Clinical efficacy of sildenafil in treatment of pulmonary arterial hypertension in dogs.

BACKGROUND: Pulmonary arterial hypertension (PAH) in dogs carries a poor prognosis. Sildenafil increases exercise capacity and improves hemodynamics in people with PAH. HYPOTHESIS/OBJECTIVES: Dogs receiving sildenafil will have lower pulmonary arterial pressure, increased exercise capacity, and better quality of life (QOL) than dogs receiving placebo. ANIMALS: Thirteen dogs with echocardiographic evidence of PAH. METHODS: Prospective short-term, randomized, placebo controlled, double-blind, crossover study. Dogs with PAH were randomly allocated to receive sildenafil or placebo for 4 weeks, followed by the alternative treatment for 4 weeks. RESULTS: Dogs receiving sildenafil had a significantly lower estimated pulmonary arterial pressure (median, 56 mmHg; range, 34-83 mmHg) than at baseline (median, 72 mmHg; range, 61-86 mmHg; P=.018), but not significantly lower than those receiving placebo (median, 62 mmHg; range, 49-197 mmHg). Exercise capacity was significantly greater in dogs receiving sildenafil than those receiving placebo (mean activity count per minute: 101+/-47 versus 74+/-32; P=.05). QOL scores were significantly higher in dogs receiving sildenafil than dogs receiving placebo. CONCLUSIONS AND CLINICAL IMPORTANCE: Sildenafil decreases systolic pulmonary arterial pressure from baseline in dogs with PAH and is associated with increased exercise capacity and QOL when compared to treatment with placebo.

Perceptions of quality of life and priorities of owners of cats with heart disease.

BACKGROUND: Owners' perceptions and priorities regarding quality of life (QoL) are important considerations given the unknown efficacy of many commonly administered medications, stress of hospital visits, difficulties providing home care, and personal choices including euthanasia. OBJECTIVE: To describe the relative importance of quality versus quantity of life to owners of cats with heart disease. ANIMALS: Two hundred and thirty-nine cats with heart disease. METHODS: Prospective questionnaire-based clinical study. Cat owners completed a questionnaire to identify important parameters when assessing their cat's QoL, the relative importance of quality versus quantity of life, and willingness to trade survival time for QoL. Variables associated with these parameters were evaluated with multivariate analyses. RESULTS: Appetite, owner interaction, sleep patterns, and litterbox habits were deemed important to QoL. Concern over pet suffering was significantly greater than concern over life expectancy. Ninety-three percent of owners were willing to trade survival time for good QoL; 57% of these were willing to trade up to 6 months. On multivariate analysis, the only factor significantly (P=.002) associated with willingness to trade 6 months was study site. Owner concern regarding stress of administering medications at home increased with number and frequency of medications. CONCLUSIONS AND CLINICAL RELEVANCE: These results indicated that QoL is more important to owners of cats with heart disease than longevity. The various priorities and concerns of cat owners should be taken into account in order to provide optimal care.

Clinical characterization of cardiovascular abnormalities associated with feline mucopolysaccharidosis I and VI.

OBJECTIVE: The purpose of this study was to define the cardiovascular abnormalities present in young and adult cats affected with the lysosomal storage diseases mucopolysaccharidosis (MPS) I and MPS VI. METHOD: Eighteen cats affected with MPS I and 10 cats affected with MPS VI were evaluated by physical examination, electrocardiography and echocardiography. Electrocardiography (ECG) was performed on all MPS I and 9 of the MPS VI cats. Twelve unaffected cats underwent complete examinations for comparison purposes. RESULTS: No cardiovascular abnormalities were noted on physical examination. Measured ECG intervals were normal in affected cats; however, sinus arrhythmia was noted more frequently than in the unaffected cats. Significant echocardiographic abnormalities included aortic valve thickening, regurgitation and aortic root dilation. Significant mitral valve thickening was also noted. The severity of changes increased in older affected cats. CONCLUSION: As affected animals increased in age, more cardiac abnormalities were found with increasing severity. Significant lesions included the mitral and aortic valves and ascending aorta, but myocardial changes were not recognized. MPS I and MPS VI cats have similar cardiovascular findings to those seen in children and constitute important models for testing new MPS therapies.

Eisenmenger ventricular septal defect in a Humboldt penguin (Spheniscus humboldti).

The Eisenmenger ventricular septal defect is an uncommon type of ventricular septal defect characterised in humans by a traditionally perimembranous ventricular septal defect, anterior deviation (cranioventral deviation in small animal patients) of the muscular outlet septum causing malalignment relative to the remainder of the muscular septum, and overriding of the aortic valve. This anomaly is reported infrequently in human patients and was identified in a 45-day-old Humboldt Penguin, Spheniscus humboldti, with signs of poor growth and a cardiac murmur. This case report describes the findings in this penguin and summarises the anatomy and classification of this cardiac anomaly. To the authors' knowledge this is the first report of an Eisenmenger ventricular septal defect in a veterinary patient.

Gene therapy ameliorates cardiovascular disease in dogs with mucopolysaccharidosis VII.

BACKGROUND: Mucopolysaccharidosis VII (MPS VII) is a lysosomal storage disease caused by deficient beta-glucuronidase (GUSB) activity resulting in defective catabolism of glycosaminoglycans (GAGs). Cardiac disease is a major cause of death in MPS VII because of accumulation of GAGs in cardiovascular cells. Manifestations include cardiomyopathy, mitral and aortic valve thickening, and aortic root dilation and may cause death in the early months of life or may be compatible with a fairly normal lifespan. We previously reported that neonatal administration of a retroviral vector (RV) resulted in transduction of hepatocytes, which secreted GUSB into the blood and could be taken up by cells throughout the body. The goal of this study was to evaluate the effect on cardiac disease. METHODS AND RESULTS: Six MPS VII dogs were treated intravenously with an RV-expressing canine GUSB. Echocardiographic parameters, cardiovascular lesions, and biochemical parameters of these dogs were compared with those of normal and untreated MPS VII dogs. CONCLUSIONS: RV-treated dogs were markedly improved compared with untreated MPS VII dogs. Most RV-treated MPS VII dogs had mild or moderate mitral regurgitation at 4 to 5 months after birth, which improved or disappeared when evaluated at 9 to 11 and at 24 months. Similarly, mitral valve thickening present early in some animals disappeared over time, whereas aortic dilation and aortic valve thickening were absent at all times. Both myocardium and aorta had significant levels of GUSB and reduction in GAGs.

Familial dilated cardiomyopathy of young Portuguese water dogs.

A novel dilated cardiomyopathy (DCM) in 12 related Portuguese Water Dogs was identified by retrospective analysis of postmortem and biopsy case records. Male and female puppies born to clinically healthy parents typically died at 13 (+/- 7.3) weeks of age (range, 2-32 weeks) because of congestive heart failure. Puppies died suddenly without previous signs or with mild depression followed by clinical signs of congestive heart failure 1-5 days before death. There was no sex predilection. The hearts were enlarged and rounded, with marked left ventricular and atrial dilation. No other significant structural cardiac defects were noted. The histologic changes in the myocardium were diffuse and characterized by myofibers of irregular sizes separated by an edematous interstitium. The myofibers had multifocal swollen, cleared segments often involving perinuclear areas that contained granular, phosphotungstic-acid-hematoxylin-positive material consistent with mitochondria. There was loss of the cross-striation pattern, and intercalated discs were difficult to identify. There was no evidence of concurrent myocardial fibrosis; rare chronic inflammatory infiltrates were noted in one dog. Noncardiac skeletal muscles were not affected. The underlying cause is unknown. From the pedigree analysis, an autosomal recessive pattern of inheritance is suspected. Based on the histologic findings, this DCM is most likely due to an underlying molecular (biochemical or structural) defect. The early onset and rapid progression of the disease makes this a clinically distinctive form of canine DCM.

Cardiac troponin I in the normal dog and cat.

Cardiac troponin I (cTnI) has proven to be a highly specific and sensitive marker for myocardial cellular damage in many mammalian species. The structure of cTnI is highly conserved across species, and assays for human cTnI (including the one used in the current study) have been validated in the dog. Blood concentrations of cTnI rise rapidly after cardiomyocyte damage, and assay of cTnI potentially may be valuable in many clinical diseases. The purpose of this study was to establish the normal range of cTnI in heparinized plasma of dogs and cats. Forty one clinically normal dogs and 21 cats were included in the study. One to 3 milliliters of blood were collected by venipuncture into lithium heparin vacutainers for analysis of cTnI (Stratusz CS). The range of plasma cTnI concentrations in dogs was <0.03 to 0.07 ng/mL with a mean of 0.02 ng/mL, with the upper tolerance limit (0.07 ng/mL) at the 90th percentile with 95% confidence. In cats, the range was <0.03 to 0.16 ng/mL with a mean of 0.04 ng/mL, and the upper tolerance limit (0.16 ng/mL) at the 90th percentile as well with 90% confidence. This study establishes preliminary normal ranges of plasma cTnI in normal dogs and cats for comparison to dogs and cats with myocardial injury or disease.

Vertebral scale system to measure heart size in growing puppies.

OBJECTIVE: To determine relative heart size in clinically normal puppies and assess whether relative heart size changes with growth. DESIGN: Prospective radiographic study. ANIMALS: 11 puppies without evidence of disease. PROCEDURE: Standardized measurements of the long and short axes of the heart, midthoracic vertebrae, and other structures were made at 3, 6, 12, and 36 months of age. Measurements were recorded in millimeters and number of thoracic vertebral lengths spanned by each dimension, measured caudally from T4 on lateral radiographic views. The long and short axis measurements of the heart, expressed in vertebral lengths, were added to yield vertebral heart size. RESULTS: Mean +/- SD vertebral heart sizes on lateral radiographic views at 3, 6, 12, and 36 months of age were 10.0 +/- 0.5, 9.8 +/- 0.4, 9.9 +/- 0.6, and 10.3 +/- 0.6 vertebrae, respectively. Significant differences were not detected. CONCLUSIONS AND CLINICAL RELEVANCE: Vertebral heart size measurements in puppies are within the reference range for adult dogs (9.7 +/- 0.5 vertebrae) and do not change significantly with growth to 3 years of age. Standards for determining cardiac enlargement are similar in puppies and adult dogs.

Aortic root disease in four horses.

Clinical findings in 4 horses with aortic root disease are described. Three of the horses had aneurysms of the right aortic sinus, and in 2 of the 3, the aneurysm ruptured, creating a fistula between the aorta and right ventricle. One of these horses had had a murmur since birth, and the aortic sinus aneurysm may have been a congenital anomaly. In a second horse, the aneurysm may have been an acquired condition that developed secondary to chronic aortic regurgitation. Another horse had a large subendocardial hematoma associated with dissection of blood from the aorta to the interventricular septum because of a tear in the aortic root near the right aortic sinus. Ventricular ectopy and signs of abdominal pain were the most common initial signs in these horses.

Cardiotoxicity, inflammation, and immune response after rattlesnake envenomation in the horse.

BACKGROUND: Cardiac abnormalities are reported in rattlesnake-bitten horses. The prevalence and cause are unknown. OBJECTIVES: To detect cardiac damage in rattlesnake-bitten horses by measuring cardiac troponin I (cTnI) and evaluating ECG recordings for presence of arrhythmias, and explore causes of this cardiac damage by measuring venom excretion, anti-venom antibodies, and tumor necrosis factor alpha (TNFα). ANIMALS: A total of 20 adult horses with a clinical diagnosis of rattlesnake bite and 6 healthy adult horses. METHODS: In a prospective clinical study, bite site swabs, blood samples, and urine samples were collected at various time points from 20 horses with a clinical diagnosis of snake bite. Continuous ECG recordings were obtained on the 20 affected horses and 6 normal control horses using 24-hour holter monitors. Plasma samples were assayed for cTnI, serum samples were assayed for TNFα and anti-venom antibodies, and bite site swabs and urine were assayed for venom. RESULTS: Forty percent of rattlesnake-bitten horses (8/20) experienced myocardial damage (increased cTnI). Seventy percent (14/20) experienced a cardiac arrhythmia. There was a positive correlation between cTnI and TNFα (P < .02). Horses with cTnI ≥ 2 ng/mL were more likely to have antibody titers >5,000 (P < .05). No correlations were found between venom concentration and cTnI, anti-venom antibody titers, TNFα, or presence of arrhythmias. CONCLUSIONS AND CLINICAL IMPORTANCE: Cardiac abnormalities in this population of horses indicate that cardiac damage after rattlesnake bite is common. Rattlesnake-bitten horses should be monitored for signs of cardiac damage and dysfunction. Long-term follow-up should be encouraged to detect delayed cardiac dysfunction.

Cardiac magnetic resonance in the differentiation of neoplastic and nonneoplastic pericardial effusion.

BACKGROUND: Cardiac magnetic resonance (CMR) is the imaging modality of choice for cardiac tumors in people. Although neoplastic pericardial effusion (PE) carries a poor prognosis, benign idiopathic pericardial effusion does not. Definitive diagnosis is critical for surgical intervention, but currently available diagnostic techniques such as echocardiography and pericardial fluid cytology often are inconclusive. HYPOTHESIS/OBJECTIVE: Describe CMR findings associated with PE and determine whether CMR aids in differentiation of benign and neoplastic causes of PE. ANIMALS: Eight client-owned dogs with PE diagnosed by transthoracic echocardiography (TTE). METHODS: CMR was performed with a 1.5 T, including dark blood, steady-state free procession cine, pre- and postcontrast T1-weighted imaging, and delayed inversion recovery prepped imaging. RESULTS: CMR confirmed a cardiac mass and supported suspected tumor type in 4 dogs with suspected hemangiosarcoma. In 1 equivocal TTE case, CMR did not demonstrate a mass, but neoplasia was later diagnosed. In another equivocal case, CMR did not demonstrate a mass but showed findings consistent with a pericardiocentesis complication. In 1 dog without evidence of cardiac neoplasia, abdominal magnetic resonance imaging identified presumptive hepatic and splenic metastases. On reevaluation of the original CMR study, the 2 equivocal cases that were interpreted as tumor negative were reassessed as tumor positive. CONCLUSIONS AND CLINICAL IMPORTANCE: CMR did not substantially improve diagnosis of cardiac tumors compared with TTE in these 8 cases, but it yielded useful descriptive information regarding extent, anatomic location, and potential tumor type and confirmed that CMR requires extensive additional training for tumor identification.

Effect of azotemia on serum N-terminal proBNP concentration in dogs with normal cardiac function: a pilot study.

OBJECTIVES: To evaluate amino-terminal pro-B type natriuretic peptide (NT-proBNP) concentration in dogs with renal dysfunction and normal cardiac structure and function. ANIMALS: Eight dogs with renal disease, 23 healthy control dogs. METHODS: Serum NT-proBNP concentration was measured in healthy dogs and dogs with renal disease using an ELISA validated for use in dogs. Affected dogs were eligible for inclusion if renal dysfunction was diagnosed based on urinalysis and serum chemistry, and if they were free of cardiovascular disease based on physical exam, systolic blood pressure, and echocardiography. RESULTS: The geometric mean serum NT-proBNP concentration was significantly higher in dogs with renal disease (617 pmol/L; 95% CI, 260-1467 pmol/L) than in healthy control dogs (261 pmol/L; 95% CI, 225-303 pmol/L; P=0.0014). There was a modest positive correlation between NT-proBNP and BUN and creatinine. Median NT-proBNP concentration was not significantly different between groups when indexed to BUN (median NT-proBNP:BUN ratio; renal, 14.2, IQR, 3.93-17.7 vs. control, 16.3, IQR, 9.94-21.2; P=0.29) or creatinine (median NT-proBNP:creatinine ratio; renal, 204, IQR, 72.6-448 vs. control, 227, IQR, 179-308; P=0.67). CONCLUSION: Dogs with renal disease had significantly higher mean serum concentration of NT-proBNP than control dogs. Renal function should be considered when interpreting NT-proBNP results as concentrations may be falsely elevated in dogs with renal dysfunction and normal cardiac function. The effect of renal disease was lessened by indexing NT-proBNP to BUN or creatinine. Future studies in dogs with both renal and heart disease are warranted.

Endurance exercise is associated with increased plasma cardiac troponin I in horses.

REASON FOR PERFORMING STUDY: Information is lacking regarding the influence of long distance exercise on the systemic concentration of cardiac troponin I (cTnI) in horses. OBJECTIVES: To determine if the concentration of cTnI in horses competing in 80 and 160 km endurance races increases with exercise duration and if cTnI concentrations can be correlated with performance data. METHODS: Blood samples for the measurement of cTnI and 3 min electrocardiogram recordings were obtained from horses prior to, during and after completion of 80 and 160 km endurance races at 3 ride sites during the 2004 and 2005 American Endurance Ride Conference competition seasons. RESULTS: Full data sets were obtained from 100 of the 118 horses. Endurance exercise was associated with a significant increase in cTnI over baseline in both distance groups. Failure to finish competition (poor performance) was also associated with an increased cTnI concentration over baseline at the time of elimination when data from both distances were combined. Other than one horse that developed paroxysmal atrial fibrillation, no arrhythmias were noted on the 3 minute ECG recordings that were obtained after endurance exercise in either distance group. CONCLUSIONS: Systemic concentrations of cTnI increase in endurance horses competing in both 80 and 160 km distances. Although final cTnI concentrations were significantly increased over their baseline values in horses that failed to finish competition, the degree of increase was not greater than the increase over baseline seen in the horses that successfully completed competition. The clinical significance of increased cTnI in exercising horses could not be ascertained from the results of this study. POTENTIAL RELEVANCE: These data indicate that cardiac stress may occur in horses associated with endurance exercise. Future studies utilising echocardiograpy to assess cardiac function in horses with increased cTnI are warranted.

Inheritance, biochemical abnormalities, and clinical features of feline mucolipidosis II: the first animal model of human I-cell disease.

Mucolipidosis II (ML II), also called I-cell disease, is a unique lysosomal storage disease caused by deficient activity of the enzyme N-acetylglucosamine-1-phosphotransferase, which leads to a failure to internalize enzymes into lysosomes. We report on a colony of domestic shorthair cats with ML II that was established from a half-sibling male of an affected cat. Ten male and 9 female kittens out of 89 kittens in 26 litters born to clinically normal parents were affected; this is consistent with an autosomal recessive mode of inheritance. The activities of three lysosomal enzymes from affected kittens, compared to normal adult control cats, were high in serum (11-73 times normal) but low in cultured fibroblasts (9-56% of normal range) that contained inclusion bodies (I-cells), reflecting the unique enzyme defect in ML II. Serum lysosomal enzyme activities of adult obligate carriers were intermediate between normal and affected values. Clinical features in affected kittens were observed from birth and included failure to thrive, behavioral dullness, facial dysmorphia, and ataxia. Radiographic lesions included metaphyseal flaring, radial bowing, joint laxity, and vertebral fusion. In contrast to human ML II, diffuse retinal degeneration leading to blindness by 4 months of age was seen in affected kittens. All clinical signs were progressive and euthanasia or death invariably occurred within the first few days to 7 months of life, often due to upper respiratory disease or cardiac failure. The clinical and radiographic features, lysosomal enzyme activities, and mode of inheritance are homologous with ML II in humans. Feline ML II is currently the only animal model in which to study the pathogenesis of and therapeutic interventions for this unique storage disease.