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REVIEW ARTICLE

PULMONARY ATRESIA WITH VENTRICULAR SEPTAL

DEFECT: SYSTEMATIC REVIEW
1
Duraisamy Balaguru, M.D.; 2Muhammad Dilawar, M.D.
1
Tufts University School of Medicine, Boston, MA, USA; 2Cardiology and Cardiovascular Surgery
Department, Hamad Medical Corporation, Doha, Qatar
Introduction
ulmonary atresia with ventricular septal therefore it remains multifactorial in nature.

P defect (PA-VSD) is synonymous with

Tetralogy of Fallot-pulmonary atresia and this
defect may be considered as an extreme form of
classic Tetralogy of Fallot. Classic Tetralogy of
Fallot consists of right ventricular outflow tract
stenosis, malaligned ventricular septal defect,
overriding of aorta and right ventricular
hypertrophy. In contrast, PA-VSD consists of
atresia of right ventricular outflow tract along with
remaining three features of classic Tetralogy of
Fallot. Other synonyms for this defect are Type IV
truncus and Pseudotruncus. PA-VSD has been
proposed by the international nomenclature
committee of Congenital Heart Surgery
Nomenclature and Database Project as a unifying
term1. The variabilities of pulmonary blood supply in
PA-VSD make this defect heterogeneous and
challenging for surgical repair. Relatively poorer
outcome for PA-VSD compared to classic
Tetralogy of Fallot stems from the complexity of its
pulmonary blood supply. Strategies combining
catheter-based therapies for rehabilitation of
pulmonary arteries with appropriately-timed
surgical repair have helped to achieve better
results in recent years2.
Baltimore-Washington infant study provides us
with some pointers to the etiology of Tet-PA. In
BWIS3, 73.3% of patients with PA-VSD did not
have any associated extra-cardiac
abnormalities. The remaining 26.7% of the
patients with PA-VSD had chromosomal
abnormality, a recognizable syndrome, or other
single organ defects. PA-VSD occurs more
often with DiGeorge syndrome and associated
with Chromosome 22q11 microdeletion. Other
recognizable syndromes associated with this
lesion include VACTER, CHARGE and Alagille
syndromes. Chromosomal anomalies such as
Trosomy 13, Trisomy 21 and Deletion 5p have
also been reported in babies with PA-VSD. A
ten-fold higher incidence of PA-VSD has been
reported in infants of diabetic mothers
compared to non-diabetic mothers and the
incidence is 20-fold higher if diabetes was
severe enough to need treatment with insulin.
Maternal intake of benzodiazepines was
associated with congenital heart disease with an
Odds ratio of 2.15.
III. Natural History of the disease

I. Epidemiology Early natural history reports did not address PA-

VSD separate from Tetralogy of Fallot. Limited
Baltimore-Washington Infant Study 3 (BWIS) natural history information is available for PA-VSD
recorded 4390 infants with cardiovascular group from two recent reports, though some
malformations from 1981 – 1989. Of this, 296 patients in these studies underwent surgical
(6.7%) were reported to be Tetralogy of Fallot. repair. A cohort study of 26 adults managed at
Sixty of 296 (20%) infants in the Tetralogy group UCLA (UCLA adult congenital heart disease
were Tet-PA. Tet-PA accounted for 1.4% of all registry 1978 – 1992) was studied for outcome
forms of congenital heart disease and 0.07 per during a 14 year period4. At the time of referral as
100 live births. adults, 16 of them did not have any prior surgery
and the remaining 10 have had some palliative
II. Etiology surgery (mainly systemic to pulmonary artery
shunting). All patients were symptomatic at the
Genetic, environmental, and familial factors play time of referral with cyanosis or functional
a causative role in etiology of PA-VSD and limitation.
1. Assistant Professor of Pediatrics, Tufts University School of Medicine, Boston, MA, USA.
2. Consultant Pediatric Cardiologist, Cardiology & Cardiovascular Surgery Dept. Hamad Medical Corporation & Assistant
professor of Pediatrics Weil Cornell Medical College, Doha, Qatar
Corresponding address: Duraisamy Balaguru MD, MRCP (UK), FAAP, FACC, Children's Heart Center, Children's Hospital of
New Jersey at Newark Beth Israel Medical Center, 201 Lyons Avenue, Newark, NJ 07112. dbalaguru@sbhcs.com

52 HEART VIEWS VOLUME 8 NO.2 JUNE–AUGUST 2005:52–61

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Pulmonary Atresia with Ventricular Septal Defect: Systematic Review
Twenty of these patients had aortic
regurgitation by echocardiogram and 10 of them
were classified as moderate or severe by semi-
quantitative echocardiography. None of the
patients survived beyond the third decade. This
is a small group of self or naturally selected
group of patients who have survived to
adulthood with cyanosis and pulmonary blood
supply supported by collateral arteries.
A recent European study5 documents the
outcome in 218 patients who were treated in two
leading cardiac centers in London over a period
of 26 years (1965 – 1991) and followed up to 40
years of age. This study sheds light on the
course of the disease modified by state of the art
surgical management that was available during
the study period. It is notable that cardiac
surgical therapy and catheterization techniques
and the understanding of the disease itself had
greatly improved during this study period. This
study however helps to set the goals for future
management planning.
Overall, 60% of infants survived to 1 year
highlighting the greatest attrition that occurs
during infancy with or without palliation. Of the
patients who survived to 1 year, 65% lived to 10
years. Only 16% of these patients who lived up
to 10 years were alive at 35 years of age.
Cardiovascular complications included infective
endocarditis (n = 17), stroke (n = 15) and RV
failure (n = 16). Aortic regurgitation has been
recognized in 62% of patients by the age of 30
years. Thirty one percent of patients who
underwent definitive surgical repair died within
30 days of surgery and thirty eight percent of
them died by 3 months. There was no difference
in survival up to 2 years between the patients
who underwent definitive repair versus no
definitive repair. A difference was only noted
after 5 years from definitive surgery.
Thus, the overall outcome in the first 3
decades of surgical approach to this lesion has
not been encouraging despite significant
progress in treatment of other complex
congenital heart lesions. The survivors after
definitive repair remain functionally well and are
less symptomatic than the non-repaired
patients. Evolution of newer management
strategies in the past two decades appears to
have considerably improved outcome. All
patients face periodic re-operations and
therapeutic catheterization procedures
throughout their life time after complete repair,
for replacement of RV – PA conduit and for
correction of any residual obstruction in RVOT.
HEART VIEWS VOLUME 8 NO.2 JUNE–AUGUST 2005:52–61
IV. Pathology
Description of pathology of this defect falls under
two categories namely intracardiac anatomy and
pulmonary blood supply.
IV.1: Intracardiac anatomy
PA-VSD is characterized by atresia of both the
pulmonary valve and a variable length of main
pulmonary artery (MPA). Ventricular septal
defect (VSD) is an integral part of the lesion and
is typically large, malaligned, membranous type
and can occasionally be of the infundibular type.
There is variable degree of aortic override, and
right ventricle (RV) hypertrophy develops as a
consequence of hemodynamic effects.
It should be noted that PA-VSD is different
from pulmonary atresia-intact ventricular septum
(PA -IVS) in that the latter lesion has no VSD and
is generally associated with hypoplastic tricuspid
valve and RV, or dilated and dysfunctional RV
with regurgitant tricuspid valve. Generally,
pulmonary artery abnormalities are not seen in
PA-IVS. Moreover, presence of coronary
sinusoids is a significant issue in PA-IVS. Unlike
tetralogy of Fallot, coronary arteries in
PA-VSD are usually normal with a prominent
conal branch.
IV.2: Pulmonary blood supply
Abnormalities in pulmonary artery anatomy and
pulmonary blood supply are significant features
of PA-VSD that sets it apart from classic
Tetralogy of Fallot. Variations in pulmonary blood
supply makes each patient unique and warrant
individualized planning of surgical and catheter-
based strategies. Complexity in the management
of Tet-PA stems from the complexity of
pulmonary blood flow. The discussion of
pulmonary blood flow in PA-VSD includes the
extent of MPA atresia, patent ductus arteriosus,
native pulmonary arteries, aortopulmonary
collaterals and distal pulmonary vascular
arborization.
Extent of pulmonary valve atresia varies from
only a plate-like atresia of the pulmonary valve to
absence of both valve and a variable length of
MPA. Extension of MPA atresia to its bifurcation
results in non-confluent central pulmonary
arteries (PAs). Presence or absence of confluent
PAs significantly influences surgical outcome. At
birth, PDA becomes an essential source of
pulmonary blood flow when confluent pulmonary
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Pulmonary Atresia with Ventricular Septal Defect: Systematic Review
Fig.1 (Type A, B, C): Classification of PA - VSD according to the status of native pulmonary arteries (NPAs), aorto-pulmonary
collaterals (APCs) and patent ductus arteriosus (PDA).
Type A: Native pulmonary arteries present, no APCs.
Type B: Native pulmonary arteries and APCs present.
Type C: No native pulmonary arteries, only APCs maintain pulmonary blood flow.
arteries are present. In PA-VSD, PDA typically
originates from either the undersurface of the
arch (67%) or from the undersurface of the
innominate artery (33%). Unilateral PDA is
usually associated with confluent PAs, while PDA
can be bilateral as is usual with non-confluent
PAs. When PDA is present, PAs are confluent in
80% of cases. All patients with PDA have central
PAs6. Notably, PDA is absent in 1/3 of cases and
is associated with absent central PAs6.
Aortopulmonary collaterals (APCs) are
muscular arteries until they enter the lung
parenchyma, but the muscular layer is gradually
replaced by elastic lamina that resembles true
pulmonary arteries. APCs are seen in 30 – 65%
of patients with PA - VSD7 and are usually 2 – 6
in number. Known sites of origin of APCs include
descending thoracic aorta at the level of carina,
subclavian arteries, abdominal aorta, and
coronary arteries. Sixty percent of APCs have
stenosis either at diagnosis or it develops over a
period of time during follow up.
The differentiation between PDA and APCs is
important in newborns, who have balanced
pulmonary blood flow and therefore, are
candidates for a relatively late definitive repair. In
such patients, a reliable source of pulmonary
blood flow is necessary until cardiac repair is
performed. PDA is considered a less reliable
source beyond the first few days of life due to its
tendency to close. Though APCs are also prone
for stenosis over a period of weeks to months,
they remain patent more reliably than PDA until
surgical repair is performed at few months of
54 HEART VIEWS VOLUME 8 NO.2 JUNE–AUGUST 2005:52–61
age. Color Doppler flow studies have been
shown to be reliable in making this distinction
between PDA and APCs based on the direction
of blood flow in the proximal mediastinal
segment of PAs6. Furthermore, PDA is straight
and do not branch while APCs in general, are
tortuous and may branch.
V. Classification
The anatomic spectrum varies from atresia of
pulmonary valve, presence of MPA and
confluent normal sized PAs that are supplied by
a PDA; to atresia of MPA with diminutive and/or
non-confluent PAs, absent PDA and pulmonary
blood supply solely provided by multiple APCs
and bronchial arteries. There are several
degrees of severity in between these two
extremes of the spectrum. Consequently, it has
been difficult to classify this lesion and compare
the outcome. A practical classification has been
proposed by Congenital Heart Surgeons Society
based on complexity of pulmonary blood supply
which in turn indicates the complexity of surgical
repair1 (Figure 1).
Type A: Native PAs present, pulmonary
vascular supply through PDA and no APCs.
Type B: Native PAs and APCs present
Type C: No native PAs, pulmonary blood
supply through APCs only.
Surgical approach for type B and C is similar
except that more extensive unifocalization of
APCs will be needed in Type C, before the total
repair is achieved.
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Pulmonary Atresia with Ventricular Septal Defect: Systematic Review
VI. Evaluation of a child with PA-VSD
VI.1: Clinical presentation
Approximately 65% of Tet-PA patients present to
a cardiac center during infancy. The remainder
presents later presumably because of high
enough pulmonary blood flow which lead to
clinically undetectable cyanosis during the early
months of life. Overall, the modes of
presentation in Tet-PA consisted of cyanosis
(50%), heart failure (25%) or murmur with mild
cyanosis with or without failure to thrive (25%)5.
Newborns present with cyanosis with or
without a heart murmur. Such newborns have
duct dependent pulmonary circulation. The
presentation occurs when the duct starts to
constrict. Severe hypoxia, acidosis and shock
ensues closure of PDA. If the babies had gone
home by this time, they present to the
emergency department in extreme shock and
acidosis. Typical age of presentation in this
group is 3 – 7 days. Sepsis, congenital adrenal
hyperplasia, other duct-dependent congenital
heart diseases or severe illnesses affecting
other systems comprise the differential
diagnosis.
There may or may not be a murmur which is
typically continuous in nature representing
aortopulmonary collateral artery flow if present.
Immediate resuscitation with prostaglandin E1
(PGE1) infusion will help to stabilize the patient.
This is the type with good-sized native PAs
which are supplied by a duct. Usually, these
patients do not require unifocalization and are
good candidates for neonatal repair with right
ventricle to pulmonary artery (RV-PA) conduit.
However, babies with more complex pulmonary
blood flow tend to be less dependent on ductal
flow since the proportion of pulmonary blood flow
derived via native PAs is much less than that
derived via the APCs. If the pulmonary blood
flow is adequate and well-balanced, these
babies will only have mild cyanosis and will
escape detection as a newborn.
Presentation in early infancy occurs when the
baby has “balanced circulation” with adequate
pulmonary blood flow via APCs. These babies
often present after 4 – 6 weeks of age either with
increasing cyanosis or signs of heart failure.
Development of stenosis in APCs progressively
reduces pulmonary blood flow causing
progressive cyanosis. Alternatively, pulmonary
over circulation occurs from the physiologic
reduction in pulmonary vascular resistance as
HEART VIEWS VOLUME 8 NO.2 JUNE–AUGUST 2005:52–61
the newborn gets older and leads to heart failure.
These infants may have only mild cyanosis and
escape recognition until later.
There is yet another subset of patients with
adequate and “balanced” pulmonary blood flow
throughout early infancy and may present during
late infancy. Such patients may present with a
heart murmur that was heard during routine
physical examination and cyanosis or heart
failure was not clinically obvious. As a general
rule, in complete mixing lesions such as
pulmonary atresia, systemic oxygen saturation
of 85% is achieved by Qp/Qs of at least 2.5
(mixed venous saturation 60%). Symptoms of
heart failure in childhood imply a Qp/Qs ≥ 4. The
so-called “balanced circulation” with
asymptomatic infants occurs when Qp/Qs
ranges between 2.5 and 4 during infancy5.
Failure to thrive in the absence of heart failure
has been reported as a presenting symptom but
the mechanism is unclear and can be secondary
to underlying genetic abnormality.
Adult patients, either unoperated since they
were deemed inoperable or had undergone only
a palliative procedure, are infrequently seen in
the current era. In a recent report of 26 adult
patients4, all were cyanotic (mean oxygen
saturation of 85%) and polycythemic (mean
hematocrit 57%) at presentation. They were all
symptomatic with signs of heart failure such as
effort dyspnea or decreased exercise tolerance
and were NYHA functional class II or III.
VI.2: Physical examination
The severity of cyanosis depends upon the
amount of pulmonary blood flow. Close clinical
follow up with regular measurement of oxygen
saturations is essential until surgical repair is
accomplished. On the other hand, fall of
pulmonary vascular resistance during early
infancy allows increase in pulmonary blood flow
leading to heart failure and present with feeding
difficulty, failure to thrive, signs of respiratory
distress, tachypnea, tachycardia and
hepatomegaly. A bounding pulse in these infants
is usual and signified large pulmonary blood flow
with run-off from systemic arteries through
APCs. Auscultation reveals the absence of
pulmonary component of second heart sound
and therefore, a single S2. Continuous bruit of
the flow through APCs could be heard over the
chest wall. As the infancy progresses, cyanosis
usually worsens and polycythemia and clubbing
may develop.
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Pulmonary Atresia with Ventricular Septal Defect: Systematic Review

VI.3: Chest X ray blood flow. In newborns, presence of right

Boot shaped heart: The left heart border on chest
X-ray from above downwards is constituted of
aortic arch, main pulmonary artery, left atrial
appendage and left ventricular apex. In Tetralogy
of Fallot with or without pulmonary atresia, the
main pulmonary artery segment is small or
absent creating a concavity below the aortic arch.
The right ventricular hypertrophy leads to upward
pointing of the cardiac apex from the right dome
of the diaphragm. The combination of concavity
at the upper mid part of the left heart border with
the uplifting of the cardiac apex creates a boot
shape appearance of the cardiac silhouette on
chest X-ray. Right aortic arch (25 – 50%), is more
common in this lesion than classic Tetralogy of
Fallot (20 – 25%) and can be diagnosed on chest
X-ray and more precisely by echocardiogram.
Pulmonary vascular markings have a typical
reticular pattern when there are multiple
collaterals supplying the lungs. Overall extent of
pulmonary vascular markings will depend on the
extent of pulmonary blood flow.
VI.4: Electrocardiogram
The EKG findings depends on the age of the
patient. Right axis deviation, right ventricular
hypertrophy and possibly right atrial enlargement
are usual features. Biventricular hypertrophy is
noted in patients with increased pulmolnary
ventricular hypertrophy differentiates it from PA-
IVS which has diminutive RV forces in the
anterior chest leads. However, there is less
emphasis on EKG findings in the era of
advanced echocardiographic technology.
VI.5: Echocardiography
Echocardiography is the key diagnostic modality
for the diagnosis of congenital heart diseases.
While echocardiography has supplanted
diagnostic catheterization studies to a
considerable extent in the evaluation of infants
with PA-VSD, creative use of other non-invasive
modalities such as computed tomography (CT)
and magnetic resonance imaging (MRI) are
increasingly used to define pulmonary blood flow.
Echocardiography is the gold standard to
delineate intracardiac defects but has limitations
for the extracardiac vascular structures. Direction
of blood flow in central PAs helps to differentiate
PDA from APCs. The blood flow by color Doppler
typically is antegrade if the source is PDA since
PDA joins the PA in the mediastinum while the
collateral arteries join PAs in the lung hilum, and
hence, the flow in the central PAs will be
retrograde. In general, if there is evidence of
significant APCs, a diagnostic catheterization
angiography or CT/MR angiography is generally
performed to define the precise anatomy and
distribution of blood flow in the APCs.

Fig.2 (A, B): PA-VSD with confluent native pulmonary arteries (NPAs) and aortopulmonay collaterals (APCs).
A: Aortic arch angiography by pigtail in anteroposterior (AP) view showing confluent NPAs and APCs.
B: Selective left lung collateral angiography using Judkins right catheter in AP view showing retrograde filling of NPAs via the
APC that originates from descending thoracic aorta.

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VI.6: Cardiac Catheterization
The technological advances in
echocardiography with color Doppler imaging
over the past 2-3 decades, have diminished
the indications for diagnostic catheterization.
The focus of catheterization has shifted from
making the diagnosis to filling in missing
information in the diagnosis such as the
hemodynamic data regarding pulmonary blood
supply. Other specific questions unanswered
by echocardiography such as: 1) coronary
anatomy; 2) aorto-pulmonary collateral arteries
(number, size, distribution, any stenosis and
blood pressure in each collateral vessel)
(Figure 2: A, B); 3) confirmation of presence or
absence of native PAs and a retrograde
pulmonary vein wedge injection if needed to
identify their presence if not clear on
aortography; 4) number of lung segments
connected to native Pas; and 5) lung segments
with dual blood supply.
VI.7: CT / MR angiography
CT/MR angiography provides an alternative
modality to conventional angiography to define
RVOT, MPA, branch PAs and APCs8.
VI.8: Nuclear perfusion scan
Quantitative lung perfusion scan using nuclear
scintigraphy is useful in defining relative
distribution of RV output to each lung and to
individual lung segments. Such lung perfusion
scans help to guide and gauge interventional
catheterization therapy during pulmonary arterial
rehabilitation postoperatively and is generally not
helpful preoperatively in the presence of APCs.
VI.9: Evaluation of adequacy of
pulmonary arteries
The complexity of pulmonary blood supply
determines the extent of surgical exploration
necessary to perform unifocalization. Eligibility
for complete repair is dependent on this since
the RV-PA conduit needs to be placed to the
vessel which is connected to maximum possible
pulmonary vascular bed. Furthermore, closing
the VSD at the time of placement of RV – PA
conduit needs to be determined. Adequacy of
the pulmonary vascular bed and the pulmonary
vascular resistance are the determinants of
postoperative RV pressure which in turn has
HEART VIEWS VOLUME 8 NO.2 JUNE–AUGUST 2005:52–61
been closely correlated with surgical outcome. At
least 10 – 16 lung segments need to be
connected to the RV-PA conduit in order to have
satisfactory hemodynamic result after complete
repair9. If the central native PAs were not
identified on echo, it is prudent to demonstrate
them angiographically. Furthermore, a
simultaneous contrast injection into the proximal
stump of the pulmonary artery and the
pulmonary vein wedge injection will help to
define the length of discontinuity that need to be
“bridged” surgically during repair10.
Preoperative evaluation of adequacy of
pulmonary artery size is difficult because of
under filling of PAs and therefore, the potential
size of these PAs after surgical repair is
unpredictable. However, several pulmonary
artery indices have been developed by several
investigators:
1) McGoon's ratio: McGoon's ratio is
calculated by dividing the sum of the diameters
of RPA (at the level of crossing the lateral margin
of vertebral column on angiogram) and LPA (just
proximal to its upper lobe branch), divided by the
diameter of aorta at the level above the
diaphragm [DRPA /DDTAO)+( DLPA / DDTAO)].
An average value of 2.1 was noted in normal
subjects. Ratio above 1.2 is associated with
acceptable postoperative RV systolic pressure in
Tetralogy of Fallot. Ratio below 0.8 is deemed
inadequate for complete repair of PA – VSD.
VSD closure is deferred in such patients at the
time of repair or they underwent aortopulmonary
shunt procedure as first stage11,12. However, this
ratio tends to overestimate the adequacy of the
size of PAs since this is derived using the
diameter of descending thoracic aorta at the
level of diaphragm which is frequently smaller in
patients with PA-VSD.
2) Nakata index: Nakata PA index is
calculated from the diameter of PAs measured
immediately proximal to the origin of upper lobe
branches of the respective branch PAs13. The
sum of the cross sectional area (CSA) of right
and left PAs is divided by the body surface area
of the patient [Nakata index = CSA of RPA
(mm2) + CSA of LPA (mm2)/ BSA (m2)]. A
Nakata index of >150 mm2/m2 is acceptable for
complete repair without prior palliative shunt14.
While Nakata index is widely used in
preoperative assessment of adequacy of
pulmonary vascular bed, it is not useful in
patients with multifocal pulmonary blood supply,
who are evaluated for single-stage repair of PA -
VSD. UCSF group had proposed a total Neo-
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pulmonary artery index for use in patients with
such complex lesions.
3) Total Neo-pulmonary artery index (TNPAI):
Nakata index is of limited use for evaluation of
the adequacy of PAs in single stage repair
strategy where unifocalization of several APCs is
followed by total repair at the same operation. In
Nakata index, there is no provision for the
additional vascular bed that will be added by
unifocalization. A composite index of native PAs
and the APCs that will be unifocalized was
needed, in order to determine whether the VSD
could be closed at surgery.
The UCSF group proposed TNPAI in order to
help preoperative planning in these patients15.
Nakata PA index was measured as described
above. Then, APCs index was calculated by
addition of CSA of all significant APCs divided by
the BSA. CSA of each APC was calculated from
diameter of the respective vessels measured on
preoperative cineangiogram. The sum of total
APC index and PA index is called TNPAI. A
TNPAI index >200 mm2/m2 correlated well with
low postoperative RV/LV pressure ratio and
identified patients who were clear candidates for
VSD closure at the time of single-stage surgical
repair. These indices are limited in value since
they are based on the size of the proximal
Fig.3: Cartoon showing repaired Pulmonary atresia -
Ventricular septal defect. Right ventricle to pulmonary
artery (RV - PA) conduit is shown, VSD patch not shown in
the cartoon.
58 HEART VIEWS VOLUME 8 NO.2 JUNE–AUGUST 2005:52–61
vessels only. The nature of the distal pulmonary
vascular bed and pulmonary vascular resistance
are not expressed in these calculations. Since
these latter factors play an important role in
postoperative RV pressure and in turn the
hemodynamic outcome of surgical repair, an
intraoperative method to assess the adequacy of
pulmonary vascular bed has been proposed15.
VII. Management
VII.1: General principles of surgical therapy of
PA-VSD: Heterogeneity of pulmonary blood
supply in PA-VSD precludes uniformally
applicable management to all the patients.
However, certain guiding principles of
management have evolved over the past 3
decades based on earlier observations in these
patients. Connecting as many lung segments as
possible to the blood flow from RV during early
infancy is essential since early attrition of these
patients occurs during infancy and significant
histologic changes occurs in pulmonary
vasculature during young age5,9. Development of
pulmonary vascular occlusive disease from
unrestricted pulmonary blood flow from APCs
can develop as early as 4 weeks16. Recruitment
of lung segments into RV-PA conduit supply is
more successful when blood flow to it is restored
early in life and complete repair should be
attempted within weeks to months during
infancy. Therapeutic catheterization procedures
such as balloon angioplasty help to rehabilitate
pulmonary arteries with stenosis and should be
combined with surgical repairs to optimize the
overall outcome.
VII.2: Components of surgical repair:
Regardless of the surgical strategy that is used
for a given patient, the components of total repair
of PA-VSD consist of (a) placement of RV - PA
conduit, (b) unifocalization of APCs and (c) VSD
closure. These components are performed in
one-stage, or at different operations depending
on the anatomy and institutional policy.
a) RV – PA conduit placement: Typically a
cadaveric, cryopreserved homograft is used to
connect right ventricle to available central
pulmonary arteries. In complex cases, where a
central pulmonary artery is absent or the
pulmonary blood flow is multifocal,
unifocalization of the diminutive native
pulmonary arteries and APCs will be performed
before RV – PA conduit is placed (Figure 3).
b) Unifocalization of APCs: It was shown in
the mid seventies that unifocalization will enable
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Pulmonary Atresia with Ventricular Septal Defect: Systematic Review
connecting more lung segments to central
Pas17,18, and the current practice is to unifocalize
significant APCs during the first 3 months of life.
Median sternotomy is the preferred method
especially if single stage repair is planned. In
multi stage surgical approach, unifocalization is
done through lateral thoracotomies. During
unifocalization, APCs are ligated at the origin
and mobilized to maximize their length with
creative rerouting. Such mobilized vessels are
anastomosed in the mediastinum before being
connected to RV-PA conduit.
c) VSD closure: Closure of VSD at the time of
initial repair is desirable in order to avoid the need
for further surgery. However, if there were any
concerns about the adequacy of the pulmonary
vascular bed, it is customary to defer VSD
closure. Leaving the VSD unrepaired, helps to
avoid supra-systemic RV pressure in the
immediate postoperative period by allowing RV to
decompress through the VSD. Over a period of
months, pulmonary vascular development occurs
and the VSD can be closed safely with sub-
systemic RV pressure. The strategy of delayed
VSD closure has reduced the operative mortality.
With the single stage surgical repair strategy it
is important to ensure that pulmonary
vasculature is adequate, both in diameter of
proximal pulmonary vessels and development of
distal pulmonary vascular bed, for the safe
closure of VSD. Preoperative PA indices
mentioned earlier help to assess the adequacy
of PA size and the nature of distal pulmonary
vascular bed that is connected to central PAs.
However when a single-stage repair strategy
is adopted with unifocalization of APCs at the
same operation, preoperatively-determined PA
indices will not be able to predict the level of
pulmonary vascular bed added by unifocalization
of APCs. Therefore, an intraoperative method to
evaluate adequacy of pulmonary vascular bed
was proposed by the UCSF group15. After
completion of unifocalization and distal
anastamosis of RV - PA conduit, a perfusion
cannula and a PA catheter are inserted from the
proximal end of the conduit and left atrial vent is
placed. The conduit is connected to the bypass
machine. The bypass machine is run at
increasing flow rates to 2.5 L/min/m2 and the PA
pressure is monitored. VSD is closed if the mean
conduit pressure is < 25 mmHg, and left open if
it is higher. Alternative strategy in borderline
cases is to close the VSD with a fenestrated
patch and the fenestration can be closed later
either by surgery or transcatheter technique,
HEART VIEWS VOLUME 8 NO.2 JUNE–AUGUST 2005:52–61
when applicable. When VSD closure is deferred
at initial repair, it is surgically closed after 6 - 12
months, if and when left to right shunt is
established via the VSD with Qp/Qs exceeding
2:1 by catheter evaluation15.
VIII. Multi-stage versus single-stage
approach
VIII.1: Multi-stage approach: A multi-stage
correction evolved from the early surgical
experiences. Inevitably, the strategy changed
based on individual patient's anatomy and clinical
features. Traditional approach consisted of a
palliative shunt in all patients (patients with “good
size”, confluent central PA in particular) during
neonatal period or early infancy to relieve
cyanosis and allow for growth of distal pulmonary
arteries. However, with diminutive PAs, RV – PA
continuity is established by placing a RV – PA
conduit. This provides catheter access to
peripheral PAs to perform balloon angioplasty of
the pulmonary arteries. The VSD is typically left
open at this first stage. Any possible
unifocalization of APCs will also be performed.
A subsequent operation will be done to close
the VSD, relieve any residual right ventricular
outflow tract obstruction and place a valved
conduit. With absent mediastinal PAs, the
surgical approach is further complicated. Two
modified Blalock Taussig shunts are performed
to each PA via bilateral thoracotomies.
Unifocalization of any significant APCs will be
preformed. Each thoracotomy is done during the
same hospitalization but separated by few days.
This will relieve cyanosis and allow growth of
native pulmonary arteries. The babies would
have catheter evaluation prior to next operation.
The second operation will consist of RV – PA
homograft, connection of all branches of PA with
or without VSD closure. Modifications to above
mentioned generalized outlines will be made
dependent upon individual patient's condition.
VIII.2: Single-stage approach: Current
surgical approach attempts to perform APCs
unifocalization and cardiac repair at the same
operation, through median sternotomy. The
choice between multi-stage and single-stage
repair is dependent on various factors: Nature of
PAs (small vs. good size), (duct-dependent or
collateral-dependent PBF), age of the patient at
presentation, status of APCs, and availability of
surgical skills and results of the institution.
Newborns with no PDA and adequate collateral
dependent pulmonary blood supply with
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Pulmonary Atresia with Ventricular Septal Defect: Systematic Review
acceptable systemic oxygen saturations, are the
typical candidates for elective single-stage
unifocalization and cardiac repair that is
performed at about 3 months of age.
VIII.3: Comparison of outcome between multi
and single-stage repair: Several theoretical
advantages of the single-stage approach over the
more traditional multi-stage approach exist. Single
stage repair allows for early normalization of
cardiovascular physiology by recruitment of all
possible lung segments into RV derived circulation
as early in life as possible. This alleviates cyanosis
and polycythemia during infancy. Early repair also
preserves pulmonary vascular bed and avoids
development of pulmonary vaso-occlusive disease
in the lung segments exposed to systemic
pressure via APCs, and hypoplasia of the distal
pulmonary vasculature in under-perfused lung
segments. There is also evidence to suggest that
long term cardiac function is preserved by avoiding
ventricular dysfunction from prolonged cyanosis
and arrhythmias19. When we compare outcome
between patients treated in same surgical era20, 21,
the ultimate results are comparable but patients in
the single stage group undergo one or two
operations less than the patients in multi-stage
group do.
IX. Complementary role of
interventional catheterization
Interventional catheterization has assumed an
important complementary role in rehabilitation of
pulmonary arteries in the management of
patients with PA - VSD by the use of balloon
angioplasty and stent placements 22.
Catheterization helped avoiding surgery in case
of stenosis in proximal segments of the PAs and
by being able to reach distal stenosis within lung
parenchyma that are inaccessible to the
surgeon. Coil occlusion of APCs, stent
placement in RVOT and palliative stenting of
stenotic APCs are some of the other procedures
that interventional catheterization has to offer to
the patients with PA – VSD.
X. Long term sequelae/outcome
Many of the long term sequelae have been
mentioned earlier under the natural history
section. Patients who were unsuitable for
complete surgical repair and therefore were
palliated with systemic to pulmonary artery
shunts only, develop progressive cyanosis and
polycythemia as they survive into adulthood.
60 HEART VIEWS VOLUME 8 NO.2 JUNE–AUGUST 2005:52–61
Aortic regurgitation (AR) develops in a significant
number of patients with or without complete
surgical repair. Development of AR occurs more
often with patients who had palliative shunts only
since they add to the LV volume overload and
therefore LV dilatation. The resultant aortic
annular dilatation worsens aortic regurgitation.
Infective endocarditis affecting aortic valve is
another mechanism of AR. Progressive LV
dilatation due to volume overload from AR,
systemic to pulmonary artery shunt or collateral
flow eventually leads to LV dysfunction.
In patients who have had complete repair, there
is a gradual deterioration of conduit function23 from
loss of luminal diameter, calcification, peel
formation and from the deterioration of valve
function. The valve in the conduit is prone for
calcification, stenosis and regurgitation.
Pulmonary regurgitation worsens with any residual
stenosis in distal pulmonary arteries. While
pulmonary regurgitation is well tolerated for years,
RV dilatation and hypertrophy eventually ensues
leading to RV dysfunction24. There is evidence that
RV dilatation with dysfunction can eventually
impact LV function by ventricle-ventricle
interaction. However, optimal timing of re-
operation either to replace the deteriorated conduit
or implantation of pulmonary valve to stop
pulmonary regurgitation is still unclear.
Development of ventricular arrhythmias has been
documented after tetralogy repair. This is thought
to account for the relatively high incidence of
sudden deaths noted in patients long after
tetralogy repair. Co-existing poor hemodynamic
parameters such as high RV pressure is thought to
be a risk factor for arrhythmias. Correction of
hemodynamic abnormalities by pulmonary valve
implantation or replacement of RV – PA conduit is
expected to help reduce this risk25. The outcome
from the current modified approach combining
surgery and therapeutic cardiac catheterization
techniques has improved the outcome and long
term studies in future will provide proof of such
improved outcome.♦
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