Wendy A. Ware

Cardiac Tumors in Dogs: 1982–1995

A Veterinary Medical Database search from 1982 to 1995 identified 1,383 dogs with tumors of the heart from a total population of 729,265 dogs (0.19% incidence). Hemangiosarcoma (HSA) was the most common cardiac tumor identified. In the subset of dogs with specific histologic diagnoses, the number with HSA was almost 10-fold that of the 2nd most common tumor, aortic body tumor. Primary heart tumors were more common than cardiac metastases. When biologic behavior was noted, most heart tumors were classified as malignant. Cardiac tumors (excluding lymphoma) occurred most often in dogs between the ages of 7 and 15 years. In very old dogs (>15 years), the frequency of cardiac tumors was the same or lower than that of the youngest age group. Tumors occurred with similar frequency in males and females, but the relative risk for spayed females was >4 times that for intact females. For HSA, spayed females had >5 times greater relative risk than did intact females. The risk for castrated males was slightly greater than that for intact males, which had 2.4 times the relative risk of intact females. Thus, neutering appeared to increase the risk of cardiac tumor in both sexes. Intact females were least likely to develop a cardiac tumor, whereas spayed females were most likely to develop a tumor. Twelve breeds had greater than average risk of developing a cardiac tumor, whereas 17 had lower risk.

Replacing the Enzyme α-l-Iduronidase at Birth Ameliorates Symptoms in the Brain and Periphery of Dogs with Mucopolysaccharidosis Type I

Replacing the enzyme α-l-iduronidase at birth ameliorates symptoms in the brain and periphery of dogs with mucopolysaccharidosis type I. When Dogs Really Are Man’s Best Friend For certain diseases, dogs provide an excellent large-animal model and the lysosomal storage disorder mucopolysaccharidosis type I is no exception. In this disease, a defect in the enzyme α-l-iduronidase prevents breakdown of glycosaminoglycans, resulting in their accumulation in the lysosomes of cells, leading to engorged and dysfunctional cells. A variety of serious complications ensue such as enlarged organs, skeletal defects, corneal clouding, abnormal heart valves, and cognitive deficits. Although a human recombinant form of the enzyme has proved successful in treating patients with less severe forms of the disease, only some of the symptoms are ameliorated and patients often develop antibodies to the enzyme. Dierenfeld and colleagues reasoned that starting enzyme replacement therapy at birth could halt or even reverse the more serious disease symptoms such as heart valve defects, skeletal deformities, and cognitive impairment and might prevent antibodies from forming against human recombinant α-l-iduronidase. Working in a naturally occurring dog model of mucopolysaccharidosis type I in which the animals have a defective α-l-iduronidase enzyme and show most of the symptoms of the human disease, Dierenfeld et al. administered two different doses of α-l-iduronidase (0.58 and 1.57 mg/kg) intravenously every week starting a few days after birth. The authors show that starting enzyme replacement therapy at such a young age prevented the formation of antibodies against the enzyme due to neonatal immune tolerance. Treated dogs showed marked reductions in glycosaminoglycans in a variety of different tissues including the mitral heart valve, which has been refractory to traditional enzyme treatment administered at later ages. Furthermore, treated dogs showed relatively normal skeletons and lacked the stiff gait, lax joints, upturned nose, and poor neck flexibility exhibited by untreated animals with the disease. Compellingly, glycosaminoglycan levels and cortical atrophy in the brain decreased and corneal clouding improved slightly (at the higher dose) in the treated dogs. These results show that starting intravenous administration of α-l-iduronidase at higher doses and as soon as possible after birth increases the efficacy of enzyme replacement therapy and ensures immune tolerance to the enzyme. These promising results in man’s best friend suggest that children with severe mucopolysaccharidosis type I or other early-onset lysosomal storage diseases should start enzyme replacement therapy as soon as possible after birth. Mucopolysaccharidosis type I (MPS I) is a lysosomal storage disease caused by loss of activity of α-l-iduronidase and attendant accumulation of the glycosaminoglycans dermatan sulfate and heparan sulfate. Current treatments are suboptimal and do not address residual disease including corneal clouding, skeletal deformities, valvular heart disease, and cognitive impairment. We treated neonatal dogs with MPS I with intravenous recombinant α-l-iduronidase replacement therapy at the conventional 0.58 mg/kg or a higher 1.57 mg/kg weekly dose for 56 to 81 weeks. In contrast to previous results in animals and patients treated at a later age, the dogs failed to mount an antibody response to enzyme therapy, consistent with the induction of immune tolerance in neonates. The higher dose of enzyme led to complete normalization of lysosomal storage in the liver, spleen, lung, kidney, synovium, and myocardium, as well as in the hard-to-treat mitral valve. Cardiac biochemistry and function were restored, and there were improvements in skeletal disease as shown by clinical and radiographic assessments. Glycosaminoglycan levels in the brain were normalized after intravenous enzyme therapy, in the presence or absence of intrathecal administration of recombinant α-l-iduronidase. Histopathological evidence of glycosaminoglycan storage in the brain was ameliorated with the higher-dose intravenous therapy and was further improved by combining intravenous and intrathecal therapy. These findings argue that neonatal testing and early treatment of patients with MPS I may more effectively treat this disease.

Echocardiographic and Radiographic Changes Associated with Systemic Hypertension in Cats

The purpose of this study was to assess the effects of systemic hypertension (SHT) on echocardiographic and radiographic cardiovascular variables in affected cats compared with healthy geriatric cats. Secondary objectives were to determine whether there were any relationships between these findings and age or systolic blood pressure (SBP). Fifteen healthy cats (>8 years of age with normal SBP) and 15 hypertensive cats (SBP > 180 mm Hg) were studied. Each cat was evaluated for standard echocardiographic parameters and 4 different aortic root dimensions. Seventeen variables were measured from right lateral and dorsoventral radiographic views. Left ventricle wall thickness was greater in the SHT group (5.1 +/- 0.9 mm) than in the healthy cats (4.2 +/- 0.5 mm). Left ventricular hypertrophy in the SHT cats often was not severe, and mean measures were considered normal. Some cats had asymmetrical septal hypertrophy (ASH) in the basilar portion of the septum as determined from the 2-dimensional view of the left ventricular outflow tract. ASH was greater in cats with SHT. Comparisons of the proximal ascending aorta indicated the presence of dilatation in the SHT cats, and comparison of the ascending aorta to the aortic annulus was helpful in differentiating between the 2 groups. The distal aortic root measurements and ratios evaluated by echocardiography were significantly different between the 2 groups of cats (P = .0001) and were significantly correlated with SBP (P = .0001) but not age (P > .3).

Cardiovascular disease in small animal medicine

Introduction and Normal Reference Information The normal cardiovascular system The cardiovascular examination Cardiac radiography Electrocardiography Echocardiography Cardiovascular Problems Murmurs and abnormal heart sounds Cardiomegaly Cough Respiratory difficulty Jugular vein distension or pulsations Abdominal distension Subcutaneous edema Abnormal heart rate or rhythm Syncope and intermittent collapse Thromboembolic disease Management of heart failure Management of arrhythmias Cardiovascular Diseases Congenital cardiovascular diseases Acquired valve diseases Myocardial diseases of the dog Moycardial diseases of the cat Pericardial diseases and cardiac tumours Pulmonary distension Heartworm disease Systemic hypertension Index

Myocardial Toxicity in a Group of Greyhounds Administered Ractopamine

Ractopamine, a synthetic β2-adrenoceptor agonist, is widely used as a feed additive in the United States to promote a reduction in body fat and enhance muscle growth in cattle, pigs, and turkeys. It has the potential for illegal use in show and racing animals because it may affect performance via its β-adrenergic agonist properties or anabolic activities. Nine greyhounds were orally administered 1 mg/kg of ractopamine to investigate the ability to detect the drug in urine. Postdosing, 7 of 9 dogs developed cardiac arrhythmias and had elevated troponin levels indicating myocardial damage. One dog necropsied 4 days postdosing had massive myocardial necrosis, mild to focally moderate skeletal muscle necrosis, and widespread segmental arterial mediolysis. A second dog necropsied 17 days postdosing had mild myocardial necrosis and fibrosis. Scattered arteries exhibited segmental medial and perimedial fibromuscular dysplasia. This is the first reported case of arterial, cardiac, and skeletal muscle damage associated with ractopamine.

Cardiac toxicity from phenylpropanolamine overdose in a dog.

A 5-year-old, 29-kg, female Labrador retriever developed tachypnea, tachycardia, and ataxia following ingestion of approximately 48 mg/kg of phenylpropanolamine. Initial diagnostic tests showed multiform ventricular tachycardia, left ventricular dilatation with a focal dyskinetic region in the dorsal interventricular septum, and elevations in creatinine kinase and cardiac troponin I. All abnormalities resolved within 6 months. The transient electrocardiographic, echocardiographic, and biochemical abnormalities were consistent with myocardial necrosis from infarction or direct catecholamine-induced myocardial toxicity.

Sudden Death Associated with QT Interval Prolongation and KCNQ1 Gene Mutation in a Family of English Springer Spaniels

Background A 5‐year‐old, healthy English Springer Spaniel died suddenly 4 months after delivering a litter of 7 puppies. Within 4 months of the dams death, 3 offspring also died suddenly. Hypothesis Abnormal cardiac repolarization, caused by an inherited long QT syndrome, is thought to be responsible for arrhythmias leading to sudden death in this family. Animals Four remaining dogs from the affected litter and 11 related dogs. Methods Physical examination and resting ECG were done on the littermates and 9 related dogs. Additional tests on some or all littermates included echocardiogram with Doppler, Holter monitoring, and routine serum biochemistry. Blood for DNA sequencing was obtained from all 15 dogs. Results Three of 4 littermates examined, but no other dogs, had prolonged QT intervals with unique T‐wave morphology. DNA sequencing of the KCNQ1 gene identified a heterozygous single base pair mutation, unique to these 3 dogs, which changes a conserved amino acid from threonine to lysine and is predicted to change protein structure. Conclusions and Clinical Importance This family represents the first documentation in dogs of spontaneous familial QT prolongation, which was associated with a KCNQ1 gene mutation and sudden death. Although the final rhythm could not be documented in these dogs, their phenotypic manifestations of QT interval prolongation and abnormal ECG restitution suggested increased risk for sudden arrhythmic death. The KCNQ1 gene mutation identified is speculated to impair the cardiac repolarizing current I Ks, similar to KCNQ1 mutations causing long QT syndrome 1 in humans.

International collaborative study to assess cardiovascular risk and evaluate long‐term health in cats with preclinical hypertrophic cardiomyopathy and apparently healthy cats: The REVEAL Study

Background Hypertrophic cardiomyopathy is the most prevalent heart disorder in cats and principal cause of cardiovascular morbidity and mortality. Yet, the impact of preclinical disease is unresolved. Hypothesis/Objectives Observational study to characterize cardiovascular morbidity and survival in cats with preclinical nonobstructive (HCM) and obstructive (HOCM) hypertrophic cardiomyopathy and in apparently healthy cats (AH). Animals One thousand seven hundred and thirty client‐owned cats (430 preclinical HCM; 578 preclinical HOCM; 722 AH). Methods Retrospective multicenter, longitudinal, cohort study. Cats from 21 countries were followed through medical record review and owner or referring veterinarian interviews. Data were analyzed to compare long‐term outcomes, incidence, and risk for congestive heart failure (CHF), arterial thromboembolism (ATE), and cardiovascular death. Results During the study period, CHF, ATE, or both occurred in 30.5% and cardiovascular death in 27.9% of 1008 HCM/HOCM cats. Risk assessed at 1, 5, and 10 years after study entry was 7.0%/3.5%, 19.9%/9.7%, and 23.9%/11.3% for CHF/ATE, and 6.7%, 22.8%, and 28.3% for cardiovascular death, respectively. There were no statistically significant differences between HOCM compared with HCM for cardiovascular morbidity or mortality, time from diagnosis to development of morbidity, or cardiovascular survival. Cats that developed cardiovascular morbidity had short survival (mean ± standard deviation, 1.3 ± 1.7 years). Overall, prolonged longevity was recorded in a minority of preclinical HCM/HOCM cats with 10% reaching 9‐15 years. Conclusions and Clinical Importance Preclinical HCM/HOCM is a global health problem of cats that carries substantial risk for CHF, ATE, and cardiovascular death. This finding underscores the need to identify therapies and monitoring strategies that decrease morbidity and mortality.

Evaluation of point-of-care thoracic ultrasound and NT-proBNP for the diagnosis of congestive heart failure in cats with respiratory distress

Background The diagnosis of congestive heart failure (CHF) in cats is challenging. Point‐of‐care (POC) thoracic ultrasound and NT‐proBNP testing are emerging tools that may aid in diagnosis. Hypothesis/Objectives To assess the diagnostic accuracy of POC lung ultrasound (LUS), focused cardiac ultrasound (FCU), and NT‐proBNP in predicting a final diagnosis of CHF. Animals Fifty‐one cats in respiratory distress. Methods Blood NT‐proBNP, LUS, and FCU evaluating left atrial (LA) size and presence of pericardial effusion (PCEFF) were performed in all cats. Lung ultrasound findings including pleural effusion (PLEFF), number of B‐lines, and sub‐pleural abnormalities were noted. Medical records were evaluated for final diagnosis. Results Thirty‐three of 51 (65%) cats were diagnosed with CHF. Lung ultrasound and blood NT‐proBNP were significant predictors of CHF in a multivariate model. The LUS criterion that maximized accuracy for CHF diagnosis was presence of >1 site strongly positive for B‐lines (>3 B‐lines per site), resulting in sensitivity of 78.8%, specificity of 83.3%, and area under the curve (AUC) of 0.833. Subjective LA enlargement was 97.0% sensitive and 100% specific for CHF (AUC 0.985). Presence of PCEFF also was 100% specific, but only 60.6% sensitive, for CHF (AUC 0.803). A positive blood NT‐proBNP test was 93.9% sensitive and 72.2% specific for the diagnosis of CHF (AUC 0.831). Conclusions and Clinical Importance Point‐of‐care diagnostic techniques of LUS, FCU, and NT‐proBNP are useful to diagnose CHF in cats with respiratory distress.

Effects of short-term anti-inflammatory glucocorticoid treatment on clinicopathologic, echocardiographic, and hemodynamic variables in systemically healthy dogs

OBJECTIVE To investigate mechanisms by which anti-inflammatory doses of orally administered intermediate-acting glucocorticoids (prednisone) could predispose dogs to progression of heart disease or congestive heart failure. ANIMALS 11 client-owned dogs with allergic dermatitis and 11 matched healthy control dogs. PROCEDURES Clinicopathologic, echocardiographic, and hemodynamic variables were measured. Dogs with allergic dermatitis then received prednisone (1 mg/kg, PO) once daily for 14 consecutive days beginning on day 0 (baseline), followed by a tapering and washout period; control dogs received no treatment. Measurements were repeated on days 7, 14, and 35. Linear mixed modeling was used to compare changes in variables across measurement points and between dog groups. RESULTS Prednisone administration caused no significant changes in serum sodium or potassium concentration, blood glucose concentration, or target echocardiographic variables. The change from baseline in systolic arterial blood pressure at day 7 was significantly greater in prednisone-treated dogs than in control dogs. Expected changes in hematologic and serum biochemical values with prednisone administration (neutrophilia, eosinopenia, isosthenuria, and high serum alkaline phosphatase and alanine aminotransferase activities) also occurred in the prednisone-treated dogs. CONCLUSIONS AND CLINICAL RELEVANCE Findings suggested that anti-inflammatory doses of orally administered glucocorticoids have the potential to adversely impact cardiac function in dogs by causing an increase in blood pressure and thus increased cardiac afterload.