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      Right ventricular afterload predicts long-term transition from parenteral to oral treprostinil in pulmonary arterial hypertension

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          Abstract

          Despite the increasing trends, reports on long-term follow-up are limited on transitioning from parenteral to oral treprostinil therapy in patients with pulmonary arterial hypertension (PAH). We investigated both the effectiveness of parenteral to oral treprostinil transition and the characteristics associated with transition failure over a duration of two years. The study included 37 Group I functional class I and II patients with PAH on combination therapy. Patients were excluded if cardiac index ≤2.2 L/min/m 2, right atrial pressure ≥11 mmHg, or 6-min walk distance ≤250 m. Patients were categorized as successful ( S Transition) or unsuccessful ( U Transition) transition based on clinical stability, or a parenteral comparator ( C Parenteral) if they remained on parenteral therapy (no transition). All patients underwent two right heart catheterizations, one at enrollment and a second post transition. Of 24 total transition patients, 46% were classified as U Transition. U Transition occurred on average 577 days post transition. Both U Transition and S Transition had similar hemodynamics at diagnosis and treprostinil dose before and after transition. Before transition, the pulmonary vascular resistance (PVR) was significantly higher in the U Transition (6.7 ± 2 WU) vs. S Transition group (3.5 ± 1.5 WU). At follow-up catheterization, the U Transition group demonstrated further increases in PVR, greater than the C Parenteral group, without recovery despite “rescue” therapy in the U Transition group. A pre-transition PVR of 4.16 WU discriminated the U Transition from the S Transition group. While a subset of PAH patients on combination therapy may be safely transitioned from parenteral to oral treprostinil, caution should be exercised in patients with elevated baseline PVR to avoid irreversible destabilization.

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          Controlling the False Discovery Rate: A Practical and Powerful Approach to Multiple Testing

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            Initial Use of Ambrisentan plus Tadalafil in Pulmonary Arterial Hypertension.

            Data on the effect of initial combination therapy with ambrisentan and tadalafil on long-term outcomes in patients with pulmonary arterial hypertension are scarce.
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              Right heart adaptation to pulmonary arterial hypertension: physiology and pathobiology.

              Survival in patients with pulmonary arterial hypertension (PAH) is closely related to right ventricular (RV) function. Although pulmonary load is an important determinant of RV systolic function in PAH, there remains a significant variability in RV adaptation to pulmonary hypertension. In this report, the authors discuss the emerging concepts of right heart pathobiology in PAH. More specifically, the discussion focuses on the following questions. 1) How is right heart failure syndrome best defined? 2) What are the underlying molecular mechanisms of the failing right ventricle in PAH? 3) How are RV contractility and function and their prognostic implications best assessed? 4) What is the role of targeted RV therapy? Throughout the report, the authors highlight differences between right and left heart failure and outline key areas of future investigation. Copyright © 2013 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.
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                Author and article information

                Journal
                Pulm Circ
                Pulm Circ
                PUL
                sppul
                Pulmonary Circulation
                SAGE Publications (Sage UK: London, England )
                2045-8932
                2045-8940
                20 August 2018
                Oct-Dec 2018
                : 8
                : 4
                : 2045894018797270
                Affiliations
                [1 ]Department of Medicine, University of Arizona, Tucson, AZ, USA
                [2 ]Division of Pulmonary, Critical Care, Sleep, and Allergy Medicine, University of Arizona, Tucson, AZ, USA
                [3 ]Division of Translational and Regenerative Medicine, University of Arizona, Tucson, AZ, USA
                [4 ]Division of Cardiology, University of Arizona, Tucson, AZ, USA
                [5 ]Sarver Heart Center, University of Arizona, Tucson, AZ, USA
                [6 ]BIO5 Institute, University of Arizona, Tucson, AZ, USA
                [7 ]Creighton School of Medicine, Phoenix, AZ, USA
                [8 ]Arizona Pulmonary Specialists, Phoenix, AZ, USA
                Author notes
                [*]Franz P. Rischard, Division of Pulmonary, Critical Care, Allergy, and Sleep Medicine, Division of Translational and Regenerative Medicine, 1501 N. Campbell Avenue, Tucson, AZ 85724, USA. Email: frischard@ 123456deptofmed.arizona.edu
                Article
                10.1177_2045894018797270
                10.1177/2045894018797270
                6122247
                30124133
                45a7c722-ab0b-4782-8304-71679329a080
                © The Author(s) 2018

                Creative Commons Non Commercial CC BY-NC: This article is distributed under the terms of the Creative Commons Attribution-NonCommercial 4.0 License ( http://www.creativecommons.org/licenses/by-nc/4.0/) which permits non-commercial use, reproduction and distribution of the work without further permission provided the original work is attributed as specified on the SAGE and Open Access pages ( https://us.sagepub.com/en-us/nam/open-access-at-sage).

                History
                : 28 May 2018
                : 2 August 2018
                Categories
                Research Article
                Custom metadata
                October-December 2018

                Respiratory medicine
                drug delivery,pulmonary arterial hypertension,right ventricle function and dysfunction

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