Assessment of left ventricular volume and function in healthy dogs by use of one-, two-, and three-dimensional echocardiography versus multidetector computed tomography.

OBJECTIVE To compare left ventricle (LV) volume and function variables obtained by use of 1-D, 2-D, and real-time 3-D echocardiography versus ECG-gated multidetector row CT (MDCT) angiography, which was considered the criterion-referenced standard. ANIMALS 6 healthy, purpose-bred dogs. PROCEDURES Dogs were anesthetized and administered a constant rate infusion of esmolol, and 1-D, 2-D, and 3-D echocardiography and ECG-gated, contrast-enhanced MDCT were performed. End-diastolic volume (EDV), end-systolic volume (ESV), stroke volume, and ejection fraction (EF) were calculated by use of the Teichholz method for 1-D echocardiography, single-plane and biplane modified Simpson method of disks (MOD) and area-length method for 2-D echocardiography, and real-time biplane echocardiography (RTBPE) and real-time 3-D echocardiography (RT3DE) for 3-D echocardiography. Volumes were indexed to body surface area and body weight. Median values, correlations, and limits of agreement were compared between echocardiographic modalities and MDCT. RESULTS EDV and ESV measured by use of RTBPE and RT3DE had the strongest correlations with results for MDCT. Values obtained for EDV, ESV, stroke volume, and EF did not differ significantly between echocardiographic methods and MDCT. Use of RT3DE and RTBPE slightly underestimated EDV, ESV, and EF, compared with values for MDCT, as determined with Bland-Altman analysis. CONCLUSIONS AND CLINICAL RELEVANCE Values for EDV and ESV obtained by use of 3-D echocardiography, including RTBPE and RT3DE, had the highest correlation with slight underestimation, compared with values obtained by use of MDCT. This was similar to results for 3-D echocardiography in human medicine.

Detection by ELISA of C-terminal proBNP in plasma from cats with cardiomyopathy.

The B-type natriuretic peptide prohormone (proBNP) is enzymatically cleaved into an inactive N-terminal peptide and a biologically active C-terminal peptide with many beneficial cardiorenal effects. The purpose of this study was to develop and test in cats with cardiomyopathy an immunoassay to quantify the concentrations of C-terminal proBNP in feline plasma. An anti-canine proBNP monoclonal antibody (UI-1021) was shown to have adequate binding affinity to proBNP 80-106 for use in a solid-phase immunoassay, and by epitope mapping to bind within positions 84-87 of feline proBNP. UI-1021 was paired with an affinity-purified rabbit polyclonal detection antibody to feline proBNP 100-106, in a sandwich ELISA with feline proBNP 80-106 standard. The linearity and analytical range and sensitivity of the assay were confirmed from 1.4 to 85 pmol/L. Spike recovery averaged 106.5% (95% confidence interval 78-135%). Within run and intra-assay coefficients of variation were <12%. A protease inhibitor mixture preserved proBNP 80-106 immunoreactivity for at least 5 days in plasma. Clinical verification of the ELISA was done using plasma from 13 cats with cardiomyopathy, whose C-terminal proBNP concentrations ranged from 1.7 to 78.8 pmol/L vs. <1.4-1.8 pmol/L in plasma from 18 healthy cats. Concentrations were found to be substantially lower than reported N-terminal proBNP concentrations, and similar to those of human heart failure patients where relative C-terminal BNP deficiencies have been proposed as contributory to the progression of the disease.

Biologic variability in NT-proBNP and cardiac troponin-I in healthy dogs and dogs with mitral valve degeneration.

BACKGROUND: The N-terminal fragment of the prohormone B-type natriuretic peptide (NT-proBNP) and cardiac troponin-I are candidate biomarkers for cardiac disease in dogs. The degree of biologic variation in these biomarkers has not previously been reported in healthy dogs or dogs with mitral regurgitation. OBJECTIVES: The purpose of the study was to derive estimates of intrinsic biologic variability and reference change values for NT-proBNP and cardiac troponin-I in healthy dogs and dogs with mitral regurgitation grade IB and II according to the International Small Animal Cardiac Health Council (ISACHC) grading system. METHODS: Plasma and sera were collected weekly for up to 7 weeks from 12 control dogs and 9 dogs with mitral regurgitation. NT-proBNP and troponin-I (C-TnI) concentrations were determined. Indices of biologic variation such as reciprocal index of individuality (r-IoI) and reference change values (RCV) were calculated in both the groups. RESULTS: Individuality was high in control dogs and dogs with grade IB and II mitral valve regurgitation for both C-TnI (r-IoI 1.6 and 2) and NT-proBNP (1.5 and 2.7), while the 2-sided RCV for NT-proBNP was significantly lower in dogs with mitral regurgitation (52.5% vs 99.4%, P<0.01.). CONCLUSIONS: High individuality of these cardiac biomarkers suggests that, following diagnosis, these assays are best interpreted by serial determination in individual canine patients rather than by comparison to a population-based reference interval. The smaller RCV values for dogs with mitral regurgitation suggest that smaller relative changes in NT-proBNP are clinically meaningful in these patients.

Long-term outcome of physiologic VDD pacing versus non-physiologic VVI pacing in dogs with high-grade atrioventricular block.

OBJECTIVE: To compare the long-term outcome associated with physiologic VDD and non-physiologic VVI or VVIR pacing in dogs with high-grade atrioventricular block. ANIMALS: Forty-nine paced dogs with high-grade atrioventricular block were included. METHODS: Retrospective review of medical records, thoracic radiographs and echocardiograms for all dogs. Patient owners and referring veterinarians were contacted for survival times and a satisfaction questionnaire was submitted to the owners. Survival times, complication rates, resolution of clinical signs, and owner satisfaction were compared between the pacing modalities. RESULTS: A single lead VDD pacemaker was implanted in 19 dogs (39%) whereas 30 dogs (61%) were treated with VVI pacing. The median survival time for all dogs post-pacemaker implantation was 24.5 months. Survival time was significantly decreased in dogs that were older at the time of presentation or that presented with ventricular tachycardia or reduced left ventricular fractional shortening. Median survival times after implantation were not significantly different between pacing modalities (P = 0.29). Major complication rates were 11% within the VDD group and 20% within the VVI group and were not significantly different (P = 0.46). Minor complications were significantly higher within the VDD group than within the VVI group (47% versus 7% respectively; P < 0.01) due to a higher number of dogs in the VDD group experiencing transient ventricular premature contractions in the immediate post-implantation time period. Resolution of clinical signs, owner satisfaction, and quality of life perception were considered excellent in both groups. CONCLUSIONS: No long-term clinical benefit of VDD over VVI pacing could be identified in the present study.

Management of incidentally detected heart murmurs in dogs and cats.

A dog or a cat has an incidentally detected heart murmur if the murmuris an unexpected discovery during a veterinary consultation that was not initially focused on the cardiovascular system. This document presents approaches for managing dogs and cats that have incidentally-detected heart murmurs, with an emphasis on murmur characteristics, signalment profiling, and multifactorial decision-making to choose an optimal course for a given patient.

Validation of a commercially available enzyme immunoassay for measurement of plasma antidiuretic hormone concentration in healthy dogs and assessment of plasma antidiuretic hormone concentration in dogs with congestive heart failure.

OBJECTIVE: To validate the use of a human enzyme immunoassay (EIA) kit for measurement of plasma antidiuretic hormone (ADH) concentration in dogs and evaluate plasma ADH concentrations in dogs with congestive heart failure (CHF) attributable to acquired cardiac disease, compared with findings in healthy dogs. ANIMALS: 6 healthy dogs and 12 dogs with CHF as a result of chronic degenerative valve disease or dilated cardiomyopathy. PROCEDURES: Plasma samples from the 6 healthy dogs were pooled and used to validate the EIA kit for measurement of plasma ADH concentration in dogs by assessing intra-assay precision, dilutional linearity, and spiking recovery. Following validation, plasma ADH concentrations were measured in the 6 healthy dogs and in the 12 dogs with CHF for comparison. RESULTS: The EIA kit measured ADH concentrations in canine plasma samples with acceptable intra-assay precision, dilutional linearity, and spiking recovery. The intra-assay coefficient of variation was 11%. By use of this assay, the median plasma concentration of ADH in dogs with CHF was 6.15 pg/mL (SD, 3.2 pg/mL; range, 4.18 to 15.47 pg/mL), which was significantly higher than the median concentration in healthy dogs (3.67 pg/mL [SD, 0.93 pg/mL; range, 3.49 to 5.45 pg/mL]). CONCLUSIONS AND CLINICAL RELEVANCE: Plasma ADH concentrations in dogs can be measured with the tested EIA kit. Plasma ADH concentrations were higher in dogs with CHF induced by acquired cardiac disease than in healthy dogs. This observation provides a basis for future studies evaluating circulating ADH concentrations in dogs with developing heart failure.

Hypoplastic aberrant left subclavian artery in a dog with a persistent right aortic arch.

Vascular ring anomalies (VRA) are relatively uncommon cardiovascular disorders in canine patients. The most common VRA is a persistent right aortic arch (PRAA) with a left ligamentum arteriosum, however various other vascular anomalies resulting in tracheoesophageal compression have also been reported. We report a case of a dog with a PRAA and left ligamentum arteriosum with a hypoplastic aberrant left subclavian artery resulting in asymmetric cervicobrachial circulation. Selective angiography and ECG-gated multi-detector computed tomography were utilized in the evaluation of these defects. The case presented represents a unique vascular anomaly of the aortic arch not previously described in veterinary medicine.

Anomalous left-to-right shunting communication between the ascending aorta and right pulmonary artery in a dog.

Anomalies of conotruncal septation are rare in dogs and uncommon in humans. Congenital conotruncal defects most commonly reported in veterinary medicine include aorto-pulmonary window and persistent truncus arteriosus. We report a case of an anomalous vessel connecting the ascending aorta to the right pulmonary artery causing left-to-right shunting, left-sided volume overload, and pulmonary overcirculation. Transesophageal echocardiography, cardiac catheterization, and contrast-enhanced computed tomography assisted in the diagnosis and facilitated the surgical correction of the anomalous vessel. The authors hypothesize this defect represents an unusual anomalous vessel connecting the ascending aorta to the right pulmonary artery.

Aortic dissection associated with an obstructive aortic chondrosarcoma in a dog.

A 6-year-old, 35-kg, female spayed German wirehaired pointer was referred for evaluation of collapse/seizure-like activity and a suspected mediastinal mass. Echocardiographic examination revealed an obstructive, intraluminal aortic mass with aortic dissection. Gross and histopathological findings confirmed the aortic dissection with right pulmonary artery compression and an aortopulmonary fistula. The mass was histologically consistent with an intraluminal chondrosarcoma. To the authors knowledge this case represents only the second case of aortic chondrosarcoma in a dog, and interestingly the first case in either a dog or human to have aortic dissection associated with aortic obstruction by an intraluminal aortic tumor.

Doppler-derived deformation imaging in unsedated healthy adult dogs.

OBJECTIVES: To evaluate feasibility, repeatability and reproducibility (R&R) of Doppler-derived deformation imaging (DI) in healthy adult dogs. ANIMALS, MATERIALS AND METHODS: Forty-nine dogs underwent physical examination, ECG, blood pressure measurement and echocardiography. Doppler-derived DI parameters obtained from six selected Regions of Interest (ROI) within the left ventricle (LV) were: strain (S), systolic strain rate (SSR), strain rate E wave (SRE), and strain rate A wave (SRA). The averages of the six ROIs were calculated and labeled avS, avSSR, avSRE, and avSRA. Randomly selected dogs underwent two echocardiographic studies to evaluate intraoperator (n=14) and interoperator (n=17) variability. RESULTS: DI data were obtained in 87.2% of dogs and 77.2% of ROIs. Compared to controls, avSSR was significantly reduced in Doberman Pinchers (DP) and it was increased in dogs < 30 kg, compared to dogs > 30 kg. The intraoperator Coefficient of Variability (CV) for some ROIs was greater than 15% but for averaged measurements it was < or = 5.0%. Interoperator CV varied widely but were all < 15% for avSSR, avS, and avSRA. CONCLUSIONS: The CV for Doppler-derived DI varied widely. Averaging values from multiple ROIs improved R&R. DI may help elucidate differences in LV mechanics between canine breeds.

Percutaneous occlusion of a muscular ventricular septal defect with an Amplatzer muscular VSD occluder.

Ventricular septal defects are a relatively common congenital cardiac disease that, when severe, can be associated with substantial morbidity and mortality. Several minimally invasive methods of repair have been described in the human literature. This report describes the first case of percutaneous closure of a naturally occurring muscular septal defect using an Amplatzer occluder in a dog affected by concurrent pulmonic stenosis. Based on this experience catheter-based occlusion of muscular ventricular septal defects is a feasible option in dogs. Further studies are necessary to identify the attributes and limitations of the technique.

Canine heterophilic antibodies as a source of false-positive B-type natriuretic peptide sandwich ELISA results.

BACKGROUND: Interference by heterophilic antibodies is a well-known cause of false-positive sandwich ELISA results in human medicine. They are considered rarely in veterinary species and have not been characterized but could become important as newer, highly sensitive sandwich immunoassay technologies are developed. OBJECTIVES: The goals of this study were to use a B-type natriuretic peptide (BNP-32) sandwich ELISA to determine the effect of heterophilic antibodies on test performance; to characterize canine heterophilic antibodies; and to develop and test a method for heterophilic antibody removal. METHODS: A sandwich ELISA was developed using a mouse IgG(1)K monoclonal and a rabbit polyclonal antibody to two synthetic peptides of canine BNP-32. The effects on false-positive results of heterophilic antibody depletion and blocking by various techniques were compared. The titers of canine heterophilic antibodies were compared with various blood antigens from other species and the relative amount of canine IgG was compared with that of IgM heterophilic antibody. RESULTS: Heterophilic antibodies in dog plasma were shown to be capable of causing false-positive ELISA results. They reacted with blood proteins from a variety of animal species at relatively low titers and consisted of both IgG and IgM. Protein A agarose antibody precipitation, in conjunction with mouse IgG(1)K blocking antibody, was effective in eliminating false-positive sandwich ELISA results while retaining adequate test performance. CONCLUSIONS: Canine heterophilic antibodies can interfere with sandwich ELISA assays and cause false-positive test results. An effective technique for their removal that has a potentially broad application was developed, and allows measurement of canine blood constituents at low picomolar concentrations.

Third degree atrioventricular block and sudden death secondary to acute myocarditis in a dog.

Third degree atrioventricular (AV) block in dogs is thought to be most frequently characterized by non-specific fibrotic changes in the AV node. However, it may occur secondary to an undiagnosed inflammatory process. We report a case of third degree AV block in a dog, secondary to acute lymphocytic-plasmacytic myocarditis that resulted in sudden death. This dog had cardiac troponin I levels of 44.65 ng/mL (normal <0.11 ng/mL). The serum cardiac troponin I level was five times higher than any other AV block patient measured in our laboratory, and was also substantially higher than in dogs with chronic valve disease or dilated cardiomyopathy. The severe myocardial necrosis observed at necropsy correlated with the degree of cardiac troponin I elevation. This report suggests that measurement of cardiac troponin I may be an indicated test before pacemaker implantation in dogs with third degree AV block.

Distinguishing cardiac and noncardiac dyspnea in 48 dogs using plasma atrial natriuretic factor, B-type natriuretic factor, endothelin, and cardiac troponin-I.

BACKGROUND: It is challenging to differentiate congestive heart failure (CHF) from noncardiac cause of dyspnea. HYPOTHESIS: Circulating concentrations of atrial natriuretic peptide (NT-proANP), B-type natriuretic peptide (BNP), endothelin-I (ET-1), and cardiac troponin-I (cTnI) can be used to help distinguish between cardiac and noncardiac causes of dyspnea in dogs. ANIMALS: Forty-eight client-owned dogs admitted to a veterinary teaching hospital for respiratory distress. METHODS: Blood samples from patients were prospectively obtained. The etiology of dyspnea was determined by using physical examination, thoracic radiographs, and echocardiography. RESULTS: CHF was diagnosed in 22 dogs, and dyspnea of noncardiac origin (noHD group) was diagnosed in 26 dogs. Analyses revealed significant difference between groups for NT-proANP (geometric mean, 95% confidence [CI]; no HD: 0.26 nmol/mL, 95% CI 0.17-1.09; CHF: 1.38 nmol/mL, 95% CI 1.09-1.74 nmol/mL; P < .0001), BNP (noHD: 12.18 pg/mL, 95% CI 10.91-16.17 pg/mL; CHF: 34.97 pg/mL, 95% CI 23.51-52.02 pg/mL; P < .0001), and ET-1 (noHD: 0.32 fmol/mL, 95% CI 0.23-0.46 fmol/mL; CHF: 1.26 fmol/mL, 95% CI 0.83-1.91 fmol/mL; P < .0001). Plasma cTnI concentrations were not significantly different between groups (noHD: 0.29 ng/mL, 95% CI 0.12-0.72 ng/mL; CHF: 0.42 ng/mL, 95% CI 0.18-0.97, P = .53). Receiver operating curves indicated areas under the curve for NT-proANP, BNP, and ET-1 of 0.946, 0.886, and 0.849, respectively. CONCLUSIONS AND CLINICAL IMPORTANCE: Plasma NT-proANP, BNP, and ET-1, but not cTnI, appear useful for distinguishing between dogs with cardiac and noncardiac causes of dyspnea, with plasma NT-proANP having the highest sensitivity (95.5%) and specificity (84.6%).

Prospective screening for occult cardiomyopathy in dogs by measurement of plasma atrial natriuretic peptide, B-type natriuretic peptide, and cardiac troponin-I concentrations.

OBJECTIVE: To evaluate the use of measuring plasma concentrations of atrial natriuretic peptide (ANP), B-type natriuretic peptide (BNP), and cardiac troponin-I (cTnI) to detect dogs with occult dilated cardiomyopathy (DCM). ANIMALS: 118 client-owned dogs. PROCEDURES: Dogs were prospectively examined by use of ECG; echocardiography; and evaluation of concentrations of ANP, BNP, and cTnI. Occult DCM was diagnosed by evaluation of echocardiographic left ventricular dimensions and detection of ventricular arrhythmias on ECG. Sensitivity and specificity of assays for measurement of plasma concentrations of ANP, BNP, and cTnI to detect dogs with occult DCM were determined. RESULTS: Occult DCM was diagnosed in 21 dogs. A concentration of > 6.21 pg/mL for BNP had a sensitivity of 95.2% and specificity of 61.9% for identifying dogs with occult DCM. In contrast, concentrations of ANP and cTnI had relatively low predictive values. CONCLUSIONS AND CLINICAL RELEVANCE: Blood-based screening for occult DCM in dogs can be accomplished by use of a BNP assay. Additional studies should be performed to optimize this method of screening dogs to detect occult DCM.

Carvedilol in dogs with dilated cardiomyopathy.

BACKGROUND: Dilated cardiomyopathy (DCM) is characterized by reduced systolic function, heightened sympathetic tone, and high morbidity and mortality. Little is known regarding the safety and efficacy of beta-blocker treatment in dogs with DCM. HYPOTHESIS: Carvedilol improves echocardiographic and neurohormonal variables in dogs with DCM over a 4-month treatment period. METHODS: Prospective, placebo-controlled, double-blinded randomized study. Dogs with DCM underwent echocardiography, ECG, thoracic radiographs, and neurohormonal profiling, followed by titration onto carvedilol (0.3 mg/kg q12h) or placebo over a 4-week period and subsequently received 3 months of therapy. Primary study endpoints included left ventricular volume and function. RESULTS: Sixteen dogs received carvedilol and 7 received placebo. At study end, 13 carvedilol dogs and 5 placebo dogs were alive. There was no difference in the mean percentage change in left ventricular volume at end-diastole (LVVd), left ventricular end-systolic volume (LVVs), and ejection fraction (EF) between treatment groups, suggesting that both groups experienced similar amounts of disease progression. Carvedilol treatment did not result in significant changes in neurohormonal activation, radiographic heart size, heart rate, or owner perceived quality-of-life. Baseline B-type natriuretic peptide (BNP) predicted dogs in the carvedilol-treated group that maintained or improved their EF over the study duration. CONCLUSIONS AND CLINICAL IMPORTANCE: Carvedilol administration did not improve echocardiographic or neurohormonal indicators of heart function. The lack of effect may be related to severity of disease, carvedilol dose, or brevity of follow-up time. Statistical power of the present study was adversely affected by a high fatality rate in study dogs and small sample size.

Characterization of canine mitochondrial protein expression in natural and induced forms of idiopathic dilated cardiomyopathy.

OBJECTIVE: To map canine mitochondrial proteins and identify qualitative and quantitative differences in heart mitochondrial protein expression between healthy dogs and dogs with naturally occurring and induced dilated cardiomyopathy (DCM). SAMPLE POPULATION: Left ventricle samples were obtained from 7 healthy dogs, 7 Doberman Pinschers with naturally occurring DCM, and 7 dogs with induced DCM. PROCEDURES: Fresh and frozen mitochondrial fractions were isolated from the left ventricular free wall and analyzed by 2-dimensional electrophoresis. Protein spots that increased or decreased in density by >or= 2-fold between groups were analyzed by matrix-assisted laser desorption/ionization time-of-flight mass spectrometry or quadrupole selecting, quadrupole collision cell, time-of-flight mass spectrometry. RESULTS: Within narrow pH gradients of control canine heart mitochondrial samples, a total of 1,528 protein spots were revealed. Forty subunits of heart mitochondrial proteins that differ significantly from control tissues were altered in tissue specimens from dogs with naturally occurring and induced forms of DCM. The most affected heart mitochondrial proteins in both groups were those of oxidative phosphorylation (55%). Upregulation of manganese superoxide dismutase was suggestive of heart oxidative injury in tissue specimens from dogs with both forms of DCM. Evidence of apoptosis was associated with overexpression of the heart mitochondrial voltage-dependent anion channel-2 protein and endonuclease G in tissue specimens from dogs with induced DCM. CONCLUSIONS AND CLINICAL RELEVANCE: Alterations of heart mitochondrial proteins related to oxidative phosphorylation dysfunction were more prevalent in tissue specimens from dogs with induced or naturally occurring DCM, compared with those of control dogs.

Correlation of mitochondrial protein expression in complexes I to V with natural and induced forms of canine idiopathic dilated cardiomyopathy.

OBJECTIVE: To identify qualitative and quantitative differences in cardiac mitochondrial protein expression in complexes I to V between healthy dogs and dogs with natural or induced dilated cardiomyopathy (DCM). SAMPLE POPULATION: Left ventricle samples were obtained from 7 healthy dogs, 7 Doberman Pinschers with naturally occurring DCM, and 7 dogs with DCM induced by rapid right ventricular pacing. PROCEDURES: Fresh and frozen mitochondrial fractions were isolated from the left ventricular free wall and analyzed by 2-dimensional electrophoresis. Protein spots that increased or decreased in density by 2-fold or greater between groups were analyzed by matrix-assisted laser desorption/ionization time-of-flight mass spectrometry or quadrupole selecting, quadrupole collision cell, time-of-flight mass spectrometry. RESULTS: A total of 22 altered mitochondrial proteins were identified in complexes I to V. Ten and 12 were found in complex I and complexes II to V, respectively. Five were mitochondrial encoded, and 17 were nuclear encoded. Most altered mitochondrial proteins in tissue specimens from dogs with naturally occurring DCM were associated with complexes I and V, whereas in tissue specimens from dogs subjected to rapid ventricular pacing, complexes I and IV were more affected. In the experimentally induced form of DCM, only nuclear-encoded subunits were changed in complex I. In both disease groups, the 22-kd subunit was downregulated. CONCLUSIONS AND CLINICAL RELEVANCE: Natural and induced forms of DCM resulted in altered mitochondrial protein expression in complexes I to V. However, subcellular differences between the experimental and naturally occurring forms of DCM may exist.