Sildenafil-induced priapism in a dog : an unusual case report.

BACKGROUND: Priapism is defined as erection that lasts for more than 4 h without sexual stimulation. There are various causes of priapism, but there are no reports of sildenafil-induced priapism in dogs. In human medicine, there were no pre-marketing reports of priapism caused by sildenafil, but post-marketing surveillance has shown that it is rare. In cases of pulmonary hypertension in dogs, sildenafil is the first-line drug of choice for symptomatic relief. CASE PRESENTATION: An 11-year-old neutered male Maltese dog that presented with tachypnea and cough was diagnosed with myxomatous mitral valve disease, American College of Veterinary Internal Medicine (ACVIM) stage C, and was treated medically. Eighteen months after the diagnosis, severe pulmonary hypertension occurred due to left heart disease. At 20 months postdiagnosis, pleural effusion occurred, and sildenafil (2 mg/kg twice daily) was added to the existing treatment. Two weeks later, the dyspnea recurred, confirming pleural fluid recurrence, and sildenafil was increased to 2 mg/kg thrice daily. One day later, the patient developed persistent erections and penile pain. Penile amputation and urethrostomy were recommended but were refused; therefore, analgesia and palliative care were provided. The patient died of acute dyspnea 22 months after the first presentation, with no specific priapism recurrence at the time of death. CONCLUSION: To the best of our knowledge, this is the first report of sildenafil-induced priapism in a dog with pulmonary hypertension.

Mycoplasma spp. pneumonia and subsequent pulmonary hypertension in a domestic ferret (Mustela putorius furo).

Treatment of Mycoplasma spp. pneumonia has rarely been described in domestic ferrets (Mustela putorius furo). A 10-month-old, 0.53 kg, female spayed domestic ferret was presented for oxygen-dependent, chronic dyspnea of one-month's duration. Physical examination findings included dyspnea, tachypnea, increased bronchovesicular sounds bilaterally, and an intermittent non-productive cough. Bloodwork abnormalities included a mild leukocytosis (8.6×103/µL), mild neutrophilia (4.0×103/µL), mild hypoalbuminemia (2.7 g/dL), mild hyperglobulinemia (3.3 g/dL), mild hyponatremia (147 mEq/L), and mild hypochloremia (111.4 mEq/L). Radiographs revealed a marked diffuse bronchial pattern with peribronchial cuffing, a mild main pulmonary artery bulge, distended caudal lobar pulmonary arteries, and decreased serosal detail within the abdomen. An echocardiogram revealed indications of moderate pulmonary hypertension and systolic anterior motion of the mitral valve. Polymerase chain reaction testing for Mycoplasma spp. was positive, and treatment was initiated with doxycycline (10 mg/kg PO q 12 h for 16 weeks), prednisolone (0.4 mg/kg PO q 12 h for 13 weeks, tapered to 0.2 mg/kg PO q 12 h for two weeks, then eventually increased to 0.7 mg/kg PO q 12 h until further notice), sildenafil (0.3 mg/kg PO q 24 h for 13 weeks), and oxygen supplementation via an oxygen cage for six weeks. On repeat echocardiogram eleven weeks after initiation of doxycycline therapy, the pulmonary hypertension had resolved. At follow up six months later, the ferret was stable on previously prescribed medications and did not require oxygen supplementation. Mycoplasma spp. and pulmonary hypertension should be considered in cases of respiratory distress in ferrets.

Retrospective analysis of dogs and cats with a mixed form of pulmonary hypertension and suspected pulmonary capillary hemangiomatosis in comparison to animals with predomination of precapillary pulmonary hypertension.

Background: Pulmonary capillary hemangiomatosis (PCH) is an idiopathic disease with the anomalous proliferation of a small capillary-like vessel in the pulmonary tissue, which can lead to a severe form of PH. There are only several cases of PCH described in veterinary literature: 27 cases in dogs and 2 cases in cats. In veterinary medicine, PH is mostly recognized as a consequence of left heart failure as a progression of the postcapillary PH to the precapillary form. PCH is mostly described as a primary disease, but resistant postcapillary PH with the high possibility of pulmonary edema raises speculation that PCH could be a secondary malformation to the left heart disease. Aim: Discover the features associated with the shift between left- and right-sided heart disease in the context of PH development. Methods: Retrospective analysis of materials from cats and dogs with histological markers of PCH (sPCH) versus those with right heart failure (RHF). Results: Animals with histological and immunohistochemistry markers of PCH had a previous history of disease with left heart volume overload. There were no differences between the groups in radiography and gross pathology. Histologically, pulmonary fibrosis and arteriopathy could be found in RHF; in sPCH-a duplication of capillaries in alveolar septa and bizarre proliferation in surrounding structures. Conclusion: PCH could be a secondary pattern of vascular remodeling due to volume overload.

Retrospective evaluation of a right heart parameter score in the assessment of precapillary pulmonary hypertension in dogs (2017-2021): 135 cases.

OBJECTIVE: To determine if emergency and critical care residents can identify moderate to severe precapillary pulmonary hypertension on cardiologist-obtained cineloops using a pulmonary hypertension score (PHS) and report the interobserver variability of the PHS. DESIGN: Multicenter, retrospective, case-control study from 2017 to 2021. SETTING: Private referral center and veterinary teaching hospital. ANIMALS: One hundred and thirty-five client-owned dogs that underwent diagnostic echocardiography. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Medical records of dogs with stage B1 myxomatous mitral valve disease (MMVD) and dogs diagnosed with precapillary pulmonary hypertension (PCPH) via echocardiograms were reviewed. Dogs were categorized by a cardiologist into 5 groups (normal, B1 MMVD, mild, moderate, and severe PCPH) based on Doppler pulmonary pressure gradients and right heart morphology. Cineloops from each case were subjectively evaluated by emergency and critical care residents for the presence of right atrial and ventricular enlargement, right ventricular hypertrophy, interventricular septal flattening, and pulmonary artery and trunk enlargement to form a composite pulmonary hypertension score out of 8 (PHS8). When available, signs of peritoneal effusion and distention of the caudal vena cava were subjectively assessed to generate a pulmonary hypertension score out of 10 (PHS10). There was excellent discrimination of moderate to severe PCPH versus grouped absent to mild PCPH using PHS8 (area under the receiver operator curve [AUC] [95% confidence interval, CI] = 0.90 [0.84-0.95], P < 0.0001) and PHS10 (AUC [95% CI] = 0.89 [0.81-0.97], P < 0.0001). PHS8 ≥3 was 64% sensitive and 98% specific for moderate to severe PCPH (positive likelihood ratio [LR+] 32, negative likelihood ration [LR-] 0.37). PHS10 ≥ 3.3 was 64% sensitive and 92% specific for moderate to severe PCPH (LR+ 8, LR- 0.39). Interobserver agreement was good to excellent (intraclass correlation coefficient [ICC] = 0.74 [95% CI: 0.66-0.80], n = 135). CONCLUSIONS: Residents identified moderate to severe PCPH in dogs using PHS on cineloops previously obtained by a cardiologist. The interrater agreement was good to excellent with limited training. Prospective studies to determine if residents can obtain diagnostic images for PHS are warranted.

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.

The echocardiographic pulmonary to left atrial ratio: A noninvasive variable for the hemodynamic classification of pulmonary hypertension in dogs.

BACKGROUND: Hemodynamic classification of pulmonary hypertension (PH) has important clinical implications. However, only a few echocardiographic variables have been used to hemodynamically classify PH in dogs. OBJECTIVE: To evaluate the echocardiographic pulmonary to left atrial ratio index (ePLAR) in dogs with PH. ANIMALS: Forty-six dogs with intermediate to high probability of PH. METHODS: Cross-sectional study. Variables were compared between dogs with precapillary PH [PrePH (n = 24)] vs postcapillary PH [PostPH (n = 22)], and with combined PH [CombPH (n = 14)] vs isolated PH [IsoPH (n = 8)] using the t-, Mann-Whitney, Pearson's Chi, or Fisher's exact test. The receiver operating characteristic curve and Youden index were used to identify the optimal ePLAR cutoff value to differentiate among the groups, intraclass correlation coefficients (ICC) were used to determine the reliability of measurements. RESULTS: The mean (SD) ePLAR of the PrePH was higher than that of the PostPH group [0.36 (0.13) vs 0.26 (0.09), respectively; P = .005]. The median (interquartile range) ePLAR of the CombPH was higher than that of the IsoPH subgroup [0.29 (0.24-0.38), vs 0.20 (0.16-0.23), respectively; P = .001]. The best cutoff value of ePLAR for identifying IsoPH was <0.245 [AUC at cutoff point = 0.86; sensitivity (95% confidence interval [CI]) = 0.71 (0.47-0.95); specificity (95% CI) = 1 (0.76-1)]. The ICC analysis indicated a high degree of reliability. CONCLUSIONS AND CLINICAL IMPORTANCE: ePLAR can be considered a valid noninvasive variable to hemodynamically classify PH in dogs with an intermediate to high probability of PH. Assessment of ePLAR can be useful in the therapeutic management of PH in dogs.

Platelet hyperresponsiveness and increased platelet-neutrophil aggregates in dogs with myxomatous mitral valve disease and pulmonary hypertension.

BACKGROUND: Pulmonary hypertension (PH) in dogs with myxomatous mitral valve disease (MMVD) is caused by increased pulmonary venous pressure. Thrombosis, vascular remodeling, and vasoconstriction mediated by platelets could exacerbate PH. HYPOTHESIS: Dogs with PH will exhibit a hypercoagulable state, characterized by increased platelet activation, platelet-leukocyte, and platelet-neutrophil aggregate formation. ANIMALS: Eleven dogs (≥3.5 kg) diagnosed with MMVD and PH and 10 dogs with MMVD lacking PH. METHODS: Prospective cohort ex vivo study. All dogs underwent echocardiographic examination, CBC, 3-view thoracic radiographs, and heartworm antigen testing. Severity of PH and MMVD were assessed by echocardiography. Viscoelastic monitoring of coagulation was assessed using thromboelastography (TEG). Platelet activation and platelet-leukocyte/platelet-neutrophil interactions were assessed using flow cytometry. Plasma serotonin concentrations were measured by ELISA. RESULTS: Unstimulated platelets from dogs with MMVD and PH expressed more surface P-selectin than MMVD controls (P = .03). Platelets from dogs with MMVD and PH had persistent activation in response to agonists. The number of platelet-leukocyte aggregates was higher in dogs with MMVD and PH compared with MMVD controls (P = .01). Ex vivo stimulation of whole blood resulted in higher numbers of platelet-neutrophil aggregates in dogs with MMVD and PH (P = .01). Assessment of hypercoagulability based on TEG or plasma serotonin concentrations did not differ between groups. CONCLUSION AND CLINICAL IMPORTANCE: Platelet hyperresponsiveness and increased platelet-neutrophil interaction occur in dogs with MMVD and PH, suggesting that platelets play a role of in the pathogenesis of PH. Clinical benefits of antiplatelet drugs in dogs with MMVD and PH require further investigation.

Pulmonary thrombotic pulmonary hypertension managed using antithrombotic and pulmonary vasodilator treatment.

An 8-year-old Leonberger receiving immunosuppressive treatment with clinical signs of acute dyspnea, cyanosis, and difficulty standing was referred to our institution (Day 1). Treatment including oxygen, clopidogrel, and low-molecular-weight heparin was initiated for suspected pulmonary thrombosis. However, exertional dyspnea persisted until Day 10, and increased tricuspid regurgitation velocity, pulmonary vascular resistance, and McConnell's signs also were observed. Thus, beraprost sodium was administered PO on Day 11 to treat suspected pulmonary hypertension. On Day 13, contrast-enhanced computed tomography identified extensive contrast defects in the pulmonary arteries, and IV monteplase was administered on Days 14 and 18, with marked improvement in respiratory status and exertional dyspnea on Day 20. Right ventricular function and McConnell signs also improved, and tricuspid regurgitation velocity and pulmonary vascular resistance decreased. On Day 250, echocardiography indicated further improvement in pulmonary hypertension pathophysiology. The patient was still progressing well with antithrombotic and pulmonary vasodilator treatment 400 days later.

Myxomatous mitral valve disease and associated pulmonary hypertension might increase serum angiopoietin-2 in dogs.

OBJECTIVE: To evaluate the relationships between the severity of myxomatous mitral valve disease (MMVD) and pulmonary hypertension (PH) and serum angiopoietin (Ang)-1 and Ang-2 concentrations in dogs with MMVD. ANIMALS: 74 dogs (control, n = 12; MMVD, n = 62) were included. METHODS: Serum Ang-1 and Ang-2 concentrations were estimated using the canine-specific ELISA kit. The concentrations were compared between dogs with MMVD and healthy dogs, and they were analyzed according to the severity of MMVD and PH. RESULTS: The median serum Ang-1 concentration did not differ among the study groups. The median serum Ang-2 concentration was higher in dogs with stage B2 MMVD (P = .041) and acute congestive heart failure (P = .002) than in control dogs. In addition, the median serum Ang-2 concentration was higher in MMVD dogs with PH than in those without PH (P = .031). Serum Ang-2 concentration was correlated with vertebral heart score (rs = 0.36, P = .004) and vertebral left atrial score (r = 0.50, P < .001) in dogs with MMVD, and correlated with vertebral heart score (r = 0.63, P = .01), maximum E wave amplitude of the diastolic transmitral flow (rs = 0.61, P = .018), ejection fraction (rs = -0.77, P < .001) and fractional shortening (rs = -0.56, P = .032) in dogs with acute congestive heart failure. CLINICAL RELEVANCE: Circulating Ang-2 levels increase in dogs with the severity of MMVD and the presence of PH.

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.

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.

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.

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.