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ORIGINAL ARTICLE
Relationships between Left Heart Chamber Dilatationon Echocardiography and Left-to-Right Ventricle ShuntingQuantified by Cardiac Catheterization in Childrenwith Ventricular Septal Defects
Selman Gokalp • Ayse Guler Eroglu •
Levent Saltik • Bulent Koca
Received: 2 July 2013 / Accepted: 6 November 2013
� Springer Science+Business Media New York 2013
Abstract Left atrium and/or left ventricle dilatation on
echocardiography is considered to be an indication for
closure of ventricular septal defects (VSD). No study has
addressed the accuracy of using dilated left heart chambers
when defining significant left-to-right shunting quantified
by cardiac catheterization in isolated small or moderate
VSDs. In this study, the relation between dilated left heart
chambers, measured by echocardiography, and left-to-right
ventricle shunting, quantified by cardiac catheterization,
was evaluated in patients with isolated VSD. The medical
records of all patients with isolated VSD who had under-
gone catheterization from 1996 to 2010 were examined
retrospectively. Normative data for left heart chambers
adjusted for body weight (BW) and body surface area
(BSA) were used. The pulmonary-to-systemic flow ratio
(Qp:Qs) was calculated by an oximetry technique. A total
of 115 patients (mean age 7.3 ± 5 years) fulfilled the
inclusion criteria. There was a statistically significant dif-
ference in terms of Qp:Qs between the patient groups with
normal and dilated left heart chambers, when adjusted for
BW and BSA (p = 0.001 and p = 0.002, respectively).
But the relationships between Qp:Qs and left heart cham-
ber sizes on echocardiography were not strong enough to
be useful for making surgical decisions, as left heart
chamber dilatation was not significantly associated with
Qp:Qs C 2 (p = 0.349 when adjusted for BW, p = 0.107
when adjusted for BSA). Left heart chamber dilatation was
significantly associated with Qp:Qs C 1.5 only when it was
adjusted for BSA (for BW p = 0.022, for BSA p = 0.006).
As a result, left heart chamber dilatation measured by
echocardiography does not show significant left-to-right
ventricle shunting, as quantified by catheterization. We still
advocate that catheter angiography should be undertaken
when left heart chambers are dilated in echocardiography
in order to make decisions about closing small- to mod-
erate-sized VSD.
Introduction
The medical management of patients with a ventricular
septal defect (VSD) has not changed much over recent
years, but the surgical and interventional management of
these patients has changed significantly. Although the
indications for surgical repair of large VSDs in infancy are
well defined, there is ongoing discussion about the indi-
cations for closure of small- to moderate-sized VSDs. In
older, asymptomatic children with normal pulmonary
artery pressure, it is generally accepted that VSD closure is
indicated if the pulmonary to systemic flow ratio (Qp:Qs)
is [ 2 [23]. However, changes in surgical management and
the development of transcatheter closure methods have
lowered the threshold for closure of small- to moderate-
sized VSDs. Currently, Qp:Qs [ 1.5 or dilatation of the
left atrium (LA), and dilatation of the left ventricle (LV) on
S. Gokalp (&)
Cocuk Kardiyoloji Bilim Dali, Trakya Universitesi Tip
Fakultesi, Balkan Yerleskesi, Edirne, Turkey
e-mail: [email protected]
S. Gokalp
Division of Pediatric Cardiology, Trakya University Medical
Faculty, Edirne, Turkey
A. Guler Eroglu � L. Saltik
Division of Pediatric Cardiology, Istanbul University Cerrahpasa
Medical Faculty, Istanbul, Turkey
B. Koca
Division of Pediatric Cardiology, Harran University Medical
Faculty, Sanliurfa, Turkey
123
Pediatr Cardiol
DOI 10.1007/s00246-013-0839-5
echocardiography are considered to be indications for VSD
closure [31, 32]. However, no previous studies have
reported on the accuracy of left heart chamber dilatation
measured by echocardiography for predicting significant
LV to right ventricle (RV) shunting as quantified by car-
diac catheterization in patients with isolated small- and
moderate-sized VSDs.
In general, we recommend VSD closure only if
Qp:Qs C 2. All our patients with isolated small- to mod-
erate-sized VSDs who are considered for surgery therefore
undergo cardiac catheterization to determine Qp:Qs, pul-
monary artery pressure, and pulmonary vascular resistance.
The aim of this study was to evaluate the relationships
between LA and LV size measured by echocardiography
and LV-to-RV shunting quantified by cardiac catheteriza-
tion in patients with isolated small- to moderate-sized
VSDs.
Materials and Methods
Patients
The medical records of all children with VSDs who
underwent cardiac catheterization and angiography from
1996 to 2010 were retrospectively examined. Patients with
additional diagnoses that could affect left-to-right shunting
and patients with pulmonary hypertension were excluded.
Pulmonary hypertension was defined as a mean pulmonary
arterial pressure of [25 mmHg on cardiac catheterization.
The main indication for cardiac catheterization and
angiocardiography was LV or LA dilatation on echocar-
diography. Other indications included excessive LV-to-RV
shunting, suspected pulmonary hypertension based on
transthoracic echocardiography findings, and clinical find-
ings that could not be explained solely by the VSD. We
identified 115 patients who met the inclusion criteria.
Informed consent was obtained from each patient’s family
prior to cardiac catheterization and angiography. The study
was approved by the Ethical Committee of Istanbul Uni-
versity Cerrahpasa Medical Faculty.
Echocardiographic Examinations
Transthoracic echocardiography was performed using a
Siemens Acuson CV70 system with a 4-2 (2–4 MHz) or
9-4 (4–9 MHz) transducer, or a General Electric Vivid 3
system with a 3S (1.5–2.6 MHz) or 7S (3–7 MHz) trans-
ducer. Infants were sedated with intranasal midazolam
when necessary. Two-dimensional M-mode, color-flow
Doppler, pulsed Doppler, and continuous-wave Doppler
echocardiography were performed in all patients. Mea-
surements of the LV, LA, interventricular septum, LV
posterior wall, and aorta were performed by M-mode
echocardiography in the long axis view [27]. Normative
data for cardiovascular structures adjusted for body weight
(BW) were used during routine echocardiographic evalu-
ations [11], and normative data adjusted for body surface
area (BSA) were used retrospectively for study purposes
[17]. BSA was calculated using Costeff’s formula [5].
VSDs were classified according to their location and rela-
tionships to the tricuspid annulus and semilunar valves
[30]. Defect size was expressed in terms of the size of the
aortic root. Defects were classified as large if the diameter
of the VSD was at least two-thirds of the diameter of the
aorta, moderate if the diameter of the VSD was one-third to
two-thirds of the diameter of the aorta, and small if the
diameter of the VSD was less than one-third of the diam-
eter of the aorta [23].
Cardiac Catheterization and Angiography
Cardiac catheterization and angiography were performed
under general anesthesia, and local anesthetic was infil-
trated at the puncture sites. Right-sided cardiac catheteri-
zation was performed in all patients to measure the
pressure and oxygen saturation in the pulmonary artery,
superior vena cava, right atrium, and inferior vena cava. In
patients with a patent foramen ovale, the LA, pulmonary
veins, and LV were evaluated in a retrograde fashion. Left-
sided cardiac catheterization was performed in patients
without a patent foramen ovale. The Qp:Qs, pulmonary
vascular resistance, and systemic vascular resistance were
calculated from oximetry and adjusted oxygen consump-
tion parameters according to the age of the patient. A
clinically important shunt was defined as Qp:Qs C 2.
Angiocardiography was performed in the long axial
oblique or four-chamber view depending on the location of
the VSD.
Statistical Analysis
The results are expressed as median, mean ± standard
deviation, or frequency and percentage. The normality of
data was tested using the Shapiro–Wilk test and histo-
grams. Multiple groups were compared using Kruskal–
Wallis one-way analysis of variance. If the Kruskal–Wallis
test showed a significant difference among groups, com-
parisons between groups were performed using post hoc
Mann–Whitney U tests with Bonferroni correction. The
normality of these data was tested using the one-sample
Kolmogorov–Smirnov test. Considering the number and
distribution of patients, a p value of \0.008 was considered
statistically significant. Data analysis was performed using
SPSS statistical software for Windows (Version 17.0; SPSS
Inc., Chicago, IL, USA).
Pediatr Cardiol
123
Results
The 115 patients included in this study were 62 males
(54 %) and 53 females (46 %), with a mean age of
7.3 ± 5 years (range 8 months to 18 years), mean BW of
16 ± 14.3 kg (range 7–73), and mean BSA of
0.87 ± 0.34 m2 (range 0.36–1.83). The locations and sizes
of the VSDs on echocardiographic examination are shown
in Table 1, the 131 concomitant anomalies detected are
shown in Table 2, and the catheter angiography findings
are shown in Table 3.
M-mode echocardiographic measurements adjusted for
BW showed that 25 patients (21.7 %) had normal LA and
LV measurements, 8 (6.9 %) had LA dilatation only, 51
(44.4 %) had LV dilatation only, and 31 (27 %) had both
LA and LV dilatation. The Qp:Qs values were significantly
different among these groups (p = 0.001) (Table 4).
Comparisons between groups showed significant differ-
ences in Qp:Qs between patients with normal LV mea-
surements and patients with LV dilatation (p \ 0.002),
between patients with normal LA and LV measurements
and patients with both LA and LV dilatation (p \ 0.007),
and between patients with LA dilatation and patients with
LV dilatation (p \ 0.008).
M-mode echocardiographic measurements adjusted for
BSA showed that 22 patients (19.1 %) had normal LA and
LV measurements, 20 (17.4 %) had LA dilatation only, 34
(29.6 %) had LV dilatation only, and 39 (33.9 %) had both
LA and LV dilatation. The Qp:Qs values were significantly
different among these groups (p = 0.002) (Table 5).
Comparisons between groups showed significant differ-
ences in Qp:Qs between patients with normal LV mea-
surements and patients with LV dilatation (p \ 0.005) and
between patients with normal LA and LV measurements
and patients with both LA and LV dilatation (p \ 0.001).
When the left heart chamber sizes were classified
according to BW, 2 of 25 patients (8 %) with normal LA
Table 1 Locations and sizes of the ventricular septal defects (VSD)
on echocardiographic examination
VSD type n Small Moderate Total
Muscular
Inlet 3 1 2
Trabecular 6 5 1 18
Outlet 9 7 2
Perimembranous 96 29 67 96
Doubly committed subarterial 1 – 1 1
Total 115 42 73 115
Table 2 Concomitant anomalies in patients with ventricular septal
defects
Pathologic findings N
Ventricular septal aneurysm 80
Aortic valve prolapsus 24
Sub-aortic ridge (non-obstructive) 9
Left persistent superior vena cava 6
Bicuspid aortic valve 4
Right aortic arch 3
Mitral valve prolapsus 3
Double aortic arch 2
Total 131
Table 3 Catheter angiography findings in patients with ventricular
septal defects
Parameter Mean (±SD)
PA systolic pressure (mmHg) 27.13 (7.36)
PA diastolic pressure (mmHg) 11.53 (3.60)
PA mean pressure (mmHg) 17.64 (4.58)
Qp:Qs 1.52 (0.43)
PVR (Wood unit m2) 2.07 (1.17)
SVR (Wood unit m2) 21.49 (8.14)
Total 115
PA pulmonary artery, PVR pulmonary vascular resistance, Qp:Qs
pulmonary to systemic flow ratio, SD standard deviation, SVR sys-
temic vascular resistance
Table 4 Qp:Qs values in patients with normal and dilated left heart
chambers adjusted for body weight
Left heart chambers N (%) Qp:Qs [mean (±SD)]
Normal 25 (21.7) 1.34 (0.35)
LA dilated 8 (6.9) 1.24 (0.26)
LV dilated 51 (44.4) 1.63 (0.48)
LA and LV dilated 31 (27) 1.56 (0.35)
Total 115 (100) 1.52 (0.43)
p = 0.001
LA left atrium, LV left ventricle, Qp:Qs pulmonary to systemic flow
ratio, SD standard deviation
Table 5 Qp:Qs values in patients with normal and dilated left heart
chambers adjusted for body surface area
Left heart chambers N (%) Qp:Qs [mean (±SD)]
Normal 22 (19.1) 1.31 (0.33)
LA dilated 20 (17.4) 1.40 (0.37)
LV dilated 34 (29.6) 1.56 (0.48)
LA and LV dilated 39 (33.9) 1.66 (0.40)
Total 115 (100) 1.52 (0.43)
p = 0.002
LA left atrium, LV left ventricle, Qp:Qs pulmonary to systemic flow
ratio, SD standard deviation
Pediatr Cardiol
123
and LV measurements, 10 of 51 patients (19.6 %) with LV
dilatation only, and 5 of 31 patients (16.1 %) with both LA
and LV dilatation had Qp:Qs C 2 (Table 6). When the left
heart chamber sizes were classified according to BSA, 1 of
22 patients (4.5 %) with normal LA and LV measurements,
2 of 20 patients (10 %) with LA dilatation only, 4 of 34
patients (11.8 %) with LV dilatation only, and 10 of 39
patients (25.6 %) with both LA and LV dilatation had
Qp:Qs C 2 (Table 7). The proportions of patients with
Qp:Qs C 2 did not differ significantly among these groups
classified according to BW (p = 0.349) or BSA
(p = 0.107). Seventy-five of the 90 patients (83.3 %) with
dilatation of one or both left heart chambers adjusted for
BW and 77 of the 93 patients (82.7 %) with dilatation of
one or both left heart chambers adjusted for BSA had
Qp:Qs \ 2.
When the left heart chamber sizes were classified
according to BW, 6 of 25 patients (24 %) with normal LA
and LV measurements, 2 of 8 patients (25 %) with LA
dilatation only, 29 of 51 patients (56.8 %) with LV dila-
tation only, and 17 of 31 patients (54.8 %) with both LA
and LV dilatation had Qp:Qs C 1.5 (Table 8). The pro-
portions of patients with Qp:Qs C 1.5 did not differ sig-
nificantly among these groups classified according to BW
(p = 0.022). Thirty-eight of the 90 patients (42.2 %) with
dilatation of one or both left heart chambers adjusted for
BW had Qp:Qs \ 1.5. When the left heart chamber sizes
were classified according to BSA, 4 of 22 patients (18.1 %)
with normal LA and LV measurements, 8 of 20 patients
(40 %) with LA dilatation only, 17 of 34 patients (50 %)
with LV dilatation only, and 25 of 39 patients (64.1 %)
with both LA and LV dilatation had Qp:Qs C 1.5
(Table 9). The proportions of patients with Qp:Qs C 1.5
were significantly different among these groups classified
according to BSA (p = 0.006). There was a significant
difference in the proportion of patients with Qp:Qs C 1.5
between the group with normal LA and LV measurements
and the group with both LA and LV dilatation (p \ 0.001).
Forty-three of the 93 patients (46.2 %) with dilatation of
one or both left heart chambers adjusted for BSA had
Qp:Qs \ 1.5.
Discussion
In recent years, the risks associated with VSD surgery have
decreased substantially, and the mortality rate is now less
Table 6 Patients with Qp:Qs C 2 and Qp:Qs \ 2 in the groups with
normal and dilated left heart chambers adjusted for body weight
Left heart chambers [n (%)] Qp:Qs C 2 Qp:Qs \ 2 Total
Normal 2 (11.8) 23 (23.5) 25 (21.7)
LA dilated 0 (0) 8 (8.2) 8 (7)
LV dilated 10 (58.8) 41 (41.8) 51 (44.3)
LA and LV dilated 5 (29.4) 26 (26.5) 31 (27)
Total 17 (100) 98 (100) 115 (100)
p = 0.349
LA left atrium, LV left ventricle, Qp:Qs pulmonary to systemic flow
ratio
Table 7 Patients with Qp:Qs C 2 and Qp:Qs \ 2 in the groups with
normal and dilated left heart chambers adjusted for body surface area
Left heart chambers [n (%)] Qp:Qs C 2 Qp:Qs \ 2 Total
Normal 1 (5.9) 21 (21.4) 22 (19.1)
LA dilated 2 (11.8) 18 (18.4) 20 (17.4)
LV dilated 4 (23.6) 30 (30.6) 34 (29.6)
LA and LV dilated 10 (58.7) 29 (29.6) 39 (33.9)
Total 17 (100) 98 (100) 115 (100)
p = 0.107
LA left atrium, LV left ventricle, Qp:Qs pulmonary to systemic flow
ratio
Table 8 Patients with Qp:Qs C 1.5 and Qp:Qs \ 1.5 in the groups
with normal and dilated left heart chambers adjusted for body weight
Left heart
chambers [n (%)]
Qp:Qs C 1.5 Qp:Qs \ 1.5 Total
Normal 6 (11.1) 19 (31.1) 25 (21.7)
LA dilated 2 (3.7) 6 (9.8) 8 (7.0)
LV dilated 29 (53.7) 22 (36.1) 51 (44.3)
LA and LV dilated 17 (31.5) 14 (23.0) 31 (27.0)
Total 54 (100) 61 (100) 115 (100)
p = 0.022
LA left atrium, LV left ventricle, Qp:Qs pulmonary to systemic flow
ratio
Table 9 Patients with Qp:Qs C 1.5 and Qp:Qs \ 1.5 in the groups
with normal and dilated left heart chambers adjusted for body surface
area
Left heart
chambers [n (%)]
Qp:Qs C 1.5 Qp:Qs \ 1.5 Total
Normal 4 (7.4) 18 (29.5) 22 (19.1)
LA dilated 8 (14.8) 12 (19.7) 20 (17.4)
LV dilated 17 (31.5) 17 (27.9) 34 (29.6)
LA and LV dilated 25 (46.3) 14 (23.0) 39 (33.9)
Total 54 (100) 61 (100) 115 (100)
p = 0.006
LA left atrium, LV left ventricle, Qp:Qs pulmonary to systemic flow
ratio
Pediatr Cardiol
123
than 1 % [1, 24]. Additionally, transcatheter VSD closure
using various devices has become increasingly popular
because of the low complication rates and high rates of
successful closure without residual shunting [33]. The
indications for VSD closure have therefore been extended,
and closure is now suggested for small-sized VSDs with
Qp:Qs C 1.5, or even in patients with LA or LV dilatation
on echocardiography [32]. Pediatric cardiology textbooks
still advise that VSD closure is indicated when Qp:Qs [ 2,
but the indications have changed for adults. In asymp-
tomatic patients without pulmonary hypertension who have
left-sided volume overload, many centers recommend VSD
closure with the aim of avoiding late LV dysfunction
secondary to dilatation [7]. The 2008 Guidelines for the
Management of Adults with Congenital Heart Disease
published by the American Heart Association recommend
device closure of a muscular VSD if it is associated with
severe left-sided heart chamber enlargement or hemody-
namically significant left-to-right shunting (Qp:Qs [ 1.5)
[31]. These recommendations will probably be extended to
include children in the future.
Although the mortality rates associated with surgery and
transcatheter closure are very low, these procedures are not
risk free. Several studies reported good long-term out-
comes and low complication rates in patients with small
VSDs who were treated conservatively, and closure should
not considered as the only treatment option [8–10].
In this study, we evaluated the relationships between LA
and LV measurements on echocardiography and LV-to-RV
shunting quantified by cardiac catheterization in patients
with isolated small- to moderate-sized VSDs. To our
knowledge, no previous studies have reported on the rela-
tionships between left heart chamber sizes measured by
echocardiography and LV-to-RV shunting quantified by
cardiac catheterization in patients with isolated VSDs.
Currently, the main indications for cardiac catheteriza-
tion in children with isolated VSDs are estimation of pul-
monary artery pressure and pulmonary vascular resistance
in case of suspected pulmonary hypertension [22].
Although quantification of Qp:Qs is no longer performed in
many centers, we still perform routine cardiac catheteri-
zation to quantify Qp:Qs in patients with small- to mod-
erate-sized VSDs who are being considered for surgery [3,
20]. There has been considerable interest in developing
non-invasive methods of shunt quantification. Radionu-
clide angiography, Doppler and color-flow echocardiogra-
phy, and cardiac magnetic resonance imaging (CMR)
techniques have been evaluated. Maltz and Treves [21]
described a radionuclide angiocardiography technique for
shunt quantification in 1973. However, scintigraphy can
only provide accurate shunt quantification when Qp:Qs is
between 1.2 and 3.0, as it cannot eliminate the recirculation
effect on the lung dilution curve. Other sources of error
include the non-uniformity of the bolus reaching the heart
and sudden changes in pulmonary blood flow due to crying
or irregular respiration [21]. Later improvements resulted
in an increase in the correlation coefficient of the Qp:Qs
obtained by this method compared with the oximetry
method to as high as 0.92 [12]. However, scintigraphy is
expensive and exposes the patient to radiation, and has
therefore never been a popular method of measuring left-
to-right shunting.
Our clinic used pulsed-wave Doppler ultrasonography
for quantification of intracardiac shunts until the mid-
1990s, but discontinued this because it has some pitfalls
and may induce false quantification. This procedure has
several limitations, as follows. (i) In the presence of LV-to-
RA shunting, the measured RV systolic pressure may be
unreliable. (ii) The pressure gradient between the ventricles
may appear to be lower than the actual pressure gradient
when the defect is small or becomes smaller with con-
traction, and the Doppler beam is not parallel to the
bloodstream. (iii) The Doppler gradient may differ from the
peak-to-peak gradient measured by catheter angiography.
(iv) The calculations assume that the shunt is always in one
direction only, which is inaccurate. (v) Depending on
which method is chosen, either the pulmonary artery and
aorta or the tricuspid and mitral orifices are used for
quantification. These orifices are assumed to be circular,
the flow through them is assumed to be laminar, and the
orifice sizes are assumed to be constant throughout the
cardiac cycle, which is inaccurate. (vi) The VSD is
assumed to have a constant shape and size during systole,
which is inaccurate. A concomitant aneurysm also changes
the geometry and flow through the defect during systole.
(vii) Calculations of the valve areas and the Doppler flow
velocity waveforms depend on manual procedures that are
subject to measurement errors and inter-observer variabil-
ity [4, 26, 29]. The proximal isovelocity surface area
method can also be used for shunt quantification, but is
limited by the difficulty in determining the flow borders in
addition to the above-mentioned limitations [19]. Although
echocardiography measurements show some correlations
with catheter angiography measurements, there are also
some differences between the measurements obtained by
these two modalities.
The American Heart Association guidelines suggest
that, in centers with adequate expertise, CMR or computed
tomography might be useful for assessment of the pul-
monary artery, pulmonary veins, and aorta as well as the
anatomical features of unusual VSDs [31]. CMR may also
be useful for shunt quantification in patients with VSDs
[14]. Velocity-encoded, phase-contrast magnetic resonance
imaging (MRI) measurements of shunt magnitude have
been used for shunt quantification. Data from these studies
indicate that MRI can rapidly and accurately quantify shunt
Pediatr Cardiol
123
magnitude in patients with intracardiac left-to-right
shunting, and can reliably differentiate between patients
with Qp:Qs \ 1.5 and those with Qp:Qs C 1.5 [13].
Beerbaum et al. [2] evaluated this method in pediatric
patients and reported that it was fast, safe, and reliable
compared with oximetry, except in patients with atrial
septal defects. Real-time magnetic resonance velocity
mapping was introduced to save time and overcome the
limitations of phase-contrast CMR [18]. Although these
methods are useful and the results are comparable with
those obtained by oximetry, the long acquisition time,
sedation requirements for children, poor quality of cardiac
gated images in patients with arrhythmias, and high costs
limit their widespread use in clinical practice.
An important limitation common to all methods of shunt
quantification is that sedation affects cardiac physiology.
The required level of sedation differs among echocardi-
ography, radionuclide scintigraphy, CMR, and catheter
angiography. CMR may be the most promising of these
methods of shunt quantification, but cardiac MRI is not
available in our clinic. Cardiac catheterization is therefore
still our gold standard diagnostic technique.
Parameters such as the serum B-type natriuretic peptide
(BNP) level may be useful in combination with the Qp:Qs
value for making operative decisions. The serum levels of
BNP and N-terminal proBNP may increase in response to
volume and pressure overloading, or systolic and diastolic
ventricular dysfunction. These levels are useful for the
diagnosis and management of a variety of clinical condi-
tions, especially in adults with congestive heart failure.
Although a number of studies have evaluated BNP levels in
patients with congenital heart disease, the clinical useful-
ness of serum BNP levels in these patients is less clear, and
the reported data are inconsistent [6, 15, 25]. As we did not
measure serum BNP levels routinely before cardiac cath-
eterization, they are available for only a few of our
patients. Even though there is a positive correlation
between the degree of shunting and the BNP level, there is
no defined cut-off value that can be used for making
operative decisions. The serum BNP level is also affected
by many other factors including sex, obesity, renal disease,
and age, which makes its value more questionable.
In this study, we found significant differences in Qp:Qs
between patients with normal and dilated left heart cham-
bers adjusted for BW and BSA. The Qp:Qs values were
significantly different among patients grouped according to
left heart chamber size adjusted for BW and BSA
(p = 0.001, p = 0.002, respectively). This reflects the
increasing sizes of the left heart chambers as the shunt
increases. The Qp:Qs was higher in patients with either LV
or combined LA and LV dilatation on echocardiography
(adjusted for BW) than in patients with normal LA and LV
measurements. It was interesting that the Qp:Qs was lower
in patients with LA dilatation only than in patients with
normal LA and LV measurements. LA dilatation had no
effect on shunt size, whereas LV dilatation was the echo-
cardiographic finding most strongly associated with shunt
size. Jarmakani et al. [16] reported that VSDs have earlier
and more significant effects on LV and LA end-diastolic
volume than on LV mass. They postulated that there is a
strong relationship between increased LV end-diastolic
volume and increased pulmonary artery blood flow,
resulting in an increase in Qp:Qs. Our findings partially
support this theory, as increased shunting results in LV
dilatation, which was associated with increased Qp:Qs.
However, this association was not strong enough to
determine clinically significant shunting based on echo-
cardiography findings. As shunting causes concurrent
dilatation of the LA and LV, it was unexpected that there
was no association between LA dilatation and Qp:Qs. But
LA size is not linearly correlated with weight or BSA, even
in healthy children. There is also substantial overlap in LA
size between healthy children and children with VSDs. It is
therefore accepted that LA size is variable in childhood
[28]. Our finding might reflect natural variations in LA
size.
The relationships between Qp:Qs and left heart chamber
sizes on echocardiography were not strong enough to be
useful for making surgical decisions, as left heart chamber
dilatation was not significantly associated with Qp:Qs C 2
(p = 0.349 when adjusted for BW, p = 0.107 when
adjusted for BSA). However, left heart chamber dilatation
was significantly associated with Qp:Qs C 1.5 (p = 0.022
when for adjusted BW, p = 0.006 when adjusted for BSA).
It is not clear why the results became statistically signifi-
cant when the measurements were adjusted for BSA rather
than BW. This may have occurred because adjustment for
BSA resulted in an increase in the number of patients who
were considered to have LA dilatation, and consequently
an increase in the number of patients with both LA and LV
dilatation, resulting in a significant difference between
patients with normal LA and LV measurements and
patients with both LA and LV dilatation (p \ 0.001).
If we had based our decisions regarding VSD closure on
echocardiography findings, closure would have been con-
sidered unnecessary in nearly three-quarters of these
patients according to the classical indications. According to
measurements adjusted for BW, two patients with normal
LA and LV measurements on echocardiography who had
Qp:Qs C 2 would have been followed clinically instead of
undergoing surgery; and according to measurements
adjusted for BSA, one such patient would not have
undergone surgery. If we had lowered the threshold for
significant shunting to Qp:Qs C 1.5, as some centers do,
VSD closure would have been considered unnecessary in
nearly half of the patients. According to measurements
Pediatr Cardiol
123
adjusted for BW, six patients with normal LA and LV
measurements on echocardiography who had Qp:Qs C 1.5
would have been followed clinically instead of undergoing
surgery; and according to measurements adjusted for BSA,
four such patients would not have undergone surgery.
The results of this study indicate that the associations
between left heart chamber dilatation on echocardiography
and shunt size are not strong enough to be useful for
making decisions regarding VSD closure in patients with
dilated left heart chambers and small- to moderate-sized
VSDs.
Conclusions
Left heart chamber dilatation measured by echocardiogra-
phy is not significantly associated with significant LV-to-
RV shunting quantified by cardiac catheterization. We
advise that catheter angiography should be performed
when left heart chamber dilatation is observed on trans-
thoracic echocardiography before making decisions
regarding closure of small- to moderate-sized VSDs.
Study Limitations
Quantification of Qp:Qs by catheter angiography was
accepted as the gold standard and was not compared with
other methods of shunt quantification such as Doppler
ultrasonography, scintigraphy, or CMR. The effects of left
heart chamber dilatation on biochemical markers of vol-
ume overload such as BNP and N-terminal proBNP levels
were not compared with Qp:Qs values. The Qp:Qs was
calculated using the oxygen consumption method, even
though several alternative methods are available. Calcula-
tions of Qp and Qs have major limitations, but these lim-
itations may be less important if the Qp:Qs value is used.
Ventricular septal aneurysms and aortic valve prolapse are
known to affect the defect size and the degree of left-to-
right shunting. However, as the aim of this study was to
evaluate the relationships between left heart chamber
dilatation detected on echocardiography and Qp:Qs quan-
tified by cardiac catheterization, we do not consider that
these limitations interfere with the validity of our findings.
Conflict of interest The authors have no conflicts of interest to
disclose.
References
1. Backer CL, Winters RC, Zales VR, Takami H, Muster AJ,
Benson DW, Mavroudis C (1993) Restrictive ventricular septal
defect: how small is too small to close? Ann Thorac Surg
56:1014–1018
2. Beerbaum P, Korperich H, Barth P, Esdorn H, Gieseke J, Meyer
H (2001) Non invasive quantification of left-to-right shunt in
pediatric patients. Phase-contrast cine magnetic resonance
imaging compared with invasive oximetry. Circulation
103:2476–2482
3. Carotti A, Marino B, Bevilacqua M, Marcelletti C, Rossi E,
Santoro G, De Simone G, Pasquini L (1997) Primary repair of
isolated ventricular septal defect in infancy guided by echocar-
diography. Am J Cardiol 79:1498–1501
4. Colan SD (2009) Hemodynamic measurements. In: Lai WW,
Mertens LL, Cohen MS, Geva T (eds) Echocardiography in
pediatric and congenital heart disease: from fetus to adult. Wiley-
Blackwell, West Sussex, pp 63–75
5. Costeff H (1966) A simple empirical formula for calculating
approximate surface area in children. Arch Dis Child 41:681–683
6. Cowley CG, Bradley JD, Shaddy RE (2004) B-type natriuretic
peptide levels in congenital heart disease. Pediatr Cardiol
25:336–340
7. Daniel J, Penny G Wesley, Vick III (2011) Ventricular septal
defect. Lancet 377:1103–1112
8. Eroglu AG, Oztunc F, Saltik L, Bakari S, Dedeoglu S, Ahunbay
G (2003) Evolution of ventricular septal defect with special ref-
erence to spontaneous closure rate, subaortic ridge and aortic
valve prolapse. Pediatr Cardiol 24:31–35
9. Gabriel HM, Heger M, Innerhofer P, Zehetgruber M, Mundigler
G, Wimmer M, Maurer G, Baumgartner H (2002) Long term
outcome of patients with ventricular septal defect considered not
to require surgical closure during childhood. J Am Coll Cardiol
39:1066–1071
10. Gersony WM (2001) Natural history and decision-making in
patients with ventricular septal defect. Prog Pediatr Cardiol
14:125–132
11. Henry WL, Ware J, Gardin JM, Hepner SI, McIllay, Weiner M
(1978) Echocardiographic measurements in normal subjects:
growth-related changes that occur between infancy and early
adulthood. Circulation 57:278–285
12. Houser TS, Maclntyre WJ, Cook SA, Go RT, Moodie DS, Ceimo
J, Gallagher JH (1981) Recirculation subtraction for analysis of
left-to-right cardiac shunts: concise communication. J Nucl Med
22:1033–1038
13. Hundley WG, Li HF, Lange RA, Pfeifer DP, Meshack BM,
Willard JE, Landau C, Willett D, Hillis LD, Peshock RM (1995)
Assessment of left-to-right intracardiac shunting by velocity-
encoded, phase-difference magnetic resonance imaging: a com-
parison with oximetric and indicator dilution techniques. Circu-
lation 91:2955–2960
14. Hundley WG, Bluemke DA, Finn JP, Flamm SD, Fogel MA,
Friedrich MG et al (2010) ACCF/ACR/AHA/NASCI/SCMR
2010 expert consensus document on cardiovascular magnetic
resonance: a report of the American College of Cardiology
foundation task force on expert consensus documents. Circulation
121:2462–2508
15. Jan SL, Fu YC, Hwang B, Lin SJ (2012) B-type natriuretic
peptide in children with atrial or ventricular septal defect: a
cardiac catheterization study. Biomarkers 17:166–171
16. Jarmakani MM, Graham TP, Canent RV, Spach M, Capp P
(1969) Effect of site of shunt on left heart-volume characteristics
in children with ventricular septal defect and patent ductus arte-
riosus. Circulation 40:411–418
17. Kampmann C, Wiethoff CM, Wenzel A, Stolz G, Betancor M,
Wippermann CF, Huth RG, Habermehl P, Knuf M, Emscher-
mann T, Stopfkuchen H (2000) Normal values of M mode
echocardiographic measurements of more than 2000 healthy
infants and children in central Europe. Heart 83:667–672
Pediatr Cardiol
123
18. Korperich H, Gieseke J, Barth P, Hoogeveen R, Esdorn H, Pet-
erschroder A, Meyer H, Beerbaum P (2004) Flow volume and
shunt quantification in pediatric congenital heart disease by real-
time magnetic resonance velocity mapping: a validation study.
Circulation 109:1987–1993
19. Kosecik M, Sagin-Saylam G, Unal N, Kir M, Paytoncu S (2007)
Non-invasive assessment of left-to-right shunting in ventricular
septal defects by the proximal isovelocity surface area method on
Doppler colour flow mapping. Can J Cardiol 23:1049–1053
20. Magee AG, Boutin C, McCrindle BW, Smallhorn JE (1998)
Echocardiography and cardiac catheterization in the preoperative
assessment of ventricular septal defect in infancy. Am Heart J
135:907–913
21. Maltz DL, Treves S (1973) Quantitative radionuclide angiocardiog-
raphy: determination of Qp/Qs in children. Circulation 47:1049–1056
22. Mavroudis C, Backer CL, Jacobs JP (2003) Ventricular septal
defect. In: Mavroudis C, Backer CL (eds) Pediatric cardiac sur-
gery, 3rd edn. Mosby, Philadelphia, pp 298–320
23. McDaniel NL, Gutgesell HP (2008) Ventricular septal defects. In:
Allen HD, Driscoll DJ, Shaddy RE, Feltes TF (eds) Moss and
Adams heart disease in infants, children and adolescents includ-
ing the fetus and young adult, 6th edn. Lippincott Williams &
Wilkins, Philadelphia, pp 667–682
24. Nygren A, Sunnegardh J, Berggren H (2000) Preoperative eval-
uation and surgery in isolated ventricular septal defects: a 21 year
perspective. Heart 83:198–204
25. Ozhan H, Albayrak S, Uzun H, Ordu S, Kaya A, Yazici M (2007)
Correlation of plasma B-type natriuretic peptide with shunt
severity in patient with atrial or ventricular septal defect. Pediatr
Cardiol 28:272–275
26. Sabry AF, Reller MD, Silberbach GM, Rice MJ, Sahn DJ (1995)
Comparison of four Doppler echocardiographic methods for
calculating pulmonary-to-systemic shunt flow ratios in patients
with ventricular septal defect. Am J Cardiol 75:611–614
27. Shan DJ, Demaria A, Kisslo J, Weyman A (1978) Recommen-
dation regarding quantitation in M-mod echocardiography:
results of a survey of echocardiographic measurement. Circula-
tion 58:1072–1083
28. Taggart NW, Cetta F, O’Leary PW, Seward JW, Eidem BW
(2010) Left atrial volume in children without heart disease and in
those with ventricular septal defect or patent ductus arteriosus or
hypertrophic cardiomyopathy. Am J Cardiol 106:1500–1504
29. Teien D, Karp K, Wendel M, Human DG, Nanton MA (1991)
Quantification of left to right shunt by echo Doppler cardiography
in patients with ventricular septal defects. Acta Paediatr Scand
80:335–360
30. Tynan M, Anderson RH (2002) Ventricular septal defect. In:
Anderson RH, Baker EJ, Macartney FJ, Rigby ML, Shinebourne
EA, Tynan M (eds) Paediatric cardiology, 2nd edn. Churchill
Livingstone, Edinburgh, pp 983–1014
31. Warnes CA, Williams RG, Bashore TM et al (2008) ACC/AHA
2008 guidelines for the management of adults with congenital
heart disease: a report of the American College of Cardiology/
American Heart Association Task Force on Practice Guidelines
(writing committee to develop guidelines for the management of
adults with congenital heart disease). J Am Coll Cardiol 52:e143–
e263
32. Working Group on Management of Congenital Heart Disease
(2008) Consensus on timing of intervention for common con-
genital heart disease. Indian J Pediatr 45:117–126
33. Zuo J, Xie J, Yi W, Yang J, Zhang J, Li J, Yi D (2010) Results of
transcatheter closure of perimembranous ventricular septal
defect. Am J Cardiol 106:1034–1037
Pediatr Cardiol
123