Fluid-electro-mechanical model of the human heart for supercomputers

The heart is a complex system. From the transmembrane cell activity to the spatial organization in helicoidal fibers, it includes several spatial and temporal scales. The heart muscle is surrounded by two main tissues that modulate how it deforms: the pericardium and the blood. The former constrains the epicardial surface and the latter exerts a force in the endocardium. The main function of this peculiar muscle is to pump blood to the pulmonary and systemic circulations. In this way, solid dynamics of the heart is as important as the induced fluid dynamics. Despite the work done in computational research of multiphysics heart modelling, there is no reference of a tightly-coupled scheme that includes electrophysiology, solid and fluid mechanics in a whole human heart. In this work, we propose, develop and test a fluid-electro-mechanical model of the human heart. To start, the heartbeat phenomenon is disassembled in the different composing problems. The first building block is the electrical activity of the myocytes, that induces the mechanical deformation of the myocardium. The contraction of the muscle reduces the intracavitary space, that pushes out the contained blood. At the same time, the inertia, pressure and viscous stresses in this fluid exerts a force on the solid wall. In this way, we can understand the heart as a fluid-electro-mechanical problem. All the models are implemented in Alya, the Barcelona Supercomputing Center simulation software. A multi-code approach is used, splitting the problem in a solid and a fluid domain. In the former, electrophysiology coupled with solid mechanics are solved. In the later, fluid dynamics in an arbitrary Lagrangian-Eulerian domain are computed. The equations are spatially discretized using the finite element method and temporally discretized using finite differences. Facilitated by the multi-code approach, a novel high performance quasi-Newton method is developed to deal with the intrinsic issues of fluid-structure interaction problems in iomechanics. All the schemes are optimized to run in massively parallel computers. A wide range of experiments are shown to validate, test and tune the numerical model. The different hypothesis proposed — as the critical effect of the atrium or the presence of pericardium — are also tested in these experiments. Finally, a normal heartbeat is simulated and deeply analyzed. This healthy computational heart is first diseased with a left bundle branch block. After this, its function is restored simulating a cardiac resynchronization therapy. Then, a third grade atrioventricular block is simulated in the healthy heart. In this case, the pathologic model is treated with a minimally invasive leadless intracardiac pacemaker. This requires to include the device in the geometrical description of the problem, solve the structural problem with the tissue, and the fluid-structure interaction problem with the blood. As final experiment, we test the parallel performance of the coupled solver. In the cases mentioned above, the results are qualitatively compared against experimental measurements, when possible. Finally, a first glance in a coupled fluid-electro-mechanical cardiovascular system is shown. This model is build adding a one dimensional model of the arterial network created by the Laboratório Nacional de Computação Científica in Petropolis, Brasil. Despite the artificial geometries used, the outflow curves are comparable with physiological observations. The model presented in this thesis is a step towards the virtual human heart. In a near future computational models like the presented in this thesis will change how pathologies are understood and treated, and the way biomedical devices are designed.El corazón es un sistema complejo. Desde la actividad celular hasta la organización espacial en fibras helicoidales, incluye gran cantidad de escalas espaciales y temporales. El corazón está rodeado principalmente por dos tejidos que modulan su deformación: el pericardio y la sangre. El primero restringe el movimiento del epicardio, mientras el segundo ejerce fuerza sobre el endocardio. La función principal de este músculo es bombear sangre a la circulación sistémica y a la pulmonar. Así, la deformación del miocardio es tan importante como la fluidodinámica inducida. Al día de hoy, solo se han propuesto modelos parciales del corazón. Ninguno de los modelos publicados resuelve electrofisiología, mecánica del sólido, y dinámica de fluidos en una geometría completa del corazón. En esta tesis, proponemos, desarrollamos y probamos un modelo fluido -electro -mecánico del corazón. Primero, el problema del latido cardíaco es descompuesto en los distintos subproblemas. El primer bloque componente es la actividad eléctrica de los miocitos, que inducen la deformación mecánica del miocardio. La contratación de este músculo, reduce el espacio intracavitario, que empuja la sangre contenida. Al mismo tiempo, la inercia, presión y fuerzas viscosas del fluido inducen una presión sobre la pared del sólido. De esta manera, podemos entender el latido cardíaco como un problema fluido-electro-mecánico. Los modelos son implementados en Alya, el software de simulación del Barcelona Supercomputing Center. Se utiliza un diseño multi-código, separando el problema según el dominio en sólido y fluido. En el primero, se resuelve electrofisiología acoplado con mecánica del sólido. En el segundo, fluido dinámica en un dominio arbitrario Lagrangiano-Euleriano. Las ecuaciones son discretizadas espacial y temporalmente utilizando elementos finitos y diferencias finitas respectivamente. Facilitado por el diseño multi-codigo, se desarrolló un novedoso método quasi-Newton de alta performance, pensado específicamente para lidiar con los problemas intrínsecos de interacción fluido-estructura en biomecánica. Todos los esquemas fueron optimizados para correr en ordenadores masivamente paralelos.Se presenta un amplio espectro de experimentos con el fin de validar, probar y ajustar el modelo numérico. Las diferentes hipótesis propuestas tales como el efecto producido por la presencia de las aurículas o el pericardio son también demostradas en estos experimentos. Finalmente un latido normal es simulado y sus resultados son analizados con profundidad. El corazón computacional sano es, primeramente enfermado de un bloqueo de rama izquierda. Posteriormente se restaura la función normal mediante la terapia de resincronización cardíaca. Luego se afecta al corazón de un bloqueo atrioventricular de tercer grado. Esta patología es tratada mediante la implantación de un marcapasos intracardíaco. Para esto, se requiere incluir el dispositivo en la descripción geométrica, resolver el problema estructural con el tejido y la interacción fluido-estructura con la sangre. Como experimento numérico final, se prueba el desempeño paralelo del modelo acoplado.Finalmente, se muestran resultados preliminares para un modelo fluido-electro-mecánico del sistema cardiovascular. Este modelo se construye agregando un modelo unidimensional del árbol arterial. A pesar de las geometrías artificiales usadas, la curva de flujo en la raíz aórtica es comparable con observaciones experimentales. El modelo presentado aquí representa un avance hacia el humano virtual. En un futuro, modelos similares, cambiarán la forma en la que se entienden y tratan las enfermedades y la forma en la que los dispositivos biomédicos son diseñados.Postprint (published version

VIDEO KINEMATIC EVALUATION OF THE HEART (VI.KI.E.): AN IDEA, A PROJECT, A REALITY

Introduction: The technological development of the last 20 years pledges the intensity of efforts for implementing novel imaging contactless modalities that accelerate the translation from the research bench to the patient bedside, especially in the cardiac field. In this work, a novel intraoperative cardiac imaging approach, named Video Kinematic Evaluation (Vi.Ki.E.), is presented and explained in detail. This technology is able to monitor, contactless, the cardiac mechanics and deformation in-situ during heart surgery. Cardiac kinematics have been deeply evaluated ranging from the experimental animal approach to the human myocardial pathologies in both left and right ventricles. Methods: Vi.Ki.E. can be defined \u201cas simple as innovative\u201d. It only consists of a high-speed camera placed upon an exposed beating heart in-situ to record cardiac cycles. Afterwards a tracker software is used on the recorded video to follow the epicardial tissue movements. This tracker provides information about trajectories of the epicardium and, thanks to a custom-made algorithm, the technology supplies heart mechanical information such as: Force of contraction or cardiac fatigue, Energy expenditure, Contraction velocity, displacement of the marker and epicardial torsion. This approach has been tested on 21 rats (9 ischemia/reperfusion and/or for validation, 12 for the gender difference study) and on 37 patients who underwent different surgery between 2015 and 2019. In detail 10 patients underwent Coronary Artery Bypass Grafting, 12 underwent Valve Replacement after Tetralogy of Fallot correction surgery, 6 implanted a Left Ventricular Assist Device (1 is moved in the case study section), 6 patients with Hypoplastic Heart Syndrome underwent GLENN or FONTAN surgery, 2 patients underwent Heart Transplantation and finally 1 patient underwent double valve replacement (this patient is moved into case study section). Results: The patients\u2019 results demonstrated that the Vi.Ki.E. technology was able to discriminate, with statistic potency, the kinematic differences before and after the surgery in real-time, suggesting possible clinical implications in the treatment of the patients before the chest closure and/or in the intensive care unit. As it concerns the experimental animals, the results are the basics of the validation technology. Some of them were used as accepted model in comparison with the Vi.Ki.E. results on patients. Conclusions: In conclusion, this study has shown that Vi.Ki.E. is a safe and contactless technology with promising possible clinical application. The ease in the evaluation and the algorithm-based approach makes Video Kinematic Evaluation a widespread technique from cellular level to human cases covering the entire experimental field with in-vivo evaluation and possibly Langendorff/Working Heart approaches

VIDEO KINEMATIC EVALUATION OF THE HEART (VI.KI.E.): AN IDEA, A PROJECT, A REALITY

Introduction: The technological development of the last 20 years pledges the intensity of efforts for implementing novel imaging contactless modalities that accelerate the translation from the research bench to the patient bedside, especially in the cardiac field. In this work, a novel intraoperative cardiac imaging approach, named Video Kinematic Evaluation (Vi.Ki.E.), is presented and explained in detail. This technology is able to monitor, contactless, the cardiac mechanics and deformation in-situ during heart surgery. Cardiac kinematics have been deeply evaluated ranging from the experimental animal approach to the human myocardial pathologies in both left and right ventricles. Methods: Vi.Ki.E. can be defined \u201cas simple as innovative\u201d. It only consists of a high-speed camera placed upon an exposed beating heart in-situ to record cardiac cycles. Afterwards a tracker software is used on the recorded video to follow the epicardial tissue movements. This tracker provides information about trajectories of the epicardium and, thanks to a custom-made algorithm, the technology supplies heart mechanical information such as: Force of contraction or cardiac fatigue, Energy expenditure, Contraction velocity, displacement of the marker and epicardial torsion. This approach has been tested on 21 rats (9 ischemia/reperfusion and/or for validation, 12 for the gender difference study) and on 37 patients who underwent different surgery between 2015 and 2019. In detail 10 patients underwent Coronary Artery Bypass Grafting, 12 underwent Valve Replacement after Tetralogy of Fallot correction surgery, 6 implanted a Left Ventricular Assist Device (1 is moved in the case study section), 6 patients with Hypoplastic Heart Syndrome underwent GLENN or FONTAN surgery, 2 patients underwent Heart Transplantation and finally 1 patient underwent double valve replacement (this patient is moved into case study section). Results: The patients\u2019 results demonstrated that the Vi.Ki.E. technology was able to discriminate, with statistic potency, the kinematic differences before and after the surgery in real-time, suggesting possible clinical implications in the treatment of the patients before the chest closure and/or in the intensive care unit. As it concerns the experimental animals, the results are the basics of the validation technology. Some of them were used as accepted model in comparison with the Vi.Ki.E. results on patients. Conclusions: In conclusion, this study has shown that Vi.Ki.E. is a safe and contactless technology with promising possible clinical application. The ease in the evaluation and the algorithm-based approach makes Video Kinematic Evaluation a widespread technique from cellular level to human cases covering the entire experimental field with in-vivo evaluation and possibly Langendorff/Working Heart approaches

Fluid-electro-mechanical model of the human heart for supercomputers

The heart is a complex system. From the transmembrane cell activity to the spatial organization in helicoidal fibers, it includes several spatial and temporal scales. The heart muscle is surrounded by two main tissues that modulate how it deforms: the pericardium and the blood. The former constrains the epicardial surface and the latter exerts a force in the endocardium. The main function of this peculiar muscle is to pump blood to the pulmonary and systemic circulations. In this way, solid dynamics of the heart is as important as the induced fluid dynamics. Despite the work done in computational research of multiphysics heart modelling, there is no reference of a tightly-coupled scheme that includes electrophysiology, solid and fluid mechanics in a whole human heart. In this work, we propose, develop and test a fluid-electro-mechanical model of the human heart. To start, the heartbeat phenomenon is disassembled in the different composing problems. The first building block is the electrical activity of the myocytes, that induces the mechanical deformation of the myocardium. The contraction of the muscle reduces the intracavitary space, that pushes out the contained blood. At the same time, the inertia, pressure and viscous stresses in this fluid exerts a force on the solid wall. In this way, we can understand the heart as a fluid-electro-mechanical problem. All the models are implemented in Alya, the Barcelona Supercomputing Center simulation software. A multi-code approach is used, splitting the problem in a solid and a fluid domain. In the former, electrophysiology coupled with solid mechanics are solved. In the later, fluid dynamics in an arbitrary Lagrangian-Eulerian domain are computed. The equations are spatially discretized using the finite element method and temporally discretized using finite differences. Facilitated by the multi-code approach, a novel high performance quasi-Newton method is developed to deal with the intrinsic issues of fluid-structure interaction problems in iomechanics. All the schemes are optimized to run in massively parallel computers. A wide range of experiments are shown to validate, test and tune the numerical model. The different hypothesis proposed — as the critical effect of the atrium or the presence of pericardium — are also tested in these experiments. Finally, a normal heartbeat is simulated and deeply analyzed. This healthy computational heart is first diseased with a left bundle branch block. After this, its function is restored simulating a cardiac resynchronization therapy. Then, a third grade atrioventricular block is simulated in the healthy heart. In this case, the pathologic model is treated with a minimally invasive leadless intracardiac pacemaker. This requires to include the device in the geometrical description of the problem, solve the structural problem with the tissue, and the fluid-structure interaction problem with the blood. As final experiment, we test the parallel performance of the coupled solver. In the cases mentioned above, the results are qualitatively compared against experimental measurements, when possible. Finally, a first glance in a coupled fluid-electro-mechanical cardiovascular system is shown. This model is build adding a one dimensional model of the arterial network created by the Laboratório Nacional de Computação Científica in Petropolis, Brasil. Despite the artificial geometries used, the outflow curves are comparable with physiological observations. The model presented in this thesis is a step towards the virtual human heart. In a near future computational models like the presented in this thesis will change how pathologies are understood and treated, and the way biomedical devices are designed.El corazón es un sistema complejo. Desde la actividad celular hasta la organización espacial en fibras helicoidales, incluye gran cantidad de escalas espaciales y temporales. El corazón está rodeado principalmente por dos tejidos que modulan su deformación: el pericardio y la sangre. El primero restringe el movimiento del epicardio, mientras el segundo ejerce fuerza sobre el endocardio. La función principal de este músculo es bombear sangre a la circulación sistémica y a la pulmonar. Así, la deformación del miocardio es tan importante como la fluidodinámica inducida. Al día de hoy, solo se han propuesto modelos parciales del corazón. Ninguno de los modelos publicados resuelve electrofisiología, mecánica del sólido, y dinámica de fluidos en una geometría completa del corazón. En esta tesis, proponemos, desarrollamos y probamos un modelo fluido -electro -mecánico del corazón. Primero, el problema del latido cardíaco es descompuesto en los distintos subproblemas. El primer bloque componente es la actividad eléctrica de los miocitos, que inducen la deformación mecánica del miocardio. La contratación de este músculo, reduce el espacio intracavitario, que empuja la sangre contenida. Al mismo tiempo, la inercia, presión y fuerzas viscosas del fluido inducen una presión sobre la pared del sólido. De esta manera, podemos entender el latido cardíaco como un problema fluido-electro-mecánico. Los modelos son implementados en Alya, el software de simulación del Barcelona Supercomputing Center. Se utiliza un diseño multi-código, separando el problema según el dominio en sólido y fluido. En el primero, se resuelve electrofisiología acoplado con mecánica del sólido. En el segundo, fluido dinámica en un dominio arbitrario Lagrangiano-Euleriano. Las ecuaciones son discretizadas espacial y temporalmente utilizando elementos finitos y diferencias finitas respectivamente. Facilitado por el diseño multi-codigo, se desarrolló un novedoso método quasi-Newton de alta performance, pensado específicamente para lidiar con los problemas intrínsecos de interacción fluido-estructura en biomecánica. Todos los esquemas fueron optimizados para correr en ordenadores masivamente paralelos.Se presenta un amplio espectro de experimentos con el fin de validar, probar y ajustar el modelo numérico. Las diferentes hipótesis propuestas tales como el efecto producido por la presencia de las aurículas o el pericardio son también demostradas en estos experimentos. Finalmente un latido normal es simulado y sus resultados son analizados con profundidad. El corazón computacional sano es, primeramente enfermado de un bloqueo de rama izquierda. Posteriormente se restaura la función normal mediante la terapia de resincronización cardíaca. Luego se afecta al corazón de un bloqueo atrioventricular de tercer grado. Esta patología es tratada mediante la implantación de un marcapasos intracardíaco. Para esto, se requiere incluir el dispositivo en la descripción geométrica, resolver el problema estructural con el tejido y la interacción fluido-estructura con la sangre. Como experimento numérico final, se prueba el desempeño paralelo del modelo acoplado.Finalmente, se muestran resultados preliminares para un modelo fluido-electro-mecánico del sistema cardiovascular. Este modelo se construye agregando un modelo unidimensional del árbol arterial. A pesar de las geometrías artificiales usadas, la curva de flujo en la raíz aórtica es comparable con observaciones experimentales. El modelo presentado aquí representa un avance hacia el humano virtual. En un futuro, modelos similares, cambiarán la forma en la que se entienden y tratan las enfermedades y la forma en la que los dispositivos biomédicos son diseñados

Aerospace medicine and biology: A continuing bibliography with indexes (supplement 297)

This bibliography lists 89 reports, articles and other documents introduced into the NASA scientific and technical information system in April, 1987

The role of mechanical forces in cardiomyocyte differentiation in 3D culture

Heart disease is the leading cause of death in many developing and industrialized countries. The loss of cardiomyocyte (CM) proliferation in the post-natal myocardium is the major barrier to myocardial regeneration, which leads to a loss of functional myocytes and thus contractile function after injury. While significant advances in cardiac tissue engineering as an alternative strategy for treatment have been made in the recent years, the application for repair of the injured myocardium remains to be realized. However, tissue engineering as an in vitro model system for characterizing functional properties of cardiac tissue can be used as a powerful tool now. The overall goal of this doctoral thesis was to determine the role of mechanical strain on CM differentiation within a 3D engineered tissue to use as a system for evaluation of strategies for enhancing directed CM differentiation and tissue contractile properties. Substantial progress towards this goal was made by a combination of testing new strategies for monitoring differential CM differentiation and contractile function, such as using MDSCs in a 3D collagen gel bioreactor to induce CM differentiation and applying mechanical strain to determine the responsive cell type, and by developing new tools and methods for characterizing CM differentiation and cell morphology changes. Our in vitro engineered cardiac tissue from fetal/developing native cardiac cells maintained CM proliferative activity and contractile properties similar to the native myocardium which increased in response to mechanical stretch. The implanted graft maintained CM proliferative activity in vivo, survived as a donor myocardial tissue, and contributed to the cardiac functional recovery of injured myocardium better than a graft with post-natal cardiac cells. Skeletal muscle derived stem cell (MDSC) aggregate formation and 3D collagen gel bioreactor (3DGB) culture (MDSC-3DGB) triggered differentiation of cells with an immature functioning CM phenotype in vitro. In addition, mechanical strain directed cell morphology changes were significant factors in directing CM differentiation from MDSCs within MDSC-3DGB. In conclusion, our 3D collagen gel bioreactor culture, with capabilities for spatial and temporal monitoring, represents a powerful model for elucidating the role of specific environmental factors and their underlying mechanisms on directed cell proliferation and differentiation

Development of a prosthetic heart valve with inbuilt sensing technology, to aid in continuous monitoring of function under various stenotic conditions

In spite of technological advances in the design of prosthetic heart valves, they are still often subject to complications after implantation. One of the common complications is valve stenosis, which involves the obstruction of the valve orifice caused by biological processes. The greatest challenge in diagnosing the development of valve failure and complications is related to the fact that the valve is implanted and isolated. To continuously monitor the state of the valve and its performance would be of great benefit but practically can only be achieved by instrumenting the implanted valve. In this thesis, we explore the development of a prosthetic valve with inbuilt sensing technology to aid in continuous monitoring of valve function under various stenotic conditions. 22mm polyurethane valves were designed via dipcoating. A custom made mock circulatory system was designed and hydrodynamic testing of the polyurethane valves under different flow rates were performed with Effective orifice area (EOA) and Transvalvular Pressure Gradient (TVPG) being the parameters of interest. Valves were subjected to varying levels of obstruction to investigate the effect obstruction has on the pressure gradient across the valves. Similar tests were performed on a Carpentier Edwards SAV 2650 model bioprosthetic valve for comparison. Polyurethane valves were then instrumented with strain gauges to measure peak to peak strain difference, in response to varying levels of obstructions. All the polyurethane valves exhibited good hydrodynamic performance with EOA (>1cm2) under baseline physiological conditions. It was also discovered that pressure difference across the valves was directly proportional to the flow rate. The pressure difference also demonstrated a slow increase during the initial stages of simulated stenosis and a sudden increase as the obstruction became severe. This provides further evidence to support the ideal that stenosis is a slow progressive disease which may not present symptoms until severe. The peak to peak strain differences also tend to decrease as the severity of the obstruction was increased. The peak to peak strain difference is indicative of the pressures within the valve (intravalvular pressure). The results suggest that directly monitoring the pressures within the valve could be a useful diagnostic tool for detecting valve stenosis. Future works involves miniaturisation of the sensors and also the incorporation of telemetry into the sensor design.In spite of technological advances in the design of prosthetic heart valves, they are still often subject to complications after implantation. One of the common complications is valve stenosis, which involves the obstruction of the valve orifice caused by biological processes. The greatest challenge in diagnosing the development of valve failure and complications is related to the fact that the valve is implanted and isolated. To continuously monitor the state of the valve and its performance would be of great benefit but practically can only be achieved by instrumenting the implanted valve. In this thesis, we explore the development of a prosthetic valve with inbuilt sensing technology to aid in continuous monitoring of valve function under various stenotic conditions. 22mm polyurethane valves were designed via dipcoating. A custom made mock circulatory system was designed and hydrodynamic testing of the polyurethane valves under different flow rates were performed with Effective orifice area (EOA) and Transvalvular Pressure Gradient (TVPG) being the parameters of interest. Valves were subjected to varying levels of obstruction to investigate the effect obstruction has on the pressure gradient across the valves. Similar tests were performed on a Carpentier Edwards SAV 2650 model bioprosthetic valve for comparison. Polyurethane valves were then instrumented with strain gauges to measure peak to peak strain difference, in response to varying levels of obstructions. All the polyurethane valves exhibited good hydrodynamic performance with EOA (>1cm2) under baseline physiological conditions. It was also discovered that pressure difference across the valves was directly proportional to the flow rate. The pressure difference also demonstrated a slow increase during the initial stages of simulated stenosis and a sudden increase as the obstruction became severe. This provides further evidence to support the ideal that stenosis is a slow progressive disease which may not present symptoms until severe. The peak to peak strain differences also tend to decrease as the severity of the obstruction was increased. The peak to peak strain difference is indicative of the pressures within the valve (intravalvular pressure). The results suggest that directly monitoring the pressures within the valve could be a useful diagnostic tool for detecting valve stenosis. Future works involves miniaturisation of the sensors and also the incorporation of telemetry into the sensor design

MODELING AND ANALYSIS OF INTERACTIONS BETWEEN A PULSATILE PNEUMATIC VENTRICULAR ASSIST DEVICE AND THE LEFT VENTRICLE

The use of a ventricular assist device (VAD) is a promising option for the treatment of end-stage heart failure. In many cases VADs provide not only temporary support, but contribute to the recovery of the native ventricle. Many studies have reported incidences where the native ventricle has recovered function, leading to device explantation and eliminating the need for heart transplantation. Despite strong interest in the subject for many years, the determinants of the recovery process are poorly understood and number of patients successfully weaned from chronic support remains low.A mathematical model was developed to gain an understanding of the complex mechanical interactions between a pneumatic, pulsatile VAD and the left ventricle. The VAD model was verified in-vitro using a mock circulatory loop. Over a wide range of experimental conditions, it correctly described observed dynamic behaviors and was accurate in predicting both VAD stroke volume and fill-to-empty rate within 6% error. This validated VAD model was coupled to a simple, lumped parameter cardiovascular model. The coupled model qualitatively reproduced the temporal patterns of various hemodynamic variables observed in clinical data. A concept of VAD characteristic frequency (fc) was developed to facilitate the analysis of VAD-ventricle synchrony. Characteristic frequency, defined as VAD rate in the absence of ventricular contraction, was essentially independent of cardiovascular parameters. For a given set of VAD parameters, synchrony was found to occur over a range of native heart rates. While the lower bound was determined by fc alone, the upper bound was a function of various cardiovascular parameters (e.g., left ventricular contractility, EMAX and systemic vascular resistance, SVR). In the case of synchronous behavior, the VAD and native heart have matched rates and counter-pulse, resulting in reduced ventricular loading. A decrease in EMAX or an increase in SVR increases asynchrony, resulting in frequent occurrences of co-pulsed beats (i.e., high ventricular loading). In conclusion, we found that VAD-ventricle synchrony is determined by a complex interaction between VAD and cardiovascular parameters. Our model-based analysis of VAD-ventricle interaction may be useful for optimizing the VAD operation, characterizing native ventricular contractility, and better understanding of the recovery process