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.

Caudal vena cava point-of-care ultrasound in dogs with degenerative mitral valve disease without clinically important right heart disease.

OBJECTIVES: Caudal vena cava (CVC) diameter and collapsibility index (CVCD and CVCCI) have been used to assess intravascular volume status (IVS). Maladaptations with progressive degenerative mitral valve disease (DMVD) lead to hypervolemia. We hypothesised that stages of DMVD will affect ultrasonographic CVC variables in dogs without clinically important right heart disease. ANIMALS, MATERIALS AND METHODS: This retrospective study included 79 dogs with DMVD presented to the cardiology department between January 2017 and 2019. Subxiphoid views were used to obtain CVC cineloops. By visual inspection, CVC was subjectively scored as flat, normal or fat. Maximal and minimal CVCD were measured and indexed to aortic diameter (CVCD-max/Ao and CVCD-min/Ao); CVCCI was calculated as (CVCD-max-CVCD-min)/CVCD-max. Fisher's exact and Kruskal-Wallis tests were used to compare CVC variables. RESULTS: Subjective assessment was associated with American College of Veterinary Internal Medicine (ACVIM) stages (P < 0.001). The proportion of fat CVC was greater in stages C and D. In stage D, CVCD-max/Ao was larger compared with stages B1, B2 and C (P = 0.002, P = 0.002 and P = 0.035, respectively). In stages C and D, CVCD-min/Ao was larger compared with B1 (P = 0.016 and P = 0.001) and B2 (P = 0.002 and P < 0.001. In stages C and D, CVCCI was less than stage B1 (P = 0.016 and P = 0.044) and B2 (P = 0.001 and P = 0.010). CONCLUSIONS: In dogs with DMVD without clinically important right heart disease, CVC variables differ across ACVIM stage. Subjective and objective CVC variables may be used to predict hypervolemia.

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.

Interbreed variation in serum serotonin (5-hydroxytryptamine) concentration in healthy dogs.

INTRODUCTION: Serotonin (5-hydroxytryptamine [5-HT]) has several biological functions. In different species, excessive 5-HT has been linked to valvular lesions, similar to those seen in dogs with myxomatous mitral valve disease. Previous studies suggest higher 5-HT in healthy Cavalier King Charles Spaniels (CKCSs), a breed highly affected by myxomatous mitral valve disease, compared to other breeds. OBJECTIVE: To investigate potential interbreed variation in serum 5-HT in healthy dogs. ANIMALS: 483 healthy dogs of nine breeds aged 1-7 years. METHODS: Dogs were examined at five European centers. Absence of cardiovascular, organ-related, or systemic diseases was ensured by thorough clinical investigations including echocardiography. Serum was frozen and later analyzed by enzyme-linked immunosorbent assay (ELISA). RESULTS: Median 5-HT concentration was 252.5 (interquartile range = 145.5-390.6) ng/mL. Overall breed difference was found (p<0.0001), and 42% of pairwise breed comparisons were significant. Univariate regression analysis showed association between serum 5-HT concentration and breed, center of examination, storage time, and sex, with higher 5-HT in females. In multiple regression analysis, the final model had an adjusted R2 of 0.27 with breed (p<0.0001), center (p<0.0001), and storage time (p=0.014) remaining significant. Within centers, overall breed differences were found at 3/5 centers (p≤0.028), and pairwise comparisons within those centers showed breed differences in 42% of comparisons. Among the included breeds, Newfoundlands, Belgian Shepherds and CKCSs had highest 5-HT concentrations. CONCLUSIONS: Interbreed variation in serum 5-HT concentration was found in healthy dogs aged 1-7 years. These differences should be taken into account when designing clinical studies.

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.

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.

Clinical findings and prevalence of the mutation associated with primary ciliary dyskinesia in Old English Sheepdogs.

BACKGROUND: Primary ciliary dyskinesia (PCD) is generally a recessively inherited disorder characterized by dysfunction of motile cilia. A mutation in a new causative gene (CCDC39) has been identified in the Old English Sheepdog (OES). OBJECTIVES: To describe the clinical findings and the molecular changes of affected dogs and estimate the worldwide prevalence of the mutation in a large cohort of OES. ANIMALS: 578 OES, including 28 affected and 550 clinically healthy dogs. METHODS: This retrospective study reviewed the data of OES diagnosed with PCD and OES tested for the mutation. Clinical data including results of physical examination and further investigations were obtained on 11/28 dogs. CCDC39 expression was assessed by qRT-PCR and Western blot analysis in affected dogs and healthy dogs. DNA was extracted on 561/578 dogs and a genetic test by Taqman technology was developed to genotype the CCDC39 mutation in these dogs. RESULTS: Clinical findings were recurrent nasal discharge and cough, pyrexia, leucocytosis, and bronchopneumonia. Ultrastructural defects were characterized by central microtubular abnormalities and decreased number of inner dynein arms (IDAs). Molecular analysis revealed a reduced expression of CCDC39 RNA and an absence of CCDC39 protein in affected dogs compared to healthy dogs. The mutation was more frequent in nonrandomly selected European OES population with a higher proportion of carriers (19%) compared to non-European dogs (7%). CONCLUSION AND CLINICAL IMPORTANCE: CCDC39 mutation is dispersed in a worldwide population and is responsible for PCD in this breed. Genetic testing might enable control of this disease.

Breed differences in natriuretic peptides in healthy dogs.

BACKGROUND: Measurement of plasma concentration of natriuretic peptides (NPs) is suggested to be of value in diagnosis of cardiac disease in dogs, but many factors other than cardiac status may influence their concentrations. Dog breed potentially is 1 such factor. OBJECTIVE: To investigate breed variation in plasma concentrations of pro-atrial natriuretic peptide 31-67 (proANP 31-67) and N-terminal B-type natriuretic peptide (NT-proBNP) in healthy dogs. ANIMALS: 535 healthy, privately owned dogs of 9 breeds were examined at 5 centers as part of the European Union (EU) LUPA project. METHODS: Absence of cardiovascular disease or other clinically relevant organ-related or systemic disease was ensured by thorough clinical investigation. Plasma concentrations of proANP 31-67 and NT-proBNP were measured by commercially available ELISA assays. RESULTS: Overall significant breed differences were found in proANP 31-67 (P < .0001) and NT-proBNP (P < .0001) concentrations. Pair-wise comparisons between breeds differed in approximately 50% of comparisons for proANP 31-67 as well as NT-proBNP concentrations, both when including all centers and within each center. Interquartile range was large for many breeds, especially for NT-proBNP. Among included breeds, Labrador Retrievers and Newfoundlands had highest median NT-proBNP concentrations with concentrations 3 times as high as those of Dachshunds. German Shepherds and Cavalier King Charles Spaniels had the highest median proANP 31-67 concentrations, twice the median concentration in Doberman Pinschers. CONCLUSIONS AND CLINICAL IMPORTANCE: Considerable interbreed variation in plasma NP concentrations was found in healthy dogs. Intrabreed variation was large in several breeds, especially for NT-proBNP. Additional studies are needed to establish breed-specific reference ranges.

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.

Progressive juvenile glomerulonephropathy in 16 related French Mastiff (Bordeaux) dogs.

BACKGROUND: Familial juvenile glomerulonephropathy (JGN) is reported in several breeds of dogs. The mode of inheritance and spectrum of pathological lesions vary among breeds. A progressive JGN was detected in a pedigree of French Mastiff (FM) dogs. OBJECTIVES: To describe clinical, laboratory, and histopathologic findings in related FM dogs suffering from progressive JGN and to determine the mode of inheritance of this condition. ANIMALS: Sixteen affected and 35 healthy related FM dogs METHODS: FM dogs < 24 months of age and diagnosed with chronic kidney disease with evidence of proteinuria entered the study. Clinical, laboratory, histopathologic findings, and pedigree data were recorded. RESULTS: Clinical signs were typical of progressive glomerulopathy with resultant renal failure. Increased blood urea nitrogen, creatinine and total cholesterol concentrations, and proteinuria were found in all patients. Affected dogs had abnormal kidney structure on abdominal ultrasound examination. Histopathologic examination revealed extensive cystic glomerular atrophy, glomerular hypercellularity, and capillary wall thickening without immune complex deposition when tested with immunohistochemistry or immunofluorescence. Electron microscopy did not disclose specific primary glomerular lesions. Mean age at death was 20 months and mean length of survival after diagnosis was 6 months. Both males and females from healthy parents were affected. An autosomal recessive mode of transmission is suspected, but a more complex mode of inheritance cannot be excluded. CONCLUSIONS AND CLINICAL IMPORTANCE: Progressive familial JGN occurs in FM dogs. Characterization of the pathogenesis and mode of inheritance of this disease warrants additional study.