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      Surfing the right ventricular pressure waveform: methods to assess global, systolic and diastolic RV function from a clinical right heart catheterization

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          Abstract

          Right ventricular (RV) function strongly associates with mortality in patients with pulmonary arterial hypertension (PAH). Current methods to determine RV function require temporal measurements of pressure and volume. The aim of the study was to investigate the feasibility of using right heart catheterization (RHC) measurements to estimate systolic and diastolic RV function. RV pressure and volume points were fit to P = α(e βV-1) to assess diastolic stiffness coefficient (β) and end-diastolic elastance (Eed). Single-beat methods were used to assess RV contractility (Ees). The effects of a non-zero unstressed RV volume (V 0), RHC-derived stroke volume (SV RHC), and normalization of the end-diastolic volume (EDV) on estimates of β, Eed, and Ees were tested using Bland–Altman analysis in an incident PAH cohort (n = 32) that had both a RHC and cardiac magnetic resonance (CMR) test. RHC-derived measures of RV function were used to detect the effect of prostacyclin therapy in an incident PAH cohort and the severity of PAH in prevalent PAH (n = 21). A non-zero V 0 had a minimal effect on β with a small bias and limits of agreement (LOA). Stroke volume (SV) significantly influenced estimates of β and Ees with a large LOA. Normalization of EDV had minimal effect on both β and Eed. RHC-derived β and Eed increased due to the severity of PAH and decreased due to three months of prostacyclin therapy. It is feasible to detect therapeutic changes in specific stiffness and elastic properties of the RV from signal-beat pressure-volume loops by using RHC-derived SV and normalizing RV EDV.

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          Pathophysiology of the right ventricle and of the pulmonary circulation in pulmonary hypertension: an update

          The function of the right ventricle determines the fate of patients with pulmonary hypertension. Since right heart failure is the consequence of increased afterload, a full physiological description of the cardiopulmonary unit consisting of both the right ventricle and pulmonary vascular system is required to interpret clinical data correctly. Here, we provide such a description of the unit and its components, including the functional interactions between the right ventricle and its load. This physiological description is used to provide a framework for the interpretation of right heart catheterisation data as well as imaging data of the right ventricle obtained by echocardiography or magnetic resonance imaging. Finally, an update is provided on the latest insights in the pathobiology of right ventricular failure, including key pathways of molecular adaptation of the pressure overloaded right ventricle. Based on these outcomes, future directions for research are proposed.
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            Right ventricular diastolic impairment in patients with pulmonary arterial hypertension.

            The role of right ventricular (RV) diastolic stiffness in pulmonary arterial hypertension (PAH) is not well established. Therefore, we investigated the presence and possible underlying mechanisms of RV diastolic stiffness in PAH patients. Single-beat RV pressure-volume analyses were performed in 21 PAH patients and 7 control subjects to study RV diastolic stiffness. Data are presented as mean ± SEM. RV diastolic stiffness (β) was significantly increased in PAH patients (PAH, 0.050 ± 0.005 versus control, 0.029 ± 0.003; P 200%; Pinteraction <0.001), indicating stiffening of RV sarcomeres. An important regulator of sarcomeric stiffening is the sarcomeric protein titin. Therefore, we investigated titin isoform composition and phosphorylation. No alterations were observed in titin isoform composition (N2BA/N2B ratio: PAH, 0.78 ± 0.07 versus control, 0.91 ± 0.08), but titin phosphorylation in RV tissue of PAH patients was significantly reduced (PAH, 0.16 ± 0.01 arbitrary units versus control, 0.20 ± 0.01 arbitrary units; P<0.05). RV diastolic stiffness is significantly increased in PAH patients, with important contributions from increased collagen and intrinsic stiffening of the RV cardiomyocyte sarcomeres.
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              Assessment of Right Ventricular Function in the Research Setting: Knowledge Gaps and Pathways Forward. An Official American Thoracic Society Research Statement

              Background: Right ventricular (RV) adaptation to acute and chronic pulmonary hypertensive syndromes is a significant determinant of short- and long-term outcomes. Although remarkable progress has been made in the understanding of RV function and failure since the meeting of the NIH Working Group on Cellular and Molecular Mechanisms of Right Heart Failure in 2005, significant gaps remain at many levels in the understanding of cellular and molecular mechanisms of RV responses to pressure and volume overload, in the validation of diagnostic modalities, and in the development of evidence-based therapies. Methods: A multidisciplinary working group of 20 international experts from the American Thoracic Society Assemblies on Pulmonary Circulation and Critical Care, as well as external content experts, reviewed the literature, identified important knowledge gaps, and provided recommendations. Results: This document reviews the knowledge in the field of RV failure, identifies and prioritizes the most pertinent research gaps, and provides a prioritized pathway for addressing these preclinical and clinical questions. The group identified knowledge gaps and research opportunities in three major topic areas: 1 ) optimizing the methodology to assess RV function in acute and chronic conditions in preclinical models, human studies, and clinical trials; 2 ) analyzing advanced RV hemodynamic parameters at rest and in response to exercise; and 3 ) deciphering the underlying molecular and pathogenic mechanisms of RV function and failure in diverse pulmonary hypertension syndromes. Conclusions: This statement provides a roadmap to further advance the state of knowledge, with the ultimate goal of developing RV-targeted therapies for patients with RV failure of any etiology.
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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
                19 February 2020
                Jan-Mar 2020
                : 10
                : 1
                : 2045894019850993
                Affiliations
                [1 ]Division of Translational and Regenerative Medicine, The University of Arizona College of Medicine, Tucson, AZ, USA
                [2 ]Division of Pulmonary, Allergy, Critical Care and Sleep Medicine, The University of Arizona College of Medicine, Tucson, AZ, USA
                [3 ]Division of Cardiology, Department of Medicine, The University of Arizona College of Medicine, Tucson, AZ, USA
                [4 ]Department of Medicine, Indiana University, Indianapolis, IN, USA
                [5 ]Department of Physiology, The University of Arizona College of Medicine, Tucson, AZ, USA
                [6 ]Department of Medicine, University of California, San Diego, La Jolla, CA, USA
                Author notes
                [*]Rebecca R. Vanderpool, Division of Translational and Regenerative Medicine, Department of Biomedical Engineering, The University of Arizona, Medical Research Building Room 423, 1656 E Mabel Street, Tucson, AZ 85724, USA. Email: vanderpoolrr@ 123456email.arizona.edu
                Author information
                https://orcid.org/0000-0001-6038-0568
                Article
                10.1177_2045894019850993
                10.1177/2045894019850993
                7031797
                31032737
                4942cd7a-f504-4da0-957e-ba6bb314dd20
                © The Author(s) 2020

                Creative Commons Non Commercial CC BY-NC: This article is distributed under the terms of the Creative Commons Attribution-NonCommercial 4.0 License ( https://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 September 2018
                : 1 April 2019
                Funding
                Funded by: Arizona Biomedical Research Commission, FundRef https://doi.org/http://10.13039/100008335;
                Award ID: ABRC NIA ADHS18-198871
                Categories
                Research Article
                Custom metadata
                January-March 2020
                ts2

                Respiratory medicine
                pulmonary hypertension,right ventricle,diastolic stiffness,single-beat,pressure-volume loop

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