Desmosomal gene evaluation in Boxers with arrhythmogenic right ventricular cardiomyopathy

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.     

Use of signal-averaged electrocardiography in the evaluation of arrhythmogenic right ventricular cardiomyopathy in boxers

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). DESIGN: Prospective study. ANIMALS: 94 Boxers with ARVC and 49 clinically normal non-Boxers (controls). 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.     

Assessment of heart rate variability in Boxers with arrhythmogenic right ventricular cardiomyopathy

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. DESIGN: Prospective study. ANIMALS: 24 Boxers with ARVC and 10 clinically normal non-Boxer dogs. PROCEDURE: Boxers were categorized as dogs with congestive heart failure (CHF), dogs with < or = 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.     

An index of myocardial performance applied to the right ventricle of Boxers with arrhythmogenic right ventricular cardiomyopathy

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 > or = 1,000 ventricular premature complexes (VPCs)/24 h and 10 Boxers with < or = 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.     

Magnetic Resonance Imaging of Right Ventricular Morphology and Function in Boxer Dogs with Arrhythmogenic Right Ventricular Cardiomyopathy

Background: Arrhythmogenic right ventricular cardiomyopathy (ARVC) is a myocardial disease characterized by fibrofatty replacement of the right ventricle and ventricular tachyarrhythmias, reported most commonly in the Boxer dog. Although ARVC is characterized as a myocardial disease, the impact of the disease on the function of the right ventricle has not been well studied.
Objective: To noninvasively evaluate the function and anatomy of the right ventricle in Boxer dogs with ARVC.
Animals: Five adult Boxer dogs with ARVC and 5 healthy size-matched hound dogs.
Methods: Magnetic resonance imaging was performed on an ECG-gated conventional 1.5-T scanner using dark blood imaging and cine acquisitions. Images were evaluated by delineation of endocardial right and left ventricular contours in the end-diastolic and end-systolic phases of each slice. Right and left end-systolic and end-diastolic volumes were generated using Simpson's rule and ejection fraction was calculated. Images were evaluated for right ventricular (RV) aneurysms and wall motion abnormalities. Spin echo images were reviewed for the presence of RV myocardial fatty replacement or scar.
Results: RV ejection fraction was significantly lower in Boxers with ARVC compared with the controls (ARVC 34%± 11 control 53%± 10, P < .01). There was an RV aneurysm in 1 dog with ARVC but not in any of the controls. RV myocardial gross fatty changes were not observed in dogs of either group.
Conclusions and Clinical Importance: These findings could be interpreted to suggest that arrhythmias and myocardial dysfunction precede the development of morphological abnormalities in dogs with ARVC.     

Evaluation of serum cardiac troponin I concentration in Boxers with arrhythmogenic right ventricular cardiomyopathy

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 > or = 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.     

Assessment of plasma brain natriuretic peptide concentration in Boxers with arrhythmogenic right ventricular cardiomyopathy

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.     

Evaluation of spontaneous variability in the frequency of ventricular arrhythmias in Boxers with arrhythmogenic right ventricular cardiomyopathy

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). DESIGN: Prospective study. ANIMALS: 10 Boxers with ARVC with prior ambulatory ECG recordings that included > or = 500 ventricular premature complexes/24 h. 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 < or = 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.     

Serum Cardiac Troponin I Concentration in Retired Racing Greyhounds

Background: Cardiac troponin I (cTnI) is a polypeptide found specifically in cardiac muscle tissue that has been used as a diagnostic and prognostic indicator of cardiomyopathy. Increases in cTnI are associated with myocardial pathologic processes. However, high serum cTnI concentrations have been observed in normal Greyhounds.
Hypothesis: We hypothesized that Greyhounds have cTnI concentrations higher than non-Greyhound dogs, and that a separate reference range should be established for Greyhounds.
Animals: Blood samples were collected from the jugular vein from a group of 20 healthy Greyhound blood donors.
Methods: Analysis of serum cTnI was performed with an immunoassay system with a detection level of 0.01 ng/mL, as described previously. The Greyhound values were compared with 2 groups of Boxers with and without arrhythmogenic right ventricular cardiomyopathy (ARVC), and to a group of non-Boxer control dogs from a previous study.
Results: The mean cTnI concentration in Greyhounds was significantly higher ( P < .0001) than that in non-Greyhound control dogs, although not significantly different from normal Boxers ( P = .50), or Boxers with ARVC ( P = .58). Greyhound serum cTnI concentrations were in the range found in Boxers with ARVC. The proposed reference range for cTnI in Greyhounds is 0.05–0.16 ng/mL.
Conclusions and Clinical Importance: Greyhounds have a reference range for serum cTnI concentrations that differs from that of other previously published reference ranges for dogs of other breeds. Until a broader database and more precise reference range can be established, caution should be exercised in interpreting serum cTnI concentrations in Greyhounds with suspected cardiac disease.     

Arrhythmogenic right ventricular cardiomyopathy in Bulldogs: Evaluation of clinical and histopathologic features,progression, and outcome in 71 dogs (2004–2016)

ObjectivesThis study aimed to characterize the clinical and histopathological features of arrhythmogenic right ventricular cardiomyopathy (ARVC) in English Bulldogs, American Bulldogs, and Bulldog-type mixed breed dogs and assess affected Bulldogs for a striatin gene mutation previously reported in Boxers with ARVC.AnimalsSeventy-one Bulldogs fit the inclusion criteria. Genetic analysis was performed on five dogs. Cardiac post-mortem evaluations were performed on two dogs.MethodsMedical records from a single veterinary cardiology group (CVCA) were retrospectively evaluated. Tissue and blood samples were submitted for histopathological analysis and genetic testing in select patients.ResultsPresenting complaints included syncope (38%), arrhythmia (81.7%), or murmur (34.2%) documented on examination. On presentation, congestive heart failure (CHF) was diagnosed in 22 (31%) dogs, and 58 (81.7%) had ventricular arrhythmias. On bivariable analyses, the two-dimensional (2D) left atrial-to-aortic root ratio (LA:Ao) was the only prognostic variable significantly associated with survival time. Dogs with 2D LA:Ao below the mean (1.41) had longer median survival to all-cause mortality (12 months; 95% confidence interval [CI] six–15 months) than those with 2D LA:Ao above the mean (four months; 95% CI two–six months; p=0.0384). Most dogs (54%) died from cardiac disease, with 42.1% experiencing sudden death. The median time from diagnosis to cardiac death was four months.ConclusionsArrhythmogenic right ventricular cardiomyopathy affects Bulldogs with both arrhythmogenic and dilated-type phenotypes. Despite variable arrhythmia severity and predominantly right-sided involvement in many dogs, an increase in left atrial size was the only significant predictor of mortality in this sample of dogs.     

Clinical, echocardiographic, and electrocardiographic abnormalities in Boxers with cardiomyopathy and left ventricular systolic dysfunction: 48 cases (1985-2003)

OBJECTIVE: To identify clinical, echocardiographic, and electrocardiographic abnormalities in Boxers with cardiomyopathy and echocardiographic evidence of left ventricular systolic dysfunction. DESIGN: Retrospective study. ANIMALS: 48 mature Boxers. PROCEDURE: Medical records were reviewed for information on age; sex; physical examination findings; and results of electrocardiography, 24-hour ambulatory electrocardiography, thoracic radiography, and echocardiography. RESULTS: Mean age of the dogs was 6 years (range, 1 to 11 years).Twenty (42%) dogs had a systolic murmur, and 9 (19%) had ascites. Congestive heart failure was diagnosed in 24 (50%) dogs. Seventeen (35%) dogs had a history of syncope. Mean fractional shortening was 14.4% (range, 1% to 23%). Mean left ventricular systolic and diastolic diameters were 4.5 cm (range, 3 to 6.3 cm) and 5.3 cm (range, 3.9 to 7.4 cm), respectively. Twenty-eight (58%) dogs had a sinus rhythm with ventricular premature complexes (VPCs), and 20 had supraventricular arrhythmias (15 with atrial fibrillation and 5 with sinus rhythm and atrial premature complexes). Sixteen of the dogs with supraventricular arrhythmias also had occasional VPCs. Morphology of the VPCs seen on lead II ECGs was consistent with left bundle branch block in 25 dogs, right bundle branch block in 8, and both in 11. CONCLUSIONS AND CLINICAL RELEVANCE: Results suggest that Boxers with cardiomyopathy and left ventricular dysfunction frequently have arrhythmias of supraventricular or ventricular origin. Whether ventricular dysfunction was preceded by electrical disturbances could not be determined from these data, and the natural history of myocardial disease in Boxers requires further study.     

Omega-3 fatty acids in Boxer dogs with arrhythmogenic right ventricular cardiomyopathy

BACKGROUND: Omega-3 fatty acids have been shown to reduce arrhythmia in animal models and people. These effects have not been studied in dogs with spontaneously occurring arrhythmia. HYPOTHESIS: Fish oil will reduce the frequency of ventricular arrhythmia in Boxer dogs with arrhythmogenic right ventricular cardiomyopathy (ARVC). ANIMALS: Twenty-four Boxers with ARVC were included in this study. METHODS: Asymptomatic Boxers not receiving antiarrhythmic medications were evaluated with echocardiogram and electrocardiogram. Dogs with at least 1 ventricular premature contraction (VPC) received 24-hour ambulatory electrocardiography (AECG) recordings. Dogs with > 95 VPCs in 24 hours were randomized to 1 of 3 treatments: (1) Fish oil, 2 g; (2) Flax oil, 2 g; or (3) sunflower oil, 2 g (Control group), for 6 weeks. Investigators and owners were blinded to the treatment groups. All baseline measurements were repeated after the 6-week supplementation. RESULTS: There were no differences at baseline for age, sex, blood pressure, weight, echocardiographic measurements, or VPCs. Median number of VPCs in 24 hours for all dogs was 543 (range, 96-40,063) at baseline and 193 (range, 6-14,825) after 6 weeks of supplementation. VPCs/24 h were reduced for the Fish oil group (baseline median = 397 [range, 249-10,587]; 6-week median = 162 [range, 16-3,781]; P = .02), but not for the Flax oil (P = .58) or Control (P = .48) groups. CONCLUSIONS AND CLINICAL IMPORTANCE: These data suggest that fish oil, but not flax oil, supplementation for 6 weeks reduces arrhythmia in Boxers with ARVC and that it could be useful in treating this common disease. Further studies are needed to determine optimal dose and duration of treatment.     

Temporal Variability of Ventricular Arrhythmias in Boxer Dogs with Arrhythmogenic Right Ventricular Cardiomyopathy

Background: Arrhythmogenic right ventricular cardiomyopathy (ARVC) is prevalent in the Boxer. There is little information on the temporal variability of ventricular arrhythmias within affected dogs.
Objective: To evaluate ambulatory electrocardiograms (AECG) from Boxers with ARVC for hourly variation in premature ventricular complexes (PVC) and heart rate (HR).
Animals: One hundred and sixty-two Boxer dogs with ARVC.
Methods: Retrospective, observational study of 1,181 AECGs collected from Boxer dogs at The Ohio State University from 1997 to 2004 was evaluated. The proportion of depolarizations that were PVCs was compared across each hour of the day, during six 4-hour periods of day, to the time after AECG application, and to the maximum and minimum HR.
Results: A lower proportion of PVCs was noted during early morning (midnight to 0400 hours) as compared with the morning (0800–1200 hours) and late (1600–2000 hours) afternoon ( P = .012). There was no increase in PVC proportion in the 1st hour after AECG application as compared with all other hours of the day ( P = .06). There was poor correlation between maximum (ρ= 0.19) and minimum (ρ= 0.12) HR and PVC proportion.
Conclusions and Clinical Importance: The likelihood of PVC occurrence in Boxer dogs with ARVC was relatively constant throughout the day, although slightly greater during the hours of 0800–1200 and 1600–2000. A biologically important correlation with HR was not apparent. The role of autonomic activity in the modulation of electrical instability in the Boxer with ARVC requires further study.     

Echocardiographic assessment of right ventricular systolic function in Boxers with arrhythmogenic right ventricular cardiomyopathy

Objectives

To determine whether there are differences in measures of longitudinal right ventricular (RV) systolic function among Boxers with arrhythmogenic right ventricular cardiomyopathy (ARVC) compared with healthy control Boxer dogs. To explore relationships between markers of RV systolic function and age, body weight, gender, arrhythmia frequency, and markers of left ventricular (LV) systolic function in Boxer dogs.

Correlation of QT dispersion with indices used to evaluate the severity of familial ventricular arrhythmias in Boxers

OBJECTIVE: To measure QT interval duration and QT dispersion in Boxers and to determine whether QT variables correlate with indices of disease severity in Boxers with familial ventricular arrhythmias, including the number of ventricular premature complexes per day, arrhythmia grade, and fractional shortening. ANIMALS: 25 Boxers were evaluated by ECG and echocardiography. PROCEDURE: The QT interval duration was measured from 12-lead ECG and corrected for heart rate (QTc), using Fridericia's formula. The QT and QTc were calculated for each lead, from which QT and QTc dispersion were determined. Echocardiography and 24-hour ambulatory ECG were performed to evaluate for familial ventricular arrhythmias. Total number of ventricular premature complexes, arrhythmia grade, and fractional shortening were determined and used as indices of disease severity. RESULTS: There was no correlation between any QT variable and total number of ventricular premature complexes, arrhythmia grade, or fractional shortening. No difference between QT dispersion and QTc dispersion was identified, and correction for heart rate did not affect the results. CONCLUSIONS AND CLINICAL RELEVANCE: QT interval duration and dispersion did not correlate with indices of disease severity for familial ventricular arrhythmias. Heart rate correction of the QT interval did not appear to be necessary for QT dispersion calculation in this group of dogs. QT dispersion does not appear to be a useful noninvasive diagnostic tool in the evaluation of familial ventricular arrhythmias of Boxers. Identification of affected individuals at risk for sudden death remains a challenge in the management of this disease.     

Arrhythmogenic right ventricular cardiomyopathy in a weimaraner

Arrhythmogenic right ventricular cardiomyopathy (ARVC) was diagnosed postmortem in a weimaraner dog. Syncope, ventricular arrhythmias, and sudden death in this patient combined with the histopathological fatty tissue infiltration affecting the right ventricular myocardium are consistent with previous reports of ARVC in non-boxer dogs. Arrhythmogenic right ventricular cardiomyopathy has not been previously reported in weimaraners.     

Morphology of ventricular arrhythmias in the boxer as measured by 12-lead electrocardiography with pace-mapping comparison

The QRS amplitude and polarity were determined in 12-lead electrocardiograms recorded from 22 Boxers with ventricular arrhythmias. Eighty-one percent (18/22) of dogs displayed a positive QRS morphology in the caudoventral leads (II, III, and aVF) and 77% (17/22) of dogs displayed a positive QRS morphology in the left precordial leads (V2-V6). In leads I and V1, the polarity of the QRS complex was variable (positive or negative). To determine if these morphologic features were suggestive of ventricular complexes arising from the right or left ventricle, a comparison was made to the QRS complexes in a pace-mapping study performed in 7 healthy mixed-breed dogs. A total of 3 right and 4 left ventricular sites were paced. None of the left ventricular paced sites resulted in a QRS morphology similar to the most common spontaneous ventricular arrhythmia in the Boxers. In contrast, QRS morphology in each of the 3 right ventricular sites was similar to that observed in the Boxers (P < .033). Each of these produced positive deflections in the caudoventral and left precordial leads, but both positive and negative QRS complexes were observed in leads I and V1 only when the right ventricular septum was paced. This finding suggested that the right ventricular septum might be a site of origin for the ventricular rhythm observed in the Boxers because in the Boxers the polarity of leads I and V1 also varied. Pacing the right ventricular outflow tract always resulted in a negative QRS complex in lead 1, whereas pacing the right ventricular apex always resulted in a positive QRS complex in lead I and a negative QRS complex in V1. However, these locations cannot be excluded as possible sites of origin for the spontaneous ventricular arrhythmias in the Boxers because the arrhythmias could be originating from both of these locations. The spontaneous ventricular arrhythmia of the Boxer is most similar to that of paced ventricular rhythms arising from the right ventricle. More precise localization to a region of the right ventricle such as outflow tract, septal, or apical could not be made.     

Echocardiographic ratio indices in overtly healthy Boxer dogs screened for heart disease

BACKGROUND: Boxer dogs are routinely screened by echocardiography to exclude congenital and acquired heart disease. Individuals of a given breed may span a large range of body sizes, potentially invalidating linear regression of M-mode measurements against body weight. Echocardiographic ratio indices (ERIs) provide a novel method of characterizing echocardiographic differences between Boxers and other dog breeds. HYPOTHESIS: ERIs obtained from overtly healthy Boxer dogs presented for cardiac screening will be different from ERIs established for normal non-Boxer dogs, and those differences will be unrelated to aortic velocity or systolic blood pressure. ANIMALS: Eighty-one Boxers with no outward clinical signs of heart disease were studied. METHODS: All dogs were examined by 2-dimensional, M-mode, and Doppler echocardiography. M-mode measurements were used to perform ERI calculations, and the indices in Boxers were compared between Boxers with varying severity of arrhythmia and those of normal non-Boxer dogs. RESULTS: Differences in weight-based ERIs, which reflect increased thickness of the left ventricular free wall (LVW) and interventricular septum (IVS) and smaller aortic size, were found in overtly healthy Boxer dogs compared with normal non-Boxer dogs. ERIs of left atrial and LV cavity size in overtly healthy Boxers were not significantly different from those of non-Boxer dogs. CONCLUSIONS AND CLINICAL IMPORTANCE: Boxer dogs may have an increased relative thickness of the LVW and IVS that is independent of aortic size, aortic velocity, or arterial blood pressure, and this morphology should be taken into consideration when screening Boxers by echocardiography.     

Familial Ventricular Arrhythmias in Boxers

The purposes of this study were to evaluate families of Boxers with ventricular arrhythmias to determine whether this disorder is a familial trait and, if so, to determine the mode of inheritance. Eighty-two Boxers were evaluated by physical examination, electrocardiogram, echocardiogram, and 24-hour ambulatory electrocardiogram. Dogs were considered affected if at least 50 premature ventricular complexes (PVCs) were observed during a 24-hour period. All dogs were at least 6 years of age at evaluation. Complete cardiovascular examinations were performed on dogs from 6 extended families. The 2 most complete pedigrees were used to determine the pattern of inheritance. The number of PVCs observed during a 24-hour period in affected dogs ranged from 112 to 4,894 (mean +/- SD, median; 1,309 +/- 2,609, 1,017). The number of PVCs observed during a 24-hour period in the unaffected dogs ranged from 0 to 16 (7 +/- 10, 12). Pedigree evaluation was performed to determine pattern of inheritance. An autosomal dominant pattern was determined to be most likely because a sex predisposition was not observed, affected individuals were observed in every generation, and 2 affected individuals produced unaffected offspring. We conclude that familial ventricular arrhythmias is inherited as an autosomal dominant trait in some Boxers.     

Genetics of canine diabetes mellitus: Are the diabetes susceptibility genes identified in humans involved in breed susceptibility to diabetes mellitus in dogs?

Diabetes mellitus is a common endocrinopathy in companion animals, characterised by hyperglycaemia, glycosuria and weight loss, resulting from an absolute or relative deficiency in the pancreatic hormone insulin. There are breed differences in susceptibility to diabetes mellitus in dogs, with the Samoyed breed being overrepresented, while Boxers are relatively absent in the UK population of diabetic dogs, suggesting that genetic factors play an important role in determining susceptibility to the disease. A number of genes, linked with susceptibility to diabetes mellitus in humans, are associated with an increased risk of diabetes mellitus in dogs, some of which appear to be relatively breed-specific. Diabetes mellitus in dogs has been associated with major histocompatibility complex (MHC) class II genes (dog leucocyte antigen; DLA), with similar haplotypes and genotypes being identified in the most susceptible breeds. A region containing a variable number of tandem repeats (VNTR) and several polymorphisms have been identified in the canine insulin gene, with some alleles associated with susceptibility or resistance to diabetes mellitus in a breed-specific manner. Polymorphisms in the canine CTLA4 promoter and in other immune response genes are associated with susceptibility to diabetes mellitus in a number of pedigree breeds. Genome wide association studies are currently underway that should shed further light on the genetic factors responsible for the breed profile seen in the diabetic dog population.