Mitral valve transcriptome analysis in thirty-four age-matched Cavalier King Charles Spaniels with or without congestive heart failure caused by myxomatous mitral valve disease.

We here report the results of a mitral valve transcriptome study designed to identify genes and molecular pathways involved in development of congestive heart failure (CHF) following myxomatous mitral valve disease (MMVD) in dogs. The study is focused on a cohort of elderly age-matched dogs (n = 34, age ~ 10 years) from a single breed-Cavalier King Charles Spaniels (CKCS)-with a high incidence of MMVD. The cohort comprises 19 dogs (10♀, 9♂) without MMVD-associated CHF, and 15 dogs (6♀, 9♂) with CHF caused by MMVD; i.e., we compare gene expression in breed and age-matched groups of dogs, which only differ with respect to CHF status. We identify 56 genes, which are differentially expressed between the two groups. In this list of genes, we confirm an enrichment of genes related to the TNFß-signaling pathway, extracellular matrix organization, vascular development, and endothelium damage, which also have been identified in previous studies. However, the genes with the greatest difference in expression between the two groups are CNTN3 and MYH1. Both genes encode proteins, which are predicted to have an effect on the contractile activity of myocardial cells, which in turn may have an effect on valvular performance and hemodynamics across the mitral valve. This may result in shear forces with impact on MMVD progression.

Inflammatory and immune variables as predictors of survival in dogs with myxomatous mitral valve disease.

BACKGROUND: We aimed to investigate the association between selected inflammatory and immune variables and survival of dogs with myxomatous mitral valve disease (MMVD). We evaluated data of 62 client-owned dogs with MMVD, grouped into preclinical, stable congestive heart failure (CHF) and unstable CHF. Univariate Cox proportional hazards regression analysis was used to quantify the association of white blood cell count, concentrations and percentages of T lymphocytes and their subtypes (T helper lymphocytes, cytotoxic T lymphocytes, double positive T lymphocytes, double negative T lymphocytes) and B lymphocytes with survival. P values < 0.1 in individual groups and P values < 0.05 in the group of all patients were considered significant. Spearman correlation coefficients between significant covariates were calculated to assess the relationships among variables and with survival. RESULTS: In the preclinical group, percentage of double positive T lymphocytes was negatively associated with survival (hazard ratio (HR) = 2.328; P = 0.051). In the unstable CHF, T lymphocyte (HR = 1.613; P = 0.085), cytotoxic T lymphocyte (HR = 1.562; P = 0.048), double positive (HR = 1.751; P = 0.042), and double negative T lymphocyte (HR = 1.613; P = 0.096) concentrations were negatively associated with survival, as well as cytotoxic T lymphocyte (HR = 1.502; P = 0.007) concentration in the group of all patients. The percentage of T helper lymphocytes was positively associated with survival in the unstable CHF (HR = 0.604; P = 0.053) and in the group of all patients (HR = 0.733; P = 0.044). The concentration of cytotoxic T lymphocytes positively correlated with left atrial to aortic ratio (LA/Ao) (rho = 0.259, P = 0.037), and peak velocity of early diastolic mitral flow (rho = 0.259, P = 0.039), whereas the percentage of T helper lymphocytes negatively correlated with left atrial to aortic ratio (LA/Ao) (rho = -0.212, P = 0.090) and early to late mitral flow ratio (rho = -0.232, P = 0.072). CONCLUSIONS: Cytotoxic T lymphocytes, T helper lymphocytes, double positive and double negative T lymphocytes as well as biomarkers cardiac troponin I, N-terminal pro-B-type natriuretic peptide, C-reactive protein are implicated in the progression of MMVD.

Effects of acute atrial fibrillation and cardioversion on left and right atrial pressures in a dog.

The occurrence of right-sided congestive heart failure (CHF) in dogs with left-sided heart disease is well-recognized, but its mechanisms are incompletely understood. A 12-year-old Maltese dog was admitted to the clinic for left atrial decompression to treat recurrent CHF due to severe myxomatous mitral valve disease (MMVD). Left atrial decompression was successful but atrial fibrillation (AF) occurred during the procedure. Electric cardioversion restored normal sinus rhythm (NSR) and the dog's recovery was uneventful. This sequence of events made it possible to study intracameral pressures individually in each atrium in a dog with naturally occurring MMVD during AF and again during NSR. Although pressures in both atria declined following cardioversion, the right atrial pressure declined to a greater degree. These findings indicated a disproportionate effect of AF on right atrial pressure. This difference was noteworthy given the long-standing clinical observation that dogs with MMVD have a higher prevalence of right-sided CHF when AF is present. Key clinical message: A dog with MMVD had a greater reduction in right atrial pressure than in left atrial pressure when its AF was cardioverted as part of a cardiac catheterization procedure. This observation proposed a mechanism for the well-known but unexplained observation that dogs with MMVD manifest right-sided CHF disproportionately more often when they have AF.

Effets de la fibrillation auriculaire aiguë et de la cardioversion sur les pressions auriculaires gauche et droite chez un chien. La présence d'une insuffisance cardiaque congestive du côté droit (ICC) chez les chiens atteints d'une cardiopathie du côté gauche est bien connue, mais ses mécanismes ne sont pas complètement compris. Un chien maltais de 12 ans a été admis à la clinique pour une décompression auriculaire gauche afin de traiter une ICC récurrente due à une grave maladie myxomateuse de la valvule mitrale (MMVD). La décompression auriculaire gauche a réussi, mais une fibrillation auriculaire (FA) s'est produite pendant la procédure. La cardioversion électrique a rétabli le rythme sinusal normal (NSR) et la récupération du chien s'est déroulée sans incident. Cette séquence d'événements a permis d'étudier les pressions individuellement dans chaque oreillette chez un chien atteint de MMVD d'origine naturelle pendant la FA et à nouveau pendant la NSR. Bien que les pressions dans les deux oreillettes aient diminué après la cardioversion, la pression de l'oreillette droite a diminué dans une plus grande mesure. Ces résultats ont indiqué un effet disproportionné de la FA sur la pression auriculaire droite. Cette différence était remarquable compte tenu de l'observation clinique de longue date selon laquelle les chiens atteints de MMVD ont une prévalence plus élevée d'ICC du côté droit en cas de FA.Message clinique clé :Un chien atteint de MMVD présentait une réduction plus importante de la pression auriculaire droite que de la pression auriculaire gauche lorsque sa FA était cardiovertie dans le cadre d'une procédure de cathétérisme cardiaque. Cette observation propose un mécanisme pour l'observation bien connue mais inexpliquée selon laquelle les chiens atteints de MMVD manifestent une ICC du côté droit de manière disproportionnée plus souvent lorsqu'ils souffrent de FA.(Traduit par Dr Serge Messier).

Resolution of dynamic left ventricular outflow tract obstruction and reversible left ventricular hypertrophy in 4 cats.

This case series describes spontaneous resolution of systolic anterior motion of the mitral valve, cessation of a dynamic left ventricular outflow tract obstruction, and reverse cardiac remodeling in 4 young cats. Following initial presentation with or without congestive heart failure, subsequent rechecks documented resolution of systolic anterior motion of the mitral valve and normalization of left heart dimensions. Those cats originally presented with congestive heart failure were successfully weaned off diuretic medications. Atenolol was prescribed to all 4 cats, and all remained on oral atenolol through the final recheck. There was no documented recurrence of progressive heart disease and heart failure in any of the cats. Consideration is given to transient myocardial thickening, spontaneous resolution of mitral valve dysplasia, and response to beta-1 adrenergic antagonism as possible underlying mechanisms. Key clinical message: When presented with young cats with hypertrophic obstructive cardiomyopathy, veterinarians should consider multiple differential diagnoses, as lifespan in these cases may be longer than typically expected for cats with primary hypertrophic cardiomyopathy, even with concurrent congestive heart failure.

Résolution d'une obstruction dynamique de la voie d'éjection du ventricule gauche et d'une hypertrophie réversible du ventricule gauche chez 4 chatsCette série de cas décrit la résolution spontanée du mouvement antérieur systolique de la valve mitrale, la cessation d'une obstruction dynamique de la voie d'éjection du ventricule gauche et le remodelage cardiaque inverse chez 4 jeunes chats. Après une présentation initiale avec ou sans insuffisance cardiaque congestive, des vérifications ultérieures ont documenté la résolution du mouvement antérieur systolique de la valve mitrale et la normalisation des dimensions du cœur gauche. Les chats initialement présentés avec une insuffisance cardiaque congestive ont été sevrés avec succès des médicaments diurétiques. De l'aténolol a été prescrit aux 4 chats, et tous sont restés sous aténolol oral jusqu'au dernier contrôle. Aucune récidive de maladie cardiaque progressive et d'insuffisance cardiaque n'a été documentée chez aucun des chats. L'épaississement transitoire du myocarde, la résolution spontanée de la dysplasie de la valve mitrale et la réponse à l'antagonisme bêta-1 adrénergique sont pris en compte comme mécanismes sous-jacents possibles.Message clinique clé :Lorsqu'ils sont confrontés à de jeunes chats atteints de cardiomyopathie hypertrophique obstructive, les vétérinaires doivent envisager plusieurs diagnostics différentiels, car la durée de vie dans ces cas peut être plus longue que celle généralement attendue pour les chats atteints de cardiomyopathie hypertrophique primaire, même en cas d'insuffisance cardiaque congestive concomitante.(Traduit par Dr Serge Messier).

Successful Resuscitation of Neonatal Kittens Delivered by a Perimortem Cesarean Section Following Maternal Cardiopulmonary Arrest.

A 9 yr old, unknown weight, intact female domestic shorthair presented for evaluation of dystocia with dyspnea. En route to the hospital for treatment, the owners noted the queen stopped breathing. On presentation, cardiopulmonary arrest was confirmed. The exact cause was unknown but suspected to be secondary to acute fulminant congestive heart failure or acute respiratory distress syndrome due to a large volume of serosanguineous fluid within the mouth and nose. Cardiopulmonary resuscitation (CPR) was immediately started. After 2 min of CPR without return of spontaneous circulation, the owners consented to perimortem Cesarean section. Two kittens were removed via emergency hysterotomy within 3-4 min. Both kittens were successfully resuscitated. CPR efforts were continued on the queen for 2 min after delivery of the kittens, at which time the owners elected to stop further resuscitative efforts. Both kittens were discharged from the hospital and were alive at last follow-up, 2 yr and 4 mo after birth. There are no previous reports regarding the use of a perimortem Cesarean section to deliver neonates in small animal medicine. Therefore, this report represents a novel treatment approach that can be considered in the case of maternal arrest during dystocia.

The repeatability, reproducibility, and influencing factors of intrarenal Doppler ultrasonography in dogs without heart disease.

Renal impairment is concurrent with adverse outcomes such as heart disease in humans and dogs. Intrarenal Doppler ultrasonography (IRD) is used to assess intrarenal hemodynamics, and resistance index (RI) and venous impedance index (VII) are used to evaluate intrarenal hemodynamics in humans with heart failure. However, only a few studies have assessed the efficacy of IRD, especially VII, in dogs, and the methods differ between studies. Additionally, repeatability, reproducibility, and factors influencing IRD values have not been validated in dogs. This prospective, analytical study aimed to assess repeatability and reproducibility of IRD, and to clarify influencing factors of IRD in dogs without heart disease. We enrolled 78 dogs without heart disease. The RI and VII were highly reproducible, and the reference intervals for VII were 0.13-0.37. Differences in transducer (sector and convex) and posture (right lateral and supine decubitus position) had no effect on the IRD values. In contrast, RI and VII were higher in the renal vessels than in interlobar vessels. Age affected RI values (r = 0.39, P < 0.001), but there was no correlation between age, body weight, and VII. In conclusion, IRD is a repeatable and reproducible method to assess intrarenal hemodynamics in dogs. The findings also suggest that age should be considered while interpreting RI.

Incidences of steroid-induced diabetes mellitus and congestive heart failure in cats given non-immunosuppressive doses of methylprednisolone acetate: 1042 cats.

Objective: Corticosteroids are indicated to treat many feline diseases. However, side effects are a limiting factor in their use. The most concerning side effects are steroid-induced diabetes mellitus (SI-DM) and steroid-induced congestive heart failure (SI-CHF). This study aims to determine the incidences of these diseases in a large population of domestic cats seen at a privately-owned, feline-only practice. Animals: Cats in the study were client-owned patients of Alamo Feline Health Center in San Antonio, Texas. Control cats (controls) were examined as part of their routine health care. Procedures: The records of 732 cats that received methylprednisolone acetate (MPA) for various clinical indications were reviewed to determine how many developed SI-DM and SI-CHF. A similar record review of 310 controls was made to determine the incidence of spontaneous diabetes mellitus (Sp-DM) and spontaneous congestive heart failure (Sp-CHF). Control cats never received any oral or injectable corticosteroids. Results: Of the cats that received MPA, 28 developed SI-DM (3.83%) and 6 developed SI-CHF (0.82%). Of the controls, 22 developed Sp-DM (7.10%) and 6 developed Sp-CHF (1.90%). Conclusion: The incidences of developing SI-DM and SI-CHF were 3.83% and 0.82%, respectively; and the risk was not increased even when repeated doses of MPA were given. Clinical relevance: The authors consider the risk-benefit ratio sufficient to justify the use of MPA when it is indicated, especially if another drug cannot be substituted with the same therapeutic results.

Incidences du diabète sucré et de l'insuffisance cardiaque congestive induits par les stéroïdes chez des chats ayant reçu des doses non immunosuppressives d'acétate de méthylprednisolone : 1042 chats. Objectif: Les corticoïdes sont indiqués pour traiter de nombreuses maladies félines. Cependant, les effets secondaires constituent un facteur limitant leur utilisation. Les effets secondaires les plus préoccupants sont le diabète sucré induit par les stéroïdes (SI-DM) et l'insuffisance cardiaque congestive induite par les stéroïdes (SI-CHF). Cette étude vise à déterminer l'incidence de ces maladies dans une large population de chats domestiques vus dans une pratique privée exclusivement féline. Animaux: Les chats de l'étude étaient des patients appartenant à des clients du Alamo Feline Health Center à San Antonio, au Texas. Les chats témoins (témoins) ont été examinés dans le cadre de leurs soins de santé de routine. Procédures: Les dossiers de 732 chats ayant reçu de l'acétate de méthylprednisolone (MPA) pour diverses indications cliniques ont été examinés afin de déterminer combien d'entre eux ont développé du SI-DM et du SI-CHF. Un examen similaire des dossiers de 310 témoins a été réalisé pour déterminer l'incidence du diabète sucré spontané (Sp-DM) et de l'insuffisance cardiaque congestive spontanée (Sp-CHF). Les chats témoins n'ont jamais reçu de corticostéroïdes oraux ou injectables. Résultats: Parmi les chats ayant reçu du MPA, 28 ont développé du SI-DM (3,83 %) et 6 ont développé du SI-CHF (0,82 %). Parmi les témoins, 22 ont développé du Sp-DM (7,10 %) et 6 ont développé du Sp-CHF (1,90 %). Conclusion: Les incidences de développement de SI-DM et de SI-CHF étaient respectivement de 3,83 % et 0,82 %; et le risque n'a pas augmenté même lorsque des doses répétées de MPA ont été administrées. Pertinence clinique: Les auteurs considèrent le rapport bénéfice/risque suffisant pour justifier l'utilisation du MPA lorsqu'il est indiqué, notamment si un autre médicament ne peut lui être substitué avec les mêmes résultats thérapeutiques.(Traduit par Dr Serge Messier).

Heart failure in a cat due to hypertrophic cardiomyopathy phenotype caused by chronic uncontrolled hyperthyroidism.

A 16-year-old castrated male Persian cat was presented with weight loss, anorexia and dyspnoea. Tachycardia and tachypnoea were observed upon presentation. The cat was previously diagnosed with hyperthyroidism and left ventricular hypertrophy and received methimazole, but was subsequently not followed up and treated appropriately. Thoracic radiography revealed mild pleural effusion, interstitial lung pattern, moderate cardiomegaly and moderate-to-severe dilation of the pulmonary artery and pulmonary vein. On echocardiography, the left ventricular hypertrophy, identified earlier, shoed partial regression. Therefore, the previous myocardial hypertrophy was diagnosed as a hypertrophic cardiomyopathy phenotype related to hyperthyroidism. ST-segment elevation was identified on electrocardiography, and the thyroid profile examination revealed increased total thyroxine and free thyroxine and decreased thyroid-stimulating hormone levels, suggesting myocardial injury and uncontrolled hyperthyroidism, respectively. In addition, normal N-terminal pro-B-type natriuretic peptide and high cardiac troponin I levels were found. Based on these findings, the observed congestive heart failure was considered as a sequel of myocardial injury caused by uncontrolled hyperthyroidism. Clinical signs resolved after intravenous administration of furosemide and butorphanol, oxygen supply and thoracocentesis. Furosemide and pimobendan were additionally administered, and the cat was discharged. This case demonstrates that myocardial damage due to chronic uncontrolled hyperthyroidism may cause heart failure in cats.

Evidence of altered fatty acid metabolism in dogs with naturally occurring valvular heart disease and congestive heart failure.

INTRODUCTION: Myxomatous mitral valve disease (MMVD) is the most common cardiac condition in adult dogs. The disease progresses over several years and affected dogs may develop congestive heart failure (HF). Research has shown that myocardial metabolism is altered in cardiac disease, leading to a reduction in ß-oxidation of fatty acids and an increased dependence upon glycolysis. OBJECTIVES: This study aimed to evaluate whether a shift in substrate use occurs in canine patients with MMVD; a naturally occurring model of human disease. METHODS: Client-owned dogs were longitudinally evaluated at a research clinic in London, UK and paired serum samples were selected from visits when patients were in ACVIM stage B1: asymptomatic disease without cardiomegaly, and stage C: HF. Samples were processed using ultra-performance liquid chromatography mass spectrometry and lipid profiles were compared using mixed effects models with false discovery rate adjustment. The effect of disease stage was evaluated with patient breed entered as a confounder. Features that significantly differed were screened for selection for annotation efforts using reference databases. RESULTS: Dogs in HF had altered concentrations of lipid species belonging to several classes previously associated with cardiovascular disease. Concentrations of certain acylcarnitines, phospholipids and sphingomyelins were increased after individuals had developed HF, whilst some ceramides and lysophosphatidylcholines decreased. CONCLUSIONS: The canine metabolome appears to change as MMVD progresses. Findings from this study suggest that in HF myocardial metabolism may be characterised by reduced ß-oxidation. This proposed explanation warrants further research.

Retrospective analysis of radiographic signs in feline pleural effusions to predict disease aetiology.

BACKGROUND: The objectives of the study were to determine the prevalence of underlying conditions causing pleural effusion in cats and to calculate the positive predictive values, negative predictive values, sensitivity and specificity of radiographic signs to predict aetiology of the pleural fluid. METHODS: Data from 148 cats with pleural effusion and diagnosed with known aetiologies were retrospectively analysed. Sixty one cats had thoracic radiographs evaluated by consensus through pre-defined radiographic signs by two radiologists blinded to the diagnoses. RESULTS: Congestive heart failure (53.4%) was the most common diagnosis, followed by neoplasia (20.3%), pyothorax (10.8%), idiopathic chylous effusion (5.4%), feline infectious peritonitis (1.4%) and "other" or cats with multiple diagnoses (total 8.8%). Cats with an enlarged cardiac silhouette had a high positive predictive value of congestive heart failure (90%). Mediastinal masses (100%)and pulmonary masses (100%) were highly predictive of neoplastic disease. Pulmonary nodules (50%) were poorly predictive of neoplastic disease. The remainder of the radiographic variables were not informative predictors of underlying disease. CONCLUSIONS: In our sample of cats, congestive heart failure was the most common cause of pleural effusion. Radiographically enlarged cardiac silhouette and presence of a mediastinal mass may be useful predictors of aetiology, however there are limitations to the use of radiography alone as a diagnostic tool.

Myocardial Iba1, MHC class II, and CD3 are diffusely increased in canine myocarditis: A step toward antemortem myocarditis diagnostics.

Canine myocarditis is a rare but serious health concern, potentially causing heart failure and death. Antemortem diagnosis is hampered by the numerous causes, nonspecific course, and dearth of diagnostic criteria. Currently, definitive diagnosis can only be made after death. The current human diagnostic gold standard is endomyocardial biopsy pairing cardiac histopathology with immunohistology to enhance detection of often-multifocal disease. We evaluated immune response markers in the canine heart to establish similar immunohistologic criteria. We hypothesized that myocardial major histocompatibility complex class II (MHCII), cluster of differentiation 3 (CD3), and ionized calcium binding adapter molecule 1 (Iba1), markers increased in human myocarditis, would be increased in canine myocarditis cases. Archived paraffin-embedded myocardial tissue from 22 histopathologically confirmed cases of adult and juvenile myocarditis and 23 controls was analyzed by immunohistochemistry for MHCII, CD3, and Iba1, and the fraction of myocardium with labeling was determined. All 3 markers were significantly increased compared with controls across the entire section: Iba1, 10.1× (P < .0001, Mann-Whitney U test); MHCII, 3.04× (P = .0019); and CD3, 4.4× (P = .0104). To mimic off-target biopsy, samples from 2 mm2 outside of inflammatory foci were analyzed, and these showed significant increases in Iba1 by 3.2× (P = .0036, Mann-Whitney U test) and CD3 by 1.2× (P = .0026). These data show diffusely increased immune response markers with canine myocarditis, with detection potentially independent of tissue sampling. Thus, endomyocardial biopsy and immunohistochemical detection of MHCII, CD3, and Iba1 may permit sensitive antemortem diagnosis of canine myocarditis.

Acquired Systolic Dysfunction and Subsequent Congestive Heart Failure Following Treatment of Hypoadrenocorticism in Two Dogs.

Acquired cardiomyopathies have been described in human patients with hypoadrenocorticism. Several mechanisms have been described to explain the cardiac effects of primary adrenal insufficiency, but, clinically, these manifestations may be underappreciated in dogs. In humans, there is an infrequently described, reversible dilated cardiomyopathy in patients with hypoadrenocorticism. Two dogs were presented to a single referral center for evaluation of weakness or collapse and were subsequently diagnosed with hypoadrenocorticism after a full diagnostic workup. Following the diagnosis of hypoadrenocorticism and administration of glucocorticoids and desoxycorticosterone pivalate, both dogs developed left-sided congestive heart failure and had systolic dysfunction diagnosed by echocardiogram. Both dogs were euthanized; one because of recurrent congestive heart failure and another because of a concern for poor long-term prognosis and decreased quality of life. The purpose of this case report is to document multiple cases of hypoadrenocorticism-associated systolic dysfunction and subsequent cardiogenic pulmonary edema in dogs.

Mineralized, obstructive cardiac myxoma with chondroid differentiation in a cocker spaniel.

A 12-year-old castrated male cocker spaniel dog was referred for evaluation of signs consistent with right-sided heart failure. Thoracic radiography revealed mineralization in the region of the right atrium. Echocardiography identified a mass partially filling the right atrium and right ventricle and obstructing flow through the right heart. These findings were confirmed at necropsy and histopathologic features were consistent with myxoma with chondroid differentiation.

Myxome cardiaque obstructif minéralisé avec différenciation chondroïde chez un cocker. Un chien cocker mâle castré de 12 ans a été référé pour une évaluation de signes compatibles avec une insuffisance cardiaque droite. La radiographie thoracique a révélé une minéralisation dans la région de l'oreillette droite. L'échocardiographie a identifié une masse remplissant partiellement l'oreillette droite et le ventricule droit et obstruant le flux à travers le cæur droit. Ces résultats ont été confirmés à l'autopsie et les caractéristiques histopathologiques étaient compatibles avec un myxome à différenciation chondroïde.(Traduit par Dr Serge Messier).

DIAGNOSIS AND MANAGEMENT OF SUSPECTED CONGESTIVE HEART FAILURE SECONDARY TO DILATED CARDIOMYOPATHY IN A SAND TIGER SHARK (CARCHARIAS TAURUS) WITH ESTABLISHMENT OF PRELIMINARY NORMAL ECHOCARDIOGRAPHIC INDICES.

Elasmobranch cardiac anatomy and physiology has been well described; however, there is a dearth of information regarding cardiac disease. In support of a clinical case of suspected congestive heart failure in a 22-yr-old male sand tiger shark (Carcharias taurus), a study was undertaken to identify feasible echocardiographic imaging planes and preliminary indices for this species. Eleven echocardiograms were performed on six apparently healthy sand tiger sharks. Echocardiographic parameters are presented using descriptive statistics, including mean, median, standard deviation (SD), minimum and maximum values. These data were utilized for the diagnosis and clinical management of the affected shark. The shark initially presented with increased respiratory effort, dependent, peripheral edema, and anemia. Echocardiography revealed atrial, ventricular, and sinus venosus dilation. As congestive heart failure secondary to dilated cardiomyopathy was strongly suspected, therapy was initiated with oral benazepril and torsemide, and later pimobendan. After a year of therapy, clinical signs resolved. Cardiac size and function improved on echocardiography with a reduction in sinus venosus dilation, maximum and minimum atrial and ventricular inner diameters, and an increase in atrial and ventricular fractional shortening. Cardiac disease in elasmobranchs may be underdiagnosed, so it may be necessary to develop standardized ultrasound techniques and cardiac measurements for each species of elasmobranch managed within zoos and aquaria.

Inflammation and its association with oxidative stress in dogs with heart failure.

BACKGROUND: Inflammation and oxidative stress can contribute to the development and progression of heart failure. This study aimed to investigate the association between inflammatory and oxidative stress markers in dogs with congestive heart failure (CHF). Associations between the disease severity marker N-terminal pro-B-type natriuretic peptide (NT-proBNP) and markers of inflammation and oxidative stress were also determined. RESULTS: Thirty-seven dogs with cardiovascular diseases (dilated cardiomyopathy, DCM (16 dogs), myxomatous mitral valve disease, MMVD (21 dogs)) and ten healthy dogs were included in this prospective study. The patients were further divided into groups with (26) and without CHF (11). We found a significantly higher serum concentration of C-reactive protein (P = 0.012), white blood cell (P = 0.001), neutrophil (P = 0.001) and monocyte counts (P = 0.001) in patients with CHF compared to control dogs. The concentration of tumor necrosis factor-alpha (TNF-α) was significantly higher in patients with CHF compared to patients without CHF (P = 0.030). No significant difference was found in most of the measured parameters between MMVD and DCM patients, except for glutathione peroxidase (GPX) and NT-proBNP. In patients with CHF, TNF-α correlated positively with malondialdehyde (P = 0.014, r = 0.474) and negatively with GPX (P = 0.026, r = - 0.453), and interleukin-6 correlated negatively with GPX (P = 0.046, r = - 0.412). NT-proBNP correlated positively with malondialdehyde (P = 0.011, r = 0.493). In patients without CHF none of the inflammatory and oxidative stress markers correlated significantly. Furthermore, in the group of all cardiac patients, GPX activity significantly negatively correlated with NT-proBNP (P = 0.050, r = - 0.339) and several markers of inflammation, including TNF-α (P = 0.010, r = - 0.436), interleukin-6 (P = 0.026, r = - 0.382), white blood cell (P = 0.032, r = - 0.369), neutrophil (P = 0.027, r = - 0.379) and monocyte counts (P = 0.024, r = - 0.386). CONCLUSION: Inflammatory and oxidative stress markers are linked in canine CHF patients, but not in patients without CHF. These results suggest complex cross communication between the two biological pathways in advanced stages of CHF.

Early detection of myocardial dysfunction in a cat that gradually progressed to endomyocardial form of restrictive cardiomyopathy.

BACKGROUND: Restrictive cardiomyopathy (RCM) is a common myocardial disease in cats, characterized by diastolic dysfunction and atrial enlargement without myocardial hypertrophy. Especially, endomyocardial form of RCM, one of the subtypes in RCM, is characterized by endocardial fibrosis, endocardial scar bridging the interventricular septum and left ventricular (LV) free wall, and deformation and distortion of the LV. However, it is unclear how the myocardial dysfunction and the endocardial scar contribute to the pathophysiology of RCM disease progression. CASE PRESENTATION: A 3 years and 2 months old, intact male, Domestic shorthaired cat was presented for consultation of cardiac murmur. At the first visit (day 0), the notable abnormal finding was echocardiography-derived chordae tendineae-like structure bridging the interventricular septum and the LV free wall, resulting high-speed blood flow in the left ventricle. Electrocardiography, thoracic radiography and noninvasive blood pressure measurements were normal. No left atrial enlargement was observed, and LV inflow velocity showed an abnormal relaxation pattern. Although there was no abnormality in tissue Doppler imaging-derived myocardial velocity, two-dimensional speckle tracking echocardiography (2D-STE) revealed a decrease in the LV longitudinal strain and an increase in endocardial to epicardial ratio of the LV circumferential strain on day 0. On day 468, obvious left atrium enlargement and smoke like echo in the left atrium were observed. The LV inflow velocity was fused, and the tissue Doppler imaging-derived early-diastolic myocardial velocity of the septal mitral annulus decreased. Regarding 2D-STE, LV circumferential strain was further decreased, and right ventricular strain was additionally decreased. Although the general condition was good, we made a clinical diagnosis of endomyocardial RCM based on the above findings. On day 503, the cat showed the radiographic evidence of pulmonary edema and congestive heart failure signs. CONCLUSIONS: Cats with abnormal LV structure and associated myocardial dysfunction like this case needs careful observation. Additionally, 2D-STE indices may be useful for early detection of myocardial dysfunction in feline RCM.

Pathophysiology and pathological remodelling associated with dilated cardiomyopathy in broiler chickens predisposed to heart pump failure.

Broiler chickens selected for rapid growth are highly susceptible to dilated cardiomyopathy (DCM). In order to elucidate the pathophysiology of DCM, the present study examines the fundamental features of pathological remodelling associated with DCM in broiler chickens using light microscopy, transmission electron microscopy (TEM), and synchrotron Fourier Transform Infrared (FTIR) micro-spectroscopy. The morphological features and FTIR spectra of the left ventricular myocardium were compared among broiler chickens affected by DCM with clinical signs of heart pump failure, apparently normal fast-growing broiler chickens showing signs of subclinical DCM (high risk of heart failure), slow-growing broiler chickens (low risk of heart failure) and Leghorn chickens (resistant to heart failure, used here as physiological reference). The findings indicate that DCM and heart pump failure in fast-growing broiler chickens are a result of a complex metabolic syndrome involving multiple catabolic pathways. Our data indicate that a good deal of DCM pathophysiology in chickens selected for rapid growth is associated with conformational changes of cardiac proteins, and pathological changes indicative of accumulation of misfolded and aggregated proteins in the affected cardiomyocytes. From TEM image analysis it is evident that the affected cardiomyocytes demonstrate significant difficulty in the disposal of damaged proteins and maintenance of proteostasis, which leads to pathological remodelling of the heart and contractile dysfunction. It appears that the underlying causes of accumulation of damaged proteins are associated with dysregulated auto phagosome and proteasome systems, which, in susceptible individuals, create a milieu conducive for the development of DCM and heart failure. RESEARCH HIGHLIGHTS The light and electron microscopy image analyses revealed degenerative changes and protein aggregates in the cardiomyocytes of chickens affected by DCM. The analyses of FTIR spectra of the myocardium revealed that DCM and heart pump failure in broiler chickens are associated with conformational changes of myocardial proteins. The morphological changes in cardiomyocytes and conformational changes in myocardial proteins architecture are integral constituents of pathophysiology of DCM in fast-growing broiler chickens.

Platelet proteome changes in dogs with congestive heart failure.

BACKGROUND: Platelets play a central role in the development of cardiovascular diseases and changes in their proteins are involved in the pathophysiology of heart diseases in humans. There is lack of knowledge about the possible role of platelets in congestive heart failure (CHF) in dogs. Thus, this study aimed to investigate the changes in global platelet proteomes in dogs with CHF, to clarify the possible role of platelets in the physiopathology of this disease. Healthy-dogs (n = 10) and dogs with acute CHF due to myxomatous mitral valve disease (MMVD, n = 10) were used. Acute CHF was defined based on the clinical (increased respiratory rate or difficulty breathing) and radiographic findings of pulmonary edema. Dogs Blood samples were collected into tubes with acid-citrate-dextrose, and platelet-pellets were obtained by centrifuge and washing steps. Platelet-proteomes were identified using LC-MS based label-free differential proteome expression analysis method and matched according to protein database for Canis lupus familiaris. RESULTS: Totally 104 different proteins were identified in the platelets of the dogs being 4 out of them were significantly up-regulated and 6 down-regulated in acute CHF dogs. Guanine-nucleotide-binding protein, apolipoproteins (A-II and C-III) and clusterin levels increased, but CXC-motif-chemokine-10, cytochrome-C-oxidase-subunit-2, cathepsin-D, serine/threonine-protein-phosphatase-PP1-gamma-catalytic-subunit, creatine-kinase-B-type and myotrophin levels decreased in acute CHF dogs. These proteins are associated with several molecular functions, biological processes, signaling systems and immune-inflammatory responses. CONCLUSION: This study describes by first time the changes in the protein composition in platelets of dogs with acute CHF due to MMVD. Our findings provide a resource for increase the knowledge about the proteome of canine platelets and their roles in CHF caused by MMVD and could be a tool for further investigations about the prevention and treatment of this disease.

Tolerance of torasemide in cats with congestive heart failure: a retrospective study on 21 cases (2016-2019).

BACKGROUND: In dogs with congestive heart failure (CHF), the efficacy of torasemide, a loop diuretic, has been demonstrated. However, unlike in dogs and humans little has been described about the use of torasemide in the cat with spontaneous CHF. The objectives of this retrospective study were therefore to describe the therapeutic use of oral torasemide in cats with spontaneous CHF, document its potential adverse effects while reporting the clinical course of this feline population following torasemide administration in addition to standard medical therapy. RESULTS: Medical records of 21 client-owned cats with CHF (median age = 10.6 years [interquartile range (IQR) = 6.5-11.2]) receiving torasemide were reviewed. Data collected included torasemide dosages, other concurrent medications, physical examination features, echocardiographic data, and potential adverse effects during follow-up. A survival analysis was performed to estimate the time from diagnosis to cardiac death. Dyspnea related to CHF was identified in all cats (pleural effusion [8/21], pulmonary edema [5/21] or both [8/21]), associated with ascites in 4/21 cats. The CHF cause was determined by echocardiography in all cats: hypertrophic (n = 10), restrictive (n = 6), arrhythmogenic right ventricular (n = 3), dilated (n = 1) cardiomyopathies, and aortic valve abnormality (n = 1). At initiation, median torasemide dosage was 0.21 mg/kg [IQR = 0.17-0.23] q24h. Clinical signs declined in most cats (20/21) during the first 2 weeks with no remarkable adverse events. Median survival time after torasemide prescription was 182 days [IQR = 46-330]. A contemporary control group including 54 cats with CHF, receiving furosemide as sole loop diuretic treatment was compared with the study group. Median (IQR) survival time of cats in the control group was not significatively different (p = 0.962) from that of the torasemide group, i.e., 148 days (9-364), although the torasemide group included significantly more cats with recurrent episodes of CHF (52%) that the control group (19%). CONCLUSIONS: This case series demonstrates that torasemide can be used in cats with spontaneous CHF. This therapeutic interest needs to be confirmed by prospective clinical trials.

Changes of inflammatory and oxidative stress biomarkers in dogs with different stages of heart failure.

BACKGROUND: Heart failure (HF) is associated with changes in inflammatory and oxidative stress biomarkers. This study aimed to evaluate the changes of a panel of inflammatory and oxidative stress biomarkers in dogs with different stages of HF and its relation with the severity of the disease and echocardiographic changes. A total of 29 dogs with HF as a result of myxomatous mitral valve degeneration or dilated cardiomyopathy were included and classified as stage-A (healthy), B (asymptomatic dogs), C (symptomatic dogs) and D (dogs with end-stage HF) according to the ACVIM staging system. In these dogs an ecnhocardiographic examination was performed and cytokines, and inflammatory and oxidative stress markers were evaluated in serum. RESULTS: KC-like was significantly increased in dogs of stage-C (P < 0.01) and -D (P < 0.05) compared with stage-A and -B. Stage-D dogs showed significantly higher serum CRP and Hp (P < 0.05) but lower serum antioxidant capacity (PON1, TEAC, CUPRAC, and thiol) compared to stage-A and -B (P < 0.05). After the treatment, serum levels of CRP, Hp and KC-like decreased and serum antioxidant levels increased compared to their pre-treatment values. Left ventricular dimension and LA/Ao ratio correlated positively with CRP, MCP-1, and KC-like but negatively with PON1, GM-CSF, IL-7 and antioxidant biomarkers (P < 0.01). CONCLUSION: Our results showed that dogs with advanced HF show increases in positive acute-phase proteins and selected inflammatory cytokines such as KC-like, and decreases in antioxidant biomarkers, indicating that inflammation and oxidative stress act as collaborative partners in the pathogenesis of HF. Some of these biomarkers of inflammation and oxidative stress could have the potential to be biomarkers to monitor the severity of the disease and the effect of treatment.