Phosphoproteomics analysis of serum from dogs affected with pulmonary hypertension secondary to degenerative mitral valve disease.

Pulmonary hypertension (PH), a common complication in dogs affected by degenerative mitral valve disease (DMVD), is a progressive disorder characterized by increased pulmonary arterial pressure (PAP) and pulmonary vascular remodeling. Phosphorylation of proteins, impacting vascular function and cell proliferation, might play a role in the development and progression of PH. Unlike gene or protein studies, phosphoproteomic focuses on active proteins that function as end-target proteins within signaling cascades. Studying phosphorylated proteins can reveal active contributors to PH development. Early diagnosis of PH is crucial for effective management and improved clinical outcomes. This study aimed to identify potential serum biomarkers for diagnosing PH in dogs affected with DMVD using a phosphoproteomic approach. Serum samples were collected from healthy control dogs (n = 28), dogs with DMVD (n = 24), and dogs with DMVD and PH (n = 29). Phosphoproteins were enriched from the serum samples and analyzed using liquid chromatography-tandem mass spectrometry (LC-MS/MS). Data analysis was performed to identify uniquely expressed phosphoproteins in each group and differentially expressed phosphoproteins among groups. Phosphoproteomic analysis revealed nine uniquely expressed phosphoproteins in the serum of dogs in the DMVD+PH group and 15 differentially upregulated phosphoproteins in the DMVD+PH group compared to the DMVD group. The phosphoproteins previously implicated in PH and associated with pulmonary arterial remodeling, including small nuclear ribonucleoprotein G (SNRPG), alpha-2-macroglobulin (A2M), zinc finger and BTB domain containing 42 (ZBTB42), hemopexin (HPX), serotransferrin (TRF) and complement C3 (C3), were focused on. Their unique expression and differential upregulation in the serum of DMVD dogs with PH suggest their potential as biomarkers for PH diagnosis. In conclusion, this phosphoproteomic study identified uniquely expressed and differentially upregulated phosphoproteins in the serum of DMVD dogs with PH. Further studies are warranted to validate the diagnostic utility of these phosphoproteins.

Pulmonary hypertension is associated with hypocoagulability in dogs: a retrospective analysis of 66 cases (2013-2021).

OBJECTIVE: To describe coagulation profiles in dogs with echocardiographic evidence of pulmonary hypertension (PH), to compare them to coagulation profiles in dogs without echocardiographic evidence of PH, and to determine the relationship between coagulation profiles and echocardiographic probability of PH. ANIMALS: 66 dogs with PH (cases) and 86 dogs without PH (controls). METHODS: Retrospective evaluation of records between 2013 and 2021 of dogs that had both an echocardiogram and a coagulation panel performed within 7 days. Dogs that received antithrombotics within 7 days of evaluation and dogs diagnosed with congenital or acquired coagulopathy or other severe systemic disease that could lead to coagulopathy were excluded. Dogs with a low echocardiographic probability of PH were also excluded. The dogs were divided into a PH group and non-PH group based on echocardiographic results. Demographic, clinicopathologic, and traditional coagulation parameters and VCM Vet (Entegrion) parameters were compared between the 2 groups. RESULTS: Dogs with PH were significantly older (median, 11 years vs 9.5 years, P = .02) and had a significantly lower body weight (median, 7.3 kg vs 19.3 kg, P < .001) than controls. Dogs with PH also had a significantly greater percent increase in prothrombin time (PT; P = .02), partial thromboplastin time (PTT; P < .0001), and fibrinogen (P = .045); however, their antithrombin concentration was lower (P = .005) compared to controls. Eight of 65 dogs (12.3%) in the PH group and 1/86 (1.2%) dogs in the non-PH group had an elevation of PT and/or PTT greater than 50% above the reference interval (P = .005). Dogs with PH had 11.9 times (95% CI, 1.5 to 97.9; P = .02) greater odds of being hypocoagulable than dogs without PH based on PT and PTT. CLINICAL RELEVANCE: This study demonstrated an association between a moderate to high echocardiographic probability of PH and a hypocoagulable state in dogs as determined by traditional coagulation assays. It underscores the importance of monitoring the coagulation status in canine patients with PH, particularly before initiating antithrombotic medications.

Disturbance of mitochondrial dynamics in myocardium of broilers with pulmonary hypertension syndrome.

1. The following study investigated the relationship between pulmonary hypertension syndrome (PHS) and mitochondrial dynamics in broiler cardiomyocytes.2. An animal model for PHS was established by injecting broiler chickens with CM-32 cellulose particles. Broiler myocardial cells were cultured under hypoxic conditions to establish an in vitro model. The ascites heart index, histomorphology, mitochondrial ultrastructure, and mitochondrial dynamic-related gene and protein expression were evaluated.3. The myocardial fibres from PHS broilers had wider spaces and were wavy and twisted and the number of mitochondria increased. Compared with the control group, the gene and protein expression levels were decreased for Opa1, Mfn1, and Mfn2 in the myocardium of PHS broilers. The gene and protein expression was significantly increased for Drp1 and Mff.4. This study showed that PHS in broilers may cause myocardial mitochondrial dysfunction, specifically by diminishing mitochondrial fusion and enhancing fission, causing disturbances in the mitochondrial dynamics of the heart.

Proteomic analysis of pulmonary arteries and lung tissues from dogs affected with pulmonary hypertension secondary to degenerative mitral valve disease.

In dogs with degenerative mitral valve disease (DMVD), pulmonary hypertension (PH) is a common complication characterized by abnormally elevated pulmonary arterial pressure (PAP). Pulmonary arterial remodeling is the histopathological changes of pulmonary artery that has been recognized in PH. The underlying mechanisms that cause this arterial remodeling are poorly understood. This study aimed to perform shotgun proteomics to investigate changes in protein expression in pulmonary arteries and lung tissues of DMVD dogs with PH compared to normal control dogs and DMVD dogs without PH. Tissue samples were collected from the carcasses of 22 small-sized breed dogs and divided into three groups: control (n = 7), DMVD (n = 7) and DMVD+PH groups (n = 8). Differentially expressed proteins were identified, and top three upregulated and downregulated proteins in the pulmonary arteries of DMVD dogs with PH including SIK family kinase 3 (SIK3), Collagen type I alpha 1 chain (COL1A1), Transforming growth factor alpha (TGF-α), Apoptosis associated tyrosine kinase (AATYK), Hepatocyte growth factor activator (HGFA) and Tyrosine-protein phosphatase non-receptor type 13 (PTPN13) were chosen. Results showed that some of the identified proteins may play a role in the pathogenesis of pulmonary arterial remodeling. This study concluded shotgun proteomics has potential as a tool for exploring candidate proteins associated with the pathogenesis of PH secondary to DMVD in dogs.

Left ventricular eccentricity index to assess precapillary pulmonary hypertension in dogs.

INTRODUCTION: Interventricular septal flattening, frequently present in pulmonary hypertension (PH) can be quantified by the left ventricular eccentricity index (EI) measured at end-diastole (EId), end-systole (EIs) and at maximal septal flattening (EIm). In humans, EI correlates with invasive pulmonary arterial pressure. The aim of this study was to evaluate if EI correlates with parameters of right heart remodeling (RHR) and if EI is a quantitative marker of PH in dogs. MATERIALS AND METHODS: Left ventricular eccentricity indices were retrospectively measured in four groups (no, mild, moderate and severe PH) with interpretable tricuspid and/or pulmonary regurgitation. RESULTS: Ninety-seven dogs were included, with no (n = 29), mild (n = 13), moderate (n = 25) and severe (n = 30) PH. The intra- and inter-observer variability for EI measurements ranged from 2 % to 11 %. All EI were significantly elevated in severe compared to no, mild and moderate PH (P < 0.0005). In the moderate group, EIs and EIm were higher compared to the no PH group (P < 0.01). Tricuspid and pulmonary regurgitation pressure gradients and RHR parameters correlated with EId, EIs and EIm in all groups. Optimal cut-off values discriminating moderate and severe PH from no and mild PH were 1.24 (Sensitivity (Se) 60 %; Specificity (Sp) 90 %) for EId, 1.34 (Se 67 %; Sp 95 %) for EIs and 1.37 (Se 76 %; Sp 83 %) for EIm. CONCLUSIONS: Left ventricular eccentricity indices are reproducible echocardiographic variables increasing with severity of PH. Dogs with moderate and severe PH can be discriminated from dogs with no or mild PH using EIs and EIm.

Diagnostic value of two-dimensional echocardiographic measurements of the pulmonary artery diameter and the pulmonary artery distensibility index to detect pulmonary hypertension in horses.

INTRODUCTION/OBJECTIVES: Echocardiographic diagnosis of pulmonary hypertension (PH) in horses is usually based on Doppler interrogation of tricuspid (TR) or pulmonic regurgitation (PR). This study aimed at investigating two-dimensional echocardiographic (2DE) variables, including pulmonary artery diameter (PAD) and pulmonary artery distensibility index (PADI), to diagnose PH. ANIMALS, MATERIALS AND METHODS: 41 healthy horses; 82 horses with TR or PR and normal intracardiac pressure gradients; and 35 horses with TR or PR velocities indicating PH. The 2DE variables were compared between groups, cut-offs for the diagnosis of PH were determined, and conditional inference trees served to identify the variable best predicting PH in the absence of TR or PR. RESULTS: Horses with PH had larger end-diastolic cross-sectional (short-axis) PAD (PADed-sx) (5.8 ± 1.0 cm; mean ± SD) and smaller PADI[/PADps] (15.4 ± 7.7%) than healthy horses (5.0 ± 0.6 cm, P<0.0001; 20.5 ± 4.4%, P<0.001) and horses with TR or PR but no PH (5.3 ± 0.6 cm, P=0.003; 18.8 ± 4.2%, P=0.005). PADed-sx predicted PH with sensitivity (Se) = 36% and specificity (Sp) = 94% (cut-off 6.0 cm, AUC = 0.668, P=0.002), while PADI[/PADps] predicted PH with Se = 43% and Sp = 92% (cut-off 13.7%, AUC = 0.662, P=0.004). In the absence of TR, PADed-sx and the end-diastolic long-axis aortic diameter-to-PADed-sx ratio (AoDed-lx/PADed-sx) were most suitable to diagnose PH. CONCLUSION: Pulmonary artery crosssectional (short-axis) diameter at end-diastole measured in a right-parasternal long axis view of the left ventricular outflow tract and Pulmonary artery distensibility index were moderately specific but not very sensitive to diagnosing PH. Nonetheless, they may be used as complementary indices suggesting PH in the absence of TR or PR.

Hyperthyroid cats have altered pulmonary arterial hemodynamics but rarely have intermediate or high probability of pulmonary hypertension.

OBJECTIVE: Apply the 3-site echocardiographic metrics utilized to assess pulmonary hypertension (PH) probability in dogs and humans to feline echocardiographic examinations to investigate the translatability of this scheme and subsequent enhancement of detection of PH in cats. ANIMALS: 27 client-owned cats (euthyroid [n = 11] and hyperthyroid [16]). METHODS: This was a single-center, prospective, observational case-control study. Demographic, physical examination, and echocardiographic data from hyperthyroid and euthyroid cats were compared via Fisher exact test and Kruskal-Wallis test. RESULTS: Hyperthyroid versus euthyroid cats had significantly greater right atrial area index values and were more likely to have late-peaking main pulmonary artery pulsed-wave flow profiles. Two hyperthyroid cats had measurable tricuspid regurgitation tracings (one with a high probability of PH and another with a low probability of PH). CLINICAL RELEVANCE: Hyperthyroid cats demonstrated altered pulmonary arterial hemodynamics and lacked consistent intermediate or high probability of PH. The 3-site echocardiographic metrics scheme is applicable for the evaluation of right-sided cardiac and pulmonary arterial hemodynamics in cats. Further research is needed to determine reference ranges in larger populations of healthy cats and those with high clinical suspicion for PH.

Echocardiographic characteristics of dogs with pulmonary hypertension secondary to respiratory diseases.

BACKGROUND: Pulmonary hypertension (PH) secondary to respiratory disease is caused by pulmonary vascular remodeling and hypoxia. Severe PH can induce various clinical signs, including syncope and right-sided heart failure. HYPOTHESIS/OBJECTIVES: To investigate the echocardiographic characteristics in dogs with PH secondary to respiratory diseases. ANIMALS: Thirty-one dogs with respiratory diseases with or without PH and 15 healthy dogs. METHODS: Prospective cross-sectional study. Dogs were classified according to respiratory disease (obstructive airway/lung disease [OALD] or restrictive lung disease [RLD]) and PH-relevant signs. The association between echocardiographic variables and PH (classified by respiratory disease and PH-relevant signs) was investigated. RESULTS: Twenty-one dogs were diagnosed with PH; of these, 11 showed PH-related signs (OALD, n = 2; RLD, n = 9), 14 had right ventricular hypertrophy, and 19 had pulmonary arterial enlargement. Right ventricular dysfunction and dilatation were observed only in dogs with PH-related signs (n = 10). Left and right ventricular stroke volumes were significantly lower in dogs with PH (median [interquartile range]: 17.2 [12.4-20.8] and 16.8 [15.3-29.5] mL/m2 , respectively). Dogs with RLD had higher echocardiography-estimated pulmonary vascular resistance than those with OALD (median [interquartile range]: 3.1 [1.9-3.3] and 1.6 [1.3-2.2], respectively). CONCLUSIONS AND CLINICAL IMPORTANCE: Pulmonary arterial enlargement was the most common echocardiographic finding in dogs with PH secondary to respiratory diseases. Right ventricular dysfunction, dilatation, and decreased left and right ventricular stroke volume were significantly associated with the PH-related signs, indicating that comprehensive echocardiography is recommended in dogs with respiratory disease. Restricted lung disease might induce more severe PH than OALD.

Evaluation of improved transvenous heartworm extraction brush in dogs with caval syndrome.

BACKGROUND: Heartworm infection in dogs is caused by Dirofilaria immitis and common in shelter animals and outdoors dogs. Caval syndrome can develop with severe infection and physical heartworm removal is essential with heartworm burdens. In this study, we used an improved transvenous heartworm extraction brush, which was expected to cause less cardiovascular damage and allow easier manipulation. OBJECTIVES: This study aims to evaluate efficacy of this improved transvenous heartworm extraction brush. METHODS: The brush was designed to improve upon the limitations of the previous brush-type devices. The brush was made of a polyvinyl chloride tube and threads of polyamides or polyglyconates. Metal material was inserted at the front tip for easy visualization under fluoroscopy. The eight dogs diagnosed with caval syndrome with large numbers of heartworms and pulmonary hypertension were used in this study. The removal procedure began with the dissection of the subcutaneous tissue around the right jugular vein. The device was inserted through the jugular vein. After insertion, the tube was rotated to catch the heartworms and extracted with the heartworms hanging on the threads. The procedure was repeated several times. Lastly, jugular vein and skin sutures were made. Adulticidal therapy was administered after heartworm removal. RESULTS: The mean number of removed heartworms was 10.5 ± 4.24 and mean number of remaining heartworms was 0.63 ± 1.06. Total procedure time was 72.63 ± 51.36. Except for three cases, heartworms were not detected on ultrasonography after the procedure. No procedure-related side effects were observed within the 1- to 2-mon. CONCLUSIONS: An improved transvenous heartworm extraction brush is efficient for heartworm removal in dogs with caval syndrome.

Usefulness of NT-proBNP in dogs with heartworm: could this biomarker be useful to evaluate pulmonary hypertension?

BACKGROUND: In recent years, the usefulness of echocardiography and serum biomarkers in the diagnosis of pulmonary hypertension (PH) in dogs with heartworm disease has been studied. Previously, N-terminal pro B-type natriuretic peptide (NT-proBNP) has shown high concentrations in dogs with heart disease and/or PH as well as its usefulness as a prognostic indicator, but it has never been evaluated in the diagnosis and prognosis of PH in dogs with heartworm disease. The aim was to evaluate the serum concentrations of NT-proBNP in dogs infected by Dirofilaria immitis to determine its usefulness as a tool to detect precapillary PH. METHODS: NT-proBNP was determined in 50 heartworm-infected dogs. Presence/absence of PH was determined echocardiographically, using the Right Pulmonary Artery Distensibility Index (RPAD Index) and the systolic flow of tricuspid regurgitation mainly, together with other echocardiographic measurements following the guidelines of the American College of Veterinary Internal Medicine (ACVIM) for the diagnosis of PH. Other epidemiological parameters (breed, age, sex, status: client-owned or shelter dogs) and clinical parameters (microfilaremia, parasite burden, presence of symptoms, body condition) were collected as well. RESULTS: Moderate-severe PH was present in 40% of the dogs (RPAD Index < 29.5%), NT-proBNP concentrations being significantly higher compared with dogs that did not have PH. A cutoff for NT-proBNP of ≥ 1178.45 pmol/l showed a sensitivity of 64.3% and a specificity of 95.5% for the presence of moderate-severe PH. Older dogs and dogs from shelters showed significantly higher NT-proBNP concentrations. Dogs with symptoms and low body condition presented significantly higher NT-proBNP concentrations as well. CONCLUSIONS: The determination of NT-pro-BNP concentration can be a useful tool in the diagnostic work-up of dogs with heartworm disease and associated PH and can help to identify animals in the more advanced stage of this disorder.

Prognostic value of pulmonary vascular resistance estimated by echocardiography in dogs with myxomatous mitral valve disease and pulmonary hypertension.

BACKGROUND: Progression to combined post- and pre-capillary pulmonary hypertension (PH) provides prognostic information in human patients with post-capillary PH. Pulmonary vascular resistance estimated by echocardiography (PVRecho) is useful for the stratification of dogs with myxomatous mitral valve disease (MMVD) and detectable tricuspid regurgitation. OBJECTIVES: To evaluate the prognostic value of PVRecho in dogs with MMVD. ANIMALS: Fifty-four dogs with MMVD and detectable tricuspid regurgitation. METHODS: Prospective cohort study. All dogs underwent echocardiography. The PVRecho was calculated based on tricuspid regurgitation and the velocity-time integral of the pulmonary artery flow. To evaluate the influence of echocardiographic variables on cardiac-related deaths, Cox proportional hazard analysis was performed. Additionally, Kaplan-Meier curves classified by PVRecho tertiles were made and compared using log-rank tests to evaluate the influence of PVRecho on all-cause mortality and cardiac-related death. RESULTS: The median follow-up time was 579 days. Forty-one dogs with MMVD (PH severity [number]: no or mild, 21/33; moderate, 11/11; severe, 9/10) died during the study. In the multivariable Cox proportional hazard analysis adjusted for age, sildenafil administration, and American College of Veterinary Internal Medicine stage of MMVD, left atrial to aortic diameter ratio and PVRecho remained significant (adjusted hazard ratio [95% confidence interval]: 1.2 [1.1-1.3] and 2.1 [1.6-3.0], respectively). Higher PVRecho showed a significant association with lower survival rates. CONCLUSIONS AND CLINICAL IMPORTANCE: Left atrial enlargement and high PVRecho were independent prognostic factors in dogs with MMVD and detectable tricuspid regurgitation.

Perivascular inflammatory cells and their association with pulmonary arterial remodelling in dogs with pulmonary hypertension due to myxomatous mitral valve disease.

Pulmonary hypertension (PH), an increase in pulmonary arterial pressure (PAP), may occur in dogs affected with myxomatous mitral valve disease (MMVD). Recent studies suggest that an accumulation of perivascular inflammatory cells may be involved with medial thickening which is a sign of the pulmonary artery remodelling in PH. The aim of this study was to characterise perivascular inflammatory cells in the surrounding pulmonary arteries of dogs with PH due to MMVD compared to MMVD dogs and healthy control dogs. Nineteen lung samples were collected from cadavers of small-breed dogs (control n = 5; MMVD n = 7; MMVD + PH n = 7). Toluidine blue stain and multiple IHC targeting α-SMA, vWF, CD20, CD68 and CD3 was performed to examine intimal and medial thickening, assess muscularisation of the small pulmonary arteries and characterise perivascular leucocytes. Medial thickening without intimal thickening of pulmonary arteries and muscularisation of normally non-muscularised small pulmonary arteries was observed in the MMVD and MMVD + PH groups compared with the control group. The perivascular numbers of B lymphocytes, T lymphocytes and macrophages was significantly increased in the MMVD + PH group compared with the MMVD and control groups. In contrast, the perivascular number of mast cells was significantly higher in the MMVD group compared with the MMVD + PH and control groups. This study suggested that pulmonary artery remodelling as medial thickening and muscularisation of the normally non-muscular small pulmonary arteries is accompanied by the accumulation of perivascular inflammatory cells.

Effect of sage (Salvia officinalis L.) extract in antioxidant status and intestinal morphology of pulmonary hypertensive chickens.

OBJECTIVES: The effects of dietary sage on the growth performance, antioxidant status, intestinal mucosa morphology, and pulmonary hypertensive response were investigated in broiler chickens with pulmonary hypertension. METHODS: Chicks (Ross 308) were reared under cold stress for 35 days and treated with 0.05% vitamin C (positive control) and 0 (control), 0.1 or 0.2% sage extracts, then performance, oxidant and antioxidant status, and intestinal morphology were evaluated. RESULTS: The index of pulmonary hypertension (RV:TV) was decreased, and weight gain (days 22-35) was increased in all treatments (except for sage 0.1%) compared with control (P < 0.05). Lipid peroxidation was decreased, whereas the activity of antioxidant enzymes (GPX, CAT, and SOD) was increased in the sage 0.2% group compared with control (P < 0.05). In the lung, SOD, CAT, and GPX transcripts were decreased in the sage 0.2% group compared with control (P < 0.05). In the right ventricle of the heart, SOD and CAT transcripts were increased in the sage 0.2% group compared with other groups of chickens, whereas GPX transcript was decreased (P < 0.05). The jejunal villus length in the chickens fed sage was significantly lower than in control (P < 0.05). The ileal villus width, villus surface area, and lamina proporia thickness in the chickens fed sage (0.2%) were increased compared with control (P < 0.05). CONCLUSIONS: Dietary supplementation of sage (0.2%) could modulate pulmonary hypertensive response, improve antioxidant status (enzymatic activity), intestinal morphometry, and absorptive surface in the broiler chickens.

Caudal pulmonary artery to vein ratio on radiography can predict pulmonary hypertension in dogs with mitral regurgitation.

Pulmonary hypertension (PH) is an important predictor of poor outcomes in dogs with mitral regurgitation (MR). The feasibility of radiography to predict PH in dogs with MR is unknown. This retrospective, observational, and analytic study aimed to identify a radiographic parameter to predict PH in dogs with MR. A total of 302 dogs diagnosed with MR on echocardiography were enrolled. Medical record and radiographic findings such as the size of the main pulmonary artery, left atrium, left ventricle, and right chamber, and cranial and caudal pulmonary arteries and veins were evaluated according to the presence of PH. The diameters of the cranial and caudal pulmonary vessels were compared to the fourth rib and the ninth rib, respectively, and the ratio of the pulmonary artery to the corresponding vein (CdPA/CdPV) was calculated. Pulmonary hypertension was diagnosed in 77 dogs (25.5%) and the prevalence of PH increased with MR grade. The CdPA/CdPV was significantly higher (P < 0.001) in the presence of PH. Multivariate analysis showed that the CdPA/CdPV was the only independent radiographic parameter that had a significant association with PH in dogs with MR (P = 0.028). The cut-off value of the CdPA/CdPV = 1.10 showed 90.6% specificity and 31.1% sensitivity for detecting PH in dogs with MR. In dogs with MR, PH can be predicted with high specificity when the caudal pulmonary artery is 1.1 times larger than the corresponding vein on radiographs.

No evidence of pulmonary hypertension revealed in an echographic evaluation of right-sided hemodynamics in hyperthyroid cats.

OBJECTIVES: Hyperthyroidism is a common endocrinopathy affecting middle-aged to elderly cats, with multisystemic repercussions. Hyperthyroid humans show decreased lung compliance and increased cardiac output with subsequent left heart failure leading to pulmonary capillary congestion. Prognosis worsens with the development of increased pulmonary vascular pressures (ie, pulmonary hypertension [PH]) in hyperthyroid humans. The effect of excess thyroid hormone concentration on pulmonary arterial hemodynamics is unknown in cats. Assessing pulmonary vascular pressures in veterinary medicine relies heavily on echocardiographic measurements performed at the level of the heart and pulmonary trunk. This study investigated right-sided cardiac and pulmonary arterial hemodynamics in hyperthyroid cats using echocardiography. METHODS: Echocardiographic examinations of hyperthyroid cats identified through a bi-institutional database search were reviewed for the determination of systolic pulmonary arterial pressure (PAP) and 20 other metrics. Values were compared with those of a healthy cat group using non-parametric statistical analyses. RESULTS: Systolic PAP could not be determined in 23/26 hyperthyroid and 13/14 healthy cats owing to unmeasurable tricuspid regurgitation flow velocity. Hyperthyroid cats were roughly twice as old (P <0.001) and had 2-4-fold higher respiratory rates (P <0.001) than healthy cats. Hyperthyroid cats showed an increase in acceleration time-to-ejection time ratio of pulmonary flow (1.4-fold, P = 0.001), pulmonary artery velocity time integral (1.2-1.6-fold, P = 0.001), maximal pulmonary velocity (1.3-1.7-fold, P = 0.002), stroke volume (1.5-fold, P = 0.001) and cardiac output (1.6-fold, P <0.001) vs healthy cats. None of the other echocardiographic metrics reached statistical significance. CONCLUSIONS AND RELEVANCE: Systolic PAP estimation proved unsuitable as a sole measurement for the assessment of PH in hyperthyroid cats owing to the frequent inability to interrogate tricuspid regurgitant flow velocity. Hyperthyroid cats have altered echocardiographic measures of pulmonary hemodynamics dissimilar to those reported in hyperthyroid humans. Differential effects of thyrotoxic cardiomyopathy on ventricular systolic function may underlie species differences.

Feline pulmonary hypertension: are we overlooking an important comorbidity?

Pulmonary hypertension (PH) is a potential complication in many disease states, yet it has been largely overlooked in feline medicine. Recently, increased awareness of potential underlying causes has led to a wider understanding of the disease process in humans, with a focus on tailoring therapy to include specific treatment of the underlying etiology. Most of these treatments are not yet available in veterinary medicine, but as they move from the human to the veterinary field, it would be beneficial to better understand the forms of PH encountered in different species. Recently, diagnosis and classification of PH in dogs has been the focus of an American College of Veterinary Internal Medicine consensus statement, yet this condition has received little attention in cats. It is therefore our intention to raise awareness of this condition in cats and to propose a classification system for the types of PH seen in feline patients. As new medications are developed for the treatment of PH, it is important to recognize which forms of PH are seen in feline patients and understand the etiology of the disease. There are many reports of PH (or suspected PH based on echocardiographic assessment) in cats. In this review, we highlight the large number of conditions, and different etiologies, that are associated with PH. Improving understanding of this condition will bring us closer to being able to investigate the benefits of potential new diagnostics and therapies as they become available.

Right ventricular size and function evaluated by various echocardiographic indices in dogs with pulmonary hypertension.

BACKGROUND: Three-dimensional (3D) echocardiography and 2-dimensional (2D) strain measurements of the right ventricle (RV) are important indices in humans with pulmonary hypertension (PH) and need further evaluation in dogs with PH. OBJECTIVES: To evaluate various RV size and function indices in dogs with PH and to examine differences between pre- and postcapillary PH. ANIMALS: A total of 311 client-owned dogs: 100 dogs with PH, 31 with postcapillary and 69 with precapillary PH, and 211 healthy control dogs. METHODS: Retro- and prospective, multicenter study. Size and function of the RV was determined using several indices, derived using dedicated RV software, including 3D RV end-diastolic volume (EDVn), end-systolic volume (ESVn), ejection fraction, 2D global and free wall RV longitudinal strain (RVLS), end-diastolic area, end-systolic area, fractional area change, tricuspid annular plane systolic excursion, and tissue Doppler imaging-derived systolic myocardial velocity of the lateral tricuspid annulus (S'n). RESULTS: The EDVn (1.8 vs 2.5 mL/kg0.942 , P < .01) and ESVn (0.8 vs 1.2 mL/kg0.962 , P < .001) were significantly larger in the PH group compared to healthy controls. Free wall RVLS was decreased in dogs with severe PH compared to controls (-24% vs -29.6%, P < .001). Dogs with precapillary PH had worse RV systolic function than dogs with postcapillary PH. CONCLUSION: Three-dimensional echocardiography of the RV is a promising tool to detect RV changes in dogs with PH. Also, 2D strain measurements are able to detect decreased RV function and offer several advantages compared to conventional indices.

Pre- and postcapillary pulmonary hypertension in dogs: Circulating biomarkers.

Background: Pulmonary hypertension (PH) in dogs is a syndrome that could be primary or secondary due to pulmonary disease, pulmonary thromboembolism, heartworm disease, and heart failure. Due to the inability of right heart catheterization in veterinary patients, there is a lack of differential criteria between PH forms. In some acute cases, it is impossible to provide a full EchoCG or catheterization study. In this situation, circulating markers may be useful to discover the possible mechanism of PH form and provide specific therapy. Aim: Following all previous data in human and veterinary studies, we assumed that plasm concentration of serotonin, endothelin-1 (ET-1), and vascular endothelial growth factor D (VEGF-D) would show a predominance in affected part of pulmonary circulation. Methods: We studied 59 small-breed dogs of different sexes and ages. Groups were formed according to a primary pathology: healthy dogs (n = 8); dogs with myxomatous mitral valve disease (MMVD) and postcapillary PH (PostPH, n = 23); dogs with MMVD and precapillary PH (PrePH, n = 28). Animals in the study were diagnosed with the primary disease by standard echocardiographic methods and algorithms. Blood samples were collected at the moment of presentation and frozen in a -80°C fridge. For biochemistry analysis, we used species-specific ELISA kits, provided by Cloud-Clone Corp. (USA). The tests were provided by the means of Almazov National Medical Research Center, IEM laboratory. Results: Dogs with EchoCG-proved PostPH had a higher concentration of VEGF-D in comparison to control and PrePH (р <0.001, for both). There was no difference between the control and PrePH groups (р >0.05). ET-1 was higher in PrePH in comparison to PostPH and control dogs (р <0.001, for both). In addition, there was no difference between the control and PostPH groups (р >0.05). Serotonin concertation did not have a difference between controls and PostPH. However, it was higher in PrePH than in control (р <0.033) and PostPH group (р <0.006). Receiver operating curve analysis showed that plasma concentrations of ET-1 (0.99) and VEGF-D (0.92) had high effectiveness in the differentiation of PostPH and PrePH. Conclusion: This study showed a correlation between circulating biomarkers (serotonin, ET-1, and VEGF-D). We found a connection between ET-1 and right-sided heart failure as well as VEGF-D and left heart failure in the PH context.

Evaluation of acute phase proteins, adiponectin and endothelin-1 to determine vascular damage in dogs with heartworm disease (Dirofilaria immitis), before and after adulticide treatment.

Previous studies have shown the existence of an acute phase response in dogs with heartworm (Dirofilaria immitis), probably caused by the vascular inflammation that occurs during the pathogenesis of this disease. In addition, it has been seen that this acute phase response persists after finishing treatment, especially in dogs with pulmonary hypertension (PH). Furthermore, echocardiographic studies have shown that PH and endarteritis appear to persist for at least 10 months after completion of adulticide treatment, suggesting that the vascular changes in these dogs may not be reversible. Therefore, the objective of this study was to evaluate the serum concentrations of different positive acute phase proteins (APP) [C reactive-protein (CRP), haptoglobin and ferritin] and negative APP (albumin and paraoxonase-1 (PON-1)), and the usefulness of the endothelin-1 (ET-1) and adiponectin, in dogs infected by D. immitis to evaluate their usefulness as diagnostic biomarkers of vascular damage and PH and their progression throughout therapy up to 7 months after the end of adulticide treatment. Twenty-five heartworm-infected dogs received adulticide treatment, and serum measurements were performed on the day of diagnosis (day 0), day of discharge (day 90), and 6 months after discharge (day 270). In addition, presence or absence of PH was also echocardiographically determined using the Right Pulmonary Artery Distensibility Index. PH was present in 44% of the dogs on day 0 and day 90, and in 48% of dogs on day 270. Alterations were observed in the concentrations of all APP throughout the study, persisting the alterations in PON-1 and ferritin on day 270. Depending on the presence or absence of PH, CRP showed significant differences throughout the study, as did ET-1. On the other hand, adiponectin did not show variations throughout the study, so it did not seem a useful marker in this disease. These results could reflect the possible persistence of vascular inflammation up to 7 months after finishing treatment, whether or not there was PH, and consolidate the study of APP as useful markers in heartworm disease. Moreover, persistent PH could be the consequent clinical manifestation in dogs with more severe vascular alterations so the study of APP, especially CRP, and ET-1 could be especially advantageous in these patients in the early evaluation of the disease, as well as for the determination of disease severity, monitoring therapeutic responses, and predicting outcomes.

Characterization of Doppler spectrum of hepatic veins in dogs with pulmonary hypertension.

Pulmonary hypertension (PH) triggers hemodynamic changes within the right heart, which may affect hepatic venous flow. The aims of this study were three-fold: to investigate, prospectively, the reliability of the hepatic vein Doppler waveform to diagnose and characterize the magnitude of PH in dogs; to evaluate whether a correlation exists between hepatic venous flow waves and the structural and functional characteristics of the right ventricle (RV); and to determine whether age, gender, body weight, heart rate (HR), heart rhythm and systolic blood pressure affect the hepatic venous waveform pattern. A cross-sectional observational study was carried out in 43 dogs with varying degrees of PH and a control group of 15 healthy dogs. The velocities of the hepatic A, S, V and D spectral waves and the phasic pattern varied according to the severity of PH. Weak to moderate correlations were documented between hepatic vein waves and age, HR, and the structural and functional variables of the RV. A D Wave cut-off of 11.6 cm ∙ s-1 had a sensitivity of 100% and specificity of 35% for differentiation of dogs with severe PH from healthy dogs. Doppler assessment of hepatic venous flow was shown to be a reliable technique for screening dogs for PH.