John M. MacGregor

Retrospective Evaluation of Sildenafil Citrate as a Therapy for Pulmonary Hypertension in Dogs

Pulmonary arterial hypertension (PH) is a pathologic condition in dogs characterized by abnormally high pressures in the pulmonary circulation and has been associated with a poor outcome. Sildenafil is a type V phosphodiesterase inhibitor that produces nitric oxide mediated vasodilatation. Sildenafil treatment decreases pulmonary arterial pressure and pulmonary vascular resistance in people with PH. The purpose of this study was to describe the clinical characteristics and outcome of dogs with PH treated with sildenafil. The cardiology database was searched for dogs with PH treated with sildenafil. PH was defined as systolic pulmonary arterial pressure (PAPs) > or = 25 mmHg at rest. Medical records were reviewed for the following information: signalment, duration and type of clinical signs before treatment, underlying disease, estimated or measured PAPs, dosage and dosing interval of sildenafil, and the effect of treatment on clinical signs and pulmonary arterial pressure and survival time. Thirteen affected dogs were identified. Clinical signs included collapse, syncope, respiratory distress, and cough. Duration of clinical signs before presentation ranged from 3 days to 5 months. An underlying cause was identified in 8 dogs. The median sildenafil dosage was 1.9 mg/kg. Ten dogs received concurrent medications. Median PAPs was 90 mmHg; 8 dogs were reevaluated after therapy, and the median decrease in PAPs was 16.5 mmHg. The median survival time of all dogs was 91 days. Sildenafil appeared to be well tolerated in dogs with PH and was associated with decreased PAPs and amelioration of clinical signs in most. Sildenafil represents a reasonable treatment option for dogs with pulmonary hypertension.

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.

Comparison of pharmacodynamic variables following oral versus transdermal administration of atenolol to healthy cats.

OBJECTIVE To describe the disposition of and pharmacodynamic response to atenolol when administered as a novel transdermal gel formulation to healthy cats. ANIMALS 7 healthy neutered male client-owned cats. PROCEDURES Atenolol was administered either orally as a quarter of a 25-mg tablet or as an equal dose by transdermal gel. Following 1 week of treatment, an ECG and blood pressure measurements were performed and blood samples were collected for determination of plasma atenolol concentration at 2 and 12 hours after administration. RESULTS 2 hours after oral administration, 6 of 7 cats reached therapeutic plasma atenolol concentrations with a mean peak concentration of 579 +/- 212 ng/mL. Two hours following transdermal administration, only 2 of 7 cats reached therapeutic plasma atenolol concentrations with a mean peak concentration of 177 +/- 123 ng/mL. The difference in concentration between treatments was significant. Trough plasma atenolol concentrations of 258 +/- 142 ng/mL and 62.4 +/- 17 ng/mL were achieved 12 hours after oral and transdermal administration, respectively. A negative correlation was found between heart rate and plasma atenolol concentration. CONCLUSIONS AND CLINICAL RELEVANCE Oral administration of atenolol at a median dose of 1.1 mg/kg every 12 hours (range, 0.8 to 1.5 mg/kg) in cats induced effective plasma concentrations at 2 hours after treatment in most cats. Transdermal administration provided lower and inconsistent plasma atenolol concentrations. Further studies are needed to find an effective formulation and dosing scheme for transdermal administration of atenolol.

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.

Auscultatory, echocardiographic, biochemical, nutritional, and environmental characteristics of mitral valve disease in Norfolk terriers.

OBJECTIVES In order to more fully understand degenerative mitral valve disease (DMVD) in the Norfolk terrier, we sought to characterize findings from the physical and echocardiographic examination; biochemical, biomarker, and nutritional profiles; and select environmental variables from a cohort of apparently healthy Norfolk terriers. ANIMALS, MATERIALS AND METHODS Overtly healthy Norfolk terriers ≥ 6 yrs old were recruited by 3 different veterinary hospitals and underwent historical, physical, electrocardiographic (ECG), and 2D/color-flow Doppler echocardiographic examinations. Anterior mitral valve leaflet length, maximal thickness, area, and degree of prolapse were measured or calculated from two-dimensional images. Blood samples were obtained for serum biochemistry, serum serotonin, plasma NT-proBNP, amino acid profile, C-reactive protein, and cardiac troponin I. RESULTS Of the 48 dogs entered into the study, 23 (48%) had murmurs, 2 (4%) had mid-systolic clicks, 11 (23%) had ECG P pulmonale, and 41 (85%) were deemed to have echocardiographic evidence of DMVD, including 18 Norfolk terriers without a murmur. Seven (15%), 28 (58%), and 13 (27%) dogs were classified as normal (stage 0), International Small Animal Cardiac Health Council (ISACHC) stage 1a, and 1b, respectively. Mean indexed echocardiographic mitral leaflet thickness (P = 0.017), area (P = 0.0002), prolapse (P = 0.0004), and left atrial to aortic diameter (P = 0.01) were significantly different between ISACHC 0, 1a, and 1b. CONCLUSION DMVD is relatively common in Norfolk terriers and echocardiographic changes consistent with mild DMVD can be seen in dogs without a heart murmur.

Presumptive primary cardiac lymphoma in a cat causing pericardial effusion

We report a case of primary cardiac lymphoma in a cat, causing pericardial effusion. A 13-year-old castrated male Himalayan cat was evaluated for chronic weight loss and radiographic finding of cardiomegaly. Pericardial effusion and a heart mass were detected via echocardiography. Pericardiocentesis and ultrasound-guided fine needle aspirate of the heart mass were performed under sedation. Antemortem diagnosis of cardiac lymphoma was made based on cytology of pericardial fluid. Based on physical examination, laboratory tests and abdominal radiographs, primary cardiac lymphoma was established as the presumptive clinical diagnosis. Treatment with chemotherapeutic agents was initiated.

Congenital cardiac malformation with three-chambered right atrium and a persistent left cranial vena cava in a dog

This report describes an unusual congenital abnormality in a dog in which multiple distinct membranes were observed within the right atrium, creating obstruction to venous return from both the cranial vena cava and the caudal vena cava. A persistent left cranial vena cava was also identified. In addition to a membrane in the typical location for cor triatriatum dexter, the dog also had a perforated membrane separating the main right atrial body and tricuspid valve from a more cranial right atrial chamber and the right cranial vena cava. Balloon dilation was performed successfully to alleviate the obstruction to systemic venous return created by the two membranes. Due to the unusual anatomic features, angiography plus echocardiography was useful to completely characterize the congenital abnormality prior to intervention.

Clinical Features of English Bulldogs with Presumed Arrhythmogenic Right Ventricular Cardiomyopathy: 31 Cases (2001–2013)

Arrhythmogenic right ventricular cardiomyopathy (ARVC) is an important cause of sudden death in people and boxer dogs that has recently been described in English bulldogs. The objective of this retrospective study was to describe the clinical characteristics of English bulldogs with presumed ARVC. The medical records were searched for English bulldogs examined between 2001 and 2013 with a clinical diagnosis of ARVC. The average age of the 31 dogs identified was 9.2 ± 1.6 yr (range 7-13 yr). Males were overrepresented by a factor of 2.9 to 1. At initial presentation, 5 dogs had subclinical arrhythmia, 10 dogs had clinical signs attributable to arrhythmia, and 16 dogs had congestive heart failure. Eighteen dogs (58%) had ventricular tachycardia and five (16%) also had supraventricular arrhythmias. Four dogs experienced sudden death, 2 dogs died from congestive heart failure, 11 dogs were euthanized for cardiac causes, and 2 dogs died or were euthanized for noncardiac causes. Kaplan-Meier analysis showed a median survival time of 8.3 mo. This is the first study to describe the clinical characteristics of a population of English bulldogs with presumed ARVC. Further studies are needed to better characterize the clinical features of the disease in this breed.