Journal of Veterinary Cardiology (2018) -, -e-

www.elsevier.com/locate/jvc

Echocardiographic assessment of right

ventricular systolic function in Boxers
with arrhythmogenic right ventricular
cardiomyopathy
S.M. Cunningham, DVM a,*, B.D. Aona, DVM b, K. Antoon,
CVT, VTS a, J.E. Rush, DVM, MS a, B.A. Barton, Ph.D. c

a
Department of Clinical Sciences, Cummings School of Veterinary Medicine at Tufts
University, 200 Westboro Road, North Grafton, MA, USA, 01536
b
Department of Clinical Sciences, College of Veterinary Medicine, North Carolina State
University, Raleigh, NC, USA, 27607
c
Department of Quantitative Health Sciences, University of Massachusetts Medical
School, Worcester, MA, USA, 01605

Received 26 September 2017; received in revised form 10 July 2018; accepted 18 July 2018

KEYWORDS Abstract Objectives: To determine whether there are differences in measures of

Canine; longitudinal right ventricular (RV) systolic function among Boxers with arrhythmo-
Cardiac; genic right ventricular cardiomyopathy (ARVC) compared with healthy control Box-
Arrhythmia; er dogs. To explore relationships between markers of RV systolic function and age,
Right ventricle body weight, gender, arrhythmia frequency, and markers of left ventricular (LV)
systolic function in Boxer dogs.
Animals: The study included 50 client-owned Boxer dogs.
Methods: This is a retrospective echocardiographic study. Tricuspid annular plane
systolic excursion (TAPSE) and pulsed wave tissue Doppler imagingederived systolic
myocardial velocity of the lateral tricuspid annulus (S’) were measured in healthy
control Boxers (n ¼ 18), Boxers with ARVC and normal LV systolic function
(n ¼ 19), and Boxers with ARVC and reduced LV systolic function (n ¼ 13).
Results: Tricuspid annular plane systolic excursion (p¼0.002) and S’ (p¼0.001) were
significantly different between affected and control groups. Significant correlations
were found between measures of left heart size and function and both TAPSE and
S’. No correlations were found between RV function parameters and age, gender, or
body weight in this fairly homogeneous, single-breed population. Receiver

* Corresponding author. Suzanne Cunningham

E-mail address: suzanne.cunningham@tufts.edu (S.M. Cunningham).

https://doi.org/10.1016/j.jvc.2018.07.005
1760-2734/ª 2018 Elsevier B.V. All rights reserved.

Please cite this article in press as: Cunningham SM, et al., Echocardiographic assessment of right ventricular systolic function in
Boxers with arrhythmogenic right ventricular cardiomyopathy, Journal of Veterinary Cardiology (2018), https://doi.org/10.1016/
j.jvc.2018.07.005
2 S.M. Cunningham et al.

operating characteristic curve analysis revealed that both TAPSE and S’ had an area
under the curve of 0.77 in distinguishing healthy Boxers from those with ARVC.
Conclusions: Tricuspid annular plane systolic excursion and S’ are reduced in Boxers
with ARVC. In contrast to prior studies evaluating these parameters in dogs of dif-
ferent breeds and body types, no correlation was found between markers of RV
function and body weight in this population of Boxer dogs.
ª 2018 Elsevier B.V. All rights reserved.

changes and systolic dysfunction in Boxers with

Abbreviation
ARVC arrhythmogenic right ventricular
cardiomyopathy
CHF congestive heart failure
FS fractional shortening
LV left ventricle
RV right ventricle
TAPSE tricuspid annular plane systolic
excursion
S’ pulsed wave tissue Doppler imaging
derived systolic myocardial velocity
of the lateral tricuspid annulus
VPC ventricular premature complex
Introduction
Arrhythmogenic right ventricular cardiomyopathy
(ARVC) is an inherited cardiomyopathy of Boxer
dogs which predominantly affects the right ven-
tricle (RV) [1,2]. The pathophysiology of the dis-
ease is characterized by progressive replacement
of normal ventricular myocardium with fatty or
fibrofatty tissue, frequently accompanied by
inflammatory infiltrates. The resulting electrical
instability manifests in ventricular tachyar-
rhythmias, which may lead to syncope or sudden
cardiac death. In advanced disease, the left ven-
tricle (LV) can also be affected, and progressive
systolic dysfunction and biventricular dilation
appearing grossly indistinguishable from dilated
cardiomyopathy (DCM) may result in congestive
heart failure (CHF).
In people, echocardiography plays an important
role in the evaluation of patients with ARVC [3e5].
Echocardiographic evidence of LV dysfunction has
been associated with adverse outcomes in both
people [4e8] and Boxers with ARVC [9,10]. Left
ventricular involvement may represent an end-
stage complication of ARVC in people, manifest-
ing after a prolonged period of cardiac arrhythmias
and/or RV dilation and dysfunction [11]. The nat-
ural history and progression of structural cardiac
ARVC is less well characterized [12,13]. Echo-
cardiographic assessment of RV systolic function in
dogs with ARVC may allow for earlier detection of
structural cardiac abnormalities and aid in the
diagnosis, monitoring, and prognostication of the
disease.
Right ventricular dysfunction has been docu-
mented in many cardiovascular disease states in
people, and the echocardiographic assessment of
RV function plays an important role in the evalu-
ation of patients with cardiac disease. Historically,
clinical assessment of RV function via echo-
cardiography has been infrequently reported in
animals [14e18]. Tricuspid annular plane systolic
excursion (TAPSE) and pulsed wave tissue Doppler
imagingederived systolic myocardial velocity of
the lateral tricuspid annulus (S’) are easily
obtained echocardiographic measures of longi-
tudinal RV systolic function that have been well
validated in people with cardiac disease
[4,6,19e23]. Recent studies have established ref-
erence ranges and shown that measurement of
these indices is both feasible and repeatable in
healthy dogs [24e26] and may have utility in the
evaluation of animals with cardiac disease
[18,27e32]. In people, both TAPSE and S’ have
been shown to correlate well with other measures
of global RV systolic function [33e36] and have
shown utility in the screening and monitoring of
ARVC [3,4,6,37e39]. A recent study suggested that
reduced TAPSE may serve as a negative prognostic
indicator in Boxers with arrhythmias [30]; how-
ever, to date, there are no studies comparing
TAPSE or S’ in healthy Boxers and Boxers with
ARVC.
The aim of this study was to determine whether
Boxers with ARVC have differences in TAPSE and S’
compared with healthy control Boxer dogs and to
explore relationships between these indices and
age, body weight, gender, arrhythmia frequency,
and markers of LV systolic function. We hypothe-
sized that both measures of RV systolic function
would be reduced in Boxer dogs with ARVC in
comparison to normal control Boxer dogs and that

Please cite this article in press as: Cunningham SM, et al., Echocardiographic assessment of right ventricular systolic function in
Boxers with arrhythmogenic right ventricular cardiomyopathy, Journal of Veterinary Cardiology (2018), https://doi.org/10.1016/
j.jvc.2018.07.005
RV systolic function in Boxers with ARVC
a further reduction in these measurements would
be noted in dogs with LV systolic dysfunction.
Animals, materials, and methods
Animals
Boxer dogs evaluated between 2013 and 2016 were
eligible for inclusion in this retrospective study if
they underwent a complete echocardiographic
study that included measurement of TAPSE and S’,
a 6-lead electrocardiogram, and a 24-h Holter
monitor. This testing was performed either as part
of routine clinical evaluation or as a component of
other prospective clinical studies evaluating blood-
based biomarkers in Boxers with ARVC. The latter
studies were approved by the school’s Clinical
Studies Review Committee, and clients signed an
informed consent form before enrollment. Clinical
data were collected from the electronic medical
record system of the Cummings School of Veteri-
nary Medicine at Tufts University.
Dogs were selected for inclusion as healthy
controls if they were aged at least 5 years with no
clinical signs of cardiac disease or other systemic
illness, had a normal echocardiogram, were on no
cardiac medications, and had <100 ventricular
premature complexes (VPCs)/24 hr on a 24-hour
Holter monitor. Dogs were considered to be
affected with ARVC if they had RV origin ven-
tricular ectopy with greater than 100 VPCs/24 hr
on Holter monitoring [2,40]. Dogs with ARVC could
be on cardiac medications, and this was not an
exclusion criterion for the study. Concurrent LV
systolic dysfunction was defined by at least two of
the three following criteria: LV internal diameter
at end-diastole >4.8 cm, LV internal diameter at
end-systole >3.3 cm, or LV fractional shortening
(FS) < 25% [41,42]. These values were selected
based on being outside of previously reported
reference ranges for adult Boxers [42]. Dogs were
classified into one of the three clinical groups
based on Holter and echocardiographic data at
the time of study inclusion: group 1, healthy
control dogs; group 2, ARVC with normal LV sys-
tolic function; and group 3, ARVC with concurrent
echocardiographic evidence of LV systolic
dysfunction.
Dogs with congenital heart disease, including a
subcostal aortic velocity of >2.25 m/sec measured
either by pulsed wave or continuous wave Doppler
echocardiography, were excluded from the study
[43]. Additionally, dogs were excluded if they were
found to have moderate to marked azotemia, a
known infection, inflammatory leukogram, or
Please cite this article in press as: Cunningham SM, et al., Echocardiographic assessment of right ventricular systolic function in
Boxers with arrhythmogenic right ventricular cardiomyopathy, Journal of Veterinary Cardiology (2018), https://doi.org/10.1016/
j.jvc.2018.07.005
3
other concurrent systemic disease. Thyroid testing
and measurement of cardiac biomarkers were not
prerequisites for inclusion in the study.
Echocardiography
Standardized 2-dimensional (2D), M-mode, and
Doppler echocardiographic studies were per-
formed by a board-certified cardiologist
(S.M.C.) or by a cardiology resident under the
direct supervision of a board-certified cardiologist.
Echocardiograms were performed with simulta-
neous ECG monitoring with echocardiographic
systems using either a 3 d or 5 e MHz transducer.
Dogs were manually restrained without sedation
for acquisition of standardized echocardiographic
views in right and then left lateral recumbency. M-
mode recordings were obtained with 2D guidance
in accordance with the American Society of Echo-
cardiography standards [44]. Measurements inclu-
ded interventricular septum, LV internal
dimension, and LV free wall at end-diastole and
systole. Transverse short-axis 2D left atrial and
aortic diameters were measured in early ven-
tricular diastole, as previously described [45].
During the observation period of this study, our
institutional approach was to prospectively
measure TAPSE and tricuspid annular S’ in all
Boxer dogs that were examined. All efforts were
made to ensure optimal lineup with the RV free
wall during acquisition of left apical views to
avoid underestimating TAPSE, and anatomic M-
mode was not used. All echocardiographic meas-
urements were performed by the same individual
(S.M.C.), and echocardiographic measurements
were not remeasured at a later date for the pur-
poses of this study. Tricuspid annular plane sys-
tolic excursion and S’ were measured in all dogs as
previously described [24]. As such, TAPSE was
measured as the maximal longitudinal excursion
of the lateral tricuspid annulus in systole, using
standard M-mode recordings with the cursor as
parallel to the RV free wall as possible. Measure-
ments of TAPSE were obtained at sweep speeds of
100 mm/sec. Three consecutive measurements
were obtained during sinus rhythm in all dogs. The
velocity of longitudinal RV free wall excursion in
systole was also measured using pulsed wave tis-
sue Doppler imaging of the lateral tricuspid
annulus. The cursor was aligned as parallel to the
longitudinal plane of RV free wall as possible, and
d
Vivid 7 Dimension, GE Medical Systems, Waukesha, WI, USA.
e
Vivid E9 Vet with XD Clear and 4D package, GE Medical
Systems, Waukesha, WI, USA.
4 S.M. Cunningham et al.
pulsed wave sample volume was maintained at
4e5 mm. Measurements of S’ were made at sweep
speeds of at least 66 mm/sec.
Statistical analysis
Data were graphically inspected and the Kolmo-
goroveSmirnov test was used to assess normality.
Because some variables were not normally dis-
tributed, data are presented as median (range).
Categorical data were compared by use of c2 tests
or Fisher’s exact test for small expected cell
counts, while continuous data were analyzed by
Mann-Whitney U tests to determine pairwise sig-
nificance levels. Each of the pairwise comparisons
was made without corrections for multiple testing
[46]. Spearman’s rank order correlation coefficient
was used to test the strength of correlations
between TAPSE, STAPSE, S’ and selected clinical
parameters of interest (age, body weight, VPC/
24 hr, FS, LV internal dimension at end-diastole
and end-systole, the ratio of short-axis 2D left
atrial to aortic diameter, early diastolic velocity of
mitral inflow, ratio of early to late diastolic mitral
inflow velocities), and Mann-Whitney U test was
used to test the difference in TAPSE and S’ for
gender, presence or absence of CHF, and admin-
istration or sotalol or pimobendan. Multiple linear
regression was used to further evaluate whether
TAPSE could be predicted by the clinical variables
found to be significantly correlated with it. Varia-
bles were selected to include in the model based
on Spearman’s non-parametric correlation with
TAPSE (p<0.1). Although some of the variables
were not normally distributed, we used a general
linear model approach because no non-parametric
multivariable regression approach is available. We
validated the assumptions of the models presented
to verify the normality of residuals at each pre-
dictor value and for equality of variance across the
predictor values and to statistically check that the
standardized residuals followed a standard normal
distribution. Receiver operating characteristic
curve analysis was used to investigate the ability of
TAPSE and S’ to distinguish between normal and
affected Boxers. Statistical analysis was per-
formed using commercially available software.f p
values 0.05 were considered statistically sig-
nificant. Outliers in the box and whisker plots
(denoted by dots) were defined as cases with val-
ues between 1.5 and 3 times the interquartile
range.
f
IBM SPSS Statistics, version 22, IBM Corp, Armonk, NY, USA.
Please cite this article in press as: Cunningham SM, et al., Echocardiographic assessment of right ventricular systolic function in
Boxers with arrhythmogenic right ventricular cardiomyopathy, Journal of Veterinary Cardiology (2018), https://doi.org/10.1016/
j.jvc.2018.07.005
Results
Fifty-three dogs were evaluated for the study;
three dogs were excluded because they did not
clearly fulfill the inclusion criteria with one dog
having mostly supraventricular tachycardia on
Holter, one dog with poor Holter signal quality, and
one dog with historical but unconfirmed ven-
tricular tachycardia but fewer than 100 VPCs/24 h
on Holter. Fifty dogs were included in the study, 23
males (18 castrated) and 27 females (23 spayed).
The median body weight of all dogs was 31.1
(20e43) kg, and the median age was 7 (3e13)
years. Eighteen dogs (36%) were classified as group
1; 19 dogs (38%) were included in group 2; and 13
dogs (26%) were included in group 3. Three dogs
with LV systolic dysfunction had CHF. There were
no differences among these groups with regard to
age, sex, or body weight (Table 1). Nine animals
with ARVC were not receiving any medications at
the time of evaluation. Cardiac medications in
dogs with ARVC included sotalol (n ¼ 16), mex-
iletine (n ¼ 7), pimobendan (n ¼ 6), lidocaine
(n ¼ 6), enalapril (n ¼ 5), furosemide (n ¼ 3),
amiodarone (n ¼ 2), atenolol (n ¼ 1), spi-
ronolactone (n ¼ 1), and benazepril (n ¼ 1).
Tricuspid annular plane systolic excursion
Tricuspid annular plane systolic excursion was
measured in all dogs. Dogs with ARVC (groups 2 and
3) had significantly lower TAPSE compared with
group 1 (p¼0.002). Group 3 had lower TAPSE
(10.3 mm [range, 7.7e15.8 mm]) compared with
both group 1 (14.2 mm [range, 10.2e18.2 mm];
p<0.001) and group 2 (12.4 mm [range,
8.2e22.0 mm]; p¼0.027) (Table 1, Fig. 1). Group 2
also had lower TAPSE compared with group 1
(p¼0.05; Fig. 1). Significant correlations were
found between TAPSE and S’ (r ¼ 0.70; p<0.001),
LV FS (r ¼ 0.48; p<0.001; Fig. 2), the ratio of short-
axis 2D left atrial to aortic diameter (r ¼ 0.45,
p¼0.001), the ratio of early to late diastolic mitral
inflow velocities (r ¼ 0.44; p¼0.002), presence of
CHF (p¼0.01), and administration of pimobendan
(p¼0.03); however, in multivariate analysis, nei-
ther CHF nor pimobendan administration were
significant predictors of TAPSE when the FS was
included as a covariate. There was no correlation
between TAPSE and sotalol administration, and no
significant associations were seen between TAPSE
and age, gender, body weight, or Holter VPC fre-
quency when evaluating all dogs (Table 2). Sim-
ilarly, no significant correlations were found
between TAPSE and age (p¼0.578), gender
RV systolic function in Boxers with ARVC 5

Table 1 Clinical characteristics of 50 healthy and affected Boxers.

Clinical parameter Normal (n ¼ 18) ARVC with normal ARVC with reduced
LV systolic function LV systolic function
(n ¼ 19) (n ¼ 13)
Age (years) 6.5 (5e13) 7.0 (3e10) 8.0 (4e12)
Body weight (kg) 31.3 (25.0e36.6) 31.3 (22.6e39) 32.0 (20.0e43.0)
Gender (M/F) 9/9 6/13 8/5
Total VPC (per 24 hr) 5 (1e64) 1599 (154e8273) 2506 (168e26,789)
Pimobendan (Y/N) 0/18a 0/19a 4/9b
Sotalol (Y/N) 0/18a 7/12b 4/9b
Atenolol (Y/N) 0/18 0/19 1/12
FS 36 (29e44) 31 (25e42) 17 (11e24)
LVIDd (cm) 3.8 (3.0e4.5) 4.1 (3.3e4.5) 4.9 (4.3e6.3)
LVIDs (cm) 2.5 (1.9e2.9) 2.8 (2.1e3.1) 4.0 (3.6e5.6)
LA (cm) 3.4 (2.9e3.8)a 3.6 (3.0e4.2)a 4.8 (3.2e6.1)b
Ao (cm) 2.0 (1.6e2.4) 2.0 (1.7e2.5) 2.1 (1.9e2.2)
LA:Ao 1.7 (1.4e2.0)a 1.8 (1.4e2.1)a 2.3 (1.5e3.2)b
TAPSE (mm) 14.2 (10.2e18.2)a 12.4 (8.2e22.0)b 10.3 (7.7e15.8)c
S’ (cm/s) 17.0 (10.0e28.0)a 14.0 (8.0e27.0)a 10.0 (7.0e15.0)b
VPC, ventricular premature complex; FS, fractional shortening %; LVIDd, left ventricular internal dimension at end-diastole;
LVIDs, left ventricular internal dimension at end-systole; LA, short-axis two-dimensional left atrial dimension; Ao, short-axis
two-dimensional aortic dimension; LA:Ao, ratio of short-axis left atrial to aortic diameter; TAPSE; tricuspid annular plane sys-
tolic excursion; S’, pulsed wave tissue Doppler imagingederived systolic myocardial velocity of the lateral tricuspid annulus.
Data are presented as median (range). Different superscripts indicate significant differences in indices between one or more
individual Boxer groups.

Figure 1 Box and whisker plots of TAPSE (A) and tricuspid annular S’ (B) measurements in 50 Boxer dogs. Dogs were
categorized as normal (healthy controls, n ¼ 18); ARVC with arrhythmia only (n ¼ 19); and ARVC with LV systolic
dysfunction (dilated cardiomyopathy [DCM] phenotype; n ¼ 13). The dots denote outliers. TAPSE, tricuspid annular
plane systolic excursion; S’ pulsed wave tissue Doppler imagingederived systolic myocardial velocity of the lateral
tricuspid annulus; ARVC, arrhythmogenic right ventricular cardiomyopathy; LV, left ventricular.

(p¼0.243), body weight (p¼0.800), or Holter VPC
frequency (p¼0.201) when including only normal
Boxers in the analysis.
Receiver operating characteristic curve analysis
performed on all 50 dogs yielded an area under the
curve of 0.77 to distinguish healthy from affected
Boxers (Fig. 3). At an optimal cutoff value of
13.0 mm, the sensitivity was 75.0% and the spe-
cificity was 66.7%.
Tissue Doppler imagingederived tricuspid
annular systolic longitudinal velocity
Tricuspid annular S’ was measured in all dogs. Dogs
with ARVC (groups 2 and 3) had significantly lower
S’ compared with group 1 (p¼0.001), and S’ was
lower in group 3 (10.0 cm/sec [range, 7.0e15.0
cm/sec]) compared with group 1 (17.0 cm/sec
[range, 10.0e28.0 cm/sec]; p¼0.001; Fig. 1). The

Please cite this article in press as: Cunningham SM, et al., Echocardiographic assessment of right ventricular systolic function in
Boxers with arrhythmogenic right ventricular cardiomyopathy, Journal of Veterinary Cardiology (2018), https://doi.org/10.1016/
j.jvc.2018.07.005
6 S.M. Cunningham et al.

Figure 2 Scatter plot illustrating the relationship between tricuspid annular plane systolic excursion (TAPSE) and
left ventricular fractional shortening (FS) %.

difference in S’ between group 2 (14.0 cm/sec

Table 2 Correlation of tricuspid annular plane sys- [range, 8.0e27.0 cm/sec]) and group 1 did not
tolic excursion (TAPSE) with selected clinical param- reach statistical significance (p¼0.06). Significant
eters in 50 Boxers. correlations were found between S’ and LV FS
Clinical parameter r p (r ¼ 0.57; p¼0.001), the ratio of short-axis 2D left
Age 0.01 0.51 atrial to aortic diameter (r ¼ 0.40, p¼0.005), the
Weight 0.21 0.41 ratio of early to late diastolic mitral inflow veloc-
Gender e 0.35* ities (r ¼ 0.32; p¼0.029), Holter VPC number
Total VPC on 24-hr Holter 0.25 0.08 (r ¼ 0.37; p¼0.009), and administration of
FS 0.48 <0.001 pimobendan (p¼0.038). As with TAPSE, no associ-
LVIDd 0.33 0.02 ations were seen between S’ and age, weight,
LVIDs 0.43 0.002 gender, or sotalol administration.
LA:Ao 0.45 0.001 Receiver operating characteristic curve analysis
MV E 0.35 0.01 performed on all 50 dogs showed that S’ had an
MV E/A 0.44 0.002
area under the curve of 0.77 to distinguish healthy
S’ 0.70 <0.001
CHF (Y/N) e 0.01*
from affected Boxers (Fig. 3). At a cutoff value of
Sotalol administration (Y/N) e 0.50* 14.0 cm/s, the sensitivity was 71.9% and the spe-
Pimobendan administration (Y/N) e 0.03* cificity was 72.2%.
VPC, ventricular premature complex; FS, left ventricular
fractional shortening %; LVIDd, left ventricular internal
diameter at end-diastole; LVIDs left ventricular internal Discussion
diameter at end-systole; LA:Ao, ratio of short-axis two-
dimensional left atrial to aortic diameter; MV E, early dia-
stolic velocity of mitral inflow; MV E/A ratio of early to late
The results of this study show that TAPSE is
diastolic mitral inflow velocities; S’ pulsed wave tissue reduced in Boxers with ARVC, with and without
Doppler imagingederived systolic myocardial velocity of the overt LV systolic dysfunction. A further reduction
lateral tricuspid annulus; CHF, congestive heart failure. in TAPSE, as well as decreased tricuspid S’, was
*p-value for Mann-Whitney U test of TAPSE difference for seen in dogs with concurrent LV systolic failure. In
categorical variables.
this study, a strong correlation was seen between

Please cite this article in press as: Cunningham SM, et al., Echocardiographic assessment of right ventricular systolic function in
Boxers with arrhythmogenic right ventricular cardiomyopathy, Journal of Veterinary Cardiology (2018), https://doi.org/10.1016/
j.jvc.2018.07.005
RV systolic function in Boxers with ARVC 7

Figure 3 Receiver operating characteristic curves depicting the sensitivity and specificity of TAPSE (A) and S’ (B) in
discerning between healthy Boxers and those with ARVC. The area under the curve for both RV function parameters
was 0.77. TAPSE, tricuspid annular plane systolic excursion; S’ pulsed wave tissue Doppler imagingederived systolic
myocardial velocity of the lateral tricuspid annulus; ARVC, arrhythmogenic right ventricular cardiomyopathy; RV, right
ventricular.

TAPSE and S’. Although both of these indices only
directly measure longitudinal systolic function of a
portion of the RV free wall, longitudinal shortening
plays a particularly important role in RV systolic
function [19]. Accordingly, both parameters have
shown good correlation with other measures of
global RV systolic function in people, including RV
fractional area change and magnetic resonance
imaginge and radionucleotide-derived RV ejection
fraction [33,35,47].
In the present study, both TAPSE and S’ were
correlated with several markers of LV size and
function. This is in accordance with the results of
another recent study by Poser et al., in which
TAPSE was found to be correlated with LV diameter
and FS in dogs with myxomatous mitral valve dis-
ease [27]. Although primarily a measure of RV
systolic function, TAPSE is also commonly reduced
in people with primary LV systolic failure [48e50],
and in people with idiopathic DCM, reduced TAPSE
provides prognostic information that appears to be
independent of the severity of LV dysfunction [48].
Decreased TAPSE is also associated with a poorer
prognosis in people with heart failure [50,51],
congenital heart disease [52], pulmonary hyper-
tension [53], hypertrophic cardiomyopathy [23],
and ARVC [4,6,7].
In human patients with ARVC, TAPSE can be
used to distinguish between healthy and affected
individuals, including asymptomatic carriers of
pathogenic ARVC mutations [38,39]. Reduced
TAPSE and RV fractional area change are asso-
ciated with an increased risk for major adverse
cardiovascular events in patients with ARVC, and
can be used to monitor disease progression, with
progressive reductions in TAPSE seen with longi-
tudinal follow-up [4,6,7]. Tricuspid annular S’ has
also shown utility in screening for early ARVC in
people [3,37]. The results of the present study
suggest that TAPSE and S’ may also have utility in
identifying RV systolic dysfunction in Boxers with
ARVC. However, based on the receiver operating
characteristic curve analysis and the degree of
overlap seen between groups, these indices do not
appear sufficiently sensitive in distinguishing
between normal and affected Boxers to serve as
stand-alone screening tests. Further studies are
needed to evaluate whether serial measurement
of these parameters can identify progressive
changes in RV systolic dysfunction that may occur
over time in affected animals.
In veterinary patients, TAPSE has been eval-
uated in healthy dogs [18,24e26], dogs with pul-
monary hypertension [18] and myxomatous mitral
valve disease [27], Boxers with ventricular
arrhythmias [30], and cats with hypertrophic car-
diomyopathy [31,32]. In a prior study of TAPSE in
Boxers, Kaye et al. found that TAPSE <15.1 mm
was associated with a shorter time to cardiac
death in Boxers with >50 VPCs/24 hrs [30]. The

Please cite this article in press as: Cunningham SM, et al., Echocardiographic assessment of right ventricular systolic function in
Boxers with arrhythmogenic right ventricular cardiomyopathy, Journal of Veterinary Cardiology (2018), https://doi.org/10.1016/
j.jvc.2018.07.005
8 S.M. Cunningham et al.
TAPSE cutoff of 15.1 used in that study is higher
than the median value of the healthy control
Boxers in the study reported herein. It also falls
within the normal range of the body weightespe-
cific reference intervals proposed by both Visser
and Pariaut; however, those studies did not spe-
cifically evaluate Boxers [18,24,25]. This differ-
ence may be secondary to differences in technique
as the study by Kaye et al. retrospectively meas-
ured TAPSE using anatomic M-mode, whereas the
other aforementioned studies and the study pre-
sented herein prospectively acquired RV images
aligned for measurement of TAPSE.
Tricuspid annular S’ has previously been eval-
uated in healthy client-owned [24,25] and exper-
imental dogs [54], in dogs with varying etiologies
of pulmonary hypertension [55], and in dogs with
DCM [56] and myxomatous mitral valve disease
[27,28]. In healthy dogs, S’ has been shown to be
repeatable and reproducible [24,55] and to cor-
relate well with the invasive measurement of RV
contractility as measured by þ dP/dt [54]. Tri-
cuspid S’ has been shown to increase in response to
administration of positive inotropic agents [25,54]
and to decrease after a single oral dose of atenolol
[25]. In prior studies of dogs with DCM, [56] and in
dogs with pulmonary hypertension of varying eti-
ologies [29], S’ was found to be reduced and to
vary with the severity of disease. However, in two
recent studies evaluating markers of RV function
on dogs with myxomatous mitral valve disease with
or without pulmonary hypertension, no differences
in RV tissue Doppler imaging variables were seen
[27,28]. The present study is the first to evaluate
pulsed wave tricuspid S’ in dogs with ARVC.
Although S’ was reduced in Boxers with LV systolic
dysfunction and had a similar area under the curve
of 0.77 for detecting ARVC in receiver operating
characteristic curve analysis, it was not sig-
nificantly reduced in affected dogs with normal LV
function as compared with healthy Boxers. Further
studies are needed to establish normal reference
ranges of this parameter in the Boxer and to
evaluate the utility of S’ as a marker of RV systolic
function in various cardiac disease states.
In contrast to other recent studies of RV func-
tion indices in dogs [18,24,27], the present study
did not show a significant relationship between
body weight and either TAPSE or S’ in this more
homogeneous population of Boxer dogs. Visser
et al. recently demonstrated strong correlations
between body weight and RV function parameters
in a heterogeneous population of dogs of widely
varying breed and body size, ranging from 3.9 to
42.3 kg [24]. This study demonstrated the impor-
tance of considering body weight when
Please cite this article in press as: Cunningham SM, et al., Echocardiographic assessment of right ventricular systolic function in
Boxers with arrhythmogenic right ventricular cardiomyopathy, Journal of Veterinary Cardiology (2018), https://doi.org/10.1016/
j.jvc.2018.07.005
interpreting indices of RV function and provided
weight-specific reference values for clinical use
[24]. Prior studies by Pariaut and Poser et al. also
examined heterogeneous populations of dogs of
varying breeds and weights and similarly demon-
strated positive correlations between TAPSE and
body weight [18,27]. Conversely, Kaye et al. [30]
found a weak negative association with body
weight in Boxers, and the present study did not
show any significant correlation between body
weight and either TAPSE or S’. In the present
study, the lack of correlation with body weight was
seen when evaluating all Boxers and also when
including only normal Boxers in the analysis. The
reason for this is uncertain but may be related to
the more homogeneous single-breed populations
examined in the latter studies, and the narrower
range of body weights included (20e43 kg). Thus,
TAPSE was analyzed as an absolute measurement
rather than an index, similar to the current
guidelines for echocardiographic evaluation of
right heart function in humans which use single
cutoff values [19,33]. However, further studies are
needed to confirm this finding in a larger pop-
ulation of normal Boxers and to establish whether
breed-specific reference ranges are appropriate
for measurements of RV function.
No correlation with TAPSE and arrhythmia fre-
quency was documented in this study; however,
this finding should be interpreted with caution as
some of these dogs were already on antiar-
rhythmics at the time of study enrollment and no
standardized antiarrhythmic protocol was used. A
prior study examining the effects of pimobendan
and atenolol on RV systolic function in healthy
client-owned dogs showed a positive and negative
effect of these drugs on RV systolic function,
respectively [25]. In the present study, there was
no apparent relationship between sotalol admin-
istration and either TAPSE or S’. The negative
association seen between administration of pimo-
bendan and RV function is likely due to the fact
that dogs that were administered pimobendan all
had significant pre-existing systolic dysfunction
that prompted administration of the drug. This is
supported by the results of the multivariate anal-
ysis, in which neither CHF nor pimobendan
administration were significant predictors of TAPSE
when the LV FS was included as a covariate.
Limitations
Interpretation of both TAPSE and S’ assumes that
the displacement of the annular segment of the RV
is representative of global RV function, an
RV systolic function in Boxers with ARVC
assumption that may not be valid in all conditions.
However, several human studies have demon-
strated strong correlations between both of these
parameters and more global measures of RV sys-
tolic function, including radionucleotide angiog-
raphy [33e36]. Both measurements are also angle
dependent and can be underestimated by poor
alignment with the tricuspid annulus. This study is
also limited by the relatively small number of dogs
evaluated and the potential confounding effects of
the various cardiac medications that dogs in the
affected groups were receiving at the time of the
study. Additionally, echocardiographic measure-
ments were recorded retrospectively and not
remeasured for the purposes of this study. There-
fore, the investigator performing these measure-
ments was not blinded to the clinical diagnosis of
the dogs, thus potentially biasing the results.
Conventionally, comparisons of continuous varia-
bles from more than two groups are first made
through an omnibus test such as analysis of var-
iance or Kruskal-Wallis, and then post hoc com-
parisons are made through tests that consider the
possibility that random error might result in ‘false
positive’ results. Because the present study was
designed to test these outcomes a priori, the
pairwise comparisons were made without these
allowances, [46] however, the authors concede
that some small detected differences might reflect
chance, rather than clinically important findings.
Conclusions
Boxers with ARVC have reduced echocardiographic
indices of RV systolic function compared with
normal Boxer dogs, and these changes are more
pronounced in dogs with concurrent LV systolic
dysfunction. Both TAPSE and S’ are associated with
markers of LV dilation and systolic dysfunction. No
association with body weight, age, or gender was
seen in this population of age- and breed-matched
dogs. Additional studies are warranted to deter-
mine the clinical utility and prognostic significance
of these and other measurements of RV function in
dogs with ARVC and other cardiac disease states.
Acknowledgments
A portion of the costs for diagnostic testing for
some of the dogs in this study was covered by a
grant from the American Kennel Club Canine
Health Foundation. The authors gratefully
acknowledge the technical assistance of Dawn
Meola and Diane Welsh, CVT, and the contributions
Please cite this article in press as: Cunningham SM, et al., Echocardiographic assessment of right ventricular systolic function in
Boxers with arrhythmogenic right ventricular cardiomyopathy, Journal of Veterinary Cardiology (2018), https://doi.org/10.1016/
j.jvc.2018.07.005
9
of Drs. Vicky Yang, Kursten Pierce, Emily Karlin,
and Amelie Beaumier-Primeau.
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