Angiotensin-converting enzyme inhibitors in preclinical myxomatous mitral valve disease in dogs: systematic review and meta-analysis.

OBJECTIVES: To determine the efficacy and adverse events of the administration of angiotensin--converting enzyme inhibitors for the management of preclinical myxomatous mitral valve disease in dogs. MATERIALS AND METHODS: A compre- hensive search using Pubmed/MEDLINE, LILACS and CAB abstracts databases was performed. Ran- domised clinical trials that assessed efficacy and adverse events of angiotensin-converting enzyme inhibitors for the management of preclinical myxomatous mitral valve disease in dogs were included. Certainty of evidence was rated using GRADE methods. RESULTS: Four randomised clinical trials were included. While safe, angiotensin-converting enzyme inhibitors administration to dogs with myxomatous mitral valve disease and cardiomegaly results in little to no difference in the risk of development congestive heart failure (high certainty of evidence; relative risk: 1.03; 95% confidence interval: 0.87 to 1.23) and may result in little to no difference in cardiovascular-related (low certainty of evidence; relative risk: 1.01; 95% confidence interval: 0.54 to 1.89) and all-cause mortality (low certainty of evidence; relative risk: 0.93; 95% confidence interval: 0.63 to 1.36). Administration of angiotensin-converting enzyme inhibitors to dogs with myxomatous mitral valve disease without cardiomegaly may result in a reduced risk of congestive heart failure development. However, the range in which the actual effect for this outcome may be, the "margin of error," indicates it might also increase the risk of congestive heart failure development (low certainty of evidence; relative risk: 0.86; 95% confidence interval: 0.54 to 1.35). CLINICAL SIGNIFICANCE: Administration of angiotensin-converting enzyme inhibitors to dogs with -preclinical myxoma- tous mitral valve disease and cardiomegaly results in little to no difference in the risk of the develop- ment of congestive heart failure and may result in little to no difference in -cardiovascular-related and all-cause mortality. The certainty of evidence of the efficacy of angiotensin-converting enzyme inhibi- tors administration to dogs without cardiomegaly was low.

Prevalence of Proteinuria in Owned Dogs from Italy: A Multicentric Study.

Even though proteinuria is related to different causes, when it is persistent and associated with inactive urinary sediment, it is primarily due to kidney disease. Early detection of proteinuria allows us to identify several pathological conditions. The aim of the study was screening a canine population not known as being proteinuric, by the urinary dipstick. The study was carried out in seven Italian veterinary clinics during a period of six weeks. Dogs were enrolled with no restriction of sex or age. Females in estrus, dogs with signs of genitourinary diseases, or those previously diagnosed with proteinuric nephropathy were excluded. Dogs were considered "nonproteinuric" (NP) in case of negative dipstick test or "suspected proteinuric" (SP), if positive at the dipstick. When possible, proteinuria was confirmed by UPC ratio. A total of 1156 dogs were evaluated: 414 were from northern Italy and 742 from southern Italy. Based on dipstick test, 655 (56.6%) dogs were NP, while 501 (43.3%) were SP. Among the NP dogs 225 out of 414 (54.3%) were in northern Italy and 430 of 742 (57.9%) in southern Italy. One hundred eighty-nine of 414 (45.7%) SP dogs were identified in northern Italy and 312 of 742 (42.1%) in southern Italy. No statistical difference was found between the North and the South of Italy. UPC was available in 412 out of 501 SP samples: proteinuria was confirmed in 263 (63.86%) samples. Results from our study showed a high percentage of suspected proteinuric dogs, apparently not affected by renal diseases, together with the absence of statistically significant differences based on geographical area.

Flow Cytometric Characterization of S-phase Fraction and Ploidy in Lymph Node Aspirates from Dogs with Lymphoma.

Canine lymphoma is a multifaceted disease encompassing numerous entities with different prognosis. Objective assessment of the proliferation rate is of importance from the pathological and clinical perspectives. Different methods have been described in the literature to assess proliferation rate, including evaluation of Ki67 expression in fresh lymph node (LN) aspirates measured by flow cytometry (FC). This test has a high accuracy in discriminating between low- and high-grade lymphomas, and provides prognostic information among high-grade B-cell lymphomas. DNA content analysis is less expensive and suitable for well-preserved samples. We describe DNA-content analysis using LN aspirates from 112 dogs with lymphoma. S-phase fraction (SPF) accurately discriminated between low- and high-grade lymphomas, with 3.15% being the best discriminating cut-off value. SPF values strongly correlated with Ki67 expression as assessed by FC. Survival analyses were restricted to 33 dogs with high-grade B-cell lymphoma receiving standardized multi-agent chemotherapy, but no significant result was obtained for SPF. We also describe a subset of aneuploid cases and their respective follow-up. We conclude that DNA content analysis may be combined with morphological examination of LN aspirates to improve the objectivity in lymphoma subtype classification in dogs. Further studies are needed to assess the possible prognostic role of SPF and ploidy status within specific lymphoma subtypes in dogs.

Accuracy of Ultrasonographic Measurements of Adrenal Glands in Dogs: Comparison with Necroscopic Findings.

Ultrasonographic evaluation of the adrenal glands was performed in 85 dogs, followed by macroscopic and histopathological examination either post-mortem or after adrenalectomy. This retrospective cross-sectional study evaluated the difference between gross and ultrasonographic measurements to determine the diagnostic accuracy of ultrasonography in the evaluation of canine adrenal gland size. The differences were assessed for gland length, thickness at cranial, middle and caudal regions, and surface area. In our sample, ultrasound error accuracy ranged between 0% in measurement of the right adrenal gland surface area and 25.21% for left cranial pole thickness. The parameters with minor errors were caudal pole thickness (3.64% right side and 3.49% left side) and length (5.75% right side and 2.19% left side). The ultrasonographic measurements generally underestimated the actual size of the adrenal glands. No statistically significant differences were observed for measurement errors between normal and pathological adrenal glands. This study confirmed that the caudal pole of both glands is the best parameter for ultrasonographic evaluation of normal and pathological adrenal glands size in dog. Furthermore, the surface area could be considered as a dimensional parameter for better assessment of the complex shape and the global aspect of the adrenal glands, while standardize ultrasonographic projections are needed to measure the cranial pole of both adrenal glands.

Right atrial appendage aneurysms in veal calves and beef cattle: anatomopathological investigations and aetiopathogenetic hypotheses.

OBJECTIVES: Right atrial aneurysms have been reported in bovine species, but a clear aetiopathogenesis has never been elucidated. ANIMALS: One thousand and seventy-nine veal calves (6-9 months old) and 313 beef cattle (10-24 months old) housed in intensive livestock farming systems and regularly slaughtered were included in the present study. METHODS: Hearts were externally examined and the identified right atrial aneurysms were submitted for gross and histopathological investigations. RESULTS: Right atrial aneurysms, which involved the right auricle, were detected in both veal calves (4.63%) and beef cattle (8.63%). Two types of aneurysms were observed: one type showing communications with the atrial lumen, the other one having no connections with it. Aneurysms communicating with the atrial lumen were characterized by endocardial fibrosis, whereas the other ones showed arterial characteristics (intimal fibromuscular hyperplasia and medial elastic fibre and fibrous tissue deposition). CONCLUSIONS: Considering the similarities with the right atrial aneurysms reported in people, the aneurysms communicating with the atrial lumen were considered to be caused by an inherent atrial weakness (so called 'loci minoris resistentiae' areas). On the contrary, the aneurysms with no communications with the atrial lumen, whose localization suggested an origin from the intramural coronary arteries of the pectinate muscles, may be subsequent to systemic hypertension due to intensive livestock farming conditions.

Clinical evaluation and endoscopic classification of bronchomalacia in dogs.

BACKGROUND: Little information is available about the association between bronchomalacia and historical or clinicopathologic data. Also, studies applying an endoscopic classification scheme that differentiates between static and dynamic bronchial collapse and based on a scoring system are lacking. OBJECTIVES: To describe the clinical presentation of bronchomalacia in dogs, to classify endoscopic findings, and to evaluate associations among historical, clinicopathologic data, and endoscopic findings. ANIMALS: Fifty-nine client-owned dogs with an endoscopic diagnosis of bronchomalacia. METHODS: In this retrospective study, medical records were analyzed and video documentation was reviewed to assign a score to endoscopic findings. Univariate analysis was performed on categorical variables organized in contingency tables, and a stepwise logistic regression model was used for multivariate analysis. RESULTS: Of the 59 dogs included in the study, 2 were affected by static bronchial collapse (SBC), 35 by dynamic bronchial collapse (DBC), and 22 by both SBC and DBC. The association between SBC and DBC was more frequently seen in the dogs with higher body weight, pulmonary hypertension, a bronchial type of radiographic pattern, and nodularity at endoscopic examination. Thirty-one dogs were presented with tracheomalacia and bronchomalacia; an association emerged between these concurrent disorders in dogs living indoors. Multivariate analysis of the endoscopic scores showed a correlation between DBC severity and cough duration. CONCLUSION AND CLINICAL IMPORTANCE: Results of this study provide evidence for 2 different types of bronchial collapse. Endoscopic scoring scheme has proved to be promising in the bronchomalacia classification, although further evaluation of its applicability in larger canine populations is needed.

Diagnostic performance of P wave duration in the identification of left atrial enlargement in dogs.

OBJECTIVES: To determine sensitivity and specificity of P wave duration in the identification of left atrial enlargement in dogs. METHODS: Electrocardiograms from normal dogs and dogs with various cardiovascular diseases were evaluated. Inclusion criteria were the availability of an electrocardiogram showing a stable isoelectric line, easily recognizable P waves and good quality two-dimensional echocardiographic estimate of left atrial dimensions using the left atrial to aortic root ratio. Using a metal caliper system, P wave duration was measured to the nearest 10 milliseconds for six consecutive heart beats; data were then averaged for each dog. The accuracy of P wave duration in predicting left atrial enlargement was determined using a receiver operating characteristic analysis. RESULTS: One hundred and fifty-six dogs were included in the study. Average P wave durations of 20, 30, 40 and 50 milliseconds yielded sensitivities of 100, 85, 68 and 40% and specificities of 0, 16, 64 and 93%, respectively, for the diagnosis of Left Atrial Enlargement by echocardiography. The estimated area under curve of the receiver operating characteristic curve was 0·70 (95% confidence interval: 0·60 to 0·80). CLINICAL SIGNIFICANCE: The diagnostic performance of P wave duration for identification of left atrial enlargement in dogs presents considerable limitations.

Survival characteristics and prognostic variables of dogs with preclinical chronic degenerative mitral valve disease attributable to myxomatous degeneration.

BACKGROUND: Preclinical myxomatous mitral valve degeneration (MMVD) includes a heterogeneous group of dogs. Therefore, identifying risk factors for progression of the disease is of clinical importance. OBJECTIVES: To investigate survival time and risk factors for clinical and echocardiographic variables taken at initial examination for clinical progression in preclinical MMVD dogs. ANIMALS: A total of 256 dogs with stage B1 or B2 MMVD. MATERIALS AND METHODS: Medical records of 256 dogs with preclinical MMVD were reviewed retrospectively. Long-term outcome was assessed by telephone interview. Dogs alive at the time of phone interview were asked to return to the hospital for re-evaluation of their cardiac status. RESULTS: Seventy of 256 (27.3%) dogs died during the observation period. The median survival time, regardless of cause of death, was 588 (range 75-1,668) days. The presence of a murmur was associated with an increased risk of death (AHR 2.14; 95% CI 1.12, 4.11; P = 0.022). Thirty (12%) deaths were considered cardiac related. LA/Ao > 1.4 was the only negative predictor (AHR 2.64; 1.13, 6.13; P = 0.024) for cardiac-related deaths. Eighty-three dogs were re-examined, of which 34 progressed to a more advanced stage of MMVD. The presence of Emax > 1.2 (AHR 2.75; 95% CI 1.01, 7.48; P = 0.047) and cough (AHR 7.89; 95% CI 3.18, 20.07; P < 0.001) were significant in the multivariate analysis. CONCLUSIONS AND CLINICAL IMPORTANCE: Preclinical MMVD represents a relatively benign condition in dogs. Clinicians might find stratification of this dog population according to risk factors based on clinical and echocardiographic findings helpful in determining treatment.

Holter monitoring in 36 dogs with myxomatous mitral valve disease.

OBJECTIVE: Describe the presence of arrhythmias in dogs with myxomatous mitral valve disease (MMVD) and the potential association with class of heart failure and left atrial enlargement. Compare the standard electrocardiogram (ECG) with Holter monitoring for assessing heart rate (HR). EXPERIMENTAL PROCEDURE: The study group of 36 dogs weighing less than 20 kg was divided into MMVD and no clinical signs (preclinical) or MMVD and clinical signs (clinical). A standard echocardiogram, ECG and 24-h Holter recording were obtained in all dogs. RESULTS: Minimum and mean Holter HRs were higher in the clinical group than in the preclinical group. Clinical dogs had more ventricular arrhythmias than preclinical dogs. An enlarged left atrium was associated with the presence of more supraventricular arrhythmias. CONCLUSIONS: Arrhythmias are a common finding in dogs with MMVD and Holter monitoring is a reliable tool for both HR monitoring and diagnosis.

Survival characteristics and prognostic variables of dogs with mitral regurgitation attributable to myxomatous valve disease.

BACKGROUND: There are few studies evaluating the natural history and prognostic variables in chronic mitral valve disease (CMVI) in a heterogeneous population of dogs. OBJECTIVES: To estimate survival and prognostic value of clinical and echocardiographic variables in dogs with CMVI of varying severity. Five hundred and fifty-eight dogs belonging to 36 breeds were studied. METHODS: Dogs were included after clinical examination and echocardiography. Long-term outcome was assessed by telephone interview with the owner. RESULTS: The mean follow-up time was 22.7 +/- 13.6 months, and the median survival time was 19.5 +/- 13.2 months. In univariate analysis, age>8 years, syncope, HR>140 bpm, dyspnea, arrhythmias, class of heart failure (International Small Animal Cardiac Health Council), furosemide therapy, end-systolic volume-index (ESV-I)>30 mL/m(2), left atrial to aortic root ratio (LA/Ao)>1.7, E wave transmitral peak velocity (Emax)>1.2 m/s, and bilateral mitral valve leaflet engagement were associated with survival time when all causes of death were included. For the cardiac-related deaths, all the previous variables except dyspnea and EDV-I>100 mL/m(2) were significantly associated with survival time. Significant variables in multivariate analysis (all causes of death) were syncope, LA/Ao>1.7 m/s, and Emax>1.2 m/s. For cardiac-related death, the only significant variable was LA/Ao>1.7. CONCLUSIONS AND CLINICAL IMPORTANCE: Mild CMVI is a relatively benign condition in dogs. However, some clinical variables can identify dogs at a higher risk of death; these variables might be useful to identify individuals that need more frequent monitoring or therapeutic intervention.

Blood lymphocyte subsets in canine idiopathic pericardial effusion.

The immunophenotype of peripheral blood lymphocytes was investigated in 23 dogs diagnosed with idiopathic pericardial effusion in order to provide information about a possible role of the immune system in this pathology. Flow cytometric analysis showed a significant reduction in nearly all lymphocyte subsets examined and a strong, significant (P < 0.001) reduction of the CD4 subset, which gave rise to a significantly lower CD4/CD8 ratio. Our data suggest that an imbalance in the immune system is present during the course of the disease, preferentially affecting the T helper cell response.

Prevalence of Chlamydophila felis and feline herpesvirus 1 in cats with conjunctivitis in northern Italy.

The prevalence of Chlamydophila felis and feline herpesvirus 1 (FHV-1) infection in cats with conjunctivitis in northern Italy was investigated by conventional polymerase chain reaction (PCR) testing. In cats with conjunctivitis, C felis and FHV-1 were detected in 14 of 70 (20%) and in 23 of 70 (33%) animals, respectively. None of the 35 control cats were positive for C felis, whereas 7 (20%) of these cats were positive for FHV-1. Mixed infections were present in 5 of 70 cats (7%). Cats positive for C felis were significantly younger than control animals (P = .02), whereas no significant age differences were observed between FHV-1-positive cats and control cats (P = .41) or between FHV-1-positive animals and C felis-positive animals (P = .16). Cats sampled during acute-phase conjunctivitis were also investigated for the presence of C felis by conjunctival scrapings. In this acute phase, substantial agreement was found when comparing the results of the 2 methods (K = .80). The association between PCR results and conjunctivitis was evaluated for the 2 pathogens. The presence of C felis was significantly associated with conjunctivitis (P = .004), whereas the detection of FHV-1 did not significantly correlate with the clinical sign (P = .25), suggesting that, by itself. PCR is not suitable for the diagnosis of FHV-1-related conjunctivitis.

Canine idiopathic dilated cardiomyopathy. Part II: pathophysiology and therapy.

Dilated cardiomyopathy (DCM) in dogs is characterized by ventricular and atrial enlargement, and systolic and diastolic dysfunction, with congestive heart failure (CHF) often developing at some stage. With greater understanding of the impact of neuroendocrine stimulation in heart disease, the understanding of the pathophysiology for CHF has changed considerably. It is no longer considered only to be a simple haemodynamic consequence of pump dysfunction, but is now characterized as a complex clinical syndrome with release of many neurohormones, which are believed to have impact on the progression of disease. This change in our understanding of the pathophysiology of CHF has important therapeutic implications. There are strong indications, although not yet proven, that drugs designed to influence the neuroendocrine activity, such as Angiotensin Converting Enzyme (ACE) inhibitors and beta-receptors antagonists, are efficacious as adjunct therapy of heart failure attributable to DCM in dogs. The benefits of drugs designed to influence the myocardial contractile state (positive inotropes) have not been fully evaluated. However, evidence has emerged in recent years indicating that new types of positive inotropes may be beneficial in dogs with DCM. This review focuses on the neuroendocrine aspects of DCM and their possible therapeutic implications and the place for long-term inotropic support in dogs with DCM.

Canine idiopathic dilated cardiomyopathy. Part I: Aetiology, clinical characteristics, epidemiology and pathology.

Dilated cardiomyopathy (DCM), characterized by chamber dilatation and myocardial systolic and diastolic dysfunction, is one of the most common heart diseases in dogs. The aetiology of the myocardial hypokineis is seldom known in the individual case of DCM, although several theories concerning genetic, nutritional, metabolic, inflammatory, infectious, or drug- or toxin-induced myocardial disease have been discussed. DCM is often referred to as being breed-specific for Boxers, Doberman Pinschers, English Cocker Spaniels and other breeds. Review of reports on histopathologic findings in canine DCM reveals two histologically distinct forms of DCM; (1) cardiomyopathy of boxers and of Doberman pinschers, corresponding to the "fatty infiltration-degenerative" type, and (2) the form seen in many giant, large- and medium-sized breeds, including some boxers and Doberman pinschers, which can be classified as the "attenuated wavy fiber" type of DCM. The classification of canine idiopathic DCM according to histologic findigns seems superior to classification suggesting breed-specific syndromes, as some breeds (i.e. boxers and Doberman pinschers) may be affected by both diseases. However, ante mortem aetiological diagnosis of DCM is difficult. DCM carries a poor prognosis in dogs, and few prognostic indicators have been identified.

Canine dilated cardiomyopathy: lymphocyte and cardiac alpha(1)- and beta-adrenoceptor concentrations in normal and affected great danes.

Serum catecholamine levels and myocardial and lymphocyte adrenergic receptor (AR) concentrations were measured in adult great danes affected by canine dilated cardiomyopathy (DCM) and compared to those of healthy animals. A non-homogeneous population of beta -AR, consisting of beta(1)-AR and beta(2)-AR, was observed in healthy (41 and 59%, respectively) and affected (17 and 83%, respectively) dog lymphocytes. Binding assays revealed that total beta -AR, beta(1)-AR and alpha(1)-AR were significantly downregulated (P<0.05;P<0.01;P<0. 001), both in lymphocyte and myocardial cell membranes of affected dogs. beta(2)-Adrenergic receptor concentrations were significantly reduced only in lymphocyte and right atrium cell membranes (P<0.05). Downregulation was not associated with alterations in receptor binding characteristics, as no significant differences in K(d)values were found. Mean plasma catecholamine levels were significantly higher (P<0.01) in DCM dogs (939+/-41) than in normal subjects (348+/-32), thus suggesting a sympathetic activation. The present study indicates a condition similar to that observed in human patients affected by DCM and that adrenergic receptors in canine lymphocytes reflect the fluctuation of adrenergic receptor concentrations in the myocardium.

Lymphocyte beta -adrenoceptor downregulation in great danes with occult dilated cardiomyopathy (DCM) and with DCM and heart failure.

The importance of the adrenergic nervous system in supporting the failing heart has long been known. The adrenergic drive on cardiac structure and function has however some adverse effects, which include myocardial beta-adrenoceptor (beta-AR) downregulation and decreased beta-adrenergic responsiveness to cathecolamines. In dog lymphocytes, beta(1)-AR and beta(2)-AR populations are almost equally represented (with a slight prevalence of beta(2)) and a significant correlation between cardiac and lymphocytic adrenoceptors has been found. The aim of the present study was to investigate possible differences between the concentration of lymphocytic beta-AR in healthy dogs, dogs with dilated cardiomyopathy (DCM) and dogs with occult DCM. Three groups of great danes were considered: a control group (n =10), dogs with DCM (n =9) and dogs with occult DCM (n =4). Lymphocytic beta-AR populations were determined in all dogs. A substantial and significant decrease (P<0.05) in total-AR, beta(1)-AR and beta(2)-AR concentrations in the lymphocytes of dogs with symptomatic DCM and occult DCM compared to the control group was found. Although the mean value of the lymphocyte beta(1)-AR number in the asymptomatic group was double compared to the DCM group, this difference was not statistically significant. We conclude that in dogs beta-AR downregulation occurs early in the course of dilated cardiomyopathy. This finding may suggest the value of early use of a beta-blocker in the therapeutic regimen. Moreover, the continuous monitoring of lymphocytic beta-AR may represent a useful tool for the development of a more effective individual therapy.