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      Towards Personalized Cardiology: Multi-Scale Modeling of the Failing Heart

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          Abstract

          Background

          Despite modern pharmacotherapy and advanced implantable cardiac devices, overall prognosis and quality of life of HF patients remain poor. This is in part due to insufficient patient stratification and lack of individualized therapy planning, resulting in less effective treatments and a significant number of non-responders.

          Methods and Results

          State-of-the-art clinical phenotyping was acquired, including magnetic resonance imaging (MRI) and biomarker assessment. An individualized, multi-scale model of heart function covering cardiac anatomy, electrophysiology, biomechanics and hemodynamics was estimated using a robust framework. The model was computed on n=46 HF patients, showing for the first time that advanced multi-scale models can be fitted consistently on large cohorts. Novel multi-scale parameters derived from the model of all cases were analyzed and compared against clinical parameters, cardiac imaging, lab tests and survival scores to evaluate the explicative power of the model and its potential for better patient stratification. Model validation was pursued by comparing clinical parameters that were not used in the fitting process against model parameters.

          Conclusion

          This paper illustrates how advanced multi-scale models can complement cardiovascular imaging and how they could be applied in patient care. Based on obtained results, it becomes conceivable that, after thorough validation, such heart failure models could be applied for patient management and therapy planning in the future, as we illustrate in one patient of our cohort who received CRT-D implantation.

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          Most cited references28

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          ESC guidelines for the diagnosis and treatment of acute and chronic heart failure 2012: The Task Force for the Diagnosis and Treatment of Acute and Chronic Heart Failure 2012 of the European Society of Cardiology. Developed in collaboration with the Heart Failure Association (HFA) of the ESC.

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            Whole-heart modeling: applications to cardiac electrophysiology and electromechanics.

            Recent developments in cardiac simulation have rendered the heart the most highly integrated example of a virtual organ. We are on the brink of a revolution in cardiac research, one in which computational modeling of proteins, cells, tissues, and the organ permit linking genomic and proteomic information to the integrated organ behavior, in the quest for a quantitative understanding of the functioning of the heart in health and disease. The goal of this review is to assess the existing state-of-the-art in whole-heart modeling and the plethora of its applications in cardiac research. General whole-heart modeling approaches are presented, and the applications of whole-heart models in cardiac electrophysiology and electromechanics research are reviewed. The article showcases the contributions that whole-heart modeling and simulation have made to our understanding of the functioning of the heart. A summary of the future developments envisioned for the field of cardiac simulation and modeling is also presented. Biophysically based computational modeling of the heart, applied to human heart physiology and the diagnosis and treatment of cardiac disease, has the potential to dramatically change 21st century cardiac research and the field of cardiology.
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              Coupling of a 3D finite element model of cardiac ventricular mechanics to lumped systems models of the systemic and pulmonic circulation.

              In this study we present a novel, robust method to couple finite element (FE) models of cardiac mechanics to systems models of the circulation (CIRC), independent of cardiac phase. For each time step through a cardiac cycle, left and right ventricular pressures were calculated using ventricular compliances from the FE and CIRC models. These pressures served as boundary conditions in the FE and CIRC models. In succeeding steps, pressures were updated to minimize cavity volume error (FE minus CIRC volume) using Newton iterations. Coupling was achieved when a predefined criterion for the volume error was satisfied. Initial conditions for the multi-scale model were obtained by replacing the FE model with a varying elastance model, which takes into account direct ventricular interactions. Applying the coupling, a novel multi-scale model of the canine cardiovascular system was developed. Global hemodynamics and regional mechanics were calculated for multiple beats in two separate simulations with a left ventricular ischemic region and pulmonary artery constriction, respectively. After the interventions, global hemodynamics changed due to direct and indirect ventricular interactions, in agreement with previously published experimental results. The coupling method allows for simulations of multiple cardiac cycles for normal and pathophysiology, encompassing levels from cell to system.
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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
                31 July 2015
                2015
                : 10
                : 7
                : e0134869
                Affiliations
                [1 ]Department of Medicine III, University of Heidelberg, Heidelberg, Germany
                [2 ]DZHK (German Centre for Cardiovascular Research), Heidelberg, Germany
                [3 ]Siemens Corporation, Corporate Technology, Imaging and Computer Vision, Princeton, New Jersey, United States of America
                [4 ]Siemens AG, Corporate Technology, Erlangen, Germany
                [5 ]Siemens Corporation, Corporate Technology, Sensor Technologies, Princeton, New Jersey, United States of America
                [6 ]Biomarker Discovery Center Heidelberg, Heidelberg, Germany
                [7 ]Department of Human Genetics, Saarland University, Homburg, Germany
                [8 ]Klaus Tschira Institute for Computational Cardiology, Heidelberg, Germany
                Medical University Innsbruck, AUSTRIA
                Author notes

                Competing Interests: This work was in part conducted within an industry supported project (Siemens AG, Siemens Research Project). TM, DN, BG, PS, AK, EQ, VK and DC are employed by Siemens. Following patents are to be declared 20150045644, System and Method for Estimating Artery Compliance and Resistance from 4D Cardiac Images and Pressure Measurements. 20130197884, Method and System for Advanced Measurements Computation and Therapy Planning from Medical Data and Images Using a Multi-Physics Fluid-Solid Heart Model. 20130197881, Method and System for Patient Specific Planning of Cardiac Therapies on Preoperative Clinical Data and Medical Images. 20120022843, Method and System for Comprehensive Patient-Specific Modeling of the Heart. Siemens has also have granted patents regarding the image segmentation algorithms used to estimate the cardiac geometry. All these patents are on the model and do not interfere with publishing this paper. This does not alter the authors' adherence to all the PLOS ONE policies on sharing data and materials, as detailed online in the guide for authors.

                Conceived and designed the experiments: EK TM FS-H. Performed the experiments: TM DN BG PS AK SB DM EZ. Analyzed the data: EK TM FS-H AA JH KSF MI AK. Contributed reagents/materials/analysis tools: HAK DC BM EW VK. Wrote the paper: EK FS-H HAK BM.

                Article
                PONE-D-15-06628
                10.1371/journal.pone.0134869
                4521877
                26230546
                6214613c-1848-4ebb-be77-a6a0ed772d80
                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
                : 14 February 2015
                : 14 July 2015
                Page count
                Figures: 5, Tables: 4, Pages: 18
                Funding
                This work has been supported by the DZHK (German Centre for Cardiovascular Research), by the BMBF (German Ministry of Education and Research), and by the European Union FP7 (BestAgeing, GA 306031). This work was in part conducted within an industry supported project (Siemens AG, Siemens Research Project). Siemens provided support in the form of salaries for authors TM, DN, BG, PS, AK, EW, VK and DC, but did not have any additional role in the study design, data collection and analysis, decision to publish, or preparation of the manuscript. The specific roles of these authors are articulated in the ‘author contributions’ section.
                Categories
                Research Article
                Custom metadata
                All relevant data are within the paper and its Supporting Information files.

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