(Circulation. 1995;92:886-892.)
© 1995 American Heart Association, Inc.
Articles |
Quantitative Morphometric Analysis of Progressive Infundibular Obstruction in Tetralogy of Fallot
A Prospective Longitudinal Echocardiographic Study
From the Lillie Frank Abercrombie Section of Cardiology and the Department of Pathology, Texas Children's Hospital, and the Departments of Pediatrics and Pathology, Baylor College of Medicine, Houston, Tex.
Correspondence to Tal Geva, MD, Department of Cardiology, Children's Hospital, 300 Longwood Ave, Boston, MA 02115.
 |
Abstract |
|---|
 Top Abstract IntroductionMethods Results Discussion References |
|---|
Background The morphological hallmark of tetralogy of Fallot is controversial, with much disagreement as to whether the subpulmonary infundibulum in this lesion is hypoplastic. In addition, few quantitative data are available regarding the morphometry of the subpulmonary infundibulum, what anatomic characteristics are acquired in the postnatal period, and at what rate they progress. We also sought to determine whether echocardiographic morphometric analysis of the infundibulum can predict clinical course in infants with tetralogy of Fallot.
Methods and Results Twenty-one infants with tetralogy of Fallot (median age at initial study, 1.6 months) were prospectively followed with serial echocardiograms until the time of first surgical intervention (median age at surgery, 10 months). Selected video still frames were digitized off-line with a computerized system. Compared with age-matched normal control infants (n=37), the following indexed infundibular dimensions in patients with tetralogy of Fallot were significantly smaller: length (1.86±0.54 versus 2.7±0.56 cm/BSA0.5, P<.0001), cross-sectional area (1.6±0.49 versus 4.7±1.3 cm2/BSA, P<.0001), and volume (1.24±0.62 versus 7.2±3 mL/BSA1.5, P<.0001). The following measurements were increased in tetralogy patients: infundibular septal thickness (0.83±0.21 versus 0.54±0.06 cm/BSA0.5, P=.0002) and infundibular free-wall thickness (0.62±0.13 versus 0.49±0.06 cm/BSA0.5, P=.006). The angle between infundibular septum and ventricular septum had a greater degree of anterosuperior deviation in tetralogy patients, resulting in a larger infundibuloventricular septal angle (77±8.2° versus 31±6.5°, P<.0001). During follow-up, infundibular volume in tetralogy patients decreased from 1.24±0.62 to 0.81±0.47 mL/BSA1.5 (P=.002), correlating with infundibular septal thickness (r=-.63, P<.003). The mean rate of decrease of indexed infundibular volume was 0.1±0.13 mL · BSA-1.5 · mo-1. Correlation analysis revealed a nonlinear correlation between the degree of infundibular septal malalignment and indexed infundibular volume (r=.93, P<.0001). Tetralogy patients who required early surgical intervention (4.8±0.9 versus 10.7±1.7 months, P<.0001) had a smaller infundibulum at presentation (0.92±0.35 versus 1.41±0.67 mL/BSA1.5, P=.04) and an accelerated rate of infundibular narrowing (0.17±0.18 versus 0.06±0.08 mL · BSA-1.5 · mo-1, P=.04).
Conclusions Compared with normal infants, the subpulmonary infundibulum in tetralogy of Fallot is characterized by a smaller volume, shorter and thicker infundibular septum, and anterosuperior deviation of the infundibular septum. Infundibular obstruction in tetralogy patients is progressive, with an average rate of decrease in indexed infundibular volume of 0.1±0.13 mL · BSA-1.5 · mo-1. Infants who are likely to require early therapeutic intervention may be identified on their initial echocardiogram as having an infundibular volume of <0.9 to 1.0 mL/BSA1.5.
Key Words: tetralogy of Fallot • echocardiography • longitudinal studies • surgery
|
Introduction |
|---|
|
TopAbstractIntroductionMethods Results Discussion References |
|---|
Although considerable progress has been made in the diagnosis and management of patients with tetralogy of Fallot,1 2 3 4 5 6 7 8 the morphological basis of the malformation has remained controversial.9 10 11 12 13 More than two centuries after the first anatomic description by Stensen, Fallot was the first to recognize, in 1888, that most patients with "la maladie bleue" had a consistent combination of cardiac malformations, including obstruction of the right ventricular outflow tract, ventricular septal defect, overriding of the aorta above the ventricular septum, and right ventricular hypertrophy.14 15 Fallot was also the first to recognize that the coexistence of these abnormalities was likely to be related to a single defect of the subpulmonary infundibulum and the pulmonary valve.14 15 His view was subsequently endorsed by Abbott and Dawson,16 who named the malformation "tetralogy of Fallot." In 1970, Van Praagh and his colleagues9 advocated that the underlying morphogenetic abnormality in tetralogy of Fallot is hypoplasia of the subpulmonary infundibulum, with all other lesions being sequelae. This opinion was later disputed by Becker et al10 11 and Anderson et al,12 who argued that the principal abnormality in tetralogy of Fallot is anterosuperior deviation of the infundibular septum and not hypoplasia of the subpulmonary infundibulum.
The morphology and morphometry of the subpulmonary infundibulum also have important clinical and surgical relevance. The progressive nature of right ventricular outflow tract obstruction has often been observed clinically,7 17 although not studied quantitatively. The acquired progressive physiological changes in tetralogy of Fallot are exemplified by patients who present in early infancy with minimal or no cyanosis and later develop increasing cyanosis.17 18 It is not known, however, what morphometric factors determine the dimensions and geometry of the subpulmonary infundibulum, what morphometric changes occur during infancy, the rate at which they progress, and whether echocardiographic morphometric analysis of the infundibulum can predict clinical course in infants with tetralogy of Fallot.
|
Methods |
|---|
|
TopAbstractIntroductionMethods Results Discussion References |
|---|
Study Patients
This study was designed as a prospective longitudinal echocardiographic study. Patients who were diagnosed with tetralogy of Fallot between July 1990 and December 1992 at Texas Children's Hospital and who fulfilled the following criteria were included: (1) had complete two-dimensional and Doppler echocardiographic examination before 6 months of age; (2) had at least one additional echocardiographic examination before any surgical intervention; and (3) were evaluated clinically at the time of presentation and before surgical intervention. Tetralogy of Fallot was diagnosed by two-dimensional echocardiography according to the criteria set forth by Snider and Serwer13 and Williams et al.19 Patients with tetralogy of Fallot and atresia of the pulmonary outflow tract were not included in this study.
For most
statistical analyses, all tetralogy of Fallot
patients were included in a single group. To evaluate whether
morphometric measurements of the subpulmonary infundibulum may
predict clinical course, study patients were divided into two groups
according to age at surgery: group 1 consisted of patients who
underwent surgical intervention at age <6 months, and group 2
consisted of patients who were operated on at age 
6 months. The
decision to operate was made by the managing staff cardiologist and was
not affected by this study. In all cases, the indication for surgery
was progressive cyanosis, and primary surgical repair of tetralogy of
Fallot was performed in all patients.
A control group consisted of infants who underwent a complete echocardiographic examination for a heart murmur and were found to have a structurally normal heart. For each echocardiographic examination in a patient with tetralogy of Fallot, an aged-matched control infant was selected.
Echocardiographic Analysis
Echocardiograms were performed
with several commercially
available cardiac scanners with transducer frequency appropriate for
the patient's size. Studies were recorded on 1.27-cm super VHS
videocassette tapes. A complete two-dimensional and Doppler
examination was performed in each patient from the subxiphoid, apical,
parasternal, and suprasternal notch views. Sedation with chloral
hydrate (75 to 100 mg/kg, maximal dose 1 g) was used when necessary.
Heart rate, blood pressure, and arterial oxygen saturation
(by pulse oximetry) were monitored in sedated patients. The
echocardiograms were reviewed and selected still frames identified for
subsequent measurements. Hard copies were obtained with a video page
printer (Sony Videographic Printer UP-910), and measurements were made
with a digitizing tablet (Summagraphic II) attached to a personal
computer (Compaq 386 SX) with commercially available software
(Digisonics EchoPro 3.3) and with customized software (courtesy of
Steven D. Colan, MD, Children's Hospital, Boston, Mass). Each
measurement was obtained in triplicate, and the average value was used
for data analysis. To determine interobserver variability,
measurements were obtained independently by two investigators (F.A.P.,
R.P.).
The subpulmonary infundibulum was visualized from two
orthogonal views. The subxiphoid short-axis view displays the long axis
of the right ventricular outflow tract and provides the
anteroposterior and superoinferior coordinates of the
infundibulum (Fig 1A
). The subxiphoid long-axis view
displays a coronal view of the infundibulum and provides
superoinferior and right-left coordinates. Aortic
valve–mitral valve fibrous contiguity was evaluated from the
parasternal long-axis view. Measurements of the subpulmonary
infundibulum were performed in systole because its dimensions are
clinically most relevant and blood is ejected during that period of the
cardiac cycle. The following dimensions were measured on the first
video frame after semilunar valve opening.
|
The diameter of the proximal
os infundibulum was measured from the
subxiphoid short-axis view between the inferior free margin
of the infundibular septum and the infundibular anterior free wall (1
in Fig 1B
).
The pulmonary valve annulus diameter was
measured at the hinge
point of the valve leaflets (2 in Fig 1B).
The length of
the subpulmonary infundibulum was measured from
the subxiphoid short-axis view from the midpoint of the
pulmonary valve annulus to the midpoint of the proximal os
infundibular diameter (3 in Fig 1B).
The infundibular
cross-sectional area was planimetered in the
subxiphoid short-axis view as illustrated in Fig 1B.
The infundibular septal thickness was measured from the subxiphoid short-axis view at the midpoint between pulmonary valve annulus and proximal os infundibulum.
The infundibular free-wall thickness was measured from the subxiphoid short-axis view at the midpoint between pulmonary valve annulus and proximal os infundibulum.
The diameter of the main pulmonary artery above the pulmonary sinuses of Valsalva and the diameters of branch pulmonary arteries immediately distal to their bifurcation from the main pulmonary artery were measured from the parasternal short-axis or suprasternal notch views.
The infundibuloventricular
septal angle was defined as the
angle formed by the plane of the superior half of the
ventricular septum and the "long axis" of the
infundibular septum as profiled from the subxiphoid short-axis view
(Fig 1C).
The infundibular volume was calculated with two algorithms: (1) the single plane area-length method,20 in which infundibular volume=0.849xA2/L, where A is planimetered cross-sectional area and L is infundibular length; and (2) assumption of a truncated cone geometry, with V=0.3xLx[B+b+(Bxb)0.5], where L is length, B is the area of the lower base, and b is the area of the upper base.21
Linear measurements were indexed to the square root of body surface area (BSA0.5), cross-sectional area measurements were indexed to BSA, and volumetric measurements were indexed to BSA1.5.22 Doppler velocity across the right ventricular outflow tract was recorded, and maximal instantaneous gradient was estimated with the modified Bernoulli equation [gradient=4x(velocity)2].23
Data Analysis
Numerical data are expressed as mean±SD.
Differences between
the means of echocardiographic measurements at first
and last studies were compared by paired Student's t test.
The unpaired Student's t test was used to compare results
in patients with tetralogy of Fallot and control subjects and between
tetralogy patients who required early surgery (<6 months) and those
who underwent surgery later (6 months). Simple linear regression
analysis by the least-squares method was used to examine the
relations between continuous variables.24 To further
examine the relations between infundibular volume, infundibular
thickness, infundibuloventricular septal angle,
pulmonary arterial diameters, and
Doppler-derived right ventricular outflow tract
gradient, linear and nonlinear regression analyses were
performed. For each regression, the F and t tests were
applied to determine whether there was a significant deviation from
linearity.25 For those regressions that were significantly
nonlinear, the best-fit curve was calculated with polynomial regression
models and the least-squares method.25 Where appropriate,
z values were computed as follows: (measured value-mean
value of healthy control subjects)/SD of healthy control subjects.
Results of interobserver variability with respect to infundibular
volume and infundibuloventricular septal angle were
expressed as the mean difference between observations divided by their
average measurements.26 Data analysis was
performed on a Macintosh Quadra 900 personal computer with a
commercially available statistical package (STATVIEW 4.0,
Abacus Concepts Inc). For all tests, a value of P<.05 was
considered significant.
|
Results |
|---|
|
TopAbstractIntroductionMethods Results Discussion References |
|---|
Twenty-one patients with tetralogy of Fallot, 10 boys and 11 girls, met the inclusion criteria for this study. Their clinical profile is summarized in Table 1
. Early surgical repair
was performed in 7 infants (mean age at surgery, 4.8±0.9 months)
because of rapidly progressive cyanosis. The remaining 14 patients
underwent surgical repair at 10.7±1.7 months. The control group
consisted of 37 infants who were age-matched with the study
patients.
|
Echocardiographic Morphometric Findings
The salient
morphometric measurements are summarized in
Table 2. Compared with healthy control subjects, the
infundibular septum in patients with tetralogy of Fallot was deviated
anterosuperiorly, resulting in a much larger
infundibuloventricular septal angle (77±8.2° versus
31±6.5°, P<.0001). In addition, patients with tetralogy
of Fallot had a shorter infundibulum (1.86±0.54 versus 2.7±0.56
cm/BSA0.5, P<.0001), a thicker
infundibular septum (0.83±0.21 versus 0.54±0.06
cm/BSA0.5, P=.002), a smaller
infundibular cross-sectional area (1.6±0.49 versus 4.7±1.3
cm2/BSA, P<.0001), and a much smaller
infundibular volume (1.24±0.62 versus 7.2±3
mL/BSA1.5, P<.0001). On average, the
indexed diameters of the pulmonary valve and main
pulmonary artery were significantly hypoplastic, but the
diameters of the branch pulmonary arteries were closer to the
lower limit of the normal range for BSA (Tables 2 and
3). Correlation analysis revealed a close
nonlinear correlation between the degree of infundibular septal
malalignment (quantified as infundibuloventricular septal
angle) and indexed infundibular volume, with a correlation coefficient
of .93 and a probability value of P<.0001 (Fig 2).
The
relation between infundibuloventricular septal angle (X)
and indexed infundibular volume (Y) is described by the equation
Y=Xx8.43e-2-8.73e-4xX2,
which describes a nonlinear decrease in infundibular volume as the
angle between the infundibular septum and the muscular
ventricular septum increases (Fig 2).
Infundibular volume decreased steeply when
infundibuloventricular angle exceeded 65°. No significant
correlation was found between either infundibular volume or
infundibuloventricular septal angle and the diameters of
the pulmonary valve or main or branch pulmonary
arteries or the Doppler gradient across the right
ventricular outflow tract at presentation or
during follow-up.
|
|
|
Measurements of infundibular volume derived with a truncated cone geometry showed up to 90% variability. This could be explained by the fact that small differences in measurements of the diameters of the lower and upper bases of the truncated cone resulted in large differences in the areas of the bases, thus greatly affecting the calculated volume. In contrast, use of the area-length algorithm for determining infundibular volume resulted in much more consistent values, with only 10.4% variability. Consequently, only area-length–derived infundibular volume data were used for analysis.
Follow-up Echocardiographic Data
During the follow-up period
in patients with tetralogy of
Fallot, the absolute dimensions of the subpulmonary
infundibulum (not indexed to BSA) did not change significantly while
significant somatic growth occurred (Tables 1 and
4).
When infundibular area and volume were indexed to BSA, it became
apparent that the subpulmonary infundibulum became
progressively smaller (Table 4, Fig 3). Most
significantly, indexed infundibular volume decreased from 1.24±0.62 to
0.81±0.47 mL/BSA1.5 (P=.002). The mean rate
of
decrease of indexed infundibular volume was 0.1±0.13
mL · BSA-1.5 · mo-1. The rate
of
change of indexed infundibular volume did not correlate with initial
infundibular volume at presentation or with
infundibuloventricular septal angle. Similarly, no
correlation was found between rate of decrease of indexed infundibular
volume and the diameters of the pulmonary valve or
pulmonary arteries. Infundibular septal thickness increased
significantly, from 0.41±0.1 to 0.52±0.07 cm
(P<.0001),
and infundibular free-wall thickness increased from 0.3±0.07 to
0.37±0.08 cm (P=.008). The increase in infundibular
septal
and free-wall thickness was proportional to somatic growth, with no
significant change when indexed to BSA (Table 4). A significant
negative linear correlation was found between infundibular septal
thickness and indexed infundibular volume at the end of the follow-up
period (r=-.63, P<.003). Hence, a thicker
infundibular septum was associated with a smaller indexed infundibular
volume (indexed infundibular volume=2.6-3.4xinfundibular
septal
thickness). The indexed diameters of the pulmonary valve and
main and branch pulmonary arteries did not change significantly
during the follow-up period. The same observation was made when these
measurements were compared with normal control data and expressed as
z scores (Table 3). Infundibuloventricular
septal angle did not change significantly during the study period
(77±8.2° at presentation versus 79.5±9.6° before
surgery, P=.17). In contrast to patients with tetralogy of
Fallot, in control patients the absolute dimensions of the
subpulmonary infundibulum (not indexed to BSA) increased
significantly during the first year of life with linear correlation to
BSA (r=.43, P=.015) and age
(r=.53,
P=.002). The gradient across the right
ventricular outflow tract increased from 66±12 to 78±18
mm Hg (P=.006). No correlation was found between
Doppler gradient and indexed infundibular volume, rate of decrease
of indexed infundibular volume, infundibuloventricular
septal angle, or the diameter of the pulmonary valve or
pulmonary arteries.
|
|
Effect of Infundibular Morphometry on Age at Surgery
Of the
21 patients with tetralogy of Fallot, 7 patients
underwent surgical repair before 6 months of age because of rapidly
progressive cyanosis (mean age at surgery, 4.8±0.9 months), and 14
patients underwent elective surgical repair at 10.7±1.7 months of age
(P<.0001) (Table 5). Comparison between the
two groups revealed that indexed infundibular volume on initial
echocardiographic examination was significantly smaller
in patients who required early surgery (0.92±0.35 versus
1.41±0.67
mL/BSA1.5, P=.04) and the rate of
decrease of indexed infundibular volume was faster (0.17±0.18 versus
0.06±0.08
mL · BSA-1.5 · mo-1,
P=.038). No additional significant differences between
groups were found (Table 5).
|
Interobserver Variability
For both infundibuloventricular
septal angle and
infundibular volume, close interobserver agreements were found.
For infundibuloventricular septal angle, the mean
difference between observers was 10.3±12.7%, or 3.3±5.7°.
Close
correlation was found between the two observers, with a .91 correlation
coefficient (P=.001). For infundibular volume (using the
area-length algorithm), the mean interobserver variability was
13.6±27% or 0.47±1.6 mL/BSA1.5 and the correlation
coefficient was .88 (P=.001).
|
Discussion |
|---|
|
TopAbstractIntroductionMethods Results Discussion References |
|---|
This study shows that both major hypotheses regarding the morphological "essence" of tetralogy of Fallot9 10 11 12 are valid. Our data indicate that the subpulmonary infundibulum in tetralogy of Fallot is hypoplastic in terms of its length, cross-sectional area, and volume (Table 2
) and that the
infundibular
septum is deviated anterosuperiorly relative to the
ventricular septum. Furthermore, we found that infundibular
hypoplasia and infundibular septal deviation are closely linked, with a
negative nonlinear relation between them. The more anterocephalad
infundibular septum is deviated (larger
infundibuloventricular septal angle), the more infundibular
volume decreases (Fig 2). The degree of infundibular hypoplasia
was
considerably more prominent when measured in terms of volume, being, on
average, 17.2% of normal infundibular volume, whereas infundibular
length averaged 68.9% of normal. The close association between
infundibuloventricular septal angle and infundibular volume
found in our study suggests that the conotruncal anomaly seen in
tetralogy of Fallot may relate to the same underlying morphogenetic
mechanism rather than several different mechanisms, as previously
suggested.27 28 29 30 The
specific nature and, most importantly,
the cause of the morphogenetic mechanism leading to tetralogy of Fallot
were not addressed in this study.
Progression of right ventricular outflow tract obstruction
in patients with tetralogy of Fallot has been widely observed
clinically and has been attributed by many authors to acquired
infundibular
hypertrophy.17 18 31 32 33
However,
these clinical observations have not been substantiated with
quantitative data. We found that between the time of
presentation (median age, 1.6 months) and the time of
surgical repair (median age, 10 months), the absolute dimensions of the
subpulmonary infundibulum did not change significantly (Table
4). However, when somatic growth was taken into consideration,
it
became apparent that infundibular volume did not keep up with somatic
growth and became significantly smaller, decreasing from 1.24±0.62
mL/BSA1.5 at presentation to 0.81±0.47
mL/BSA1.5 before surgery (P=.002). At the same
time that indexed infundibular volume decreased 34.7%, infundibular
septal thickness increased 21.1% and infundibular free-wall thickness
increased 16.4%. Indeed, significant negative linear correlation was
found between infundibular septal thickness and indexed infundibular
volume (r=-.63, P<.003), suggesting that
progressive infundibular obstruction in tetralogy of Fallot can be
attributed, at least in part, to infundibular hypertrophy.
Other factors, such as abnormal infundibular growth due to intrinsic
infundibular myocardial abnormality, should be kept in mind. The
concept that infundibular musculature may have distinct genetic,
molecular, and biochemical properties is supported by previous
observations.34 35 36 37 38
The pulmonary valve annulus and main pulmonary artery were grossly hypoplastic at presentation, whereas the branch pulmonary arteries were frequently within or toward the lower limit of the normal range. These data substantiate the impression of other investigators that in "simple" tetralogy of Fallot, the branch pulmonary arteries are seldom discontinuous or markedly hypoplastic, as is often seen in tetralogy with pulmonary atresia.33 Interestingly, no significant changes were observed during the study period in the indexed diameters of the pulmonary valve or main or branch pulmonary arteries. It should be kept in mind, however, that 20 of our 21 patients underwent surgical repair during the first year of life and that the "natural history" of pulmonary arterial growth beyond the first year of life was not evaluated in this study.
The data presented in this study also have clinical prognostic
implications. Whereas many infants with tetralogy of Fallot present
with a prominent systolic heart murmur and little or no cyanosis, a
distinct subgroup of patients either present with significant
cyanosis or develop rapidly progressive cyanosis in early infancy,
necessitating early surgical or catheter
intervention.5 17 18 The role of
hemodynamic variables, including the varying
balance between the resistances of the systemic and pulmonary
vascular beds, is well
appreciated.17 18 31 33
However,
little is known regarding morphometric predictors of early surgical
intervention. We found that patients who required surgical repair of
tetralogy of Fallot before 6 months of age (mean age, 4.8±0.9 months)
had a significantly smaller infundibular volume compared with those who
had their repair in the second half of the first year (mean age,
10.7±1.7 months) (Table 5). Furthermore, the rate of
decrease in
indexed infundibular volume was significantly accelerated in the former
group. Hence, tetralogy patients who require therapeutic intervention
in early infancy have a smaller infundibular volume at
presentation that tends to rapidly fall behind the demands
created by somatic growth. Other morphometric measurements of the
infundibulum, the dimensions of the pulmonary valve and
pulmonary arteries, and Doppler gradient across the right
ventricular outflow tract did not differ between
groups.
Study Limitations
The follow-up period in this study was
limited to the first year
of life because 20 of 21 patients required surgical repair of their
tetralogy of Fallot before their first birthday. Indeed, in view of the
excellent surgical results of primary surgical repair during infancy
(no mortality in this series),2 4 33
delaying therapeutic
intervention in patients with "simple" tetralogy cannot be
justified. Measurements in this study were obtained by two-dimensional
echocardiography, which is a cross-sectional
imaging technique with inherent limitations in terms of lateral and
spatial resolution. However, the same technique was used in all study
patients and healthy control subjects with good reproducibility,
allowing valid intragroup and intergroup comparisons. Finally, patients
with rare forms of tetralogy of Fallot (such as complete absence of the
infundibular septum) were not encountered during the study period.
Conclusions
(1) Compared with healthy infants, the
subpulmonary
infundibulum in tetralogy of Fallot is characterized by a smaller
volume, shorter and thicker infundibular septum, and anterosuperior
deviation of the infundibular septum. (2) Infundibular obstruction in
tetralogy of Fallot is progressive and is associated with infundibular
hypertrophy. (3) Infants who are likely to require early
therapeutic intervention may be identified on their initial
echocardiogram as having an infundibular volume of 
0.9 to 1.0
mL/BSA1.5.
|
Acknowledgments |
|---|
We thank Tim C. McQuinn, MD, for his useful comments.
|
Footnotes |
|---|
Guest editor for this article was Joseph K. Perloff, MD, UCLA School of Medicine, Los Angeles, Calif.
Received January 9, 1995; accepted February 6, 1995.
|
References |
|---|
|
TopAbstractIntroductionMethods Results Discussion References |
|---|
1. Zhao H, Miller DC, Reitz BA, Shumway NE. Surgical repair of tetralogy of Fallot. J Thorac Cardiovasc Surg. 1985;89:204-220. [Abstract]
2.
Walsh EP, Rockenmacher S, Keane JF, Hougen TJ, Lock
JE, Castaneda AR. Late results in patients with tetralogy of
Fallot repaired during infancy.
Circulation. 1988;77:1062-1067.
3. Touati GD, Vouhe PR, Amodeo A, Pouard P, Mauriant P, Leca F, Neveux JY. Primary repair of tetralogy of Fallot in infancy. J Thorac Cardiovasc Surg. 1990;99:396-403. [Abstract]
4. Di Donato RM, Jonas RA, Lang P, Rome JJ, Mayer JE, Castaneda AR. Neonatal repair of tetralogy of Fallot with and without pulmonary atresia. J Thorac Cardiovasc Surg. 1991;101:126-137. [Abstract]
5. Sreeram N, Saleem M, Jackson M, Peart I, McKay R, Arnold R, Walsh K. Results of pulmonary valvuloplasty as a palliative procedure in tetralogy of Fallot. J Am Coll Cardiol. 1990;18:159-165.
6. Wessel HU, Cunningham WJ, Paul MH, Bastanier CK, Muster AJ, Idriss AS. Exercise performance in tetralogy of Fallot after intracardiac repair. J Thorac Cardiovasc Surg. 1980;80:582-593. [Abstract]
7.
Bonchek LI, Starr A, Sunderland CO, Menashe VD.
Natural history of tetralogy of Fallot in infancy.
Circulation. 1973;48:392-397.
8.
Murphy JG, Gersh BJ, Mair DD, Fuster V, McGoon MD,
Ilstrup DM, McGoon DC, Kirklin JW, Danielson GK. Long-term
outcome in patients undergoing surgical repair of tetralogy of
Fallot. N Engl J Med. 1993;329:593-599.
9. Van Praagh R, Van Praagh S, Nebesar RA, Muster AJ, Sinha SN, Paul MH. Tetralogy of Fallot: underdevelopment of the pulmonary infundibulum and its sequelae. Am J Cardiol. 1970;26:25-33. [Medline] [Order article via Infotrieve]
10. Becker AE, Connor M, Anderson RH. Tetralogy of Fallot: a morphometric and geometric study. Am J Cardiol. 1975;35:402-412. [Medline] [Order article via Infotrieve]
11. Becker AE. Surgical anatomy of tetralogy of Fallot: the variables. In: Crupi G, Parenzan L, Anderson RH, eds. Perspectives in Pediatric Cardiology. Mount Kisco, NY: Futura Publishing Co; 1989:145-148.
12. Anderson RH, Allwork SP, Ho SY, Lenox CC, Zuberbuhler JR. Surgical anatomy of tetralogy of Fallot. J Thorac Cardiovasc Surg. 1981;81:887-896. [Abstract]
13. Snider RA, Serwer GA. Tetralogy of Fallot. In: Echocardiography in Pediatric Heart Disease. Chicago, Ill: Year Book Medical Publishers, Inc; 1990:150-153.
14. Van Praagh R. Etienne-Louis Arthur Fallot and his tetralogy: a new translation of Fallot's summary and a modern reassessment of this anomaly. Eur J Cardiothorac Surg. 1989;3:381-386. [Abstract]
15. Allwork SP. Tetralogy of Fallot: the centenary of the name: a new translation of the first of Fallot's papers. Eur J Cardiothorac Surg. 1988;2:386-392. [Abstract]
16. Abbott ME, Dawson WT. The clinical classification of congenital cardiac disease, with remarks upon its pathological anatomy, diagnosis and treatment. Int Clin. 1924;4:156-188.
17. Zuberbuhler JR. Tetralogy of Fallot. In: Adams FH, Emmanouilides GC, Riemenschneider TA, eds. Heart Disease in Infants, Children, and Adolescents. Baltimore, Md: Williams & Wilkins; 1989:273-288.
18. Fyler DC. Tetralogy of Fallot. In: Nadas AS, Fyler DC, eds. Nadas' Pediatric Cardiology. 4th ed. Philadelphia, Pa: Henley & Belfus; 1992:471-491.
19. Williams RG, Bierman FZ, Sanders SP. Echocardiographic Diagnosis of Cardiac Malformations. Boston, Mass: Little, Brown & Co; 1986:155-162.
20. Silverman NH, Hudson S. Evaluation of right ventricular volume and ejection fraction in children by two-dimensional echocardiography. Pediatr Cardiol. 1983;4:197-204. [Medline] [Order article via Infotrieve]
21. Nielsen KL. Mathematics for Practical Use. New York, NY: Barnes & Noble; 1962:101-105.
22. Gutgesell HP, Rembold CM. Growth of the human heart relative to body surface area. Am J Cardiol. 1990;65:662-668. [Medline] [Order article via Infotrieve]
23. Hatle L, Angelsen B. Doppler Ultrasound in Cardiology: Physical Principles and Clinical Implications. 2nd ed. Philadelphia, Pa: Lea & Febiger; 1985:24.
24. Glantz SA. Primer of Biostatistics. New York, NY: McGraw-Hill; 1987:191-244.
25. Haycock KA, Roth J, Gagnon J, Finzer WF, Soper C. Statview 4.0 Software Manual. Berkeley, Calif: 1992:300-320.
26. Hinelman RB, Cassidy MM, Landzberg JS, Schiller NB. Reproducibility of quantitative two-dimensional echocardiography. Am Heart J. 1988;115:425-431. [Medline] [Order article via Infotrieve]
27. Van Mierop LHS, Patterson DF. Pathogenesis of conotruncal defects and some other cardiovascular anomalies in the Keeshond dog. In: Van Praagh R, Takao A, eds. Etiology and Morphogenesis of Congenital Heart Disease. Mt Kisco, NY: Futura Publishing Co; 1980:177-193.
28. Van Mierop LHS, Wiglesworth FW. Pathogenesis of transposition complexes, II: anomalies due to faulty transfer of the posterior great artery. Am J Cardiol. 1963;12:226-232. [Medline] [Order article via Infotrieve]
29. Goor DA, Lillehei CW, Edwards JE. Ventricular septal defects and pulmonic stenosis with and without dextroposition: anatomic features and embryologic implications. Chest. 1971;60:117-128.
30. De la Cruz MV, da Rocha JP. An ontogenetic theory for the explanation of congenital malformations involving the truncus and conus. Am Heart J. 1956;51:782-805. [Medline] [Order article via Infotrieve]
31. Neches WH, Park SC, Ettedgui JA. Tetralogy of Fallot and tetralogy of Fallot with pulmonary atresia. In: Garson A Jr, Bricker JT, McNamara DG, eds. The Science and Practice of Pediatric Cardiology. Philadelphia, Pa: Lea & Febiger; 1990:1073-1100.
32. Smolinsky A, Tamarkin M, Goor DA. Fractional gradients along the outflow tract of the right ventricle in tetralogy of Fallot. J Thorac Cardiovasc Surg. 1981;81:774-780. [Abstract]
33. Castaneda AR, Jonas RA, Mayer JE, Hanley FL. Tetralogy of Fallot. In: Cardiac Surgery of the Neonate and Infant. Philadelphia, Pa: WB Saunders; 1994:215-234.
34. McGrath LB, Chen C, Gu J, Bianchi J, Levett JM. Determination of infundibular innervation and amine receptor content in cyanotic and acyanotic myocardium: relation to clinical events in tetralogy of Fallot. Pediatr Cardiol. 1991;12:155-160. [Medline] [Order article via Infotrieve]
35. Yancey SB, Biswal S, Revel JP. Spatial and temporal patterns of distribution of the gap junction protein connexin 43 during mouse gastrulation and organogenesis. Development. 1992;114:203-212. [Abstract]
36. De Groot IJM, Lamers WH, Moorman AFM. Isomyosin expression patterns during rat heart morphogenesis: an immunohistochemical study. Anat Rec. 1989;224:365-373. [Medline] [Order article via Infotrieve]
37. Wessels A, Vermeulen JLM, Viragh SZ, Kalman F, Morris GE, Thi Man N, Lamers WH, Moorman AFM. Spatial distribution of `tissue specific' antigens in the developing human heart and skeletal muscle. Anat Rec. 1990;228:163-176. [Medline] [Order article via Infotrieve]
38.
Van Kempen MJA, Fromaget C, Gros D, Moorman AFM, Lamers
WH. Spatial distribution of connexin 43, the major cardiac gap
junction protein, in the developing and adult rat heart.
Circ Res. 1991;68:1638-1651.
This article has been cited by other articles:
 |
|
 |
|
  J. Kolcz and C. Pizarro Neonatal repair of tetralogy of Fallot results in improved pulmonary artery development without increased need for reintervention Eur. J. Cardiothorac. Surg., September 1, 2005; 28(3): 394 - 399. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 U. Dyamenahalli, B. W. McCrindle, G. A. Barker, W. G. Williams, R. M. Freedom, and D. J. Bohn Influence of perioperative factors on outcomes in children younger than 18 months after repair of tetralogy of Fallot Ann. Thorac. Surg., April 1, 2000; 69(4): 1236 - 1242. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M.A. Gatzoulis, S.Y. Ho, and R.H. Anderson A reply Eur. Heart J., November 2, 1999; 20(22): 1682 - 1682. [PDF]
|
|
|
|
|
|
M.A. Gatzoulis, N. Soukias, S.Y. Ho, M. Josen, and R.H. Anderson Echocardiographic and morphological correlations in tetralogy of Fallot Eur. Heart J., February 1, 1999; 20(3): 221 - 231. [Abstract] [PDF]
|
|
| |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||