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      ACVIM consensus statement guidelines for the diagnosis, classification, treatment, and monitoring of pulmonary hypertension in dogs

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          Abstract

          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.

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          Most cited references221

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          Clinical classification of pulmonary hypertension.

          In 1998, during the Second World Symposium on Pulmonary Hypertension (PH) held in Evian, France, a clinical classification of PH was proposed. The aim of the Evian classification was to individualize different categories sharing similarities in pathophysiological mechanisms, clinical presentation, and therapeutic options. The Evian classification is now well accepted and widely used in clinical practice, especially in specialized centers. In addition, this classification has been used by the U.S. Food and Drug Administration and the European Agency for Drug Evaluation for the labeling of newly approved medications in PH. In 2003, during the Third World Symposium on Pulmonary Arterial Hypertension held in Venice, Italy, it was decided to maintain the general architecture and philosophy of the Evian classification. However, some modifications have been proposed, mainly to abandon the term "primary pulmonary hypertension" and to replace it with "idiopathic pulmonary hypertension"; to reclassify pulmonary veno-occlusive disease and pulmonary capillary hemangiomatosis; to update risk factors and associated conditions for pulmonary arterial hypertension and to propose guidelines in order to improve the classification of congenital systemic-to-pulmonary shunts.
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            Pulmonary hypertension due to left heart diseases.

            Pulmonary hypertension (PH), a common complication of left heart diseases (LHD), negatively impacts symptoms, exercise capacity, and outcome. Although the true prevalence of PH-LHD is unknown, a subset of patients might present significant PH that cannot be explained by a passive increase in left-sided filling pressures. The term "out-of-proportion" PH has been used to identify that population without a clear definition, which has been found less than ideal and created confusion. We propose a change in terminology and a new definition of PH due to LHD. We suggest to abandon "out-of-proportion" PH and to distinguish "isolated post-capillary PH" from "post-capillary PH with a pre-capillary component" on the basis of the pressure difference between diastolic pulmonary artery pressure and pulmonary artery wedge pressure. Although there is no validated treatment for PH-LHD, we provide insights into management and discuss completed and randomized trials in this condition. Finally, we provide recommendations for future clinical trials to establish safety and efficacy of novel compounds to target this area of unmet medical need. Copyright © 2013 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.
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              Imatinib mesylate as add-on therapy for pulmonary arterial hypertension: results of the randomized IMPRES study.

              By its inhibitory effect on platelet-derived growth factor signaling, imatinib could be efficacious in treating patients with pulmonary arterial hypertension (PAH). Imatinib in Pulmonary Arterial Hypertension, a Randomized, Efficacy Study (IMPRES), a randomized, double-blind, placebo-controlled 24-week trial, evaluated imatinib in patients with pulmonary vascular resistance ≥ 800 dyne·s·cm(-5) symptomatic on ≥ 2 PAH therapies. The primary outcome was change in 6-minute walk distance. Secondary outcomes included changes in hemodynamics, functional class, serum levels of N-terminal brain natriuretic peptide, and time to clinical worsening. After completion of the core study, patients could enter an open-label long-term extension study. Of 202 patients enrolled, 41% patients received 3 PAH therapies, with the remainder on 2 therapies. After 24 weeks, the mean placebo-corrected treatment effect on 6-minute walk distance was 32 m (95% confidence interval, 12-52; P=0.002), an effect maintained in the extension study in patients remaining on imatinib. Pulmonary vascular resistance decreased by 379 dyne·s·cm(-5) (95% confidence interval, -502 to - 255; P<0.001, between-group difference). Functional class, time to clinical worsening, and mortality did not differ between treatments. Serious adverse events and discontinuations were more frequent with imatinib than placebo (44% versus 30% and 33% versus 18%, respectively). Subdural hematoma occurred in 8 patients (2 in the core study, 6 in the extension) receiving imatinib and anticoagulation. Imatinib improved exercise capacity and hemodynamics in patients with advanced PAH, but serious adverse events and study drug discontinuations were common. Further studies are needed to investigate the long-term safety and efficacy of imatinib in patients with PAH. URL: http://www.clinicaltrials.gov. Unique identifier: NCT00902174 (core study); NCT01392495 (extension).
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                Author and article information

                Contributors
                reineroc@missouri.edu
                Journal
                J Vet Intern Med
                J. Vet. Intern. Med
                10.1111/(ISSN)1939-1676
                JVIM
                Journal of Veterinary Internal Medicine
                John Wiley & Sons, Inc. (Hoboken, USA )
                0891-6640
                1939-1676
                17 February 2020
                March 2020
                : 34
                : 2 ( doiID: 10.1111/jvim.v34.2 )
                : 549-573
                Affiliations
                [ 1 ] Department of Veterinary Medicine and Surgery, College of Veterinary Medicine University of Missouri Columbia Missouri
                [ 2 ] Department of Medicine and Epidemiology, School of Veterinary Medicine University of California, Davis Davis California
                [ 3 ] Department of Medical Sciences, School of Veterinary Medicine University of Wisconsin Madison Wisconsin
                [ 4 ] Department of Sciences Cliniques, Faculté de Médecine Vétérinaire Université de Montréal Saint‐Hyacinthe Quebec Canada
                [ 5 ] Department of Clinical Sciences, Cummings School of Veterinary Medicine Tufts University Medford Massachusetts
                [ 6 ] Department of Clinical Sciences of Companion Animals and Equine University of Liège Liège Belgium
                [ 7 ] Department of Pathobiology and Diagnostic Investigation, College of Veterinary Medicine Michigan State University East Lansing Michigan
                [ 8 ] Department of Small Animal Clinical Sciences, College of Veterinary Medicine University of Tennessee Knoxville Tennessee
                [ 9 ] Department of Small Animal Clinical Sciences Virginia Maryland College of Veterinary Medicine Blacksburg Virginia
                [ 10 ] Department of Clinical Sciences Colorado State University Fort Collins Colorado
                Author notes
                [*] [* ] Correspondence

                *Carol Reinero, Department of Veterinary Medicine and Surgery, College of Veterinary Medicine, University of Missouri, 900 East Campus Drive, Columbia, MO 65211.

                Email: reineroc@ 123456missouri.edu

                Author information
                https://orcid.org/0000-0002-6382-5582
                https://orcid.org/0000-0002-3563-0737
                https://orcid.org/0000-0003-3233-8930
                https://orcid.org/0000-0001-6981-8968
                https://orcid.org/0000-0001-7427-2402
                Article
                JVIM15725
                10.1111/jvim.15725
                7097566
                32065428
                12346185-55ad-40d3-990c-c11d8738a7ae
                © 2020 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 http://creativecommons.org/licenses/by/4.0/ License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.

                History
                : 08 January 2020
                : 30 January 2020
                Page count
                Figures: 7, Tables: 7, Pages: 25, Words: 21489
                Categories
                Consensus Statement
                Consensus Statement
                Custom metadata
                2.0
                March 2020
                Converter:WILEY_ML3GV2_TO_JATSPMC version:5.7.8 mode:remove_FC converted:26.03.2020

                Veterinary medicine
                echocardiography,pulmonary arterial hypertension,respiratory disease,tricuspid regurgitation velocity

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