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 the pulmonary vein-to-right pulmonary artery ratio in dogs with pulmonary hypertension of precapillary origin.

INTRODUCTION: Non-invasive diagnosis of pulmonary hypertension (PH) relies on estimation of pulmonary arterial pressure (PAP) via Doppler echocardiographic measurement of tricuspid regurgitation pressure gradient (TRPG). The pulmonary vein-to-right pulmonary artery ratio (PV/PA) recently has been described for the detection of pulmonary venous congestion. Whether this variable could be used to detect the presence of precapillary PH is unknown. The objective of the present study was to investigate the diagnostic value of PV/PA for prediction of TRPG, as a surrogate of PAP, in dogs with PH of precapillary origin. ANIMALS: Sixty-seven client-owned dogs were included in the study. METHODS: This was a retrospective study. Dogs with a measurable TRPG were included and classified into group 1 (TRPG < 30 mmHg), group 2 (TRPG 30-49 mmHg), group 3 (TRPG 50-80 mmHg), or group 4 (TRPG > 80 mmHg). The PV/PA, acceleration time-to-ejection time ratio of pulmonary artery flow, main pulmonary artery diameter-to-aortic diameter ratio, and right pulmonary artery distensibility index were measured retrospectively from cineloops in each dog. RESULTS: The PV/PA measured by both two-dimensional (2D) and time-motion mode(MM) echocardiography decreased proportionally with PH severity. Using regression analysis, PV/PA (2D) was identified as the strongest predictor for TRPG (R2 = 0.70, p < 0.0001) among other variables studied, with a good diagnostic accuracy (area under the curve = 0.94) for moderate PH (TRPG > 50 mmHg) using a cutoff value of < 0.70 (sensitivity = 96%, specificity = 82%). CONCLUSIONS: Results of the present study suggest that PV/PA can be useful as an additional, non-invasive, and indirect variable to identify precapillary PH in dogs.

Effect of Breed on Plasma Endothelin-1 Concentration, Plasma Renin Activity, and Serum Cortisol Concentration in Healthy Dogs.

BACKGROUND: There are breed differences in several blood variables in healthy dogs. OBJECTIVE: Investigate breed variation in plasma endothelin-1 (ET-1) concentration, plasma renin activity, and serum cortisol concentration. ANIMALS: Five-hundred and thirty-one healthy dogs of 9 breeds examined at 5 centers (2-4 breeds/center). METHODS: Prospective observational study. Circulating concentrations of ET-1 and cortisol, and renin activity, were measured using commercially available assays. Absence of organ-related or systemic disease was ensured by thorough clinical investigations, including blood pressure measurement, echocardiography, ECG, blood and urine analysis. RESULTS: Median ET-1 concentration was 1.29 (interquartile range [IQR], 0.97-1.82) pg/mL, median cortisol concentration 46.0 (IQR, 29.0-80.8) nmol/L, and median renin activity 0.73 (IQR, 0.48-1.10) ng/mL/h in all dogs. Overall, breed differences were found in ET-1 and cortisol concentrations, and renin activity (P < .0001 for all). Pair-wise comparisons between breeds differed in 67% of comparisons for ET-1, 22% for cortisol, and 19% for renin activity, respectively. Within centers, breed differences were found at 5/5 centers for ET-1, 4/5 centers for cortisol, and 2/5 centers for renin activity. Newfoundlands had highest median ET-1 concentration, 3 times higher than Cavalier King Charles Spaniels, Doberman Pinschers, and Dachshunds. Median renin activity was highest in Dachshunds, twice the median value in Newfoundlands and Boxers. Median cortisol concentration was highest in Finnish Lapphunds, almost 3 times higher than in Boxers. CONCLUSIONS AND CLINICAL IMPORTANCE: Breed variation might be important to take into consideration when interpreting test results in clinical studies.

Pulmonary Vein-to-Pulmonary Artery Ratio is an Echocardiographic Index of Congestive Heart Failure in Dogs with Degenerative Mitral Valve Disease.

BACKGROUND: Early recognition of left-sided congestive heart failure (CHF) in dogs with degenerative mitral valve disease (DMVD) is important because it influences medical therapy, timing of follow-up, and outcome. HYPOTHESIS: Pulmonary vein diameter-to-pulmonary artery diameter ratio (PV/PA) measured by echocardiography can predict CHF. ANIMALS: Ninety-eight client-owned dogs, 37 controls, and 61 dogs with DMVD. METHODS: Prospective clinical cohort study. History, physical examination and Doppler-echocardiography were performed. Dogs were classified as International Small Animal Cardiac Health Council class I, II or III. Congestive heart failure was identified in a subset of 56 dogs based on radiographic findings. The PV/PA was measured in bidimensional (2D) and M-mode by 2 investigators blinded to the radiologists' conclusions. RESULTS: Interobserver coefficients of variation for PV/PA acquisition and measurement were <10%. The PV/PA in control dogs was approximately 1 and increased with class of heart failure. The presence of CHF could be best predicted by measuring PV/PA in 2D echocardiography (cut-off, 1.7; area under the curve, 0.98; CI, 0.97-0.98; P < .001) with a sensitivity of 96% and a specificity of 91%. CONCLUSION AND CLINICAL IMPORTANCE: The PV/PA is a simple and reproducible echocardiographic variable that increases with class of heart failure and may help discriminate dogs in CHF from asymptomatic dogs with DMVD. Additional studies are required to determine whether PV/PA might provide additional information in the integrated interpretation of Doppler-echocardiographic indices of left ventricular filling pressures and could be used for rapid assessment of CHF in dogs in a critical care setting.

Transforming growth factor beta 1 activation, storage, and signaling pathways in idiopathic pulmonary fibrosis in dogs.

BACKGROUND: The pathogenesis of idiopathic pulmonary fibrosis (IPF) in dogs is poorly understood. In human, transforming growth factor ß1 (TGF-ß1) is considered central in the pathogenesis. OBJECTIVES: To investigate TGF-ß1 pathway in IPF. ANIMALS: Lung tissues from 12 affected and 11 control dogs. Serum from 16 affected West Highland white Terriers (WHWTs) and healthy dogs from predisposed (13 WHWTs, 12 Scottish Terriers and 13 Bichons Frise) and nonpredisposed breeds (10 Whippets, 10 Belgian shepherds, 8 Labradors). METHODS: In this prospective study, immunohistochemistry was used to evaluate expression and localization of TGF-ß1 protein and proteins involved in TGF-ß1 signaling (TGF-ß receptor type I and phospho-Smad2/3). Pulmonary expression of TGF-ß1 and molecules involved in its storage (latent TGF-ß binding proteins [LTBP] 1, 2, and 4), activation (ανß6 and ανß8 integrins, thrombospondin-1) and signal inhibition (Smad 7) was analyzed by quantitative reverse transcriptase PCR. Circulating TGF-ß1 concentration was measured by ELISA. RESULTS: In IPF, high level of TGF-ß1 protein was found in areas of fibrosis, epithelial cells had strong expression of TGF-ß receptor type 1 and phospho-Smad2/3, gene expression was decreased for LTBP 4 (P = .009) and ß8 integrin (P < .001) and increased for thrombospondin-1 (P = .016); no difference was seen for Smad7, LTBP1 and 2. Serum TGF-ß1 concentration was higher in predisposed compared with nonpredisposed breeds (P < .0001). CONCLUSIONS AND CLINICAL IMPORTANCE: This study identified an enhanced TGF-ß1 signaling activity in IPF. TGF-ß1 storage and activation proteins with altered expression represent potential therapeutic targets. Higher circulating TGF-ß1 concentration in predisposed breeds might partly explain their susceptibility for IPF.

Effect of physiological determinants and cardiac disease on plasma adiponectin concentrations in dogs.

BACKGROUND: In humans, a high concentration of adiponectin is associated with a favorable cardiovascular risk profile whereas, in patients with heart failure (HF), a high concentration of adiponectin is associated with a less favorable prognosis. HYPOTHESIS/OBJECTIVES: To evaluate the physiological determinants of plasma adiponectin concentration in dogs and the influence of heart disease, myxomatous mitral valve disease (MMVD), and dilated cardiomyopathy (DCM). ANIMALS: One hundred and fourteen client-owned dogs and 9 Beagles from the research colony of the Clinical Veterinary Unit of the University of Liège. METHODS: We prospectively measured circulating adiponectin concentration in healthy control dogs (n = 77), dogs with MMVD (n = 22) and dogs with DCM (n = 15) of various degrees of severity. Diagnosis was confirmed by Doppler echocardiography. Plasma adiponectin concentration was measured by a canine-specific sandwich ELISA kit. RESULTS: An analysis of covariance showed an association between adiponectin concentration and age, neuter status, and heart disease. No association between adiponectin concentration and class of HF, sex, body condition score, body weight, circadian rhythm, or feeding was found. Plasma adiponectin concentration was negatively correlated with age (P = .001). Adiponectin was lower in neutered (P = .008) compared to intact dogs. Circulating adiponectin concentration was increased in dogs with DCM compared to healthy dogs (P = .018) and to dogs with MMVD (P = .014). CONCLUSIONS AND CLINICAL IMPORTANCE: Age and neutering negatively influence circulating adiponectin concentration. Plasma adiponectin concentration increased in dogs with DCM. Additional research is required to investigate if this hormone is implicated in the pathophysiology of DCM and associated with clinical outcome.

Effect of heart failure on dipeptidyl peptidase IV activity in plasma of dogs.

BACKGROUND: In congestive heart failure (HF), plasma B-type natriuretic peptide (BNP) seems devoid of biological effectiveness. BNP(1-32) could be truncated into BNP(3-32) by dipeptidyl peptidase IV (DPP4), and BNP(3-32) has reduced biological activities. HYPOTHESIS: Increased DPP4 activity is associated with pathophysiology of HF. ANIMALS: One hundred twenty-eight client-owned dogs and 9 experimental Beagles from the Clinical Veterinary Unit of the University of Liège. METHODS: We prospectively measured plasma DPP4 activity in 5 groups of dogs: normal growing dogs (n = 21), normal adult dogs (n = 60), healthy Beagle (n = 9), dogs with myxomatous mitral valve disease (n = 35), and dogs with dilated cardiomyopathy (n = 12). The final diagnosis and the severity of HF were determined by Doppler echocardiography. Plasma DPP4 activity was measured kinetically by a fluorimetric method. RESULTS: In growing dogs, DPP4 activity was higher than in adults (P < .001) and inversely correlated with age (r = -0.57, P < .01). In adults, DPP4 activity increased linearly with body weight (r = 0.39, P < .01), but there was no influence of age or sex. No effect of the circadian rhythm was noted. DPP4 activity was significantly higher in HF ISACHC I (16.3 ± 1.14 U/L) compared with healthy adults (12.4 ± 0.65 U/L, P < .05) and HF ISACHC III (11.0 ± 1.50 U/L, P < .05). Mean DPP4 activity in ISACHC II was 15.1 ± 1.4 U/L. CONCLUSION AND CLINICAL IMPORTANCE: We did not find evidence that plasma DPP4 activity is responsible for the "BNP resistance" in overt congestive HF, but it may be implicated in early stages.

Serum and bronchoalveolar lavage fluid endothelin-1 concentrations as diagnostic biomarkers of canine idiopathic pulmonary fibrosis.

BACKGROUND: Diagnosis of canine idiopathic pulmonary fibrosis (IPF) is challenging. Endothelin-1 (ET1) is a biomarker of IPF in humans, but whether ET1 can detect and differentiate IPF from other canine respiratory diseases is unknown. OBJECTIVE: To evaluate whether measurement of the concentration of ET1 in serum and bronchoalveolar lavage fluid (BALF) can be used to distinguish canine IPF from chronic bronchitis (CB) and eosinophilic bronchopneumopathy (EBP). ANIMALS: Twelve dogs with IPF, 10 dogs with CB, 6 dogs with EBP, 13 privately owned healthy West Highland White Terriers (WHWT), and 9 healthy Beagle dogs. METHODS: Prospective, case control study. ET1 concentration was determined by ELISA in serum and in BALF. RESULTS: No significant difference in serum ET1 concentration was detected between healthy Beagle dogs and WHWT. Serum ET1 concentration was higher in dogs with IPF (median interquartile range; 2.32 pg/mL, 2.05-3.38) than healthy Beagle dogs (1.28, 1.07-1.53; P < .001), healthy WHWT (1.56, 1.25-1.85; P < .001), dogs with EBP (0.94 0.68-1.01; P = .001), and dogs with CB (1.54 0.74-1.82; P = .005). BALF ET1 concentration was below the detection limit in healthy WHWT and in dogs with CB, whereas it was measurable in all dogs with IPF. A cut-off serum concentration of 1.8 pg/mL had a sensitivity of 100% and a specificity of 81.2% for detection of IPF, with an area under the receiver operating characteristic curve of 0.818. CONCLUSIONS AND CLINICAL IMPORTANCE: Serum ET1 can differentiate dogs with IPF from dogs with EBP or CB. ET1 can be detected in BALF of dogs with IPF.

Metabolic and structural abnormalities in dogs with early left ventricular dysfunction induced by incessant tachycardia.

OBJECTIVE: To assess morphologic and metabolic abnormalities in dogs with early left ventricular dysfunction (ELVD) induced by rapid right ventricular pacing (RRVP). ANIMALS: 7 Beagles. PROCEDURE: Plasma carnitine concentrations were measured before and after development of ELVD induced by RRVP. At the same times, transvenous endomyocardial biopsy was performed, and specimens were submitted for determination of myocardial carnitine concentrations and histologic, morphometric, and ultrastructural examination. RESULTS: In 4 dogs in which baseline plasma total carnitine concentration was normal, RRVP induced a decrease in myocardial total and free carnitine concentrations and an increase in myocardial esterified carnitine concentration. In 3 dogs in which baseline plasma total carnitine concentration was low, plasma and myocardial carnitine concentrations were unchanged after pacing. Structural changes associated with pacing included perinuclear vacuolization in 3 dogs. Morphometric analyses indicated there was a decrease in myofiber cross-sectional diameter and area following pacing. Electron microscopy revealed changes in myofibrils and mitochondria following pacing. CONCLUSIONS AND CLINICAL RELEVANCE: Results indicated that moderate to severe alterations in myocyte cytoarchitecture are present in dogs with ELVD induced by RRVP and that in dogs with normal plasma carnitine concentrations, myocardial carnitine deficiency may be a biochemical marker of ELVD. Results also indicated that transvenous endomyocardial biopsy can be used to evaluate biochemical and structural myocardial changes in dogs with cardiac disease.

Usefulness of dobutamine stress tests for detection of cardiac abnormalities in dogs with experimentally induced early left ventricular dysfunction.

OBJECTIVE: To determine whether dobutamine stress tests (DST) can be used to detect cardiac dysfunction in dogs with early left ventricular dysfunction (ELVD) induced by rapid right ventricular pacing (RRVP). ANIMALS: 7 adult male Beagles. PROCEDURE: A pacemaker was surgically implanted in each dog at the level of the right ventricular apex. Electrocardiography, Doppler sphygmomanometry, and Doppler echocardiography were performed before and during a DST prior to activation of the pacemaker and every 3 to 4 days during the period of RRVP. Dobutamine stress tests were performed by infusing dobutamine at incremental dosages ranging from 12.5 to 42.5 microg/kg of body weight/min. RESULTS: Clinical signs of congestive heart failure were not observed during the pacing period. However, all dogs developed ELVD associated with significant changes in values for most Doppler echocardiographic variables obtained prior to DST Adverse cardiac effects were not detected during DST. Most Doppler echocardiographic indices of cardiac function were significantly altered in response to dobutamine infusion during the pacing period, compared with prepacing values. However, a dobutamine-induced 2-fold increase in cardiac output was maintained. CONCLUSIONS AND CLINICAL RELEVANCE: Dobutamine stress tests can be safely performed in dogs with experimentally induced ELVD. Dobutamine stress tests may be a sensitive, noninvasive diagnostic method, complementary to standard clinical examinations, for detection of early cardiac dysfunction in dogs asymptomatic for dilated cardiomyopathy.

Hormonal response to dobutamine cardiac stress testing in a conscious canine model of early left ventricular dysfunction induced by chronic rate overload.

The aims of this study were to investigate (1) hormonal activation before and during dobutamine cardiac stress testing (DST) in a canine model of early left ventricular dysfunction (ELVD) induced by rapid right ventricular pacing (RRVP) and (2) the relationship between this hormonal profile and carnitine concentrations. Before the pacing period, the 6 dogs were assigned to 2 groups according their baseline total plasma carnitine concentration. A DST was performed on each dog before activation of the pacemaker and every 3 to 4 days during development of 3 progressive stages of ELVD (stages 1, 2 and 3). Plasma atrial natriuretic factor (ANF), angiotensin II (ANG II) and endothelin-1 (ET-1) levels were measured at the start and at the end of each DST. Effects of ELVD, DST and plasma carnitine concentration on these measurements were tested. The RRVP induced a significant increase of ANF and ANG II and a non significant trend toward increase of ET-1 in all dogs. Before the pacing period, ANF remained constant during the DST in dogs with normal total plasma carnitine concentration, while it significantly decreased in dogs with low total plasma carnitine concentration. Dobutamine stress testing induced a significant decrease in ANF in all dogs in ELVD. Dobutamine infusion induced a significant increase in ANG II in all dogs before as well as during the pacing period while ET-1 was unchanged. These results suggest that investigation of the hormonal profile before and after a dobutamine challenge might provide important diagnostic information in dogs with asymptomatic or mildly symptomatic cardiac dysfunction of different origins.

Treatment of patent ductus arteriosus by placement of intravascular coils in a pup.

A 3-month-old female mixed-breed pup was referred for evaluation and treatment of patent ductus arteriosus (PDA). Selective angiography was performed to confirm the diagnosis. A cone-shaped PDA with a large aortic base was outlined. A second selective angiographic procedure was performed to functionally close the PDA by use of thrombotic coils; complete obstruction was obtained. Twenty-four hours after the procedure, the murmur disappeared. One month later, the dog was reexamined and found to be clinically normal.