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      A publicly available virtual cohort of four-chamber heart meshes for cardiac electro-mechanics simulations

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          Abstract

          Computational models of the heart are increasingly being used in the development of devices, patient diagnosis and therapy guidance. While software techniques have been developed for simulating single hearts, there remain significant challenges in simulating cohorts of virtual hearts from multiple patients. To facilitate the development of new simulation and model analysis techniques by groups without direct access to medical data, image analysis techniques and meshing tools, we have created the first publicly available virtual cohort of twenty-four four-chamber hearts. Our cohort was built from heart failure patients, age 67±14 years. We segmented four-chamber heart geometries from end-diastolic (ED) CT images and generated linear tetrahedral meshes with an average edge length of 1.1±0.2mm. Ventricular fibres were added in the ventricles with a rule-based method with an orientation of -60° and 80° at the epicardium and endocardium, respectively. We additionally refined the meshes to an average edge length of 0.39±0.10mm to show that all given meshes can be resampled to achieve an arbitrary desired resolution. We ran simulations for ventricular electrical activation and free mechanical contraction on all 1.1mm-resolution meshes to ensure that our meshes are suitable for electro-mechanical simulations. Simulations for electrical activation resulted in a total activation time of 149±16ms. Free mechanical contractions gave an average left ventricular (LV) and right ventricular (RV) ejection fraction (EF) of 35±1% and 30±2%, respectively, and a LV and RV stroke volume (SV) of 95±28mL and 65±11mL, respectively. By making the cohort publicly available, we hope to facilitate large cohort computational studies and to promote the development of cardiac computational electro-mechanics for clinical applications.

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          Left ventricular remodeling in heart failure: current concepts in clinical significance and assessment.

          Ventricular remodeling, first described in animal models of left ventricular (LV) stress and injury, occurs progressively in untreated patients after large myocardial infarction and in those with dilated forms of cardiomyopathy. The gross pathologic changes of increased LV volume and perturbation in the normal elliptical LV chamber configuration is driven, on a histologic level, by myocyte hypertrophy and apoptosis and by increased interstitial collagen. Each of the techniques used for tracking this process-echocardiography, radionuclide ventriculography, and cardiac magnetic resonance-carries advantages and disadvantages. Numerous investigations have demonstrated the value of LV volume measurement at a single time-point and over time in predicting clinical outcomes in patients with heart failure and in those after myocardial infarction. The structural pattern of LV remodeling and evidence of scarring on cardiac magnetic resonance have additional prognostic value. Beyond the impact of abnormal cardiac structure on cardiovascular events, the relationship between LV remodeling and clinical outcomes is likely linked through common local and systemic factors driving vascular as well as myocardial pathology. As demonstrated by a recent meta-analysis of heart failure trials, LV volume stands out among surrogate markers as strongly correlating with the impact of a particular drug or device therapy on patient survival. These findings substantiate the importance of ventricular remodeling as central in the pathophysiology of advancing heart failure and support the role of measures of LV remodeling in the clinical investigation of novel heart failure treatments. 2011 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.
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            Reference ranges for cardiac structure and function using cardiovascular magnetic resonance (CMR) in Caucasians from the UK Biobank population cohort

            Background Cardiovascular magnetic resonance (CMR) is the gold standard method for the assessment of cardiac structure and function. Reference ranges permit differentiation between normal and pathological states. To date, this study is the largest to provide CMR specific reference ranges for left ventricular, right ventricular, left atrial and right atrial structure and function derived from truly healthy Caucasian adults aged 45–74. Methods Five thousand sixty-five UK Biobank participants underwent CMR using steady-state free precession imaging at 1.5 Tesla. Manual analysis was performed for all four cardiac chambers. Participants with non-Caucasian ethnicity, known cardiovascular disease and other conditions known to affect cardiac chamber size and function were excluded. Remaining participants formed the healthy reference cohort; reference ranges were calculated and were stratified by gender and age (45–54, 55–64, 65–74). Results After applying exclusion criteria, 804 (16.2%) participants were available for analysis. Left ventricular (LV) volumes were larger in males compared to females for absolute and indexed values. With advancing age, LV volumes were mostly smaller in both sexes. LV ejection fraction was significantly greater in females compared to males (mean ± standard deviation [SD] of 61 ± 5% vs 58 ± 5%) and remained static with age for both genders. In older age groups, LV mass was lower in men, but remained virtually unchanged in women. LV mass was significantly higher in males compared to females (mean ± SD of 53 ± 9 g/m2 vs 42 ± 7 g/m2). Right ventricular (RV) volumes were significantly larger in males compared to females for absolute and indexed values and were smaller with advancing age. RV ejection fraction was higher with increasing age in females only. Left atrial (LA) maximal volume and stroke volume were significantly larger in males compared to females for absolute values but not for indexed values. LA ejection fraction was similar for both sexes. Right atrial (RA) maximal volume was significantly larger in males for both absolute and indexed values, while RA ejection fraction was significantly higher in females. Conclusions We describe age- and sex-specific reference ranges for the left ventricle, right ventricle and atria in the largest validated normal Caucasian population. Electronic supplementary material The online version of this article (doi:10.1186/s12968-017-0327-9) contains supplementary material, which is available to authorized users.
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              Randomized trial of cardiac resynchronization in mildly symptomatic heart failure patients and in asymptomatic patients with left ventricular dysfunction and previous heart failure symptoms.

              We sought to determine the effects of cardiac resynchronization therapy (CRT) in New York Heart Association (NYHA) functional class II heart failure (HF) and NYHA functional class I (American College of Cardiology/American Heart Association stage C) patients with previous HF symptoms. Cardiac resynchronization therapy improves left ventricular (LV) structure and function and clinical outcomes in NYHA functional class III and IV HF with prolonged QRS. Six hundred ten patients with NYHA functional class I or II heart failure with a QRS > or =120 ms and a LV ejection fraction < or =40% received a CRT device (+/-defibrillator) and were randomly assigned to active CRT (CRT-ON; n = 419) or control (CRT-OFF; n = 191) for 12 months. The primary end point was the HF clinical composite response, which scores patients as improved, unchanged, or worsened. The prospectively powered secondary end point was LV end-systolic volume index. Hospitalization for worsening HF was evaluated in a prospective secondary analysis of health care use. The HF clinical composite response end point, which compared only the percent worsened, indicated 16% worsened in CRT-ON compared with 21% in CRT-OFF (p = 0.10). Patients assigned to CRT-ON experienced a greater improvement in LV end-systolic volume index (-18.4 +/- 29.5 ml/m2 vs. -1.3 +/- 23.4 ml/m2, p < 0.0001) and other measures of LV remodeling. Time-to-first HF hospitalization was significantly delayed in CRT-ON (hazard ratio: 0.47, p = 0.03). The REVERSE (REsynchronization reVErses Remodeling in Systolic left vEntricular dysfunction) trial demonstrates that CRT, in combination with optimal medical therapy (+/-defibrillator), reduces the risk for heart failure hospitalization and improves ventricular structure and function in NYHA functional class II and NYHA functional class I (American College of Cardiology/American Heart Association stage C) patients with previous HF symptoms. (REsynchronization reVErses Remodeling in Systolic Left vEntricular Dysfunction [REVERSE]; NCT00271154).
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                Author and article information

                Contributors
                Role: Data curationRole: Formal analysisRole: InvestigationRole: MethodologyRole: SoftwareRole: VisualizationRole: Writing – original draftRole: Writing – review & editing
                Role: MethodologyRole: SoftwareRole: Writing – review & editing
                Role: MethodologyRole: SoftwareRole: Writing – review & editing
                Role: MethodologyRole: Software
                Role: MethodologyRole: Software
                Role: MethodologyRole: Software
                Role: MethodologyRole: Software
                Role: MethodologyRole: Software
                Role: MethodologyRole: Software
                Role: Data curation
                Role: Data curation
                Role: Data curation
                Role: Data curation
                Role: ConceptualizationRole: SupervisionRole: Writing – review & editing
                Role: MethodologyRole: SoftwareRole: SupervisionRole: Writing – review & editing
                Role: ConceptualizationRole: Funding acquisitionRole: MethodologyRole: Project administrationRole: 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
                2020
                26 June 2020
                : 15
                : 6
                : e0235145
                Affiliations
                [1 ] School of Biomedical Engineering and Imaging Sciences, King’s College London, London, City of London, United Kingdom
                [2 ] Institute of Biophysics, Medical University of Graz, Graz, Steiermark, Austria
                [3 ] IHU Liryc, Electrophysiology and Heart Modeling Institute, fondation Bordeaux Université, F-33600 Pessac- Bordeaux, France
                [4 ] University of Bordeaux, IMB, UMR 5251, F-33400 Talence, France
                [5 ] Guy’s and St Thomas’ NHS Foundation Trust, London, City of London, United Kingdom
                [6 ] NumeriCor GmbH, Graz, Austria
                Beijing University of Technology, CHINA
                Author notes

                Competing Interests: Miss Strocchi M. was supported by an unrestricted Abbott educational grant through the Centre for Doctoral Training in Medical Imaging at King’s College London. Abbott had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. Dr Neic A. is an employee for NumeriCor GmbH and assisted with meshing tools and simulation software development. This does not alter our adherence to PLOS ONE policies on sharing data and materials.

                Author information
                http://orcid.org/0000-0003-1312-251X
                http://orcid.org/0000-0002-4496-1933
                Article
                PONE-D-19-34424
                10.1371/journal.pone.0235145
                7319311
                32589679
                30f5bdfe-74a4-4301-8be8-cd4a7b8e75c6
                © 2020 Strocchi 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 January 2020
                : 9 June 2020
                Page count
                Figures: 8, Tables: 4, Pages: 26
                Funding
                Funded by: funder-id http://dx.doi.org/10.13039/501100000266, Engineering and Physical Sciences Research Council;
                Award ID: EP/M012492/1, NS/A000049/1, EP/L015226/1 and EP/P01268X/1
                Award Recipient :
                Funded by: funder-id http://dx.doi.org/10.13039/501100000274, British Heart Foundation;
                Award ID: PG/15/91/31812 and PG/13/37/30280
                Award Recipient :
                Funded by: Kings Health Partners London National Institute for Health Research (NIHR) Biomedical Research Centre
                Award Recipient :
                Funded by: funder-id http://dx.doi.org/10.13039/100010665, H2020 Marie Skłodowska-Curie Actions;
                Award ID: 750835
                Award Recipient :
                Funded by: Austrian Science Fund (FWF)
                Award ID: PI2760-B30
                Award Recipient :
                S. A. N. received support from the UK Engineering and Physical Sciences Research Council ( https://epsrc.ukri.org/), grant numbers: EP/M012492/1, NS/A000049/1, EP/L015226/1 and EP/P01268X/1; from the British Heart Foundation ( https://www.bhf.org.uk/), grant numbers: PG/15/91/31812 and PG/13/37/30280; from the Kings Health Partners London National Institute for Health Research (NIHR) Biomedical Research Centre ( http://www.guysandstthomasbrc.nihr.ac.uk/). C. M. A. received support from the Marie Sklodowska-Curie fellowship ( https://ec.europa.eu/research/mariecurieactions/), grant number 750835. G. P. received support from the Austrian Science Fund (FWF) ( https://fwf.ac.at/en/); grant number PI2760-B30. This work made use of ARCHER ( http://www.archer.ac.uk/), the UK national high-performance computing service located at the University of Edinburgh and funded by the Office of Science and Technology through Engineering and Physical Sciences Research Councils High End Computing Programme. Miss Strocchi M. was supported by an unrestricted Abbott educational grant through the Centre for Doctoral Training in Medical Imaging at King’s College London. Abbott had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. Dr Neic A. is an employee for NumeriCor GmbH and assisted with meshing tools and simulation software development. This does not alter our adherence to PLOS ONE policies on sharing data and materials.
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                The data are uploaded to Zenodo and publicly accessible via the following URL: https://doi.org/10.5281/zenodo.3890034.

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