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      Altered Right Ventricular Kinetic Energy Work Density and Viscous Energy Dissipation in Patients with Pulmonary Arterial Hypertension: A Pilot Study Using 4D Flow MRI

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          Abstract

          Introduction

          Right ventricular (RV) function has increasingly being recognized as an important predictor for morbidity and mortality in patients with pulmonary arterial hypertension (PAH). The increased RV after-load increase RV work in PAH. We used time-resolved 3D phase contrast MRI (4D flow MRI) to derive RV kinetic energy (KE) work density and energy loss in the pulmonary artery (PA) to better characterize RV work in PAH patients.

          Methods

          4D flow and standard cardiac cine images were obtained in ten functional class I/II patients with PAH and nine healthy subjects. For each individual, we calculated the RV KE work density and the amount of viscous dissipation in the PA.

          Results

          PAH patients had alterations in flow patterns in both the RV and the PA compared to healthy subjects. PAH subjects had significantly higher RV KE work density than healthy subjects (94.7±33.7 mJ/mL vs. 61.7±14.8 mJ/mL, p = 0.007) as well as a much greater percent PA energy loss (21.1±6.4% vs. 2.2±1.3%, p = 0.0001) throughout the cardiac cycle. RV KE work density and percent PA energy loss had mild and moderate correlations with RV ejection fraction.

          Conclusion

          This study has quantified two kinetic energy metrics to assess RV function using 4D flow. RV KE work density and PA viscous energy loss not only distinguished healthy subjects from patients, but also provided distinction amongst PAH patients. These metrics hold promise as imaging markers for RV function.

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          Most cited references29

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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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            Progressive right ventricular dysfunction in patients with pulmonary arterial hypertension responding to therapy.

            The purpose of this study was to examine the relationship between changes in pulmonary vascular resistance (PVR) and right ventricular ejection fraction (RVEF) and survival in patients with pulmonary arterial hypertension (PAH) under PAH-targeted therapies. Despite the fact that medical therapies reduce PVR, the prognosis of patients with PAH is still poor. The primary cause of death is right ventricular (RV) failure. One possible explanation for this apparent paradox is the fact that a reduction in PVR is not automatically followed by an improvement in RV function. A cohort of 110 patients with incident PAH underwent baseline right heart catheterization, cardiac magnetic resonance imaging, and 6-min walk testing. These measurements were repeated in 76 patients after 12 months of therapy. Two patients underwent lung transplantation, 13 patients died during the first year, and 17 patients died in the subsequent follow-up of 47 months. Baseline RVEF (hazard ratio [HR]: 0.938; p = 0.001) and PVR (HR: 1.001; p = 0.031) were predictors of mortality. During the first 12 months, changes in PVR were moderately correlated with changes in RVEF (R = 0.330; p = 0.005). Changes in RVEF (HR: 0.929; p = 0.014) were associated with survival, but changes in PVR (HR: 1.000; p = 0.820) were not. In 68% of patients, PVR decreased after medical therapy. Twenty-five percent of those patients with decreased PVR showed a deterioration of RV function and had a poor prognosis. After PAH-targeted therapy, RV function can deteriorate despite a reduction in PVR. Loss of RV function is associated with a poor outcome, irrespective of any changes in PVR. Copyright © 2011 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.
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              Tricuspid annular displacement predicts survival in pulmonary hypertension.

              Right ventricular (RV) function is an important determinant of prognosis in pulmonary hypertension. However, noninvasive assessment of the RV function is often limited by complex geometry and poor endocardial definition. To test whether the degree of tricuspid annular displacement (tricuspid annular plane systolic excursion [TAPSE]) is a useful echo-derived measure of RV function with prognostic significance in pulmonary hypertension. We prospectively studied 63 consecutive patients with pulmonary hypertension who were referred for a clinically indicated right heart catheterization. Patients underwent right heart catheterization immediately followed by transthoracic echocardiogram and TAPSE measurement. In the overall cohort, a TAPSE of less than 1.8 cm was associated with greater RV systolic dysfunction (cardiac index, 1.9 vs. 2.7 L/min/m2; RV % area change, 24 vs. 33%), right heart remodeling (right atrial area index, 17.0 vs. 12.1 cm(2)/m), and RV-left ventricular (LV) disproportion (RV/LV diastolic area, 1.7 vs. 1.2; all p < 0.001), versus a TAPSE of 1.8 cm or greater. In patients with pulmonary arterial hypertension (PAH; n = 47), survival estimates at 1 and 2 yr were 94 and 88%, respectively, in those with a TAPSE of 1.8 cm or greater versus 60 and 50%, respectively, in subjects with a TAPSE less than 1.8 cm. The unadjusted risk of death (hazard ratio) in patients with a TAPSE less than 1.8 versus 1.8 cm or greater was 5.7 (95% confidence interval, 1.3-24.9; p = 0.02) for the PAH cohort. For every 1-mm decrease in TAPSE, the unadjusted risk of death increased by 17% (hazard ratio, 1.17; 95% confidence interval, 1.05-1.30; p = 0.006), which persisted after adjusting for other echocardiographic and hemodynamic variables and baseline treatment status. TAPSE powerfully reflects RV function and prognosis in PAH.
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                Author and article information

                Contributors
                Role: Editor
                Journal
                PLoS One
                PLoS ONE
                plos
                plosone
                PLoS ONE
                Public Library of Science (San Francisco, CA USA )
                1932-6203
                29 September 2015
                2015
                : 10
                : 9
                : e0138365
                Affiliations
                [1 ]Cardiovascular Division, University of Pennsylvania, Philadelphia, PA, United States of America
                [2 ]Department of Radiology, University of Pennsylvania, Philadelphia, PA, United States of America
                [3 ]Department of Bioengineering, University of Pennsylvania, Philadelphia, PA, United States of America
                [4 ]Department of Radiology, Northwestern University, Chicago, IL, United States of America
                [5 ]Cardiovascular Division, Temple University, Philadelphia, PA, United States of America
                Nippon Medical School Graduate School of Medicine, JAPAN
                Author notes

                Competing Interests: The authors have declared that no competing interests exist.

                Conceived and designed the experiments: WRTW YH. Performed the experiments: QJH WRTW YH. Analyzed the data: QJH WRTW CMFY JSA AJB. Contributed reagents/materials/analysis tools: PRF AJB. Wrote the paper: QJH WRTW CMFY JSA AJB PRF YH. Provided and cared for participating subjects: PRF.

                Article
                PONE-D-15-16885
                10.1371/journal.pone.0138365
                4587751
                26418553
                92a3d7bd-dfc8-45d3-b4d6-99560a2a0225
                Copyright @ 2015

                This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited

                History
                : 18 April 2015
                : 27 August 2015
                Page count
                Figures: 5, Tables: 3, Pages: 14
                Funding
                The study is funded by FOCUS Junior Faculty Award for Research in Women's Cardiovascular Health funded by the Edna G. Kynett Memorial Foundation (to YH) and the Cardiovascular Medical Research and Education Fund ( http://www.ipahresearch.org/)(to YH). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.
                Categories
                Research Article
                Custom metadata
                The data contains human subject information that is limited to a small patient population in a single institution. On the IRB form, it clearly states that the data obtained from the patients will be stored on secure computers within the hospital of the University of Pennsylvania. Data are available upon request from the University of Pennsylvania Institutional Ethics Committee for researchers who meet the criteria for access to confidential data.

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