Relationship of plasma N-terminal pro-brain natriuretic peptide concentrations to heart failure classification and cause of respiratory distress in dogs using a 2nd generation ELISA assay.

BACKGROUND: Cardiac biomarkers provide objective data that augments clinical assessment of heart disease (HD). HYPOTHESIS/OBJECTIVES: Determine the utility of plasma N-terminal pro-brain natriuretic peptide concentration [NT-proBNP] measured by a 2nd generation canine ELISA assay to discriminate cardiac from noncardiac respiratory distress and evaluate HD severity. ANIMALS: Client-owned dogs (n = 291). METHODS: Multicenter, cross-sectional, prospective investigation. Medical history, physical examination, echocardiography, and thoracic radiography classified 113 asymptomatic dogs (group 1, n = 39 without HD; group 2, n = 74 with HD), and 178 with respiratory distress (group 3, n = 104 respiratory disease, either with or without concurrent HD; group 4, n = 74 with congestive heart failure [CHF]). HD severity was graded using International Small Animal Cardiac Health Council (ISACHC) and ACVIM Consensus (ACVIM-HD) schemes without knowledge of [NT-proBNP] results. Receiver-operating characteristic curve analysis assessed the capacity of [NT-proBNP] to discriminate between dogs with cardiac and noncardiac respiratory distress. Multivariate general linear models containing key clinical variables tested associations between [NT-proBNP] and HD severity. RESULTS: Plasma [NT-proBNP] (median; IQR) was higher in CHF dogs (5,110; 2,769-8,466 pmol/L) compared to those with noncardiac respiratory distress (1,287; 672-2,704 pmol/L; P < .0001). A cut-off >2,447 pmol/L discriminated CHF from noncardiac respiratory distress (81.1% sensitivity; 73.1% specificity; area under curve, 0.84). A multivariate model comprising left atrial to aortic ratio, heart rate, left ventricular diameter, end-systole, and ACVIM-HD scheme most accurately associated average plasma [NT-proBNP] with HD severity. CONCLUSIONS AND CLINICAL IMPORTANCE: Plasma [NT-proBNP] was useful for discriminating CHF from noncardiac respiratory distress. Average plasma [NT-BNP] increased significantly as a function of HD severity using the ACVIM-HD classification scheme.

Familial subvalvular aortic stenosis in golden retrievers: inheritance and echocardiographic findings.

OBJECTIVES: To describe the echocardiographic findings and pedigree analysis of golden retrievers with subvalvular aortic stenosis. METHODS: Seventy-three golden retrievers were evaluated by auscultation and echocardiography. A subcostal continuous-wave Doppler aortic velocity ê2·5 m/s and presence of a left basilar systolic ejection murmur were required for diagnosis of subvalvular aortic stenosis. Three echocardiographic characteristics were recorded: evidence of aortic insufficiency, subvalvular ridge or left ventricular hypertrophy. A disease status score was calculated by totalling the number of echocardiographic -characteristics per subject. RESULTS: Thirty-two of 73 dogs were affected and their aortic velocities were as follows: range 2·5 to 6·8 m/s, median 3·4 m/s and standard deviation 1·2 m/s. Echocardiographic characteristics of 32 affected dogs were distributed as follows: left ventricular hypertrophy 12 of 32, aortic insufficiency 20 of 32 and subvalvular ridge 20 of 32. Disease status score ranged from 0 to 3 with a median of 2. There was a statistically significant correlation between aortic velocity and disease status score (r=0·644, P<0·0001). Subvalvular aortic stenosis was observed in multiple generations of several families and appears familial. CLINICAL SIGNIFICANCE: Subvalvular aortic stenosis in the golden retriever is familial. Severity of stenosis correlates well with cumulative presence of echocardiographic characteristics (left ventricular hypertrophy, subvalvular ridge and aortic insufficiency).

Multicenter evaluation of plasma N-terminal probrain natriuretic peptide (NT-pro BNP) as a biochemical screening test for asymptomatic (occult) cardiomyopathy in cats.

BACKGROUND: B-type natriuretic peptide concentrations reliably distinguish between cardiac and respiratory causes of dyspnea, but its utility to detect asymptomatic cats with occult cardiomyopathy (OCM) is unresolved. HYPOTHESIS/OBJECTIVES: Determine whether plasma N terminal probrain natriuretic peptide (NT-proBNP) concentration can discriminate asymptomatic cats with OCM from normal cats, and whether NT-proBNP concentration correlates with clinical, biochemical, and echocardiographic parameters. ANIMALS: One hundred and fourteen normal, healthy cats; 113 OCM cats. METHODS: Prospective, multicenter, case-controlled study. NT-proBNP was prospectively measured and cardiac status was determined from history, physical examination, and M-mode/2D/Doppler echocardiography. Optimal cut-off values were derived using receiver operating characteristic (ROC) curve analysis. RESULTS: NT-proBNP was higher (median, interquartile range [25th and 75th percentiles]) in (1) OCM (186 pmol/L; 79, 478 pmol/L) versus normal (24 pmol/L; 24, 32 pmol/L) (P < .001); and (2) hypertrophic obstructive cardiomyopathy (396 pmol/L; 205, 685 pmol/L) versus hypertrophic cardiomyopathy (112 pmol/L; 48, 318 pmol/L) (P < .001). In OCM, NT-proBNP correlated (1) positively with LVPWd (ρ = 0.23; P = .01), LA/Ao ratio (ρ = 0.31; P < .001), LVs (ρ = 0.33; P < .001), and troponin-I (ρ = 0.64; P < .001), and (2) negatively with %FS (ρ = -0.27; P = .004). Area under ROC curve was 0.92; >46 pmol/L cut-off distinguished normal from OCM (91.2% specificity, 85.8% sensitivity); >99 pmol/L cut-off was 100% specific, 70.8% sensitive. CONCLUSIONS AND CLINICAL IMPORTANCE: Plasma NT-proBNP concentration reliably discriminated normal from OCM cats, and was associated with several echocardiographic markers of disease severity. Further studies are needed to assess test performance in unselected, general feline populations, and evaluate relationships between NT-proBNP concentrations and disease progression.

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.

Practices and outcome of artificial cardiac pacing in 154 dogs.

Artificial pacing (AP) is a treatment for symptomatic bradyarrhythmias unresponsive to medical therapy. This retrospective study was designed to define the practices and outcome of AP in dogs at 7 referral institutions participating in the Companion Animal Pacemaker Registry and Repository (CANPACERS). The indications, implantation techniques, complications, long-term outcome, and owner satisfaction were examined. One hundred fifty-four dogs were identified as undergoing AP from January 1, 1991, to January 1, 1996. Third-degree atrioventricular (AV) block (n = 91; 59%) and sinus node dysfunction (n = 45; 29%) were the most common indications for AP Transvenous endocardial AP systems were implanted in 136 dogs (88%), and epicardial systems were implanted in 18 (12%). Complications associated with AP were reported in 84 dogs (55%). Major complications occurred in 51 dogs (33%), including dislodgement of the pacing lead (n = 15; 10%), generator failure (n = 10; 6%), cardiac arrest during implantation (n = 9; 6%), and infection (n = 7; 5%). Minor complications occurred in 47 dogs (31%), including seroma formation (n = 18; 12%), muscle twitch (n = 17; 11%), and inconsequential arrhythmias (n = 15; 10%). Fourteen dogs (9%) experienced both major and minor complications. Survival analysis revealed 1-, 2-, and 3-year survival rates of 70, 57, and 45%, respectively. Age and presence of preexisting congestive heart failure (CHF) had a negative effect on survival (P = .001). Sixty percent of dogs with preexisting CHF died within 1 year of implantation, whereas 25% of dogs without heart failure died during the same period. Owners rated their satisfaction with the procedure as high in 80% of the dogs.

Polymerase chain reaction analysis for viruses in paraffin-embedded myocardium from dogs with dilated cardiomyopathy or myocarditis.

OBJECTIVE: To perform polymerase chain reaction (PCR) analysis on paraffin-embedded myocardium from dogs with dilated cardiomyopathy (DCM) and dogs with myocarditis to screen for canine parvovirus, adenovirus types 1 and 2, and herpesvirus. SAMPLE POPULATION: Myocardial specimens from 18 dogs with an antemortem diagnosis of DCM and 9 dogs with a histopathologic diagnosis of myocarditis were evaluated. PROCEDURE: Paraffin-embedded myocardial specimens were screened for viral genome by PCR analysis. Positive-control specimens were developed from cell cultures as well as paraffin-embedded tissue specimens from dogs with clinical and histopathologic diagnoses of viral infection with canine parvovirus, adenovirus types 1 and 2, and herpesvirus. The histologic characteristics of all myocardial specimens were classified regarding extent, location, and type of inflammation and fibrosis. RESULTS: Canine adenovirus type 1 was amplified from 1 specimen from a dog with DCM. Canine parvovirus, adenovirus type 2, and herpesvirus were not amplified from any myocardial specimens. Histologic analysis of specimens from dogs with DCM revealed variable amounts of fibrosis; myocardial inflammation was observed in 1 affected dog. Histopathologic analysis of specimens from dogs with myocarditis disclosed variable degrees of inflammation and fibrosis. CONCLUSIONS AND CLINICAL RELEVANCE: Viral agents canine parvovirus, adenovirus types 1 and 2, and herpesvirus are not commonly associated with DCM or active myocarditis in dogs. Additional studies evaluating for nucleic acid from viruses that less commonly affect dogs or different types of infectious agents may be warranted to gain insight into the cause of DCM and myocarditis in dogs.

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.

Radiotelemetry catheter implantation: surgical technique and results in cats.

Arterial blood pressure in cats can be measured by direct or indirect techniques. Most direct measurement techniques require sedation or anesthesia, which decreases blood pressure. The restraint and human intervention needed for indirect techniques cause blood pressure to increase. These limitations make the accurate assessment of blood pressure and the response to antihypertensive medications difficult to interpret. Radiotelemetry allows for direct measurement of the arterial blood pressure and heart rate without sedation, anesthesia, or animal handling during measurement. A surgical technique for the placement of radiotelemetry catheters and the complications associated with the technique have not been described in cats. Our purpose is to provide a detailed description of the placement of the modified implant model TA11PA-C40 (Data Sciences International), with accompanying illustrations, and to discuss complications associated with the procedure. Radiotelemetry catheters were surgically placed in the left femoral artery of 12 cats. The surgical procedure was completed within 50 min, and no surgical complications occurred in any cat. The radiotelemetry catheters were used for an average of 6.5 weeks (range, 5.5 to 9.5 weeks). This technique allows for long-term monitoring of ambulatory blood pressure and heart rate in the research setting. This methodology is especially useful for studies of the pathophysiology of hypertension and assessment of the efficacy of antihypertensive medications.

Retrospective analysis of the clinical utility of ambulatory electrocardiographic (Holter) recordings in syncopal dogs: 44 cases (1991-1995).

The objective of this study was to evaluate retrospectively the clinical utility of ambulatory (Holter) electrocardiographic monitoring in syncopal dogs and to compare the Holter recording with the clinic electrocardiogram (ECG) in these animals. Fifty Holter reports and 44 medical records from 44 dogs were evaluated. A syncopcal episode occurred during monitoring in 24% of the recordings. No obvious relationship was found between the frequency of syncope occurring before Holter recording and the likelihood of a dog having an episode during recording. Holter recordings were helpful in establishing a diagnosis 42% of the time, but no relationship was detected between the frequency of episodes occurring before Holter recording and the likelihood of a diagnostically useful Holter. An arrhythmia was ruled out as the cause of syncope in 12% of the recordings and was implicated as the cause of syncope in 30% of recordings. Of these, 20% were ventricular tachyarrhythmias and 10% were bradyarrhythmias including pacemaker failure. Ambulatory electrocardiographic recordings led to a therapeutic change in 38% of cases. A comparison of the Holter recordings and clinic ECGs documented the expected increased sensitivity for Holter detection of arrhythmias. The average clinic ECG heart rate consistently exceeded the average Holter heart rate with a mean difference between the average heart rates recorded by the two techniques of 31 bpm (range -8-87 bpm).

Effect of enalapril on blood pressure, renal function, and the renin-angiotensin-aldosterone system in cats with autosomal dominant polycystic kidney disease.

OBJECTIVE: To evaluate blood pressure, renal function, and the renin-angiotensin-aldosterone system (RAAS) in cats with autosomal dominant polycystic kidney disease (ADPKD) and to assess the effect of enalapril on these variables. ANIMALS: 6 cats with ADPKD and 6 age-matched healthy cats. PROCEDURE: To measure blood pressure and heart rate, a radiotelemetry catheter was placed in the left femoral artery of each cat. Baseline data collection included 24-hour blood pressure, heart rate, and motor activity. Blood was then collected for analysis of RAAS status and renal function. Enalapril (0.5 mg/kg of body weight, p.o., q 24 h) was administered for 1 week, and data collection was repeated. RESULTS: Differences in baseline blood pressure, heart rate, motor activity, RAAS status, and renal function were not detected between cats with ADPKD and control cats. Hypertension was not documented in cats with ADPKD. Blood pressure was significantly reduced for 15 to 17 hours after treatment with enalapril in both groups. Administration of enalapril also resulted in significant increases in plasma renin activity and significant decreases in angiotensin converting enzyme activity and atrial natriuretic peptide concentration but only minimal changes in glomerular filtration rate and effective renal plasma flow in both groups of cats. CONCLUSIONS AND CLINICAL RELEVANCE: Although hypertension is common in humans with ADPKD, cats with ADPKD were normotensive. Treatment with enalapril (0.5 mg/kg, p.o., q 24 h) significantly reduced blood pressure in normotensive healthy cats and cats with ADPKD, and resulted in predictable changes in RAAS enzyme activities and hormone concentrations. Enalapril had minimal effects on renal function.

Radiographic evaluation of caudal vena cava size in dogs.

Dilation of the caudal vena cava (CVC) on lateral thoracic radiographs is often interpreted as suggestive of right-sided congestive heart failure. To quantitate the clinical utility of evaluating CVC size as an indicator of right-sided heart disease, we compared the ratio of the diameter of the CVC as measured on a left lateral thoracic radiograph to the descending aorta (Ao), length of the thoracic vertebra above the tracheal bifurcation (VL), and width of the right fourth rib (R4) in 35 dogs with right heart disease and 35 control dogs. Each CVC ratio (CVC/Ao, CVC/VL, CVC/R4) was statistically larger in dogs with right heart disease. Response operating characteristic curves and likelihood ratios were used to determine ratios helpful in identifying dogs with right heart disease. A CVC/Ao > 1.50, CVC/VL > 1.30, or CVC/R4 > 3.50 are strongly suggestive of a right-sided heart abnormality in a patient.

Comparison of catheterization and Doppler-derived pressure gradients in a canine model of subaortic stenosis.

The relationship between Doppler-estimated and catheterization-measured pressure gradients was examined by repeated-measures linear regression analysis and difference plots in 15 dogs with naturally occurring subvalvular aortic stenosis. Thirty left ventricular outflow tract gradients were compared during sinus rhythm and 142 gradients during premature or postextrasystolic beats for the following pairs of data: (1) mean catheterization gradient versus mean Doppler gradient, (2) maximal instantaneous catheterization gradient versus maximal Doppler gradient, and (3) peak-to-peak catheterization gradient versus maximal Doppler gradient. The correlation between Doppler-derived and catheterization-derived pressure gradients was excellent (r = 0.99; p < 0.001) for the maximal instantaneous (sinus rhythm: standard error of the estimate [SEE] = 5.7 mm Hg; premature and postextrasystolic beats: SEE = 6.7 mm Hg) and mean gradients (sinus rhythm: SEE = 3.6 mm Hg; premature and postextrasystolic beats: SEE = 4.5 mm Hg). There was also a strong correlation between the peak-to-peak catheterization gradient and the maximal Doppler gradient (sinus rhythm: r = 0.99, p < 0.001, SEE = 5.3 mm Hg; premature and postextrasystolic beats: r = 0.97, p < 0.001, SEE = 7.2 mm Hg). Agreement between the two techniques was best for mean gradients and most disparate for the comparisons of maximal Doppler gradients and peak-to-peak catheterization gradients.

Comparison of transducer placement sites for Doppler echocardiography in dogs with subaortic stenosis.

Effects of transducer placement site and various operators on Doppler echocardiographic measures were evaluated in 12 dogs with subaortic stenosis. Dogs sedated by IV administration of acepromazine and buprenorphine were examined by 2 observers. Maximal aortic velocity and aortic velocity time integral were determined from Doppler aortic velocity spectra recorded, using a 1.9-MHz continuous wave nonimaging transducer placed at 3 echocardiographic sites: left ventricular apex (LA), suprasternal notch (SSN), and subcostal (SC). Doppler-estimated left ventricular-to-aortic pressure gradients were calculated from the traced velocity spectra by application of the modified Bernoulli equation. Each observer recorded high-quality Doppler spectral signals in all dogs from the SC and LA transducer sites and in 83% of dogs from the SSN window. Mean values for maximal aortic velocity and velocity time integral differed among sites (P < 0.05), but not between observers. Maximal velocity and velocity time integral measured from the SC transducer site were higher than those measured from the SSN or LA positions. Presumably, SC transducer placement provided the highest aortic velocities because of optimal alignment with aortic outflow. The maximal pressure gradient estimated from SC velocities exceeded SSN values by 27 mm of Hg and LA measurements by 38 mm of Hg. In this study, the optimal site for the Doppler echocardiographic detection of subaortic stenosis and assessment of this lesion's hemodynamic importance in most affected dogs was the SC position.

Mitral stenosis in 15 dogs.

Mitral stenosis was diagnosed in 15 young to middle-aged dogs. There were 5 Newfoundlands and 4 bull terriers affected, suggesting a breed predisposition for this disorder. Clinical signs included cough, dyspnea, exercise intolerance, and syncope. Soft left apical diastolic murmurs were heard only in 4 dogs, whereas 8 dogs had systolic murmurs characteristic of mitral regurgitation. Left atrial enlargement was the most prominent radiographic feature. Left-sided congestive heart failure was detected by radiographs in 11 dogs within 1 year of diagnosis. Electrocardiographic abnormalities varied among dogs and included atrial and ventricular enlargement, as well as atrial and ventricular arrhythmias. Abnormalities on M-mode and two-dimensional echocardiograms included abnormal diastolic motion of the mitral valve characterized by decreased leaflet separation, valve doming, concordant motion of the parietal mitral valve leaflet, and a decreased E-to-F slope. Increased mitral valve inflow velocities and prolonged pressure half-times were detected by Doppler echocardiography. Cardiac catheterization, performed in 8 dogs, documented a diastolic pressure gradient between the left atrial, pulmonary capillary wedge, or pulmonary artery diastolic pressures and the left ventricular diastolic pressure. Necropsy showed mitral stenosis caused by thickened, fused mitral valve leaflets in 5 dogs and a supramitral ring in another dog. The outcome in affected dogs was poor; 9 of 15 dogs were euthanatized or died by 2 1/2 years of age.