Seminar

Tetralogy of Fallot
Christian Apitz, Gary D Webb, Andrew N Redington
Lancet 2009; 374: 146271
Published Online
August 17, 2009
DOI:10.1016/S01406736(09)60657-7
Division of Cardiology, Labatt
Family Heart Centre, Hospital
for Sick Children, Toronto, ON,
Canada (C Apitz MD,
Prof A N Redington MD); and
Philadelphia Adult Congenital
Heart Center, Hospital of the
University of Pennsylvania,
Philadelphia, PA, USA
(Prof G D Webb MD)
Correspondence to:
Prof Andrew N Redington,
Division of Cardiology, Labatt
Family Heart Centre, Hospital for
Sick Children, 555 University
Avenue Toronto, ON M5G 1X8,
Canada
andrew.redington@sickkids.ca

Tetralogy of Fallot is the most common form of cyanotic congenital heart disease, and one of the rst to be successfully
repaired by congenital heart surgeons. Since the rst procedures in the 1950s, advances in the diagnosis, perioperative
and surgical treatment, and postoperative care have been such that almost all those born with tetralogy of Fallot can
now expect to survive to adulthood. The startling improvement in outcomes for babies born with congenital heart
disease in generaland for those with tetralogy of Fallot in particularis one of the success stories of modern
medicine. Indeed, in many countries adults with tetralogy of Fallot outnumber children. Consequently, new issues
have emerged, ranging from hitherto unpredicted medical complications to issues with training for caregivers and
resource allocation for this population of survivors. Therefore, evolution of treatment, recognition of late complications,
research on disease mechanisms and therapieswith feedback to changes in care of aected children born
nowadaysare templates on which the timely discussion of organisation of care of those aected by congenital heart
diseases from the fetus to the elderly can be based. Here, we focus on new developments in the understanding of the
causes, diagnosis, early treatment, and late outcomes of tetralogy of Fallot, emphasising the continuum of
multidisciplinary care that is necessary for best possible lifelong treatment of the 1% of the population born with
congenital heart diseases.

Introduction
Tetralogy of Fallot was rst described by Niels Stenson
in 1671, although its precise anatomical description was
elegantly illustrated by William Hunter at St Georges
Hospital Medical School in London in 1784: the
passage from the right ventricle into the pulmonary
artery, which should have admitted a nger, was not so
wide as a goose quill; and there was a hole in the partition
of the two ventricles, large enough to pass the thumb
from one to the other. The greatest part of the blood in
the right ventricle was driven with that of the left ventricle
into the aorta, or great artery, and so lost all the advantage
which it ought to have had from breathing.1,2 His
description of a large outlet ventricular septal defect
together with subpulmonary and pulmonary valve
stenosis, and its resulting physiology, was rened by
Etienne-Louis Fallot in 1888 in his description of
Lanatomie pathologique de la maladie bleu, but the term
tetralogy of Fallot (a tetrad of (i) ventricular septal defect
with (ii) over-riding of the aorta, (iii) right ventricular
outow obstruction, and (iv) right ventricular hypertrophy) is attributed to Canadian Maude Abbott in 1924.
We now regard tetralogy as a family of diseases, all
characterised by a similar intracardiac anatomy (gure 1),

Search strategy and selection criteria

We searched PubMed with the search term tetralogy of
Fallot. We mainly selected publications from the past 5 years,
but did not exclude commonly referenced and highly
regarded older publications. We also searched the reference
lists of articles identied by this search strategy and selected
those we judged relevant. Several reviews or book chapters
were included because they provide comprehensive
overviews that are beyond the scope of this Seminar. The
reference list has been modied during the peer-review
process on the basis of comments from reviewers.

1462

but highly variable in terms of pulmonary artery anatomy,

associated abnormalities, and outcomes. Here, we focus
on the most common form, in which the heart has
normal segmental anatomical structure, the right
ventricular outow tract is patent at birth, and no other
major intracardiac abnormalities, such as atrioventricular
septal defect, exist.
About 35% of all infants born with a congenital heart
disease have tetralogy of Fallot, corresponding to one in
3600 or 028 every 1000 livebirths, with males and females
being aected equally.3 Its precise cause is unknown, as for
most congenital heart diseases. Most cases seem sporadic,
although the risk of recurrence in siblings is about 3% if
there are no other aected rst-degree relatives.
However, a strong and increasingly recognised genetic
substrate to tetralogy can aect the outcome after
surgical repair.4 One study showed that a microdeletion
of the q11 region of chromosome 22 was present in up to
25% of patients, suggesting that investigation with
uorescent in-situ hybridisation for such a deletion
should be undertaken in all patients when diagnosed.5
Indeed, tetralogy is closely associated with, and
frequently diagnosed in those with, overt Di George
syndrome or velocardiofacial syndrome, both of which
have 22q11 deletions.6,7 In those without an overt
syndrome, the prevalence of deletions has been estimated
at 6%.8 22q11 deletion is becoming increasingly important
not only because of its cardiac and syndromic
associations, but also because of its association with
late-onset neuropsychiatric disorders. Bassett and
colleagues9 showed that adults with 22q11.2 deletion
syndrome have a rate of schizophrenia of almost 25%;
about 1% of patients with schizophrenia therefore have
an associated 22q11.2 deletion.10

Pathophysiology
The ventricular septal defect is almost always large and
non-restrictive in tetralogy of Fallot, ensuring that the
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Seminar

pressure is equal in the two ventricles. Consequently, the

loud systolic murmur typical in aected infants originates
from the dynamic narrowing of the right ventricular
outow tract. The direction and magnitude of ow
through the defect depends on the severity of the
obstruction of the right ventricular outow tract. If
obstruction to right ventricular outow is severe, or if
there is atresia, a large right-to-left shunt with low
pulmonary blood ow and severe cyanosis requiring
intervention at birth are present.11
However, most patients have adequate pulmonary
blood ow at birth but develop increasing cyanosis during
the rst few weeks and months of life. In countries with
well developed paediatric cardiac services, severe
cyanosis, recurrent hypercyanotic spells, squatting, and
other consequences of severely reduced pulmonary blood
ow are nowadays rare because diagnosis is seldom
delayed and infants undergo palliative procedures, or
frequently complete repair within the rst few days,
weeks, or months of life. Temporary treatment with
propranolol, which decreases right ventricular
hypercontractility and heart rate and increases systemic
vascular resistance, is sometimes used to reduce the
incidence of hypercyanotic spells before surgery.

Diagnosis
Similar to many complex congenital heart diseases,
tetralogy of Fallot is frequently diagnosed during fetal life
(gure 2). For those with severely obstructed pulmonary
blood ow, fetal diagnosis allows better planning of
perinatal management and facilitates early prostaglandin
therapy to maintain ductal patency, thus avoiding
life-threatening cyanosis in the early newborn period.
Nonetheless, most children present with the condition
after birth. Although an experienced paediatrician or
cardiologist usually suspects the diagnosis clinically,
transthoracic cross-sectional echocardiography provides
a comprehensive description of the intracardiac anatomy
(gure 3). With the exception of patients with major
aortopulmonary collateral arteries and rare cases in
whom echocardiographic assessment is incomplete, any
other diagnostic investigations (eg, cardiac catheterisation)
are now rarely done before palliative or corrective
surgery.

Management
Before the advent of surgical intervention, about 50% of
patients with tetralogy of Fallot died in the rst few years
of life, and it was unusual for a patient to survive longer
than 30 years.12 Nowadays, almost all those born with this
disease in all its variants can expect to survive surgical
correction and reach adult life. Since the rst reported
intracardiac repair of tetralogy in 1955,13 the age of
patients receiving primary corrective surgery has
gradually decreased, with some units advocating surgery
at diagnosis, even within the rst few days of life. Most
centres prefer to operate on children aged 36 months,
www.thelancet.com Vol 374 October 24, 2009

reserving earlier open-heart surgery for those presenting

with severe cyanosis or hypercyanotic spells. Some
centres continue to oer surgical palliation by
construction of a systemic-to-pulmonary arterial shunt,
balloon dilation, or placement of a stent in the right
ventricular outow, in neonates and young infants,
thereby deferring intracardiac repair.14
Potential disadvantages of this staged approach include
long-lasting pressure overload of the right ventricle and
persistent cyanosis. Long-term hypoxaemia contributes
to cardiomyocytic degeneration and interstitial brosis,
which have been implicated in myocardial dysfunction
and ventricular arrhythmias.15 However, the opponents of
early palliation point to the frequent need for aggressive
outow tract procedures, the adverse eects of early
bypass surgery on the neonatal brain,16 the often
complicated and lengthy postoperative recovery in small
infants, and implications of all these factors for late
adverse outcomes.
The best age for repair has been previously discussed
in a review17 of results obtained at the Hospital for Sick
Children in Toronto (Canada) during the transitional
period towards a policy of primary complete repair.
Between 1993 and 1998, 227 consecutive children
underwent complete repair, with the incidence of
previous palliation with a systemic-to-pulmonary artery
shunt falling from 38% to 0% during that time. The
overall mortality was only 26%, but this also fell with
transition to primary repair, becoming 0% in 199698.
Nonetheless, primary repair in babies younger than
3 months of age has been associated with longer intensive
care and hospital stay than in those older than 3 months,
suggesting that the optimum age of elective repair is
36 months of age.
Whenever done, reparative surgery should ideally
result in complete closure of the ventricular septal

Aorta

Pulmonary
trunk

VSD
Right
atrium
Right
ventricle

Figure 1: Morphological features of tetralogy of Fallot

The subpulmonary narrowing (arrow) is formed between the malaligned
muscular outlet septum (asterisk), which is deviated anterocephalad relative to
the limbs of the septomarginal trabeculation and the hypertrophied
septoparietal trabeculations. There is a large ventricular septal defect with
over-riding of the aorta, which is partly committed to the hypertrophied right
ventricle. Note the dysplastic and stenotic pulmonary valve. VSD=ventricular
septal defect. Image kindly provided by Robert H Anderson.

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Complications

The early postoperative period

Outlet
septum

Aorta

Right
ventricle

Right
ventricle

Pulmonary
trunk
Left
ventricle

Figure 2: Prenatal diagnosis of tetralogy of Fallot

The long-axis view of the fetal echocardiogram (A) shows a large ventricular septal defect with over-riding of the
aorta. The typical anterocephalad deviation of the outlet septum is seen (B), causing obstruction to the ow into
the pulmonary trunk. Image kindly provided by Edgar Jaeggi.

defect, preservation of right ventricular form and

function, with an unobstructed right ventricular outow
tract incorporating a competent pulmonary valve.
Unfortunately, the nature of the subpulmonary
obstruction rarely makes this possible. Surgical repair
has made consistent progress over the past 50 years.
Early techniques included repair of the ventricular septal
defect via a large right ventriculotomy and extensive
resection of the right ventricular outow musculature
and pulmonary valve leaets. Improvements of the
transatrialtranspulmonary approach have beneted
early and middle-term outcomes by avoiding right
ventriculotomy and its associated scarring and
dysfunction.18 Furthermore, in the past 20 years a shift
from the need for complete relief of obstruction19
towards a policy to preserve the pulmonary valve, even
at the expense of a modest residual stenosis, has
occurred.20 This shift might keep adverse late eects of
pulmonary incompetence to a minimum and retain the
integrity of the outow tract, avoiding late aneurysmal
dilation. Changes in the management of children born
with tetralogy of Fallot in the 21st century are being
guided by results of surgery done in the second half of
the 20th century.
Indeed, the evolution of complications in adult life,
their careful cataloguing, and the new understanding of
their mechanisms provide ample evidence that follow-up
of patients with congenital heart disease needs to be a
continuous process, not only because of the burgeoning
needs of adult survivors but also as a responsibility to the
children requiring treatment today. Understanding the
causes of complications during the early postoperative
period and the late postoperative period after repair of
tetralogy of Fallot has led to the description of unique
pathophysiological changes and development of novel
treatments that have implications for cardiovascular
diseases as a whole, and are important for the progress of
research on adult congenital heart disease as its own
subspecialty.
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Most children undergoing complete repair have an

uncomplicated postoperative recovery and are discharged
within a week of surgery. For a minority, the early
postoperative course is complicated by a low cardiac
output syndrome despite an apparently adequate repair
with preserved biventricular systolic function. Echocardiographic doppler studies in these patients often
show evidence of what is known as restrictive right
ventricular physiology.21 Occurrence of restrictive
physiology is related to the degree of myocardial damage
that takes place during repair.
Chaturvedi and colleagues22 showed that the development of restrictive physiology was associated with
signicantly increased troponin concentrations on
release of the aortic cross clamp and throughout the
early postoperative period. Interestingly, it does not
seem to be related to age at operation, but is more
common on follow-up of patients in whom a transannular patch had been inserted across the ventriculopulmonary junction.23,24 Early postoperative restrictive
physiology requires a longer duration of inotropic
support, longer stay in an intermediate care station,
and higher doses of diuretics.25 However, it is a transient
phenomenon, usually resolving within 72 h, although
reappearance in the later postoperative follow-up period
can occur.23,26

Pulmonary incompetence
Not long ago, residual pulmonary incompetence was
regarded as an inevitable, but unimportant, late sequel of
repair. Much emphasis was placed on the need for
complete relief of obstruction, often at the expense of a
freely regurgitant and ever-dilating outow tract.
Although data for the relation between residual outow
tract obstruction and early postoperative mortality were
concerning,19 they are not anymore. Indeed, during the
past decade the degree of residual pulmonary
incompetence has been related to the most severe adverse
outcomes of progressive exercise intolerance, right heart
failure, ventricular arrhythmia, and sudden death.
The misguided assertions of investigators that
pulmonary incompetence was an unimportant late
outcome of tetralogy can be understood when one
considers the time course of the eects of postoperative
pulmonary regurgitation. The problems of tetralogy
occur decades after repair and might be incompletely
dened because of the expected decades of further
survival, even for the earliest cohorts of survivors of
surgical repair. This prolonged time course also illustrates
the need for continuous and vigilant follow-up of all
patients in whom intracardiac repairs have been done in
childhood. Even so, there was circumstantial evidence
more than two decades ago that the late outcome of
tetralogy might be adversely aected by the degree of
pulmonary incompetence.
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Seminar

C
RPA
AO

RV
IVS

PT
RV

LV

AO

RV

LA
AO PT
RPA

LPA

Figure 3: Postnatal diagnosis of tetralogy of Fallot by transthoracic echocardiography

(A) The parasternal long-axis view shows the aortic valve over-riding the crest of the ventricular septum (IVS) and severe hypertrophy of the right ventricular
myocardium. (B) Subcostal right oblique view of the obstruction of the subpulmonary infundibulum due to the anterocephalad deviation of the malaligned outlet
septum (long arrow) and the abnormal arrangement of the septoparietal trabeculations (short arrows). (C) Parasternal short-axis view shows small peripheral pulmonary
arteries (RPA and LPA) with supravalvular narrowing of the pulmonary trunk (PT). LV=left ventricle. RV=right ventricle. AO=over-riding aorta. LA=left atrium.

In 1984, Shimazaki and colleagues27 showed that

symptom-free survival was decreased in patients with
isolated (ie, no other major cardiac lesions) pulmonary
incompetence. Interestingly, almost no complication was
seen during the rst 30 years of life, but thereafter a
rapidly progressive condition of right heart failure,
exercise intolerance, and death evolved, all of which
resonate with late problems of tetralogy. In the 1970s and
1980s, right heart dysfunction was known to be more
likely if an outow tract patch was needed at the time of
repair,28 as was the fact that exercise dysfunction was
related to the cardiothoracic ratio (as a surrogate of right
heart dilation) on chest radiograph.29 Nonetheless, only
in the past 10 years has direct quantication of pulmonary
regurgitation by the gold standard cardiac magnetic
resonance been possible (gure 4).
A clear relation between the amount of pulmonary
regurgitation and right ventricular dilation was
established with one of the rst quantitative methods
videodensitometrydescribed in 1981 by Falliner and
colleagues.30 In 1988, we described a technique to
quantify pulmonary regurgitation from right ventricular
pressurevolume loops measured with angiograms,31 or
with a conductance catheter technique.32 We showed a
correlation between the volume of pulmonary
regurgitation during isovolumic relaxation, and right
ventricular volumes and exercise dysfunction.33 In
another study,32 we used the uniquely dynamic nature of
conductance catheter recordings to show the relation
between increased right ventricular afterload and the
degree of pulmonary regurgitation. These data strongly
support the notion that substantial branch pulmonary
artery stenosis, especially in the setting of free
pulmonary regurgitation, should be treated aggressively
by balloon dilation with or without implantation of an
endoluminal stent.
Although restrictive physiology, characterised by
antegrade diastolic ow in the pulmonary artery
throughout the respiratory cycle, is associated with
reduced cardiac output and slowed early postoperative
recovery in children,21 its presence as a primary
phenomenon in adults is mainly benecial. In the rst
study of restrictive physiology, in adults 1535 years
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after repair, Gatzoulis and colleagues34 showed that

those with a restrictive right ventricle had a smaller
cardiothoracic ratio on chest radiograph and better
exercise performance (both of which might be entirely
normal) than those without restrictive physiology. This
is because the poorly compliant right ventricle prevents
adverse remodelling (dilation) of the right ventricle that
occurs in response to pulmonary regurgitation when
diastolic function is less abnormal. In turn, in many
studies the amount of pulmonary regurgitation has
been directly related to right heart dilatation and exercise
performance. Although these ndings have been
conrmed by others,35,36 additional studies, mainly using
magnetic resonance, have failed to show a consistent
relation between restrictive physiology, as evidenced by
antegrade diastolic ow, and either right ventricular
volumes or exercise performance.37,38
Another important observation in the study by
Gatzoulis and colleagues34 was that QRS duration on
the electrocardiogram in those with restrictive
physiology was shorter than in those without restrictive
physiology. We also showed a relation between the
duration of the QRS and both right ventricular volumes
and propensity to symptomatic arrhythmia and sudden
death.39 We proposed the term mechanoelectrical
interaction to describe the relation between the degree
and type of right ventricular remodelling and its
electrophysiological properties, and showed a threshold
for QRS prolongation of 180 ms, and the occurrence of
symptomatic ventricular tachycardia and sudden death
in a single centre analysis. This phenomenon has been
conrmed by us and others,4042 albeit with dierent
thresholds of QRS duration, and improved methods of
describing the relation between mechanical and
electrical function.
However, the most comprehensive assessment comes
from a multicentre study43 that showed in 793 patients
from ve centres that pulmonary regurgitation was the
most important haemodynamic determinant of
symptomatic arrhythmia. Furthermore, not only was
absolute duration of QRS an important predictor, but
also rate of change of duration (>3 ms per year over the
10-year assessment period) was strongly associated with
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poor outcomes. Ventricular dysrhythmia is not the only

problem that characterises the late electrophysiological
outcome of these patients. Although often less dramatic
in terms of haemodynamic sequelae, atrial arrhythmias
are almost equally as frequent.4345
Although attention has been focused on the right
ventricle, there is emerging awareness of the eect of
biventricular dysfunction on late outcomes. The right
ventricle is anatomically integrated with the left
ventricle through subepicardial bundles of aggregated
myocytes that run from the free wall of the right
ventricle to the anterior wall of the left ventricle.
Moreover, the ventricles share the septum and are
enclosed in the same pericardial cavity. Interaction of
the two ventricles results in alterations of both diastolic
and systolic function.46 Experimental studies have
shown that part of the external mechanical work
generated by the right ventricle is a direct consequence
of left ventricular contraction or contraction of shared
myocytes,47 and conversely that dilation of the right
ventricle undermines left ventricular systolic performance.48,49 Therefore, a strong correlation between
right and left ventricular ejection fractions exists in
patients after repair of tetralogy of Fallot.50 Furthermore,
those with substantial coexisting left ventricular
dysfunction have a high risk of sudden death late after
repair.51 The mechanisms for this interaction are
incompletely understood but might in part be related to
increasing dys-synchrony between contraction of the
two ventricles. Indeed, DAndrea and colleagues52
showed that patients with the longest delay between
onset of contraction of the two ventricles had worse
exercise performance and a high incidence of ventricular
arrhythmia.
Although pacing of the right ventricle might improve
the intraventricular dys-synchrony of right ventricular
contraction,53 biventricular resynchronisation might be
valuable in postoperative tetralogy patients with overt
interventricular dys-synchrony. We reported extraordinary
functional improvement after biventricular pacing under
these circumstances.54
B

1000

LV
RV

Average ow (mL/min)

800
PT

600

SFF

400
200
0
200

1 2 3 4 5 6 7 8 9 10 11 12 13141516171819

400

PR

600
800

Phase number

Figure 4: Magnetic resonance imaging in a patient with tetralogy of Fallot late after surgical correction
(A) Greatly dilated right ventricle (RV) and pulmonary trunk (PT) and (B) corresponding ow prole in the right
ventricular outow tract measured with phase-contrast imaging. Note that the pathological ow prole of
pulmonary regurgitation (PR) is about 40% of the systolic forward ow (SFF). LV=left ventricle.

1466

Thus, follow-up of adults and teenagers late after repair

of tetralogy of Fallot focuses on the assessment of the
degree of pulmonary regurgitation, its secondary eects
on ventricular remodelling, and risk stratication for
arrhythmia and sudden death. Having almost ignored
the possibility of needing pulmonary valve replacement
in the past, the assessment of need and optimum timing
of pulmonary valve implantation is one of the present hot
topics in this research area.

Timing and eects of pulmonary valve replacement

Pulmonary regurgitation as an important determinant
of many late complications of early repair set the scene
for various important studies reporting the eectiveness,
or otherwise, of surgical pulmonary valve replacement.
Although most would agree that those with new onset
symptomatic sustained ventricular tachycardia and
those with overt symptoms of exercise intolerance or
right heart failure are almost all candidates for surgery,
many more potential candidates who do not full such
criteria exist.
In 2000, Therrien and colleagues55 reported the eects
of pulmonary valve replacement in 25 consecutive
patients attending the Toronto congenital cardiac centre
for adults. The investigators concluded that operations
had taken place too late. In these adults with grossly
dilated ventricles, pulmonary valve replacement did not
have any eect on right ventricular volumes or ejection
fraction. A subsequent study56 from the same group but
in younger patients with lower degree of right ventricular
dilation suggested a threshold for adequate reverse
remodelling, measured by cardiac magnetic resonance,
of 170 mL/m for end-diastolic volume and 85 mL/m
for end-systolic volume. Similar results, but with
somewhat dierent thresholds, have been obtained by
other groups.57,58 Recovery of function is less likely to
happen above a certain degree of right ventricular
dilation.
However, many questions remain unanswered. For
example, what should we recommend to asymptomatic
patients with a borderline-sized right ventricle?
Although at low risk, surgery is not entirely favourable
and long-term viability of implanted valves is
inconsistent. What is the role for formal exercise testing
in the timing of surgery? The lack of a relation between
symptoms and measured performance is one of the
most pervasive dilemmas in the eld of adult congenital
heart disease, but the usefulness of formal exercise
testing remains to be dened. And nally, is there a
threshold above which surgery is too risky or futile? One
of the reasons why these questions remain mainly
unanswered is that too little is known about functional
responses to surgery. Exercise performance might
improve by valve replacement and seems unrelated to
the degree of ventricular remodelling,5961 but there are
no denitive data on which to base preoperative
recommendations and decision making.
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Percutaneous pulmonary valve replacement

Development of percutaneous approaches to valve
disease is one of the most exciting areas of research and
clinical innovation in cardiovascular research. The main
development has been that of transcatheter pulmonary
valve replacement for the rehabilitation of conduits
between the right ventricle and pulmonary artery in
patients after surgery for tetralogy. Although rst reported
by a Danish investigator as an experimental technique in
the early 1990s,62 this approach failed to capture the
imagination of clinicians (who were then ignorant of the
adverse eects of pulmonary regurgitation) and industry
representatives (who understandably were unconvinced
of its commercial viability). 10 years later, our
understanding of the issues of pulmonary incompetence
has changed considerably. The device and technique had
been improved and, after careful experimental and
proof-of-principle studies, were introduced clinically in
2000 by Phillip Bonhoeer (gure 5).6365 His percutaneous
pulmonary valve implantation system (Melody valve,
Medtronic, USA) is composed of a bovine internal jugular
vein, with its native valve, mounted in a platinum stent.
This valved stent is advanced into the right ventricular
outow conduit via a long sheath under uoroscopic
control, and xed in place by ination of a
balloon-in-balloon system that allows precise placement.
The device has been implanted in about 700 patients
worldwide, with encouraging early to mid-term results.66,67
The largest published report includes 155 patients treated
between 2000 and 2007. There was no periprocedural
mortality and the overall late mortality has been very low;
the freedom from reoperation was in 93%, 86%, 84%,
and 70% of patients at 10, 30, 50, and 70 months,
respectively.68
Percutaneous pulmonary valve replacement is not
without unwanted eects and complications, however.
Care must be taken during deployment to avoid
compression of coronary arteries, which might be
adjacent to the right ventricular outow tract. The most
common complication is fracture of the stent,69 but this
is rarely a problem clinically. Valve failure occurs but
usually can be treated by implantation of a second valve.70
The major limitation of the technique is that it is
unsuitable for most patients with patch reconstruction of
the right ventricular outow tract and those with a grossly
dilated native outow tract. Techniques are being
developed to deal with this issue, but the development of
this technique has already fed back to size and type of
conduit being chosen for those currently needing surgery,
anticipating the use of this device, or one of the other
similar devices under development,71,72 in the future.

Pulmonary valve replacement and arrhythmia

35 years after corrective surgery, the rate of clinical
sustained ventricular tachycardia and sudden death is
estimated at 119% and 83%, respectively.43 Right
ventricular enlargement from chronic pulmonary
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Valve ring

RVOT

PT

Percutaneous
valve
PT

Figure 5: Percutaneous pulmonary valve replacement

Lateral still-frame pulmonary artery angiograms showing the pulmonary trunk (PT) and the right ventricular
outow tract (RVOT) before (A) and after (B) percutaneous pulmonary valve replacement. The patient has
previously undergone surgical placement of a valved conduit between the right ventricle and the pulmonary
artery. Note the residual obstruction within the valve leaets (arrow), just above the valve ring. There is also dense
opacication of the right ventricular outow tract due to the pulmonary regurgitation (arrowheads) in the
preimplantation image. The obstruction is completely relieved, and there is no residual regurgitation after
percutaneous implantation of a stented valve within the previous valved conduit.

regurgitation is the most common haemodynamic substrate. Pulmonary valve replacement reduces right
ventricular size, stabilises QRS duration, and can lead to
a substantial reduction in the incidence of subsequent
monomorphic ventricular tachycardia.73 The latter is
inconsistent however,74 and most would include an
additional anti-arrhythmia procedure before, during, or
after valve replacement. This additional procedure can
take the form of preoperative electrophysiological study
with transcatheter ablation, intraoperative arrhythmia
mapping and cryoablation, postoperative implantation of
an automatic debrillator, or their combination. Patients
undergoing concomitant cryotherapy or surgical ablation
for ventricular or atrial arrhythmia have the greatest
chance of remaining arrhythmia-free after operation.73,75,76
The exact indications for primary or secondary insertion
of an implantable debrillator is a topic of continuous
investigation and debate, although patients with tetralogy
of Fallot are the largest subgroup of implantable
cardioverter debrillator recipients with congenital heart
disease.77,78

Other considerations for adults with tetralogy of Fallot

Increasing specialisation of paediatric cardiologists and
lack of appropriate training of adult cardiologists have
led to inadequate follow-up for many patients, with
inevitable casualties even in the best developed health-care
systems. Many eorts have been made over the past
20 years to establish training criteria for physicians
working with adult patients with congenital heart disease
and to provide recommendations for treatment of their
most common problems.7982 However, even with an
immediate response by training bodies and a massive
injection of resources (both of which are unlikely),
inadequate care will go on for many years, or even
decades, which is a terrible indictment of medical
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planning that undermines the much-lauded success story

of care of children with congenital heart disease.
These issues are further amplied by the need for a
multidisciplinary approach in adult patients with repaired
congenital heart disease. So far, we have emphasised the
haemodynamic consequences of tetralogy repair. However, physicians caring for these patients should also be
able to advise patients on other issues arising in
adulthood, such as associated medical problems,
pregnancy and prevention, insurance and employment,
and recommendations about exercise activities. The
importance of this inclusive expert model of care is
exemplied by a recent study of outcomes in adults with
congenital heart disease undergoing cardiac surgery,83 in
which those operated on by non-dedicated congenital
cardiac surgeons were more than twice as likely to die
than those operated on by surgeons specialised in
congenital heart abnormalities. The key to a successful
programme is a focused and dedicated approach to the
care of people with congenital heart disease that spans
the age range and incorporates expertise from all
subspecialties, no matter what their traditional orientation
(paediatric or adult) might be.

Other medical complications

Aortic root dilation is an increasingly recognised feature
of late postoperative tetralogy of Fallot and can lead to
aortic regurgitation, which in turn could necessitate
surgery. Increased aortic ow attributable to right-to-left
shunting before repair and adverse intrinsic properties
of the aortic root seem to be the underlying mechanisms.84
Prevalence of aortic root dilation varies between 15% and
87% depending on the method and denition used in the
studies.85,86 Currently, no agreement exists on which
patient or at what stage aortic root surgery should be
done, although progressive aortic regurgitation and aortic
root dilation more than 55 mm are widely accepted as
criteria for aortic root surgery, especially when the
primary indication for surgery is pulmonary valve
implantation.
A growing number of patients with tetralogy of Fallot
are reaching late adulthood and become at risk of coronary
artery disease, but only a few cases have been reported
and the exact prevalence remains unknown.87,88 However,
even if rare, typical or atypical symptoms of coronary
artery disease should be investigated thoroughly. If
revascularisation surgery is required, additional residual
lesions should be carefully documented before surgery
and addressed at revascularisation, unless contraindicated
by haemodynamic instability or emergency.

Pregnancy and contraception

The risk of pregnancy in postoperative women with
tetralogy of Fallot depends on their haemodynamic
state. The risk is lowsimilar to that of the general
populationin patients with good underlying
haemodynamics. In patients with substantial residual
1468

obstruction across the right ventricular outow tract,

severe pulmonary regurgitation, tricuspid regurgitation,
and right and left ventricular dysfunction, the increased
volume load of pregnancy could lead to right heart
failure and arrhythmias.89 Because the right ventricle
might be vulnerable to the additional volume load of
pregnancy, being already compromised from previous
surgery, and because pregnancy in these patients is
associated with persisting midterm dilatation of the
subpulmonary ventricle, patients with repaired tetralogy
of Fallot and severe pulmonary regurgitation should be
considered for pulmonary valve replacement before
becoming pregnant.90,91 Vaginal delivery is the recommended mode of delivery for most women with tetralogy
of Fallot. In rare cases of right ventricular failure during
pregnancy, delivery should be considered before term,92
but this is an unusual situation. Pre-pregnancy
assessment and counselling by an appropriately trained
specialist, and delivery in a unit specialised in the care
of high-risk mothers with cardiac disease, are highly
desirable.

Exercise activities
For young adults with congenital heart disease, exercise
capacity and participation in competitive sports are
important considerations. Sport might contribute to
improved quality of life and life expectancy. Common
sporting activities can be grouped into static or dynamic,
graded as low, moderate, or high intensity. Limitations
on sport participation vary with symptoms and extent of
residual defects. Decisions need to be made on an
individual basis. Sports should be avoided by individuals
with exercise-induced life-threatening arrhythmias. In
patients with high right ventricular pressure (>50% of
systemic values), severe pulmonary regurgitation with
right ventricular dilatation, or rhythm disturbances,
restriction to low dynamic and low static sport activities
is advised (eg, hiking, golng, or bowling), although
these recommendations can vary and are likely to change
after reoperation. Full exercise activity should be
encouraged for patients with only minimal residual
abnormalities.93,94 In some patients, exercise testing is
helpful to assess eort tolerance and to dene functional
class, but no general recommendations exist.

Insurance and employment

Access to health and life insurance and full employment
are issues for many adolescents and adults with
congenital heart disease. Specic advocacy has been
lacking, especially when compared with that of other
patient groups. Ideally, the health-care teamincluding
both physicians and specialised social workersshould
work to provide appropriate advice and to nd eective
solutions for each individual.79
Although resources are limited, government-sponsored
comprehensive health-care systems of some countries
are hugely helpful to adults with congenital heart disease.
www.thelancet.com Vol 374 October 24, 2009

Seminar

In other systems, adequate health insurance, and

therefore care, might be dicult to obtain in adulthood,
partly because of uncertainties and misconceptions about
the cost of care for adults with congenital heart disease.
Actual costs of medical care seem to be low in these
patients compared with those of survivors with other
chronic diseases that begin in childhood.80
Similarly, employment opportunities for adults with
congenital heart disease are scarce. Although some
patients require special counselling and support, most
of them can sustain normal employment. Patient
advocacy groups should have a major role in raising
awareness and emphasising discrimination when it
occurs, and in shaping social policy through pressure on
governments.

10
11

12

13

14

Conclusions
The care of children with tetralogy of Fallot and their
transition to adult life has been a success of modern
medicine. Most of them now survive early repair and
have an essentially normal childhood. However, great
challenges have come with this success. One is that many
adverse outcomes only become apparent decades after
surgery. Hitherto unanticipated complications are now
increasingly understood, and their recognition is feeding
back to improve care of infants born with the disease.
This success story has also created a resource gap for
care that urgently needs attention. Paradoxically, this
societal conundrum might be the greatest threat to the
adequate care of this population.
Contributors
CA did the literature search and wrote the rst draft of the manuscript.
ANR planned, organised, and reviewed the manuscript. GDW revised
the manuscript and made important additional contributions to its
content and structure.

15

16

17

18

19

20

21

Conicts of interest
We declare that we have no conicts of interest.
Acknowledgments
CA is supported by a research scholarship of Deutsche Herzstiftung eV,
Frankfurt, Germany.
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