Budd-Chiari-like syndrome in a dog secondary to a gunshot wound treated with balloon angioplasty and endovascular stent placement.

A 6-year-old female spayed Chihuahua mix presented with chronic recurrent ascites. Computed tomographic angiography revealed an isolated stenosis of the caudal vena cava secondary to a metallic foreign body, resulting in Budd-Chiari-like syndrome. Balloon angioplasty and endovascular stent placement successfully resolved the obstruction with long-term resolution of ascites.

Prevalence, geographic distribution, and impact on lifespan of a dilated cardiomyopathy-associated RNA-binding motif protein 20 variant in genotyped dogs.

INTRODUCTION: The study objectives were to determine the prevalence and geographic distribution of a dilated cardiomyopathy (DCM)-associated RNA-binding motif protein 20 (RBM20) variant in canine DNA samples submitted for testing and to evaluate the influence of the genotype on cardiac phenotype and lifespan. ANIMALS: Samples from 2136 dogs including 1834 Standard Schnauzers (SSNZ), 266 Giant Schnauzers (GSNZ), and 36 dogs of other breeds. METHODS: The University of Missouri Canine Genetics Laboratory's sample-accession spreadsheet and Orthopedic Foundation for Animals' database were retrospectively reviewed for samples submitted for RBM20 genotyping from November, 2013, through May, 2018. Data analyzed included breed, date of birth, RBM20 genotype (homozygous wild-type, heterozygous variant [HET], or homozygous variant [HOM]), geographic origin of submission, pedigree, cardiac phenotype, and date of death or current age if alive. RESULTS AND DISCUSSION: The RBM20 variant was only detected in SSNZ and GSNZ. A total of 389 SSNZ were variant-positive (prevalence = 21.2%), with 361 HET (19.7%) and 28 HOM (1.5%). Of the HOM SSNZ, DCM was confirmed in 26 of 28 (92.9%), with the remainder lost to follow-up. The median lifespan of HOM SSNZ (3.06 years) was significantly shorter than that for HET (15.11 years) and wild-type (15.18 years) SSNZ. Twenty-six GSNZ were variant-positive (prevalence = 9.8%), with 23 HET (8.6%) and three HOM (1.1%). Nine GSNZ belonged to one family, including the three HOM GSNZ that all had DCM. CONCLUSIONS: The HOM genotype is associated with DCM and premature death in SSNZ and GSNZ.

Pulmonary hypertension secondary to respiratory disease and/or hypoxia in dogs: Clinical features, diagnostic testing and survival.

Pulmonary hypertension (PH) is associated with substantial morbidity and if untreated, mortality. The human classification of PH is based on pathological, hemodynamic characteristics, and therapeutic approaches. Despite being a leading cause of PH, little is known about dogs with respiratory disease and/or hypoxia (RD/H)-associated PH. Therefore, our objectives were to retrospectively describe clinical features, diagnostic evaluations, final diagnoses and identify prognostic variables in dogs with RD/H and PH. In 47 dogs identified with RD/H and PH, chronic airway obstructive disorders, bronchiectasis, bronchiolar disease, emphysema, pulmonary fibrosis, neoplasia and other parenchymal disorders were identified using thoracic radiography, computed tomography, fluoroscopy, tracheobronchoscopy, bronchoalveolar lavage, and histopathology. PH was diagnosed using transthoracic echocardiography. Overall median survival was 276.0 days (SE, 95% CI; 216, 0-699 days). Dogs with an estimated systolic pulmonary arterial pressure (sPAP) ≥47mmHg (n=21; 9 days; 95% CI, 0-85 days) had significantly shorter survival times than those <47mmHg (n=16; P=0.001). Estimated sPAP at a cutoff of ≥47mmHg was a fair predictor of non-survival with sensitivity of 0.78 (95% CI, 0.52-0.94) and specificity of 0.63 (95% CI, 0.38-0.84). Phosphodiesterase-5 (PDE5) inhibitor administration was the sole independent predictor of survival in a multivariable analysis (hazard ratio: 4.0, P=0.02). Canine PH is present in a diverse spectrum of respiratory diseases, most commonly obstructive disorders. Similar to people, severity of PH is prognostic in dogs with RD/H and PDE5 inhibition could be a viable therapy to improve outcome.

Clinical efficacy of tadalafil compared to sildenafil in treatment of moderate to severe canine pulmonary hypertension: a pilot study.

INTRODUCTION: Canine pulmonary hypertension (PH) is associated with high morbidity and mortality. Tadalafil, a phosphodiesterase-5 inhibitor used commonly in humans with PH, has not been evaluated in a clinical trial in dogs with naturally occurring PH. Our objectives were to compare the efficacy of tadalafil and sildenafil on PH assessed by peak tricuspid regurgitant flow velocity, estimated systolic pulmonary arterial pressure gradient, voluntary activity, quality of life, and safety profiles in dogs with moderate to severe PH. ANIMALS: Twenty-three dogs with echocardiographic evidence of moderate to severe PH were enrolled. METHODS: A prospective short-term, randomized, double-blinded pilot study was carried out. Dogs with PH were randomly allocated to receive sildenafil or tadalafil for 2 weeks and assessed via echocardiography, activity monitors, and owner-reported outcomes. RESULTS: Collectively, phosphodiesterase-5 inhibition significantly decreased (improved) quality of life scores (p = 0.003) and visual analog score (p = 0.024) without significant between-treatment difference of these variables. Phosphodiesterase-5 inhibition did not significantly affect peak tricuspid regurgitant flow velocity (p = 0.056) or voluntary activity (p = 0.27). A total of 33% (7/21) of dogs experienced at least one adverse event during the study (tadalafil, n = 5; sildenafil, n = 2) with no significant difference between treatment type and incidence of adverse events (p = 0.36). DISCUSSION: In this pilot study, phosphodiesterase-5 inhibition led to apparent improvement in quality of life scores without documenting superiority of tadalafil over sildenafil. CONCLUSION: Tadalafil at a dose of 2 mg/kg once daily appears to be a viable alternative to sildenafil in dogs with moderate to severe PH.

Extraneuronal pathology in a canine model of CLN2 neuronal ceroid lipofuscinosis after intracerebroventricular gene therapy that delays neurological disease progression.

CLN2 neuronal ceroid lipofuscinosis is a hereditary lysosomal storage disease with primarily neurological signs that results from mutations in TPP1, which encodes the lysosomal enzyme tripeptidyl peptidase-1 (TPP1). Studies using a canine model for this disorder demonstrated that delivery of TPP1 enzyme to the cerebrospinal fluid (CSF) by intracerebroventricular administration of an AAV-TPP1 vector resulted in substantial delays in the onset and progression of neurological signs and prolongation of life span. We hypothesized that the treatment may not deliver therapeutic levels of this protein to tissues outside the central nervous system that also require TPP1 for normal lysosomal function. To test this hypothesis, dogs treated with CSF administration of AAV-TPP1 were evaluated for the development of non-neuronal pathology. Affected treated dogs exhibited progressive cardiac pathology reflected by elevated plasma cardiac troponin-1, impaired cardiac function and development of histopathological myocardial lesions. Progressive increases in the plasma activity levels of alanine aminotransferase and creatine kinase indicated development of pathology in the liver and muscles. The treatment also did not prevent disease-related accumulation of lysosomal storage bodies in the heart or liver. These studies indicate that optimal treatment outcomes for CLN2 disease may require delivery of TPP1 systemically as well as directly to the central nervous system.