Background
Pimobendan is an important therapy for dogs with myxomatous mitral valve disease (MMVD). The pharmacokinetics are reported in healthy dogs but not in dogs with heart disease.
...Hypothesis/Objectives
To determine if dog characteristics such as age, breed, body condition score, ACVIM stage of heart disease or biochemical laboratory value alter the pharmacokinetics of orally administered pimobendan and its metabolite in a cohort of dogs with naturally occurring MMVD.
Animals
Fifty‐seven client‐owned dogs with MMVD ACVIM Stage B2, C, or D and administered pimobendan to steady state blood concentrations.
Methods
Prospective, observational study. Samples were collected using a sparse‐sampling protocol at specific intervals after administration of pimobendan. Plasma pimobendan and the active metabolite (O‐desmethyl‐pimobendan, ODMP) concentrations were determined via high‐pressure liquid chromatography and fluorescence detection. Data was analyzed via a population pharmacokinetic approach and nonlinear mixed effects modeling (NLME). Numerous covariates were examined in the NLME model.
Results
The absorption and elimination half‐lives (t1/2) were approximately 1.4 and 1 hour for pimobendan and 1.4 and 1.3 hours for ODMP, respectively. Pharmacokinetic parameters were highly variable, especially the values for pimobendan absorption and elimination rate, and absorption rate of ODMP with coefficients of variation of 147.84%, 64.51% and 64.49%, respectively. No covariate evaluated was a significant source of variability.
Conclusions and Clinical Importance
The pharmacokinetic parameters were highly variable among this group of dogs with MMVD. The variability was not associated with the dog's age, body weight or condition score, stage of heart disease, dose, serum creatinine, or alkaline phosphatase.
Ultrasonographic indices of the inferior vena cava are useful for predicting right heart filling pressures in people.
To determine whether ultrasonographic indices of caudal vena cava (CVC) differ ...between dogs with right-sided CHF (R-CHF), left-sided CHF (L-CHF), and noncardiac causes of cavitary effusion (NC).
113 dogs diagnosed with R-CHF (n = 51), L-CHF (30), or NC effusion (32) were enrolled. Seventeen of the R-CHF dogs had pericardial effusion and tamponade. Focused ultrasound was performed prospectively to obtain 2-dimensional and M-mode subxiphoid measures of CVC maximal and minimal size (CVCmax and CVCmin), CVCmax indexed to aortic dimension (CVC:Ao), and CVC collapsibility index (CVC-CI). Variables were compared between study groups using Kruskal-Wallis and Dunn's-Bonferroni testing, and receiver operating characteristics curves were used to assess sensitivity and specificity.
All sonographic CVC indices were significantly different between R-CHF and NC dogs (P < 0.001). Variables demonstrating the highest diagnostic accuracy for discriminating R-CHF versus NC were CVC-CI <33% in 2D (91% sensitive and 96% specific) and presence of hepatic venous distension (84% sensitive and 90% specific). L-CHF dogs had higher CVC:Ao and lower CVC-CI compared to NC dogs (P = 0.016 and P = 0.043 in 2D, respectively) but increased CVC-CI compared to the R-CHF group (P < 0.001).
Ultrasonographic indices of CVC size and collapsibility differed between dogs with R-CHF compared to NC causes of cavitary effusions. Dogs with L-CHF have CVC measurements intermediate between R-CHF and NC dogs.
This study aimed to determine the current use of ultrasound amongst small animal veterinarians. A total of 1216 small animal veterinary practitioners responded to an electronic survey that was ...administered through the Veterinary Information Network to all its members. Descriptive statistics were generated; limited inferential statistics were performed to examine specific relationships. Eighty-four percent of respondents had access to an ultrasound unit, and 86% of respondents reported using their unit multiple times per week. The most common uses were assistance with cystocentesis (93%) and abdominocentesis (71%), pregnancy diagnosis (69%), limited abdominal evaluation (63%), to aid in thoracocentesis (59%), and limited thoracic evaluation (52%). Eighty-nine percent of respondents received some formal training in ultrasound, most commonly from continuing education courses. Most respondents (52%) reported receiving ≤25 h of training. Additionally, 88% of respondents believed it was either extremely or very important for there to be ultrasound training for veterinary students prior to graduation. Based on this survey, most small animal practitioners commonly use ultrasound for limited examinations, being most confident in the sonographic evaluation and centesis of the bladder and for the detection and centesis of effusion in a body cavity. With most respondents having ≤25 h of training in ultrasound, typically obtained in postgraduate courses, an expansion in standardized basic ultrasound training within the veterinary curriculum may be warranted.
Background
Point‐of‐care lung ultrasound (LUS) is an effective tool to diagnose left‐sided congestive heart failure (L‐CHF) in dogs via detection of ultrasound artifacts (B‐lines) caused by increased ...lung water.
Hypothesis/Objectives
To determine whether LUS can be used to monitor resolution of cardiogenic pulmonary edema in dogs, and to compare LUS to other indicators of L‐CHF control.
Animals
Twenty‐five client‐owned dogs hospitalized for treatment of first‐onset L‐CHF.
Methods
Protocolized LUS, thoracic radiographs (TXR), and plasma N‐terminal pro‐B‐type natriuretic peptide were performed at hospital admission, hospital discharge, and recheck examinations. Lung ultrasound findings were compared between timepoints and to other clinical measures of L‐CHF.
Results
From time of hospital admission to discharge (mean 19.6 hours), median number of LUS sites strongly positive for B‐lines (>3 B‐lines per site) decreased from 5 (range, 1‐8) to 1 (range, 0‐5; P < .001), and median total B‐line score decreased from 37 (range, 6‐74) to 5 (range, 0‐32; P = .002). Lung ultrasound indices remained improved at first recheck (P < .001). Number of strong positive sites correlated positively with respiratory rate (r = 0.52, P = .008) and TXR edema score (r = 0.51, P = .009) at hospital admission. Patterns of edema resolution differed between LUS and TXR, with cranial quadrants showing more significant reduction in B‐lines compared to TXR edema score (80% vs 29% reduction, respectively; P = .003).
Conclusions and Clinical Importance
Lung ultrasound could be a useful tool for monitoring resolution of pulmonary edema in dogs with L‐CHF.
Objective
To assess distribution of alveolar‐interstitial syndrome (AIS) detected by lung ultrasound (LUS) compared to thoracic radiographs (TXR).
Design
Prospective study.
Setting
University ...teaching hospital.
Animals
Seventy‐six dogs and 24 cats with acute respiratory distress or tachypnea.
Interventions
Patients underwent LUS and TXR within 6 hours. Lung ultrasound images were scored for presence and quantity of B‐lines in 4 lung quadrants (right cranial, right caudal, left cranial, left caudal). An individual LUS quadrant was scored positive if > 3 B‐lines were observed within a single intercostal space. Dorsoventral TXR were scored for presence of AIS in the same 4 quadrants. An individual TXR quadrant was scored positive if infiltrate was present in ≥ 25% of the quadrant. Medical records were evaluated for final diagnosis.
Measurements and Main Results
Quadrant‐by‐quadrant spatial agreement in assigning AIS using LUS versus TXR was fair (K = 0.24 – 0.56). Lung ultrasound scored a higher number of quadrants positive per patient (2.65 ± 1.59 vs. 2.13 ± 1.48; P = 0.012). Patterns of distribution of AIS differed significantly based on final diagnosis. Patients with left‐sided congestive heart failure were more likely to have diffuse AIS on LUS (P < 0.001) or bilateral caudal AIS on TXR (P = 0.04) while patients with noncardiac disease were more likely to have absence of AIS in all quadrants using either modality (P < 0.001). Differences in spatial distribution of AIS were also noted among disease subcategories.
Conclusions
Lung ultrasound and TXR were both useful to detect and categorize distribution of alveolar or interstitial pulmonary pathology. Spatial agreement between modalities was only fair. Overall, LUS detected a higher incidence of AIS compared to TXR. Both modalities detected differences in distribution of AIS based on final diagnosis, suggesting that a regional pattern‐based approach to thoracic imaging may prove diagnostically useful.
Cardiac emergencies are life-threatening conditions that must be diagnosed quickly to avoid delays in therapy. A timely and accurate diagnosis leads to early relief of symptoms and improved survival. ...This article provides both a comprehensive review and updated management recommendations for common cardiac emergencies in dogs and cats. Specifically, the article confers updates for the efficient clinical recognition of decompensated cardiac patients, including focused echocardiography, cardiac biomarkers, and electrocardiogram interpretation. This article also reviews the latest recommendations for the treatment of heart failure (including the use of pimobendan) and the management of arrhythmias, pericardial effusion, and aortic thromboembolism.
OBJECTIVE To determine the accuracy of a point-of-care lung ultrasonography (LUS) protocol designed to diagnose cardiogenic pulmonary edema (CPE) in dyspneic dogs and cats. DESIGN Diagnostic test ...evaluation. ANIMALS 76 dogs and 24 cats evaluated for dyspnea. PROCEDURES Dogs and cats were evaluated by LUS; B lines were counted at 4 anatomic sites on each hemithorax. A site was scored as positive when > 3 B lines were identified. Animals with ≥ 2 positive sites identified on each hemithorax were considered positive for CPE. Medical records were evaluated to obtain a final diagnosis (reference standard) for calculation of the sensitivity and specificity of LUS and thoracic radiography for the diagnosis of CPE. RESULTS Dogs and cats with a final diagnosis of CPE had a higher number of positive LUS sites than did those with noncardiac causes of dyspnea. Overall sensitivity and specificity of LUS for the diagnosis of CPE were 84% and 74%, respectively, and these values were similar to those of thoracic radiography (85% and 87%, respectively). Use of LUS generally led to the misdiagnosis of CPE (ie, a false-positive result) in animals with diffuse interstitial or alveolar disease. Interobserver agreement on LUS results was high (κ > 0.85). CONCLUSIONS AND CLINICAL RELEVANCE LUS was useful for predicting CPE as the cause of dyspnea in dogs and cats, although this technique could not be used to differentiate CPE from other causes of diffuse interstitial or alveolar disease. Point-of-care LUS has promise as a diagnostic tool for dyspneic dogs and cats.
Familial hypertrophic cardiomyopathy is a common inherited cardiovascular disorder in people. Many causal mutations have been identified, but about 40% of cases do not have a known causative ...mutation. Mutations in the ALMS1 gene are associated with the development of Alstrom syndrome, a multisystem familial disease that can include cardiomyopathy (dilated, restrictive). Hypertrophic cardiomyopathy has not been described. The ALMS1 gene is a large gene that encodes for a ubiquitously expressed protein. The function of the protein is not well understood although it is believed to be associated with energy metabolism and homeostasis, cell differentiation and cell cycle control. The ALMS1 protein has also been shown to be involved in the regulation of cell cycle proliferation in perinatal cardiomyocytes. Although cardiomyocyte cell division and replication in mammals generally declines soon after birth, inhibition of ALMS1 expression in mice lead to increased cardiomyocyte proliferation, and deficiency of Alstrom protein has been suggested to impair post-natal cardiomyocyte cell cycle arrest. Here we describe the association of familial hypertrophic cardiomyopathy in Sphynx cats with a novel ALMS1 mutation.
A G/C variant was identified in exon 12 (human exon 13) of the ALMS1 gene in affected cats and was positively associated with the presence of hypertrophic cardiomyopathy in the feline population (p < 0.0001). The variant was predicted to change a highly conserved nonpolar Glycine to a positively charged Arginine. This was predicted to be a deleterious change by three in silico programs. Protein prediction programs indicated that the variant changed the protein structure in this region from a coil to a helix. Light microscopy findings included myofiber disarray with interstitial fibrosis with significantly more nuclear proliferative activity in the affected cats than controls (p < 0.0001).
This study demonstrates a novel form of cardiomyopathy associated with ALMS1 in the cat. Familial hypertrophic cardiomyopathy is a disease of genetic heterogeneity; many of the known causative genes encoding for sarcomeric proteins. Our findings suggest that variants in genes involved with cardiac development and cell regulation, like the ALMS1 gene, may deserve further consideration for association with familial hypertrophic cardiomyopathy.
The dog provides a large animal model of familial dilated cardiomyopathy for the study of important aspects of this common familial cardiovascular disease. We have previously demonstrated a form of ...canine dilated cardiomyopathy in the Doberman pinscher breed that is inherited as an autosomal dominant trait and is associated with a splice site variant in the pyruvate dehydrogenase kinase 4 (
PDK4
) gene, however, genetic heterogeneity exists in this species as well and not all affected dogs have the
PDK4
variant. Whole genome sequencing of a family of Doberman pinchers with dilated cardiomyopathy and sudden cardiac death without the
PDK4
variant was performed. A pathologic missense variant in the titin gene located in an immunoglobulin-like domain in the I-band spanning region of the molecule was identified and was highly associated with the disease (
p
< 0.0001). We demonstrate here the identification of a variant in the titin gene highly associated with the disease in this spontaneous canine model of dilated cardiomyopathy. This large animal model of familial dilated cardiomyopathy shares many similarities with the human disease including mode of inheritance, clinical presentation, genetic heterogeneity and a pathologic variant in the titin gene. The dog is an excellent model to improve our understanding of the genotypic phenotypic relationships, penetrance, expression and the pathophysiology of variants in the titin gene.
To characterize lung ultrasonography (LUS) findings in dogs with a primary clinical complaint of cough.
100 client-owned coughing dogs.
A standardized LUS examination was performed for all dogs to ...quantify the number of B lines and identify subpleural abnormalities at 4 sites on each hemithorax. The final clinical diagnosis (reference standard) was determined by medical record review, and sensitivity and specificity of LUS for the diagnosis of selected causes of cough was determined.
Common underlying causes of cough included dynamic airway collapse (n = 37), cardiogenic pulmonary edema (CPE; 12), and bronchitis (10). Compared with dogs with other causes of cough, dogs with bacterial pneumonia (n = 7) were more likely to have subpleural shred signs, whereas dogs with pulmonary neoplasia (4) were more likely to have subpleural nodule signs. Dogs with CPE had higher total B-line scores and higher numbers of LUS sites strongly positive for B lines (> 3 B lines/site) than other dogs. The LUS criteria of total B-line score ≥ 10 and presence of ≥ 2 sites strongly positive for B lines were each 92% sensitive and 94% specific for CPE diagnosis. Notably, 18% (16/88) of dogs with noncardiac causes of cough had been treated previously with diuretics because of prior CPE misdiagnosis.
LUS profiles in dogs with cough differed by the underlying cause. In dogs with a clinical history of cough, this imaging modality could be diagnostically useful, particularly to help exclude the possibility of underlying CPE.
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