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      Association of lung diffusion capacity with cardiac remodeling and risk of heart failure: The Framingham heart study

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          Abstract

          Background

          Lung function abnormalities are ubiquitous in heart failure (HF). It is unclear, however, if abnormal lung diffusion capacity is associated with cardiac remodeling and antedates HF. We hypothesized that lower lung diffusion capacity for carbon monoxide (DLCO) is associated with worse left ventricular (LV) systolic and diastolic function cross-sectionally, and with higher risk of HF prospectively.

          Methods

          We evaluated 2423 Framingham Study participants (mean age 66 years, 55% women) free of HF who underwent routine echocardiography and pulmonary function tests. We used multivariable regression models to relate DLCO, forced vital capacity (FVC), and forced expiratory volume in 1 second (FEV1) to left ventricular ejection fraction (LVEF), left atrial (LA) emptying fraction (LAEF), E/e’, E/A, LV mass, and LA diameter (LAD). Multivariable-adjusted Cox proportional hazards regression was used to relate DLCO, FEV1, and FVC to incident HF.

          Results

          In multivariable-adjusted cross-sectional analyses, DLCO, FEV1, and FVC (dependent variables) were associated positively with LVEF (β DLCO = 0.208, β FEV1 = 0.021, and β FVC = 0.025 per 5% increment in LVEF; p<0.005 for all), and LAEF (β DLCO = 0.707, β FEV1 = 0.058 and β FVC = 0.058 per 5% increment in LAEF; p<0.002 for all). DLCO and FVC were inversely related to E/A (β DLCO = -0.289, β FVC = -0.047 per SD increment in E/A; p<0.001 for all). Additionally, DLCO, FEV1 and FVC were inversely related to HF risk (108 events, median follow-up 9.7 years; multivariable-adjusted hazard ratios per SD increment 0.90, 95% CI 0.86–0.95; 0.42, 95% CI 0.28–0.65, and 0.51, 95% CI 0.36–0.73, respectively). These results remained robust in analyses restricted to non-smokers.

          Conclusions

          Our large community-based observations are consistent with the concept that lower lung diffusion capacity and expiratory flow rates are associated with cardiac remodeling and may antedate HF. Additional studies are needed to confirm our findings and to evaluate the prognostic utility of pulmonary function testing for predicting HF.

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          Most cited references44

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          Recommendations for cardiac chamber quantification by echocardiography in adults: an update from the American Society of Echocardiography and the European Association of Cardiovascular Imaging.

          The rapid technological developments of the past decade and the changes in echocardiographic practice brought about by these developments have resulted in the need for updated recommendations to the previously published guidelines for cardiac chamber quantification, which was the goal of the joint writing group assembled by the American Society of Echocardiography and the European Association of Cardiovascular Imaging. This document provides updated normal values for all four cardiac chambers, including three-dimensional echocardiography and myocardial deformation, when possible, on the basis of considerably larger numbers of normal subjects, compiled from multiple databases. In addition, this document attempts to eliminate several minor discrepancies that existed between previously published guidelines.
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            Heart Disease and Stroke Statistics—2018 Update: A Report From the American Heart Association

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              Echocardiographic assessment of left ventricular hypertrophy: comparison to necropsy findings.

              To determine the accuracy of echocardiographic left ventricular (LV) dimension and mass measurements for detection and quantification of LV hypertrophy, results of blindly read antemortem echocardiograms were compared with LV mass measurements made at necropsy in 55 patients. LV mass was calculated using M-mode LV measurements by Penn and American Society of Echocardiography (ASE) conventions and cube function and volume correction formulas in 52 patients. Penn-cube LV mass correlated closely with necropsy LV mass (r = 0.92, p less than 0.001) and overestimated it by only 6%; sensitivity in 18 patients with LV hypertrophy (necropsy LV mass more than 215 g) was 100% (18 of 18 patients) and specificity was 86% (29 of 34 patients). ASE-cube LV mass correlated similarly to necropsy LV mass (r = 0.90, p less than 0.001), but systematically overestimated it (by a mean of 25%); the overestimation could be corrected by the equation: LV mass = 0.80 (ASE-cube LV mass) + 0.6 g. Use of ASE measurements in the volume correction formula systematically underestimated necropsy LV mass (by a mean of 30%). In a subset of 9 patients, 3 of whom had technically inadequate M-mode echocardiograms, 2-dimensional echocardiographic (echo) LV mass by 2 methods was also significantly related to necropsy LV mass (r = 0.68, p less than 0.05 and r = 0.82, p less than 0.01). Among other indexes of LV anatomy, only measurement of myocardial cross-sectional area was acceptably accurate for quantitation of LV mass (r = 0.80, p less than 0.001) or diagnosis of LV hypertrophy (sensitivity = 72%, specificity = 94%).(ABSTRACT TRUNCATED AT 250 WORDS)
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                Author and article information

                Contributors
                Role: ConceptualizationRole: InvestigationRole: Writing – original draft
                Role: Writing – review & editing
                Role: Writing – review & editing
                Role: Writing – review & editing
                Role: Writing – review & editing
                Role: Writing – review & editing
                Role: InvestigationRole: MethodologyRole: SupervisionRole: Writing – review & editing
                Role: Editor
                Journal
                PLoS One
                PLoS One
                plos
                plosone
                PLoS ONE
                Public Library of Science (San Francisco, CA USA )
                1932-6203
                16 February 2021
                2021
                : 16
                : 2
                : e0246355
                Affiliations
                [1 ] Section of Preventive Medicine and Epidemiology, Department of Medicine, Boston University School of Medicine, Boston, MA, United States of America
                [2 ] Department of Medicine, Boston Medical Center, Boston, MA, United States of America
                [3 ] Cardiovascular Engineering, Inc., Norwood, MA, United States of America
                [4 ] Department of Medicine, Pulmonary Center, Boston Medical Center, Boston University, Boston, MA, United States of America
                [5 ] Smidt Heart Institute, Cedars-Sinai Medical Center, Los Angeles, CA, United States of America
                [6 ] National Heart, Lung, and Blood Institute, Framingham Heart Study, Framingham, MA, United States of America
                [7 ] Department of Epidemiology, Boston University School of Public Health, Boston, MA, United States of America
                [8 ] Department of Biostatistics, Boston University School of Public Health, Boston, MA, United States of America
                Scuola Superiore Sant’Anna, ITALY
                Author notes

                Competing Interests: Susan Cheng has received consulting fees from Zogenix for work unrelated to this manuscript. Gary F. Mitchell has the following disclosures: a) grants: NIH, Novartis (both significant); b) consulting: Novartis, Servier, Merck, Bayer (all significant); and c) ownership: Cardiovascular Engineering, Inc. (significant). These affiliations do not alter our adherence to PLOS ONE policies on sharing data and materials.

                Author information
                https://orcid.org/0000-0002-2898-9792
                https://orcid.org/0000-0002-4211-3113
                https://orcid.org/0000-0002-4977-036X
                https://orcid.org/0000-0001-7357-5970
                https://orcid.org/0000-0002-7352-621X
                Article
                PONE-D-20-29843
                10.1371/journal.pone.0246355
                7886141
                33592021
                f121d815-44b5-44da-83d4-c0ccf626a52b
                © 2021 Yola et al

                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
                : 22 September 2020
                : 18 January 2021
                Page count
                Figures: 4, Tables: 3, Pages: 12
                Funding
                Funded by: funder-id http://dx.doi.org/10.13039/100000009, Foundation for the National Institutes of Health;
                Award ID: NO1-HC-25195, HHSN268201500001I, 75N92019D00031, 1 R01HL132320, 1R01HL131029, R01HL131015, R01 HL086875, 5T32HL125232
                Award Recipient :
                Funded by: Evans Scholar award and Jay and Louise Coffman endowment, Department of Medicine, Boston University School of Medicine
                Award Recipient :
                Funded by: Cardiovascular Engineering., Inc.
                Award Recipient :
                This work was supported by the National Heart, Lung and Blood Institute contracts NO1-HC-25195, HHSN268201500001I and 75N92019D00031; NIH/NHLBI grants 1 R01HL132320, 1R01HL131029, R01HL131015, 5T32HL125232 and R01 HL086875 (RSV); and the Evans Scholar award and Jay and Louise Coffman endowment, Department of Medicine, Boston University School of Medicine (RSV). Gary F. Mitchell was supported by Cardiovascular Engineering., Inc; this funder provided support in the form of salary for Gary F. Mitchell and various employees of Cardiovascular Engineering, Inc., who are involved in analysis of hemodynamic data. The aforementioned salary support is derived from the various NIH grants that supported the study. Cardiovascular Engineering, Inc., did not have any additional role in the study design, data collection and analysis, decision to publish, or preparation of the manuscript outside of the work done through these NIH grants. The specific role of this author is articulated in the ‘author contributions’ section. There was no additional external funding received for this study.
                Categories
                Research Article
                Medicine and Health Sciences
                Cardiology
                Heart Failure
                Medicine and Health Sciences
                Epidemiology
                Medical Risk Factors
                Medicine and Health Sciences
                Pulmonology
                Pulmonary Function
                Medicine and Health Sciences
                Endocrinology
                Endocrine Disorders
                Diabetes Mellitus
                Medicine and Health Sciences
                Medical Conditions
                Metabolic Disorders
                Diabetes Mellitus
                Medicine and Health Sciences
                Diagnostic Medicine
                Diagnostic Radiology
                Ultrasound Imaging
                Echocardiography
                Research and Analysis Methods
                Imaging Techniques
                Diagnostic Radiology
                Ultrasound Imaging
                Echocardiography
                Medicine and Health Sciences
                Radiology and Imaging
                Diagnostic Radiology
                Ultrasound Imaging
                Echocardiography
                Biology and Life Sciences
                Physiology
                Cardiovascular Physiology
                Biology and Life Sciences
                Physiology
                Physiological Parameters
                Body Weight
                Physical Sciences
                Chemistry
                Chemical Compounds
                Carbon Monoxide
                Custom metadata
                The data underlying this study cannot be shared publicly, as they contain sensitive identifying information. Interested researchers can request the data from BioLINCC after registering at https://biolincc.nhlbi.nih.gov/home/. Other data access requests may be sent to Karen Mutalik, Framingham Heart Study Data Manager, at ktmutalik@ 123456bu.edu .

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