J Vet Intern Med 2009;23:81–86
U se of A us c ul ta ti on a nd D op pl e r E c h o c a r d i o g r a p h y i n Bo x e r P u p p ies
to Predict De velopm ent of Subaor ti c o r Pulmonary Stenos is
S. Jenni, O. Gardelle, E. Zini, and T.M. Glaus
Background: Boxers are predisposed to subaortic and pulmonic stenosis (SAS, PS). Screening of puppies may be useful in
estimating the risk of their developing a defect that potentially compromises life expectancy or exercise tolerance.
Hypothesis: Presence of SAS or PS in adult Boxers can be predicted by auscultation and Doppler echocardiography at
9–10 weeks of age.
Animals: Eighty-five Boxer puppies examined at 9–10 weeks of age and at 12 months of age.
Methods: Prospective, longitudinal observational study. Auscultation by stethoscope and continuous wave-Doppler echocardiography for peak velocities (Vmax) in the aorta (Ao) and pulmonary artery (PA).
Results: Intensity of heart murmurs in puppies correlated with VmaxAo and VmaxPA in adults. VmaxAo and VmaxPA in
puppies correlated with VmaxAo and VmaxPA in adults, respectively. From puppy to adult, VmaxAo increased and VmaxPA
remained unchanged. The negative predictive value for absent or only a soft (II/VI) murmur in puppies being associated with
VmaxAo and PA 2.4 m/s as an adult was 90% and 3.5 m/s 100%. The negative predictive value of a Vmax 2.4 m/s as a
puppy still being 2.4 m/s as an adult was 94% for Ao and 96% for PA, and of a Vmax 3.5 m/s, 99% for Ao and 100% for PA.
Conclusions and Clinical Importance: Even though VmaxAo increases during growth in Boxer puppies, indicating relative
narrowing of the aorta, puppies with VmaxAo 2.4 m/s do not usually progress to clinically have relevant SAS at 12 months
of age.
Key words: Aortic; Murmur intensity; Peak velocity; Pulmonic.
oxers are predisposed to pulmonic and particularly
subaortic stenosis (PS, SAS).1–8 Dogs with moderate
to severe SAS have an increased risk of premature sudden death and sometimes at a very young age.3 In an
attempt to decrease the prevalence of SAS and PS in
Boxers, breeding dogs are increasingly screened for these
diseases. However, because echocardiographically normal Boxers can produce offspring with heart murmurs,
and sporadically with SAS or PS, there is an interest in
screening puppies to assess the relevance of a heart murmur, and to recognize objective congenital heart disease
that could limit potential use as a working dog, that
could represent a potential risk of unexpected sudden
death, or both.
The diagnosis of SAS or PS in dogs is based primarily
on auscultation and echocardiography. It is generally accepted that a normal heart is characterized by (1) absence
of a murmur, (2) normal cardiac morphology on twodimensional (2D) echocardiography, (3) laminar flow in
the aorta (Ao) and pulmonary artery (PA) across the
valves on pulse wave (PW) Doppler examination, and (4)
peak velocities (Vmax) o1.7 m/s in the Ao and o1.6 m/s
B
From the Division of Cardiology, Clinic for Small Animal Internal
Medicine, Vetsuisse Faculty, University of Zurich, Zurich, Switzerland (Jenni, Zini, Glaus); and the Vetimage, Niederglatt, Zurich,
Switzerland (Gardelle). Parts of these data have been presented as an
abstract at the 16th ECVIM-CA Congress, Amsterdam, the Netherlands, 2006.
Corresponding author: Tony M. Glaus, Division of Cardiology,
Clinic for Small Animal Internal Medicine, Vetsuisse Faculty University of Zurich, Winterthurerstr. 260, CH-8057 Zurich, Switzerland;
e-mail: [email protected].
Submitted December 13, 2007; Revised June 4, 2008; Revised
August 20, 2008; Accepted September 16, 2008.
Copyright r 2008 by the American College of Veterinary Internal
Medicine
10.1111/j.1939-1676.2008.0213.x
in the PA, respectively.9,10 For Boxers, higher Vmax are
generally considered to be normal, at 2.0 m/s for Ao
and 1.8 m/s for PA. It is also generally accepted that a
stenosis is present when (1) a crescendo–decrescendo
murmur at the left heart base is auscultable, (2) an abnormal semilunar valve or pathologic narrowing below
or above a semilunar valve is present, (3) flow is turbulent
on PW Doppler examination, and (4) Vmax is 42.4 m/s in
the Ao and 41.8 m/s in the PA by continuous wave
(CW) Doppler examination.9–12 Finally, it is generally
accepted that a (sub-) valvular stenosis of both Ao and
PA with a Vmax o 3.5 m/s is considered mild and not associated with exercise intolerance or premature death.3,13
Nevertheless, it is unknown what exact VmaxAo should
be considered the ideal cut-off between normal and abnormal dogs. The classification of normal versus
abnormal is particularly difficult if a mild murmur can
be auscultated, no 2D echocardiographic abnormalities
can be detected, flow is laminar in Ao on PW Doppler
examination, and VmaxAo is between 2.0 and 2.4 m/s.
More invasive transesophageal echocardiography has
not been shown to be more sensitive in detecting mild
subaortic lesions in dogs with soft murmurs.14 Newer
technologies investigating heart murmurs by timefrequency and complex analyses may prove to be useful
in differentiating physiologic murmurs from murmurs
caused by aortic stenosis; however, they are not currently
or widely available.15
SAS in Newfoundland dogs is a dynamic disease that
starts to develop after 3 weeks of life and progresses during growth.16 Even though progression is generally
accepted to occur in other breeds, and in adult Boxers a
mild increase in VmaxAo over time has been found,17,18
there are no published data on disease progression during early growth. If progression in growing puppies of
the Boxer and other breeds is similar to that of Newfoundland puppies, it could be assumed that puppies
82
Jenni et al
with a VmaxAo in the gray zone have an increased risk of
developing a relevant SAS over time. In contrast, PS is
mostly caused by a fixed valvular stenosis, and the stenotic area is not expected to change over time. Still,
secondary infundibular hypertrophy can complicate a
fixed stenosis.13
The evidence thus suggests that early detection of increased flow velocities in the Ao or PA could have
prognostic value in Boxers and other breeds predisposed
to stenosis. Therefore, this investigation was undertaken
to study the changes in VmaxAo and VmaxPA in Boxers
from puppyhood to adulthood. Of specific interest was
the development in puppies with VmaxAo in the outlined
gray zone (2.0–2.4 m/s), and whether there was any progression in VmaxPA. The ultimate goal was to assess the
relevance of a soft to moderate heart murmur in a Boxer
puppy and the value of Doppler echocardiography of the
Ao and PA in puppies with a gray zone to mild stenosis
to predict cardiac status at 1 year of age.
Materials and Methods
Dogs
Two hundred and fifty Boxer puppies were examined by
auscultation and echocardiography at 9–10 weeks of age. Of these,
85 were available for re-examination at 1 year. About half these
puppies had the same father, who episodically had produced offspring with SAS or PS, including dogs dying suddenly at o1 year of
age; ie, its offspring were considered to have an increased risk of
being genetically and phenotypically affected. Around 90% of the
85 dogs were examined by 1 examiner (TMG). Of the 165 puppies
not available for re-examination, 54 had a VmaxAo or VmaxPA
2.0 m/s and 15 had a VmaxAo or VmaxPA 2.4 m/s. Of the latter 15
puppies, 12 had a VmaxAo of 2.4–5.9 m/s (median 2.7) and 4 had a
VmaxPA of 2.4–2.6 m/s. Of these 15 puppies, 2 had a soft murmur,
11 had a medium murmur, and 1 had a loud murmur. Most of these
165 puppies were not available for re-examination for geographic
reasons and lack of owners’ interest. Four puppies with moderate to
severe SAS (VmaxAo 3.9, 4.1, 5.3, and 5.9 m/s) were euthanized at
the breeders’ request.
Auscultation
Auscultation was performed in a quiet room just before echocardiography while the dogs were gently restrained. All dogs were
considered to be healthy and normally hydrated based on history
and physical appearance. All puppies showed a moderate degree of
happy excitement during auscultation and no attempt was made to
relate murmur intensity to excitement level and heart rate.
Auscultation in each puppy was performed until heart sounds had
been clearly heard and clearly distinguished from respiratory
sounds for at least 5 continuous time periods of at least 10 seconds
each. Murmur intensity was recorded at the moment when excitement was considered lowest, ie, the moment when auscultation was
least disturbed by the dogs’ motion and respiration. Murmur grading in each dog was made by 1 examiner, who also performed the
subsequent echocardiography.
For classification of murmur intensity the following grading scale
was used as basis: grade 0 5 no murmur, grade 1 5 faintest murmur, only audible after listening for a while with particular effort,
grade 2 5 faint murmur that can be heard within seconds of
auscultation, grade 3 5 moderately loud and easily heard murmur,
grade 4 5 a loud murmur that does not produce a palpable thrill,
grade 5 5 very loud murmur that produces a thrill, and grade
6 5 very loud murmur with precordial thrill, still audible with the
stethoscope off the chest wall.19,20 Then, in order to compensate for
the difficulty of auscultating small hyperactive Boxer puppies and
for the confounding factor of having 3 different examiners, the
murmurs in puppies were grouped into no murmur, soft murmur
(grades 1 and 2), medium murmur (grades 3 and 4), and loud
murmur (grades 5 and 6). In 9 dogs, murmur intensity was not reported in the record. The Doppler data of these 9 dogs were
systematically included in the study. No attempt was made to estimate
the effect of a physiological anemia in puppies on murmur intensity.21
Echocardiography
For echocardiography dogs were positioned in right lateral recumbency on an echocardiographic table. No sedatives were
administered to perform these examinations. Qualitative 2D echocardiography was performed with an Accuson Sequoiaa from the
right parasternal long- and short-axis views with a 7 MHz probe in
puppies and 3.5–7 MHz probe in adults. Quantitative Doppler examinations by CW Doppler examination of blood flow across aortic
and pulmonic valves were obtained from the subcostal transhepatic
view and from the right parasternal short-axis view, respectively.22,23 The probe was positioned so as to obtain optimal
parallel alignment of the Doppler cursor with flow. In puppies, the
average of 3 ejection velocity spectra with well-defined peaks was
measured. None of the puppies had visible sinus arrhythmia. In
adults, the average of 3 consecutive well-defined ejection velocity
spectra was calculated to account for varying peak velocities associated with sinus arrhythmia. Examiners were blinded to the results
of the dogs as puppies when the latter were re-examined as adults.
The intraoperator (TMG) repeatability was obtained in 6 healthy
adult Beagles examined 3 times at monthly intervals and calculated
as coefficient of variation.24
Data Analysis
All statistical calculations were performed by a commercial programb and nonparametric tests (Spearman’s correlation coefficient
and Wilcoxon’s rank sum test). A P-value of o.05 was defined to
represent statistical significance. Considering that the point of maximum intensity of murmurs at the aortic and pulmonic valve is
similar, thus making it impossible to differentiate murmur origin on
the basis of auscultation, murmur intensity was not calculated in
relation to both VmaxAo and VmaxPA separately, but only to the
higher Vmax of the 2, indicated as VmaxAo-PA.
Correlation and statistical difference were calculated between
murmur intensity as puppy and murmur intensity as adult. Further,
correlations were calculated between murmur intensity as puppy
and the higher VmaxAo-PA as puppy as well as the higher VmaxAoPA as adult. Correlations and differences between VmaxAo as
puppy and adult and between VmaxPA as puppy and adult were
also calculated.
The negative predictive values were calculated for murmur intensities as puppy to predict VmaxAo-PA 2.0 and 2.4 m/s as adult: a
high negative predictive value has a clinically positive meaning, ie,
that a puppy with a clinically positive result (eg, no murmur) will
have a clinically positive result as adult (eg, Vmax 2.0 m/s). In addition, sensitivity, specificity, and positive and negative predictive
values were calculated for different cut-off limits of VmaxAo as
puppy to predict VmaxAo below the same cut-off as adult. Because
the VmaxAo representing the cut-off between normal and abnormal
is not known, arbitrarily chosen cut-offs were 1.8, 2.0, 2.2, and
2.4 m/s. Similar analyses were also performed for VmaxPA. Finally, for each vessel it was evaluated up to what Vmax as a puppy
the corresponding Vmax as an adult would still be 3.5 m/s (ie, cutoff between mild and moderate SAS and PS). Data of the VmaxAo
and VmaxPA are shown as mean standard deviation and range.
Prediction of SAS or PS in Boxers
Results
Murmur Intensity as Puppies and as Adults
Twenty-six puppies had no murmur, 33 had a soft
murmur, 17 had a medium murmur, and in 9 puppies
murmur intensity was not reported. The development
of heart murmurs from puppy to adult is depicted in
Table 1. Murmur intensity as a puppy correlated with
murmur intensity as an adult (r2 5 0.66, P .001). Adult
Boxers had a significantly lower murmur intensity than
puppies (P 5 .009).
VmaxAo and VmaxPA as Puppies and as Adults
The intraoperator repeatability was 3.7% (1.6–9.6%)
for VmaxAo and 8.7% (3.1–14.2%) for VmaxPA. Of the 85
Boxers examined twice, VmaxAo in puppies was 2.0 0.5 m/s (range: 1.4–3.9 m/s). Of these, 39 puppies had a
VmaxAo 1.8 m/s, 23 puppies had a VmaxAo 41.8 and
2.0 m/s, 15 puppies 42.0 and 2.4 m/s, and 8 puppies
42.4 m/s. VmaxAo in adults was 2.2 0.9 m/s (range:
1.5–7.5 m/s). Twenty-nine adult Boxers had a VmaxAo 1.8 m/s, 25 had VmaxAo 41.8 and 2.0 m/s, 19 had a
VmaxAo 42.0 and 2.4 m/s, and 12 had a VmaxAo 4
2.4 m/s. VmaxAo in puppies correlated with VmaxAo in
adults (r2 5 0.68, P .001). Adult Boxers had significantly higher VmaxAo than puppies (P .001). A
significant increase in VmaxAo from puppy to adult was
also observed when only puppies with 1.8 m/s were analyzed (n 5 39). In this subgroup, aortic flow Vmax
increased from 1.7 0.1 to 1.9 0.2 m/s (P .001).
VmaxPA in puppies (n 5 85) was 1.5 0.4 m/s (range:
0.8–3.2 m/s). Seventy puppies had a VmaxPA 1.8 m/s, 4
puppies had a VmaxPA 41.8 and 2.0 m/s, 7 puppies had
a VmaxPA 42.0 and 2.4 m/s, and 4 puppies had a
VmaxPA 4 2.4 m/s. VmaxPA in adults was 1.5 m/s 0.6 m/s (range: 0.8–3.9 m/s). Seventy-three adult Boxers
Table 1. Development of heart murmurs in Boxers
from puppy to adult (n 5 85).
Murmur Puppy
None, n 5 26
Softa, n 5 33
Mediuma, n 5 17
Not reported, n 5 9
a
Murmur Adult
0/6, n 5 22
1/6, n 5 1
2/6, n 5 1
3/6, n 5 1
Not reported, n 5 1
0/6, n 5 17
1/6, n 5 7
2/6, n 5 5
3/6, n 5 4
0/6, n 5 1
1/6, n 5 0
2/6, n 5 3
3/6, n 5 9
4/6, n 5 2
5/6, n 5 1
6/6, n 5 1
0/6, n 5 8
4/6, n 5 1
Soft, grades 1 1 2/6; medium, grades 3 1 4/6; loud, grades
5 1 6/6.
83
had a VmaxPA 1.8 m/s, 5 had a VmaxPA 42.0 and
2.4 m/s, and 7 had a VmaxPA 4 2.4 m/s. VmaxPA
in puppies correlated with Vmax in adults (r2 5 0.51,
P .001) and did not change significantly over time
(P 5 .47).
On qualitative 2D echocardiography, with 1 exception
the aortic and pulmonic outflow tracts and valves were
judged to be unremarkable in puppies. The 1 exception
was a puppy with a VmaxAo of 3.9 m/s, which had already been diagnosed with a muscular SAS at 10 weeks.
Murmur Intensity as a Puppy and Relation to Vmax
Ao-PA as an Adult
Murmur intensity in puppies correlated with VmaxAoPA in puppies (r2 5 0.74, P .001) and in adults (r2 5
0.60, P o .001). All puppies without a murmur (n 5 26)
had a VmaxAo-PA 2 m/s as puppies and 2.7 m/s as
adults. The negative predictive value of a puppy without
a murmur having a VmaxAo-PA 2.0 m/s as an adult
was 88% (23/26 dogs), and 96% (25/26 dogs) for
VmaxAo-PA 2.4 m/s.
Puppies with a soft murmur had a VmaxAo-PA of
1.5–2.5 m/s as puppies and 1.8–3.5 m/s as adults; the
negative predictive value for VmaxAo-PA as an adult being 2.0 m/s was 58% (19/33 dogs), and being 2.4 m/s
was 85% (28/33 dogs). Puppies with a medium murmur
(n 5 17) had a VmaxAo-PA of 2.0–3.9 m/s as puppies
and 2.0–7.5 m/s as adults; in 6 of these adults VmaxAo
was 42.4 and 3.5 m/s, and in 5 it was 43.5 m/s. The
negative predictive value for puppies with a moderate
murmur having a VmaxAo-PA as an adult 2.4 m/s
was 35%.
VmaxAo and PA in Puppies and Relation to VmaxAo and
PA as Adults
The prediction of VmaxAo as adults based upon status
as a puppy is shown in Table 2. The sensitivity, specificity, and positive and negative predictive values of
different Vmax cut-offs are summarized in Table 3 (for
Table 2. Vmax Ao-PA in adult Boxers in relation to their
status as puppies (n 5 85).
VmaxAo Puppies (m/s)
1.8, n 5 39
1.9–2.0, n 5 23
2.1–2.2, n 5 9
2.3–2.4, n 5 6
2.5–3.9, n 5 8
VmaxAo Adults (m/s)
1.8, n 5 23
1.8–2.0, n 5 11
2.2–2.4, n 5 4
2.7, n 5 1
2.0, n 5 17
2.0–2.2, n 5 6
2.2, n 5 6
2.4, n 5 1
2.8, n 5 1
5.9, n 5 1
2.4, n 5 4
2.8, n 5 1
3.4, n 5 1
2.4, n 5 0
3.5, n 5 5
84
Jenni et al
Table 3.
VmaxAo (m/s)
1.8
2.0
2.2
2.4
Sensitivity, specificity, and positive and negative predictive values at different VmaxAo as puppy.
Sensitivity (%)
Specificity (%)
1 Predictive Value (%)
71
65
63
58
59
94
97
99
87
87
86
88
Ao) and Table 4 (for PA). With regard to Ao, of 39 puppies with a Vmax 1.8 m/s, Vmax was still 1.8 m/s in 23
as adults, the negative predictive value being 59%. Of 62
puppies with a Vmax 2.0 m/s, Vmax was still 2.0 m/s in
51 as adults, the negative predictive value being 82%. Of
71 puppies with a Vmax 2.2 m/s, Vmax was still 2.2 m/s
in 64 as adults, the negative predictive value being 90%.
Of 77 puppies with a Vmax 2.4 m/s, Vmax was still
2.4 m/s in 72 as adults, the negative predictive value being 94%. Twelve dogs had developed a VmaxAo 4 2.4 m/
s and 4 of these had reached 43.5 m/s as adults; only 1
puppy with a VmaxAo 2.4 m/s developed a Vmax 4
3.5 m/s as adult (Table 5).
With regard to PA, of 70 puppies with a Vmax 1.8 m/s,
Vmax was still 1.8 m/s in 68 as adults, the negative predictive value being 97%. The remaining 2 dogs had 2.0
and 2.1 m/s. Of 74 puppies with a Vmax 2.0 m/s, Vmax
was still 2.0 m/s in 72 as adults, the negative predictive
value being 97%. The remaining 2 dogs had 2.1 and
2.7 m/s. Of 76 puppies with a Vmax 2.2 m/s, Vmax was
still 2.2 m/s in 75 as adults, the negative predictive value
being 99%. Of 81 puppies with a Vmax 2.4 m/s, Vmax
was still 2.4 m/s in 78 as adults, the negative predictive
value being 96%. Seven dogs had developed a VmaxPA
42.4 m/s, and 3 had a VmaxPA 4 3.5 m/s as adults, but
all remained o4 m/s (Table 5). None of the dogs with a
VmaxPA 2.4 m/s as a puppy developed a Vmax 4 3.5 m/
s as an adult.
Discussion
Our data indicate that screening Boxer puppies for
SAS and PS by auscultation and Doppler echocardiography at 10 weeks of age is a good indicator of cardiac
status at 1 year of age. Murmur intensity as a puppy correlates with murmur intensity and VmaxAo or PA as an
adult, and low murmur intensity and relatively low
VmaxAo and PA as a puppy allow the exclusion of a clinically relevant stenosis as an adult. Specifically, all
puppies with no or only a soft murmur had a VmaxAo
and VmaxPA 3.5 m/s as adults, ie, the upper limit of a
mild stenosis.3 The predictive value of VmaxAo 2.4 m/s
in puppies being 2.4 m/s as adults was 94%, and 84 out
Predictive Value (%)
n 5 x / 85
59
82
90
94
46
23
14
8
of 85 Boxers remained 3.5 m/s. For the PA, as there was
no average progression over time, the predictive value at
any chosen VmaxPA as a puppy staying below that cut-off
as an adult was very high, ie, 95%, and none of the
puppies with a VmaxPA 2.4 m/s as a puppy developed a
Vmax 4 3.5 m/s as an adult. Thus, puppies with no or
only a soft murmur and a VmaxAo and VmaxPA 2.4 m/s
can be quite safely sold with an assumed normal (cardiac)
life expectancy and exercise tolerance. On the other hand,
in view of increasing VmaxAo in most dogs and positive
predictive values close to 90% for all cut-offs studied, it is
very unlikely that puppies in the gray zone or above will
have lower results as adults.
Using VmaxAo as the primary indicator of an abnormal aorta, the fact that, in this study, VmaxAo
significantly increased during growth may reflect the occurrence of (dynamic) changes in the aorta, to the point
of clear SAS in some. Extrapolating from the study performed in the Newfoundland by Pyle et al,16 increasing
disease severity in dogs with SAS clearly present as a
puppy is to be expected. However, in our study the more
important question was to what degree the situation
would change in those puppies where VmaxAo was 2.0–
2.4 m/s, ie, within a gray zone between normal and disease. In this gray zone, normal as well as abnormal
Boxers may be expected, and thus progression may be
very variable. As shown in the Newfoundland, only the
mildest forms of SAS have been observed in puppies o12
weeks of age.16 With morphologically only mild SAS,
echocardiographically, only a mildly increased VmaxAo
would be expected. As severity in adult Newfoundland
dogs is very variable, examining 10-week-old puppies
may not be expected to be useful in predicting adult outcome. Nevertheless, with 1 exception, the increase in
VmaxAo was only of a small and clinically irrelevant
magnitude in Boxer puppies starting in this specific range
of 2.0–2.4 m/s.
On the other hand, VmaxAo had also significantly increased in puppies 1.8 m/s, ie in puppies more likely to
be normal. A possible conclusion may be that most or all
Boxer puppies in this study had some degree of abnormal
aorta, supporting the hypothesis mentioned that Boxers
may have a general breed specific abnormality.25
Table 4. Sensitivity, specificity, and positive and negative predictive values at different VmaxPA as puppy.
VmaxPA (m/s)
1.8
2.0
2.2
2.4
Sensitivity (%)
Specificity (%)
1 Predictive Value (%)
85
83
88
43
94
99
97
99
73
91
78
75
Predictive Value (%)
97
97
99
95
n 5 x / 85
15
11
9
4
Prediction of SAS or PS in Boxers
Table 5. Progression of VmaxAo and VmaxPA in Boxers with Vmax 4 2.4 m/s as adults.
Ao Puppy (m/s)
Ao Adult (m/s)
1.5
3.1
2.2
2.4
2.8
2.3
3.1
3.6
3.0a
3.4
2.2
3.9
PA puppy (m/s)
2.0
2.3
2.4
2.3
2.6
2.5
3.2a
2.7
2.6
2.8
2.8
2.9
3.4
3.5
3.5
3.8
3.8
5.9
7.5
PA adult (m/s)
2.7
2.8
2.8
2.9
3.7
3.9
3.9
a
Same dog.
Of additional interest were the 12 dogs that developed
SAS defined as VmaxAo 4 2.4 m/s as adults, with respect
to their baseline as a puppy and to what extent they had
shown a progression. Five of these were normal or in the
gray zone and 7 between 2.4 and 3.9 m/s as puppies. In 2
of these 12 dogs, VmaxAo had actually mildly decreased
during growth. In the other 10 dogs VmaxAo had increased by an average of 1.4 m/s (median increase of
0.7 m/s), but with 2 exceptions VmaxAo had remained
o4 m/s. In these last 2 dogs there was a most severe progression over time. Whereas one of these already had a
moderate stenosis as a puppy on 2D echocardiography
and based on a VmaxAo of 3.9 m/s, the other dog was not
initially remarkable. This last dog is a cause for concern,
because the development of severe stenosis was missed by
screening as a puppy. Nevertheless, in this study a dangerous progression of SAS was also the exception in
puppies starting in or slightly above the gray zone.
On the other hand, VmaxPA overall did not significantly increase over time. This finding was expected,
because in dogs PS is usually a congenital and fixed valvular stenosis, and a relevant secondary infundibular
hypertrophy is not expected to develop over time if a
mild stenosis is present. Nevertheless, all 7 dogs that developed a VmaxPA 4 2.4 m/s as adults showed a
progression from puppyhood with an average velocity
increase of 0.8 m/s. Of these, only puppies with VmaxPA
4 2.4 m/s developed moderate stenosis as adults (defined
as VmaxPA 4 3.5 m/s), but all remained o4 m/s. Thus, in
individual puppies with mild PS there may be an increase
in severity during growth. Even though the development
of an infundibular stenosis was not observed by 2D echocardiography in these dogs as adults, the development of
subtle morphologic abnormalities in the right outflow
tract cannot be ruled out.
85
In this study, murmur intensity decreased from puppy
to adulthood despite increasing blood-flow velocities.
The simplest explanation for this paradox would be that
physiological murmurs in puppies disappeared. Soft
murmurs in puppies have been associated with physiologically lower PCV, thin chest wall, or with relatively
larger stroke volume as compared with aortic diameter in
puppies.26 Of these factors, physiological anemia does
not seem to have been primarily responsible for the murmur, because a murmur was not detected in 26 puppies,
and most puppies with a soft murmur had a VmaxAo or
PA 1.8 m/s, ie, a velocity that may by itself cause turbulent flow.18 A larger stroke volume in relation to aortic
diameter that normalized over time does not appear responsible for the murmur, because this should have been
accompanied by a decreasing Vmax. Thin chest wall thus
seems the most logical explanation for higher murmur
intensity as puppies despite lower VmaxAo-PA as compared with adults. Summarizing these considerations, a
soft murmur in a Boxer puppy likely implies a VmaxAoPA higher than what would be considered normal in
other breeds.9–11 Or, in other words, in 9–10-week-old
puppies with a physiologically anemic PCV,21 a soft murmur may not simply be accepted as being physiological.
Limitations of Study
Echocardiography in these puppies focused only on
Vmax, and did not attempt to assess the anatomy of the
aorta or the aortic size with respect to left ventricular
size. At the beginning of the study, Vmax was believed to
be the most objective and most important determinant of
a mild stenosis, and it is still the authors’ perception that
dogs with a Vmax in the range of 2.0–2.4 m/s may be considered to be susceptible for a mild defect. Furthermore,
the primary goal of this project was not to study why or
how Boxer dogs were different compared with other
breeds with respect to anatomy, but rather to evaluate
the degree of potential progression during growth. As up
to now no data have been published showing to what
degree such puppies may progress over time, this information should be valuable.
It would have been very interesting to include a large
number of puppies with VmaxAo 4 2.4 m/s and a mild
SAS on 2D echo to evaluate the disease dynamic in such
dogs. However, in our 250 initially examined puppies
there were not many such dogs, and breeders have been
reluctant to sell (or keep) such puppies, because premature death in such dogs was a concern. For this reason,
this study does not permit assessing the risk of developing a serious SAS when mild SAS is present as a puppy.
In conclusion, flow velocities across the aortic valve
increase in most Boxer puppies during growth. This increase is usually mild and of no clinical relevance.
However, in individual cases, increase may be pronounced to a point where premature death or exercise
intolerance is anticipated. With few exceptions, flow velocities across the pulmonic valve do not change in most
Boxer puppies during growth. Because of the variable increases in flow velocities, eligibility for breeding cannot
be predicted at 9–10 weeks of age. Nevertheless, in Boxer
86
Jenni et al
puppies that are considered to have a certain genetic risk
of developing SAS or PS, cardiac screening at 9–10 weeks
of age, ie just before they are sold, appears to be valuable
to predict cardiac status as adults with respect to the
clinical relevance of a potential SAS or PS.
Footnotes
a
b
Siemens, Glattbrugg, Switzerland
SPSSR 11.0 for Windows, SPSS Inc, Chicago, IL
Acknowledgment
Acknowledgements to the breeders, Mrs Hofmann,
Halter, Pfeiffer-Nagel, and Reiss, for participating in the
study.
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