Prospective evaluation of the combined value of physical examination and biomarker variables in screening for preclinical dilated cardiomyopathy in Doberman Pinschers.

INTRODUCTION: Screening to assess likelihood of preclinical dilated cardiomyopathy (PC-DCM) prior to advanced diagnostic tests in Doberman Pinschers (DP) is desirable. OBJECTIVE: To investigate the combined value of physical examination (PE), N-terminal pro B-type natriuretic peptide (NTproBNP) and cardiac troponin I (cTnI) for identifying PC-DCM in DP. ANIMALS, MATERIALS AND METHODS: All dogs underwent: PE, echocardiogram, 3-min ECG and cardiac biomarker measurement. Asymptomatic DP (414) were classified based on 3-min ECG and echocardiogram as: No-DCM/MMVD or myxomatous mitral valve disease (MMVD), PC-DCM based on echocardiogram (PC-DCM-Echo), PC-DCM based on arrhythmias with a normal echocardiogram (PC-DCM-ECG), equivocal DCM (EQ-DCM), and MMVD. Receiver operator characteristic curves and prediction models were derived. RESULTS: Heart murmurs and arrhythmias were rare and gallop sounds were absent in No-DCM/MMVD DP. Dogs ≥ four years old and males had higher probabilities of PC-DCM-Echo. Prediction models incorporating PE variables with NTproBNP had an area under the curve (AUC) of 0.940 for distinguishing between PC-DCM-Echo and all other groups, which was similar to the AUC for NTproBNP (0.939) or cTnI (0.932) alone. Discrimination between No-DCM/MMVD and all other groups was similar for NTproBNP (0.781) and cTnI (0.742) as individual tests, however, models combining PE variables and NTproBNP increased the AUC to 0.812. An NTproBNP cut-off of ≥548 pmol/L, was 100% sensitive and 77.3% specific for detecting PC-DCM-Echo. CONCLUSIONS: Both NTproBNP and cTnI had good utility as sole tests to discriminate PC-DCM-Echo DP from all others. Models differentiating No-DCM/MMVD DP from all other DP were improved by using PE and NTproBNP together.

Efficacy of pimobendan in the prevention of congestive heart failure or sudden death in Doberman Pinschers with preclinical dilated cardiomyopathy (the PROTECT Study).

BACKGROUND: The benefit of pimobendan in delaying the progression of preclinical dilated cardiomyopathy (DCM) in Dobermans is not reported. HYPOTHESIS: That chronic oral administration of pimobendan to Dobermans with preclinical DCM will delay the onset of CHF or sudden death and improve survival. ANIMALS: Seventy-six client-owned Dobermans recruited at 10 centers in the UK and North America. METHODS: The trial was a randomized, blinded, placebo-controlled, parallel group multicenter study. Dogs were allocated in a 1:1 ratio to receive pimobendan (Vetmedin capsules) or visually identical placebo. The composite primary endpoint was prospectively defined as either onset of CHF or sudden death. Time to death from all causes was a secondary endpoint. RESULTS: The proportion of dogs reaching the primary endpoint was not significantly different between groups (P = .1). The median time to the primary endpoint (onset of CHF or sudden death) was significantly longer in the pimobendan (718 days, IQR 441-1152 days) versus the placebo group (441 days, IQR 151-641 days) (log-rank P = 0.0088). The median survival time was significantly longer in the pimobendan (623 days, IQR 491-1531 days) versus the placebo group (466 days, IQR 236-710 days) (log-rank P = .034). CONCLUSION AND CLINICAL IMPORTANCE: The administration of pimobendan to Dobermans with preclinical DCM prolongs the time to the onset of clinical signs and extends survival. Treatment of dogs in the preclinical phase of this common cardiovascular disorder with pimobendan can lead to improved outcome.

Efficacy of benazepril hydrochloride to delay the progression of occult dilated cardiomyopathy in Doberman Pinschers.

BACKGROUND: Angiotensin converting enzyme inhibitors (ACEIs) are recommended in people to treat asymptomatic (occult) dilated cardiomyopathy (DCM). Efficacy of therapy in occult DCM in dogs is unknown. HYPOTHESIS: ACEIs, specifically benazepril hydrochloride (BH), will delay the onset of overt DCM in Doberman Pinschers. ANIMALS: Ninety-one Doberman Pinschers were studied, 57 dogs received BH, and 34 dogs no ACEI. METHODS: Retrospective study of the medical records of all Doberman Pinschers with occult DCM that received BH or no ACEI between April 1989 and February 2003. Two criteria of left ventricular enlargement were used for enrollment: one independent of body weight (BW) (C1) and the other indexed to BW (C2). Cox proportional hazards analyses were used to identify variables associated with the onset of overt DCM. RESULTS: On univariate analysis the median time to onset of overt DCM was significantly longer for the benazepril group (for C1: 425 days for BH, 95% confidence interval [CI] 264-625 days; 339 days for no ACEI, CI 172-453 days, P= .02; for C2: 454 days for BH, CI 264-628 days; 356 days for no ACEI, CI 181-547 days, P= .02). The hazard ratio (HR) (benazepril/no ACEI) was 0.57, CI 0.35-0.94, P= .03 for C1; HR = 0.56, CI 0.34-0.93, P= .02 for C2. On multivariate analysis, BH significantly delayed onset of overt DCM (HR [benazepril/no ACEI] = 0.45, CI 0.26-0.78, P < .01, for C1; HR = 0.36, CI 0.21-0.63, P < .01, for C2). CONCLUSIONS: BH in particular and ACEIs in general might delay the progression of occult DCM. Prospective studies are warranted to test this theory.

Effect of pimobendan on case fatality rate in Doberman Pinschers with congestive heart failure caused by dilated cardiomyopathy.

BACKGROUND: Despite traditional therapy of a diuretic, angiotensin converting enzyme inhibitor, digoxin, or a combination of these drugs, survival of dogs with dilated cardiomyopathy (DCM) is low. Pimobendan, an inodilator, has both inotropic and balanced peripheral vasodilatory properties. HYPOTHESIS: Pimobendan when added to conventional therapy will improve morbidity and reduce case fatality rate in Doberman Pinschers with congestive heart failure (CHF) caused by DCM. ANIMALS: Sixteen Doberman Pinschers in CHF caused by DCM. METHODS: A prospective randomized, double-blind, placebo-controlled study with treatment failure as the primary and quality of life (QoL) indices as secondary outcome variables. Therapy consisted of furosemide (per os [PO] as required) and benazepril hydrochloride (0.5 mg/kg PO q12h) and dogs were randomized in pairs and by sex to receive pimobendan (0.25 mg/kg PO q12h) or placebo (1 tablet PO q12h). RESULTS: Pimobendan-treated dogs had a significant improvement in time to treatment failure (pimobendan median, 130.5 days; placebo median, 14 days; P= .002; risk ratio = 0.35, P= .003, lower 5% confidence limit = 0.13, upper 95% confidence limit = 0.71). Number and rate of dogs reaching treatment failure in the placebo group precluded the analysis of QoL. CONCLUSIONS AND CLINICAL IMPORTANCE: Pimobendan should be used as a first-line therapeutic in Doberman Pinschers for the treatment of CHF caused by DCM.

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.

Resting and dobutamine stress echocardiographic factors associated with the development of occult dilated cardiomyopathy in healthy Doberman pinscher dogs.

In 29 healthy Doberman Pinschers, echocardiographic parameters evaluating systolic and diastolic function were examined prospectively at rest and during dobutamine constant rate infusion (5 micrograms/kg/minute) to determine if any parameters were associated with the development of occult dilated cardiomyopathy (DCM). A resting echocardiogram was repeated 1 year later to determine which dogs had met our criteria for occult DCM. Six dogs developed occult DCM during the follow-up period. Univariate logistic regression analysis showed that at rest, an increased left ventricular internal dimension in systole (LVID-S) (P = .02), preejection period (PEP) (P = .03), ratio of PEP to left ventricular ejection time (P = .02), and isovolumic relaxation time (P = .02) were significantly associated with the development of occult DCM. During dobutamine stress echocardiography (DSE), high LVID-S (P = .02) and systolic wall stress index (P = .04) and reduced fractional shortening (P = .02) and ratio of peak early to late diastolic mitral filling velocity (E/A) (P = .05) were associated with the development of occult DCM. Multiple logistic regression showed that LVID-S (P = .002) and E/A (P = .002) measured during dobutamine infusion also were associated with the development of occult DCM. Reclassification based on the DSE data was not significantly different than reclassification based on the resting echocardiographic data. Resting echocardiography and DSE have the potential to be clinically applicable screening tests for very early systolic and diastolic dysfunction in Doberman Pinschers, heralding the onset of occult DCM as it is currently defined.

Plasma concentrations and cardiovascular influence of lidocaine infusions during isoflurane anesthesia in healthy dogs and dogs with subaortic stenosis.

OBJECTIVE: To determine the plasma concentrations and cardiovascular changes that occur in healthy dogs and dogs with aortic stenosis that are given an infusion of lidocaine during isoflurane anesthesia. STUDY DESIGN: Phase 1, controlled randomized cross-over trial; Phase 2, before and after trial ANIMALS: Phase 1, 6 healthy dogs (4 female, 2 male) weighing 23.8 +/- 7.4 kg; Phase 2, 7 dogs (4 female, 3 male) with moderate to severe subaortic stenosis (confirmed by Doppler echocardiography) weighing 31.1 +/- 14.5 kg. METHODS: After mask induction, intubation, and institution of positive pressure ventilation, instrumentation was performed to measure hemodynamic variables. After baseline, measurement at an end-tidal isoflurane concentration of 1.9% (phase 1) or 1.85% (phase 2), a loading dose infusion of lidocaine at 400 microg/kg/min was given. Phase 1: Maintenance doses of lidocaine were administered consecutively (40, 120, and 200 microg/kg/min) after the loading dose (given for 10, 10, and 5 minutes, respectively) in advance of each maintenance concentrations. Measurements were taken at the end of each loading dose and at 25 and 35 minutes during each maintenance level. The same animals on a different day were given dextrose 5% and acted as the control. Phase 2: Dogs were studied on a single occasion during an infusion of lidocaine at 120 microg/kg/ min given after the loading dose (10 minutes). Measurements occurred after the loading dose and at 25 and 35 minutes. A blood sample for lidocaine concentration was taken at 70 minutes. Data were compared using a one-way ANOVA for phase 1, and between phase 1 and 2. Statistical analysis for phase 2 was performed using a paired t-test with a Bonferroni correction. A P value < or = .05 was considered significant. RESULTS: Phase 1: Plasma lidocaine concentrations achieved with 40, 120, and 200 microg of lidocaine/kg/min were 2.70, 5.27, and 7.17 microg/mL, respectively. A significant increase in heart rate (HR) (all concentrations), central venous pressure (CVP), mean pulmonary arterial pressure (PAP), and a decrease in stroke index (SI) (200 microg/kg/min) were observed. An increase in systemic vascular resistance (SVR) and mean PAP, and a decrease in SI also followed the loading dose given before the 200 microg/kg/min infusion. No other significant differences from the control measurements, during dextrose 5% infusion alone, were detected. Phase 2: Plasma lidocaine concentrations achieved were 5.35, 4.23, 4.23, and 5.60 microg/mL at 10, 25, 35, and 70 minutes, respectively. They were not significantly different from concentrations found in our healthy dogs at the same infusions. A significant but small increase in CVP compared with baseline was noted after the loading dose. There were no significant differences from baseline shown in all other cardiovascular data. There were no statistically significant differences in any measurements taken during the lidocaine infusion between the dogs in phase 1 and phase 2. Dogs with aortic stenosis tended to have a lower cardiac index than healthy dogs at baseline (88 v 121 mL/kg/min) and during lidocaine infusion (81 v 111 mL/kg/min). A small, statistically significant difference in systolic PAP was present at baseline. CONCLUSIONS: There does not appear to be any detrimental cardiovascular effects related to an infusion of lidocaine at 120 microg/kg/min during isoflurane anesthesia in healthy dogs or dogs with aortic stenosis. The technique used in this study resulted in therapeutic plasma concentrations of lidocaine. CLINICAL RELEVANCE: Methods shown in the study can be used in clinical cases to achieve therapeutic lidocaine levels without significant cardiovascular depression during isoflurane anesthesia.

Heart rate variability in the dog: is it too variable?

The purpose of the study was to evaluate resting heart rate variability (HRV) as a simple noninvasive screening test for early autonomic derangement, heralding the development of occult dilated cardiomyopathy (DCM). Time and frequency domain HRV parameters were evaluated in 32 healthy Doberman pinschers, as potential predictors of the development of occult DCM within the following year and correlated with plasma catecholamines, markers of sympathoexcitation. Ten Dobermans with occult DCM and 8 Dobermans with congestive heart failure (CHF) were positive controls. Seven of the 32 "healthy" dogs developed occult DCM over the course of the study. None of the HRV parameters were associated with the development of occcult DCM based on univariate logistic regression. In dogs who developed occult DCM, plasma norepinephrine (NE) was inversely correlated with % fractal power (r = -0.81, P = 0.05). In dogs with occult DCM (positive controls), plasma NE was inversely correlated with fractal power (r = -0.81, r = 0.03), total power (r = -0.08, P = 0.03), high frequency power (r = -0.75, P = 0.05) and the standard deviation of the RR (r = -0.83, P = 0.02). The great inherent variability of the test may have limited our ability to discriminate between physiologic and pathophysiologic data, rendering this methodology inadequate as a screening test for early occult DCM. However, the negative correlations of NE with various forms of spectral power in dogs with occult DCM suggests that early in the natural history of DCM, there is parasympathetic withdrawal. A reduction in the nonharmonic, fractal component may be the first recognizable abnormality in the power spectrum of dogs who will develop DCM.

Cardiac muscle mass distribution in the domestic turkey and relationship to electrocardiogram.

Ventricular weights were measured in 20-week-old male and female heavy turkeys, and electrocardiograms (ECGs) were recorded in 10- and 20-week-old male and female heavy turkeys. Twenty-week-old males had heavier relative left ventricular and total ventricular weights than females of the same age. Left-to-right ventricular weight ratios were 4.4:1 in males and 4.5:1 in females. Heart rate was faster in young birds and in females, and that influenced the duration of the intervals of the ECG. Wave amplitudes were smaller in 10-week-old turkeys than in 20-week-old turkeys. There was no correlation between electrocardiographic parameters and ventricular weights of male and female turkeys. Two-dimensional ECGs were therefore found to be of minimal value for detecting turkeys with heavier ventricles.

Echocardiographic results and clinical considerations in dogs with right atrial/auricular masses.

The case records of 26 dogs with pericardial effusion were examined. Sixteen dogs with confirmed right atrial/auricular masses were found. Eighteen masses were identified, of which 16 were confirmed as hemangiosarcomas. Eleven dogs had an abnormal mass detected during the echocardiographic examination, and tumor location was correctly predicted in nine of the 11 dogs. Six of seven tumors, which were not detected during the echocardiogram, were located in the right auricle. Pericardial effusion was apparently not necessary for the echocardiographic detection of a right atrial/auricular mass. Of ten dogs with pericardial effusion due to causes other than a cardiac mass, one abnormal mass-like lesion was seen during echocardiographic examination.

Doppler-derived velocity of blood flow across the cardiac valves in the normal dog.

Doppler echocardiography is a relatively new procedure used to assess certain cardiovascular disorders in the dog. The objectives of this study were to determine the range of values for the maximal peak velocity of blood flow across each of the four cardiac valves in a sample population of normal adult dogs, using duplex continuous wave Doppler echocardiography, and to determine the optimal tomographic planes to use for an adequate continuous wave Doppler evaluation of the canine heart. Twenty normal dogs were examined to obtain values for peak transvalvular velocity for each of the four cardiac valves. The mean values +/- 1 SD, in cm/s were: 98.1 +/- 9.4 for the pulmonary valve imaged from the left side of the chest, 95.5 +/- 10.3 for the pulmonary valve imaged from the right side of the chest (n = 19), 118.1 +/- 10.8 for the aortic valve, 86.2 +/- 9.5 for the mitral valve and 68.9 +/- 8.4 for the tricuspid valve. Regurgitation was detected across the pulmonic valve in 14 of the 20 dogs, and across the tricuspid valve in ten dogs. The analysis of the tomographic images confirmed that for a complete assessment of a given intracardiac valve, the valve must be examined from all possible directions to obtain maximum values for peak velocity.

Canine congenital aortic stenosis: A review of the literature and commentary.

Congenital aortic stenosis usually affects the subvalvular region, and occurs mainly in Newfoundland, Golden Retriever, German Shepherd, and Boxer dogs. The disorder is inherited as a dominant trait with variable penetrance in Newfoundland dogs.The prevalence of subaortic stenosis-like heart murmurs in Golden Retriever dogs appears to be very much greater than previously suspected.Most cases of aortic stenosis represent mild lesions, are detected as incidental findings, and result in no loss of longevity or quality of life. Moderate or severe stenosis may result in exertional weakness, syncope, or sudden death. Signs of congestive heart failure are rare unless mitral valve insufficiency is present.Generally, electrocardiography and radiography are unrevealing in this disorder. Doppler echocardiography may be the best diagnostic tool to detect even mild cases of aortic stenosis.At present, therapy is limited due to the technical expertise and expense required. The prognosis depends on the severity of the lesion.