Controlling the flow balance: In vitro characterization of a pulsatile total artificial heart in preload and afterload sensitivity.

The objective of this study is to identify the preload and afterload sensitivity of the ReinHeart TAH 2.0. For adequate left-right flow balance, the concept of a reduced right stroke volume (by about 10%) and active adaption of the right diastole duration are evaluated concerning the controllability of the flow balance. This study used an active mock circulation loop to test a wide range of preload and afterload conditions. Preload sensitivity was tested at atrial pressures (APs) between 4 and 20 mm Hg. Left afterload was varied in a range of 60-140 mm Hg mean aortic pressure (MAP), right afterload was simulated between 15 and 40 mm Hg. Four scenarios were developed to verify that the flow difference fully covers the defined target range of 0-1.5 L/min. Although a positive correlation between inlet pressure and flow is identified for the right pump chamber, the left pump chamber already fills completely at an inlet pressure of 8-10 mm Hg. With increasing afterload, both the left and right flow decrease. A positive flow balance (left flow exceeds right flow) is achieved over the full range of tested afterloads. At high APs, the flow difference is limited to a maximum of 0.7 L/min. The controllability of flow balance was successfully evaluated in four scenarios, revealing that a positive flow difference can be achieved over the full range of MAPs. Under physiological test conditions, the linear relationship between flow and heart rate was confirmed, ensuring good controllability of the TAH.

Experimental investigation of right-left flow balance concepts for a total artificial heart.

A total artificial heart (TAH) must be designed to autonomously balance the flows of the systemic and pulmonary circulation to prevent potentially lethal lung damage. The flow difference between the systemic and pulmonary circulation is mainly caused by the bronchial (arteries) shunt flow and can change dynamically. The ReinHeart TAH consists of only one actuator that ejects blood alternately from the right and left pump chamber. This design entails a coupling of the right and left stroke and thus, complicates the independent adaptation of the right and left flow. In this experimental study on the ReinHeart TAH, four concepts to keep the flows well balanced were investigated using an active mock circulation loop for data acquisition. Three concepts are based on mechanical design changes (variation of pusher plate shape, flexible right pump chamber housing, and reduced right stroke volume) to achieve a static flow difference. In combination with these static concepts, a concept influencing the ratio of systole and diastole duration to respond to dynamic changes was studied. In total, four measurement series, each with 270 operating points, to investigate the influence of circulatory filling volume, heart rate, bronchial shunt flow, and lung resistance were recorded. In the course of this study, we introduce a concept deviation indicator, providing information about the efficiency of the concepts to balance the flows based on changes in lung's blood pressures. Furthermore, the distribution of the measured data was evaluated based on bubble plot visualizations. The investigated variation of the right pusher plate shape results in high lung pressures which will cause lethal lung damage. In comparison, a flexible right pump chamber housing shows lower lung pressures, but it still has the potential to damage the lungs. Reducing the stroke volume of the right pump chamber results in proper lung pressures. The flow balance can dynamically be influenced with a positive effect on the lung pressures by choosing a suitable systole-diastole-ratio. The results of this study suggest that an adequate right-left flow balance can be achieved by combining the mechanical concept of a reduced right stroke volume with an active control of the systole-diastole-ratio.

Prototype Development of an Implantable Compliance Chamber for a Total Artificial Heart.

At our institute a total artificial heart is being developed. It is directly actuated by a linear drive in between two ventricles, which comprise membranes to separate the drive and blood flow. A compliance chamber (CC) is needed to reduce pressure peaks in the ventricles and to increase the pump capacity. Therefore, the movement of the membrane is supported by applying a negative pressure to the air volume inside the drive unit. This study presents the development of the implantable CC which is connected to the drive unit of the total artificial hearts (TAH). The anatomical fit of the CC is optimized by analyzing CT data and adapting the outer shape to ensure a proper fit. The pressure peaks are reduced by the additional volume and the flexible membrane of the CC. The validation measurements of change in pressure peaks and flow are performed using the complete TAH system connected to a custom mock circulation loop. Using the CC, the pressure peaks could be damped below 5 mm Hg in the operational range. The flow output was increased by up to 14.8% on the systemic side and 18.2% on the pulmonary side. The described implantable device can be used for upcoming chronic animal trials.

Estimation of Filling and Afterload Conditions by Pump Intrinsic Parameters in a Pulsatile Total Artificial Heart.

A physiological control algorithm is being developed to ensure an optimal physiological interaction between the ReinHeart total artificial heart (TAH) and the circulatory system. A key factor for that is the long-term, accurate determination of the hemodynamic state of the cardiovascular system. This study presents a method to determine estimation models for predicting hemodynamic parameters (pump chamber filling and afterload) from both left and right cardiovascular circulations. The estimation models are based on linear regression models that correlate filling and afterload values with pump intrinsic parameters derived from measured values of motor current and piston position. Predictions for filling lie in average within 5% from actual values, predictions for systemic afterload (AoPmean , AoPsys ) and mean pulmonary afterload (PAPmean ) lie in average within 9% from actual values. Predictions for systolic pulmonary afterload (PAPsys ) present an average deviation of 14%. The estimation models show satisfactory prediction and confidence intervals and are thus suitable to estimate hemodynamic parameters. This method and derived estimation models are a valuable alternative to implanted sensors and are an essential step for the development of a physiological control algorithm for a fully implantable TAH.

Investigation of the Durability of a Diaphragm for a Total Artificial Heart.

One of the most critical components regarding the durability of the ReinHeart total artificial heart (TAH) is its biocompatible diaphragm, which separates the drive unit from the ventricles. Hence, a durability tester was designed to investigate its required 5-year lifetime. The aim of this study was to prove the validity of accelerated testing of the polyurethane diaphragm. The durability tester allows simultaneous testing of 12 diaphragms and mimics physiological conditions. To accelerate the time of testing, it operates with an increased speed at a frequency of 8 Hz. To prove the correctness of this acceleration, a servo-hydraulic testing machine was used to study the effect of different frequencies and their corresponding loads. Thereby the viscoelastic behavior of the polyurethane was investigated. Additionally, high-speed video measurements were performed. The force against frequency and the high-speed video measurements showed constant behavior. In the range of 1-10 Hz, the maximum resulting forces varied by 3%, and the diaphragm movement was identical. Frequencies below 10 Hz allow a valid statement of the diaphragm's mechanical durability. Viscoelasticity of the polyurethane in the considered frequency-range is negligible. The accelerated durability test is applicable to polyurethane diaphragms, and the results are applicable to TAH use. The reliability of the diaphragm for a lifetime of 5 years was found to be 80% with a confidence of 62%.

Mock circulation loop to investigate hemolysis in a pulsatile total artificial heart.

Hemocompatibility of blood pumps is a crucial parameter that has to be ensured prior to in vivo testing. In contrast to rotary blood pumps, a standard for testing a pulsatile total artificial heart (TAH) has not yet been established. Therefore, a new mock circulation loop was designed to investigate hemolysis in the left ventricle of the ReinHeart TAH. Its main features are a high hemocompatibility, physiological conditions, a low priming volume, and the conduction of blood through a closed tubing system. The mock circulation loop consists of a noninvasive pressure chamber, an aortic compliance chamber, and an atrium directly connected to the ventricle. As a control pump, the clinically approved Medos-HIA ventricular assist device (VAD) was used. The pumps were operated at 120 beats per minute with an aortic pressure of 120 to 80 mm Hg and a mean atrial pressure of 10 mm Hg, generating an output flow of about 5 L/min. Heparinized porcine blood was used. A series of six identical tests were performed. A test method was established that is comparable to ASTM F 1841, which is standard practice for the assessment of hemolysis in continuous-flow blood pumps. The average normalized index of hemolysis (NIH) values of the VAD and the ReinHeart TAH were 0.018 g/100 L and 0.03 g/100 L, respectively. The standard deviation of the NIH was 0.0033 for the VAD and 0.0034 for the TAH. Furthermore, a single test with a BPX-80 Bio-Pump was performed to verify that the hemolysis induced by the mock circulation loop was negligible. The performed tests showed a good reproducibility and statistical significance. The mock circulation loop and test protocol developed in this study are valid methods to investigate the hemolysis induced by a pulsatile blood pump.

Image based evaluation of mediastinal constraints for the development of a pulsatile total artificial heart.

BACKGROUND: Good anatomical compatibility is an important aspect in the development of cardiovascular implants. This work analyzes the interaction of the pump unit of an electrically driven pulsatile Total Artificial Heart (TAH) and the mediastinum. For an adequate compliance, both overall dimensions and alignment of inlets and outlets must be matched. METHODS: Cross-sectional medical image data of 27 individuals, including male and female patients suffering from end stage heart failure, was segmented and reconstructed to three dimensional (3D) surface models. Dimensions and orientations of relevant structures were identified and analyzed. The TAH surface model was virtually placed in orthotopic position and aligned with atrioventricular valves and big vessels. Additionally seven conventional cadaver studies were performed to validate different pump chamber designs based on virtual findings. Thereby 3D-coordinates were captured and introduced to the virtual environment to allow quantitative comparison between different individuals. RESULTS: Spatial parameters varied more in male patients with higher values if heart failure persists. Good correlation of the virtual analysis both to literature data and conventional cadaver studies could be shown. The full data of the 27 individuals as well as the summarized values found in literature are enclosed in the appendix. By superimposing the TAH-volume model to the anatomy, various misalignments were found and the TAH-design was adjusted. CONCLUSIONS: Virtual fitting allows implant design adjustments in realistic anatomy which has not been influenced by thoracotomy. Higher numbers of relevant individuals can be reasonably investigated in the virtual environment and quantitatively correlated. Using this approach, conventional cadaver studies can be significantly reduced but not obviated, due to the unavailable haptic feedback and immobility of potentially compressed structures.

Fluid-structure interaction modelling of a positive-displacement Total Artificial Heart.

For those suffering from end-stage biventricular heart failure, and where a heart transplantation is not a viable option, a Total Artificial Heart (TAH) can be used as a bridge to transplant device. The Realheart TAH is a four-chamber artificial heart that uses a positive-displacement pumping technique mimicking the native heart to produce pulsatile flow governed by a pair of bileaflet mechanical heart valves. The aim of this work was to create a method for simulating haemodynamics in positive-displacement blood pumps, using computational fluid dynamics with fluid-structure interaction to eliminate the need for pre-existing in vitro valve motion data, and then use it to investigate the performance of the Realheart TAH across a range of operating conditions. The device was simulated in Ansys Fluent for five cycles at pumping rates of 60, 80, 100 and 120 bpm and at stroke lengths of 19, 21, 23 and 25 mm. The moving components of the device were discretised using an overset meshing approach, a novel blended weak-strong coupling algorithm was used between fluid and structural solvers, and a custom variable time stepping scheme was used to maximise computational efficiency and accuracy. A two-element Windkessel model approximated a physiological pressure response at the outlet. The transient outflow volume flow rate and pressure results were compared against in vitro experiments using a hybrid cardiovascular simulator and showed good agreement, with maximum root mean square errors of 15% and 5% for the flow rates and pressures respectively. Ventricular washout was simulated and showed an increase as cardiac output increased, with a maximum value of 89% after four cycles at 120 bpm 25 mm. Shear stress distribution over time was also measured, showing that no more than [Formula: see text]% of the total volume exceeded 150 Pa at a cardiac output of 7 L/min. This study showed this model to be both accurate and robust across a wide range of operating points, and will enable fast and effective future studies to be undertaken on current and future generations of the Realheart TAH.

[Assisted circulation: an overview from a clinical perspective]. / Assistierte Zirkulation: ein Uberblick aus klinischer Sicht.

A higher grade cardiac failure is associated with poor prognosis. In addition to medical conservative treatment and traditional cardiac surgery, in the past years different forms of an assisted circulation evolved. Short-term devices serve to bridge an acute life-threatening situation. The chosen system is dependent on the anticipated clinical course. It is possible to fall back on slightly assisting techniques up to a complete takeover of the cardiac pump function. In the case of severe cardiac failure, the question for transplantation has to be addressed because transplantation is the treatment of choice to date. For an assisted circulation in cases of chronic congestive failure, devices of different generations are available. First generation pulsatile systems are used for assistance of the left ventricle and results have been shown to be superior to medical therapy (REMATCH). With second generation continuous-flow systems, results regarding infections, thromboembolism and also quality of life appear to be further improved. Contact-free centrifugal pumps as third generation systems are in clinical evaluation. So-called "total artificial hearts" are successfully used for bridge-to-transplantation. Taken together, a graded safe treatment of cardiac failure is available today. In the near future, it could be possible to reach results similar to those of cardiac transplantation.

Methods of design, simulation, and control for the development of new VAD/TAH concepts.

Cardiovascular diseases are a major cause of death worldwide. If medical treatments fail to restore adequate blood flow in a patient, mechanical support is needed. To date, many different types of blood pumps have been developed, but only few are clinically available. This review article describes the challenges involved in this field of research and gives an overview of the development process. Past developments as well as current and new technologies and approaches applied are summarized. Finally, a perspective for improved devices is discussed.

Driver electronics design and control for a total artificial heart linear motor.

For any implantable device size and efficiency are critical properties. Thus, a linear motor for a Total Artificial Heart was optimized with focus on driver electronics and control strategies. Hardware requirements were defined from power supply and motor setup. Four full bridges were chosen for the power electronics. Shunt resistors were set up for current measurement. Unipolar and bipolar switching for power electronics control were compared regarding current ripple and power losses. Here, unipolar switching showed smaller current ripple and required less power to create the necessary motor forces. Based on calculations for minimal power losses Lorentz force was distributed to the actor's four coils. The distribution was determined as ratio of effective magnetic flux through each coil, which was captured by a force test rig. Static and dynamic measurements under physiological conditions analyzed interaction of control and hardware and all efficiencies were over 89%. In conclusion, the designed electronics, optimized control strategy and applied current distribution create the required motor force and perform optimal under physiological conditions. The developed driver electronics and control offer optimized size and efficiency for any implantable or portable device with multiple independent motor coils. Graphical Abstract ᅟ.

Novel Optical Position Sensing for Miniaturized Applications and Validation in a Total Artificial Heart.

GOAL: This paper describes the development and testing of various position sensing systems (PSSs) for miniaturized long-term applications with a focus on their validation in a total artificial heart (TAH). After a short description of the TAH's functioning principle, the special requirements for the PSS resulting from the application in a TAH are investigated. METHODS: Three PSS's were designed according to these requirements. A specially designed test method was used to first validate each PSS for general use in a miniaturized application. This test method validated the speed, resolution, and accuracy requirements for the PSS. In a second step, the PSS's were integrated in a TAH to measure its stroke position for the drive control. In this application, further requirements apart from miniaturization were considered. Each PSS's functionality in the TAH was validated in a mock circulation loop, which simulates the human circulatory system. RESULTS: Two of the three designed PSS's showed satisfactory results for all tested requirements inside the pump, whereas the third PSS did not operate properly at full-pump capacity. The best performing PSS was chosen for further use in the TAH. It performed up to a beat rate of 220 b/m. CONCLUSION: The extensive validation resulted in an accurate, miniature PSS for a TAH. SIGNIFICANCE: Besides the use in a TAH, the presented PSS's can be employed in a wide use of miniaturized applications. The introduced testing method allows the validation for general miniaturized applications, e.g., linear motor drives.

Design and Evaluation of a Fully Implantable Control Unit for Blood Pumps.

As the number of donor hearts is limited while more and more patients suffer from end stage biventricular heart failure, Total Artificial Hearts become a promising alternative to conventional treatment. While pneumatic devices sufficiently supply the patients with blood flow, the patient's quality of life is limited by the percutaneous pressure lines and the size of the external control unit. This paper describes the development of the control unit of the ReinHeart, a fully implantable Total Artificial Heart. General requirements for any implantable control unit are defined from a technical and medical point of view: necessity of a Transcutaneous Energy Transmission, autonomous operation, safety, geometry, and efficiency. Based on the requirements, a prototype is designed; it incorporates a LiFePo4 battery pack with charger, a rectifier for transcutaneous energy transmission, the motor's driver electronics, and a microcontroller which monitors and controls all functions. In validation tests, the control unit demonstrated a stable operation on TET and battery supply and a safe switching from one supply to the other. The overall mean efficiency is 14% on TET and 22% on battery supply. The control unit is suitable for chronic animal trials of the ReinHeart.

System overview of the fully implantable destination therapy--ReinHeart-total artificial heart.

OBJECTIVES: Owing to the lack of suitable allografts, the demand for long-term mechanical circulatory support in patients with biventricular end-stage heart failure is rising. Currently available Total Artificial Heart (TAH) systems consist of pump units with only limited durability, percutaneous tubes and bulky external equipment that limit the quality of life. Therefore we are focusing on the development of a fully implantable, highly durable destination therapy total artificial heart. METHODS: The ReinHeart-TAH system consists of a passively filling pump unit driven by a low-wear linear drive between two artificial ventricles, an implantable control unit and a compliance chamber. The TAH is powered by a transcutaneous energy transmission system. The flow distribution inside the ventricles was analysed by fluid structure interaction simulation and particle image velocimetry measurements. Along with durability tests, the hydrodynamic performance and flow balance capability were evaluated in a mock circulation loop. Animal trials are ongoing. RESULTS: Based on fluid structure interaction simulation and particle image velocimetry, blood stagnation areas have been significantly reduced. In the mock circulation loop the ReinHeart-TAH generated a cardiac output of 5 l/min at an operating frequency of 120 bpm and an aortic pressure of 120/80 mmHg. The highly effective preload sensitivity of the passively filling ventricles allowed the sensorless integration of the Frank Starling mechanism. The ReinHeart-TAH effectively replaced the native heart's function in animals for up to 2 days. CONCLUSIONS: In vitro and in vivo testing showed a safe and effective function of the ReinHeart-TAH system. This has the potential to become an alternative to transplantation. However, before a first-in-man implant, chronic animal trials still have to be completed.

Design and evaluation of a hybrid mock circulatory loop for total artificial heart testing.

AIMS: A hybrid mock circulatory loop (MCL) was developed for total artificial heart (TAH) performance evaluation. The hybrid MCL consists of hydraulic hardware components and a software computer model. DESIGN: The hydraulic components are divided into the systemic and pulmonary circulation, each of which includes electrically controlled compliances, resistors, and a venous volume which can be adjusted for a wide range of physiological and pathological conditions. The software model simulates the baroreflex autoregulatory response by automatically adjusting the hydraulic parameters according to changes of condition in the MCL. RESULTS: The experimental results demonstrated a good representation of the human cardiovascular system and the capability of real-time variation of physiological and pathological conditions. The functionality of the baroreflex autoregulatory mechanism was evaluated by simulation of a postural change. CONCLUSIONS: The hybrid MCL that we developed allows variable and continuous in vitro evaluation of mechanical circulatory support devices in TAH configuration and particularly their control algorithms in response to various cardiovascular conditions. The system has been built in a modular configuration to allow testing of different types of devices and thus provides a valuable test platform prior to animal experiments.