Evaluation of Galectin-3 in Dogs with Atrial Fibrillation.

Galectin-3 (Gal-3) is a lectin associated with fibrosis and inflammation, and increased circulating concentrations are considered a risk factor for atrial fibrillation (AF) in humans. This retrospective study aimed to evaluate the serum concentration of Gal-3 in dogs with cardiac disease, both with and without AF. Dogs with AF associated with acquired heart diseases were selected, while cardiac healthy dogs and dogs with heart diseases but without AF served as controls. We statistically compared the serum concentration of Gal-3, which was assessed using a commercial canine-specific ELISA kit, among healthy dogs and dogs with heart disease with and without AF. Additionally, associations between Gal-3 and clinical and echocardiographic variables were evaluated. A total of 73 dogs were included, of which 17/73 (23.3%) were cardiac healthy and 56/73 (76.7%) had heart disease, with 26/56 (46.4%) having AF. No significant difference in Gal-3 concentration was found between cardiac healthy dogs (3.90 ± 1.65 ng/mL) and dogs with heart disease, either with or without AF (3.37 ± 1.04 ng/mL, p = 0.436 and 4.68 ± 1.80 ng/mL, p = 0.332, respectively). Gal-3 showed a significant positive correlation with age (r = 0.47, p < 0.001) and a negative correlation with body weight (r = -0.45, p < 0.001). The results of this study suggest that Gal-3 does not have an important role in the development of AF in dogs, but it is associated with advanced age.

Development of an artificial intelligence-based algorithm for predicting the severity of myxomatous mitral valve disease from thoracic radiographs by using two grading systems.

A heart-convolutional neural network (heart-CNN) was designed and tested for the automatic classification of chest radiographs in dogs affected by myxomatous mitral valve disease (MMVD) at different stages of disease severity. A retrospective and multicenter study was conducted. Lateral radiographs of dogs with concomitant X-ray and echocardiographic examination were selected from the internal databases of two institutions. Dogs were classified as healthy, B1, B2, C and D, based on American College of Veterinary Internal Medicine (ACVIM) guidelines, and as healthy, mild, moderate, severe and late stage, based on Mitral INsufficiency Echocardiographic (MINE) score. Heart-CNN performance was evaluated using confusion matrices, receiver operating characteristic curves, and t-SNE and UMAP analysis. The area under the curve (AUC) was 0.88, 0.88, 0.79, 0.89 and 0.84 for healthy and ACVIM stage B1, B2, C and D, respectively. According to the MINE score, the AUC was 0.90, 0.86, 0.71, 0.82 and 0.82 for healthy, mild, moderate, severe and late stage, respectively. The developed algorithm showed good accuracy in predicting MMVD stages based on both classification systems, proving a potentially useful tool in the early diagnosis of canine MMVD.

Risk Factors for Atrial Fibrillation in the Dog: A Systematic Review.

Different risk factors for atrial fibrillation (AF) development have been identified in numerous studies on humans, but this information is less clearly available on the dog. The aim of this systematic review is to determine the risk factors for AF in the dog. Following the PRISMA 2020 guidelines, we conducted a comprehensive search using the Web of Science and Scopus databases for articles reporting on cases of spontaneously occurring AF in dogs. The level of evidence was assessed using the Evidence Quality Grading System of the National Institute of Health. One thousand forty-three studies were initially identified, and twenty of them were included in this systematic review involving 2,359,275 dogs, of which 4807 showed spontaneously occurring AF. Genetics, for the Irish Wolfhound, increased body weight, and left atrial enlargement were the main risk factors for the development of AF in dogs with different cardiac diseases, particularly myxomatous mitral valve disease (MMVD) and dilated cardiomyopathy (DCM). However, some differences were found between these two cardiac diseases regarding additional risk factors. In particular, the presence of congestive heart failure and echocardiographic evidence of increased left atrial pressure or the presence of right atrial enlargement emerged as risk factors in dogs with MMVD or DCM, respectively. Furthermore, significant differences in risk factors were observed between dogs and humans. In particular, advanced age and male sex are not reliable indicators of an increased risk of AF in dogs.

Development of an artificial intelligence-based method for the diagnosis of the severity of myxomatous mitral valve disease from canine chest radiographs.

An algorithm based on artificial intelligence (AI) was developed and tested to classify different stages of myxomatous mitral valve disease (MMVD) from canine thoracic radiographs. The radiographs were selected from the medical databases of two different institutions, considering dogs over 6 years of age that had undergone chest X-ray and echocardiographic examination. Only radiographs clearly showing the cardiac silhouette were considered. The convolutional neural network (CNN) was trained on both the right and left lateral and/or ventro-dorsal or dorso-ventral views. Each dog was classified according to the American College of Veterinary Internal Medicine (ACVIM) guidelines as stage B1, B2 or C + D. ResNet18 CNN was used as a classification network, and the results were evaluated using confusion matrices, receiver operating characteristic curves, and t-SNE and UMAP projections. The area under the curve (AUC) showed good heart-CNN performance in determining the MMVD stage from the lateral views with an AUC of 0.87, 0.77, and 0.88 for stages B1, B2, and C + D, respectively. The high accuracy of the algorithm in predicting the MMVD stage suggests that it could stand as a useful support tool in the interpretation of canine thoracic radiographs.

Risk factors for atrial fibrillation in dogs with dilated cardiomyopathy.

Introduction: Atrial fibrillation secondary to dilated cardiomyopathy (DCM) frequently affects large-breed dogs. The aim of the present study was to identify risk factors for the development of atrial fibrillation in dogs of different breeds with an echocardiographic diagnosis of DCM. Methods: In this multicenter retrospective study, we searched the electronic databases of five cardiology referral centers for dogs with an echocardiographic diagnosis of DCM. A comparison of clinical and echocardiographic variables was performed between dogs developing atrial fibrillation and those not developing atrial fibrillation and the ability to distinguish between these two groups of dogs was evaluated by receiver operating characteristic curve analysis. Univariate and multivariable logistic regression analysis estimated the odds ratio (OR) with 95% confidence interval (CI) of developing atrial fibrillation. Results: We included 89 client-owned dogs with occult and overt echocardiographic DCM. Of these, 39 dogs (43.8%) had atrial fibrillation, 29 dogs (32.6%) maintained a sinus rhythm, and 21 dogs (23.6%) showed other cardiac arrhythmias. Left atrial diameter had high accuracy (area under the curve = 0.816, 95% CI = 0.719-0.890) to predict the development of atrial fibrillation at the cut-off of >4.66 cm. After multivariable stepwise logistic regression analysis, only increased left atrial diameter (OR = 3.58, 95% CI = 1.87-6.87; p < 0.001) and presence of right atrial enlargement (OR = 4.02, 95% CI = 1.35-11.97; p = 0.013) were significant predictors of atrial fibrillation development. Discussion: Atrial fibrillation is a common complication of DCM in the dog and is significantly associated with increased absolute left atrial diameter and right atrial enlargement.

Red Blood Cell Distribution Width as a Novel Parameter in Canine Disorders: Literature Review and Future Prospective.

Red blood cell distribution width (RDW) is a quantitative laboratory parameter applied for the measurement of anisocytosis and is a reliable and inexpensive method for clinical classification of anemia. An increased RDW reflects a great heterogeneity in the size of red blood cells typical of regenerative and iron-deficiency anemia. In humans, numerous and recent studies have shown a relationship between increased RDW and the risk of morbidity and mortality in patients with various disorders. In particular, a strong association has been established between changes in RDW and the risk of adverse outcome in humans with diseases affecting different organs or systems. Following the human literature, some studies have recently been conducted trying to clarify the clinical role of RDW in various animal disorders, particularly in dogs. In this review, we summarize and critically evaluate the results of the studies based on the measurement of RDW in dogs. We also emphasize the need for further and more extensive studies on the use of this simple and inexpensive parameter in animals.

Prevalence and prognostic role of L wave and selected clinical and echocardiographic variables in dogs with atrial fibrillation.

BACKGROUND: Information regarding the frequency of L waves and their prognostic relevance in dogs with secondary atrial fibrillation (AF) is limited. HYPOTHESIS/OBJECTIVES: To determine whether L waves occur and ascertain their prognostic role, as well as the role of other clinical and echocardiographic variables in dogs with AF. ANIMALS: Fifty-five dogs with AF associated with myxomatous mitral valve disease or dilated cardiomyopathy. METHODS: Retrospective, multicenter observational study. In addition to L waves analysis, other clinical and echocardiographic variables, including type of antiarrhythmic treatment, were evaluated. A survival analysis was performed to test for predictors of cardiac death and all-cause mortality using Cox proportional hazards regression models. RESULTS: L waves were evident in 33/55 dogs (60%, 95% confidence interval [CI] = 47%-72%) but their presence did not influence outcome. Increased left ventricular end-systolic diameter normalized for body weight (LVSDn) was a significant predictor of both cardiac death (hazard ratio [HR] = 4.41, 95% CI = 1.18-16.54; P = .03) and all-cause mortality (HR = 9.39, 95% CI = 2.49-35.32; P < .001). Heart rate assessed during echocardiography (Echo-HR) represented an additional significant predictor of cardiac death (HR = 1.01, 95% CI = 1.00-1.01; P = .04) and all-cause mortality (HR = 1.01, 95% CI = 1.00-1.01; P = .04). CONCLUSIONS AND CLINICAL IMPORTANCE: L waves occurred frequently in dogs with AF, but held no prognostic relevance. Conversely, LVSDn and Echo-HR represented independent predictors of negative outcome in these animals.

Radiographic features of cardiogenic pulmonary oedema in cats with left-sided cardiac disease: 71 cases.

OBJECTIVES: The aims of this study were to describe the radiographic features of cardiogenic pulmonary oedema (CPE) in a large group of cats with left-sided cardiac disease, and to determine the association between the radiographic features of CPE and the underlying cardiac disease. METHODS: Thoracic radiographs of cats with CPE and echocardiographic evidence of left-sided cardiac disease and left atrial enlargement (LAE) were reviewed, and cardiac silhouette, pulmonary vessels and pulmonary parenchyma evaluation were performed. Interstitial and/or alveolar patterns were classified according to their distribution (ie, diffuse, multifocal or focal) and location (ie, craniodorsal, cranioventral, caudodorsal, caudoventral and perihilar). A Student's t-test and Mann-Whitney U-test, or the two-proportion z-test, were used to compare continuous or categorical variables, respectively, between cats affected by the two most represented cardiac diseases, namely hypertrophic cardiomyopathy (HCM) and restrictive cardiomyopathy (RCM). RESULTS: Seventy-one cats were included; among them, 46 (64.7%) and 13 (18.3%) had presented for HCM and RCM, respectively. Subjective and objective cardiomegaly, and subjective and objective LAE were detected in 97.2% and 91.9% of cats and in 80.3% and 40.6% of cats, respectively. Pulmonary artery abnormalities, in particular caudal pulmonary artery dilation, were found in 77.5% of cats. Pulmonary artery to pulmonary vein ratio = 1 was found in 71.8% and 55% cats on right lateral and ventrodorsal or dorsoventral views, respectively. Interstitial (57.8%) and mixed interstitial-alveolar (38%) pattern, multifocal (84.5%) and symmetrical (75%) distribution with prevalent ventrocaudal (65.6% of cats) and ventrocranial (60.9% of cats) locations were most frequently observed. No difference was found for any of these radiographic features between cats with HCM and RCM. CONCLUSIONS AND RELEVANCE: Moderate-to-severe cardiomegaly and LAE, caudal pulmonary artery and vein dilation, as well as a ventral, multifocal and symmetrical interstitial pulmonary pattern, were the main radiographic features of CPE in evaluated cats. Underlying cardiac disease did not influence the aforementioned radiographic features.

Malassezia overgrowth in dogs in northern Italy: frequency, body distribution, clinical signs and effects of pharmacologic treatments.

The present study describes Malassezia populations in clinically healthy dogs (HD) and dogs with Malassezia overgrowth (MO), and evaluates the correlation with clinical signs and previous treatments. Thirteen clinically HD and 84 dogs with MO were enrolled. Clinical history and previous treatments were recorded. After a complete physical and dermatological examination, Canine Atopic Dermatitis Extent and Severity Index_03 scores were calculated. Samples for cytology and mycological cultures were obtained from four body regions and from skin lesions. Malassezia overgrowth was diagnosed by cytology. A global score (GS) for quantitative evaluation of the population of Malassezia was calculated. In dogs with MO, the highest frequency of yeast detection was found in skin lesions (82%, P < 0.001). Sum of GS (GSs) obtained from dogs with MO (68, 0­621) was significantly higher compared to those of HD (3, 0­48, P < 0.001). GSs in dogs previously treated with antibiotics (312.5, 30­975) was significantly higher compared to those of dogs that not have received antibiotics (80, 0­975, P = 0.015). No difference was found between dogs treated and those not treated with steroids.

Left Pulmonary Artery Coarctation Associated with Pneumonia and Pulmonary Hypertension in a Cat.

A five-month-old European shorthair female kitten was referred because of recurrent episodes of respiratory distress. Results of physical examination, thoracic radiography, and echocardiography led to a presumptive diagnosis of severe precapillary pulmonary hypertension (PH) and interstitial pneumonia associated with right-sided cardiac remodeling. The cat rapidly died because of respiratory insufficiency. Pulmonary and cardiovascular pathological findings evidenced left pulmonary artery coarctation, severe right-sided cardiac hypertrophy, and bilateral pneumonia. This is the first report of pulmonary artery coarctation associated with pneumonia and PH in a cat.

Plasmatic Dimethylarginines in Dogs With Myxomatous Mitral Valve Disease.

Plasmatic dimethylarginines, asymmetric dimethylarginine (ADMA) and symmetric dimethylarginine (SDMA) are considered biomarkers of endothelial and renal dysfunction, respectively, in humans. We hypothesize that plasmatic concentration of dimethylarginines in dogs with myxomatous mitral valve disease (MMVD) is influenced by heart disease stage. Eighty-five client-owned dogs with MMVD, including 39, 19, and 27 dogs in ACVIM stages B1, B2, and C+D, respectively, and a control group of 11 clinically healthy dogs were enrolled. A prospective, multicentric, case-control study was performed. Each dog underwent a complete clinical examination, arterial blood pressure measurement, thoracic radiography, six-lead standard electrocardiogram, transthoracic echocardiography, CBC, biochemical profile, and urinalysis. Plasmatic concentration of dimethylarginines was determined through high-performance liquid chromatography coupled with tandem mass spectrometry. Median ADMA was significantly increased in dogs of group C+D (2.5 µmol/L [2.1-3.0]) compared to those of group B1 (1.8 µmol/L [1.6-2.3]; p < 0.001) and healthy dogs (1.9 µmol/L [1.7-2.3]; p = 0.02). Median SDMA was significantly increased in dogs of group C+D (0.7 µmol/L [0.5-0.9]) compared to those of groups B1 (0.4 µmol/L [0.3-0.5]; p < 0.001), B2 (0.4 µmol/L [0.3-0.6]; p < 0.01), and the control group (0.4 µmol/L [0.35-0.45]; p = 0.001). In the final multivariable analysis, ADMA and SDMA were significantly associated with left atrium to aorta ratio (p < 0.001), and creatinine (p < 0.001), respectively. Increased plasmatic concentrations of dimethylarginines suggest a possible role as biomarkers of disease severity in dogs with decompensated MMVD.

Red Cell Distribution Width Has a Negative Prognostic Role in Dogs with Myxomatous Mitral Valve Disease.

Red cell distribution width (RDW) is a quantitative measurement of anisocytosis. This hematological parameter is an important prognostic biomarker for different cardiovascular disorders in humans but its influence on survival has been poorly investigated in dogs with cardiovascular disease. The RDW and various clinical, complete blood count, serum biochemical and echocardiographic variables were retrospectively investigated in 146 client-owned dogs with myxomatous mitral valve disease (MMVD) at various disease stages, with or without concurrent diseases and treatment. Laboratory variables, including RDW, urea, and white blood cell (WBC), in addition to the echocardiographic variable left atrium to aorta ratio were found to be independent predictors of all-cause mortality at six months in a multivariable Cox proportional hazards regression model. In particular, the hazard ratio of RDW was 1.203 (95% confidence interval = 1.045-1.384; p = 0.010). The negative effect of increased RDW on outcome was confirmed using Kaplan-Meier curve analysis. The results of this study indicate that RDW acted as an independent predictor of negative outcome in dogs with MMVD.

Prevalence and risk factors for atrial fibrillation in dogs with myxomatous mitral valve disease.

BACKGROUND: Atrial fibrillation (AF) is a common supraventricular arrhythmia more frequently observed in large breed dogs. OBJECTIVES: Estimate the prevalence of AF in dogs with myxomatous mitral valve disease (MMVD) and identify risk factors for developing AF. ANIMALS: A total of 2194 client-owned dogs with MMVD, including 1280, 588, 290, and 36 dogs in ACVIM stages B1, B2, C, and D, respectively. METHODS: Retrospective, cross-sectional study. The medical databases of 3 veterinary teaching hospitals were reviewed. Inclusion criteria were a diagnosis of MMVD after complete cardiovascular evaluation and cardiac rhythm assessment using routine 2-minute ECG or good quality ECG tracing during echocardiographic examination. RESULTS: Atrial fibrillation was diagnosed in 59 dogs with a prevalence of 2.7%. Univariate analysis showed that mixed breed, male sex, advanced ACVIM stage, left atrial and ventricular enlargement, fractional shortening (FS), and presence of pulmonary hypertension were significantly associated with development of AF. According to 2 multivariable models, the left atrium (LA)-to-aorta ratio (odds ratio [OR] = 14.011, 7.463-26.304), early trans-mitral velocity (OR = 2.204, 1.192-4.076), body weight (OR = 1.094, 1.058-1.130), and FS (OR = 0.899, 0.865-0.934) and LA (OR = 5.28, 3.377-8.092), advanced ACVIM stage (OR = 4.922, 1.481-16.353), and FS (OR = 0.919, 0.881-0.959) were significant predictors of AF for models 1 and 2, respectively. CONCLUSIONS AND CLINICAL IMPORTANCE: Atrial fibrillation is an uncommon complication of MMVD and is significantly associated with the more advanced stage of the disease, increased LA dimension and body weight, and decreased FS.

Evaluation of an automated immunoturbidimetric assay for detecting canine C-reactive protein.

C-reactive protein (CRP) is a major acute-phase protein, and it is produced by the liver in response to a pro-inflammatory stimulus. Given that human and canine CRP have a similar molecular structure, the assays used for human CRP detection have been used to measure CRP concentrations in dogs. We evaluated the use of a human CRP assay (Biotecnica CRP assay) and validated its application in dogs. We analyzed 91 canine serum samples with a fully automated analyzer. Our validation was based on the evaluation of imprecision, limits of linearity, limits of quantification, and an evaluation of interferences. The new assay was also compared with the Randox CRP assay, a validated assay for the measurement of CRP. Intra- and inter-assay repeatability were <8% and <11%, respectively. The tested assay proportionally measured canine CRP in an analytical range up to 60 mg/L; however, hemoglobin, triglycerides, and bilirubin interfered with the determination. Good agreement, with the presence of proportional systematic bias, was observed between Biotecnica and Randox assays. The Biotecnica CRP assay provides reliable measurement of CRP in canine serum, provided that samples are free of interferents.

Symmetric dimethylarginine in dogs with myxomatous mitral valve disease at various stages of disease severity.

Symmetric dimethylarginine (SDMA) is a serum biomarker of renal damage in dogs. Moreover, SDMA concentration is an independent predictor of development of severe heart failure (HF) in humans with cardiac disease. This study evaluates whether the serum concentration of SDMA in dogs with myxomatous mitral valve disease (MMVD) is influenced by the severity of heart disease, pulmonary hypertension (PH) and treatment of HF. A total of 99 client-owned dogs were included in this retrospective case-control study; 78 dogs were affected by MMVD and classified according to the American College of Veterinary Internal Medicine (ACVIM) guidelines, and 21 were healthy controls. For each dog, history, physical examination, complete blood count, biochemical profile, thoracic radiography, 6-lead standard electrocardiogram and trans-thoracic echocardiography were available. Comparisons were performed between groups of dogs belonging to different ACVIM stages and between dogs with and without PH. The median SDMA concentration was neither significantly different among groups of dogs in different disease stages (overall P = 0.010), nor among dogs with MMVD, nor between those with [14.5 µg/dl (10.5-18.8)] and without PH [13 µg/dl (9-17.2)] (P = 0.295). The concentration of SDMA did not differ between dogs when considering the combined effect of the ACVIM group and cardiac treatment (overall P = 0.486). Furthermore, no correlation was found between SDMA concentration and radiographic and echocardiographic parameters associated with increased MMVD severity. In conclusion, this study failed to demonstrate the presence of renal impairment in dogs with MMVD, and the increase in renal parameters in some dogs in the more advanced stage of MMVD could be attributed to pre-renal azotemia.