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

Effect of type of diet on blood and plasma taurine concentrations, cardiac biomarkers, and echocardiograms in 4 dog breeds

BACKGROUND: Associations of diet with dilated cardiomyopathy are under investigation. OBJECTIVES: That cardiac assessment would show abnormalities in healthy dogs eating grain-free (GF) diets or diets with Food and Drug Administration (FDA)-listed ingredients of concern (peas, lentils, or potatoes) as top 10 ingredients (FDA-PLP), but not in dogs eating grain-inclusive (GI) diets or diets without FDA-listed ingredients of concern (PLP) in the top 10 ingredients (NoFDA-PLP). ANIMALS: One hundred eighty-eight healthy Doberman Pinschers, Golden Retrievers, Miniature Schnauzers, and Whippets. METHODS: This study was an observational cross-sectional study. Echocardiograms, cardiac biomarkers, and blood and plasma taurine concentrations were compared between dogs eating GF (n = 26) and GI (n = 162) diets, and between FDA-PLP (n = 39) and NoFDA-PLP (n = 149) diets, controlling for age and breed. Demographic characteristics, murmurs, genetic status, and ventricular premature complexes (VPCs) during examination were compared between dogs eating different diet types. RESULTS: No differences in echocardiographic variables, N-terminal pro-B-type natriuretic peptide or whole blood taurine were noted between dogs eating different diet types. Dogs eating GF diets had higher median high-sensitivity cardiac troponin I (hs-cTnI) (GF 0.076 ng/mL [Interquartile range (IQR), 0.028-0.156] vs. GI 0.048 [IQR, 0.0026-0.080]; P \u3c .001) and higher median plasma taurine (GF 125 nmol/mL [IQR, 101-148] vs GI 104 [IQR, 86-123]; P = .02) than dogs eating GI diets. Dogs eating FDA-PLP diets had higher median hs-cTnI (0.059 ng/mL [IQR, 0.028-0.122]) than dogs eating NoFDA-PLP diets (0.048 [IQR, 0.025-0.085]; P = .006). A greater proportion of dogs eating FDA-PLP diets (10%) had VPCs than dogs eating NoFDA-PLP diets (2%; P = .04). CONCLUSIONS AND CLINICAL IMPORTANCE: Higher hs-cTnI in healthy dogs eating GF and FDA-PLP diets might indicate low-level cardiomyocyte injury

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

Non-invasive right ventricular efficiency using 4D flow MRI

Pulmonary arterial hypertension (PH) is a progressive disease of increased resistance to flow through the lungs, leading to right ventricular (RV) failure [1]. MRI is increasingly used to assess right ventricular (RV) function in PH. RV stroke work (SW) based on invasive pressure and volume measurements, is used to assess ventricular work. Determining RV work from MRI could enable a more complete characterization of RV and PA interactions in PH. The purpose of this study was to non-invasively estimate RV work from simultaneously acquired RV volume (VRV) and pulmonary artery flow (QPA) using a 4D flow-sensitive MRI sequence in a canine model

Non-invasive assessment of cardiac function and pulmonary vascular resistance in an canine model of acute thromboembolic pulmonary hypertension using 4D flow cardiovascular magnetic resonance

BackgroundThe purpose of this study was to quantify right (RV) and left (LV) ventricular function, pulmonary artery flow (QP), tricuspid valve regurgitation velocity (TRV), and aorta flow (QS) from a single 4D flow cardiovascular magnetic resonance (CMR) (time-resolved three-directionally motion encoded CMR) sequence in a canine model of acute thromboembolic pulmonary hypertension (PH).MethodsAcute PH was induced in six female beagles by microbead injection into the right atrium. Pulmonary arterial (PAP) and pulmonary capillary wedge (PCWP) pressures and cardiac output (CO) were measured by right heart catheterization (RHC) at baseline and following induction of acute PH. Pulmonary vascular resistance (PVRRHC) was calculated from RHC values of PAP, PCWP and CO (PVRRHC = (PAP-PCWP)/CO). Cardiac magnetic resonance (CMR) was performed on a 3 T scanner at baseline and following induction of acute PH. RV and LV end-diastolic (EDV) and end-systolic (ESV) volumes were determined from both CINE balanced steady-state free precession (bSSFP) and 4D flow CMR magnitude images. QP, TRV, and QS were determined from manually placed cutplanes in the 4D flow CMR flow-sensitive images in the main (MPA), right (RPA), and left (LPA) pulmonary arteries, the tricuspid valve (TRV), and aorta respectively. MPA, RPA, and LPA flow was also measured using two-dimensional flow-sensitive (2D flow) CMR.ResultsBiases between 4D flow CMR and bSSFP were 0.8 mL and 1.6 mL for RV EDV and RV ESV, respectively, and 0.8 mL and 4 mL for LV EDV and LV ESV, respectively. Flow in the MPA, RPA, and LPA did not change after induction of acute PAH (p = 0.42-0.81). MPA, RPA, and LPA flow determined with 4D flow CMR was significantly lower than with 2D flow (p < 0.05). The correlation between QP/TRV and PVRRHC was 0.95. The average QP/QS was 0.96 ± 0.11.ConclusionsUsing both magnitude and flow-sensitive data from a single 4D flow CMR acquisition permits simultaneous quantification of cardiac function and cardiopulmonary hemodynamic parameters important in the assessment of PH

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

ObjectivesTo 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.Animals14 healthy female beagle dogs.MethodsComparison of ECHO and RHC measures of PAP, both at normal PAP and increased PAP generated by microbead embolization.ResultsNoninvasive 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).ConclusionsSpectral 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

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