Objective—To determine whether Boxers with a clinical
diagnosis of arrhythmogenic right ventricular cardiomyopathy
(ARVC) have increased plasma concentrations
of brain natriuretic peptide (BNP), compared
with concentrations in clinically normal dogs.
Animals—13 Boxers with ARVC, 9 clinically normal
Boxers, 10 clinically normal non-Boxer dogs, and 5
hound dogs with systolic dysfunction.
Procedure—All Boxers were evaluated via 24-hour
ambulatory electrocardiography and echocardiography;
the number of ventricular premature contractions
(VPCs) per 24 hours was assessed. Hound
dogs with cardiac pacing-induced systolic dysfunction
(positive control dogs) and clinically normal non-Boxer
dogs (negative control dogs) were evaluated
echocardiographically. Three milliliters of blood was
collected from each dog for measurement of plasma
BNP concentration by use of a radioimmunoassay.
Results—Mean ± SD plasma BNP concentration for
the ARVC-affected Boxers, clinically normal Boxers,
negative control dogs, and positive control dogs was
11.0 ± 4.6 pg/mL, 7.9 ± 3.2 pg/mL, 11.5 ± 4.9 pg/mL,
and 100.8 ± 56.8 pg/mL, respectively. Compared with
findings in the positive control group, plasma BNP
concentration in each of the other 3 groups was significantly
different. There was no significant difference
in BNP concentration between the 2 groups of
Boxers. A significant correlation between plasma BNP
concentration and number of VPCs per 24 hours in
the ARVC-affected Boxers was not identified.
Conclusions and Clinical Relevance—A significant
difference in BNP concentration between Boxers with
ARVC and clinically normal Boxers was not identified.
Results suggest that BNP concentration may not be
an indicator of ARVC in Boxers. (Am J Vet Res
Objective—To use an index of myocardial performance (IMP) to assess right ventricular function in Boxers with arrhythmogenic right ventricular cardiomyopathy (ARVC).
Animals—22 Boxers (12 Boxers with ARVC diagnosed by the detection of ≥ 1,000 ventricular premature complexes (VPCs)/24 h and 10 Boxers with ≤ 5 VPCs/24 h (control dogs).
Procedures—Pulsed-wave Doppler recordings of tricuspid inflow and pulmonic outflow were acquired. Preejection period (PEP), ejection time (ET), PEP/ET, and IMP were determined for the right ventricle by use of data from separate cardiac cycles.
Results—A significant difference was not identified between groups for right ventricular PEP, right ventricular ET, right ventricular PEP/ET, or right ventricular IMP. Right ventricular IMP was not significantly correlated with VPC number (r = 0.21) or VPC grade (r = −0.3) in Boxers with ARVC.
Conclusions and Clinical Relevance—Boxers with ARVC did not have significant differences in right ventricular IMP, compared with results for control Boxers. This would suggest that right ventricular dysfunction does not develop in Boxers with ARVC or that a more severe phenotype of the disease may be necessary for detection of dysfunction. Additional studies that use more sensitive techniques to evaluate myocardial function may be warranted.
Objective—To sequence the exonic and splice site regions of the 4 desmosomal genes associated with the human form of familial arrhythmogenic right ventricular cardiomyopathy (ARVC) in Boxers with ARVC and identify a causative mutation.
Animals—10 unrelated Boxers with ARVC and 2 unaffected Labrador Retrievers (control dogs).
Procedures—Exonic and splice site regions of the 4 genes encoding the desmosomal proteins plakophilin-2, plakoglobin, desmoplakin, and desmoglein-2 were sequenced. Sequences were compared for nucleotide sequence changes between affected dogs and the published sequences for clinically normal dogs and between affected dogs and the control dogs. Base-pair changes were considered to be causative for ARVC if they were detected in an affected dog but not in unaffected dogs, and if they involved a conserved amino acid and changed that amino acid to one of a different polarity, acid-base status, or structure.
Results—A causative mutation for ARVC in Boxers was not identified, although single nucleotide polymorphisms were detected in some affected dogs within exon 3 of the plakophilin-2 gene; exon 3 of the plakoglobin gene; exons 3 and 7 of the desmoglein-2 gene; and exons 6, 14, 15, and 24 of the desmoplakin gene. None of these changed the amino acid of the respective protein.
Conclusions and Clinical Relevance—Mutations within the desmosomal genes associated with the development of ARVC in humans do not appear to be causative for ARVC in Boxers. Genomewide scanning for genetic loci of interest in dogs should be pursued.
Objective—To sequence the exonic and splice site regions of 5 cardiac genes associated with the human form of familial dilated cardiomyopathy (DCM) in Doberman Pinschers with DCM and to identify a causative mutation.
Animals—5 unrelated Doberman Pinschers with DCM and 2 unaffected Labrador Retrievers (control dogs).
Procedures—Exonic and splice site regions of the 5 genes encoding the cardiac proteins troponin C, lamin A/C, cysteine- and glycine-rich protein 3, cardiac troponin T, and the β-myosin heavy chain were sequenced. Sequences were compared for nucleotide changes between affected dogs and the published canine sequences and 2 control dogs. Base pair changes were considered to be causative for DCM if they were present in an affected dog but not in the control dogs or published sequences and if they involved a conserved amino acid and changed that amino acid to a different polarity, acid-base status, or structure.
Results—A causative mutation for DCM in Doberman Pinschers was not identified, although single nucleotide polymorphisms were detected in some dogs in the cysteine- and glycine-rich protein 3, β-myosin heavy chain, and troponin T genes.
Conclusions and Clinical Relevance—Mutations in 5 of the cardiac genes associated with the development of DCM in humans did not appear to be causative for DCM in Doberman Pinschers. Continued evaluation of additional candidate genes or a focused approach with an association analysis is warranted to elucidate the molecular cause of this important cardiac disease in Doberman Pinschers.
Objective—To evaluate serum cardiac troponin I (cTnI) concentrations in Boxers with arrhythmogenic right ventricular cardiomyopathy (ARVC), unaffected (control) Boxers, and control non-Boxers.
Animals—10 Boxers with a clinical diagnosis of ARVC defined by ≥ 1,000 ventricular premature complexes (VPCs)/24 h on an ambulatory ECG, 10 control Boxers assessed as normal by the presence of < 5 VPCs/24h, and 10 control non-Boxers.
Procedures—Serum was extracted from a blood sample from each dog. Analysis of serum cTnI concentrations was performed.
Results—Mean ± SD serum cTnI concentration was 0.142 ± 0.05 ng/mL for Boxers with ARVC, 0.079 ± 0.03 ng/mL for control Boxers, and 0.023 ± 0.01 ng/mL for control non-Boxers. A significant difference in serum cTnI concentrations was observed among the 3 groups. In the combined Boxer population (ie, Boxers with ARVC and control Boxers), a significant correlation was found between serum cTnI concentration and number of VPCs/24 h (r = 0.78) and between serum cTnI concentration and grade of ventricular arrhythmia (r = 0.77).
Conclusions and Clinical Relevance—Compared with clinically normal dogs, Boxers with ARVC had a significant increase in serum cTnI concentration. For Boxers, correlations were found between serum cTnI concentration and number of VPCs/24 h and between concentration and the grade of arrhythmia. Because of the overlap in serum cTnI concentrations in control Boxers and Boxers with ARVC, future studies should evaluate the correlation of serum cTnI concentration with severity of disease in terms of degree of myocardial fibrofatty changes.
Objective—To determine clinical features of dilated
cardiomyopathy (DCM) in Great Danes and to determine
whether DCM is familial in this breed.
Animals—17 Great Danes with DCM.
Procedure—Medical records of Great Danes in which
DCM was diagnosed on the basis of results of
echocardiography (fractional shortening < 25%, endsystolic
volume index > 30 ml/m2 of body surface
area) were reviewed. Pedigrees were obtained for
affected animals, as well as for other Great Danes in
which DCM had been diagnosed.
Results—Dilated cardiomyopathy appeared to be
familial and was characterized by ventricular dilatation,
congestive heart failure (left-sided or biventricular),
and atrial fibrillation. Pedigree analysis suggested
that DCM was inherited as an X-linked recessive trait,
but the mode of inheritance could not be definitively
Conclusions and Clinical Relevance—Results suggest
that DCM may be an X-linked recessive trait in
Great Danes. Thus, dogs with DCM probably should
not be used for breeding, and female offspring of
affected dogs should be used cautiously. Male offspring
of affected females are at an increased risk of
developing DCM and should be evaluated periodically
for early signs of disease. Results of pedigree
analysis were preliminary and should be used only
as a guide for counseling breeders, rather than as a
basis for making breeding decisions. (J Am Vet Med
Objective—To assess signal-averaged electrocardiography
(SAECG) for evaluation of Boxers with arrhythmogenic
right ventricular cardiomyopathy (ARVC) and
identify dogs at risk for sudden death (SD) or death
related to congestive heart failure (CHF).
Animals—94 Boxers with ARVC and 49 clinically normal
Procedure—Boxers were screened for ARVC, and
severity was estimated by use of echocardiography,
24-hour ambulatory ECG, and SAECG. Statistical evaluation
was performed to identify significant differences
in SAECG variables relative to clinical outcome,
frequency of ventricular arrhythmias, and systolic
function. Sensitivity, specificity, and positive and negative
predictive values were evaluated for each
SAECG variable for occurrence of SD or death related
to CHF. Late potentials were also evaluated as a predictor
of cardiac-related death.
Results—Differences were detected in SAECG variables
on the basis of clinical outcome, systolic function,
and frequency of ventricular arrhythmias. More
severely affected dogs had significantly more abnormal
SAECG findings. The presence of late potentials,
defined as 2 abnormal root mean square values (of 4),
was associated with high sensitivity, specificity, and
negative predictive value for cardiac-related SD or
death secondary to CHF.
Conclusions and Clinical Relevance—Results suggest
that SAECG is a useful noninvasive diagnostic
test to evaluate dogs affected with ARVC and identify
individuals at risk for cardiac-related death. ( J Am Vet
Med Assoc 2004;225:1050–1055)
Objective—To evaluate spontaneous variability in the
frequency of ventricular arrhythmias and assess the
influence of day of ECG recording and day of week on
arrhythmia frequency in Boxers affected with arrhythmogenic
right ventricular cardiomyopathy (ARVC).
Animals—10 Boxers with ARVC with prior ambulatory
ECG recordings that included ≥ 500 ventricular premature
Procedure—Consecutive 24-hour ambulatory ECG
recordings were obtained during a 7-day period in
each dog. The number of ventricular premature complexes
and grade of the arrhythmia were obtained
from each recording. For each dog, the number of
ventricular premature complexes for each recording
was evaluated to identify any differences relative to
the day of recording (recording 1 to 7) and day of the
week (Monday through Sunday).
Results—Spontaneous variability accounted for as
much as 80% of the change in frequency of ventricular
premature complexes in dogs with frequent
arrhythmias; this value was almost 100% in dogs with
less frequent arrhythmias. Grade of arrhythmia was
less variable but was also inversely related to frequency
of arrhythmia. No significant differences in
frequency values were identified among days of
recording or among days of the week.
Conclusions and Clinical Relevance—Changes of
≤ 80% in the frequency of ventricular arrhythmias
may be within the limit of spontaneous variability in
dogs with ARVC. This degree of variability should be
considered in evaluations of ambulatory ECG recordings,
particularly in the assessment of the efficacy of
antiarrhythmic drugs. ( J Am Vet Med Assoc 2004;224:
Objective—To assess heart rate variability (HRV) in
Boxers with arrhythmogenic right ventricular cardiomyopathy
(ARVC), assess the ability of HRV analysis
to identify differences in Boxers on the basis of
severity of their arrhythmia, and evaluate the use of
HRV to determine whether persistently high sympathetic
tone is present in these dogs.
Animals—24 Boxers with ARVC and 10 clinically normal
Procedure—Boxers were categorized as dogs with
congestive heart failure (CHF), dogs with ≤ 2 ventricular
premature complexes (VPCs)/24 h (designated
unaffected), or dogs with > 1,000 VPCs/24 h (designated
affected). Ambulatory electrocardiography (24
hours) was performed in each dog. Recordings were
analyzed for HRV variables at a commercial laboratory;
differences in HRV variables among groups were
compared with 1-way ANOVA.
Results—Compared with control non-Boxer dogs and
Boxers without CHF (affected and unaffected Boxers),
HRV was reduced in Boxers with CHF. No differences
in HRV variables were detected between affected and
unaffected Boxers. Inconsistent differences were
identified between the control dogs and Boxers without
CHF that had various degrees of arrhythmias.
Conclusions and Clinical Relevance—Results suggest
that persistently high sympathetic tone is not a
consistent feature of ARVC. Differences in some HRV
variables between Boxers without CHF and control
dogs suggest that Boxers may have different autonomic
control of heart rate, compared with that of
clinically normal non-Boxer dogs. The usefulness of
HRV analysis appears limited to Boxers with ARVC
that have systolic dysfunction and CHF. ( J Am Vet
Med Assoc 2004;224:534–537)
Objective—To evaluate the breed distribution of the ABCB1-1Δ polymorphism in a large number of dogs in North America, including dogs of several herding breeds in which this polymorphism has been detected and other breeds in which this polymorphism has not yet been identified.
Animals—5,368 dogs from which buccal swab samples were collected for purposes of ABCB1 genotyping.
Procedures—From May 1, 2004, to September 30, 2007, DNA specimens derived from buccal swab samples collected from 5,368 dogs underwent ABCB1 genotyping. These data were reviewed, and results for each dog were recorded in a spreadsheet, along with the dog's breed. The genotypes for each breed were tallied by use of a sorting function.
Results—The ABCB1-1Δ allele was identified in 9 breeds of dogs and in many mixed-breed dogs. Breeds that had the ABCB1-1Δ allele included Collie, Longhaired Whippet, Australian Shepherd (standard and miniature), Shetland Sheepdog, Old English Sheepdog, Border Collie, Silken Windhound, and German Shepherd Dog (a breed in which this mutation had not been detected previously).
Conclusions and Clinical Relevance—The ABCB1-1Δ polymorphism is associated with increased susceptibility to many adverse drug reactions and with suppression of the hypothalamic-pituitary-adrenal axis and is present in many herding breeds of dog. Veterinarians should be familiar with the breeds that have the ABCB1-1Δ polymorphism to make appropriate pharmacologic choices for these patients.