Natural history of arrhythmogenic right ventricular cardiomyopathy in the boxer dog: a prospective study.

BACKGROUND: Boxer arrhythmogenic right ventricular cardiomyopathy (ARVC) is a disease that may result in sudden death or heart failure. HYPOTHESIS/OBJECTIVES: To prospectively study the natural history of Boxer ARVC. ANIMALS: 72 dogs (49 ARVC, 23 controls). METHODS: Boxers >1 year of age were recruited for annual reevaluation. CONTROLS were defined as being ≥6 years of age and having <50 ventricular premature complex (VPCs)/24 h. ARVC was defined as ≥300 VPCs/24 h in the absence of other disease. Dogs were genotyped for the striatin deletion when possible. Descriptive statistics were determined for age; VPC number; annual change in VPC number; and left ventricular (LV) echocardiographic dimensions. Survival time was calculated. RESULTS: Controls: median age of 7 years (range, 6-10); number of VPCs 12 (range, 4-32). Median time in study of 6 years (range, 2-9). Seventeen of 23 were genotyped (5 positive, 12 negative). ARVC: median age of diagnosis of 6 (range, 1-11). Median time in study 5 years (range, 3-8). A total of 33% were syncopal and 43/49 were genotyped (36 positive, 7 negative). Yearly change in VPCs was 46 (range, -7,699 to 33,524). Annual percentage change in LV dimensions was 0, and change in fractional shortening (FS%) was 2%. Two dogs had FS% <20%. Although ARVC dogs died suddenly, there was no difference in survival time between groups. ARVC median age of survival was 11 years, and for controls was 10 years. CONCLUSIONS/CLINICAL IMPORTANCE: Arrhythmogenic right ventricular cardiomyopathy is a disease of middle age and frequently is associated with the striatin deletion. Syncope occurs in approximately 1/3 of affected dogs; systolic dysfunction is uncommon. The prognosis in many affected dogs is good.

Hemodynamic and biochemical alterations in dogs with lymphoma after induction of chemotherapy.

BACKGROUND: Doxorubicin is a common antineoplastic agent with dose-dependent cardiotoxic adverse effects, and pre-existing myocardial dysfunction is a contraindication to its use. OBJECTIVES: To systematically define the hemodynamic and biochemical alterations in dogs undergoing chemotherapy for newly diagnosed lymphoma and assess the reversibility of these alterations with fluid administration. ANIMALS: Twenty-one client-owned dogs with newly diagnosed lymphoma were evaluated 1 week after induction of chemotherapy. Underlying degenerative valve disease was exclusionary. Eighteen healthy age- and weight-matched dogs were used as controls. METHODS: Physical examination, blood pressure by Doppler, echocardiography, and biochemical evaluation (routine serum biochemistry, plasma renin activity and aldosterone concentrations, plasma and urine osmolalities, and urine electrolyte concentrations) were measured in dogs with lymphoma and compared to controls. Dogs with lymphoma received crystalloids IV at 6 mL/kg/h for 24 hours. All variables were reassessed at 4 and 24 hours. Deuterium oxide dilution and bromide dilution were used to determine total body water and extracellular water space, respectively. RESULTS: Baseline echocardiograms showed significantly smaller chamber dimensions in dogs with lymphoma compared to controls. These changes were reversed by fluid administration. Systolic blood pressure and urine sodium concentration were significantly increased, and bromide dilution space, PCV, urine specific gravity, and urine potassium concentration were significantly decreased compared to controls. CONCLUSION AND CLINICAL IMPORTANCE: Echocardiographic and biochemical abnormalities in dogs with lymphoma appear consistent with volume depletion, and may be the result of systemic hypertension and subsequent pressure natriuresis.

Echocardiographic assessment of hemodynamic changes produced by two methods of inducing fluid deficit in dogs.

BACKGROUND: Hydration status is important to the cardiovascular system because of its effects on preload. Decreased preload can alter echocardiographic measurements of systolic and diastolic function, potentially confounding interpretation of results. HYPOTHESIS/OBJECTIVES: Mild fluid deficits are associated with measurable echocardiographic changes that are validated by physical and biochemical markers of decreased intravascular volume. ANIMALS: Twenty-five healthy staff/student-owned dogs with no evidence of cardiac or renal disease. METHODS: Prospective, interventional laboratory study. Dogs were randomly assigned to water deprivation (WD) alone for 8 hours (n = 13) or to furosemide treatment (FTx, 2.5mg/kg IV) followed by WD for 8 hours (n = 12). Echocardiograms, biochemical sampling, and physical parameters were measured at baseline, and after 4 and 8 hours. RESULTS: Both protocols induced fluid deficit as indicated by significant (P < .00001) decreases in weight at 4 hours (WD, 1.1%; FTx, 3.7%) and 8 hours (WD, 2.7%; FTx, 4.5%). Furosemide significantly decreased left ventricular end-diastolic volume (54.3 +/- 19.3-42.1 +/- 17.3 mL, P < .0001), cardiac index (4.2 +/- 1.1-2.9 +/- 0.9 L/min/M2, P < .0001), and mitral valve E wave velocity (0.79 +/- 0.2-0.66 +/- 0.2 m/s, P = .0004). These changes were accompanied by significant increases in blood urea nitrogen concentration (13.8 +/- 2.6-14.8 +/- 2.7 mg/dL, P = .04), vasopressin concentration (1.4 +/- 1.2-3.3 +/- 1.9 pg/mL, P = .045), and PCV (49.8 +/- 4.5-53.2 +/- 6.5%, P = .006). Effects of water deprivation alone were similar, but less pronounced. CONCLUSIONS AND CLINICAL IMPORTANCE: Mild fluid deficits have measurable hemodynamic effects in dogs. Hydration status should be considered when evaluating cardiac function by echocardiogram.

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 (rho= 0.19) and minimum (rho= 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.

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.

Use of ambulatory electrocardiography for detection of ventricular premature complexes in healthy dogs.

OBJECTIVE: To evaluate the use of 24-hour ambulatory electrocardiography (AECG) for the detection of ventricular premature complexes (VPC) in healthy dogs. DESIGN: Case series. ANIMALS: 50 healthy mature dogs. PROCEDURE: A 24-hour AECG was performed on each dog and evaluated for the presence of VPC. RESULTS: Fifty dogs weighing between 18.2 to 40.9 kg (40 and 90 lb) representing 13 breeds were evaluated; there were 4 sexually intact females, 21 spayed females, 4 sexually intact males, and 21 castrated males. Ages ranged from 1 to 12 years. Thirty-four dogs had no VPC; 16 dogs had between 1 and 24 VPC. The grade of arrhythmia ranged from 1 to 4, with 4 dogs having an arrhythmia with a grade > 1. Significant differences were not detected between the group of dogs with VPC and those without VPC with regard to sex, age, and minimum, maximum, or mean heart rate. CONCLUSIONS AND CLINICAL RELEVANCE: We conclude that healthy mature dogs have infrequent VPC, as detected by use of 24-hour AECG. The presence of numerous or sequential VPC may be suggestive of cardiac or systemic disease and may indicate the need for thorough clinical evaluation.

Comparison of in-hospital versus 24-hour ambulatory electrocardiography for detection of ventricular premature complexes in mature Boxers.

OBJECTIVE: To evaluate the use of in-hospital electrocardiography (ECG) for detection of ventricular premature complexes (VPC), compared with 24-hour ambulatory ECG. DESIGN: Original study. ANIMALS: 188 Boxers > 9 months old; 31 had a history of syncope, and 157 were healthy (no history of syncope). PROCEDURE: In-hospital ECG was performed on all Boxers for at least 2 minutes. Within 7 days after the in-hospital ECG was completed, 24-hour ambulatory ECG was performed. RESULTS: The specificity of in-hospital ECG was 100% for the detection of at least 50 VPC in a 24-hour period in dogs with syncope and 93% in healthy dogs. In-hospital ECG had poor sensitivity, although sensitivity increased as the number of VPC per 24 hours increased. CONCLUSIONS AND CLINICAL RELEVANCE: Use of in-hospital ECG is highly specific for detection of at least 50 VPC during a 24-hour period. However, in-hospital ECG is insensitive, and a lack of VPC does not suggest that the dog does not have a substantial number of VPC during that same period. The use of in-hospital ECG appears to be inadequate for screening purposes and therapeutic evaluations in mature Boxers with ventricular arrhythmic disease.

Evaluation of the cardiac actin gene in Doberman Pinschers with dilated cardiomyopathy.

OBJECTIVE: To evaluate the coding region of the cardiac actin gene in Doberman Pinschers with dilated cardiomyopathy (DCM) for mutations that could be responsible for the development of the condition ANIMALS: 28 dogs (16 Doberman Pinschers with DCM and 12 mixed-breed control dogs). PROCEDURE: Ten milliliters of blood was collected from each dog for DNA extraction. Polymerase chain reaction (PCR) primers were designed to amplify canine exonic regions, using the sequences of exons 2 to 6 of the cardiac actin gene. Single-stranded conformational polymorphism analysis was performed for each exon with all samples. Autoradiographs were analyzed for banding patterns specific to affected dogs. The DNA sequencing was performed on a selected group of affected and control dogs. RESULTS: Molecular analysis of exons 2 to 6 of the cardiac actin gene did not reveal any differences in base pairs between affected dogs and control dogs selected for DNA evaluation. CONCLUSIONS: Mutations in exons 5 and 6 of the cardiac actin gene that have been reported in humans with familial DCM do not appear to be the cause of familial DCM in Doberman Pinschers. Additionally, evaluation of exons 2 to 6 for causative mutations did not reveal a cause for inherited DCM in these Doberman Pinschers. Although there is evidence that DCM in Doberman Pinschers is an inherited problem, a molecular basis for this condition remains unresolved. Evaluation of other genes coding for cytoskeletal proteins is warranted.

Use of western immunoblot for evaluation of myocardial dystrophin, alpha-sarcoglycan, and beta-dystroglycan in dogs with idiopathic dilated cardiomyopathy.

OBJECTIVE: To evaluate the potential importance of dystrophin, alpha-sarcoglycan (adhalin), and beta-dystroglycan, by use of western blot analysis, in several breeds of dogs with dilated cardiomyopathy. SAMPLE POPULATION: Myocardial samples obtained from 12 dogs were evaluated, including tissues from 7 dogs affected with dilated cardiomyopathy, 4 control dogs with no identifiable heart disease (positive control), and 1 dog affected with Duchenne muscular dystrophy (negative control for dystrophin). Of the affected dogs, 4 breeds were represented (Doberman Pinscher, Dalmatian, Bullmastiff, and Irish Wolfhound). PROCEDURE: Western blot analysis was used for evaluation of myocardial samples obtained from dogs with and without dilated cardiomyopathy for the presence of dystrophin and 2 of its associated glycoproteins, alpha-sarcoglycan and beta-dystroglycan. RESULTS: Detectable differences were not identified between dogs with and without myocardial disease in any of the proteins evaluated. CONCLUSIONS AND CLINICAL RELEVANCE: Abnormalities in dystrophin, alpha-sarcoglycan, and beta-dystroglycan proteins were not associated with the development of dilated cardiomyopathy in the dogs evaluated in this study. In humans, the development of molecular biological techniques has allowed for the identification of specific causes of dilated cardiomyopathy that were once considered to be idiopathic. The use of similar techniques in veterinary medicine may aid in the identification of the cause of idiopathic dilated cardiomyopathy in dogs, and may offer new avenues for therapeutic intervention.

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.