Marie-Claude Bélanger

Effect of Pimobendan or Benazepril Hydrochloride on Survival Times in Dogs with Congestive Heart Failure Caused by Naturally Occurring Myxomatous Mitral Valve Disease: The QUEST Study

BACKGROUND Myxomatous mitral valve disease (MMVD) continues to be an important cause of morbidity and mortality in geriatric dogs despite conventional therapy. HYPOTHESIS Pimobendan in addition to conventional therapy will extend time to sudden cardiac death, euthanasia for cardiac reasons, or treatment failure when compared with conventional therapy plus benazepril in dogs with congestive heart failure (CHF) attributable to MMVD. ANIMALS Two hundred and sixty client-owned dogs in CHF caused by MMVD were recruited from 28 centers in Europe, Canada, and Australia. METHODS A prospective single-blinded study with dogs randomized to PO receive pimobendan (0.4-0.6 mg/kg/d) or benazepril hydrochloride (0.25-1.0 mg/kg/d). The primary endpoint was a composite of cardiac death, euthanized for heart failure, or treatment failure. RESULTS Eight dogs were excluded from analysis. One hundred and twenty-four dogs were randomized to pimobendan and 128 to benazepril. One hundred and ninety dogs reached the primary endpoint; the median time was 188 days (267 days for pimobendan, 140 days for benazepril hazard ratio = 0.688, 95% confidence limits [CL]=0.516-0.916, P= .0099). The benefit of pimobendan persisted after adjusting for all baseline variables. A longer time to reach the endpoint was also associated with being a Cavalier King Charles Spaniel, requiring a lower furosemide dose, and having a higher creatinine concentration. Increases in several indicators of cardiac enlargement (left atrial to aortic root ratio, vertebral heart scale, and percentage increase in left ventricular internal diameter in systole) were associated with a shorter time to endpoint, as was a worse tolerance for exercise. CONCLUSIONS AND CLINICAL IMPORTANCE Pimobendan plus conventional therapy prolongs time to sudden death, euthanasia for cardiac reasons, or treatment failure in dogs with CHF caused by MMVD compared with benazepril plus conventional therapy.

N‐Acetyl‐β‐d‐Glucosaminidase Index as an Early Biomarker for Chronic Kidney Disease in Cats with Hyperthyroidism

BACKGROUND Hyperthyroid cats are at risk of developing azotemic chronic kidney disease (CKD) and diagnostic tools currently used to screen for CKD in hyperthyroid cats are either unreliable or impractical. HYPOTHESIS Urine N-acetyl-beta-D-glucosaminidase index (NAG(i)) is a good biomarker for azotemic CKD in hyperthyroid cats. ANIMALS Twenty-four newly diagnosed nonazotemic hyperthyroid cats and 10 healthy cats. METHODS All cats were evaluated for hyperthyroidism at baseline. Hyperthyroid cats were treated with methimazole and reevaluated once euthyroid. At the end of the study, cats were divided into 3 groups: healthy cats, nonazotemic, and azotemic euthyroid cats. Baseline group characteristics were compared to predict azotemic CKD. The influence of treatment on NAG(i) was evaluated. RESULTS Baseline NAG(i) was significantly different among groups (P= .004). Azotemic cats had a higher median value (13.12 U/g) when compared with healthy cats (1.38 U/g). With NAG(i) >2.76 U/g, negative and positive predictive values for development of azotemia were 77.7 and 50%, whereas the combination of a urine specific gravity (USG) <or=1.035 and T(4) >7.80 microg/dL enhanced predictive values to 88.9 and 83.3%, respectively. NAG(i) values decreased significantly over time in treated nonazotemic cats. CONCLUSIONS AND CLINICAL RELEVANCE Baseline NAG(i) did not differentiate azotemic from nonazotemic euthyroid cats. NAG(i) could be used to assess renal function during medical therapy allowing the clinician to adjust methimazole dosage accordingly. The combination of USG and T(4) could optimize identification of appropriate candidates for permanent treatment of hyperthyroidism.

Longitudinal Analysis of Quality of Life, Clinical, Radiographic, Echocardiographic, and Laboratory Variables in Dogs with Myxomatous Mitral Valve Disease Receiving Pimobendan or Benazepril: The QUEST Study

BACKGROUND Myxomatous mitral valve disease (MMVD) is an important cause of morbidity and mortality in dogs. OBJECTIVES To compare, throughout the period of follow-up of dogs that had not yet reached the primary endpoint, the longitudinal effects of pimobendan versus benazepril hydrochloride treatment on quality-of-life (QoL) variables, concomitant congestive heart failure (CHF) treatment, and other outcome variables in dogs suffering from CHF secondary to MMVD. ANIMALS A total of 260 dogs in CHF because of MMVD. METHODS A prospective single-blinded study with dogs randomized to receive pimobendan (0.4-0.6 mg/kg/day) or benazepril hydrochloride (0.25-1.0 mg/kg/day). Differences in outcome variables and time to intensification of CHF treatment were compared. RESULTS A total of 124 dogs were randomized to pimobendan and 128 to benazepril. No difference was found between groups in QoL variables during the trial. Time from inclusion to 1st intensification of CHF treatment was longer in the pimobendan group (pimobendan 98 days, IQR 30-276 days versus benazepril 59 days, IQR 11-121 days; P = .0005). Postinclusion, dogs in the pimobendan group had smaller heart size based on VHS score (P = .013) and left ventricular diastolic (P = .035) and systolic (P = .0044) dimensions, higher body temperature (P = .030), serum sodium (P = .0027), and total protein (P = .0003) concentrations, and packed cell volume (P = .030). Incidence of arrhythmias was similar in treatment groups. CONCLUSIONS AND CLINICAL IMPORTANCE Pimobendan versus benazepril resulted in similar QoL during the study, but conferred increased time before intensification of CHF treatment. Pimobendan treatment resulted in smaller heart size, higher body temperature, and less retention of free water.

Effect of Pimobendan on Echocardiographic Values in Dogs with Asymptomatic Mitral Valve Disease

BACKGROUND Pimobendan (PIMO) is a novel inodilator that has shown promising results in the treatment of advanced mitral valve disease (MVD), but little is known about its hemodynamic effects, especially regarding the mitral regurgitant volume in naturally occurring MVD. HYPOTHESIS The addition of pimobendan to treatment decreases the regurgitant fraction (RF) in dogs with asymptomatic MVD. ANIMALS Twenty-four client-owned dogs affected by International Small Animal Cardiac Health Council class Ib MVD. METHODS Prospective, blinded, and controlled clinical trial. Dogs were assigned to a PIMO treatment group (n = 19) (0.2-0.3 mg/kg q12h) or a control group (n = 5). Echocardiographic evaluations were performed over a 6-month period. RESULTS The addition of PIMO to treatment did not decrease the RF of dogs affected by asymptomatic class 1b MVD over the study period (P= .85). There was a significant increase in the ejection fraction of the PIMO treated dogs at 30 days (80.8 +/- 1.42 versus 69.0 +/- 2.76, corrected P= .0064), and a decrease in systolic left ventricular diameter (corrected P= .011) within the PIMO group compared with baseline. However, this improvement in systolic function was not sustained over the 6-month trial period. CONCLUSION AND CLINICAL IMPORTANCE This study did not identify beneficial long-term changes in the severity of mitral regurgitation after addition of PIMO to angiotensin converting enzyme inhibitor treatment of dogs with asymptomatic MVD.

Sensory Experience Differentially Modulates the mRNA Expression of the Polysialyltransferases ST8SiaII and ST8SiaIV in Postnatal Mouse Visual Cortex

Polysialic acid (PSA) is a unique carbohydrate composed of a linear homopolymer of α-2,8 linked sialic acid, and is mainly attached to the fifth immunoglobulin-like domain of the neural cell adhesion molecule (NCAM) in vertebrate neural system. In the brain, PSA is exclusively synthesized by the two polysialyltransferases ST8SiaII (also known as STX) and ST8SiaIV (also known as PST). By modulating adhesive property of NCAM, PSA plays a critical role in several neural development processes such as cell migration, neurite outgrowth, axon pathfinding, synaptogenesis and activity-dependent plasticity. The expression of PSA is temporally and spatially regulated during neural development and a tight regulation of PSA expression is essential to its biological function. In mouse visual cortex, PSA is downregulated following eye opening and its decrease allows the maturation of GABAergic synapses and the opening of the critical period for ocular dominance plasticity. Relatively little is known about how PSA levels are regulated by sensory experience and neuronal activity. Here, we demonstrate that while both ST8SiaII and ST8SiaIV mRNA levels decrease around the time of eye opening in mouse visual cortex, only ST8SiaII mRNA level reduction is regulated by sensory experience. Using an organotypic culture system from mouse visual cortex, we further show that ST8SiaII gene expression is regulated by spiking activity and NMDA-mediated excitation. Further, we show that both ST8SiaII and ST8SiaIV mRNA levels are positively regulated by PKC-mediated signaling. Therefore, sensory experience-dependent ST8SiaII gene expression regulates PSA levels in postnatal visual cortex, thus acting as molecular link between visual activity and PSA expression.

Effect of cardiac and respiratory cycles on vertebral heart score measured on fluoroscopic images of healthy dogs

OBJECTIVE To assess the variability in vertebral heart score (VHS) measurement induced by cardiac and respiratory cycles in dogs. DESIGN Prospective observational study. ANIMALS 14 healthy Beagles. PROCEDURES Dogs underwent fluoroscopic examination by 4 observers, and VHS was measured at end-tidal inspiration and end-tidal expiration during end systole and end diastole in left and right lateral recumbency. Mean VHS was compared within and among cardiac and respiratory phases and recumbency type, and correlation between VHS and heart rate was investigated. Interobserver variability was assessed. RESULTS Mean VHS for each combination of respiratory and cardiac cycle was larger on images obtained in right lateral versus left lateral recumbency. The greatest differences were observed between VHS measured in the diastolic inspiratory phase (mean ± SD, 10.59 ± 0.49 vertebral units [VU] and 10.35 ± 0.50 VU for right and left lateral recumbency, respectively) and the systolic expiratory phase (10.11 ± 0.37 VU and 9.92 ± 0.50 VU for right and left lateral recumbency, respectively). The combination of respiratory and cardiac cycles induced a maximal difference in VHS of up to 0.97 VU and 1.11 VU in the inspiratory and expiratory phases, respectively. Heart rate was not correlated with the difference between VHS in systolic and diastolic phases. CONCLUSIONS AND CLINICAL RELEVANCE Clinicians should be aware of the potential influence of these factors when assessing VHS in dogs; in addition to allowing optimal pulmonary assessment, consistently taking radiographs at end-inspiratory tidal volume may help to limit VHS variability attributable to the respiratory cycle. Further research is needed to assess the effects of cardiac and respiratory phases on VHS in dogs with cardiac or respiratory disease.

Prospective evaluation of Doppler echocardiography, tissue Doppler imaging and biomarkers measurement for the detection of doxorubicin-induced cardiotoxicity in dogs: A pilot study.

The purpose of this pilot study was to evaluate the usefulness of selected echocardiographic parameters, NT-proBNP and cardiac troponin I (cTnI) in the detection of cardiotoxicity in dogs treated with doxorubicin for various malignancies. Echocardiographic studies and biomarker measurements were performed before each administration of doxorubicin, then 1 and 3 months after completion of therapy. Thirteen dogs were included, with a total cumulative dose of doxorubicin ranging from 30 to 150 mg/m(2). E/A ratio significantly decreased during doxorubicin administration (p=0.047). cTnI level was also significantly affected by treatment (p=0.046), increasing above normal at least at one time point in 11 of 13 dogs. The results of this pilot study suggest that monitoring of left ventricular diastolic function and cTnI level measurement might be useful in the early detection of cardiotoxic signs of doxorubicin therapy in dogs.

Comparison of peak flow velocity through the left ventricular outflow tract and effective orifice area indexed to body surface area in Golden Retriever puppies to predict development of subaortic stenosis in adult dogs

OBJECTIVE To evaluate the usefulness of Doppler-derived peak flow velocity through the left ventricular outflow tract (LVOT Vmax) and effective orifice area indexed to body surface area (EOAi) in puppies to predict development of subaortic stenosis (SAS) in the same dogs as adults. DESIGN Prospective, longitudinal, observational study. ANIMALS 38 Golden Retrievers. PROCEDURES Cardiac auscultation and echocardiography were performed on 2- to 6-month-old puppies, then repeated at 12 to 18 months. Subaortic stenosis was diagnosed when LVOT Vmax was ≥ 2.3 m/s in adult dogs with left basilar systolic murmurs. RESULTS All puppies with EOAi < 1.46 cm(2)/m(2) had SAS as adults. All adults with EOAi < 1.29 cm(2)/m(2) had SAS. An LVOT Vmax > 2.3 m/s in puppyhood was 63% sensitive and 100% specific for SAS in adulthood. In puppies, LVOT Vmax was more strongly associated with a future diagnosis of SAS (area under the curve [AUC], 0.89) than was EOAi (AUC, 0.80). In puppies, the combination of LVOT Vmax and EOAi yielded slightly higher sensitivity (69%) and specificity (100%) for adult SAS than did LVOT Vmax alone. In unaffected and affected dogs, LVOT Vmax increased significantly from puppyhood to adulthood but EOAi did not. CONCLUSIONS AND CLINICAL RELEVANCE In Golden Retriever puppies, LVOT Vmax > 2.3 m/s and EOAi < 1.46 cm(2)/m(2) were both associated with a diagnosis of SAS at adulthood. The combination of these 2 criteria may result in higher sensitivity for SAS screening. Unlike LVOT Vmax, EOAi did not change during growth in either unaffected Golden Retrievers or those with SAS.

Left coronary aneurysmal dilation and subaortic stenosis in a dog

A 6-month-old German shepherd dog was referred for evaluation of a cardiac murmur. Upon physical examination, the auscultated heart rate was 120 beats/min, and a grade IV/VI systolic heart murmur with a point of maximal intensity over the left heart base radiating up the neck was heard. The standard echocardiographic examination showed subaortic stenosis and an anechoic tubular structure extending from the sinus of Valsalva to the left ventricular posterior wall. Aneurysmal left coronary artery (CA) was confirmed by angiography. The dog was euthanized and post-mortem examination showed severe dilatation of the proximal left CA and confirmed the subaortic stenosis. Histopathology did not demonstrate abnormalities in the walls of the CA, aorta or pulmonary artery. The exact cause of the CA aneurysmal dilation remains unknown. Subaortic stenosis, elevated coronary vascular resistance or a congenital anomaly may have contributed to the dilation. To our knowledge, coronary aneurysmal dilation has never been described in dogs. Standard echocardiography provides reliable information on coronary anatomy.

Association between Aortoseptal Angle in Golden Retriever Puppies and Subaortic Stenosis in Adulthood

Background Predicting subaortic stenosis (SAS) in adult Golden Retriever dogs (GRs) by evaluating them as puppies is hampered by the progressive expression of the SAS phenotype in youth. In some children who develop SAS as adults, an abnormal aortoseptal angle (AoSA) precedes development of stenosis. Objectives To determine the normal AoSA in young adult GRs using echocardiography; to assess the value of AoSA in GR puppies for predicting development of the SAS phenotype. Animals Forty‐eight 2‐ to 6‐month‐old GR puppies. Methods Prospective study. Puppies were recruited from clients and breeders. Puppies were evaluated with a physical examination and an echocardiogram, and this evaluation was repeated when they were 12–18‐month‐old adults. Puppies were classified as unaffected (WNL) or affected (SAS) retroactively, based on their results as adults. Results In WNL young adult GRs, mean ± SD AoSA was 152.3 ± 6.5°. Mean ± SD AoSA in SAS puppies (144.9 ± 8.6°) was significantly different from mean AoSA in WNL puppies (155.7 ± 8.8°, P < .01). No puppy with AoSA >160° had the SAS phenotype as a young adult; 93% (75.7–99.1%) of puppies with AoSA <145° had the SAS phenotype as young adults. Peak LVOT velocity increased significantly between evaluations (P < .0001) whereas AoSA did not (P = .45). Conclusion and Clinical Significance A steep AoSA in GR puppies is associated with the SAS phenotype in young adulthood. Some GR puppies have an abnormal AoSA that persists in young adulthood and is detectable before peak LVOT velocity reaches levels consistent with SAS.