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      Short‐Term Efficacy and Safety of Torasemide and Furosemide in 366 Dogs with Degenerative Mitral Valve Disease: The TEST Study

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          Abstract

          Background

          Furosemide is the only loop diuretic recommended by the ACVIM consensus guidelines for treatment of congestive heart failure (CHF) in dogs related to degenerative mitral valve disease (DMVD). Torasemide is another potent loop diuretic with a longer half‐life and a higher bioavailability.

          Objectives

          (1) To demonstrate that torasemide given once a day (q24h) is noninferior to furosemide given twice a day (q12h) for treating dogs with CHF; (2) and to compare the effect of the 2 drugs on the time to reach a composite cardiac endpoint “spontaneous cardiac death, euthanasia due to heart failure or CHF class worsening.”

          Animals

          A total of 366 dogs with CHF attributable to DMVD.

          Methods

          Analysis of 2 prospective randomized single‐blinded reference‐controlled trials was performed. Dogs orally received either torasemide q24h (n = 180) or furosemide q12h (n = 186) in addition to standard CHF therapy over 3 months. The primary efficacy criterion was the percentage of dogs with treatment success assessed in each study. The time to reach the composite cardiac endpoint was used as secondary criterion in the overall population.

          Results

          Torasemide was noninferior to furosemide ( P torasemide −  P furosemide = +7%; 95% CI [−8%; +22%] and P torasemide −  P furosemide = +1%; 95% CI [−12%; +14%], respectively, in Study 1 and Study 2). Torasemide (median dose = 0.24 mg/kg/d q24h; range = 0.10–0.69 mg/kg/d) was associated with a 2‐fold reduction in the risk of reaching the composite cardiac endpoint (adjusted HR = 0.47; 95% CI = 0.27–0.82; P = 0.0077) as compared with furosemide (median dose = 1.39 mg/kg q12h; range = 0.70–6.30 mg/kg q12h).

          Conclusions and Clinical Importance

          Torasemide q24h is an effective oral diuretic in dogs with CHF.

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          Most cited references60

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          ACC/AHA guidelines for the evaluation and management of chronic heart failure in the adult: executive summary. A report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines (Committee to revise the 1995 Guidelines for the Evaluation and Management of Heart Failure).

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            Left atrial to aortic root indices using two-dimensional and M-mode echocardiography in cavalier King Charles spaniels with and without left atrial enlargement.

            Two-dimensional (2-D) echocardiographic measurement of the left atrium (LA) has the potential to be more accurate than the standard M-mode method, because the LA body can be measured. We evaluated a 2-D method for measuring LA and aorta (AO) in a right parasternal short-axis view and compared it to the M-mode method. An index for LA size (LA/AO) was calculated in 166 cavalier King Charles spaniels, 56 normal and 110 dogs with mitral regurgitation (MR) of varying degrees secondary to chronic valvular disease. In normal dogs, the AO-2-D and LA/AO-2-D did not correlate to body weight (BW) or BW2; whereas, all M-mode values and the LA-2-D were significantly (p < .05) related to both BW parameters. In normal dogs, there was no difference between M-mode and 2-D indices. For all dogs (normal and dogs with MR) there was an 11% bias between the M-mode and 2-D index with the LA/AO-2-D being higher than the LA/AO-M. The association between the mean and the difference of the indices demonstrated a quadratic relationship. Dogs with a mean LA/AO of 2.0-2.5 showed the largest difference between the two indices. Small values for the 2-D coefficients of variation for respiration and stage of diastole were found; 3.4 and 3.1%, respectively. The 2-D index is more sensitive to LA enlargement than the M-mode index.
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              Echocardiographic assessment of canine degenerative mitral valve disease.

              Degenerative mitral valve disease (MVD), the most common acquired heart disease in small-sized dogs, is characterized by valvular degeneration resulting in systolic mitral valve regurgitation (MR). Worsening of MR leads to several combined complications including cardiac remodeling, increased left ventricular filling pressure, pulmonary arterial hypertension, and myocardial dysfunction. Conventional two-dimensional, M-mode, and Doppler examination plays a critical role in the initial and longitudinal assessment of dogs affected by MVD, providing information on mitral valve anatomy, MR severity, left ventricular (LV) size and function, as well as cardiac and vascular pressures. Several standard echocardiographic variables have been shown to be related to clinical outcome. Some of these markers (e.g., left atrium to aorta ratio, regurgitation fraction, pulmonary arterial pressure) may also help in identifying asymptomatic MVD dogs at higher risk of early decompensation, which remains a major issue in practice. However, both afterload and preload are altered during the disease course. This represents a limitation of conventional techniques to accurately assess myocardial function, as most corresponding variables are load-dependent. Recent ultrasound techniques including tissue Doppler imaging, strain and strain rate imaging, and speckle tracking echocardiography, provide new parameters to assess regional and global myocardial performance (e.g., myocardial velocities and gradients, deformation and rate of deformation, and mechanical synchrony). As illustration, the authors present new data obtained from a population of 91 dogs (74 MVD dogs, 17 age-matched controls) using strain imaging, and showing a significant longitudinal systolic alteration at the latest MVD heart failure stage.
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                Author and article information

                Contributors
                frederique.woehrle@vetoquinol.com
                Journal
                J Vet Intern Med
                J. Vet. Intern. Med
                10.1111/(ISSN)1939-1676
                JVIM
                Journal of Veterinary Internal Medicine
                John Wiley and Sons Inc. (Hoboken )
                0891-6640
                1939-1676
                04 October 2017
                Nov-Dec 2017
                : 31
                : 6 ( doiID: 10.1111/jvim.2017.31.issue-6 )
                : 1629-1642
                Affiliations
                [ 1 ] Alfort Cardiology Unit Université Paris‐Est Ecole Nationale Vétérinaire d'Alfort Maisons‐Alfort Cedex France
                [ 2 ] INSERM U955 Equipe 03 Créteil Cedex France
                [ 3 ] Vetoquinol SA Paris France
                [ 4 ] Vetoquinol SA Lure France
                [ 5 ] Department of Biostatistics and Clinical Epidemiology Université Paris‐Est Ecole Nationale Vétérinaire d'Alfort Maisons‐Alfort Cedex France
                Author notes
                [*] [* ]Corresponding author: F. Woehrle, Vetoquinol SA, Magny‐Vernois BP189, F‐70204 Lure, France; e‐mail: frederique.woehrle@ 123456vetoquinol.com
                Article
                JVIM14841
                10.1111/jvim.14841
                5697186
                28975664
                2af402ef-abbf-46e8-ab60-81bc12ec63bd
                Copyright © 2017 The Authors. Journal of Veterinary Internal Medicine published by Wiley Periodicals, Inc. on behalf of the American College of Veterinary Internal Medicine.

                This is an open access article under the terms of the Creative Commons Attribution‐NonCommercial License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited and is not used for commercial purposes.

                History
                : 17 January 2017
                : 05 July 2017
                : 23 August 2017
                Page count
                Figures: 2, Tables: 10, Pages: 14, Words: 12571
                Categories
                Standard Article
                SMALL ANIMAL
                Standard Articles
                Cardiology
                Custom metadata
                2.0
                jvim14841
                November/December 2017
                Converter:WILEY_ML3GV2_TO_NLMPMC version:5.2.6 mode:remove_FC converted:21.11.2017

                Veterinary medicine
                canine,clinical trial,diuretic,pulmonary edema
                Veterinary medicine
                canine, clinical trial, diuretic, pulmonary edema

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