Teresa C. DeFrancesco

Prospective clinical evaluation of an ELISA B-type natriuretic peptide assay in the diagnosis of congestive heart failure in dogs presenting with cough or dyspnea

BACKGROUND B-type natriuretic peptide (BNP) is increased in dogs with congestive heart failure (CHF). HYPOTHESIS The purpose of this study was to evaluate the clinical utility of a novel canine-specific enzyme-linked immunosorbent assay of BNP for the diagnosis of CHF in dogs presenting with either cough or dyspnea. ANIMALS Three hundred and thirty dogs from 2 large university teaching hospitals. METHODS We prospectively measured plasma BNP concentrations in 3 groups of dogs: (1) normal adult dogs (n = 75), (2) dogs with asymptomatic heart disease (n = 76), and (3) dogs with cough or dyspnea (n = 179). The final diagnosis of dogs with cough or dyspnea and the severity of CHF (International Small Animal Cardiac Health Council Heart Failure Classification [ISACHC]) were determined by medical record review by a study cardiologist who was blinded to the results of the BNP assay. RESULTS Dogs with CHF had a higher median BNP concentration (24.6 pg/mL) than dogs with noncardiac causes of cough or dyspnea (2.6 pg/mL) (P < .0001). The area under the curve was 0.91 for the receiver operating curve analysis of the diagnostic accuracy of the BNP measurement to differentiate CHF from other causes of cough or dyspnea. The median BNP concentrations in dogs were 3.0 pg/mL with ISACHC I, 17.8 pg/mL with ISACHC II, and 30.5 pg/mL with ISACHC III. (P < .0001) CONCLUSION AND CLINICAL IMPORTANCE Measurement of BNP is useful in establishing or in excluding the diagnosis of CHF in dogs with cough or dyspnea. B-type natriuretic peptide concentrations rose significantly as a function of severity of CHF.

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.

Ionized hypocalcemia in critically ill dogs.

BACKGROUND Ionized hypocalcemia (iHCa) is a common electrolyte disturbance in critically ill people, especially those with sepsis. The cause of the iHCa is not entirely understood and is likely multifactorial. Critically ill people with iHCa have longer hospital stays and higher mortality rates compared to people with normocalcemia. There are no published clinical studies evaluating the incidence and impact of iHCa in critically ill dogs. HYPOTHESIS iHCa occurs in critically ill dogs, is more prevalent in dogs with systemic inflammatory response syndrome (SIRS) or sepsis, and is associated with longer hospital stays and higher mortality. ANIMALS One hundred and forty-one client-owned dogs admitted to a companion animal intensive care unit (ICU) in a veterinary teaching hospital. METHODS Prospective observational study of sequentially enrolled dogs. Blood was collected and analyzed within an hour of admission from all dogs presented to the ICU that met study inclusion criteria. RESULTS The incidence of iHCa (iCa < 1.11 mmol/L) was 16%. The presence of iHCa was associated with longer ICU (P= .038) and hospital (P= .012) stays but not with decreased survival (P= .60). Dogs with sepsis as defined by >or=3 SIRS criteria and a positive culture were more likely to have iHCa (P= .050). CONCLUSIONS AND CLINICAL RELEVANCE In dogs not previously treated with fluids or blood products intravenously, the finding of iHCa upon admission to the ICU predicted a longer duration of ICU and hospital stay. Septic dogs with positive cultures were more likely to have iHCa.

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.

Relationship between hydration estimate and body weight change after fluid therapy in critically ill dogs and cats

Objective: To characterize the relationship between clinical estimates of hydration in dogs and cats admitted to an intensive care unit (ICU) and changes in their body weight following 24–48 hours of fluid therapy. Design: Outcome study. Setting: ICU at a veterinary teaching hospital (VTH). Animals: A total of 151 dogs and 42 cats with various medical disorders that had not had surgery within 48 hours of admission into the ICU were consecutively admitted into the study. Animals with any condition predisposing to excess fluid loss or retention were excluded: heart disease, sepsis, trauma, pancreatitis, pleural or pericardial effusion, ascites, and pathologic oliguria. Animals that acquired any of the following during the observation period were excluded: gastrointestinal fluid loss, edema or diseases predisposing to edema, oliguria, diuretic therapy, and body fluid drainage or hemorrhage. Fluid therapy was ordered based on estimate of hydration at admission. Other treatments were not modified or withheld. Interventions: Physiologic data were collected at the time of admission and 24–48 hours later. Measurements and main results: Hydration was estimated on admission to the ICU using clinical judgement with no supporting laboratory data. Each admitting clinician used this estimate to plan fluid therapy. Fluid therapy was defined as the administration of any enteral or parenteral fluids as well as any decision to withhold fluids. Paired measurements taken on admission and at 24–48 hours included packed cell volume (PCV), total plasma solids (TS), and body weight. Amount and type of fluids or blood products administered were noted. Neither clinician estimates of dehydration nor baseline PCV or TS predicted clinically significant changes in body weight following fluid therapy, and there was no relationship between weight change and changes in PCV or TS. Conclusions: A clinical diagnosis of dehydration in our ICU does not predict weight gain following fluid therapy. Neither baseline PCV/TS nor changes in these measurements following 24–48 hours of fluid therapy predicted changes in body weight.

Acute effect of pimobendan and furosemide on the circulating renin-angiotensin-aldosterone system in healthy dogs.

BACKGROUND The renin-angiotensin-aldosterone system (RAAS) is activated in states of decreased cardiac output and by certain cardiovascular therapeutic agents, such as loop diuretics and vasodilators. HYPOTHESIS Short-term treatment with the inodilator, pimobendan, will not activate the circulating RAAS because its vasodilatory action will be offset by its positive inotropic property, thereby ameliorating RAAS stimulation at the juxtaglomerular apparatus. Furthermore, pimobendan will suppress RAAS activation produced by furosemide. ANIMALS Nine healthy laboratory dogs were used in this study. METHODS Experimental, cross-over study. Dogs were administered pimobendan (0.5 mg/kg q12h) for 4 days followed by furosemide (2 mg/kg q12h) and then, after a wash-out period, a combination of the drugs. Aldosterone : creatinine (A : Cr) was measured at the end of each treatment cycle. RESULTS There was no significant increase in the average urinary A : Cr with the administration of pimobendan (control urinary A : Cr = 0.46, standard deviation (SD) 0.33; pimobendan A : Cr = 0.48, SD 0.28). There was a significant increase in the average urinary A : Cr after administration of furosemide (urinary A : Cr = 1.3, SD 0.70) and with the combination of furosemide and pimobendan (urinary A : Cr = 2.9, SD 1.6). CONCLUSIONS AND CLINICAL RELEVANCE Short-term administration of high-dose pimobendan, does not activate the RAAS in healthy dogs. Pimobendan did not prevent RAAS activation associated with furosemide therapy. These results in healthy dogs suggest that furosemide therapy, with or without pimobendan, should be accompanied by RAAS suppressive therapy.

Coagulation effects of low molecular weight heparin compared with heparin in dogs considered to be at risk for clinically significant venous thrombosis.

OBJECTIVE Compare the effects of 3 anticoagulation protocols on anti-factor Xa activity (AXa). DESIGN Prospective, randomized, double-blind study. SETTING University veterinary teaching hospital. ANIMALS Eighteen dogs considered to be at risk for venous thrombosis. INTERVENTIONS Each dog was randomly assigned to 1 of the following 3 groups (n=6/group) and was treated for 24 hours: low-dose heparin (LDH), high-dose heparin (HDH), and dalteparin (DP). Dogs in the LDH group received a constant rate infusion (CRI) of unfractionated heparin (UFH) at 300 U/kg/d, the HDH group received a bolus of 100 U/kg of UFH IV, then a CRI of 900 U/kg/day, and the DP group received 100 U/kg DP SC at 0, 12, and 24 hours. MEASUREMENTS AND MAIN RESULTS A total of 54 samples for activated partial thromboplastin time (aPTT) and AXa assays were collected at 0, 4, and 28 hours. Six samples had an AXa >0.1 U/mL, 5 of those were from the HDH group at hour 4. Two samples from the HDH group at hour 4 had a prolonged aPTT (93 and 200 seconds) and the highest AXa (0.6 and 1.0 U/mL, respectively). Four additional dogs in the HDH group did not complete the study due to hemorrhage; none of the dogs completing the study showed signs of hemorrhage. CONCLUSIONS Neither DP nor LDH increased AXa to values considered therapeutic in humans (0.5-1 and 0.35-0.75 U/mL, respectively), and both protocols appear to be inadequate to increase AXa in dogs with clinical illness. HDH increased AXa to this range in 2 of 6 dogs, but had unpredictable effects on aPTT and resulted in hemorrhage in some dogs.

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 Polymerase Chain Reaction with Bacterial 16s Primers to Blood Culture to Identify Bacteremia in Dogs with Suspected Bacterial Endocarditis

BACKGROUND Identification of the bacterial organism in dogs with endocarditis is challenging. Human studies have reported the utility of the polymerase chain reaction (PCR) to amplify and identify bacterial nucleic acid from infected valvular tissue and blood. HYPOTHESIS/OBJECTIVES We hypothesized that PCR using primers designed to amplify the bacterial 16s gene would identify circulating bacteria in dogs with suspected bacterial endocarditis more consistently than standard blood culture techniques. ANIMALS Eighteen dogs with suspected bacterial endocarditis based upon clinical and echocardiographic findings. Fifteen clinically normal dogs served as negative controls. METHODS Prospective study of dogs evaluated for suspect endocarditis at 6 veterinary hospitals. A blood sample was drawn from all dogs and evaluated with both a single-sample PCR and standard 3-sample blood culture techniques. RESULTS Blood culture identified noncontaminant bacteria in 6/18 study animals (33%) and 1 control dog; PCR identified noncontaminant bacteria in 7/18 study animals (39%). There were no study animals in which the 2 tests identified different bacteria (κ = 1.0). However, bacteria were identified by both techniques in only 2/18 study animals. When results from both PCR and blood culture were considered together, a noncontaminant bacterial organism was identified in 11/18 study animals (61%). CONCLUSION AND CLINICAL IMPORTANCE The results of this study suggest that although single sample PCR with 16s primers was not more sensitive than blood culture for detection of bacteremia in dogs with suspect endocarditis, performing both techniques simultaneously did increase the likelihood of identification of bacteria in blood.

Management of Cardiac Emergencies in Small Animals

Cardiac emergencies are life-threatening conditions that must be diagnosed quickly to avoid delays in therapy. A timely and accurate diagnosis leads to early relief of symptoms and improved survival. This article provides both a comprehensive review and updated management recommendations for common cardiac emergencies in dogs and cats. Specifically, the article confers updates for the efficient clinical recognition of decompensated cardiac patients, including focused echocardiography, cardiac biomarkers, and electrocardiogram interpretation. This article also reviews the latest recommendations for the treatment of heart failure (including the use of pimobendan) and the management of arrhythmias, pericardial effusion, and aortic thromboembolism.