Seminar
Tetralogy of Fallot
Lancet 2009; 374: 1462–71
Published Online
August 17, 2009
DOI:10.1016/S0140-
6736(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
1462
Christian Apitz, Gary D Webb, Andrew N Redington
Tetralogy of Fallot is the most common form of cyanotic congenital heart disease, and one of the first to be successfully
repaired by congenital heart surgeons. Since the first 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 general—and for those with tetralogy of Fallot in particular—is 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 therapies—with feedback to changes in care of affected children born
nowadays—are templates on which the timely discussion of organisation of care of those affected 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 but highly variable in terms of pulmonary artery anatomy,
Tetralogy of Fallot was first described by Niels Stenson associated abnormalities, and outcomes. Here, we focus
in 1671, although its precise anatomical description was on the most common form, in which the heart has
elegantly illustrated by William Hunter at St Georges normal segmental anatomical structure, the right
Hospital Medical School in London in 1784: “…the ventricular outflow tract is patent at birth, and no other
passage from the right ventricle into the pulmonary major intracardiac abnormalities, such as atrioventricular
artery, which should have admitted a finger, was not so septal defect, exist.
wide as a goose quill; and there was a hole in the partition About 3·5% of all infants born with a congenital heart
of the two ventricles, large enough to pass the thumb disease have tetralogy of Fallot, corresponding to one in
from one to the other. The greatest part of the blood in 3600 or 0·28 every 1000 livebirths, with males and females
the right ventricle was driven with that of the left ventricle being affected equally.3 Its precise cause is unknown, as for
into the aorta, or great artery, and so lost all the advantage most congenital heart diseases. Most cases seem sporadic,
which it ought to have had from breathing”.1,2 His although the risk of recurrence in siblings is about 3% if
description of a large outlet ventricular septal defect there are no other affected first-degree relatives.
together with subpulmonary and pulmonary valve However, a strong and increasingly recognised genetic
stenosis, and its resulting physiology, was refined by substrate to tetralogy can affect the outcome after
Etienne-Louis Fallot in 1888 in his description of surgical repair.4 One study showed that a microdeletion
L’anatomie pathologique de la maladie bleu, but the term of the q11 region of chromosome 22 was present in up to
tetralogy of Fallot (a tetrad of (i) ventricular septal defect 25% of patients, suggesting that investigation with
with (ii) over-riding of the aorta, (iii) right ventricular fluorescent in-situ hybridisation for such a deletion
outflow obstruction, and (iv) right ventricular hyper- should be undertaken in all patients when diagnosed.5
trophy) is attributed to Canadian Maude Abbott in 1924. Indeed, tetralogy is closely associated with, and
We now regard tetralogy as a family of diseases, all frequently diagnosed in those with, overt Di George
characterised by a similar intracardiac anatomy (figure 1), 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
Search strategy and selection criteria at 6%.8 22q11 deletion is becoming increasingly important
We searched PubMed with the search term “tetralogy of not only because of its cardiac and syndromic
Fallot”. We mainly selected publications from the past 5 years, associations, but also because of its association with
but did not exclude commonly referenced and highly late-onset neuropsychiatric disorders. Bassett and
regarded older publications. We also searched the reference colleagues9 showed that adults with 22q11.2 deletion
lists of articles identified by this search strategy and selected syndrome have a rate of schizophrenia of almost 25%;
those we judged relevant. Several reviews or book chapters about 1% of patients with schizophrenia therefore have
were included because they provide comprehensive an associated 22q11.2 deletion.10
overviews that are beyond the scope of this Seminar. The
reference list has been modified during the peer-review Pathophysiology
process on the basis of comments from reviewers. The ventricular septal defect is almost always large and
non-restrictive in tetralogy of Fallot, ensuring that the
www.thelancet.com Vol 374 October 24, 2009

pressure is equal in the two ventricles. Consequently, the
loud systolic murmur typical in affected infants originates
from the dynamic narrowing of the right ventricular
outflow tract. The direction and magnitude of flow
through the defect depends on the severity of the
obstruction of the right ventricular outflow tract. If
obstruction to right ventricular outflow is severe, or if
there is atresia, a large right-to-left shunt with low
pulmonary blood flow and severe cyanosis requiring
intervention at birth are present.11
However, most patients have adequate pulmonary
blood flow at birth but develop increasing cyanosis during
the first 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
flow are nowadays rare because diagnosis is seldom
delayed and infants undergo palliative procedures, or
frequently complete repair within the first 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
(figure 2). For those with severely obstructed pulmonary
blood flow, 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
(figure 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 first 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 first 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 first few days of life. Most
centres prefer to operate on children aged 3–6 months,
www.thelancet.com Vol 374 October 24, 2009
Seminar
reserving earlier open-heart surgery for those presenting
with severe cyanosis or hypercyanotic spells. Some
centres continue to offer surgical palliation by
construction of a systemic-to-pulmonary arterial shunt,
balloon dilation, or placement of a stent in the right
ventricular outflow, 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 fibrosis,
which have been implicated in myocardial dysfunction
and ventricular arrhythmias.15 However, the opponents of
early palliation point to the frequent need for aggressive
outflow tract procedures, the adverse effects 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 2·6%, but this also fell with
transition to primary repair, becoming 0% in 1996–98.
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
3–6 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.
1463
 Seminar
A B
Outlet
Aorta septum
Right
Right ventricle
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 flow into
the pulmonary trunk. Image kindly provided by Edgar Jaeggi.
defect, preservation of right ventricular form and
function, with an unobstructed right ventricular outflow
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 outflow musculature
and pulmonary valve leaflets. Improvements of the
transatrial–transpulmonary approach have benefited
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 effects of
pulmonary incompetence to a minimum and retain the
integrity of the outflow 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.
1464
Complications
The early postoperative period
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. Echo-
cardiographic 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 devel-
opment of restrictive physiology was associated with
significantly 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 trans-
annular patch had been inserted across the ventriculo-
pulmonary 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 outflow tract.
Although data for the relation between residual outflow
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 effects of postoperative
pulmonary regurgitation. The problems of tetralogy
occur decades after repair and might be incompletely
defined 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 affected by the degree of
pulmonary incompetence.
www.thelancet.com Vol 374 October 24, 2009

A B
RPA
RV
AO
IVS
LV AO
LA
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 first 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 outflow 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 quantification of pulmonary
regurgitation by the gold standard cardiac magnetic
resonance been possible (figure 4).
A clear relation between the amount of pulmonary
regurgitation and right ventricular dilation was
established with one of the first quantitative methods—
videodensitometry—described in 1981 by Falliner and
colleagues.30 In 1988, we described a technique to
quantify pulmonary regurgitation from right ventricular
pressure–volume 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 flow 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 beneficial. In the first
study of restrictive physiology, in adults 15–35 years
www.thelancet.com Vol 374 October 24, 2009
Seminar
C
PT
RV
RV
AO PT
LPA
RPA
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 findings have been
confirmed 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 flow, 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
confirmed by us and others,40–42 albeit with different
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 five 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
1465
 Seminar
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.43–45
Although attention has been focused on the right
ventricle, there is emerging awareness of the effect 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 per-
formance.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, D’Andrea 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
A B
1000
800
PT
600
Average flow (mL/min)
SFF
400
200
LV 0 testing remains to be defined. And finally, is there a
RV
–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 flow profile in the right
ventricular outflow tract measured with phase-contrast imaging. Note that the pathological flow profile of
pulmonary regurgitation (PR) is about 40% of the systolic forward flow (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 effects
on ventricular remodelling, and risk stratification 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 effects 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 effectiveness,
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 fulfil such
criteria exist.
In 2000, Therrien and colleagues55 reported the effects
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 effect 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/m² for end-diastolic volume and 85 mL/m²
for end-systolic volume. Similar results, but with
somewhat different 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 field of adult congenital
heart disease, but the usefulness of formal exercise
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,59–61 but there are
no definitive data on which to base preoperative
recommendations and decision making.
www.thelancet.com Vol 374 October 24, 2009

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 first 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 effects 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 Bonhoeffer (figure 5).63–65 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
outflow conduit via a long sheath under fluoroscopic
control, and fixed in place by inflation 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 effects and complications, however.
Care must be taken during deployment to avoid
compression of coronary arteries, which might be
adjacent to the right ventricular outflow 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 outflow tract and those with a grossly
dilated native outflow 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 11·9% and 8·3%, respectively.43 Right
ventricular enlargement from chronic pulmonary
www.thelancet.com Vol 374 October 24, 2009
Seminar
A Valve ring B Percutaneous
valve
RVOT PT
PT
Figure 5: Percutaneous pulmonary valve replacement
Lateral still-frame pulmonary artery angiograms showing the pulmonary trunk (PT) and the right ventricular
outflow 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 leaflets (arrow), just above the valve ring. There is also dense
opacification of the right ventricular outflow 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 sub-
strate. 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 defibrillator, 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 defibrillator is a topic of continuous
investigation and debate, although patients with tetralogy
of Fallot are the largest subgroup of implantable
cardioverter defibrillator 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 efforts 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.79–82 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
1467
 Seminar
planning that undermines the much-lauded success story
of care of children with congenital heart disease.
These issues are further amplified 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. How-
ever, 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
exemplified 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 flow 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 definition 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 low—similar to that of the general
population—in patients with good underlying
haemodynamics. In patients with substantial residual
1468
obstruction across the right ventricular outflow 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 recom-
mended 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, golfing, 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 effort tolerance and to define 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. Specific advocacy has been
lacking, especially when compared with that of other
patient groups. Ideally, the health-care team—including
both physicians and specialised social workers—should
work to provide appropriate advice and to find effective
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

In other systems, adequate health insurance, and
therefore care, might be difficult 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.
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 first 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.
Conflicts of interest
We declare that we have no conflicts of interest.
Acknowledgments
CA is supported by a research scholarship of Deutsche Herzstiftung eV,
Frankfurt, Germany.
References
1 Stensen N. Embrio monstro affinis parisiis dissectum.
Acta Med Philos Hafniensa 1671–72; 1: 202–03.
2 Hunter W. Medical observations and inquiries. London: Private
publication, 1784: 417–19.
3 Shinebourne EA, Anderson RH. Fallot’s tetralogy. In: Paediatric
cardiology. Anderson RH, Baker EJ, Macartney FJ, Rigby ML,
Shinebourne EA, Tynan M, eds. 2nd edn. Toronto:
Churchill Livingstone, London; 2002: 1213–502.
4 Michielon G, Marino B, Formigari R, et al. Genetic syndromes and
outcome after surgical correction of tetralogy of Fallot.
Ann Thorac Surg 2006; 81: 968–75.
5 Webber SA, Hatchwell EI, Barber JCK, et al. Importance of
microdeletions of chromosomal region 22q11 as a cause of selected
malformations of the ventricular outflow tracts and aortic arch:
a three-year prospective study. Pediatrics 1996; 129: 26–32.
6 Goldmuntz E, Clark BJ, Mitchell LE, et al. Frequency of 22q11
deletions in patients with conotruncal defects. J Am Coll Cardiol
1998; 32: 492–98.
7 Botto LD, May K, Fernhoff PM, et al. A population-based study of
the 22q11.2 deletion: phenotype, incidence, and contribution to
major birth defects in the population. Pediatrics 2003; 112: 101–07.
www.thelancet.com Vol 374 October 24, 2009
Seminar
8 Gioli-Pereira L, Pereira AC, Bergara D, Mesquita S, Lopes AA,
Krieger JE. Frequency of 22q11.2 microdeletion in sporadic
non-syndromic tetralogy of Fallot cases. Int J Cardiol 2008;
126: 374–78.
9 Bassett AS, Chow EWC, Husted J, et al. Clinical features of
78 adults with 22q11 deletion syndrome. Am J Med Genet 2005;
138: 307–13.
10 Bassett AS, Chow EWC. Schizophrenia and 22q11.2 deletion
syndrome. Curr Psychiatr Rep 2008; 10: 148–57.
11 Sommer RJ, Hijazi ZM, Rhodes JF. Pathophysiology of congenital
heart disease in the adult. Part III: complex congenital heart
disease. Circulation 2008; 117: 1340–50.
12 Bertranou EG, Blackstone EH, Hazelrig JB, Turner ME, Kirklin JW.
Life expectancy without surgery in tetralogy of Fallot. Am J Cardiol
1978; 42: 458–66.
13 Lillehei CW, Cohen M, Warden HE, et al. Direct vision intracardiac
surgical correction of the tetralogy of Fallot, pentalogy of Fallot, and
pulmonary atresia defects; report of first ten cases. Ann Surg 1955;
142: 418–42.
14 Dohlen G, Chaturvedi RR, Benson LN, et al. Stenting of the right
ventricular outflow tract in the symptomatic infant in tetralogy of
Fallot. Heart 2009; 95: 142–47.
15 Chowdhury UK, Sathia S, Ray R, Singh R, Pradeep KK,
Venugopal P. Histopathology of the right ventricular outflow tract
and its relationship to clinical outcomes and arrhythmias in
patients with tetralogy of Fallot. J Thorac Cardiovasc Surg 2006;
132: 270–77.
16 Zeltser I, Jarvik GP, Bernbaum J, et al. Genetic factors are
important determinants of neurodevelopmental outcome after
repair of tetralogy of Fallot. J Thorac Cardiovasc Surg 2008;
135: 91–97.
17 Van Arsdell GS, Maharaj GS, Tom J, et al. What is the optimal age
for repair of tetralogy of Fallot? Circulation 2000;
102 (suppl 3): III123–29.
18 Karl TR, Sano S, Pornviliwan S, Mee RB. Tetralogy of Fallot:
favorable outcome of nonneonatal transatrial, transpulmonary
repair. Ann Thorac Surg 1992; 54: 903–07.
19 Kirklin JW, Blackstone EH, Pacifico AD, Kirklin JK, Bargeron LM Jr.
Risk factors for early and late failure after repair of tetralogy of
Fallot, and their neutralization. Thorac Cardiovasc Surg 1984;
32: 208–14.
20 Van Arsdell G, Yun TJ. An apology for primary repair of tetralogy of
Fallot. Semin Thorac Cardiovasc Surg Pediatr Card Surg Annu 2005:
128–31.
21 Cullen S, Shore D, Redington A. Characterization of right
ventricular diastolic performance after complete repair of tetralogy
of Fallot. Restrictive physiology predicts slow postoperative recovery.
Circulation 1995; 91: 1782–89.
22 Chaturvedi RR, Shore DF, Lincoln C, et al. Acute right ventricular
restrictive physiology after repair of tetralogy of Fallot: association
with myocardial injury and oxidative stress. Circulation 1999;
100: 1540–47.
23 Norgard G, Gatzoulis MA, Moraes F, et al. Relationship between the
type of outflow tract repair and postoperative right ventricular
diastolic physiology in tetralogy of Fallot. Implications for long-term
outcome. Circulation 1996; 15: 3276–80.
24 Munkhammar P, Cullen S, Jogi P, de Leval M, Elliott M, Norgard
G. Early age at repair prevents restrictive right ventricular (RV)
physiology after surgery for tetralogy of Fallot (TOF): diastolic RV
function after TOF repair in infancy. J Am Coll Cardiol 1998;
32: 1083–87.
25 Sachdev MS, Bhagyavathy A, Varghese R, Coelho R, Kumar RS.
Right ventricular diastolic function after repair of tetralogy of Fallot.
Pediatr Cardiol 2006; 27: 250–55.
26 Norgard G, Gatzoulis MA, Josen M, Cullen S, Redington AN. Does
restrictive right ventricular physiology in the early postoperative
period predict subsequent right ventricular restriction after repair of
tetralogy of Fallot. Heart 1998; 79: 481–84.
27 Shimazaki Y, Blackstone EH, Kirklin JW. The natural history of
isolated congenital pulmonary valve incompetence: surgical
implications. Thorac Cardiovasc Surg 1984; 32: 257–59.
28 Graham TP Jr. Ventricular performance in adults after operation for
congenital heart disease. Am J Cardiol 1982; 50: 612–20.
1469
 Seminar
29 Wessell HU, Cunningham WJ, Paul MH, Bastanier CK,
Muster AJ, Idriss FS. Exercise performance in tetralogy of Fallot
after intracardiac repair. J Thorac Cardiovasc Surg 1980;
80: 582–93.
30 Falliner A, Bursch JH, Wessel A, Faltz HC, Heintzen PH. Accuracy
and performance of Roentgen-Videodensitometry for valvular
regurgitation and ventricular ejection measurements. Z Kardiol
1981; 70: 754–60.
31 Redington AN, Oldershaw PJ, Shinebourne EA, Rigby ML. A
new technique for the assessment of pulmonary regurgitation and
its application to the assessment of right ventricular function
before and after repair of tetralogy of Fallot. Br Heart J 1988;
60: 57–65.
32 Chaturvedi RR, Kilner PJ, White PA, Bishop A, Szwarc R,
Redington AN. Increased airway pressure and simulated branch
pulmonary artery stenosis increase pulmonary regurgitation after
repair of tetralogy of Fallot. Real-time analysis with a conductance
catheter technique. Circulation 1997; 95: 643–49.
33 Carvalho JS, Shinebourne EA, Busst C, Rigby ML, Redington AN.
Exercise capacity after complete repair of tetralogy of Fallot:
deleterious effects of residual pulmonary regurgitation. Br Heart J
1992; 67: 470–73.
34 Gatzoulis MA, Clark AL, Cullen S, Newman CG, Redington AN.
Right ventricular diastolic function 15 to 35 years after repair of
tetralogy of Fallot. Restrictive physiology predicts superior exercise
performance. Circulation 1995; 91: 1775–81.
35 Eroglu AG, Sarioglu A, Sarioglu T. Right ventricular diastolic
function after repair of tetralogy of Fallot: its relationship to the
insertion of a ‘transannular’ patch. Cardiol Young 1999; 9: 384–91.
36 Choi JY, Kwon HS, Yoo BW, et al. Right ventricular restrictive
physiology in repaired tetralogy of Fallot is associated with smaller
respiratory variability. Int J Cardiol 2008; 125: 28–35.
37 Helbing WA, Niezen RA, Le Cessie S, van der Geest RJ,
Ottenkamp J, de Roos A. Right ventricular diastolic function in
children with pulmonary regurgitation after repair of tetralogy of
Fallot: volumetric evaluation by magnetic resonance velocity
mapping. J Am Coll Cardiol 1996; 28: 1827–35.
38 Van den Berg J, Wielopolski PA, Meijboom FJ, et al. Diastolic
function in repaired tetralogy of Fallot at rest and during stress:
assessment with MR imaging. Radiology 2007; 243: 212–19.
39 Gatzoulis MA, Till JA, Somerville J, Redington AN.
Mechanoelectrical interaction in tetralogy of Fallot. QRS
prolongation relates to right ventricular size and predicts malignant
ventricular arrhythmias and sudden death. Circulation 1995;
92: 231–37.
40 Gatzoulis MA, Till JA, Redington AN. Depolarization–
repolarization inhomogeneity after repair of tetralogy of Fallot.
The substrate for malignant ventricular tachycardia? Circulation
1997; 95: 401–04.
41 Berul CI, Hill SL, Geggel RL, et al. Electrocardiographic markers of
late sudden death risk in postoperative tetralogy of Fallot children.
J Cardiovasc Electrophysiol 1997; 8: 1349–56.
42 Balaji S, Lau YR, Case CL, Gillette PC. QRS prolongation is
associated with inducible ventricular tachycardia after repair of
tetralogy of Fallot. Am J Cardiol 1997; 80: 160–63.
43 Gatzoulis MA, Balaji S, Webber SA, et al. Risk factors for
arrhythmia and sudden death late after repair of tetralogy of Fallot:
a multicentre study. Lancet 2000; 356: 975–81.
44 Roos-Hesselink J, Perlroth MG, McGhie J, Spitaels S. Atrial
arrythmias in adults after repair of tetralogy of Fallot. Correlations
with clinical, exercise, and echocardiographic findings. Circulation
1995; 91: 2214–19.
45 Harrison DA, Siu SC, Hussain F, MacLoghlin CJ, Webb GD,
Harris L. Sustained atrial arrhythmias in adults late after repair of
tetralogy of Fallot. Am J Cardiol 2001; 87: 584–88.
46 Bleeker GB, Steendijk P, Holman ER, et al. Assessing right
ventricular function: the role of echocardiography and
complementary technologies. Heart 2006; 92 (suppl I): i19–i26.
47 Damiano RJ, La Follette P, Cox JL, Lowe JE, Santamore WP.
Significant left ventricular contributions to right ventricular systolic
function. Am J Physiol 1991; 261: H1514–24.
48 Hoffman D, Sisto D, Frater RW, Nikolic SD. Left-to-right ventricular
interaction with a noncontracting right ventricle.
J Thorac Cardiovasc Surg 1994; 107: 1496–502.
1470
49 Brookes C, Ravn H, White P, Moeldrup U, Oldershaw P,
Redington A. Acute right ventricular dilatation in response to
ischemia significantly impairs left ventricular systolic performance.
Circulation 1999; 100: 761–67.
50 Davlouros PA, Kilner PJ, Hornung TS, et al. Right ventricular
function in adults with repaired tetralogy of Fallot assessed with
cardiovascular magnetic resonance imaging: detrimental role of
right ventricular outflow aneurysms or akinesia and adverse
right-to-left ventricular interaction. J Am Coll Cardiol 2002;
40: 2044–52.
51 Ghai A, Silversides C, Harris L, Webb GD, Siu SC, Therrien J. Left
ventricular dysfunction is a risk factor for sudden cardiac death in
adults late after repair of tetralogy of Fallot. J Am Coll Cardiol 2002;
40: 1675–80.
52 D’Andrea A, Caso P, Sarubbi B. Right ventricular myocardial
activation delay in adult patients with right bundle branch block
late after repair of tetralogy of Fallot. Eur J Echocardiogr 2004;
5: 123–31.
53 Dubin AM, Feinstein, Reddy VM. Electrical resynchronisation:
a novel therapy for the failing right ventricle. Circulation 2003;
107: 2287–89.
54 Kirsh JA, Stephenson EA, Redington AN. Images in cardiovascular
medicine. Recovery of left ventricular systolic function after
biventricular resynchronization pacing in a child with repaired
tetralogy of Fallot and severe biventricular dysfunction. Circulation
2006; 113: e691–92.
55 Therrien J, Siu SC, McLaughlin PR, Liu PP, Williams WG,
Webb GD. Pulmonary valve replacement in adults late after repair
of tetralogy of Fallot: are we operating too late? J Am Coll Cardiol
2000; 36: 1670–75.
56 Therrien J, Provost Y, Merchant N, Williams W, Colman J, Webb G.
Optimal timing for pulmonary valve replacement in adults after
tetralogy of Fallot repair. Am J Cardiol 2005; 95: 779–82.
57 Buechel ERV, Dave HH, Kellenberger CJ, et al. Remodelling of the
right ventricle after early pulmonary valve replacement in children
with repaired tetralogy of Fallot: assessment by cardiovascular
magnetic resonance. Eur Heart J 2005; 26: 2721–27.
58 Oosterhof T, van Straten A, Vliegen HW, et al. Preoperative
thresholds for pulmonary valve replacement in patients with
corrected tetralogy of Fallot using cardiovascular magnetic
resonance. Circulation 2007; 116: 545–51.
59 Eyskens B, Reybrouck T, Bogaert J, et al. Homograft insertion for
pulmonary regurgitation after repair of tetralogy of Fallot improves
cardiorespiratory exercise performance. Am J Cardiol 2000;
85: 221–25.
60 Warner KG, O’Brien PK, Rhodes J, Kaur A, Robinson DA,
Payne DD. Expanding the indications for pulmonary valve
replacement after repair of tetralogy of Fallot.
Ann Thorac Surg 2003; 76: 1066–71.
61 Frigiola A, Tsang V, Bull C, et al. Biventricular response after
pulmonary valve replacement for right ventricular outflow tract
dysfunction: is age a predictor of outcome? Circulation 2008;
118: S182–90.
62 Andersen HR, Knudsen LL, Hasenkam JM. Transluminal
implantation of artificial heart valves. Description of a new
expandable aortic valve and initial results with implantation by
catheter technique in closed chest pigs. Eur Heart J 1992;
13: 704–08.
63 Bonhoeffer P, Boudjemline Y, Saliba Z, et al. Transcatheter
implantation of a bovine valve in pulmonary position: a lamb study.
Circulation 2000; 102: 813–16.
64 Bonhoeffer P, Boudjemline Y, Saliba Z, et al. Percutaneous
replacement of pulmonary valve in a right-ventricle to
pulmonary-artery prosthetic conduit with valve dysfunction. Lancet
2000; 356: 1403–05.
65 Bonhoeffer P, Boudjemline Y, Qureshi SA, et al. Percutaneous
insertion of the pulmonary valve. J Am Coll Cardiol 2002;
39: 1664–69.
66 Khambadkone S, Coats L, Taylor A, et al. Percutaneous pulmonary
valve implantation in humans: results in 59 consecutive patients.
Circulation 2005; 112: 1189–97.
67 Khambadkone S, Bonhoeffer P. Percutaneous pulmonary valve
implantation. Semin Thorac Cardiovasc Surg Pediatr Card Surg Annu
2006: 23–28.
www.thelancet.com Vol 374 October 24, 2009

68 Lurz P, Coats L, Khambadkone S, et al. Percutaneous pulmonary
valve implantation: impact of evolving technology and learning
curve on clinical outcome. Circulation 2008; 117: 1964–72.
69 Nordmeyer J, Khambadkone S, Coats L, et al. Risk stratification,
systematic classification, and anticipatory management strategies
for stent fracture after percutaneous pulmonary valve implantation.
Circulation 2007; 115: 1392–97.
70 Nordmeyer J, Coats L, Lurz P, et al. Percutaneous pulmonary
valve-in-valve implantation: a successful treatment concept for early
device failure. Eur Heart J 2008; 29: 810–15.
71 Cribier A, Eltchaninoff H, Bash A, et al. Percutaneous transcatheter
implantation of an aortic valve prosthesis for calcific aortic stenosis:
first human case description. Circulation 2002; 106: 3006–08.
72 Garay F, Webb J, Hijazi ZM. Percutaneous replacement of
pulmonary valve using the Edwards-Cribier percutaneous heart
valve. Cathet Cardiovasc Diagn 2006; 67: 659–62.
73 Therrien J, Siu SC, Harris L, et al. Impact of pulmonary valve
replacement on arrhythmia propensity late after repair of tetralogy
of Fallot. Circulation 2001; 103: 2489–94.
74 Harrild DM, Berul CI, Cecchin F, et al. Pulmonary valve
replacement in tetralogy of Fallot: impact on survival and
ventricular tachycardia. Circulation 2009; 119: 445–51.
75 Harrison DA, Harris L, Siu SC, et al. Sustained ventricular
tachycardia in adult patients late after repair of tetralogy of Fallot.
J Am Coll Cardiol 1997; 30: 1368–73.
76 Karamlou T, Silber I, Lao R, et al. Outcomes after late reoperation in
patients with repaired tetralogy of Fallot: the impact of arrhythmia
and arrhythmia surgery. Ann Thorac Surg 2006; 81: 1786–93.
77 Khairy P, Harris L, Landzberg MJ, et al. Implantable
cardioverter-defibrillators in tetralogy of Fallot. Circulation 2008;
117: 363–70.
78 Yap SC, Roos-Hesselink JW, Hoendermis ES, et al. Outcome of
implantable cardioverter defibrillators in adults with congenital
heart disease: a multi-centre study. Eur Heart J 2007; 28: 1854–61.
79 Webb CL, Jenkins KJ, Karpawich PP, et al. Congenital cardiac
defects committee of the American Heart Association section on
cardiovascular disease in the young. Collaborative care for adults
with congenital heart disease. Circulation 2002; 105: 2318–23.
80 Skorton DJ, Garson A Jr, Allen HD, et al. Task Force 5: adults with
congenital heart disease: access to care. J Am Coll Cardiol 2001;
37: 1193–98.
81 Deanfield J, Thaulow E, Warnes C, et al. Task Force on the
management of grown up congenital heart disease, European
Society of Cardiology; ESC Committee for Practice Guidelines.
Management of grown up congenital heart disease. Eur Heart J
2003; 24: 1035–84.
www.thelancet.com Vol 374 October 24, 2009
Seminar
82 Warnes CA, Williams RG, Bashore TM, et al. ACC/AHA 2008
guidelines for the management of adults with congenital heart
disease: a report of the American College of Cardiology/American
Heart Association Task Force on practice guidelines (writing
committee to develop guidelines on the management of adults with
congenital heart disease). Circulation 2008; 118: 2395–451.
83 Karamlou T, Diggs BS, Person T, Ungerleider RM, Welke KF.
National practice patterns for management of adult congenital heart
disease: operation by pediatric heart surgeons decreases in-hospital
death. Circulation 2008; 118: 2345–52.
84 Niwa K. Aortic root dilatation in tetralogy of Fallot long-term after
repair—histology of the aorta in tetralogy of Fallot: evidence of
intrinsic aortopathy. Int J Cardiol 2005; 103: 117–19.
85 Niwa K, Siu SC, Webb GD, Gatzoulis MA. Progressive aortic root
dilatation in adults late after repair of tetralogy of Fallot. Circulation
2002; 106: 1374–78.
86 Chong WY, Wong WH, Chiu CS, Cheung YF. Aortic root dilation
and aortic elastic properties in children after repair of tetralogy of
Fallot. Am J Cardiol 2006; 97: 905–09.
87 Cusimano RJ, Guest C. Coronary artery disease following repair of
tetralogy of Fallot: implications and management. Can J Cardiol
1996; 12: 172–74.
88 Coutu M, Poirier NC, Dore A, Carrier M, Perrault LP. Late
myocardial revascularization in patients with tetralogy of Fallot.
Ann Thorac Surg 2004; 77: 1454–55.
89 Veldtman GR, Connolly HM, Grogan M, Ammash NM, Warnes CA.
Outcomes of pregnancy in women with tetralogy of Fallot.
J Am Coll Cardiol 2004; 44: 174–80.
90 Khairy P, Ouyang DW, Fernandes SM, Lee-Parritz A, Economy KE,
Landzberg MJ. Pregnancy outcomes in women with congenital
heart disease. Circulation 2006; 113: 517–24.
91 Uebing A, Arvanitis P, Li W, et al. Effect of pregnancy on clinical
status and ventricular function in women with heart disease.
Int J Cardiol 2008; published online Oct 1. DOI:10.1016/j.ijcard.
2008.09.001.
92 Uebing A, Steer PJ, Yentis SM, Gatzoulis MA. Pregnancy and
congenital heart disease. BMJ 2006; 332: 401–06.
93 Cava JR, Danduran MJ, Fedderly RT, Sayger PL. Exercise
recommendations and risk factors for sudden cardiac death.
Pediatr Clin North Am 2004; 51: 1401–20.
94 Fitzgerald DA, Sherwood M. Long-term cardio-respiratory
consequences of heart disease in childhood. Paediatr Respir Rev
2007; 8: 313–22.
1471