Sonya G. Gordon

Efficacy of Pimobendan in the Prevention of Congestive Heart Failure or Sudden Death in Doberman Pinschers with Preclinical Dilated Cardiomyopathy (The PROTECT Study)

Background The benefit of pimobendan in delaying the progression of preclinical dilated cardiomyopathy (DCM) in Dobermans is not reported. Hypothesis That chronic oral administration of pimobendan to Dobermans with preclinical DCM will delay the onset of CHF or sudden death and improve survival. Animals Seventy-six client-owned Dobermans recruited at 10 centers in the UK and North America. Methods The trial was a randomized, blinded, placebo-controlled, parallel group multicenter study. Dogs were allocated in a 1:1 ratio to receive pimobendan (Vetmedin capsules) or visually identical placebo. The composite primary endpoint was prospectively defined as either onset of CHF or sudden death. Time to death from all causes was a secondary endpoint. Results The proportion of dogs reaching the primary endpoint was not significantly different between groups (P = .1). The median time to the primary endpoint (onset of CHF or sudden death) was significantly longer in the pimobendan (718 days, IQR 441–1152 days) versus the placebo group (441 days, IQR 151–641 days) (log-rank P = 0.0088). The median survival time was significantly longer in the pimobendan (623 days, IQR 491–1531 days) versus the placebo group (466 days, IQR 236–710 days) (log-rank P = .034). Conclusion and Clinical Importance The administration of pimobendan to Dobermans with preclinical DCM prolongs the time to the onset of clinical signs and extends survival. Treatment of dogs in the preclinical phase of this common cardiovascular disorder with pimobendan can lead to improved outcome.

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.

Transarterial ductal occlusion using the Amplatz Canine Duct Occluder in 40 dogs.

OBJECTIVES Describe the result of patent ductus arteriosus (PDA) occlusion using the Amplatz Canine Duct Occluder (ACDO) in 40 dogs. ANIMALS, MATERIAL AND METHODS: Records of the first 41 dogs at Texas A&M University in which ductal occlusion with an ACDO was attempted were reviewed. RESULTS Appropriate device release was achieved in 40 of 41 dogs. Post-release angiography in 39 dogs documented complete occlusion in 27 dogs, trivial residual flow in 7, mild residual flow in 1 and moderate residual flow in 4; angiography was not recorded in one dog. The following day transthoracic color Doppler echocardiography documented complete occlusion in all 40 dogs. One dog required a larger device than could be deployed through the largest sheath accommodated by the femoral artery and the PDA was subsequently closed by surgical ligation. CONCLUSIONS Ductal occlusion using an ACDO has a high rate of initial and 24-h complete occlusion. Ductal occlusion using an ACDO is a safe and efficacious therapy for PDA in dogs. This report confirms the positive clinical outcome of the original report in a large cohort of dogs.

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.

Pimobendan in Heart Failure Therapy – A Silver Bullet?

Pimobendan is a novel agent with properties that are highly desirable in the clinical management of congestive heart failure (CHF) secondary to both dilated cardiomyopathy (DCM) and chronic degenerative valvular disease in dogs. Review of available data suggests that pimobendan is safe, well tolerated, and leads to enhanced quality of life in dogs with CHF secondary to DCM or chronic valvular disease when used in combination with furosemide or other conventional therapies (e.g., angiotensin-converting enzyme inhibitors, digoxin). Pimobendan leads to a reduction in mortality from CHF associated with DCM, and ongoing studies are evaluating its effects on mortality associated with chronic valvular disease.

Transarterial Coil Embolization of Patent Ductus Arteriosus in Small Dogs with 0.025-Inch Vascular Occlusion Coils: 10 Cases

Patent ductus arteriosus (PDA) is the most common congenital cardiac disease in the dog and generally leads to severe clinical signs, including left-sided congestive heart failure. Historically, definitive treatment consisted of surgical ligation; however, the use of vascular occlusion devices by minimally invasive techniques has gained popularity in veterinary medicine during the past decade. Adequate vascular access is a major limiting factor for these minimally invasive techniques, precluding their use in very small dogs. The clinical management of PDA with 0.025-in vascular occlusion coils in a minimally invasive transarterial technique in 10 dogs is described. The dogs were small (1.38 +/- 0.22 kg), were generally young (6.70 +/- 5.74 months), and had small minimal ductal diameters (1.72 +/- 0.81 mm from angiography). Vascular access was achieved, and coil deployment was attempted in all dogs with a 3F catheter uncontrolled release system. Successful occlusion, defined as no angiographic residual flow, was accomplished in 8 of 10 (80%) dogs. Successful occlusion was not achieved in 2 dogs (20%), and both dogs experienced embolization of coils into the pulmonary arterial tree. One of these dogs died during the procedure, whereas the other dog underwent a successful surgical correction. We conclude that transarterial PDA occlusion in very small dogs is possible with 0.025-in vascular occlusion coils by means of a 3F catheter system and that it represents a viable alternative to surgical ligation. The risk of pulmonary arterial embolization is higher with this uncontrolled release system, but this risk may decrease with experience.

Utility of Transesophageal Echocardiography for Transcatheter Occlusion of Patent Ductus Arteriosus in Dogs: Influence on the Decision-Making Process

BACKGROUND Appropriate device selection for transcatheter occlusion of patent ductus arteriosus (PDA) is essential to procedural success. OBJECTIVES To determine if transesophageal echocardiography (TEE) influences device selection for PDA occlusion and to report benefits, limitations, and complications associated with TEE. ANIMALS Twenty-two client-owned dogs with left-to-right shunting PDA. METHODS PDA dimensions were obtained via transthoracic echocardiography (TTE) and then TEE followed by angiography. Based solely on information from TTE and angiography, an initial device type and size were selected. After initial device selection, TEE measurements were disclosed and changes in device selection were recorded. After device release, angiography, TEE, or both were performed to assess occlusion. RESULTS An Amplatz canine duct occluder (ACDO) was securely positioned and released in 21 dogs and an embolization coil was deployed in 1 dog. Based on TEE evaluation, initial selected device type was unchanged but ACDO size was changed in 3 dogs. TEE was utilized throughout the procedure allowing real time visualization of device deployment, release and assessment of closure in 17 dogs. No complications occurred related to TEE. Complete PDA closure was achieved in all dogs. CONCLUSIONS AND CLINICAL IMPORTANCE TEE provided anatomic information regarding PDA morphology that closely approximated angiographic ductal dimensions while aiding in device deployment, release and confirmation of closure. We conclude that TEE provides complementary anatomical and intraprocedural information and is well tolerated in dogs.