Linda B. Lehmkuhl

Familial Ventricular Arrhythmias in Boxers

The purposes of this study were to evaluate families of Boxers with ventricular arrhythmias to determine whether this disorder is a familial trait and, if so, to determine the mode of inheritance. Eighty-two Boxers were evaluated by physical examination, electrocardiogram, echocardiogram, and 24-hour ambulatory electrocardiogram. Dogs were considered affected if at least 50 premature ventricular complexes (PVCs) were observed during a 24-hour period. All dogs were at least 6 years of age at evaluation. Complete cardiovascular examinations were performed on dogs from 6 extended families. The 2 most complete pedigrees were used to determine the pattern of inheritance. The number of PVCs observed during a 24-hour period in affected dogs ranged from 112 to 4,894 (mean +/- SD, median; 1,309 +/- 2,609, 1,017). The number of PVCs observed during a 24-hour period in the unaffected dogs ranged from 0 to 16 (7 +/- 10, 12). Pedigree evaluation was performed to determine pattern of inheritance. An autosomal dominant pattern was determined to be most likely because a sex predisposition was not observed, affected individuals were observed in every generation, and 2 affected individuals produced unaffected offspring. We conclude that familial ventricular arrhythmias is inherited as an autosomal dominant trait in some Boxers.

Utility of plasma N-terminal pro-brain natriuretic peptide (NT-proBNP) to distinguish between congestive heart failure and non-cardiac causes of acute dyspnea in cats.

BACKGROUND Circulating plasma N-terminal pro-brain natriuretic peptide (NT-proBNP) concentration facilitates emergency diagnosis of congestive heart failure (CHF) in people. Its utility to discriminate between dyspneic cats with CHF vs. primary respiratory disease requires further assessment. Our objectives were to determine if NT-proBNP (1) differentiates dyspneic cats with CHF vs. primary respiratory disease; (2) increases with renal insufficiency; (3) correlates with left atrial dimension, radiographic cardiomegaly, and estimated left ventricular filling pressure (E/E(a)). METHODS NT-proBNP was measured in 167 dyspneic cats (66 primary respiratory disease, 101 CHF) to evaluate (1) relationship with clinical parameters; (2) ability to distinguish CHF from primary respiratory disease; (3) optimal cut-off values using receiver operating characteristic (ROC) curve analysis. RESULTS NT-proBNP (1) was higher (median and inter-quartile [25th-75th] percentile) in CHF (754 pmol/L; 437, 1035 pmol/L) vs. primary respiratory disease (76.5 pmol/L; 24, 180 pmol/L) cohorts (P<0.001); (2) positively correlated in CHF cats with increased inter-ventricular septal end-diastolic thickness (rho=0.266; P=0.007) and LV free wall thickness (rho=0.218; P=0.027), but not with radiographic heart size, left atrial size, left ventricular dimensions, E/E(a) ratio, BUN, creatinine, or thyroxine; (3) distinguished dyspneic CHF cats from primary respiratory disease at 265 pmol/L cut-off value with 90.2% sensitivity, 87.9% specificity, 92% positive predictive value, and 85.3% negative predictive value (area under ROC curve, 0.94). CONCLUSIONS NT-proBNP accurately discriminated CHF from respiratory disease causes of dyspnea.

Prediction of first onset of congestive heart failure in dogs with degenerative mitral valve disease: the PREDICT cohort study.

OBJECTIVE To identify risk factors for first-onset congestive heart failure (CHF) in dogs with degenerative mitral valve disease (DMVD). ANIMALS Eighty-two dogs with and without CHF secondary to DMVD were retrospectively assigned to a derivation cohort. Sixty-five dogs with asymptomatic DMVD were recruited into a prospective validation cohort. METHODS Variables associated with risk of CHF in dogs were identified in a derivation cohort and used to construct a predictive model, which was then prospectively tested through longitudinal examination of a validation cohort. RESULTS Logistic regression analysis of the derivation cohort yielded a predictive model that included the left atrial to aortic root dimension ratio (LA:Ao) and plasma concentration of N-terminal pro-B-type natriuretic peptide (NT-proBNP). When this model was prospectively applied to the validation cohort, it correctly predicted first-onset of CHF in 69.2% of cases. Analysis of the validation cohort revealed that plasma NT-proBNP concentration and indexed left ventricular end-diastolic diameter (LVIDd:Ao) were independent risk factors for development of first-onset CHF in dogs with DMVD (NT-proBNP ≥ 1500 pmol/L, odds ratio (OR), 5.76, 95% confidence interval (CI), 1.37-24.28, P = 0.017; LVIDd:Ao ≥ 3, OR, 6.11, 95% CI, 1.09-34.05, P = 0.039). CONCLUSIONS Measures of left heart size and plasma NT-proBNP concentration independently estimate risk of first-onset of CHF in dogs with DMVD. These parameters can contribute to the management of dogs with DMVD.

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.

Assessment of serum N-terminal pro-B-type natriuretic peptide concentration for differentiation of congestive heart failure from primary respiratory tract disease as the cause of respiratory signs in dogs

OBJECTIVE To determine whether serum N-terminal pro-B-type natriuretic peptide (NT-proBNP) concentration is useful in discriminating between cardiac and noncardiac (ie, primary respiratory tract disease) causes of respiratory signs (ie, coughing, stertor, stridor, excessive panting, increased respiratory effort, tachypnea, or overt respiratory distress) in dogs. DESIGN Multicenter cross-sectional study. ANIMALS P 115 dogs with respiratory signs. PROCEDURES Dogs with respiratory signs were solicited for study. Physical examination, thoracic radiography, and echocardiography were used to determine whether respiratory signs were the result of cardiac (ie, congestive heart failure) or noncardiac (ie, primary respiratory tract disease) causes. Serum samples for NT-proBNP assay were obtained at time of admission for each dog. Receiver-operating characteristic curves were constructed to determine the ability of serum NT-proBNP concentration to discriminate between cardiac and noncardiac causes of respiratory signs. RESULTS Serum NT-proBNP concentration was significantly higher in dogs with cardiac versus noncardiac causes of respiratory signs. In dogs with primary respiratory tract disease, serum NT-proBNP concentration was significantly higher in those with concurrent pulmonary hypertension than in those without. A serum NT-proBNP cutoff concentration > 1,158 pmol/L discriminated between dogs with congestive heart failure and dogs with primary respiratory tract disease with a sensitivity of 85.5% and a specificity of 81.3%. CONCLUSIONS AND CLINICAL RELEVANCE Measuring serum NT-proBNP concentration in dogs with respiratory signs helps to differentiate between congestive heart failure and primary respiratory tract disease as an underlying cause.

Angiographic classification of patent ductus arteriosus morphology in the dog

OBJECTIVES To characterize angiographic morphology and minimum internal transverse diameter of left-to-right shunting patent ductus arteriosus (PDA) in a large series of dogs. BACKGROUND PDA is the most common congenital cardiac malformation in the dog. Transarterial ductal occlusion is increasingly performed to close this defect. While accurate assessment of ductal morphology and luminal diameter is important to assure optimal occlusion using catheter-delivered devices, such information is currently limited. ANIMALS, MATERIALS AND METHODS In 246 dogs representing 31 breeds with left-to-right shunting PDA, right lateral selective aortic angiograms were recorded and reviewed. RESULTS PDA morphology conformed to four general phenotypes (types I, IIA, IIB, and III) which varied according to degree of ductal tapering, and the presence, absence, or location of abrupt ductal narrowing. Minimum internal ductal diameter for all dogs averaged 2.9mm (median, 2.5mm; range, 1.0-9.5mm) and was not correlated to age or body weight. There was no significant difference in minimum internal diameters between types I, IIA or IIB PDA, whereas, type III PDA was significantly wider (p=0.024) than other phenotypes. The most frequently-encountered variant (type IIA) was identified in 54.4% of cases (average minimum internal diameter, 2.3mm [median, 2.2mm; range, 1.0-5.5mm]). CONCLUSIONS PDA angiographic morphology was categorized based upon the degree, presence, or absence of ductal narrowing, and the location of ductal attenuation. When planning PDA repair, this information should assist planning, selection and deployment of transcatheter occluding devices.

Temperature Controlled RF Ablation in Canine Ventricle and Coronary Sinus using 7 Fr or 5 Fr Ablation Electrodes

The safety and lesion volume of temperature controlled radiofrequency ablation (TCRFA) in the right ventricle (RV), left ventricle (LV), and coronary sinus (CS) comparing long 5 Fr to standard tip electrodes have not been previously reported In 1O canines, TCRFA was delivered at a 70°C set point for 30 seconds. Lateral and septal RV lesions were made with either a 5 Fr/5 mm or 7 Fr/4 mm tip. Lateral and septal LV lesions were made with either a 5 Fr/7 mm or 7 Fr/4 mm tip. Proximal and distal CS lesions were made with either a 7 Fr/4 mm, 5 Fr/5 mm or 5 Fr/7 mm tip. Gross and histologic examination of the lesions was completed. Lesion size, tip temperature and power required are related to electrode surface area (SA) when ablating in the RV, LV or CS. 5 Fr/7 mm tips (SA = 36 mm2) tended to create larger lesions than 7 Fr/4 mm tips (SA = 29 mm2) in the LV. 7 Fr4 mm tips tended to create larger lesions than 5 Fr/5 mm tips (SA ‐ 26 mm2) in the RV. 7 Fr/4 mm LV lesions exceeded 7 Fr/4 mm RV lesions due to thicker LV walls. In the CS, 5 Fr/7 mm tips tended to create the largest lesions. In the RV, LV and CS, tips with larger SA tended to have lower temperatures and require higher power. No high temperature or high impedance shutdowns were observed. In conclusion, varying 5 Fr tip length can safely produce larger or smaller lesions compared to those created with 7 Fr/4 mm tips.

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.

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.

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).