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      Ventricle stress/strain comparisons between Tetralogy of Fallot patients and healthy using models with different zero-load diastole and systole morphologies

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          Abstract

          Patient-specific in vivo ventricle mechanical wall stress and strain conditions are important for cardiovascular investigations and should be calculated from correct zero-load ventricle morphologies. Cardiac magnetic resonance (CMR) data were obtained from 6 healthy volunteers and 12 Tetralogy of Fallot (TOF) patients with consent obtained. 3D patient-specific CMR-based ventricle models with different zero-load diastole and systole geometries due to myocardium contraction and relaxation were constructed to qualify right ventricle (RV) diastole and systole stress and strain values at begin-filling, end-filling, begin-ejection, and end-ejection, respectively. Our new models (called 2G models) can provide end-diastole and end-systole stress/strain values which models with one zero-load geometries (called 1G models) could not provide. 2G mean end-ejection stress value from the 18 participants was 321.4% higher than that from 1G models (p = 0.0002). 2G mean strain values was 230% higher than that of 1G models (p = 0.0002). TOF group (TG) end-ejection mean stress value was 105.4% higher than that of healthy group (HG) (17.54±7.42kPa vs. 8.54±0.92kPa, p = 0.0245). Worse outcome group (WG, n = 6) post pulmonary valve replacement (PVR) begin-ejection mean stress was 57.4% higher than that of better outcome group (BG, 86.94±26.29 vs. 52.93±22.86 kPa; p = 0.041). Among 7 selected parameters, End-filling stress was the best predictor to differentiate BG patients from WG patients with prediction accuracy = 0.8208 and area under receiver operating characteristic curve (AUC) value at 0.8135 (EE stress). Large scale studies are needed to further validate our findings.

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          Factors associated with impaired clinical status in long-term survivors of tetralogy of Fallot repair evaluated by magnetic resonance imaging.

          The purpose of this study was to identify independent factors associated with impaired clinical status in late survivors of tetralogy of Fallot (TOF) repair. Repair of TOF often results in chronic pulmonary regurgitation (PR) and right ventricular (RV) dilation, which have been linked to late morbidity and mortality. However, determinants of clinical status late after TOF repair have not been fully characterized. The clinical and laboratory data of 100 consecutive patients with repaired TOF (median 21 years after repair) who completed a cardiac magnetic resonance imaging protocol were analyzed. Impaired clinical status was defined as New York Heart Association (NYHA) functional class > or =III. Of the patients, 88 were in NYHA functional class I or II and 12 were in NYHA functional class III. The degree of PR and indexed RV end-diastolic volume were not associated with impaired clinical status. By multivariate analysis, a lower left ventricular (LV) ejection fraction (EF) (odds ratio [OR] = 3.88 for 10% decrease, p = 0.002) and older age at TOF repair (OR = 1.70 for 5-year increase, p = 0.013) were the strongest independent factors associated with impaired clinical status. Among RV variables, a lower RV EF was the strongest independent factors associated with poor clinical status (OR = 2.41 for 10% decrease, p = 0.01). The LV EF correlated with RV EF (r = 0.58, p < 0.001). Moderate or severe LV or RV systolic dysfunction, but not PR fraction or RV diastolic dimensions, is independently associated with impaired clinical status in long-term survivors of TOF repair. The close relationship between LV EF and RV EF suggests unfavorable ventricular-ventricular interaction.
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            Pulmonary valve replacement in adults late after repair of tetralogy of fallot: are we operating too late?

            The purpose of this study is to evaluate right ventricular (RV) volume and function after pulmonary valve replacement (PVR) and to address the issue of optimal surgical timing in these patients. Chronic pulmonary regurgitation (PR) following repair of tetralogy of Fallot (TOF) leads to RV dilation and an increased incidence of sudden cardiac death in adult patients. We studied 25 consecutive adult patients who underwent PVR for significant PR late after repair of TOF. Radionuclide angiography was performed in all at a mean of 8.2 months (+/- 8 months) before PVR and repeated at a mean of 28.0 months (+/- 22.8 months) after the operation. Right ventricular (RV) end-systolic volume (RVESV), RV end-diastolic volume (RVEDV) and RV ejection fraction (RVEF) were measured. Mean RVEDV, RVESV and RVEF remained unchanged after PVR (227.1 ml versus 214.9 ml, p = 0.74; 157.4 ml versus 155.4 ml, p = 0.94; 35.6% versus 34.7%, p = 0.78, respectively). Of the 10 patients with RVEF > or = 0.40 before PVR, 5 patients (50%) maintained a RVEF > or = 0.40 following PVR, whereas only 2 out of 15 patients (13%) with pre-operative values or = 0.40 postoperatively (p < 0.001). Right ventricular recovery following PVR for chronic significant pulmonary regurgitation after repair of TOF may be compromised in the adult population. In order to maintain adequate RV contractility, pulmonary valve implant in these patients should be considered before RV function deteriorates.
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              Biaxial mechanical properties of the natural and glutaraldehyde treated aortic valve cusp--Part I: Experimental results.

              To date, there are no constitutive models for either the natural or bioprosthetic aortic valve (AV), in part due to experimental complications related to the AV's small size and heterogeneous fibrous structure. In this study, we developed specialized biaxial testing techniques for the AV cusp, including a method to determine the local structure-strain relationship to assess the effects of boundary tethering forces. Natural and glutaraldehyde (GL) treated cusps were subjected to an extensive biaxial testing protocol in which the ratios of the axial tensions were held at constant values. Results indicated that the local fiber architecture clearly dominated cuspal deformation, and that the tethering effects at the specimen boundaries were negligible. Due to unique aspects of cuspal fiber architecture, the most uniform region of deformation was found at the lower portion as opposed to the center of the cuspal specimen. In general, the circumferential strains were much smaller than the radial strains, indicating a profound degree of mechanical anisotropy, and that natural cusps were significantly more extensible than the GL treated cusps. Strong mechanical coupling between biaxial stretch axes produced negative circumferential strains under equibiaxial tension. Further, the large radial strains observed could not be explained by uncrimping of the collagen fibers, but may be due to large rotations of the highly aligned, circumferential-oriented collagen fibers in the fibrosa. In conclusion, this study provides new insights into the AV cusp's structure-function relationship in addition to requisite data for constitutive modeling.
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                Author and article information

                Contributors
                Role: MethodologyRole: SoftwareRole: ValidationRole: Writing – original draft
                Role: Data curationRole: Funding acquisitionRole: InvestigationRole: MethodologyRole: Project administrationRole: SoftwareRole: ValidationRole: Writing – review & editing
                Role: Data curationRole: InvestigationRole: Validation
                Role: MethodologyRole: SoftwareRole: Validation
                Role: MethodologyRole: Validation
                Role: Data curationRole: Funding acquisitionRole: Investigation
                Role: MethodologyRole: Software
                Role: MethodologyRole: Validation
                Role: Data curationRole: Funding acquisition
                Role: Editor
                Journal
                PLoS One
                PLoS ONE
                plos
                plosone
                PLoS ONE
                Public Library of Science (San Francisco, CA USA )
                1932-6203
                14 August 2019
                2019
                : 14
                : 8
                : e0220328
                Affiliations
                [1 ] School of Biological Science & Medical Engineering, Southeast University, Nanjing, China
                [2 ] Mathematical Sciences Department, Worcester Polytechnic Institute, Worcester, MA, United States of America
                [3 ] Department of Cardiology, Boston Children's Hospital, Department of Pediatrics, Harvard Medical School, Boston, MA, United States of America
                [4 ] School of Mathematical Sciences, Xiamen University, Xiamen, Fujian, China
                [5 ] Department of Biomedical Engineering, Worcester Polytechnic Institute, Worcester, MA, United States of America
                [6 ] Department of Cardiac Surgery, Boston Children’s Hospital, Department of Surgery, Harvard Medical School, Boston, MA, United States of America
                Freeman Hospital, UNITED KINGDOM
                Author notes

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

                Author information
                http://orcid.org/0000-0002-6965-6417
                http://orcid.org/0000-0002-7149-5421
                Article
                PONE-D-19-05758
                10.1371/journal.pone.0220328
                6693773
                31412062
                7aa0399b-a484-411c-8936-419b009c6e1f
                © 2019 Yu 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
                : 27 February 2019
                : 12 July 2019
                Page count
                Figures: 5, Tables: 7, Pages: 19
                Funding
                Funded by: funder-id http://dx.doi.org/10.13039/501100001809, National Natural Science Foundation of China;
                Award ID: 11672001
                Award Recipient :
                Funded by: National Natural Science Foundation of China grants
                Award ID: 81571691
                Award Recipient :
                Funded by: Postgraduate Research&Practice Innovation Program of Jiangsu Province
                Award ID: KYCX19_0110
                Award Recipient :
                This research was supported during this study in part by National Sciences Foundation of China grants 11672001, 81571691(DT; Dalin Tang) and by the Postgraduate Research & Practice Innovation Program of Jiangsu Province (grant number KYCX19_0110 awarded to Dalin Tang). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.
                Categories
                Research Article
                Biology and Life Sciences
                Anatomy
                Cardiovascular Anatomy
                Heart
                Cardiac Ventricles
                Medicine and Health Sciences
                Anatomy
                Cardiovascular Anatomy
                Heart
                Cardiac Ventricles
                Medicine and Health Sciences
                Cardiology
                Diastole
                Medicine and Health Sciences
                Cardiology
                Systole
                Biology and Life Sciences
                Cell Biology
                Cellular Types
                Animal Cells
                Muscle Cells
                Myofibrils
                Sarcomeres
                Biology and Life Sciences
                Anatomy
                Biological Tissue
                Muscle Tissue
                Muscle Cells
                Myofibrils
                Sarcomeres
                Medicine and Health Sciences
                Anatomy
                Biological Tissue
                Muscle Tissue
                Muscle Cells
                Myofibrils
                Sarcomeres
                Biology and Life Sciences
                Anatomy
                Cardiovascular Anatomy
                Heart
                Myocardium
                Medicine and Health Sciences
                Anatomy
                Cardiovascular Anatomy
                Heart
                Myocardium
                Physical Sciences
                Physics
                Classical Mechanics
                Mechanical Stress
                Biology and Life Sciences
                Physiology
                Muscle Physiology
                Muscle Contraction
                Medicine and Health Sciences
                Physiology
                Muscle Physiology
                Muscle Contraction
                Medicine and Health Sciences
                Surgical and Invasive Medical Procedures
                Custom metadata
                The public sharing of the data underlying this study has been restricted out of consideration for patient privacy by the Boston Children’s Hospital Committee on Clinical Investigation. Data are therefore only available on request. Data access queries may by directed to Mr. Michael Malone, mmalone@ 123456wpi.edu , Computer Manager, Department of Mathematical Sciences, Worcester Polytechnic Institute, or the following authors: DT ( dtang@ 123456wpi.edu ), TG ( Tal.Geva@ 123456CARDIO.CHBOSTON.ORG ), RHR ( Rahul.Rathod@ 123456CARDIO.CHBOSTON.ORG ), and PJDN ( Pedro.DelNido@ 123456CARDIO.CHBOSTON.ORG ).

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