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.

Contrast-enhanced ultrasonography in dogs with inflammatory bowel disease.

BACKGROUND: Contrast-enhanced ultrasonography (CEUS) is used to evaluate vascularity of the gastrointestinal wall in neoplastic and inflammatory diseases. OBJECTIVE: To assess the feasibility of CEUS for the evaluation of duodenal perfusion in dogs with inflammatory bowel disease (IBD). ANIMALS: Forty-two dogs with IBD and 20 clinically healthy dogs. METHODS: All CEUS studies of the duodenum were analyzed to obtain time-intensity curves and perfusion parameters. The procedure was repeated in 12 IBD dogs 2 months after a standardized treatment. RESULTS: On CEUS, the duodenal wall showed a typical perfusion pattern characterized by a radial and simultaneous enhancement of the wall in all dogs. On qualitative assessment, no differences were observed in contrast medium distribution between healthy and affected dogs, or between dogs with IBD before and after treatment. Peak intensity (PI) and area under the curve (AUC) significantly differed between healthy (PI = 3.58 arbitrary units [au; 1.86-4.93 au] and AUC = 47.63 au seconds [aus, 22.68-62.15]) and affected dogs (PI = 5.10 au [0.63-15.16 au] and AUC = 63.62 aus [5.31-212.20 aus]; P = .03 and .03, respectively). No significant differences were found for the perfusion parameters before and after treatment. CONCLUSIONS AND CLINICAL IMPORTANCE: We showed that CEUS allows discrimination between IBD affected dogs and healthy dogs by evaluation of time-intensity curves, but did not provide useful information for monitoring therapeutic response. The qualitative assessment identified no significant differences between healthy and affected dogs, or between dogs before and after treatment.

Echocardiographic predictors of first onset of atrial fibrillation in dogs with myxomatous mitral valve disease.

BACKGROUND: Atrial fibrillation (AF) occurs in dogs with myxomatous mitral valve disease (MMVD) as a consequence of left atrial (LA) dilatation, and it affects survival and quality of life. OBJECTIVES: To evaluate the usefulness of echocardiography in predicting the first occurrence of AF in dogs with MMVD. ANIMALS: Forty-four client-owned dogs with MMVD, 22 dogs that developed AF, and 22 dogs that maintained sinus rhythm. METHODS: Retrospective observational study. Medical databases were reviewed for dogs that developed AF during the year after diagnosis of MMVD (AF group). The last echocardiographic examination obtained while still in sinus rhythm was used to derive selected variables. For each dog with AF, a control dog matched for body weight, class of heart failure, and LA dimension was selected. Echocardiographic results including LA volumes and LA speckle tracking echocardiography (STE)-derived variables were measured. RESULTS: Among the tested echocardiographic variables, only LA diameter (P = .03) and left ventricular internal diameter in diastole (P = .03) differed significantly between groups, whereas body weight-indexed variables of cardiac dimension as well as LA volumes and volume-derived functional variables were not different. Among the STE-derived variables, peak atrial longitudinal strain (PALS) results differed significantly between the AF group (23.8% ± 8.6%) and the control group (30.5% ± 9.6%; P = .03). A value of PALS ≤28% predicted AF occurrence with sensitivity and specificity of 0.80 and 0.65, respectively. CONCLUSIONS AND CLINICAL IMPORTANCE: Absolute cardiac diameters and LA STE (in particular, PALS) are useful echocardiographic predictors for the development of AF in dogs with MMVD.

64-multidetector CT anatomical assessment of the feline bronchial and pulmonary vascular structures.

OBJECTIVES: The aim of the study was to provide a detailed anatomical study of the feline bronchial and vascular structures by using CT angiography (CTA). METHODS: Adult cats with no respiratory clinical signs were enrolled in a CTA protocol to provide an anatomical study of the thorax. The dimensions, number of branches and branching pattern (monopodial vs dichotomic) of both bronchial and pulmonary vascular structures were evaluated under positive inspiration apnoea. A linear generalised estimating equations analysis (Spearman's rho) was used to identify statistical correlation between tracheal diameter, age and body weight of the cats. RESULTS: Fourteen cats met the inclusion criteria. The pulmonary arteries had larger diameters than the pulmonary veins, and the pulmonary veins had larger diameters than the bronchial structures. A higher number of segmental bronchial and pulmonary vascular branches was observed in the left caudal lung lobe than in the other lobes. The monopodial branching pattern of both bronchial and pulmonary vascular structures was predominant in all cats of our study (100%) in cranial, caudal and right middle lung lobes, while a dichotomic branching pattern of the bronchial and pulmonary vascular structures of the accessory lung lobe was seen in 13 cats (93%). Thirteen cats (93%) had three pulmonary vein ostia, and one cat (7%) also presented with an additional left intermediate pulmonary vein ostium. Variation in the number of segmental pulmonary vein branches was noted in the right caudal lung lobe. There was no statistical correlation between tracheal diameter, age and weight. CONCLUSIONS AND RELEVANCE: Architecture of the feline bronchovascularr structures belongs to a mixed type of monopodial and dichotomic branching pattern. In cats, the pulmonary venous drainage system predominately presents three pulmonary vein ostia. Variations in the type of formation and the number of branches of the pulmonary venous drainage system were noted.

Prognostic value of echocardiographic indices of left atrial morphology and function in dogs with myxomatous mitral valve disease.

BACKGROUND: The prognostic relevance of left atrial (LA) morphological and functional variables, including those derived from speckle tracking echocardiography (STE), has been little investigated in veterinary medicine. OBJECTIVES: To assess the prognostic value of several echocardiographic variables, with a focus on LA morphological and functional variables in dogs with myxomatous mitral valve disease (MMVD). ANIMALS: One-hundred and fifteen dogs of different breeds with MMVD. METHODS: Prospective cohort study. Conventional morphologic and echo-Doppler variables, LA areas and volumes, and STE-based LA strain analysis were performed in all dogs. A survival analysis was performed to test for the best echocardiographic predictors of cardiac-related death. RESULTS: Most of the tested variables, including all LA STE-derived variables were univariate predictors of cardiac death in Cox proportional hazard analysis. Because of strong correlation between many variables, only left atrium to aorta ratio (LA/Ao > 1.7), mitral valve E wave velocity (MV E vel > 1.3 m/s), LA maximal volume (LAVmax > 3.53 mL/kg), peak atrial longitudinal strain (PALS < 30%), and contraction strain index (CSI per 1% increase) were entered in the univariate analysis, and all were predictors of cardiac death. However, only the MV E vel (hazard ratio [HR], 4.45; confidence interval [CI], 1.76-11.24; P < .001) and LAVmax (HR, 2.32; CI, 1.10-4.89; P = .024) remained statistically significant in the multivariable analysis. CONCLUSIONS AND CLINICAL IMPORTANCE: The assessment of LA dimension and function provides useful prognostic information in dogs with MMVD. Considering all the LA variables, LAVmax appears the strongest predictor of cardiac death, being superior to LA/Ao and STE-derived variables.

Sensitivity, specificity, and interobserver variability of survey thoracic radiography for the detection of heart base masses in dogs.

OBJECTIVE To determine the sensitivity, specificity, and interobserver variability of survey thoracic radiography (STR) for the detection of heart base masses (HBMs) in dogs. DESIGN Retrospective case-control study. ANIMALS 30 dogs with an HBM and 120 breed-matched control dogs (60 healthy dogs and 60 dogs with heart disease and no HBM). PROCEDURES In a blinded manner, 2 observers (designated as A and B) evaluated STR views from each dog for a mass-like opacity cranial to the heart, tracheal deviation, cardiomegaly, findings suggestive of pericardial effusion or right-sided congestive heart failure, and soft tissue opacities suggestive of pulmonary metastases. Investigators subsequently provided a final interpretation of each dog's HBM status (definitely affected, equivocal, or definitely not affected). RESULTS Considering equivocal interpretation as negative or positive for an HBM, the sensitivity of STR for diagnosis of an HBM was 40.0% (95% confidence interval [CI], 22.5% to 57.5%) and 56.7% (95% CI, 38.9% to 74.4%), respectively, for observer A and 63% (95% CI, 46.1% to 80.6%) and 80.0% (95% CI, 65.7% to 94.3%), respectively, for observer B. The corresponding specificity was 96.7% (95% CI, 93.5% to 99.9%) and 92.5% (95% CI, 87.8% to 97.2%), respectively, for observer A and 99.2% (95% CI, 97.5% to 100%) and 92.5% (95% CI, 87.8% to 97.2%), respectively, for observer B. The presence of a mass-like opacity cranial to the heart or tracheal deviation, or both, was significantly associated with a true diagnosis of HBM. CONCLUSIONS AND CLINICAL RELEVANCE Results indicated that STR is a highly specific but not a highly sensitive predictor of HBM in dogs.

Use of VEGFR-2 targeted ultrasound contrast agent for the early evaluation of response to sorafenib in a mouse model of hepatocellular carcinoma.

PURPOSE: The aim of this study was to assess the early response to sorafenib using ultrasound molecular imaging in a murine model of hepatocellular carcinoma (HCC). PROCEDURES: A xenograft model of HCC was established. Then, mice were divided in two groups and received treatment (sorafenib) or placebo for 14 days. The treatment group was further divided into non-responders and responders according to the degree of growth. Contrast enhanced ultrasound (CEUS) was performed using VEGFR-2 targeted microbubbles (BR55, Bracco Suisse SA, Geneva, Switzerland). Dedicated software was used to quantify the amount of bound microbubbles in the tumor as a numerical value (differential targeted enhancement (dTE)). Tumors were then excised and western blot analysis performed. RESULTS: The dTE values decreased from day 0 to day +14 both in the treatment and control groups, but were lower in the former. The non-responder group had higher dTE levels at day 2 compared to responders (p = 0.019). CONCLUSION: BR55 appears to be useful in the prediction of response to sorafenib in a xenograft model of HCC.

Diagnostic accuracy of the vertebral heart score and other radiographic indices in the detection of cardiac enlargement in cats with different cardiac disorders.

A retrospective search was conducted to evaluate the diagnostic accuracy of the vertebral heart score (VHS) and other related radiographic indices in the detection of cardiac enlargement associated with different cardiac disorders in the cat. One hundred and five cats with a complete echocardiographic examination and radiographic examination of the thorax with at least two orthogonal views were enrolled. Eighty-three cats had different cardiac disorders, 72 with left-sided cardiac disorders (LSCD) and 11 with right-sided cardiac disorders; 22 cats were free of cardiovascular abnormalities. Measurements of VHS and cardiac long and short axes on lateral (L) and dorsoventral or ventrodorsal radiographs were obtained. Receiver operating characteristic curves were calculated to evaluate the diagnostic accuracy of each radiographic index in differentiating between cats with cardiac disorders or cats with LSCD and cats without cardiac abnormalities and, among cats with LSCD, between those with no or mild left atrial enlargement (LAE) or those with moderate-to-severe LAE and healthy cats. The L-VHS at the cut-off of 7.9 had high diagnostic accuracy in distinguishing cats with LSCD and moderate-to-severe LAE from healthy cats, but all the other radiographic indices were moderately accurate in distinguishing between cats with overall cardiac disorders or LSCD, either with no or mild LAE and moderate-to-severe LAE, and healthy cats. The considered radiographic indices were also moderately accurate in predicting different degrees of LAE in cats with LSCD. Radiographic indices are reasonably specific, but less sensitive predictors of cardiac enlargement in cats with heart disorders.

Ultrasonographic measurement of the relative thickness of intestinal wall layers in clinically healthy cats.

The normal sonographic thickness of the individual layers (ie, mucosa, submucosa, muscularis and subserosa-serosa) of the intestinal wall was evaluated in 20 clinically healthy cats. The mean thickness of the wall was 2.20, 2.22, 3.00 and 2.04 mm for duodenum, jejunum, ileum (fold) and ileum (between folds), respectively. The mean thickness of the mucosal layer was 1.27, 1.20, 0.46 and 0.49 mm for duodenum, jejunum, ileum (fold) and ileum (between folds), respectively, and its contribution to wall thickness was significantly greater than that of the other layers in the duodenum (57.7%) and jejunum (55.2%). The mean thickness of the submucosal layer was 0.36, 0.36, 1.49 and 0.53 mm for duodenum, jejunum, ileum (fold) and ileum (between folds), respectively, and its contribution to wall thickness was greater than that of the muscularis in the duodenum (16.3%), jejunum (16%) and ileum (fold) (49.8 %). The mean thickness of muscularis was 0.28, 0.35, 0.66 and 0.65 mm for duodenum, jejunum, ileum (fold) and ileum (between folds), respectively, with a corresponding contribution to wall thickness of 12.7 %, 14.4%, 22% and 31.6%. Finally, the mean thickness of serosa was 0.29, 0.31, 0.38 and 0.38 mm for duodenum, jejunum, ileum (fold) and ileum (between folds), respectively, with a corresponding contribution to wall thickness of 13.3%, 14.4%, 12.7 % and 18.7%. These values can provide baseline information that might be useful in evaluating intestinal disorders affecting preferentially some of the intestinal layers.

Notch3 inhibition enhances sorafenib cytotoxic efficacy by promoting GSK3b phosphorylation and p21 down-regulation in hepatocellular carcinoma.

Sorafenib (Nexavar), a multiple kinase inhibitor, is the only clinically approved drug for patients with advanced HCC. However, its therapeutic success is limited by the emergence of drug resistance. Here we found that p21 and pGSK3ßSer9 are major players in the resistance to sorafenib. We recently reported that aberrant Notch3 expression in HCC contributes to doxorubicin resistance in vitro and, therefore, we focused on the mechanisms that associate Notch3 to acquired drug resistance. In this study we first found that Notch3 inhibition significantly increased the apoptosis inducing effect of sorafenib in HCC cells via specific down-regulation of p21 and up-regulation of pGSK3ßSer9. Using a mouse xenograft model we further found that Notch3 depletion combined with 21 days of sorafenib treatment exerts a substantial antitumor effect in vivo. Interestingly, we showed that, upon exposure to sorafenib treatment, Notch3 depleted xenografts maintain lower levels of p21 and higher levels of pGSK3ßSer9 than control xenografts. Thus, this study demonstrated that inhibition of Notch3 signaling prevents HCC-mediate drug resistance and sensitizes HCC cells to sorafenib. Finally, we validated our in vitro and in vivo results in primary human HCCs showing that Notch3 protein expression positively correlated with p21 protein expression and negatively correlated with pGSK3ßSer9 expression. In conclusion, the results presented in this study demonstrated that Notch3 silencing enhances the effect of sorafenib by overcoming drug resistance. Notch3 inhibition in combination with sorafenib can be a promising strategy for treatment of HCC.

Imaging diagnosis-cholangiocellular adenoma: contrast-enhanced ultrasonographic findings of a benign tumor mimicking malignant neoplasia in a dog.

A 9-year-old Giant Schnauzer was referred for polyuria and polydipsia. On abdominal ultrasound, a hyperechoic mass with low color Doppler signal was detected in the medial right hepatic lobe. Contrast-enhanced ultrasound (CEUS) demonstrated increased enhancement of the mass during the arterial phase, and contrast washout during portal and late phases with decreased enhancement relative to the liver. These findings were consistent with primary liver malignancy or liver metastasis. A final diagnosis of cholangiocellular adenoma was made based on histopathology. To our knowledge, this is the first description of a benign hepatic neoplasm exhibiting malignant CEUS characteristics in a dog.

Chylothorax associated with tricuspid dysplasia and atrial septal defect in a bullmastiff.

Transudate pleural effusion associated with tricuspid dysplasia and ostium secundum-type atrial septal defect was diagnosed in a 14-month-old bullmastiff. Following administration of furosemide and an angiotensin-converting enzyme (ACE) inhibitor, the dog remained free of pleural effusion for 10 months, until he showed severe dyspnea due to chylothorax. Medical therapy was unsuccessful to avoid recurrence of life-threatening pleural chylous effusion. Ligation of the thoracic duct and apposition of an omental pedicle flap were effective in the resolution of pleural chylous leakage.

High-frequency ultrasonography of the skin of clinically normal dogs.

OBJECTIVE: To assess the applicability of high-frequency diagnostic ultrasonography for evaluation and accurate measurement of the skin thickness of clinically normal dogs. ANIMALS: 26 healthy dogs (12 sexually intact males, 13 sexually intact females, and 1 spayed female) of various breeds and ages. PROCEDURE: Ultrasonographic examination of the skin and histomorphometric analysis of skin biopsy specimens obtained from the same site were performed. A 13-MHz linear-array transducer was used to obtain a series of ultrasonographic images of the skin in the flank region; images were analyzed and measured by use of imaging software. Cutaneous biopsy specimens were placed in fixative and then stained with H&E and Masson trichrome stains. Histomorphometric analysis was performed by use of an image analyzer. Thickness of the epidermis and dermis of each specimen was evaluated by use of a semiautomatic procedure of quantification. Data obtained from ultrasonographic and histologic measurements were compared by use of the Pearson correlation test. RESULTS: The ultrasonographic pattern of canine skin was consistently characterized by 3 distinct, defined echogenic layers corresponding to the epidermal entry echo, epidermis and dermis, and subcutaneous tissues. A positive correlation was found between ultrasonographic and histologic measurements of skin thickness. CONCLUSIONS AND CLINICAL RELEVANCE: Comparison between ultrasonographic and histologic appearance of the skin revealed that layering of canine skin (ie, epidermis and dermis) and the subcutaneous tissues may be recognized and measured by use of high-frequency ultrasonography. Thus, diagnostic ultrasonography may be a useful tool for the noninvasive evaluation of cutaneous disorders in dogs.

Ultrasonographic and pathologic features of intestinal smooth muscle hypertrophy in four cats.

The ultrasonographic findings for four cats with intestinal smooth muscle hypertrophy are described. In two cats, intestinal smooth muscle hypertrophy was associated with chronic enteritis. In the remaining two cats, intestinal smooth muscle hypertrophy affected the intestinal tract proximal to stenosis due to alimentary lymphoma and an intestinal foreign body, respectively. Moderate increased thickness of the affected intestinal wall, measuring 7-8 mm, was evident on abdominal ultrasonographic examination of all subjects. In addition, the ultrasonographic five-layered feature of the intestinal wall was maintained, and only the muscular layer appeared thickened. Abdominal ultrasound allowed a presumptive diagnosis of intestinal smooth muscle hypertrophy that was confirmed histologically in all cats.

Congenital facial infiltrative lipoma in a calf.

The clinical and pathologic findings related to an infiltrative facial lipoma in a 5-month-old female Holstein Friesian calf are reported. The tumor was congenital, increased in size with time, and deformed the left side of the face and cranial bones. The clinical condition of the calf was good; the only detectable abnormalities were poor weight gain and decreased motility of the left upper lip. Clinical and radiologic data indicated the mass was not removable. Muscle and lymph node invasion by tumor tissue were detected histologically. Infiltrative lipoma is a rare variety of lipoma that has been reported in dogs, cats, horses, and humans. Although its cytologic characteristics are those of a benign tumor, in this patient the invasiveness of the neoplasm was associated with poor prognosis.