Bruce W. Keene

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.

BACKGROUNDnCirculating 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)).nnnMETHODSnNT-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.nnnRESULTSnNT-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).nnnCONCLUSIONSnNT-proBNP accurately discriminated CHF from respiratory disease causes of dyspnea.

A splice site mutation in a gene encoding for PDK4, a mitochondrial protein, is associated with the development of dilated cardiomyopathy in the Doberman pinscher.

Familial dilated cardiomyopathy is a primary myocardial disease that can result in the development of congestive heart failure and sudden cardiac death. Spontaneous animal models of familial dilated cardiomyopathy exist and the Doberman pinscher dog is one of the most commonly reported canine breeds. The objective of this study was to evaluate familial dilated cardiomyopathy in the Doberman pinscher dog using a genome-wide association study for a genetic alteration(s) associated with the development of this disease in this canine model. Genome-wide association analysis identified an area of statistical significance on canine chromosome 14 (prawxa0=xa09.999e−05 corrected for genome-wide significance), fine-mapping of additional SNPs flanking this region localized a signal to 23,774,190–23,781,919 (pxa0=xa00.001) and DNA sequencing identified a 16-base pair deletion in the 5′ donor splice site of intron 10 of the pyruvate dehydrogenase kinase 4 gene in affected dogs (pxa0<xa00.0001). Electron microscopy of myocardium from affected dogs demonstrated disorganization of the Z line, mild to moderate T tubule and sarcoplasmic reticulum dilation, marked pleomorphic mitochondrial alterations with megamitochondria, scattered mitochondria with whorling and vacuolization and mild aggregates of lipofuscin granules. In conclusion, we report the identification of a splice site deletion in the PDK4 gene that is associated with the development of familial dilated cardiomyopathy in the Doberman pinscher dog.

Effect of Pimobendan in Dogs with Preclinical Myxomatous Mitral Valve Disease and Cardiomegaly: The EPIC Study—A Randomized Clinical Trial

Background Pimobendan is effective in treatment of dogs with congestive heart failure (CHF) secondary to myxomatous mitral valve disease (MMVD). Its effect on dogs before the onset of CHF is unknown. Hypothesis/Objectives Administration of pimobendan (0.4–0.6 mg/kg/d in divided doses) to dogs with increased heart size secondary to preclinical MMVD, not receiving other cardiovascular medications, will delay the onset of signs of CHF, cardiac‐related death, or euthanasia. Animals 360 client‐owned dogs with MMVD with left atrial‐to‐aortic ratio ≥1.6, normalized left ventricular internal diameter in diastole ≥1.7, and vertebral heart sum >10.5. Methods Prospective, randomized, placebo‐controlled, blinded, multicenter clinical trial. Primary outcome variable was time to a composite of the onset of CHF, cardiac‐related death, or euthanasia. Results Median time to primary endpoint was 1228 days (95% CI: 856–NA) in the pimobendan group and 766 days (95% CI: 667–875) in the placebo group (P = .0038). Hazard ratio for the pimobendan group was 0.64 (95% CI: 0.47–0.87) compared with the placebo group. The benefit persisted after adjustment for other variables. Adverse events were not different between treatment groups. Dogs in the pimobendan group lived longer (median survival time was 1059 days (95% CI: 952–NA) in the pimobendan group and 902 days (95% CI: 747–1061) in the placebo group) (P = .012). Conclusions and Clinical Importance Administration of pimobendan to dogs with MMVD and echocardiographic and radiographic evidence of cardiomegaly results in prolongation of preclinical period and is safe and well tolerated. Prolongation of preclinical period by approximately 15 months represents substantial clinical benefit.

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

BACKGROUNDnMyocardial 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.nnnHYPOTHESIS/OBJECTIVESnWe hypothesized that both presentations represent a single disease, and the development of DCM in the Boxer is associated with the striatin deletion.nnnANIMALSnThirty-three adult Boxer dogs with DCM, 29 adult Boxer dogs with the striatin deletion and ARVC, and 16 Boxers without cardiac disease.nnnMETHODSnDNA 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%.nnnRESULTSnThirty 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.nnnCONCLUSIONS AND CLINICAL IMPORTANCEnThis 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.

Secondary prevention of cardiogenic arterial thromboembolism in the cat: the double-blind, randomized, positive-controlled feline arterial thromboembolism; clopidogrel vs. aspirin trial (FAT CAT)

OBJECTIVESnTo determine if clopidogrel administration is associated with a reduced likelihood of recurrent cardiogenic arterial thromboembolism (CATE) in cats compared to aspirin administration. Secondary aims were to determine if clopidogrel administration had an effect on the composite endpoint of recurrent CATE and cardiac death and to identify adverse effects of chronic clopidogrel or aspirin therapy.nnnANIMALSnSeventy-five cats that survived a CATE event.nnnMETHODSnMulticenter, double-blind, randomized, positive-controlled study. Cats were assigned to clopidogrel (18.75 mg/cat PO q 24 h) or aspirin (81 mg/cat PO q 72 h). Kaplan-Meier survival curves were created for each endpoint and the log rank test performed to compare treatment groups with respect to time to event and the likelihood of the event occurring.nnnRESULTSnThe mean age of all cats was 8.0 ± 3.5 yr and 57/75 (76%) were male (p < 0.001); 62/75 (83%) were mixed breed with the remainder including Persian, Abyssinian, American Shorthair, Bengal, Birman, Himalayan, Maine Coon, Ragdoll, Snowshoe, and Sphynx breeds. Only 15% (11/75) of cats had a history of heart disease recorded prior to the CATE event. Clopidogrel administration was associated with significantly reduced likelihood of recurrent CATE compared to aspirin (p = 0.024) and had a longer median time to recurrence [443 (95% CI 185-990) days vs. 192 (95% CI 62-364) days, respectively]. Clopidogrel was also associated with a significantly reduced likelihood of the composite endpoint of recurrent CATE or cardiac death (p = 0.033) with a longer median time to event [346 (95% CI 146-495) days vs. 128 (95% CI 58-243) days].nnnCONCLUSIONSnClopidogrel administration significantly reduces the likelihood of recurrent CATE compared with aspirin in cats; both drugs were well tolerated.

Cutting balloon catheterization for interventional treatment of cor triatriatum dexter: 2 cases.

Cutting balloon dilatation was performed successfully in two dogs with cor triatriatum dexter and clinical signs of ascites. The cutting balloon catheter uses incisional microtomes embedded in a balloon catheter. During balloon expansion, these microtomes incise the adjacent tissue, decreasing circumferential wall stress. This theoretically reduces both the likelihood of fracturing the adjacent tissues in an uncontrolled manner and the potential neoproliferative response to standard balloon dilatation and the subsequent incidence of re-stenosis. In both cases described, clinical signs resolved completely following cutting balloon dilatation of the anomalous membrane. Based on the outcome of these 2 cases, cutting balloon dilatation appears to be a viable treatment option for dogs affected with cor triatriatum dexter.

Hybrid cutting balloon dilatation for treatment of cor triatriatum sinister in a cat

A hybrid surgical approach and balloon dilatation were performed successfully in a cat with cor triatriatum sinister and clinical signs of congestive heart failure. Left lateral thoracotomy was used to access the heart and cutting balloon followed by standard balloon dilatation were utilized to dilate the perforation in the anomalous left atrial membrane. Clinical signs resolved completely after dilation of the anomalous left atrial membrane. Based upon the outcome of this case, balloon dilatation appears to be a viable treatment option for cats affected with cor triatriatum sinister.

L-carnitine Supplementation in the Therapy of Canine Dilated Cardiomyopathy

In evaluating any novel therapeutic agent or intervention, the clinician must question the need for as well as the efficacy and safety of the proposed therapy. In an attempt to address these critical questions with regard to the role of L-carnitine supplementation in the therapy of dilated cardiomyopathy, this article reviews the currently available scientific evidence and clinical experience regarding carnitine metabolism and supplementation in the dog.

Complete atrioventricular block secondary to cardiac lymphoma in a dog

Third degree atrioventricular (AV) block was observed in a patient with a roughly spherical mass measuring approximately 1 × 1 × 1 cm, visible in the basilar portion of the interventricular septum on 2-dimensional transthoracic echocardiographic examination. The patient had a brief history of lethargy and episodic collapse, and the owner elected to euthanize the dog after the mass lesion was discovered. Necropsy revealed multiple masses within the interventricular septum, ventricular free walls and atrial myocardium. The final diagnosis was large cell (T-cell) lymphosarcoma.

Supraventricular tachycardia in dogs: 65 cases (1990–2007)

Objective – To characterize the signalment, clinical findings, and prognosis of dogs with supraventricular tachycardia (SVT). n nDesign – Retrospective study. n nSetting – North Carolina State University Veterinary Teaching Hospital. n nAnimals, Intervention, and Measurements – Case selection included all patients at the veterinary teaching hospital with SVT during years 1990–2007. Medical records from dogs with at least 1 recorded episode of SVT were extracted. The signalment, history, electrocardiographic, radiographic, and echocardiographic findings, therapy, and response to therapy were reviewed and summarized. Follow-up was conducted to determine the date and cause of death. Kaplan-Meier survival curves were constructed and analyzed. The relationships between patient characteristics and responses to therapy and prognosis were evaluated. n nMain Results – Sixty-five records documented a diagnosis of SVT. Sixty-two percent were males. Labrador Retrievers and Boxers were overrepresented compared with the general hospital population. Median age at presentation was 9 years (range 0.5–15.5 y). The median heart rate during SVT was 270/minute (range 187–375/min). The most common presenting complaint was syncope (30%), 23% were asymptomatic at the time of diagnosis. Most dogs had structural heart disease (65%). Median survival was 472 days ( 30 s) did not affect survival (P=0.50), nor did the presence of congestive heart failure (P=0.70). n nConclusions – The majority of dogs with SVT had structural heart disease or a severe concurrent illness at the time of SVT diagnosis. SVT, though often a persistent and occasionally sustained arrhythmia, does not appear to be a primary factor in mortality.