Echocardiographic values for normal conditioned and unconditioned North American whippets.

BACKGROUND: Echocardiographic reference intervals have not been reported for North American whippets, or for whippets that have undergone pet-level athletic training. OBJECTIVES: To develop normal echocardiographic reference intervals for North American whippets and investigate differences in echocardiographic parameters based on athletic conditioning in pet whippets engaged in competitive sports. ANIMALS: One-hundred healthy North American whippets. METHODS: Dogs were examined at national shows between 2005 and 2009. Echocardiographic reference intervals were constructed and the effect of athletic conditioning on parameters of structure and function was assessed. RESULTS: Two dimensional, M-mode, Doppler and tissue Doppler reference ranges for healthy North American whippets are presented. Measures of left ventricular (LV) chamber diameter were larger in conditioned whippets (N = 25) and remained significantly larger than in unconditioned whippets (N = 16) when normalized for weight using allometric equations. Calculated LV mass was higher in conditioned dogs than in unconditioned dogs, and this difference persisted when LV mass was normalized by weight. Mitral E velocity was higher in conditioned dogs than in unconditioned dogs, whereas E/A and measures related to systolic function were not different. CONCLUSIONS AND CLINICAL IMPORTANCE: Pet whippets in peak athletic condition have larger hearts than do less conditioned whippets, but measures of systolic function are similar. Whippet pet athletes may show eccentric LV hypertrophy at peak condition. Normal values for cardiac size and function in North American whippets might be considered abnormal if population-specific whippet reference intervals are not used in analysis.

Veterinary Cooperative Oncology Group-Common Terminology Criteria for Adverse Events (VCOG-CTCAE v2) following investigational therapy in dogs and cats.

The updated VCOG-CTCAE v2 guidelines contain several important updates and additions since the last update (v1.1) was released in 2011 and published within Veterinary and Comparative Oncology in 2016. As the Veterinary Cooperative Oncology Group (VCOG) is no longer an active entity, the original authors and contributors to the VCOG-CTCAE v1.0 and v1.1 were consulted for input, and additional co-authors sought for expansion and refinement of the adverse event (AE) categories. VCOG-CTCAE v2 includes expanded neurology, cardiac and immunologic AE sections, and the addition of procedural-specific AEs. It is our intent that, through inclusion of additional authors from ACVIM subspecialties and the American College of Veterinary Surgery, that we can more comprehensively capture AEs that are observed during clinical studies conducted across a variety of disease states, clinical scenarios, and body systems. It is also our intent that these updated veterinary CTCAE guidelines will offer improved application and ease of use within veterinary practice in general, as well as within clinical trials that assess new therapeutic strategies for animals with a variety of diseases. Throughout the revision process, we strived to ensure the grading structure for each AE category was reflective of the decision-making process applied to determination of dose-limiting events. As phase I trial decisions are based on these criteria and ultimately determine the maximally tolerated dose, there is impact on standard dosing recommendations for any new drug registration or application. This document should be updated regularly to reflect ongoing application to clinical studies carried out in veterinary patients.

ACVIM consensus statement guidelines for the diagnosis, classification, treatment, and monitoring of pulmonary hypertension in dogs.

Pulmonary hypertension (PH), defined by increased pressure within the pulmonary vasculature, is a hemodynamic and pathophysiologic state present in a wide variety of cardiovascular, respiratory, and systemic diseases. The purpose of this consensus statement is to provide a multidisciplinary approach to guidelines for the diagnosis, classification, treatment, and monitoring of PH in dogs. Comprehensive evaluation including consideration of signalment, clinical signs, echocardiographic parameters, and results of other diagnostic tests supports the diagnosis of PH and allows identification of associated underlying conditions. Dogs with PH can be classified into the following 6 groups: group 1, pulmonary arterial hypertension; group 2, left heart disease; group 3, respiratory disease/hypoxia; group 4, pulmonary emboli/pulmonary thrombi/pulmonary thromboemboli; group 5, parasitic disease (Dirofilaria and Angiostrongylus); and group 6, disorders that are multifactorial or with unclear mechanisms. The approach to treatment of PH focuses on strategies to decrease the risk of progression, complications, or both, recommendations to target underlying diseases or factors contributing to PH, and PH-specific treatments. Dogs with PH should be monitored for improvement, static condition, or progression, and any identified underlying disorder should be addressed and monitored simultaneously.

A Large Animal Model of Right Ventricular Failure due to Chronic Thromboembolic Pulmonary Hypertension: A Focus on Function.

Chronic thromboembolic pulmonary hypertension (CTEPH) is a debilitating disease that progresses to right ventricular (RV) failure and death if left untreated. Little is known regarding the progression of RV failure in this disease, greatly limiting effective prognoses, and therapeutic interventions. Large animal models enable the use of clinical techniques and technologies to assess progression and diagnose failure, but the existing large animal models of CTEPH have not been shown to replicate the functional consequences of the RV, i.e., RV failure. Here, we created a canine embolization model of CTEPH utilizing only microsphere injections, and we used a combination of right heart catheterization (RHC), echocardiography (echo), and magnetic resonance imaging (MRI) to quantify RV function. Over the course of several months, CTEPH led to a 6-fold increase in pulmonary vascular resistance (PVR) in four adult, male beagles. As evidenced by decreased cardiac index (0.12 ± 0.01 v. 0.07 ± 0.01 [L/(min*kg)]; p < 0.05), ejection fraction (0.48 ± 0.02 v. 0.31 ± 0.02; p < 0.05), and ventricular-vascular coupling ratio (0.95 ± 0.09 v. 0.45 ± 0.05; p < 0.05), as well as decreased tricuspid annular plane systolic excursion (TAPSE) (1.37 ± 0.06 v. 0.86 ± 0.05 [cm]; p < 0.05) and increased end-diastolic volume index (2.73 ± 0.06 v. 2.98 ± 0.02 [mL/kg]; p < 0.05), the model caused RV failure. The ability of this large animal CTEPH model to replicate the hemodynamic consequences of the human disease suggests that it could be utilized for future studies to gain insight into the pathophysiology of CTEPH development, following further optimization.

Pulmonary arterial strain- and remodeling-induced stiffening are differentiated in a chronic model of pulmonary hypertension.

Pulmonary hypertension (PH) is a debilitating vascular disease that leads to pulmonary artery (PA) stiffening, which is a predictor of patient mortality. During PH development, PA stiffening adversely affects right ventricular function. PA stiffening has been investigated through the arterial nonlinear elastic response during mechanical testing using a canine PH model. However, only circumferential properties were reported and in the absence of chronic PH-induced PA remodeling. Remodeling can alter arterial nonlinear elastic properties via chronic changes in extracellular matrix (ECM) content and geometry. Here, we used an established constitutive model to demonstrate and differentiate between strain-stiffening, which is due to nonlinear elasticity, and remodeling-induced stiffening, which is due to ECM and geometric changes, in a canine model of chronic thromboembolic PH (CTEPH). To do this, circumferential and axial tissue strips of large extralobar PAs from control and CTEPH tissues were tested in uniaxial tension, and data were fit to a phenomenological constitutive model. Strain-induced stiffening was evident from mechanical testing as nonlinear elasticity in both directions and computationally by a high correlation coefficient between the mechanical data and model (R2=0.89). Remodeling-induced stiffening was evident from a significant increase in the constitutive model stress parameter, which correlated with increased PA collagen content and decreased PA elastin content as measured histologically. The ability to differentiate between strain- and remodeling-induced stiffening in vivo may lead to tailored clinical treatments for PA stiffening in PH patients.

Vascular hamartoma in the right ventricle of a dog: Diagnosis and treatment.

A 6-month old Labrador retriever was presented with an acute history of collapse during exercise. A grade III/VI left basilar systolic murmur and thoracic radiographs showing severe right heart enlargement with an enlarged main pulmonary artery were most consistent with a clinical diagnosis of pulmonic stenosis. Echocardiography revealed an intracardiac mass partially obstructing the right ventricular outflow tract. The mass was surgically excised, and histopathology diagnosed a benign vascular hamartoma of the right ventricle. Short-term follow-up showed resolution of clinical signs with no evidence of local recurrence. Intracardiac masses should be considered a differential diagnosis for patients with acute-onset syncope.

Acute resolution of pulmonary alveolar infiltrates in 10 dogs with pulmonary hypertension treated with sildenafil citrate: 2005-2014.

OBJECTIVE: To describe clinical canine patients with naturally occurring pulmonary hypertension and radiographic pulmonary alveolar infiltrates before and after treatment with sildenafil. ANIMALS: Ten client-owned dogs. METHODS: A retrospective analysis of dogs with echocardiographically-determined pulmonary hypertension and pulmonary alveolar infiltrates on thoracic radiographs was performed before (PRE) and after (POST) sildenafil therapy. Clinical scores, pulmonary alveolar infiltrate scores and tricuspid regurgitation gradients were analyzed PRE and POST sildenafil. RESULTS: Pulmonary alveolar infiltrates associated with pulmonary hypertension developed in a diffusely patchy distribution (10/10). Sixty percent of dogs had a suspected diagnosis of interstitial pulmonary fibrosis as the etiology of pulmonary hypertension. Median PRE clinical score was 4 (range: 3-4) compared to POST score of 0 (0-2) (p = 0.005). Median alveolar infiltrate score PRE was 10 (5-12) compared to POST score of 4 (0-6) (p = 0.006). Median tricuspid regurgitation gradient PRE was 83 mmHg (57-196) compared to 55 mmHg POST (33-151) (p = 0.002). CONCLUSIONS: A subset of dogs with moderate to severe pulmonary hypertension present with diffuse, patchy alveolar infiltrates consistent with non-cardiogenic pulmonary edema. The typical clinical presentation is acute dyspnea and syncope, often in conjunction with heart murmurs suggestive of valvular insufficiency. This constellation of signs may lead to an initial misdiagnosis of congestive heart failure or pneumonia; however, these dogs clinically and radiographically improve with the initiation of sildenafil.

Accuracy of Doppler echocardiographic estimates of pulmonary artery pressures in a canine model of pulmonary hypertension.

OBJECTIVES: To compare noninvasive estimates of pulmonary artery pressure (PAP) obtained via echocardiography (ECHO) to invasive measurements of PAP obtained during right heart catheterization (RHC) across a range of PAP. To examine the accuracy of estimating right atrial pressure via ECHO (RAPECHO) compared to RAP measured by RHC (RAPRHC), and determine if adding RAPECHO improves the accuracy of noninvasive PAP estimations. ANIMALS: 14 healthy female beagle dogs. METHODS: Comparison of ECHO and RHC measures of PAP, both at normal PAP and increased PAP generated by microbead embolization. RESULTS: Noninvasive estimates of PAP were moderately but significantly correlated (r of 0.68-0.78; p < 0.0006) with invasive measurements of PAP. Wide variance was noted for all estimations, with increased variance at higher PAP. The addition of RAPECHO improved correlation and bias in all cases. RAPRHC was significantly correlated with RAPECHO (r = 0.38; p = 0.04) as estimated by the ellipse area method. Median RAPRHC was significantly different between 3 subjective assessments of right atrial size (p = 0.037). CONCLUSIONS: Spectral Doppler assessments of tricuspid and pulmonic regurgitation are imperfect methods for predicting PAP as measured by catheterization despite an overall moderate correlation between invasive and noninvasive values. Noninvasive measurements may be better utilized as part of a comprehensive assessment of PAP in canine patients. RAPRHC appears best estimated based on subjective assessment of RA size. Including estimated RAPECHO in estimates of PAP improves the correlation and relatedness between noninvasive and invasive measures of PAP, but notable variability in accuracy of estimations persists.

Multi-centered investigation of a point-of-care NT-proBNP ELISA assay to detect moderate to severe occult (pre-clinical) feline heart disease in cats referred for cardiac evaluation.

OBJECTIVE: To prospectively evaluate the diagnostic accuracy of a point-of-care (POC) N-terminal pro-B-type natriuretic peptide (NT-proBNP) ELISA to assess the likelihood of moderate to severe occult heart disease (OcHD) in a clinical population of cats suspected to have heart disease. ANIMALS: One hundred and forty-six asymptomatic client-owned cats with a heart murmur, gallop rhythm, arrhythmia, or cardiomegaly. METHODS: Physical examination, blood pressure measurement and echocardiography were performed prospectively. Point-of-care ELISA was visually assessed as either positive or negative by a reader blinded to the echocardiographic results. RESULTS: Forty-three healthy cats, 50 mild OcHD, 31 moderate OcHD, 6 severe OcHD, and 16 cats equivocal for OcHD were examined. Cats with OcHD included 65 with hypertrophic cardiomyopathy, 6 with restrictive or unclassified cardiomyopathy, 1 with arrhythmogenic right ventricular cardiomyopathy, and 15 with non-cardiomyopathic forms of heart disease. Point-of-care ELISA differentiated cats with moderate or severe OcHD with sensitivity/specificity of 83.8%/82.6% and overall accuracy of 82.9%. Positive POC ELISA increased likelihood of moderate or severe OcHD by a factor of 4.8 vs. those that tested negative. Point-of-care ELISA differentiated cats with moderate or severe cardiomyopathic OcHD with sensitivity/specificity of 88.6%/81.3% and overall accuracy of 83.2%. CONCLUSION: In a select sample of cats referred for cardiac evaluation, positive POC NT-proBNP ELISA increases likelihood of moderate to severe OcHD while negative POC NT-proBNP ELISA result excludes moderate to severe OcHD.

Pulmonary artery relative area change is inversely related to ex vivo measured arterial elastic modulus in the canine model of acute pulmonary embolization.

A low relative area change (RAC) of the proximal pulmonary artery (PA) over the cardiac cycle is a good predictor of mortality from right ventricular failure in patients with pulmonary hypertension (PH). The relationship between RAC and local mechanical properties of arteries, which are known to stiffen in acute and chronic PH, is not clear, however. In this study, we estimated elastic moduli of three PAs (MPA, LPA and RPA: main, left and right PAs) at the physiological state using mechanical testing data and correlated these estimated elastic moduli to RAC measured in vivo with both phase-contrast magnetic resonance imaging (PC-MRI) and M-mode echocardiography (on RPA only). We did so using data from a canine model of acute PH due to embolization to assess the sensitivity of RAC to changes in elastic modulus in the absence of chronic PH-induced arterial remodeling. We found that elastic modulus increased with embolization-induced PH, presumably a consequence of increased collagen engagement, which corresponds well to decreased RAC. Furthermore, RAC was inversely related to elastic modulus. Finally, we found MRI and echocardiography yielded comparable estimates of RAC. We conclude that RAC of proximal PAs can be obtained from either MRI or echocardiography and a change in RAC indicates a change in elastic modulus of proximal PAs detectable even in the absence of chronic PH-induced arterial remodeling. The correlation between RAC and elastic modulus of proximal PAs may be useful for prognoses and to monitor the effects of therapeutic interventions in patients with PH.

Advanced multimodality imaging of an anomalous vessel between the ascending aorta and main pulmonary artery in a dog.

A 1-year-old male German shorthaired pointer was referred for evaluation of tachypnea and hemoptysis. A grade VI/VI left basilar continuous murmur was ausculted. Multimodality imaging consisting of thoracic radiographs, transthoracic and transesophageal echocardiography, fluoroscopy-guided selective angiography, computed tomography angiogram (CTA) and magnetic resonance angiogram (MRA), was performed on this patient. The defect included a left-to-right shunting anomalous vessel between the ascending aorta and main pulmonary artery, along with a dissecting aneurysm of the main and right pulmonary artery. An MRA post-processing technique (PC VIPR) was used to allow for high resolution angiographic images and further assessment of the patient's hemodynamics prior to surgical correction. This case report describes the clinical course of a canine patient with a rare form of congenital cardiac disease, and the multiple imaging modalities that were used to aid in diagnosis and treatment.

Impact of acute pulmonary embolization on arterial stiffening and right ventricular function in dogs.

Pulmonary hypertension (PH) can impact right ventricular (RV) function and alter pulmonary artery (PA) stiffness. The response of the RV to an acute increase in pulmonary pressure is unclear. In addition, the relation between total pulmonary arterial compliance and local PA stiffness has not been investigated. We used a combination of right heart catheterization (RHC) and magnetic resonance imaging (MRI) to assess PA stiffening and RV function in dogs before and after acute embolization. We hypothesized that in moderate, acute PH the RV is able to compensate for increased afterload, maintaining adequate coupling. Also, we hypothesized that in the absence of PA remodeling the relative area change in the proximal PA (RAC, a noninvasive index of local area strain) correlates with the total arterial compliance (stroke volume-to-pulse pressure ratio). Our results indicate that, after embolization, RV function is able to accommodate the demand for increased stroke work without uncoupling, albeit at the expense of a reduction of efficiency. In this acute model, RAC showed excellent correlation with total arterial compliance. We used this correlation to assess PA pulse pressure (PP) from noninvasive MRI measurements of stroke volume and RAC. We demonstrated that in acute pulmonary embolism MRI estimates of PP are remarkably close to measurements from RHC. These results, if confirmed in chronic PH and clinically, suggest that monitoring of PH progression by noninvasive methods may be possible.

Pulmonary hypertension in canine degenerative mitral valve disease.

Pulmonary hypertension secondary to degenerative mitral valve disease has been recognized clinically for many years in veterinary medicine, and clinical diagnosis of this syndrome in dogs has been enhanced greatly by widespread use of echocardiography and Doppler echocardiography. Medical therapy is now available to treat this clinical complication of mitral valve disease, making timely diagnosis even more important to patient longevity and quality of life.

Prediction of first onset of congestive heart failure in dogs with degenerative mitral valve disease: the PREDICT cohort study.

OBJECTIVE: To identify risk factors for first-onset congestive heart failure (CHF) in dogs with degenerative mitral valve disease (DMVD). ANIMALS: Eighty-two dogs with and without CHF secondary to DMVD were retrospectively assigned to a derivation cohort. Sixty-five dogs with asymptomatic DMVD were recruited into a prospective validation cohort. METHODS: Variables associated with risk of CHF in dogs were identified in a derivation cohort and used to construct a predictive model, which was then prospectively tested through longitudinal examination of a validation cohort. RESULTS: Logistic regression analysis of the derivation cohort yielded a predictive model that included the left atrial to aortic root dimension ratio (LA:Ao) and plasma concentration of N-terminal pro-B-type natriuretic peptide (NT-proBNP). When this model was prospectively applied to the validation cohort, it correctly predicted first-onset of CHF in 69.2% of cases. Analysis of the validation cohort revealed that plasma NT-proBNP concentration and indexed left ventricular end-diastolic diameter (LVIDd:Ao) were independent risk factors for development of first-onset CHF in dogs with DMVD (NT-proBNP ≥ 1500 pmol/L, odds ratio (OR), 5.76, 95% confidence interval (CI), 1.37-24.28, P = 0.017; LVIDd:Ao ≥ 3, OR, 6.11, 95% CI, 1.09-34.05, P = 0.039). CONCLUSIONS: Measures of left heart size and plasma NT-proBNP concentration independently estimate risk of first-onset of CHF in dogs with DMVD. These parameters can contribute to the management of dogs with DMVD.

NT-proBNP, NT-proANP and cTnI concentrations in dogs with pre-capillary pulmonary hypertension.

OBJECTIVES: To compare [NT-proBNP], [NT-proANP] and [cTnI] between control dogs with respiratory disease without pulmonary hypertension (PH) and dogs with pre-capillary PH, and to assess the accuracy of [NT-proBNP], [NT-proANP], [cTnI] to predict Doppler-derived peak tricuspid regurgitation (TR) gradient. ANIMALS: 20 dogs. 8 control dogs with respiratory disease with no PH and 12 with pre-capillary PH. METHODS: [NT-proBNP], [NT-proANP] and [cTnI] were compared between the 2 groups and simple linear regression analysis was used to predict peak TR gradients from various blood biomarkers. RESULTS: Median [NT-proBNP] was higher in the dogs with PH (2011 pmol/L, 274-7713 pmol/L) compared to control dogs (744 pmol/L; 531-2710 pmol/L) (p = 0.0339). [NT-proBNP] was associated with peak TR gradient (R(2) = 0.7851, p = 0.0001). Median [NT-proANP] did not differ between dogs with PH (1747 fmol/L; 894-2884 fmol/L) and control dogs (1209 fmol/L; 976-1389 fmol/L (p = 0.058). [NT-proANP] was not associated with peak TR gradient (R(2) = 0.2780, p = 0.0781). Median [cTnI] did not differ between dogs with PH (0.2850 ng/mL; 0.19-1.13 ng/mL) and control dogs (0.2 ng/mL; 0.19-0.82 ng/mL, p = 0.3051). Median [TnI] was not associated with peak TR gradient (R(2) = 0.024, p = 0.6307). CONCLUSIONS: [NT-proBNP] concentration is significantly higher in dogs with pre-capillary PH when compared to dogs with respiratory disease without PH, and [NT-proBNP] may be useful to predict the severity of estimated PH. Elevations in [NT-proBNP] due to pre-capillary PH may complicate the interpretation of [NT-proBNP] elevations in patients presenting with cardiorespiratory abnormalities. [NT-proANP] and [cTnI] were not elevated in dogs with pre-capillary PH.

Comparison of plasma cardiac troponin I concentrations among dogs with cardiac hemangiosarcoma, noncardiac hemangiosarcoma, other neoplasms, and pericardial effusion of nonhemangiosarcoma origin.

OBJECTIVE: To determine whether plasma cardiac troponin I (cTnl) concentrations can be used to identify cardiac involvement in dogs with hemangiosarcoma, exclude cardiac hemangiosarcoma in dogs with noncardiac hemangiosarcoma, and identify cardiac hemangiosarcoma in dogs with pericardial effusion. DESIGN: Cohort study. ANIMALS: 57 dogs (18 with confirmed [5 dogs] or suspected [13] cardiac hemangiosarcoma, 14 with confirmed hemangiosarcoma involving sites other than the heart [noncardiac hemangiosarcoma], 10 with pericardial effusion not caused by hemangiosarcoma, and 15 with noncardiac nonhemangiosarcoma neoplasms). PROCEDURES: Plasma cTnl concentration was measured, and thoracic radiography, abdominal ultrasonography, and echocardiography were performed in each dog. The cTnl concentration was compared among groups. RESULTS: Median plasma cTnl concentration in dogs with cardiac hemangiosarcoma was significantly higher than the concentration in each of the other groups. A plasma cTnl concentration > 0.25 ng/mL could be used to identify cardiac involvement in dogs with hemangiosarcoma at any site (sensitivity, 78%; specificity, 71 %). A plasma cTnl concentration > 0.25 ng/mL could be used to identify cardiac hemangiosarcoma in dogs with pericardia effusion (sensitivity, 81%; specificity, 100%). CONCLUSIONS AND CLINICAL RELEVANCE: The median plasma cTnl concentration was higher in dogs with cardiac hemangiosarcoma, compared with the median concentration in dogs with hemangiosarcoma at other sites, dogs with other neoplasms, and dogs with pericardial effusion not caused by hemangiosarcoma. The plasma cTnl concentration may be used to identify cardiac involvement in dogs with hemangiosarcoma and to identify cardiac hemangiosarcoma in dogs with pericardial effusion.

Pulmonary hypertension in dogs: diagnosis and therapy.

Pulmonary hypertension (PH) has been recognized as a clinical syndrome for many years in veterinary medicine, but routine accurate clinical diagnosis in dogs was greatly enhanced by widespread use of echocardiography and Doppler echocardiography. Most cases of PH in veterinary medicine can be categorized as precapillary or postcapillary. These subsets of patients often differ with regard to clinical presentation, response to therapy, and prognosis. Effective medical therapy is now available to treat this often-devastating clinical complication of common chronic diseases, making accurate diagnosis even more important to patient longevity and quality of life.