
tionality, and appearance of the pulmonary valve and annulus can be
assessed, along with the degree and level of right ventricular outflow
tract (RVOT) obstruction. The severity of RVOT obstruction is evalu-
ated both from its appearance and anatomic measurements, and the
pressure gradient is estimated using the peak flow velocity measured
by Doppler. The size, confluence, and proximal branching of the pul-
monary arteries, in addition to the presence or absence of a PDA or
MAPCAs can be seen. Aortic arch sidedness and branching pattern
of the head and neck vessels can usually be delineated, as can the
proximal coronary artery anatomy.14 Furthermore, determination of
an atrial septal defect, anomalous pulmonary venous return, systemic
venous anomalies, or other unusual features may be seen.
Cardiac catheterization is not routinely performed in “classic”
cases of TOF. The increasing use of noninvasive imaging such as CT
| 477
angiography or MRI as a diagnostic modality has gained acceptance
in many centers. Indications for cardiac catheterization might include
concerns for coronary anomalies or for delineation of MAPCAs in
patients with PA and diminutive or absent central pulmonary arter-
ies. A right ventricular injection will define the levels of RVOT
obstruction, as well as delineate the main and proximal branch pul-
monary arteries. The VSD is often best seen with a left ventricular
injection. An aortic root injection will define the coronary and arch
anatomy with selective injection in the presence of MAPCAs. Thera-
peutic interventions in selected cases of unrepaired TOF can include
balloon pulmonary valvuloplasty and occasionally RVOT stenting.15,17
Regardless, transcatheter approaches may incur the risk of initiating
a hypercyanotic spell and be considered with caution in these
patients.
2.5 | Management
The management of patients with TOF varies. Some centers offer a
palliative transcatheter (balloon dilation of the RVOT with/without
stent placement or alternatively a PDA stent with/without balloon
dilation of the RVOT) approach15,17 or a palliative (systemic to pul-
monary artery shunt) surgical approach. Indications for such palliative
approaches may include unfavorable anatomy (coronary abnormali-
ties, multiple VSDs, or poorly defined/absent branch pulmonary
arteries), limited ability for adequate postoperative management or
surgical preference. The transcatheter approach does not require a
sternotomy or cardiopulmonary bypass (CPB). Though a systemic to
pulmonary artery shunt does not require CPB, it subjects the patient
to a sternotomy or throacotomy. Both of these approaches are pal-
liative and must ultimately be followed by full surgical repair.17
The objective of surgical palliation is to provide adequate pul-
monary blood flow and to enable not only patient growth but
growth of the pulmonary artery system. The Potts (side‐to‐side anas-
tomosis of the left pulmonary artery to the descending aorta) and
the Waterston (ascending aorta to the right pulmonary artery) shunts
were initially used for this purpose but are no longer performed. The
“classic” Blalock‐Taussig (end to side anastomosis of the subclavian
artery to the right pulmonary artery) was used in the past, but was
replaced by the “modified” Blalock‐Taussig (BT) shunt. In the modi-
fied BT shunt, an interposition graft (usually gortex) is placed
between the subclavian artery and the ipsilateral branch pulmonary
artery. The modified BT shunt allows greater control of pulmonary
blood flow and is less difficult to take down compared to the “clas-
sic” Blalock‐Taussig, Potts, or Waterston shunts.
Palliative shunt placement poses a risk of recurrent laryngeal and
phrenic nerve injury. Shunt thrombosis can be life threatening and an
imbalance in shunt flow, inadequate or excessive, can lead to cyanosis,
failure to thrive, or congestive heart failure. Ultimate repair can be
complicated by distortion of the pulmonary artery by the shunt, and
the presence of a previous sternotomy and resultant scarring can
make dissection more complicated and risky at the time of repair.17
Most centers encourage elective complete repair between 2 and
4 months of age in patients with acyanotic physiology.17 In patients
478 | WISE‐FABEROWSKI
with cyanotic physiology, earlier complete repair in the neonatal per-
iod is performed in the United States. In the United Kingdom, TOF
repair at less than 31 days of age is not a common procedure.
Patients with mild/moderate desaturation will be medically managed
until around 4‐6 months then undergo primary repair. Palliation has
probably become more popular due to greater use of endovascular
techniques. Surgery for truly “pink” TOF's would be guided by their
symptoms.
Surgical repair is performed using median sternotomy and CPB
with normothermia or moderate hypothermia based on surgeon pref-
erence. Some institutions also use deep hypothermic arrest. If a
modified Blalock‐Taussig shunt is present, it is usually ligated and
divided during cooling. After aortic cross‐clamp, cardioplegic arrest,
and topical cooling, a right atriotomy and a longitudinal pulmonary
arteriotomy are performed to access the RVOT and the pulmonary
valve. In some cases, a right ventriculotomy is performed with exten-
sion into the infundibulum and pulmonary valve annulus, if hypoplas-
tic, the VSD is closed with a patch (eg, pericardium or synthetic
patch material) either through the atriotomy and the tricuspid valve,
or through a RVOT incision. Care is taken to avoid the bundle of
HIS with VSD closure. Several measures can be used to alleviate
RVOT obstruction, including infundibular muscle resection, pul-
monary valvotomy/valvectomy, placing a right ventricular outflow
tract patch that may or may not extend across the pulmonary valve
annulus and patch augmentation of the main pulmonary artery.19 In
some instances, remnants of ductal tissue may promote left pul-
monary artery stenosis and should be considered during the repair.
A VSD closure with RV/PA conduit may be the preferred proce-
dure in patients with severe hypoplasia or atresia of the right ven-
tricular outflow tract or anomalous origin of the left anterior
descending coronary artery from the right coronary artery. After
patch closure of the VSD, a cryopreserved homograft or other type
of valved conduit is placed between the right ventricle and the main
pulmonary artery to reconstruct the RVOT.
Diminished right ventricular compliance may prompt some sur-
geons to leave or create a small atrial septal defect as a postopera-
tive pop off that may later close spontaneously. Though potentially
creating transient cyanosis, it allows off loading of a poorly function-
ing right ventricle while preserving left ventricular filling and cardiac
output. However, a sizable residual VSD, 3‐4 mm by echocardio-
graphic evaluation is not well‐tolerated and should be addressed.20
Residual RVOT obstruction in the immediate postoperative period is
for the most part tolerated, but can pose difficulties later after
repair. RVOT gradients by echocardiography always have to be inter-
preted in light of transvalvar flow, blood pressure, and other factors.
A direct RV pressure measurement less than ½ systemic pressure
provides some reassurance of an insignificant gradient. Although a
threshold numerical value for a “safe” gradient is not known, the risk
of pulmonary regurgitation and arrhythmia with further muscle bun-
21
dle resection must be considered. Bifasicular block can occur in
8%‐12% of patients and complete block in 3%‐5%. Junctional ectopic
tachycardia (JET) can occur in 15%‐20% of TOF patients in the early
22,23
postoperative period.
ET AL.
2.6 | Anesthetic considerations
The amount of right ventricular flow tract obstruction can influence
anesthetic induction and intraoperative course.24 Hypercyanotic spells
may occur during prolonged fasting and some centers advocate place-
ment of an intravenous line. This would allow for continuous hydration
or fluid bolus to increase preload and lessen the degree of right ven-
tricular obstruction. With the objective of decreasing contractility
(minimizing obstruction) and increasing afterload (increasing left to
right shunt) therefore increasing blood flow through the pulmonary
circulation (decreasing right to left shunt) to alleviate cyanosis,24 beta‐
blockers, phenylephrine, deepened sedation and/or muscle relaxation
may be required for treatment of hypercyanotic spells.
Aberrancy of the subclavian artery can influence radial arterial
line placement and this information should be reviewed preopera-
tively. Airway considerations include an anteriorly located trachea in
22q11 deletion.18 In absent pulmonary valve syndrome tracheal
compression causing either tracheomalacia or complete obstruction
from the enlarged pulmonary arteries must be considered. Placement
of a TEE probe in patients with absent pulmonary valve and in
patients with ductal dependent pulmonary blood flow should be con-
sidered with extreme caution.
Poor right ventricular compliance, residual VSD, and arrhythmias
may complicate the early postoperative period. The hypertrophied
right ventricle can be noncompliant as a result of difficulties in
achieving adequate myocardial protection during aortic cross‐clamp,
muscle resection, and the placement of a large VSD patch. Further-
more, RV hypertrophy will itself lead to diastolic dysfunction and a
small RV cavity. Formation of a transannular patch leads to cutting
of the ventricular muscle fibers and replacement with a noncontrac-
tile patch on the RV free wall. All can contribute to pulmonary valve
insufficiency, discoordinated RV contraction, which may further be
exacerbated by new bundle branch block or arrhythmia. The use of
beta‐blockers, avoidance of beta agonists (maintain pressure with
use of fluid and vasopressors if needed) have been advocated by
some, while others have questioned the liberal approach to fluid
loading after TOF repair. Thus, there is some debate about manage-
ment of apparent, right ventricular dysfunction following TOF repair,
with often quite opposite approaches being advocated.
Though all patients may have RV compromise in the postopera-
tive period, this does not appear to cause a clinical problem in the
majority and even when it does it will, in most cases, recover after a
few days. Severe or persistent RV dysfunction should lead to prompt
detailed investigation to exclude residual surgically treatable prob-
lems. Hypoxemia, rarely, is a sign of respiratory failure and a residual
VSD (closure is difficult due to muscular hypertrophy) is more
likely.20 The VSD is large and its subaortic position poses the risk of
heart block and potential arrhythmia. Most common is junctional
ectopic tachycardia for which dexmedetomidine infusion has been
successfully used while also providing sedation or administer amio-
dorone,25 along with conservative measures such as cooling and
paralysis in symptomatic patients.23 Early extubation, to improve
preload and RV filling, is a desirable postoperative goal.
WISE‐FABEROWSKI ET AL.
3 | TETRALOGY OF FALLOT (TOF) WITH
MAJOR AORTOPULMONARY COLLATERALS
(MAPCAS)
The final portion of this manuscript will describe a unique subtype
of TOF, TOF with MAPCAs. The variability in disease presentation
and the heterogeneity of the anatomy in these patients create a
challenge in management.26 Depending on the institution, the
27
approach can be variable: do nothing, a staged and/or palliative
approach,28,29 or unifocalization with complete repair (VSD closure
and right ventricle‐to‐pulmonary artery conduit). The latter proce-
dure has been performed in over 500 patients at our institution over
26,30
the past 17 years. We will focus on our management approach
to these patients, unifocalization with complete repair.
3.1 | Anatomy
In TOF with MAPCAs, PA is complete or near complete and 20%‐
25% of patients do not have a main or confluent central branch pul-
monary arteries. If the central pulmonary arteries are present and
confluent, they are usually hypoplastic with an abnormal arborization
pattern. Hypoplasia is the result of reduced flow, as the central pul-
monary arteries, rather than receiving the normal anterograde flow,
are fed retrograde through MAPCAs that connect to the pulmonary
artery branches within the lungs. Blood supply to the lung segments
is classified as single‐supply (supplied by MAPCAs or a ductus arte-
riosus only) or dual‐supply (MAPCAs connect to the native pul-
monary artery system to supply the territory). Patients with TOF and
MAPCAs can have anywhere from 1 to 9 or more MAPCAs. Most
MAPCAs arise from the descending thoracic aorta, but they can also
originate from the brachiocephalic or coronary artery branches. They
usually run posteriorly in the chest and can cause impingement on
the airway31,32 or run posterior to or through the esophagus. The
heterogeneity of arborization precludes the use of a discrete classifi-
cation system to describe MAPCA anatomy.
3.2 | Physiology
Although the variability in the anatomy and nonuniformity of perfu-
sion to the various lung segments makes it difficult to discuss the
anatomy in simple standardized terms, the physiology is more
straightforward.26,30 Most patients present in early infancy with a
relatively balanced ratio of pulmonary to systemic blood flow (Qp:
Qs). However, ~10%‐15% of patients have too little pulmonary
blood flow and a similar percentage have too much to maintain clini-
cal stability without concerted medical management. The oxygen sat-
uration, although an indicator of balanced or unbalanced pulmonary
to systemic perfusion, may not reflect the complexity of the lesion
or be an adequate indicator of disease progression. As some pul-
monary segments become less perfused, stenotic, or atretic over
time, others can develop pulmonary vascular obstructive disease due
to long‐standing high pressure and flow.
| 479
3.3 | Diagnosis
The intracardiac anatomy in TOF with MAPCAs is relatively uniform
and can be assessed by echocardiography. However, the true
heterogeneity of the pulmonary vasculature is best assessed with CT
angiography (to address airway involvement) and with cardiac
catheterization to define the location and supply (dual, single or
ghost) of the vessels to individual lung segments.
3.4 | Surgical repair
Historically, and at some institutions today, unifocalization is staged,
one lung at a time, and performed through a lateral thoracotomy,
requiring single‐lung ventilation. However, our approach is via med-
ian sternotomy.33 The objectives for the management of these
patients at our center include34:
1. Unifocalization of blood supply to all pulmonary segments, including
native pulmonary arteries and MAPCAs, to maximize incorporation
of native vascular tissue and cross‐sectional area while preserving
growth potential and minimizing total pulmonary resistance.35
2. To achieve complete biventricular repair with closure of the VSD
and placement of a valved RV to PA conduit with a right ventric-
ular systolic pressure less than half systemic. In some cases, clo-
sure of the VSD is determined on the basis of an intraoperative
flow study. The flow study uses a dedicated circuit off the CPB
machine to increase flow incrementally across the newly unifocal-
ized vascular tree. Eventually, approximately 125% of a normal
cardiac output is achieved in the flow study and pulmonary
artery pressures are then measured directly by the surgeon. If
the mean central pulmonary artery pressure is <25 mmHg, RV:
Aortic pressure <0.4, the VSD is closed.36
3. The preference is to perform complete unifocalization in infants
greater than 3 months of age. However, surgery in the neonatal
period (15%) is indicated in the following situations35:
i Unilateral lung supply by a ductus arteriosus or hemi‐truncus
(ascending aortic origin of a branch pulmonary artery) with the
contralateral lung supplied by MAPCAs.
ii Hypoplastic native pulmonary arteries with normal arborization
(ie, all MAPCAs are dual‐supply), in which case a neonatal aor-
topulmonary window is performed, followed later in infancy,
by complete repair.
iii Profound overcirculation creating failure to thrive.
iv Profound hypoxia due to low pulmonary blood flow.
Once surgical candidacy is determined, the preference is to per-
form as much of the surgery as possible prior to CPB in an effort to
minimize the amount of bleeding and reduce the duration of CPB.
Because the objective is full unifocalization, CPB times are long,
averaging around 250 minutes, with an overall case duration of
approximately 930 minutes.30
480 | WISE‐FABEROWSKI ET AL.

We have anesthetized over 500 patients at our institution, many

3.5 | Anesthetic management during surgery for
of whom have undergone a single‐stage complete repair with VSD
TOF with MAPCAs
closure. Vigilance in anesthetic management is a key component to
Most critical to the anesthetic assessment is an estimate of overall the outcomes of these patients and to maintain a low perioperative
pulmonary to systemic blood flow. Patients are categorized as having mortality rate (1.7%).30
high, low, or balanced pulmonary blood flow. In our series of over
500 patients, approximately half have balanced pulmonary and sys-
temic blood flow while approximately 30% have pulmonary flow that 4 | SUMMARY
exceeds systemic flow and the remaining 15%‐20% have low pul-
Tetralogy of Fallot (TOF) has four anatomic features: right ventricular
monary blood flow. Patients with either high or low pulmonary flow
hypertrophy (RVH), ventriculoseptal defect (VSD), overriding aorta,
pose more difficulties with anesthetic management.37 Approximately,
and right ventricular outflow tract obstruction (RVOT) with an occur-
11% of patients, in our experience, have concern for abnormal air-
rence of 3.9 /10 000 births. The pathophysiologic effects in TOF are
way anatomy, many of whom have a chromosome 22q11 deletion largely determined by the degree of RVOT and not the VSD. Intra-
and undergo prerepair bronchoscopy. Roughly 3% of patients are a
operative anesthetic management is also dependent on the degree
known difficult intubation.32 of RVOT obstruction and influenced by the extent of surgical RVOT
Anesthesiologist preferences vary, but it is common in our prac-
repair.
tice to place a radial arterial line, a central venous line, and two good However, in the extreme variant, TOF with MAPCAs, RVOT
peripheral intravenous lines. In patients undergoing re‐sternotomy,
obstruction is rare and Qp: Qs largely influences anesthetic manage-
large bore venous access is often necessary. Intravenous access can
ment. In TOF with MAPCAs, the intracardiac anatomy is straightfor-
be difficult, as the majority of patients are young, often malnour-
ward but the heterogeneity of the pulmonary vasculature and need
ished, and may have undergone IV placement (with several attempts)
for extensive dissection and repair presents many anesthetic chal-
in the cardiac catheterization lab a few days prior to surgery, reduc- lenges.
ing the number of potential access sites.37
As stated earlier, the surgical preference is to perform as much
of the surgery as possible prior to heparinization and CPB. Thus, 5 | REFLECTIVE QUESTIONS
prolonged dissection and control of MAPCAs all have implications
for the amount and balance of pulmonary blood flow. In many
1. Right ventricular dysfunction after surgical repair for TOF is
patients, active management is required to achieve an appropriate
caused by (D)
balance of pulmonary and systemic blood flow. Prolonged hypox-
ia,38,39 hypercarbia,40 and metabolic acidosis39 are common prior
a Right ventricular muscle hypertrophy limits myocardial protec-
to going on bypass. Each of these alone or combined can impact
tion during aortic cross‐clamping
pulmonary vascular resistance and consequently the pulmonary
b Right ventricular muscle bundle resection can influence the
to systemic blood flow ratio. ST segment changes are frequent
potential for arrhythmia and heart block
during the prolonged dissection. In some circumstances, the
c Right ventricular muscle hypertrophy increases the risk for
administration of low dose dopamine can help in maintaining
diastolic dysfunction and the need for high filling pressures
hemodynamic stability.37
d All of the above
Dopamine 3‐5 mcg/kg/min, milrinone 0.5 mcg/kg/min, and low‐
dose epinephrine 0.03‐0.05 mcg/kg/min are our standard inotropes 2. Junctional ectopic tachycardia, the following are true, except (B)
used upon separating from CPB. Because of the amount of dissec-
tion and the extensive vascular suture lines, post‐bypass bleeding a Onset within 12‐24 hours. after repair
can be significant ~175‐240 cc/kg and transfusion requirements sub- b Occurs in 40% of TOF patients
stantial (packed red blood cells 134 ± 34 cc/kg; platelets c Heart rates above 170 bpm
25.97 ± 7.89 cc/kg; fresh frozen plasma 57.25 ± 31.73 cc/kg; cryo- d Loss of AV synchrony
precipitate 5.26 ± 2.58 mL/kg). Because of this, we have adopted
3. Which of the following is true (B)
the use of activated four factor prothrombin complex concentrate
(FEIBA)(Shire US, Inc IL) at a dose of 10 units/kg for 1‐3 doses, and
a Pathophysiology determined by the size of the VSD
intraoperative administration of anti‐fibrinolytics has also become
b Can be associated with 22qll in 30% of the patients
common practice. Based on our experience and that of others, lower
c All present with pulmonary hypertension
right ventricle to aortic pressure ratios, 0.35 (0.32‐0.4), are associ-
d Presents uniformly with cyanosis
ated with better postoperative outcome. In an effort to reduce right
ventricular pressure and stress on the newly anastomosed vessels, 4. Complete repair for TOF with MAPCAs includes: (E)
empiric nitric oxide is instituted at 20 ppm and continued for
24 hours in the intensive care unit.37 a Unifocalization of all blood supply to the lungs
WISE‐FABEROWSKI ET AL.
b Proximal and distal pulmonary artery augmentation
c Closure of the VSD
d RV to PA conduit
e All of the above
ETHICAL APPROVAL
The authors confirm that all authors contributing to this work com-
ply with the ethical standards of the relevant national guidelines.
DISCLOSURES
There are no conflicts of interest.
ORCID
Lisa Wise‐Faberowski https://orcid.org/0000-0001-5876-5311
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How to cite this article: Wise‐Faberowski L, Asija R,
McElhinney DB. Tetralogy of Fallot: Everything you wanted
to know but were afraid to ask. Pediatr Anesth. 2019;29:475–
482. https://doi.org/10.1111/pan.13569