See discussions, stats, and author profiles for this publication at: https://www.researchgate.

net/publication/26727279

Aorto-septal angle in Boxer dogs with subaortic stenosis: An

echocardiographic study

Article  in  The Veterinary Journal · September 2009

DOI: 10.1016/j.tvjl.2009.06.027 · Source: PubMed

CITATIONS READS

14 173

4 authors, including:

Cecilia Quintavalla Stefano Guazzetti

Università di Parma Azienda USL - IRCCS - di Reggio Emilia
31 PUBLICATIONS   579 CITATIONS    46 PUBLICATIONS   1,238 CITATIONS   

SEE PROFILE SEE PROFILE

Claudio Bussadori
I.R.C.C.S. Policlinico San Donato
131 PUBLICATIONS   2,533 CITATIONS   

SEE PROFILE

Some of the authors of this publication are also working on these related projects:

Manganese neurotoxicity from neurodevelopment to neurodegeneration View project

All content following this page was uploaded by Stefano Guazzetti on 21 January 2021.

The user has requested enhancement of the downloaded file.

 The Veterinary Journal 185 (2010) 332–337

Contents lists available at ScienceDirect

The Veterinary Journal

journal homepage: www.elsevier.com/locate/tvjl

Aorto-septal angle in Boxer dogs with subaortic stenosis: An

echocardiographic study
Cecilia Quintavalla a,* , Stefano Guazzetti b, Antonia Mavropoulou a, Claudio Bussadori c
a
Dept. Animal Health, Parma University, Via del Taglio, 8, 43100 Parma, Italy
b
Local Health Unit, Reggio Emilia, Italy
c
Istituto di Medicina Cardiovascolare, Ospedale Maggiore IRCCS, University of Milan, Italy

a r t i c l e i n f o a b s t r a c t

Article history: The present study was designed to determine the aorto-septal angle (AoSA) in Boxer dogs with or without
Accepted 27 June 2009 subaortic stenosis (SAS) by using two-dimensional echocardiography. Forty-five Boxer dogs were pro-
spectively included in the study. The AoSA was steeper in the group with SAS than in healthy Boxers with
a mean difference of 10°. According to the proposed regression model, the AoSA is associated with SAS in
Keywords: Boxers, particularly because it becomes steeper as SAS severity increases. Several studies in humans dem-
Cardiology onstrate that small changes in the AoSA produce important changes in septal shear stress, which in turn
Dog
causes proliferation of the endocardial cells resulting in subaortic obstruction. A definite conclusion
Boxer
Subaortic stenosis
about the role of the AoSA on the formation and/or progression of subvalvular lesions in Boxers cannot
Aorto-septal angle be drawn from the data analysed due to the transversal nature of the observations.
Ó 2009 Elsevier Ltd. All rights reserved.

Introduction position, and exacerbated by a fourth factor (cellular prolifera-

Fixed subaortic stenosis (SAS) is by far the most common form
of aortic stenosis in the dog (MacDonald, 2006). The Boxer is one of
the canine breeds that has a tendency to harbour lesions that ob-
struct the left ventricular outflow tract (Patterson, 1968, 1989; Bu-
chanan, 1993; Fuentes et al., 1994; Corlouer, 1998; Heiene et al.,
2000; Sisson et al., 2000; Bussadori, 2000; Bussadori et al., 2001,
2009; Chetboul et al., 2006; Linde and Koch, 2006). Even though
SAS is recognised as an inherited disease and reported as a congen-
ital heart disease, there is strong evidence in some cases that the
lesion producing the fixed form of obstruction within the left ven-
tricular tract develops and progresses after birth. Consequently, it
is regarded as an acquired lesion rather than a congenital abnor-
mality (Patterson, 1968, 1989; Pyle et al., 1976). It seems likely that
the aetiology of the fixed form of SAS has both congenital and ac-
quired aspects.
In humans, the progressive nature of fixed SAS is well recog-
nised. Sigfússon et al. (1997) proposed a four-stage aetiological
process for the development of SAS in humans. The first predis-
posing factor is the presence of subtle morphological abnormal-
ities within the left ventricular outflow tract of patients who
develop SAS. These lead to the second factor, an elevation of sep-
tal shear stress (Cape et al., 1997). If elevation of shear stress is
coupled with the third potential factor, namely a genetic predis-
* Corresponding author. Tel.: +39 0521 032 694; fax: +39 0521 032 692.
E-mail address: cecilia.quintavalla@unipr.it (C. Quintavalla).
tion in response to septal shear stress), the result is the fixed
and stenotic lesion (Gewillig et al., 1992; Cilliers and Gewillig,
2002).
Sigfússon et al. (1997) addressed the first stage of this process
and demonstrated that SAS is associated with a steeper aorto-sep-
tal angle (AoSA), as defined by two-dimensional echocardiogra-
phy. They also concluded that a steeper AoSA may be a risk
factor for the development of SAS. This conclusion validated a
previous study conducted by Kleinert and Geva (1993), in which
a steeper AoSA in children with ventricular septal defect, coarcta-
tion of the aorta, or both, was linked to subsequent development
of SAS. A further study performed by Cape et al. (1997) demon-
strated that small changes in the AoSA produce important modi-
fications in septal shear stress and that the levels of stress
increase are consistent with cellular flow studies showing stimu-
lation of growth factors and cellular proliferation (Gewillig et al.,
1992; Cilliers and Gewillig, 2002). Cape et al. (1997) concluded
that a steeper AoSA may be a risk factor for the development of
SAS.
The present study was designed to determine the AoSA in Boxer
dogs with and without SAS by two-dimensional echocardiography.
By comparing the two groups of dogs, we aimed (1) to determine if
the AoSA differs between SAS-affected and -unaffected Boxer dogs;
(2) to evaluate if the AoSA relates with aortic peak velocity and gra-
dient, thus with stenosis severity; and (3) to ascertain if the AoSA
may be a risk factor for the development of SAS in Boxer dogs as
well as in humans.

1090-0233/$ - see front matter Ó 2009 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tvjl.2009.06.027
 C. Quintavalla et al. / The Veterinary Journal 185 (2010) 332–337
Materials and methods
Animals
Privately owned Boxer dogs submitted to the Veterinary Teaching Hospital of
Parma University for a cardiovascular examination from 1 January to 31 December
2007 were sequentially enrolled in the study. The animals’ care and handling were
in compliance with regulations for animal welfare. All dogs underwent a physical
examination and transthoracic echocardiography accomplished by one operator
(C.Q.).
Indirect systolic arterial blood pressure measurement was performed by Dopp-
ler flow meter in all dogs. After allowing the dogs to acclimate in a quiet room for
10 min, the mean of five blood pressure measurements was calculated. Blood pres-
sure measurements were performed by the same operator (A.M.). The cut-off value
of systolic pressure was set at 160 mm Hg (to account for possible stress-associated
rise in blood pressure).
Two-dimensional, M-mode, spectral, and colour-flow Doppler echocardio-
graphic examination was performed on conscious dogs with a Megas CPV machine
(Esaote Biomedica) equipped with two multifrequency phased array probes: 2.5–
3.5 and 3.5–5.0 MHz. Transthoracic echocardiography was performed according
to the standards of Thomas et al. (1993), with the dog in right and left lateral
recumbent positions on a table with an opening that allowed transducer manipula-
tion and examination from beneath the animal (Kienle and Thomas, 2002). Assess-
ment of left ventricular outflow obstruction, imaging, Doppler measurements and
morphological diagnosis were all in compliance with established guidelines for
echocardiographic studies of suspected SAS and pulmonic stenosis (Bussadori
et al., 2000). The severity of SAS was graded as mild (peak gradient, 649 mm Hg),
moderate (peak gradient, 50–80 mm Hg), or severe (peak gradient > 80 mm Hg)
(Boon, 1998; Bussadori et al., 2000).
Inclusion and exclusion criteria
Inclusion was restricted to Boxer dogs (1) affected by isolated SAS with no out-
ward clinical signs of heart disease and systolic arterial blood pressure 6160 mm
Hg, and (2) free from congenital or acquired heart disease and with systolic arterial
blood pressure 6160 mm Hg. Boxer dogs affected by concomitant heart disease,
hypertensive dogs (systolic arterial blood pressure >160 mm Hg), and SAS dogs
with echocardiographic evidence of left ventricular volume overload (systolic dys-
function) were excluded. These latter conditions are, in fact, possible factors affect-
ing left ventricular outflow and aortic root morphology and geometry.
Echocardiographic measurements
For the purpose of this study, the following measurements were taken into ac-
count: (1) the aortic annulus size (diameter) and the AoSA from the right paraster-
nal long axis view of the left ventricle outflow tract, and (2) the aortic peak velocity
and gradient from the subcostal view. The aortic annulus diameter was measured at
the hinge points of the aortic leaflets in early systole. Diameters were averaged from
three high-quality systolic frames.
AoSA is the angle formed by the long axis of the ascending aorta and the plane
of the interventricular septum. This measurement was performed according to
Fowles et al. (1980) at end-diastole. To measure the AoSA, the midline axis of the
aortic root was constructed by bisecting the root at the level of the aortic annulus
and above the sinotubular junction. The midline axis of the septum was constructed
by bisecting the septum at the level of the mitral leaflets tips and 2 cm apically from
that point. Three high-quality end-diastolic frames for each dog were stored. The
lines were constructed on images inserted in graphics software (Microsoft Power-
Point) and the angle between these lines then measured from hard copies obtained
using a Hewlett Packard Deskjet 815 C. The angle was averaged from the three
frames (Fig. 1).
Statistical analysis
Descriptive statistic methods, one-way ANOVA, simple and multiple linear
regression methods were used. All the analysis and graphics were done with R (R
Development Core Team, 2008).
Results
Animals
Forty-five Boxer dogs met the inclusion criteria during the study
period. Fifteen dogs were affected by isolated SAS; the remaining
30 animals were healthy. There were 24 female and 21 male dogs.
The weight ranged from 6 to 39.5 kg and the age from 2 to
120 months. Sex seemed to be associated with SAS, assuming a
random selection scheme of the cases without stenosis (Table 1).
333
Taking females as the reference category, the odds ratio of disease
(male vs. female and ignoring severity) was estimated to be 1.563
(95% C.L. 1.218–2.004).
Echocardiographic measurements
Table 2 shows the AoSA values for the different clinical classes:
unaffected, mild SAS, moderate SAS, and severe SAS. AoSAs are
broader in unaffected dogs and tend to become steeper as the
severity of SAS increases. This difference between the clinical clas-
ses should not be considered a result of chance alone; in fact, it
would be very unlikely to observe such extreme differences be-
tween the means under the hypotheses of equal means across
the groups (P = 2.555  10 8 in a one-way ANOVA). The post hoc
Dunnett–Tukey–Kramer pairwise multiple comparison test (ad-
justed for unequal sample sizes) showed that only the differences
between each stenotic sub-group (mild, moderate, severe) and the
no-stenosis group were statistically significant (P < 0.05), while no
significant difference was observed between the stenotic sub-
groups. A trend toward steeper AoSAs was seen between SAS-af-
fected and -unaffected dogs (Figs. 3 and 4). A mean difference of
10° was observed (Table 2). According to these results, the AoSA
seems to be associated with SAS.
The AoSA was also associated (i.e., correlated) with aortic peak
velocity, peak gradient, and annulus diameter, and these factors
varied with sex, age, and bodyweight so joint distribution of these
variables had to be investigated. Relationships among the variables
are shown in Fig. 2. The strong collinearity shown between peak
aortic velocity and peak aortic gradient was expected because
these variables are physically related. Moreover, patterns of con-
joint variation of the AoSA and the aortic annulus diameter were
very similar. In view of this, a regression model aimed to represent
AoSA modification in relation to haemodynamic parameters under
consideration necessarily had to have either aortic peak velocity or
aortic peak gradient as a regressor (or the regression coefficient
estimation could have been unstable and unreliable due to the
strong collinearity between the predictors).
From a clinical point of view this concept can be better under-
stood by considering that both aortic velocity and gradient mea-
sure the same process (physiological or pathological) and that
the added knowledge of one parameter does not affect the diagnos-
tic orientation of the cardiologist if the other parameter is already
known. More precisely, within an unbiased regression model it is
impossible to distinguish the individual contributions of peak aor-
tic velocity and peak aortic gradient to the variability of the AoSA.
The relationship between AoSA and aortic peak velocity was
clearly nonlinear (Fig. 3). In particular, it appeared to be curvilin-
ear, tending to flatten with increasing velocity values. At the same
time, an increasing dispersion of AoSA values was observed as aor-
tic peak velocity increased. Several possible models of linear
regression of the AoSA on aortic peak velocity were considered,
and a model that contemplates the logarithmic transformation of
aortic peak velocity was then selected. This transformation, besides
making the relationship between the two variables linear, implies
(from a biological point of view) that for the same increase in aortic
velocity, one would expect a decrease in AoSA dependent on the
aortic velocity itself (i.e., the AoSA is lower as the aortic velocity
increases).
Fig. 4 shows that the regression line of the logarithm of the aor-
tic peak velocity on the AoSA satisfactorily interpolated the data. A
summary of the regression model is reported in Table 3. This model
accounted for about 62% of AoSA variability. Assuming that the
regression model (Table 3) adequately represented the relationship
between aortic peak velocity and AoSA, the effect of the other vari-
ables individually associated with it was taken into account in a
multiple regression model. The model (summarised in Table 4)
334 C. Quintavalla et al. / The Veterinary Journal 185 (2010) 332–337

Fig. 1. (A) 152° aorto-septal angle in a healthy Boxer and (B) 138° aorto-septal angle in a Boxer with subaortic stenosis (SAS).

Table 1
Continuous variables (age in months and weight in kg were discretized according to was built on the basis of biological considerations and took into ac-
the empirical quartiles). Numbers after the percent are absolute frequencies. count the joint contributions of bodyweight and aortic diameter.
Consequently, it allowed for an estimation of the regression coeffi-
No stenosis Mild stenosis Moderate Severe stenosis
(n = 30) (n = 5) stenosis (n = 4) cient of the logarithm of aortic peak velocity on AoSA corrected for
(n = 6) bodyweight and aortic diameter. The variables sex and age were
Gender: male 30% (9) 80% (4) 67% (4) 100% (4) not retained in this final model because of the negligible strength
Age of their contributions; in part, their effect was already accounted
1st quartile [2, 27% (8) 0% (0) 33% (2) 75% (3) for by bodyweight, which was strongly correlated with these vari-
12] ables. Because it was based on aortic velocity, the variable stenosis
2nd quartile 30% (9) 20% (1) 17% (1) 0% (0)
severity was not considered in the multiple regression model to
(12, 16]
3rd quartile 23% (7) 40% (2) 17% (1) 0% (0) avoid the problem of the above-mentioned collinearity between
(16, 24] predictors.
4th quartile 20% (6) 40% (2) 33% (2) 25% (1) The interpretation of the regression coefficient (b) associated
(24, 120]
with the log of aortic peak velocity ( 12.0584) is clearer if we con-
Weight sider that b represents the effect on the AoSA of a 1 unit increase of
1st quartile [6, 27% (8) 0% (0) 33% (2) 50% (2)
the log of aortic peak velocity. Hence, according to the model pro-
23]
2nd quartile 27% (8) 20% (1) 33% (2) 0% (0) posed, if aortic velocity changes from x1 to x2, with x2 > x1, and
(23, 27.5] other variables remain unchanged, the AoSA will change by
3rd quartile 23% (7) 20% (1) 17% (1) 50% (2) b
[log(x2) log(x1)] or b
log(x2/x1) depending on the ratio of x2
(27.5, 30] to x1 rather than on their difference, e.g., the increase from 2 to
4th quartile 23% (7) 60% (3) 17% (1) 0% (0)
4 m/s of aortic velocity (corresponding to an absolute increase of
(30, 39.5]
2 m/s) will cause the same increase of that produced by a change
 C. Quintavalla et al. / The Veterinary Journal 185 (2010) 332–337 335

10 14 18 50 100 150

A A A A

160
AS_angle AA A A AA A
AA
A AA AAAA A
A AA AAA A AA
A AAAAAA A A AA
A A
AAA AA
A AA A AA AA AA
AA A AA AA
A AA
A A
A
A
A
AAAA

150
A AA A
AAA AA
AA AA A A
AAm
m M AAm mM AAm m
AmMM AM Am m
M m A
M Am M M m A
MS mA A m MM Am MM M
S SM
Am

140
S A A mM M S SS A mM M S SS S M
MM mS M m
A

130
| |||||||||||| |||||||||| | S S S S
AA AA AA A A
AA Ao_diam A A AA A A
A AA A A AAAAA AAAAA
A A A
mAA AAAA
A AM AAAAAAmmM A AAm
AAAmmM
AAA MSAAAA
Am m
SSm m AAAA
18

m A Am S S A S S AA S Am
AA AAAAAm A Am M AAA m
MMmMAAA A AA m MM
M AAAA
A mM M MAAAmAAM M
MA M M M A
14

S S S S
S A A S A S A S
M | | | | ||||||| |||||||||| || || | M M M
10

S S S S

6
S S S S
S S
Ao_Vmax
S S SS S S

5
MM M M M M
MM M MM M
M M

4
M M
M M M M MM M M
mmm m mm m
m m
mm m mm m

3
Am A A A
m mA A AmA
AAAA
A A AAAAAAA AA
A A A AA A A
AAA AAA AA
A A AA
A A A
A AAAA AAA A
AA

2
AAAAAAAA
A A AAAA A
AA A AA A A
AA
A AAA A
| ||||||||||||||| || | || || | | || | | | | AA A
150

S S S S
S S S Ao_Gmax S
100

S S S S SS S S
MM M M M M
MM M
M MM
M
M
M M
50

M M M m M M
M M M
mmm m mm mA mm
m m mm m
Am AAA AA A mA AA AAm
A A AAAA mA
AAA
A A AAAA AAAAA AAA
A AAA
AA AA AA A
AAAAA AAA
A AA
A AA A AA
A A
A
AAA
A
AA |||||
||||
|||||| ||| || | | || || | | A
AAA
AA A A
A AA

A
A A A AA AA
m A A m mM mM Body_Weight

35
m
M
A Mm
A A
A A m
AA AAA m
mA A mA A Am Am
SM mAA AA M mS AA AA m M S m
AAm M S
AA
SA A AAASMA A AAAAAAmM S AAAA S
M mMAA AAAA A m
M AAA M M M

25
A AA AAA AA AA
AAA
MA A AAA A M
A A AA A AAAAA
A M AAAA
A M
S A S A A S A S

15
S S S S
M A MA A M A M || | ||||
||| ||||
|||||| |||||| | |

5
130 140 150 160 2 3 4 5 6 5 15 25 35

Fig. 2. The pairwise scatterplot of each two variables in the dataset is shown in a matrix format. The inspection of the scatterplot matrix reveals some important features of
the data such as the correlation between the variables, and the pattern of their relationships. The diagonal of the matrix shows the density of the univariate distribution of
each variable. For each point the letters A, m, M and S are used to identify the underlying clinical condition. AS_angle, aorto-septal angle; Ao_Vmax, peak aortic velocity;
Ao_Gmax, peak aortic gradient; Ao_diam, aortic annulus diameter.

from 3 to 6 m/s (corresponding to an absolute increase of 3 m/s), stimulated several studies in humans to ascertain the foundations
equal to b
log(2) degrees of the AoSA (about 8.4°). of this malformation’s postnatal development. The progressive nat-
ure of the disease is experimentally documented in the dog,
namely in the Newfoundland (Pyle et al., 1976). Although it has
Discussion not been experimentally documented, there is also clinical evi-
dence of this particular facet of the disease in the Boxer. This
Clinical evidence that SAS is a progressive disease that develops awareness among veterinary cardiologists emerges from the liter-
postnatally and is rarely seen in the newborn or neonatal period ature and especially from published data about congenital heart
disease screening in Boxer dogs. The screenings are performed on
Table 2 dogs at least 6–12 months of age (Fuentes et al., 1994; Corlouer,
Aorto-septal angle in degrees by clinical class.
1998; Bussadori et al., 2000, 2001, 2009; Linde and Koch, 2006).
Mean Median SD Min Max n Recent theories about the pathophysiological mechanism of SAS
No stenosis 152.80 154.00 4.79 140.00 162.00 30 formation and progression suggest an abnormal underlying endo-
Mild stenosis 144.20 144.00 3.35 140.00 148.00 5 thelial substrate that is stimulated to undergo proliferation by
Moderate stenosis 142.67 142.50 3.01 139.00 147.00 6 shear stresses caused by an abnormal flow pattern and chronic tur-
Severe stenosis 138.25 140.50 4.86 131.00 141.00 4
bulence (Cilliers and Gewillig, 2002). Moreover, the fact that dis-
SAS (all levels) 142.00 142.00 4.17 131.00 148.00 15
crete SAS can recur after surgical removal strengthens the
336 C. Quintavalla et al. / The Veterinary Journal 185 (2010) 332–337

Table 4
Parameters of the multiple linear regression model. The estimates represent the
160 ‘adjusted’ change in the AoSA for an increase of one unit of each variable in the model.
The standard errors of the estimates and a statistical test against the null hypothesis
of nullity of the parameters are reported.
155
Estimate SE t Value Pr(>|t|)
(Intercept) 148.5870 7.1110 20.90 <0.0001
Aortic Velocity (m/s)

150 Weight 0.2739 0.1211 2.26 0.0290

Aortic diameter 1.0890 0.4348 2.50 0.0163
log(VMAX_AO) 12.0548 1.9495 6.18 <0.0001
145

140 alterations in morphology can produce important changes in fluid

dynamic forces such as shear stress, and cellular morphology and
biochemistry adjust to accommodate the abnormal shear stress.
135
Deviations from normal morphological development will lead to
altered shear stress on the involved chamber surfaces especially
130
by chronic flow disturbance (abnormal flow patterns and turbu-
lence). Several morphological abnormalities of the left ventricular
2 3 4 5 6
AoSA (degrees) outflow tract have been investigated in children to determine
whether they precede the development of subaortic obstruction.
Fig. 3. Scatterplot depicting the relationship between the aorto-septal angle (AoSA, In particular, a steeper AoSA was consistently associated with
degrees) and the aortic peak velocity (m/s). SAS for all patients studied, suggesting that aorto-septal angulation
may be a risk factor for subaortic stenosis. An overlap in AoSA be-
tween patients and control subjects was demonstrated, indicating
A that this measurement is not completely specific. However, a
160 threshold value exists and a critical AoSA could be defined. The
A finding of such a critical AoSA may be of value in identifying pa-
A
AA A A tients at risk for the development of SAS (Sigfússon et al., 1997).
A
155 A AA A In our study, the AoSA was significantly steeper in the group
A A AA
A A A with isolated SAS (regardless of disease severity) than in healthy
A A
Boxers. A mean difference of 10° was observed between the two
Aortic Velocity (m/s)

150 A A
A A groups. All dogs affected with SAS had an AoSA < 148° (mean
A m
A m M 142.0°, range 131.0–148.0°) and dogs free from SAS AoSA > 140°
A
145 M (mean 152.8°, range 140.0–162.0°). Like in studies conducted in
m
A M humans, an overlap in AoSA values between SAS-affected and -
m M
S S
unaffected dogs exists. These findings are consistent with those re-
140 A m M S cently reported in the Dogue de Bordeaux demonstrating a signif-
M
icantly steeper AoSA in dogs with aortic stenosis (AS) compared
with dogs free from AS (Höllmer et al., 2008). However, reference
135 A = stenosis absent
m = moderate stenosis values were different from those reported in our study. This dis-
M = mild stenosis crepancy could be explained by different anatomy of the left ven-
S = severe stenosis S
130 tricular outflow and aortic root between the two canine breeds.
2 3 4 5 6 According to the proposed multiple regression model, peak aor-
AoSA (degrees) tic velocity and, as a result, SAS severity, increase as the AoSA be-
comes steeper. The AoSA therefore seems to be associated with
Fig. 4. Relationship between the aorto-septal angle (AoSA) and the aortic peak SAS. In humans, an abnormal AoSA may not only be correlated
velocity (regression line of the logarithm of the aortic peak velocity on the AoSA).
with, but may also be a risk factor for, the development of SAS. This
could also happen in Boxers. Defining threshold angles could be of
great value in early identification of Boxers at risk for the develop-
Table 3
ment and/or progression of SAS. In our study, AoSAs < 140° were
Parameters of the simple linear regression model of the logarithm of the aortic peak
velocity on the AoSA. The estimate for the log(VMAX_AO) represents the change in measured only in SAS-affected dogs, whereas AoSA > 148° occurred
the AoSA for an increase of 1 unit of the natural logarithm of the aortic velocity. The only in healthy dogs. However, whether these values could serve as
standard errors (SE) of the estimates and a statistical test against the null hypothesis predictive criteria could not be established by our study. Further
of nullity of the parameters are reported. evidence emerged from this study that SAS is more frequent in
Estimate SE t Value Pr(>|t|) male than in female dogs. This is consistent with the results of a
(Intercept) 162.6344 1.6993 95.71 <2  10 16 recent study in Boxers (Bussadori et al., 2009). The sex of the dog
log(VMAX_AO) 14.4598 1.6979 8.52 8.92  10 11 could then be a risk factor for SAS.
Some limitations of this study must be acknowledged. A defi-
nite conclusion about the role of the AoSA in the formation and/
or progression of subvalvular lesions cannot be drawn from the
supposition that the lesion occurs as a result of a pathological pro- data analysed due to the transversal nature of observations. This
cess that is left unaltered by the surgery (Darcin et al., 2003). hypothesis should be verified by a longitudinal study using new-
Shear stress is a stress state in which the stress is parallel or born Boxers to establish the pre-existence of a steep aortic angle
tangential to a material’s face. Persistent embryonic endocardial before SAS development. It could be also interesting to follow up
cushion tissue conserves residual proliferative capacity. Small Boxer dogs with SAS in order to establish or disprove the role of
 C. Quintavalla et al. / The Veterinary Journal 185 (2010) 332–337
a steeper AoSA in the progression to more severe forms of the dis-
ease. Moreover, the left ventricular outflow tract has a dynamic
and tridimensional nature, the anatomical borders of the left ven-
tricular outflow tract in the dog are not so clearly defined as in hu-
mans, and the measurement of the AoSA from two-dimensional
still frames at one point in the cardiac cycle is a simplification of
this complex and changing morphology. However, standardisation
of imaging and systematic measurement of echocardiographic
parameters tend to reduce variability. They have been proven to
perform well in human studies (Kleinert and Geva, 1993; Cape
et al., 1997; Sigfússon et al., 1997), and they are expected to per-
form as well in Boxer dogs.
Conclusions
The AoSA, as defined by two-dimensional echocardiography, is
associated with SAS in Boxers and the AoSA becomes steeper as
SAS severity increases. Studies conducted in humans have shown
that small changes in the AoSA produce important changes in sep-
tal shear stress, which in turn causes proliferation of the endocar-
dial cells in the left ventricular outflow tract resulting in subaortic
obstruction. Therefore, it is hypothesised that a steeper AoSA could
be a risk factor for the development and/or progression of SAS in
Boxers.
Conflict of interest statement
None of the authors of this paper has a financial or personal
relationship with other people or organisations that could inappro-
priately influence or bias the content of the paper.
References
Boon, J.A., 1998. Congenital heart disease. In: Boon, J.A. (Ed.), Manual of Veterinary
Echocardiography. Williams & Wilkins, Baltimore, MD, USA, pp. 383–445.
Buchanan, J.W., 1993. Changing breed predispositions in canine heart disease.
Canine Practice 18, 12–14.
Bussadori, C., 2000. Echo patterns in boxers with subaortic stenosis. In: Proceedings
of the 18th ACVIM Forum, Seattle, WA, USA, pp. 86–87.
Bussadori, C., Amberger, C., Le Bobinnec, G., Lombard, C.W., 2000. Guidelines for the
echocardiographic studies of suspected subaortic and pulmonic stenosis.
Journal of Veterinary Cardiology 2, 17–24.
Bussadori, C., Pradelli, D., Borgarelli, M., Chiavegato, D., D’Agnolo, G., Menegazzo, L.,
Migliorini, F., Santilli, R., Zani, A., Quintavalla, C., 2009. Congenital heart disease
in boxer dogs: results of 6 years of breed screening. The Veterinary Journal 181,
187–192.
Bussadori, C.B., Quintavalla, C., Capelli, A., 2001. Prevalence of congenital heart
disease in Boxers in Italy. Journal of Veterinary Cardiology 3, 7–11.
Cape, E.G., VanAuker, M.D., Sigfússon, G., Tacy, T.A., del Nido, P.J., 1997. Potential
role of mechanical stress in the etiology of pediatric heart disease: septal shear
View publication stats
337
stress in subaortic stenosis. Journal of the American College of Cardiology 30,
247–254.
Chetboul, V., Trolle, J.M., Nicolle, A., Carlos Sampedrano, C., Gouni, V., La Forge, H.,
Benalloul, T., Tissier, R., Pouchelon, J.L., 2006. Congenital heart diseases in the
boxer dog: a retrospective study of 105 cases (1998–2005). Journal of
Veterinary Medicine Series A Physiology, Pathology, Clinical Medicine 53,
346–351.
Cilliers, A.M., Gewillig, M., 2002. Rheology of discrete subaortic stenosis. Heart 88,
335–336.
Corlouer, J.P., 1998. Boxer subaortic stenosis: epidemiology study in France, first
results. In: Proceedings of the 8th Annual ESVIM Congress, Vienna, Austria, pp.
64–66.
Darcin, O.T., Yagdi, T., Atay, Y., Levent, C.E., Buket, S., Alayunt, E.A., 2003. Discrete
subaortic stenosis: surgical outcomes and follow-up results. Texas Heart
Institute Journal 30, 286–292.
Fowles, R.E., Martin, R.P., Popp, R.L., 1980. Apparent asymmetric hypertrophy due
to angled interventricular septum. American Journal of Cardiology 46, 386–
392.
Fuentes, V.L., Darke, P.G.G., Cattanach, B.M., 1994. Aortic stenosis in Boxer dogs.
In: Proceedings of the 12th ACVIM Forum, San Francisco, CA, USA, pp. 309–
311.
Gewillig, M., Daenen, W., Dumoulin, M., Van der Hauwaert, L., 1992. Rheologic
genesis of discrete subvalvular aortic stenosis: a Doppler echocardiographic
study. Journal of the American College of Cardiology 19, 818–824.
Heiene, R., Indrebø, A., Kvart, C., Skaalnes, H.M., Ulstad, A.K., 2000. Prevalence of
murmurs consistent with aortic stenosis among Boxers in Norway and Sweden.
The Veterinary Record 147, 152–156.
Höllmer, M., Willesen, J.L., Jensen, A.T., Koch, J., 2008. Aortic stenosis in the Dogue de
Bordeaux. Journal of Small Animal Practice 49, 432–437.
Kienle, R.D., Thomas, W.P., 2002. Echocardiography. In: Nyland, T.G., Mattoon, J.S.
(Eds.), Small Animal Diagnostic Ultrasound, second ed. W.B. Saunders,
Philadelphia, PA, USA, pp. 354–423.
Kleinert, S., Geva, T., 1993. Echocardiographic morphometry and geometry of the
left ventricular outflow tract in fixed subaortic stenosis. Journal of the American
College of Cardiology 22, 1501–1508.
Linde, A., Koch, J., 2006. Screening for aortic stenosis in the Boxer: auscultatory, ECG,
blood pressure and Doppler echocardiographic findings. Journal of Veterinary
Cardiology 8, 79–86.
MacDonald, K.A., 2006. Congenital heart disease in puppies and kittens. Veterinary
Clinics of North America: Small Animal Practice 36, 503–531.
Patterson, D.F., 1968. Epidemiologic and genetic studies of congenital heart disease
in the dog. Circulation Research 23, 171–202.
Patterson, D.F., 1989. Hereditary congenital heart defects in dogs. Journal of Small
Animal Practice 30, 153–165.
Pyle, R.L., Patterson, D.F., Chacko, S., 1976. The genetics and pathology of discrete
subaortic stenosis in the Newfoundland dog. American Heart Journal 92, 324–
334.
R Development Core Team, 2008. R: A Language and Environment for Statistical
Computing. R Foundation for Statistical Computing, Vienna, Austria. ISBN: 3-
900051-07-0. <http://www.R-project.org>.
Sigfússon, G., Tacy, T.A., VanAuker, M.D., Cape, E.G., 1997. Abnormalities of the left
ventricular outflow tract associated with discrete subaortic stenosis in children:
an echocardiographic study. Journal of the American College of Cardiology 30,
255–259.
Sisson, D.D., Thomas, W.P., Bonagura, J.D., 2000. Congenital heart disease. In:
Ettinger, S.J., Feldman, E.C. (Eds.), Textbook of Veterinary Internal Medicine, fifth
ed. W.B. Saunders, Philadelphia, PA, USA, pp. 737–787.
Thomas, W.P., Gaber, C.E., Jacobs, G.J., Kaplan, P.M., Lombard, C.W., Moise, N.S.,
Moses, B.L., 1993. Recommendations for standards in transthoracic two-
dimensional echocardiography in the dog and cat. Journal of Veterinary
Internal Medicine 7, 247–252.