615
Growth of the Aortic Anastomosis, Annulus, and
Root After the Arterial Switch Procedure
Performed in Infancy
Maribeth Hourihan, MD; Steven D. Colan, MD; Gil Wernovsky, MD;
Uma Maheswari, MS, RDMS; John E. Mayer, Jr, MD; Stephen P. Sanders, MD
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Background. We investigated the size and growth potential of the neoaortic root and aortic anastomosis
after the arterial switch operation (ASO) for D-transposition of the great arteries (D-TGA) performed in
infants. Circumferential suture lines connecting the great arteries and extensive surgery on the arterial
roots to transplant the coronary arteries are essential parts of the ASO. However, little is known about the
growth of the aortic anastomosis, the neoaortic root, and the neoaortic annulus after the ASO performed
in infancy.
Methods and Results. Serial echocardiograms on 50 patients with D-TGA who underwent ASO in infancy
at our institution were reviewed, and the size of the aortic anastomosis, the neoaortic root, and the
neoaortic annulus were compared with similar structures in a group of 312 control subjects. Before
surgery, the native pulmonary root (future neoaortic root) was 1.59 SD larger (P<.001) and the native
pulmonary annulus (future neoaortic annulus) was 1.4 SD larger (P<.001) in infants with D-TGA than
the aortic root and annulus of control patients. At a mean of 22 months (12 months to 6Y2 years) after
surgery, the diameter of the aorta at the anastomosis was 0.45 SD smaller than the ascending aorta of
control subjects (P<.001). The neoaortic root was 2.9 SD larger (P<.001) and the neoaortic annulus was
1.6 SD larger (P<.001) than the comparable structures in the control population. Most important, growth
of the aortic anastomosis was commensurate with somatic growth, but the dilation of the neoaortic root
appeared to be progressive over time. The neoaortic root was significantly more dilated in patients with
a history of pulmonary artery banding (P<.001) and in patients with neoaortic regurgitation (P<.001).
The presence of a ventricular septal defect was not significantly related to postoperative neoaortic root
size.
Conclusions. This study underlines the importance of continued acquisition and examination of the data
regarding the long-term outcome of the arterial switch operation performed in infancy. (Circulation
1993;88:615-620)
KEY WoRDS * arterial switch operation * transposition * anastomosis, aortic * neoaortic root
At many institutions, the arterial switch operation
(ASO) is now the surgical procedure of choice
for infants with D-transposition of the great
arteries (D-TGA).'-4 This operation involves transsection and reanastomosis of both great arteries above the
sinuses of Valsalva and transplantation of the coronary
arteries. After the ASO, the pulmonary valve and root
function in the systemic circulation. The long-term
success of this operation depends partly upon adequate
growth of the circumferential anastomoses of the great
arteries and the capability of the native pulmonary valve
and root to function in the systemic circulation.
We used echocardiography to investigate the aortic
anastomosis, neoaortic root, and neoaortic annulus in
patients who underwent an ASO in infancy. Serial
measurements were made of all three structures to
Received September 4, 1992; revision accepted March 12, 1993.
From the Department of Cardiology and Division of Cardiovascular Surgery, Children's Hospital, and the Departments of Pediatrics and Surgery, Harvard Medical School, Boston.
Reprint requests to Dr Sanders, Department of Cardiology,
Children's Hospital, 300 Longwood Ave, Boston, MA 02115.
determine growth, and the sizes of these structures were
compared with those of normal control subjects.
Methods
Patients
The study population comprised all patients with
D-TGA who underwent an ASO at Children's Hospital,
Boston, before 6 months of age between January 1983
and December 1989 and who had two or more postoperative echocardiograms at least 12 months apart as of
December 1989. Patients in whom the echocardiographic images of the aortic anastomosis were inadequate for measurement were excluded.
The control population consisted of 312 normal patients who had undergone an echocardiogram at Boston
Children's Hospital between June of 1986 and February
of 1991 in whom acquired and congenital heart disease
had been excluded.
Data Collection
Echocardiograms were performed with a phasedarray sector scanner (Hewlett-Packard 77020 or Acuson
128) with either a 3.5- or 5.0-MHz transducer and were
616
Circulation Vol 88, No 2 August 1993
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FIG 1. Echocardiographic images of the neoaortic root and the aortic anastomosis at 2 weeks (left) and 61/2 years (right) after
arterial switch. Note that the anastomosis is well seen at 2 weeks but is indistinguishable from the rest of the ascending aorta at
6½ years.
recorded on half-inch videocassette tape. Height and
weight were recorded at the time of each echocardiogram, and body surface area (BSA) was calculated using
the formula of Haycock.5
One author (M.H.) reviewed one preoperative
echocardiogram and two to five serial postoperative
echocardiograms for each patient. Still frames were
printed of images of the native pulmonary annulus and
the native pulmonary root on the preoperative studies
and the aortic anastomosis, the neoaortic annulus, and
the neoaortic root from each postoperative echocardiogram. These images were taken from the parasternal
long-axis view whenever possible. When images from
this view were inadequate, the subxiphoid long-axis view
was used. The images were taken as close to midsystole
as possible.
The internal diameter of the aortic anastomosis was
measured at the suture line when it was obvious and just
above the aortic root if the suture line was no longer
evident (Fig 1). The internal diameter of the arterial
root was measured at the widest point in the sinuses of
Valsalva, and the diameter of the valve annulus was
measured at the hinge points of the valve leaflets.
The most recent echocardiogram on each patient was
reviewed to quantify the degree of neoaortic regurgitation (neo-AR). A four-point scale based on the proximal width of the regurgitant jet on Doppler color flow
mapping was used (0 mm, absent; 1 to 3 mm, mild; 4 to
6 mm, moderate; >6 mm, severe). The echocardiograms
of the control population were also reviewed by one
author (U.M.), and the diameter of the aortic annulus,
aortic root, and ascending aorta were measured using a
similar technique.
To assess interobserver variability, a random sample
of 9% of the echocardiograms was reviewed and measurements were made by a second author (S.P.S.).
These measurements were compared with those made
by the first reviewer.
When image quality permitted, measurements were
made from both the parasternal long-axis and the
subxiphoid long-axis views for comparison.
Data Analysis
To account for growth-related changes in the size of
cardiac structures, all echocardiographic measurements
are expressed as Z scores relative to the normal population. The normal relation between each variable and
BSA was determined in the control population; then,
the position of each measurement for the study patients
was determined within the normal distribution and
expressed as a Z score (normal deviate6), or number of
standard deviations from the expected normal mean
value, where the mean and standard deviation are BSA
dependent. Thus, a measurement at the expected nor-
Hourihan et al Aortic Growth After Arterial Switch
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mal mean for BSA has a Z score of 0, and measurements at the upper and lower 95% confidence limits
have Z scores of 1.96 and -1.96, respectively.
The mean Z score for each structure measured before
surgery (native pulmonary root and annulus) and each
structure measured after surgery (neoaortic root, annulus, and anastomosis) was compared with zero using a
single-sample t test.
One-way ANOVA was used to determine the relation
between the Z scores and the presence or absence of a
ventricular septal defect (VSD), the amount of neo-AR
present on the most recent echocardiogram, and a
history of pulmonary artery banding (PAB).
As an index of growth, the rate of change in Z score
per year was calculated for each structure. To determine statistical significance, these rates of change were
compared with zero using a single-sample t test. For
illustration purposes, growth of the three structures was
also calculated as &diameter/SVBSA.
The measurements made by two reviewers were compared using linear regression analysis, as were the
measurements made from subxiphoid and parasternal
images. For all statistical analyses, a value of P<.05 was
considered significant.
Results
Patients
Of the 309 patients who underwent ASO at our
institution during the study period, 50 patients met the
inclusion criteria for this study. The mean age at ASO
was 32 days, and the median age was 8 days. The male
to female ratio was 2.3 to 1. Thirty-two patients had an
intact ventricular septum and underwent an ASO as the
primary surgical procedure. Fifteen patients had a VSD
that was repaired surgically at the time of ASO. Six
patients underwent PAB before the ASO. In three
cases, the band was placed to "prepare" a left ventricle
functioning at low pressure for an ASO.7 The band was
left in place an average of 14 days before ASO. PAB was
performed as palliation in three patients with transposition of the great arteries and a large VSD and
remained in place an average of 87 days before ASO.
Three patients underwent surgical repair of coarctation
of the aorta.
The control population comprised 312 subjects, age 1
week to 19 years (172 male subjects, 140 female subjects), with BSA of 0.2 m2 to 2.11 M2.
Of the 50 study patients, 44 had preoperative studies
from this institution available for review. One study did
not have adequate image quality for measurements.
Therefore, 43 of the 50 study patients had preoperative
echocardiograms reviewed and measurements made.
Preoperative echocardiograms were performed at a
mean age of 24 days and a median age of 4 days.
Preoperative measurements were available of the native
pulmonary valve annulus in 43 patients and of the native
pulmonary root in 41 patients.
One hundred thirty-two postoperative echocardiograms were reviewed on these 50 patients. In 8 of these
132 studies, the image quality was not adequate for
measurements. Therefore, 124 postoperative echocardiograms provided measurements for the study population. Postoperative echocardiograms were performed
617
between 1 day and 61/2 years after the ASO at a mean of
22 months after surgery.
Serial postoperative measurements of the aortic anastomosis were available in all 50 study patients, of the
aortic root in 35, and of the aortic annulus in 29. Of the
312 control patients, 215 had measurements made of
the aortic annulus, 185 of the aortic root, and 141 of the
proximal ascending aorta.
Preoperative Studies
Annulus. The mean Z score for the native pulmonary
annulus diameter before surgery was 1.4, indicating that
in patients with D-TGA at a median age of 4 days, the
mean diameter of the native pulmonary annulus (the
future neoaortic annulus) was 1.4 SD larger than the
mean native aortic annulus diameter in normal subjects.
This difference is highly significant (P<.00001) and
represents a 21%, or, on average, a 1.6-mm difference.
The Z score for the pulmonary annulus diameter among
patients with a VSD (Z=2.3) was significantly larger
(P=.01) than the Z score among patients with no VSD
(Z=0.94). In both groups, the annulus was significantly
larger than the native aortic annulus in the control
population.
Root. The mean Z score for the preoperative pulmonary root diameter was 1.59, showing that in patients
with D-TGA at a median age of 4 days, the mean
diameter of the native pulmonary root (future neoaortic
root) was 1.59 SD larger than the native aortic root
diameter in normal subjects. This difference was also
highly significant (P<.00001) and represents on average
a 25%, or 2.3-mm difference in size. The Z scores for
the preoperative root measurements were not significantly related to the presence or absence of a VSD.
Postoperative Studies
Fig 2 demonstrates the relation between the size of
the three structures studied after surgery and the
square root of the BSA in the study and control
populations.
Anastomosis. The mean Z score for the aortic anastomosis in the study population was -0.45, indicating
that the anastomosis after ASO was smaller than the
normal ascending aorta. Although this difference was
highly significant (P<.0001), the average difference in
diameter was only 16%, or 2 mm.
Annulus. The mean Z score for the neoaortic annulus
in the ASO patients was 1.6, indicating that the neoaortic annulus after ASO was significantly larger (P<.0001)
than the aortic annulus in control subjects. This represents an average difference in diameter of 7 mm, or
50%.
Root. The mean Z score for the neoaortic root in the
ASO patients was 2.9, indicating that the neoaortic root
after ASO was significantly larger than the aortic root in
control subjects (P<.0001). This represents an average
difference in diameter of 16 mm, or 90%.
Pulmonary artery band. The mean Z score for the
neoaortic annulus in patients with no history of PAB
(Z= 1.7) was significantly larger (P=.002) than the Z
score for the neoaortic annulus in patients who had
undergone prior PAB (Z=-0.7). The neoaortic annulus was significantly larger than the aortic annulus of
control subjects only in patients with no history of PAB.
Circulation Vol 88, No 2 August 1993
618
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30
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Is
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aI
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VSD a
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Square Root of BSA (cm)
The mean Z score for the neoaortic root in the
patients with no history of PAB (Z= 2.7) was significantly smaller (P=.0003) than the mean Z score for the
neoaortic root in patients with a history of PAB
(Z=4.5). The neoaortic root in both groups was significantly larger than the aortic root of the control group.
The Z scores for the measurement of the aortic anastomosis were not related to a history of PAB.
Neoaortic regurgitation. Thirty-three of the 50 study
patients (66%) had no neo-AR on the most recent
echocardiogram, 16 (32%) had mild regurgitation, 1
(2%) had moderate regurgitation, and no patient had
severe regurgitation. Therefore, reliable statistical comparisons could only be made between those with no
neo-AR and those with mild neo-AR.
The mean Z score for the aortic anastomosis measurement in patients with mild neo-AR (Z= -0.07) was
significantly larger (P=.00015) than the mean Z score
for the aortic anastomosis in patients with no neo-AR
(Z= -0.77). The aortic anastomosis was significantly
smaller than the ascending aorta of control subjects only
in patients with no neo-AR.
The mean Z score for the neoaortic root in patients with
mild neo-AR (Z=3.3) was also significantly larger
(P=.023) than the mean Z score for the neoaortic root in
patients with no neo-AR (Z=2.6). The neoaortic root was
significantly larger than the native aortic root of control
subjects in both groups. The Z scores for the neoaortic
annulus diameter were not related to the presence of
neo-AR.
Ventricular septal defect. The Z scores for none of the
postoperative measurements were related significantly
to a history of VSD.
Growth. The rate of change in size for the aortic
anastomosis was 0.29±1.45 SD per year; for the neoaortic root, 0.58±1.12 SD per year; and for the neoaortic
annulus, 0.22±1.05 SD per year (Fig 3). All three
FIG 2. Scatterplots: Postoperative measurements of the aortic anastomosis (graph A), the neoaortic annulus (graph B),
and the neoaortic root (graph C) are plotted vs the square root
of body surface area (BSA). The solid line and small dashed
lines represent the mean and 95% confidence intervals,
respectively, for the study patients. The large dashed line and
shaded area represent the mean and 95% confidence intervals, respectively, for comparable structures in the control
population. Patients with a ventricular septal defect (VSD) are
shown as open circles, patients with intact ventricular septum
(IVS) as open squares, and patients with a pulmonary artery
band (PAB) as solid squares.
structures tended to increase in size in excess of that
expected for normal somatic growth, although this was
statistically significant only for the aortic root (P=.002).
The rates of change in Z scores for all three structures
were unrelated to neo-AR or the presence of VSD
before surgery.
Measurement Variability
The interobserver variability was low for all measurements. The values obtained by the two observers were
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Root
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FIG 3. Plot ofgrowth rate of the neoaortic annulus and root
and of the aortic anastomosis after the arterial switch operation shown in relation to somatic growth and expressed as
increment in diameter per increment in the square root ofbody
surface area (BSA). Open circles indicate growth rates for
individual patients with ventricular septal defect; open
squares, patients with intact ventricular septum; solid squares,
patients with pulmonary artery band. Solid circles and vertical
bars indicate group mean and standard deviation, respectively.
Horizontal bars represent the mean growth rate for the control
population.
Hourihan et al Aortic Growth After Arterial Switch
highly correlated (r=.94), with a standard error of the
estimate of 1.9 mm. The measurements made from the
parasternal long-axis view and those made from the
subxiphoid long-axis view were also highly correlated
(r=.94), with a standard error of the estimate of 1.4 mm.
Discussion
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Aortic Anastomosis
Although the diameter of the aortic anastomosis in
our patients was statistically smaller than the diameter
of the ascending aorta in the control population, the
absolute difference in size was small (2 mm, or 16% of
the lumen diameter). Previous studies in patients with
coarctation of the aorta indicate that a reduction in
lumen diameter of at least 50% is required to create a
pressure gradient.8 Therefore, the difference in diameter that we found at the anastomosis is unlikely to be of
physiological significance. More important, we did find
that the size of the anastomosis increased with time
since repair at a rate commensurate with somatic
growth.
Our data on the aortic anastomosis are in contrast to
those of Arensman et al,9 who reported an angiographic
study in 25 patients that demonstrated no significant
difference between the size of the aortic anastomosis in
patients after ASO and the ascending aorta of control
subjects at a mean of 18.8 months after surgery. However, all of the patients in that study were 9 months of
age or older at the time of surgery and all either had a
large VSD or aorticopulmonary window or had undergone PAB. To our knowledge, there are no other
reports of the size and growth of the aortic anastomosis
after primary ASO performed in infants.
Long-term follow-up of infants and children who have
undergone repair of coarctation of the aorta'0 and
experimental data in animals11-13 suggest that circumferential anastomoses do not always grow normally. On
this basis, many have voiced concern about the growth
potential of the aortic anastomosis created in the
ASO.14-16 Our data are reassuring regarding the growth
of the aortic anastomosis created during the ASO
performed in infancy. However, the longer-term growth
potential of this anastomosis after ASO remains to be
determined and warrants continued study.
Neoaortic Root and Annulus
The dilation of the neoaortic root and annulus in our
patients before and after ASO was surprising. Before
ASO, the native pulmonary root and annulus (future
neoaortic root and annulus) were significantly larger in
patients with transposition of the great arteries than the
native aortic root and annulus in infants of comparable
size with normally related great arteries. After ASO, the
dilation of the neoaortic root and annulus persisted at a
mean of 22 months (range, 12 months to 61/2 years) after
surgery.
Our study also indicates that the dilation of the
neoaortic root after ASO is progressive, whereas the
dilation of the neoaortic annulus is not. It is difficult to
postulate a cause for this isolated progressive root
dilation. One possibility is that manipulations unique to
this root during the ASO, such as the reimplantation of
coronary arteries, somehow predispose the root to
progressive dilation over time. Another possibility is a
619
structural difference between the walls of the two
arterial roots. Sievers et a117 have reported fragmentation and shortening of the elastic fibers in the pulmonary root after banding in preparation for ASO. The
progressive root dilation is not due to excess influence
from the patients with VSD because the rate of growth
of the neoaortic root did not differ significantly between
patients with VSD and those with an intact ventricular
septum.
Prior reports have not found the native pulmonary
root to be dilated before banding or AS01718 but have
documented dilation after banding,9'17'18 and after
ASO.9,1718 All of the patients in these reports were
older at the time of ASO (mean age >2 years) and all
either had a large VSD or aorticopulmonary window or
had undergone PAB. In contrast to our data, prior
reports of aortic root growth,9'17'18 have not indicated
progression of the root dilation, although data are
available in fewer than 20 patients, most of whom had
undergone PAB. Klautz et a119 reported findings similar
to ours regarding aortic root growth in 11 or 12 patients,
some with VSD and some with an intact septum, with
surgery performed in the neonatal period. Other investigators reporting follow-up of primary ASO performed
in infants did not find aortic root dilation,20'21 but root
dimensions and the method used to determine root size
were not presented.
Neoaortic Regurgitation
Although the number of study patients with neo-AR
was small (17 of 50) and the degree of regurgitation was
only mild in all except one patient, neo-AR was significantly related to the diameter of the neoaortic root.
Whether this valvar regurgitation is a cause or an effect
of the dilated root and whether it is progressive with
time is unclear and also warrants further study. Several
recent series have demonstrated a significant incidence
of neo-AR in patients after ASO.22-29 Our results support the concerns about the native pulmonary valve in
the systemic circulation and emphasize the need for
continuing follow-up to determine if mild neo-AR will
be progressive.
Pulmonary Artery Banding
The number of patients in our study with a history of
PAB before ASO was small, and although the effects
were statistically significant, it is difficult to draw any
firm conclusions regarding the effect of this procedure
on the growth of the neoaortic root or annulus. One
could postulate that annulus diameter is primarily a
function of flow volume across the orifice, whereas root
size is more related to wall tension and shear forces
acting on the walls. By reducing pulmonary blood flow,
PAB limits annulus diameter. However, the increased
wall tension proximal to the band could lead to root
dilation. The fact that before ASO, the native pulmonary annulus diameter but not the root diameter was
influenced by the presence or absence of a VSD supports this hypothesis.
Summary
It is reassuring that growth of the aortic anastomosis
after ASO in infancy is commensurate with somatic
growth and that a nearly normal ascending aortic diameter is attained. However, the implications of our find-
620
Circulation Vol 88, No 2 August 1993
ings of significantly dilated neoaortic root and annulus
after ASO, even in patients with intact ventricular
septum operated on in infancy, are not clear. The
tendency for the neoaortic root dilation to progress with
time after repair raises some concerns and underlines
the importance of continued acquisition and examination of data regarding the long-term outcome of the
ASO.
Acknowledgments
This study was supported in part by grant HL-41786 from
the National Heart, Lung, and Blood Institute, National
Institutes of Health, Bethesda, Md.
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Circulation. 1993;88:615-620
doi: 10.1161/01.CIR.88.2.615
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