In Vivo Evaluation of a Novel Control Algorithm for Left Ventricular Assist Devices Based Upon Ventricular Stroke Work.

The physical fitness of patients with terminal heart failure and an implanted left ventricular assist device (LVAD) might be improved by load-adaptive control of the LVAD. In this study, three control strategies for LVAD were compared in eight pigs: (1) a constant stroke work (CSW) control strategy that ensures a constant ventricular load using ventricular stroke work as the control variable; (2) a work ratio (WR) controller that maintains a constant ratio of ventricular work to hydraulic pump work; and (3) a controller that maintains the pump pace at a constant speed (CS). Biventricular heart insufficiency was induced by increased isoflurane application, and preload, afterload, and contractility alterations were performed. LVAD speed changes were significantly more pronounced in all load interventions with the CSW control strategy (preload: P < 0.001 vs. CS and P = 0.004 vs. WR; afterload: P < 0.001 vs. CS and P < 0.001 vs. WR; contractility: P < 0.001 vs. CS and P < 0.001 vs. WR). However, a significant difference in systemic flow only became evident in the experiments upon afterload increase ( P < 0.001 vs. CS and P = 0.004 vs. WR). An implementation of an evolved version of the CSW control strategy that dispenses with invasively measured parameters might be feasible for clinical use.

Comparison of augmented reality and cutting guide technology in assisted harvesting of iliac crest grafts - A cadaver study.

BACKGROUND: Harvesting vascularized bone grafts with computer-assisted surgery represents the gold standard for mandibular reconstruction. However, current augmented reality (AR) approaches are limited to invasive marker fixation. This trial compared a markerless AR-guided real-time navigation with virtually planned and 3D printed cutting guides for harvesting iliac crest grafts. MATERIAL AND METHODS: Two commonly used iliac crest transplant configurations were virtually planned on 10 cadaver hips. Transplant harvest was performed with AR guidance and cutting guide technology. The harvested transplants were digitalized using cone beam CT. Deviations of angulation, distance and volume between the executed and planned osteotomies were measured. RESULTS: Both AR and cutting guides accurately rendered the virtually planned transplant volume. However, the cumulative osteotomy plane angulation differed significantly (p = 0.018) between AR (14.99 ± 11.69°) and the cutting guides (8.49 ± 5.42°). The cumulative osteotomy plane distance showed that AR-guided navigation had lower accuracy (2.65 ± 3.32 mm) than the cutting guides (1.47 ± 1.36 mm), although without significant difference. CONCLUSION: This study demonstrated the clinical usability of markerless AR-guided navigation for harvesting iliac crest grafts. Further improvement of accuracy rates might bring clinical implementation closer to reality.

Towards technically controlled bioreactor maturation of tissue-engineered heart valves.

Bioreactors are important tools for the pre-conditioning of tissue-engineered heart valves. The current state of the art mostly provides for timed, physical and biochemical stimulation in the bioreactor systems according to standard protocols (SOP). However, this does not meet to the individual biological variability of living tissue-engineered constructs. To achieve this, it is necessary to implement (i) sensory systems that detect the actual status of the implant and (ii) controllable bioreactor systems that allow patient-individualized pre-conditioning. During the maturation process, a pulsatile transvalvular flow of culture medium is generated within the bioreactor. For the improvement of this conditioning procedure, the relationship between the mechanical and biochemical stimuli and the corresponding tissue response has to be analyzed by performing reproducible and comparable experiments. In this work, a technological framework for maturation experiments of tissue-engineered heart valves in a pulsating bioreactor is introduced. The aim is the development of a bioreactor system that allows for continuous control and documentation of the conditioning process to increase reproducibility and comparability of experiments. This includes hardware components, a communication structure and software including online user communication and supervision. Preliminary experiments were performed with a tissue-engineered heart valve to evaluate the function of the new system. The results of the experiment proof the adequacy of the setup. Consequently, the concept is an important step for further research towards controlled maturation of tissue-engineered heart valves. The integration of molecular and histological sensor systems will be the next important step towards a fully automated, self-controlled preconditioning system.

Navigation of iliac crest graft harvest using markerless augmented reality and cutting guide technology: A pilot study.

BACKGROUND: Defects of the facial skeleton often require complex reconstruction with vascularized grafts. This trial elucidated the usability, visual perception and accuracy of a markerless augmented reality (AR)-guided navigation for harvesting iliac crest transplants. METHODS: Random CT scans were used to virtually plan two common transplant configurations on 10 iliac crest models, each printed four times. The transplants were harvested using projected AR and cutting guides. The duration and accuracies of the angulation, distance and volume between the planned and executed osteotomies were measured. RESULTS: AR was characterized by the efficient use of time and accurate rendition of preoperatively planned geometries. However, vertical osteotomies and complex anatomical settings displayed significant inferiority of AR guidance compared to cutting guides. CONCLUSIONS: This study demonstrated the usability of a markerless AR setup for harvesting iliac crest transplants. The visual perception and accuracy of the AR-guided osteotomies constituted remaining weaknesses against cutting guide technology.

Proof of Concept: Measuring Aortic Annulus Resistance by Means of Pressure-Volume Curves During Balloon Inflation to Guide Transcatheter Aortic Valve Implantation.

This study assessed the basic working principle to measure aortic annulus resistance during balloon inflation for transcatheter aortic valve implantation (TAVI), by acquisition of pressure-volume curve for a guided semi-automatic implantation. A modular bench-system was used which allows the incremental inflation of valvuloplasty balloons by means of a stepper-motor driven linear axis with simultaneous recording of the pressure changes inside the system. Different porcine aortic xenografts were assessed by use of a non-compliant valvuloplasty balloon. In a second step transcatheter aortic stents were implanted inside target sized xenografts. The recorded pressure volume-curves showed that the system can accurately differentiate between different xenografts and assess the quality of the tissue rendering real-time analysis of pressure-volume curves during balloon-inflation possible, which has the potential to optimize the implantation procedure by direct adaptation to the patient specific anatomy and characteristics. Further investigations and development are warranted.

In vivo evaluation of two adaptive Starling-like control algorithms for left ventricular assist devices.

The implantation of a left ventricular assist device (LVAD) is often the only therapy in terminal heart failure (HF). However, despite technical advancements, the physical fitness of the patients is still limited. One strategy to improve the benefits of ventricular assist device therapy might be the implementation of load adaptive control strategies. Two control strategies and a constant speed controller (CS) were implemented in an acute animal model where four healthy pigs received LVAD implantations. In the first strategy (preload recruitable stroke work [SW] controller, PRS), the desired pump work was computed in relation to the end-diastolic volume. In the second strategy, the controller was programmed to keep a fixed ratio of the mean hydraulic power of the assist device to the mean hydraulic power of the left ventricle (power relation controller, PR). Preload reduction, afterload increase experiments and short-term coronary artery occlusions were conducted to test the behavior of the control strategies under variable conditions. Within the experiments, the PR controller demonstrated the best preload sensitivity. The PRS controller had the best response to an increased afterload and to a reduced ventricular contractility in terms of effectively preventing ventricular overloading and increasing VAD support. No significant differences in systemic flow were observed.

Non-linearity of end-systolic pressure-volume relation in afterload increases is caused by an overlay of shortening deactivation and the Frank-Starling mechanism.

The linearity and load insensitivity of the end-systolic pressure-volume-relationship (ESPVR), a parameter that describes the ventricular contractile state, are controversial. We hypothesize that linearity is influenced by a variable overlay of the intrinsic mechanism of autoregulation to afterload (shortening deactivation) and preload (Frank-Starling mechanism). To study the effect of different short-term loading alterations on the shape of the ESPVR, experiments on twenty-four healthy pigs were executed. Preload reductions, afterload increases and preload reductions while the afterload level was increased were performed. The ESPVR was described either by a linear or a bilinear regression through the end-systolic pressure volume (ES-PV) points. Increases in afterload caused a biphasic course of the ES-PV points, which led to a better fit of the bilinear ESPVRs (r2 0.929 linear ESPVR vs. r2 0.96 and 0.943 bilinear ESPVR). ES-PV points of a preload reduction on a normal and augmented afterload level could be well described by a linear regression (r2 0.974 linear ESPVR vs. r2 0.976 and 0.975 bilinear ESPVR). The intercept of the second ESPVR (V0) but not the slope demonstrated a significant linear correlation with the reached afterload level (effective arterial elastance Ea). Thus, the early response to load could be described by the fixed slope of the ESPVR and variable V0, which was determined by the actual afterload. The ESPVR is only apparently nonlinear, as its course over several heartbeats was affected by an overlay of SDA and FSM. These findings could be easily transferred to cardiovascular simulation models to improve their accuracy.

Online cardiac output estimation during transvalvular left ventricular assistance.

BACKGROUND AND OBJECTIVES: Sufficient cardiac output is one of the main goals of ventricular assist device therapy. To date, there is no adequate method to estimate the combined amount of blood the native heart and a continuous-flow assist device pump through the circulatory system. This paper presents an approach to estimate total cardiac output based on the signals provided by optical pressure sensors mounted on the inlet and outlet of an Abiomed Impella CP pump. METHODS: Two Kalman filters were used in parallel for joint estimation of the aortic flow rate and the hydraulic resistance of the aortic valve. The filters utilized a third order nonlinear state-space representation of the cardiovascular system with two nominal parameter sets, one for ovine and another for human subjects. The accuracy of the estimated cardiac output has been investigated in a hybrid mock circulatory loop and an animal study involving two sheep with experimentally induced acute ischaemic heart disease supported by a transvalvular left ventricular assist device. RESULTS: The in vitro accuracy of the cardiac output estimation is ±3.64%. In an ovine model, the comparison of the estimated cardiac output with an ultrasonic flow measurement in the pulmonary artery showed 95% limits of agreement of -0.004 ±â€¯0.897 L min-1. The estimation errors were comparable to the accuracy of the measurement (±10%), which is the gold standard in research for invasive blood flow diagnostics. CONCLUSIONS: The online estimation of total cardiac output may give the treating physician a direct and physiologically meaningful feedback on the pump speed setting. One promising possible application of our method is physiological control, where the cardiac output can be used as the control variable for closed-loop ventricular assist device therapy.

Parametrization of an in-silico circulatory simulation by clinical datasets - towards prediction of ventricular function following assist device implantation.

BACKGROUND: Left ventricular assist device (LVAD) therapy has revolutionized the way end stage heart failure is treated today. Analysis of LVAD interaction with the whole cardiovascular system and its biological feedback loops is often conducted by means of computer models. Generating real time pressure volume loops (PV-loops) in patients, not using conductance catheters but routine diagnostics to feed an in-silico model could help to predict postoperative complications. METHODS: Routinely obtained hemodynamic measurements to evaluate myocardial function prior to LVAD implantation like pressure readings in the aorta, the left atrium and the left ventricle and simultaneous three-dimensional (3D) echocardiography recordings were assessed to parametrize a reduced computational model of the cardiovascular system. An automatic parameter identification procedure has been developed. RESULTS: The results constitute a patient-individual computational simulation model. An exemplary in-silico study focusing on the effect of different ventricular assist device (VAD) speeds has been conducted. Results allow for estimation of the resulting hemodynamic parameters and changes of the PV-loops. CONCLUSION: The model improves understanding and prediction of the interaction between pump and ventricles. Future modifications in exporting and merging routinely assessed real time hemodynamic patient data are necessary to investigate various clinical and pathological conditions of LVAD recipients.

Comparison of novel physiological load-adaptive control strategies for ventricular assist devices.

Terminal heart failure (HF) is the most prevalent cause of death in the Western world and the implantation of a left ventricular assist device (LVAD) has become the gold standard therapy today. Most of the actually implanted devices are driven at a constant speed (CS) regardless of the patient's physiological demand. A new physiological controller [power ratio (PR) controller], which keeps a constant ratio between LVAD power and left ventricular power, a previous concept [preload responsive speed (PRS) controller], which adds a variable LVAD power to reach a defined stroke work, and a CS controller were compared with an unimpaired ventricle in a full heart computer simulation model. The effects of changes in preload, afterload and left ventricular contractility are displayed by global hemodynamics and ventricular pressure-volume loops. Both physiological controllers demonstrated the desired load dependency, whereas the PR controller exceeded the PRS controller in response to an increased load and contractility. Response was inferior when preload or contractility was decreased. Thus, the PR controller might lead to an increased exercise tolerance of the patient. Additional studies are required to evaluate the controllers in vivo.

Benefits of object-oriented models and ModeliChart: modern tools and methods for the interdisciplinary research on smart biomedical technology.

Computational models of biophysical systems generally constitute an essential component in the realization of smart biomedical technological applications. Typically, the development process of such models is characterized by a great extent of collaboration between different interdisciplinary parties. Furthermore, due to the fact that many underlying mechanisms and the necessary degree of abstraction of biophysical system models are unknown beforehand, the steps of the development process of the application are iteratively repeated when the model is refined. This paper presents some methods and tools to facilitate the development process. First, the principle of object-oriented (OO) modeling is presented and the advantages over classical signal-oriented modeling are emphasized. Second, our self-developed simulation tool ModeliChart is presented. ModeliChart was designed specifically for clinical users and allows independently performing in silico studies in real time including intuitive interaction with the model. Furthermore, ModeliChart is capable of interacting with hardware such as sensors and actuators. Finally, it is presented how optimal control methods in combination with OO models can be used to realize clinically motivated control applications. All methods presented are illustrated on an exemplary clinically oriented use case of the artificial perfusion of the systemic circulation.