Suzanne M. Cunningham

Association of Dilated Cardiomyopathy with the Striatin Mutation Genotype in Boxer Dogs

BACKGROUND Myocardial disease in the Boxer dog is characterized by 1 of 2 clinical presentations, dilated cardiomyopathy (DCM) characterized by ventricular systolic dysfunction, dilatation and tachyarrhythmias, and arrhythmogenic right ventricular cardiomyopathy (ARVC) characterized by ventricular tachyarrhythmias, syncope, and sudden death. Boxer ARVC has been associated with a deletion in the striatin gene in some families. HYPOTHESIS/OBJECTIVES We hypothesized that both presentations represent a single disease, and the development of DCM in the Boxer is associated with the striatin deletion. ANIMALS Thirty-three adult Boxer dogs with DCM, 29 adult Boxer dogs with the striatin deletion and ARVC, and 16 Boxers without cardiac disease. METHODS DNA samples were evaluated for the striatin deletion. Association of the deletion with the DCM phenotype was tested by a Fishers exact test. T-tests were used to evaluate potential differences between the positive heterozygous and positive homozygous groups with DCM with regard to age, LVIDD, LVIDS, and FS%. RESULTS Thirty of 33 dogs with DCM were positive for the striatin deletion. The striatin mutation and the homozygous genotype were strongly associated with the DCM phenotype (P < .001 and P = .005). There was no statistical difference between the heterozygous and homozygous groups with regard to age and echocardiographic measurements. CONCLUSIONS AND CLINICAL IMPORTANCE This study demonstrates an association between DCM in the Boxer dog and the striatin mutation, particularly with the homozygous genotype. The observation that 3/33 dogs developed DCM and lacked the striatin mutation suggests that there is at least 1 other cause of DCM in the Boxer dog.

Use of pimobendan in 170 cats (2006–2010)

HYPOTHESIS/OBJECTIVES To describe the therapeutic use of pimobendan in cats, describe the patient population to which it was administered, document potential side effects and report the clinical course following administration of pimobendan in conjunction with standard heart failure therapy. It is hypothesized that cats with advanced heart disease including congestive heart failure from a variety of causes will tolerate pimobendan with a minimum of side effects when used in treatment in conjunction with a variety of other medications. ANIMALS, MATERIALS AND METHODS One hundred and seventy client owned cats with naturally occurring heart disease, one hundred and sixty four of which had congestive heart failure. Medical records were reviewed and owners and referring veterinarians were contacted for follow-up data. Data collected included pimobendan dose, other medications administered concurrently, data collected at physical examination, presence or absence of heart failure, adverse effects, classification of heart disease, echocardiographic data and survival time. The data were analyzed for significance between the initial visit and any follow-up visits. RESULTS All cats were treated with pimobendan. The median pimobendan dose was 0.24 mg/kg q 12 h. Pimobendan was used in combination with multiple concurrent medications including angiotensin converting enzyme inhibitors, diuretics and anti-thrombotics. Five cats (3.0%) had potential side effects associated with pimobendan. One cat (0.6%) had presumed side effects severe enough to discontinue pimobendan use. Median survival time for 164 cats with congestive heart failure after initiation of pimobendan was 151 days (range 1-870). CONCLUSION Pimobendan appears to be well tolerated in cats with advanced heart disease when used with a variety of concurrent medications. Randomized controlled studies need to be performed to accurately assess whether it is efficacious for treatment of congestive heart failure in cats.

Systemic Inflammation and Endothelial Dysfunction in Dogs with Congestive Heart Failure

BACKGROUND Congestive heart failure (CHF) is associated with endothelial dysfunction in people and in dogs with experimentally induced CHF, but this is not well characterized in dogs with naturally occurring CHF. HYPOTHESIS/OBJECTIVES To evaluate endothelial function via assessment of reactive hyperemia (RH) in healthy dogs and dogs with CHF, and to assess for relationships with plasma biomarkers of vascular function and clinical markers of disease severity. ANIMALS Twenty client-owned animals with CHF due to myxomatous mitral valve disease (n = 15) or dilated cardiomyopathy (n = 5) and 17 healthy control dogs. METHODS Prospective case-controlled observational study. Dogs underwent blood sampling, echocardiography, and Doppler assessment of brachial artery velocity (VTI) at baseline and during reactive hyperemia (RH-VTI). RH-VTIs between control dogs and dogs with CHF were compared, and the relationships between RH-VTI, clinical parameters, and plasma biomarkers were assessed. RESULTS Dogs with CHF (96.5 ± 51.7%) had an attenuated % increase in VTI during RH compared to healthy controls (134.8 ± 58.7%; P = .04). Increasing ISACHC class (R(2) = 0.24; P = .004), plasma NT-proBNP (R(2) = 0.15; P = .03) and CRP (R(2) = 0.2; P = .02) were associated with reduced RH-VTI. Increased plasma CRP, NO(x) , and NT-proBNP concentrations were found in dogs with CHF (P < .02 for all). No differences were detected in other plasma markers. CONCLUSIONS AND CLINICAL IMPORTANCE Dogs with CHF have an attenuated RH response, and increased plasma CRP and NO(x) concentrations. Doppler assessment of RH velocity could represent a novel noninvasive method of evaluating endothelial function in the dog.

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.

Successful treatment of pacemaker-induced stricture and thrombosis of the cranial vena cava in two dogs by use of anticoagulants and balloon venoplasty

CASE DESCRIPTION 2 castrated male Labrador Retrievers (dogs 1 and 2) were evaluated 3 to 4 years after placement of a permanent pacemaker. Dog 1 was evaluated because of a large volume of chylous pleural effusion. Dog 2 was admitted for elective replacement of a pacemaker. CLINICAL FINDINGS Dog 1 had mild facial swelling and a rapidly recurring pleural effusion. Previously detected third-degree atrioventricular block had resolved. Cranial vena cava (CVC) syndrome secondary to pacemaker-induced thrombosis and stricture of the CVC was diagnosed on the basis of results of ultrasonography, computed tomography, and venous angiography. Dog 2 had persistent third-degree atrioventricular block. Intraluminal caval stricture and thrombosis were diagnosed at the time of pacemaker replacement. Radiographic evidence of pleural effusion consistent with CVC syndrome also was detected at that time. TREATMENT AND OUTCOME Dog 1 improved after treatment with unfractionated heparin and a local infusion of recombinant tissue-plasminogen activator. Balloon venoplasty was performed subsequently to relieve the persistent caval stricture. In dog 2, balloon dilatation of the caval stricture was necessary to allow for placement of a new pacing lead. Long-term anticoagulant treatment was initiated in both dogs. Long-term (> 6 months) resolution of clinical signs was achieved in both dogs. CLINICAL RELEVANCE Thrombosis and stricture of the CVC are possible complications of a permanent pacemaker in dogs. Findings suggested that balloon venoplasty and anticoagulation administration with or without thrombolytic treatment can be effective in the treatment of dogs with pacemaker-induced CVC syndrome.

Multi-centered investigation of a point-of-care NT-proBNP ELISA assay to detect moderate to severe occult (pre-clinical) feline heart disease in cats referred for cardiac evaluation ☆

OBJECTIVE To prospectively evaluate the diagnostic accuracy of a point-of-care (POC) N-terminal pro-B-type natriuretic peptide (NT-proBNP) ELISA to assess the likelihood of moderate to severe occult heart disease (OcHD) in a clinical population of cats suspected to have heart disease. ANIMALS One hundred and forty-six asymptomatic client-owned cats with a heart murmur, gallop rhythm, arrhythmia, or cardiomegaly. METHODS Physical examination, blood pressure measurement and echocardiography were performed prospectively. Point-of-care ELISA was visually assessed as either positive or negative by a reader blinded to the echocardiographic results. RESULTS Forty-three healthy cats, 50 mild OcHD, 31 moderate OcHD, 6 severe OcHD, and 16 cats equivocal for OcHD were examined. Cats with OcHD included 65 with hypertrophic cardiomyopathy, 6 with restrictive or unclassified cardiomyopathy, 1 with arrhythmogenic right ventricular cardiomyopathy, and 15 with non-cardiomyopathic forms of heart disease. Point-of-care ELISA differentiated cats with moderate or severe OcHD with sensitivity/specificity of 83.8%/82.6% and overall accuracy of 82.9%. Positive POC ELISA increased likelihood of moderate or severe OcHD by a factor of 4.8 vs. those that tested negative. Point-of-care ELISA differentiated cats with moderate or severe cardiomyopathic OcHD with sensitivity/specificity of 88.6%/81.3% and overall accuracy of 83.2%. CONCLUSION In a select sample of cats referred for cardiac evaluation, positive POC NT-proBNP ELISA increases likelihood of moderate to severe OcHD while negative POC NT-proBNP ELISA result excludes moderate to severe OcHD.

Brain structural abnormalities in Doberman pinschers with canine compulsive disorder.

Obsessive compulsive disorder (OCD) is a debilitating condition, the etiology of which is poorly understood, in part because it often remains undiagnosed/untreated for a decade or more. Characterizing the etiology of compulsive disorders in animal models may facilitate earlier diagnosis and intervention. Doberman pinschers have a high prevalence of an analogous behavioral disorder termed canine compulsive disorder (CCD), which in many cases responds to treatments used for OCD. Thus, studies of CCD may help elucidate the etiology of compulsive disorders. We compared brain structure in Dobermans with CCD (N=8) and unaffected controls (N=8) to determine whether CCD is associated with structural abnormalities comparable to those reported in humans with OCD. We obtained 3 Tesla magnetic resonance structural and diffusion images from anesthetized Dobermans and subjected images to segmentation, voxel based morphometry, and diffusion tensor analyses. CCD dogs exhibited higher total brain and gray matter volumes and lower dorsal anterior cingulate cortex and right anterior insula gray matter densities. CCD dogs also had higher fractional anisotropy in the splenium of the corpus callosum, the degree of which correlated with the severity of the behavioral phenotype. Together, these findings suggest that CCD is associated with structural abnormalities paralleling those identified in humans with OCD. Accordingly, the CCD model, which has a number of advantages over other animal models of OCD, may assist in establishing the neuroanatomical basis for and etiology of compulsive disorders, which could lead to earlier diagnosis of and new treatments for humans and animals with these disorders.

Echocardiographic ratio indices in overtly healthy Boxer dogs screened for heart disease.

BACKGROUND Boxer dogs are routinely screened by echocardiography to exclude congenital and acquired heart disease. Individuals of a given breed may span a large range of body sizes, potentially invalidating linear regression of M-mode measurements against body weight. Echocardiographic ratio indices (ERIs) provide a novel method of characterizing echocardiographic differences between Boxers and other dog breeds. HYPOTHESIS ERIs obtained from overtly healthy Boxer dogs presented for cardiac screening will be different from ERIs established for normal non-Boxer dogs, and those differences will be unrelated to aortic velocity or systolic blood pressure. ANIMALS Eighty-one Boxers with no outward clinical signs of heart disease were studied. METHODS All dogs were examined by 2-dimensional, M-mode, and Doppler echocardiography. M-mode measurements were used to perform ERI calculations, and the indices in Boxers were compared between Boxers with varying severity of arrhythmia and those of normal non-Boxer dogs. RESULTS Differences in weight-based ERIs, which reflect increased thickness of the left ventricular free wall (LVW) and interventricular septum (IVS) and smaller aortic size, were found in overtly healthy Boxer dogs compared with normal non-Boxer dogs. ERIs of left atrial and LV cavity size in overtly healthy Boxers were not significantly different from those of non-Boxer dogs. CONCLUSIONS AND CLINICAL IMPORTANCE Boxer dogs may have an increased relative thickness of the LVW and IVS that is independent of aortic size, aortic velocity, or arterial blood pressure, and this morphology should be taken into consideration when screening Boxers by echocardiography.

Evaluation of a training course in focused echocardiography for noncardiology house officers

Objective To determine whether a training course in focused echocardiography can improve the proficiency of noncardiology house officers in accurately interpreting cardiovascular disease and echocardiography findings in dogs entering the emergency room setting. Design Prospective, blinded, educational study. Setting University veterinary teaching hospital. Study Subjects House officers underwent training in focused echocardiography. Fifteen dogs, including normal dogs and dogs with stable congenital or acquired cardiac disease, were used as study subjects during the laboratory session. Interventions A 6-hour curriculum on focused echocardiography was developed that included didactic lectures, clinical cases, and hands-on echocardiography. Measurements and Main Results Pre- and postcourse written examinations were administered to participants. House officers attended didactic lectures that were subsequently followed by a hands-on laboratory session and practical examination, which involved performing transthoracic echocardiography on dogs with and without cardiovascular disease. Twenty-one house officers completed the focused echocardiography training course. Written examination scores were 57 ± 12% before and 75 ± 10% after training (P 6 hours. Conclusion A focused echocardiography training course improved knowledge and yielded acceptable proficiency in some echocardiographic findings commonly identified in the emergency room. This training course was not able to provide the skills needed for house officers to accurately assess fluid volume status, identify cardiac masses, ventricular enlargement or hypertrophy, and certain cardiac diseases.OBJECTIVE To determine whether a training course in focused echocardiography can improve the proficiency of noncardiology house officers in accurately interpreting cardiovascular disease and echocardiography findings in dogs entering the emergency room setting. DESIGN Prospective, blinded, educational study. SETTING University veterinary teaching hospital. STUDY SUBJECTS House officers underwent training in focused echocardiography. Fifteen dogs, including normal dogs and dogs with stable congenital or acquired cardiac disease, were used as study subjects during the laboratory session. INTERVENTIONS A 6-hour curriculum on focused echocardiography was developed that included didactic lectures, clinical cases, and hands-on echocardiography. MEASUREMENTS AND MAIN RESULTS Pre- and postcourse written examinations were administered to participants. House officers attended didactic lectures that were subsequently followed by a hands-on laboratory session and practical examination, which involved performing transthoracic echocardiography on dogs with and without cardiovascular disease. Twenty-one house officers completed the focused echocardiography training course. Written examination scores were 57 ± 12% before and 75 ± 10% after training (P < 0.001). Following the course, 97% of participants in the practical examination were able to obtain the correct right parasternal short- or long-axis view. Posttraining, most participants correctly identified pleural effusion (90%) and pericardial effusion (95%) and discriminated normal atrial size from atrial enlargement (86%). However, successful identification of a cardiac mass, volume status, and ability to recognize a poor quality study as nondiagnostic remained relatively low. Most trainees responded that the length of hands-on laboratory training was too abbreviated and that the course should be > 6 hours. CONCLUSION A focused echocardiography training course improved knowledge and yielded acceptable proficiency in some echocardiographic findings commonly identified in the emergency room. This training course was not able to provide the skills needed for house officers to accurately assess fluid volume status, identify cardiac masses, ventricular enlargement or hypertrophy, and certain cardiac diseases.

Body size and metabolic differences in Maine Coon cats with and without hypertrophic cardiomyopathy

An interplay between growth, glucose regulation and hypertrophic cardiomyopathy (HCM) may exist, but has not been studied in detail. The purpose of this study was to characterize morphometric features, insulin-like growth factor-1 (IGF-1) and glucose metabolism in Maine Coon cats with HCM. Body weight, body condition score (BCS), head length and width, and abdominal circumference were measured in Maine Coon cats >2 years of age. Echocardiography and thoracic radiography (for measurement of humerus length, and fourth and twelfth vertebrae length) were also performed. Blood was collected for biochemistry profile, DNA testing, insulin and IGF-1. Sixteen of 63 cats had HCM [myosin binding protein C (MYBPC)+, n = 3 and MYBPC−, n = 13] and 47/63 were echocardiographically normal (MYBPC+, n = 17 and MYBPC−, n = 30). There were no significant differences in any measured parameter between MYBPC+ and MYBPC− cats. Cats with HCM were significantly older (P <0.001), heavier (P = 0.006), more obese (P = 0.008), and had longer humeri (P = 0.02) compared with the HCM− group. Cats with HCM also had higher serum glucose (P = 0.01), homeostasis model assessment (HOMA) and IGF-1 (P = 0.01) concentrations, were from smaller litters (P = 0.04), and were larger at 6 months (P = 0.02) and at 1 year of age (P = 0.03). Multivariate analysis revealed that age (P <0.001), BCS (P = 0.03) and HOMA (P = 0.047) remained significantly associated with HCM. These results support the hypothesis that early growth and nutrition, larger body size and obesity may be environmental modifiers of genetic predisposition to HCM. Further studies are warranted to evaluate the effects of early nutrition on the phenotypic expression of HCM.