Prevalence of Dilated Cardiomyopathy in Doberman Pinschers in Various Age Groups

Background: Dilated cardiomyopathy (DCM) in Doberman Pinschers is an autosomal dominant inherited disease. The prevalence of DCM in Doberman Pinschers of various age groups in Europe is currently unknown, but this information would be important to develop recommendations for screening programs. Objectives: To evaluate the prevalence of cardiomyopathy in various age groups of Dobermans. Animals: Seven hundred and seventy‐five examinations in 412 Doberman Pinschers. Methods: Dogs were included in a prospective longitudinal cohort study. Each examination included echocardiography and 24‐hour ECG (Holter) examination. A cut‐off value of >100 ventricular premature contractions (VPCs) per 24 hours on Holter examination or abnormal echocardiography was considered diagnostic for cardiomyopathy. The cumulative prevalence included all dogs with DCM and healthy dogs >7 years of age. Results: DCM prevalence in various age groups was as follows: age group 1 (1 to <2 years) 3.3%, age group 2 (2 to <4 years) 9.9%, age group 3 (4 to <6 years) 12.5%, age group 4 (6 to <8 years) 43.6%, and age group 5 (>8 years) 44.1%. The cumulative prevalence of Doberman Pinscher cardiomyopathy was 58.2%. There was an equal sex distribution, but male dogs showed earlier echocardiographic changes than did female dogs, which had significantly more VPCs. Conclusions and Clinical Importance: The prevalence of Doberman cardiomyopathy is very high in Europe. Disease manifestation and progression are different between male and female dogs. Yearly screening for DCM by Holter examination and echocardiography is recommended, starting at 2 years of age.     

Cardiac Troponin I in Doberman Pinschers with Cardiomyopathy

Background: Cardiac troponin I (cTnI) is useful for detection of cardiac myocyte damage, but its efficacy in detecting various stages of dilated cardiomyopathy (DCM) in Doberman Pinschers is unclear. Objectives: To evaluate the diagnostic value of cTnI in various stages of DCM in Dobermans. Animals: Six hundred and fifty‐three cTnI measurements of 336 Doberman Pinschers. Methods: Using a longitudinal study design, staging of the disease was based upon 24‐hour‐ambulatory‐ECG (Holter) and echocardiography. A total of 447 cTnI measurements were performed in 264 healthy Dobermans, and 206 cTnI measurements in 75 Dobermans with cardiomyopathy. Eighty‐eight cTnI samples were from dogs with >100 ventricular premature contractions (VPCs)/24 hour, but without echocardiographic changes (“VPC group”). Additional 19 samples originated from dogs with only echocardiographic changes (“ECHO group”), and 56 samples from dogs with both VPCs and echocardiographic changes (“VPC plus ECHO group”). Twenty samples were from dogs with clinical signs (“clinical group”). The group “incipient” included 23 dogs, that were considered to be normal according to Holter and echocardiography at the time of the exam, but that developed DCM within 1.5 years. Results: cTnI values of dogs in all disease groups, including the “incipient” (0.30 ± 0.20) and “VPC group” (0.36 ± 0.34), were significantly (P= .04, P < .001) higher than the control group (0.07 ± 0.16). A cut‐off value of >0.22 ng/mL had a sensitivity of 79.5% and a specificity of 84.4% to detect all forms of cardiomyopathy. Conclusions and Clinical Importance: cTnI measurement is a valuable diagnostic test that can detect cardiomyopathy in dogs that are otherwise clinically normal.     

Ability of a 5‐Minute Electrocardiography (ECG) for Predicting Arrhythmias in Doberman Pinschers with Cardiomyopathy in Comparison with a 24‐Hour Ambulatory ECG

Background: Ventricular premature contractions (VPCs) are common in the occult stage of cardiomyopathy in Doberman Pinschers. Although the gold standard for detecting arrhythmia is the 24‐hour ambulatory electrocardiography (ECG) (Holter), this method is more expensive, time‐consuming and often not as readily available as common ECG. Objectives: Comparison of 5‐minute ECGs with Holter examinations. Animals: Eight hundred and seventy‐five 5‐minute ECGs and Holter examinations of 431 Doberman Pinschers. Methods: Each examination included a 5‐minute ECG and Holter examination. A cut‐off value of >100 VPCs/24 hours using Holter was considered diagnostic for the presence of cardiomyopathy. Statistical evaluation included calculation of sensitivity, specificity, positive predictive value, and negative predictive value. Results: Holter examinations revealed >100 VPCs/24 hours in 204/875 examinations. At least 1 VPC during a 5‐minute ECG was detected in 131 (64.2%) of these 204 examinations. No VPCs were found in the 5‐minute ECG in 73 (35.8%) examinations of affected Doberman Pinschers. A 5‐minute ECG with at least 1 VPC as cut‐off had a sensitivity of 64.2%, a specificity of 96.7%, a positive predictive value of 85.6% and a negative predictive value of 89.9% for the presence of >100 VPCs/24 hours. Conclusions and Clinical Importance: A 5‐minute ECG is a rather insensitive method for detecting arrhythmias in Doberman Pinschers. However, the occurrence of at least 1 VPC in 5 minutes strongly warrants further examination of the dog, because specificity (96.7%) and positive predictive value (85.6%) are high and could suggest occult cardiomyopathy.     

Detection of Congestive Heart Failure in Dogs by Doppler Echocardiography

Background: Echocardiographic prediction of congestive heart failure (CHF) in dogs has not been prospectively evaluated. Hypothesis: CHF can be predicted by Doppler echocardiographic (DE) variables of left ventricular (LV) filling in dogs with degenerative mitral valve disease (MVD) and dilated cardiomyopathy (DCM). Animals: Sixty‐three client‐owned dogs. Methods: Prospective clinical cohort study. Physical examination, thoracic radiography, analysis of natriuretic peptides, and transthoracic echocardiography were performed. Diagnosis of CHF was based upon clinical and radiographic findings. Presence or absence of CHF was predicted using receiver‐operating characteristic (ROC) curve, multivariate logistic and stepwise regression, and best subsets analyses. Results: Presence of CHF secondary to MVD or DCM could best be predicted by E : isovolumic relaxation time (IVRT) (area under the ROC curve [AUC]=0.97, P < .001), respiration rate (AUC=0.94, P < .001), Diastolic Functional Class (AUC=0.93, P < .001), and a combination of Diastolic Functional Class, IVRT, and respiration rate (R²=0.80, P < .001) or Diastolic Functional Class (AUC=1.00, P < .001), respiration rate (AUC=1.00, P < .001), and E : IVRT (AUC=0.99, P < .001), and a combination of Diastolic Functional Class and E : IVRT (R²=0.94, P < .001), respectively, whereas other variables including N‐terminal pro‐brain natriuretic peptide, E : Ea, and E : Vp were less useful. Conclusion and Clinical Importance: Various DE variables can be used to predict CHF in dogs with MVD and DCM. Determination of the clinical benefit of such variables in initiating, modulating, and assessing success of treatments for CHF needs further study.     

Use of Simpson's Method of Disc to Detect Early Echocardiographic Changes in Doberman Pinschers with Dilated Cardiomyopathy

Background: M‐mode is the echocardiographic gold standard to diagnose dilated cardiomyopathy (DCM) in dogs, whereas Simpson's method of discs (SMOD) is the preferred method to detect echocardiographic evidence of disease in humans. Objectives: To establish reference values for SMOD and to compare those with M‐mode measurements. Animals: Nine hundred and sixty‐nine examinations of 471 Doberman Pinschers. Methods: Using a prospective longitudinal study design. Reference values for SMOD were established using 75 healthy Doberman Pinschers >8 years old with <50 ventricular premature contractions (VPCs) in 24 hours. The ability of the new SMOD cut‐off values, normalized to body surface area (BSA), for left ventricular end‐diastolic volume (LVEDV/BSA >95 mL/m²) and end‐systolic volume (LVESV/BSA > 55 mL/m²) to detect echocardiographic changes in Doberman Pinschers with DCM was compared with currently recommended M‐mode values. Dogs with elevated SMOD values but normal M‐mode measurements were followed‐up using a prospective longitudinal study design. Results: At the final examination 175 dogs were diagnosed with DCM according to both methods (M‐mode and SMOD). At previous examinations, M‐mode values were abnormal in 142 examinations only, whereas all 175 SMOD already had detected changes. Additionally, 19 of 154 dogs with >100 VPCs/24 hours and normal M‐mode values had abnormal SMOD measurement. Six dogs with increased SMOD measurements remained healthy at several follow‐up examinations (classified as false positive); in 24 dogs with increased SMOD measurements, no follow‐up examinations were available (classified as unclear). Conclusions and Clinical Importance: SMOD measurements are superior to M‐mode to detect early echocardiographic changes in Dobermans with occult DCM.     

Association of Tricuspid Annular Plane Systolic Excursion with Survival Time in Boxer Dogs with Ventricular Arrhythmias

Background

Tricuspid annular plane systolic excursion (TAPSE) is a useful estimate of right ventricular function in humans. Reference intervals for dogs have been generated, but the value of measuring TAPSE in other diseases, or investigating the association between TAPSE and outcome, is unknown.

Hypothesis

TAPSE is lower in Boxer dogs with ≥50 VPCs/24 h on Holter than in dogs with fewer ventricular ectopics, and lower TAPSE is associated with a shorter survival time.

Animals

Fifty Boxer dogs that presented for investigation of syncope or suspected arrhythmogenic right ventricular cardiomyopathy (ARVC) at a veterinary teaching hospital (2004–2011).

Methods

Retrospective study. Clinical records, Holter, and echocardiographic data were reviewed. TAPSE was measured in a blinded manner on stored echocardiographic cine‐loops using anatomic M‐mode. Outcome information was obtained and death was classified as cardiac or noncardiac. Survival analysis was performed using Kaplan‐Meier curves and Cox proportional hazards models.

Results

TAPSE was lower in Boxers with ≥50 VPCs/24 h (13.9 ± 4.04 mm) than Boxers with <50 VPCs/24 h (16.8 ± 3.21 mm; P < .001). TAPSE <15.1 mm was associated with shorter cardiac survival time in all dogs (P = .004) and also in dogs without left ventricular dysfunction (P = .035). When controlling for other variables, including ventricular tachycardia on Holter and left ventricular systolic dysfunction, multivariable analysis showed that TAPSE remained an independent predictor of time to cardiac death (HR >4.09, 95%CI 1.15–16.9, P < .029).

Conclusions and Clinical Importance

TAPSE offers prognostic value for Boxer dogs, including those with apparently normal systolic function and ≥50 VPCs/24 h on Holter analysis.     

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.     

Nutritional Alterations and the Effect of Fish Oil Supplementation in Dogs with Heart Failure

Alterations in body composition and nutritional status are common in humans with heart failure and are related, in part, to increases in cytokine concentrations. Cytokines have not been studied previously in dogs with naturally occurring cardiac disease nor has fish oil administration been used in this population to decrease cytokine production. The purposes of this study were to characterize nutritional and cytokine alterations in dogs with heart failure and to test the ability of fish oil to reduce cytokines and improve clinical outcome. Body composition, insulinlike growth factor-1, fatty acids, and cytokines were measured in 28 dogs with heart failure and in 5 healthy controls. Dogs with heart failure then were randomized to receive either fish oil or placebo for 8 weeks. All parameters were measured again at the end of the study period. At baseline, 54% of dogs with heart failure were cachectic and the severity of cachexia correlated with circulating tumor necrosis factor-α concentrations (P= .05). Cytokine concentrations at baseline, however, were not significantly increased in dogs with heart failure compared to controls. Baseline plasma arachidonic acid (P= .02), eicosapentaenoic acid (P= .03), and docosahexaenoic acid (P = .004) concentrations were lower in dogs with heart failure than in controls. Fish oil supplementation decreased interleukin-1β (IL-1) concentrations (P= .02) and improved cachexia (P= .01) compared to the placebo group. The mean caloric intake of the heart failure dogs as a group was below the maintenance energy requirement (P < .001), but no difference was found in food intake between the fish oil and placebo groups. Insulinlike growth factor-1 concentrations (P= .01) and reductions in circulating IL-1 concentrations over the study period (P= .02) correlated with survival. These data demonstrate that canine heart failure is associated with cachexia, alterations in fatty acids, and reduced caloric intake. Fish oil supplementation decreased IL-1 concentrations and improved cachexia. In addition, reductions in IL-1 predicted survival, suggesting that anticytokine strategies may benefit patients with heart failure.     

Effect of Physiological Determinants and Cardiac Disease on Plasma Adiponectin Concentrations in Dogs

Background

In humans, a high concentration of adiponectin is associated with a favorable cardiovascular risk profile whereas, in patients with heart failure (HF), a high concentration of adiponectin is associated with a less favorable prognosis.

Hypothesis/Objectives

To evaluate the physiological determinants of plasma adiponectin concentration in dogs and the influence of heart disease, myxomatous mitral valve disease (MMVD), and dilated cardiomyopathy (DCM).

Animals

One hundred and fourteen client‐owned dogs and 9 Beagles from the research colony of the Clinical Veterinary Unit of the University of Liège.

Methods

We prospectively measured circulating adiponectin concentration in healthy control dogs (n = 77), dogs with MMVD (n = 22) and dogs with DCM (n = 15) of various degrees of severity. Diagnosis was confirmed by Doppler echocardiography. Plasma adiponectin concentration was measured by a canine‐specific sandwich ELISA kit.

Results

An analysis of covariance showed an association between adiponectin concentration and age, neuter status, and heart disease. No association between adiponectin concentration and class of HF, sex, body condition score, body weight, circadian rhythm, or feeding was found. Plasma adiponectin concentration was negatively correlated with age (P = .001). Adiponectin was lower in neutered (P = .008) compared to intact dogs. Circulating adiponectin concentration was increased in dogs with DCM compared to healthy dogs (P = .018) and to dogs with MMVD (P = .014).

Conclusions and Clinical Importance

Age and neutering negatively influence circulating adiponectin concentration. Plasma adiponectin concentration increased in dogs with DCM. Additional research is required to investigate if this hormone is implicated in the pathophysiology of DCM and associated with clinical outcome.     

Comparisons of 3‐, 2‐Dimensional,and M‐Mode Echocardiographical Methods for Estimation of Left Chamber Volumes in Dogs with and without Acquired Heart Disease

Background: Real‐time 3‐dimensional echocardiography (RT3D) is a recent technique based on volumetric scanning, eliminating the need for geometric modeling of the cardiac chambers and minimizing the errors caused by foreshortened views. Hypothesis: Estimations of left ventricular (LV) end‐diastolic (EDV) and end‐systolic volume (ESV), and left atrial (LA) size, differ depending on the echocardiographic technique of estimation. Animals: Fifty‐one dogs with acquired heart disease and 34 healthy control dogs. Methods: Prospective observational study by M‐mode (Teichholz method), Simpson's modified 2‐dimensional (2D) method, and RT3D methods for estimation of LV volumes. LA size was evaluated by 2D and RT3D methods. Results: RT3D showed good agreement with 2D for EDV and ESV, whereas Teichholz method overestimated LV volumes in comparison with the other 2 methods by approximately a factor 2. There were no statistically significant differences among the 3 methods in estimating ejection fraction. Comparison between RT3D assessment of LA end‐systolic volume per kilogram (LAs/kg) and LA to aortic ratio (LA/Ao) measured by 2D relative to each other showed that the RT3D method underestimated LAs/kg at lower values, and overestimated it at higher values. The difference between methods increased with increasing LA size. Conclusions and Clinical Importance: There was good agreement between RT3D and 2D methods of estimating EDV and ESV, whereas the Teichholz method overestimated LV volumes by approximately a factor 2. In comparison with RT3D, LA/Ao underestimated LA size, especially when LA was enlarged.     

Conversion of atrial dissociation with lidocaine in a dog

A 3-year-old healthy dog was presented for abdominal surgery following ingestion of razor blades. An electrocardiogram revealed a regular sinus bradycardia with normal P waves at a heart rate of 45 bpm. In addition, low-amplitude positive deflections (p′ waves) were visualized at a regular interval and rapid rate of 250 bpm, dissociated from the normal sinus P waves. A tentative diagnosis of atrial dissociation was proposed. Administration of lidocaine abolished the p′ waves. This case describes atrial dissociation observed following premedication that was successfully terminated using lidocaine in a healthy dog.     

Evaluation of the Cortisol‐to‐ACTH Ratio in Dogs with Hypoadrenocorticism,Dogs with Diseases Mimicking Hypoadrenocorticism and in Healthy Dogs

Background

The adrenocorticotropic hormone (ACTH) stimulation test is the gold standard for diagnosing hypoadrenocorticism (HA) in dogs. However, problems with the availability of synthetic ACTH (tetracosactrin/cosyntropin) and increased costs have prompted the need for alternative methods.

Objectives

To prospectively evaluate the cortisol‐to‐ACTH ratio (CAR) as a screening test for diagnosing canine HA.

Animals

Twenty three dogs with newly diagnosed HA; 79 dogs with diseases mimicking HA; 30 healthy dogs.

Methods

Plasma ACTH and baseline cortisol concentrations were measured before IV administration of 5 μg/kg ACTH in all dogs. CAR was calculated and the diagnostic performance of ACTH, baseline cortisol, CAR and sodium‐to‐potassium ratios (SPRs) was assessed based on receiver operating characteristics (ROC) curves calculating the area under the ROC curve.

Results

The CAR was significantly lower in dogs with HA compared to that in healthy dogs and in those with diseases mimicking HA (P < .0001). There was an overlap between HA dogs and those with HA mimicking diseases, but CAR still was the best parameter for diagnosing HA (ROC AUC 0.998), followed by the ACTH concentration (ROC AUC 0.97), baseline cortisol concentration (ROC AUC 0.96), and SPR (ROC AUC 0.86). With a CAR of >0.01 the diagnostic sensitivity and specificity were 100% and 99%, respectively.

Conclusion and Clinical Importance

Calculation of the CAR is a useful screening test for diagnosing primary HA. As a consequence of the observed overlap between the groups, however, misdiagnosis cannot be completely excluded. Moreover, additional studies are needed to evaluate the diagnostic reliability of CAR in more dogs with secondary HA.     

Effect of thyroid hormone supplementation on survival of euthyroid dogs with congestive heart failure due to systolic myocardial dysfunction: a double-blind, placebo-controlled trial

Nineteen euthyroid dogs of 12 breeds with echocardiographic signs of dilated cardiomyopathy (DCM) and radiographic and clinical signs of congestive heart failure (CHF) were evaluated in a randomised, double-blind, and placebo-controlled study. The dogs received either thyroxine or placebo as an adjunct to digoxin, furosemide and propranolol. The group assignment of individual dogs and serum concentrations of thyroid hormones remained unknown to owners and investigators during the entire study period. Dogs were evaluated clinically and with electrocardiography (ECG), thoracic radiography, echocardiography and measurement of total thyroxine (tT4) and thyroid stimulating hormone (TSH) before beginning of the trial, and then one week, 2 months, 6 months and yearly after initial examination, and, when applicable, at the time of euthanasia. End-point of the study was euthanasia (n = 17) due to severe congestive heart failure or sudden death (n = 2). Survival times ranged from 17 to 1030 days (median 187 days) in the placebo group, and from 18 to 1000 days (median 73 days) in the treatment group. There was no statistically significant difference in survival times between the treatment group and the placebo group (p = 0.46). Post mortem and histopathologic examinations revealed the attenuated wavy fiber type of DCM in 11 dogs, and myocardial infarcts, arteriosclerosis and chronic valvular disease in one dog. In conclusion, there was a wide range in survival times of dogs treated with digoxin, furosemide and propranolol. Adding thyroid hormones to the treatment did not significantly influence survival.     

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.

Validation of heart rate spot-check protocol to measure circadian variation and heart rate in healthy dogs and dogs with atrial fibrillation

IntroductionAlternatives for out-of-clinic heart rate (HR) measurement are required to optimise the management of atrial fibrillation (AF) in dogs. Additionally, the presence of circadian variation (CV) in HR in pet dogs remains unknown.We aimed to identify the number and duration of spot-checks required for an accurate estimation of 24-hour HR in canine AF. Circadian variation in HR was examined in healthy dogs and dogs with AF, and spot-check-derived HR was compared with a CV-derived gold standard.Materials and methodsAmbulatory electrocardiogram data from healthy dogs and dogs with AF were retrospectively analysed. Heart rate was calculated from the entire recording and pre-defined periods (spot-checks) of one hour to 30 and 60 s in duration. Circadian variation in HR was determined by cosinor analysis. Bias and limits of agreement of means and median HR with mesor HR were determined by correlation and Bland–Altman analysis.ResultsCircadian variation in HR was identified not only in 18/22 healthy dogs and 14/21 AF dogs but only on ambulatory electrocardiogram recordings.Four-hourly spot-checks provided the most accurate estimate of mesor HR in healthy dogs (bias of the median over 30 s 7.70, limits of agreement 7.48), whereas, in dogs with AF, four, six and eight-hourly spot-checks provided reliable estimates of mesor HR (bias within −1.29 and −29.5).ConclusionsFour, six and eight-hourly HR spot-checks can estimate 24-hourly HR in dogs with AF. There was CV in HR in most healthy pet dogs and dogs with AF. Spot-check protocols cannot identify CV in HR.