Development of a radial ventricular assist device using numerical predictions and experimental haemolysis

The objective of this study was to demonstrate the potential of Computational Fluid Dynamics (CFD) simulations in predicting the levels of haemolysis in ventricular assist devices (VADs). Three different prototypes of a radial flow VAD have been examined experimentally and computationally using CFD modelling to assess device haemolysis. Numerical computations of the flow field were computed using a CFD model developed with the use of the commercial software Ansys CFX 13 and a set of custom haemolysis analysis tools. Experimental values for the Normalised Index of Haemolysis (NIH) have been calculated as 0.020 g/100 L, 0.014 g/100 L and 0.0042 g/100 L for the three designs. Numerical analysis predicts an NIH of 0.021 g/100 L, 0.017 g/100 L and 0.0057 g/100 L, respectively. The actual differences between experimental and numerical results vary between 0.0012 and 0.003 g/100 L, with a variation of 5% for Pump 1 and slightly larger percentage differences for the other pumps. The work detailed herein demonstrates how CFD simulation and, more importantly, the numerical prediction of haemolysis may be used as an effective tool in order to help the designers of VADs manage the flow paths within pumps resulting in a less haemolytic device.     

Characterization of an adult mock circulation for testing cardiac support devices

A need exists for a mock circulation that behaves in a physiologic manner for testing cardiac devices in normal and pathologic states. To address this need, an integrated mock cardiovascular system consisting of an atrium, ventricle, and systemic and coronary vasculature was developed specifically for testing ventricular assist devices (VADs). This test configuration enables atrial or ventricular apex inflow and aortic outflow cannulation connections. The objective of this study was to assess the ability of the mock ventricle to mimic the Frank-Starling response of normal, heart failure, and cardiac recovery conditions. The pressure-volume relationship of the mock ventricle was evaluated by varying ventricular volume over a wide range via atrial (preload) and aortic (afterload) occlusions. The input impedance of the mock vasculature was calculated using aortic pressure and flow measurements and also was used to estimate resistance, compliance, and inertial mechanical properties of the circulatory system. Results demonstrated that the mock ventricle pressure-volume loops and the end diastolic and end systolic pressure-volume relationships are representative of the Starling characteristics of the natural heart for each of the test conditions. The mock vasculature can be configured to mimic the input impedance and mechanical properties of native vasculature in the normal state. Although mock circulation testing systems cannot replace in vivo models, this configuration should be well suited for developing experimental protocols, testing device feedback control algorithms, investigating flow profiles, and training surgical staff on the operational procedures of cardiovascular devices.     

The 12 cc Penn State pulsatile pediatric ventricular assist device: flow field observations at a reduced beat rate with application to weaning

Ventricular assist devices (VADs) have become a viable option for adult patients with end-stage heart failure during the bridge-to-transplant period and have recently shown promise in aiding in myocardial recovery. Because the number of available organs is insufficient, mechanical circulatory support systems such as VADs are also being developed for use in pediatric patients. During myocardial recovery, the system must be weaned from the patient to prepare for explant; for pulsatile devices, this often includes a reduction in flow rate, which can change the fluid dynamics of the device. These changes in flow need to be monitored because strong diastolic rotational flow, no areas of blood stasis, low blood residence time, and wall shear rates above 500 s, can help prevent thrombus deposition. Particle image velocimetry was used to observe the planar flow patterns and wall shear rates of the 12 cc Penn State Pneumatic Pediatric VAD (PVAD) at a normal operating condition and a reduced beat rate. At the reduced beat rate, the PVAD showed an earlier loss of rotational pattern, increased blood residence time, and an overall reduction in wall shear rate at the outer walls. Because this reduction in flow rate could lead to a possible increase in thrombus deposition, it may be necessary to look into other options for weaning a patient from the PVAD.     

Successful combined use of Impella Recover 2.5 device and intra-aortic balloon pump support in cardiogenic shock from acute myocardial infarction

Ventricular assist devices (VADs) and intra-aortic balloon pumps (IABPs) are important tools that provide hemodynamic support to patients in cardiogenic shock. The Impella Recover 2.5 is a percutaneous VAD that provides temporary circulatory support. We report the case of a patient who required the combined support of both an IABP and the Impella device.     

Left ventricular and myocardial perfusion responses to volume unloading and afterload reduction in a computer simulation

Ventricular assist devices (VADs) have been used successfully as a bridge to transplant in heart failure patients by unloading ventricular volume and restoring the circulation. In a few cases, patients have been successfully weaned from these devices after myocardial recovery. To promote myocardial recovery and alleviate the demand for donor organs, we are developing an artificial vasculature device (AVD) that is designed to allow the heart to fill to its normal volume but eject against a lower afterload. Using this approach, the heart ejects its stroke volume (SV) into an AVD anastomosed to the aortic arch, which has been programmed to produce any desired afterload condition defined by an input impedance profile. During diastole, the AVD returns this SV to the aorta, providing counterpulsation. Dynamic computer models of each of the assist devices (AVD, continuous, and pulsatile flow pumps) were developed and coupled to a model of the cardiovascular system. Computer simulations of these assist techniques were conducted to predict physiologic responses. Hemodynamic parameters, ventricular pressure-volume loops, and vascular impedance characteristics were calculated with AVD, continuous VAD, and asynchronous pulsatile VAD support for a range of clinical cardiac conditions (normal, failing, and recovering left ventricle). These simulation results indicate that the AVD may provide better coronary perfusion, as well as lower vascular resistance and elastance seen by the native heart during ejection compared with continuous and pulsatile VAD. Our working hypothesis is that by controlling afterload using the AVD approach, ventricular cannulation can be eliminated, myocardial perfusion improved, myocardial compliance and resistance restored, and effective weaning protocols developed that promote myocardial recovery.     

Evaluation of computational models for hemolysis estimation

The potential for mechanical erythrocyte damage, or hemolysis, in heart valves and blood pumps has been estimated using computational fluid dynamics (CFD) analysis, combined with mathematical models of red cell damage mechanisms. To date, these prediction approaches have not been compared with each other in common benchmark cases, nor have they been evaluated in radically different flow geometries. In this study, four test devices, including a hemoresistometer, a spinning disk, a capillary tube, and a concentric cylinder viscometer were hemolysis tested and computationally simulated. A number of existing models were used to predict blood damage and these models were compared with each other and with actual measurement of hemolysis. The study indicates that the effectiveness of blood damage prediction from the existing models is similar and can potentially be improved with the consideration of a proposed repeated flow passage effect. It also indicates that the improved models can be used to more effectively predict blood damage in widely different situations.     

Use of a pulsatile ventricular assist device (Berlin Heart EXCOR) and an interventional lung assist device (Novalung) in an animal model

Pulsatile ventricular assist devices (VADs) are used in pediatric patients mainly as a bridge to heart transplantation. If severe respiratory failure occurs, extracorporeal membrane oxygenation (ECMO) is currently the treatment of choice. ECMO has the potential for severe complications. Interventional lung assist (iLA) devices, e.g., the Novalung, are used in patients with isolated lung failure. This study aimed to show the feasibility of the combined use of the EXCOR VAD (10 ml and 30 ml blood pumps) and the Novalung. There were two separate experiments within this study. First, a bench test was carried out to analyze pressure and flow through both devices. Second, 10 kg and 30 kg pigs received support with the VAD and iLA in series. Pressures and flow were measured systemically before and after the iLA. Flow was unaffected by the iLA. The mean arterial pressure was reduced (mean of 13 mm Hg) by the iLA. There were no obvious difficulties observed within the interaction of VAD and iLA. The combined use of both devices is feasible and able to provide sufficient perfusion pressures. Oxygenation and CO2 clearance was effectively supported by the iLA. Patients with myocardial and respiratory failure may benefit from this setup.     

Evaluation of Eulerian and Lagrangian models for hemolysis estimation

Hemolysis caused by flow-induced mechanical damage to red blood cells is still a problem in medical devices such as ventricular assist devices (VADs), artificial lungs, and mechanical heart valves. A number of different models have been proposed by different research groups for calculating the hemolysis, and of these, the power law-based models (HI(%)=Ct(α)τ(β)) have proved the most popular because of their ease of use and applicability to a wide range of devices. However, within this power law category of models there are a number of different implementations. The aim of this work was to evaluate different power law-based models by calculating hemolysis in a specifically designed shearing device and a clinical VAD, and comparing the estimated results with experimental measurements of the hemolysis in these two devices. Both the Eulerian scalar transport and all the Lagrangian models had fairly large percentage of errors compared with the experiments (minimum Eulerian 91% and minimum Lagrangian 57%) showing they could not accurately predict the magnitude of the hemolysis. However, the Eulerian approach had large correlation coefficients (>0.99) showing that this method can predict relative hemolysis, which would be useful in comparative analysis, for example, for ranking different devices or for design optimization studies.     

Axial flow pump support in a Marfan patient with an aortic mechanical heart valve: case report and literature review

The presence of a mechanical heart valve in the aortic position is usually considered a contraindication for the use of cardiac assist devices. Only a few cases with the combination of mechanical circulatory support and valve prostheses have been reported in the literature to date, and the experience is even more limited in the new generation of miniaturized axial flow pumps. We present a case report of a patient with a mechanical aortic heart valve who was successfully supported with a continuous flow pump and discuss the literature available on this problem. Further on, the patient was weaned from his ventricular assist device after 456 days of support.     

Blood biocompatibility analysis in the setting of ventricular assist devices

Ventricular assist devices (VADs) are increasingly applied to support patients with advanced cardiac failure. While the benefit of VADs in supporting this patient group is clear, substantial morbidity and mortality occur during the VAD implant period due to thromboembolic and infective complications. Efforts at the University of Pittsburgh aimed at evaluating the blood biocompatibility of VADs in the clinical, animal, and in vitro setting over the past decade are summarized. Emphasis is placed on understanding the mechanisms of thrombosis and thromboembolism associated with these devices.     

Current clinical status of pulsatile pediatric circulatory support

Whereas circulatory support with pulsatile assist devices is an established therapy in adults today, it remains unusual and extremely challenging in children. Specifically designed smaller size pumps are, to date, only available in Europe. This review summarizes the experience with both adult size pumps in the U.S. and pediatric pumps in Europe. Thoratec ventricular assist devices (VADs) were implanted in 101 patients worldwide who were between 7 and 17 years of age. Survival in this group was 68.8%, which is comparable with that in adult patients and was independent of age or body size. Berlin Heart VADs, available in several sizes, were implanted at the Deutsches Herzzentrum Berlin in 45 patients between 2 days and 16 years old. Survival in patients with myocarditis and cardiomyopathy was 66.7% and 71.4%, respectively; overall survival was 48.9%. In a number of European centers, 64 children up to 16 years of age received Medos devices, which are also available in several sizes, with an overall survival of 36.2%, similar for all pump sizes. End-stage congenital heart defects or failure to wean off bypass carried a poorer prognosis than cardiomyopathies or myocarditis for all devices.     

一种经皮植入式左心辅助装置的泵流量测试

目的 研究设计一种能用于心血管急危重症的经皮植入式左心辅助装置（血泵）。方法 根据机翼理论,设计一种经皮植入的左心辅助装置,通过测量3种不同参数（叶片旋转角度、血泵出水口距离、血泵出水口长度）的血泵所能产生的流量,最终选择最优化的血泵设计。结果 经过简易流量测定装置测量,当血泵采取单叶设计,血泵叶片的旋转角度为720°时,或血泵出水口与叶片的距离为0 mm时,血泵出水口长度为4 mm时,血泵流量最大。结论 选择能产生最大流量的参数值,研制出一种可在体外正常运转的经皮植入式左心辅助装置,为最终研制一种可用于临床的经皮植入式左心辅助装置提供理论和数据支持。     

Blood biocompatibility analysis in the setting of ventricular assist devices

Ventricular assist devices (VADs) are increasingly applied to support patients with advanced cardiac failure. While the benefit of VADs in supporting this patient group is clear, substantial morbidity and mortality occur during the VAD implant period due to thromboembolic and infective complications. Efforts at the University of Pittsburgh aimed at evaluating the blood biocompatibility of VADs in the clinical, animal, and in vitro setting over the past decade are summarized. Emphasis is placed on understanding the mechanisms of thrombosis and thromboembolism associated with these devices.     

Hardware-in-the-loop-simulation of the cardiovascular system, with assist device testing application

This paper presents a technique for evaluating the performance of biomedical devices by combining physical (mechanical) testing with a numerical, computerised model of a biological system. This technique is developed for evaluation of a cardiac assist device prior to in vivo trials. This device will wrap around a failing heart and provide physical beating assistance (dynamic cardiac compression). In vitro, the device to be tested is placed around a simulator comprising a mechanical simulation of the beating ventricles. This hardware model interfaces with a computerised (software) model of the cardiovascular system. In real time the software model calculates the effect of the assistance on the cardiovascular system and controls the beating motion of the hardware heart simulator appropriately. The software model of the cardiovascular system can represent ventricles in various stages of heart failure, and/or hardened or congested blood vessels as required. The software displays physiological traces showing the cardiac output, depending on the natural function of the modelled heart together with the physical assist power provided. This system was used to evaluate the effectiveness of control techniques applied to the assist device. Experimental results are presented showing the efficacy of prototype assist on healthy and weakened hearts, and the effect of asynchronous assist.     

Biventricular Assist Devices: A Technical Review

The optimal treatment option for end stage heart failure is transplantation; however, the shortage of donor organs necessitates alternative treatment strategies such as mechanical circulatory assistance. Ventricular assist devices (VADs) are employed to support these cases while awaiting cardiac recovery or transplantation, or in some cases as destination therapy. While left ventricular assist device (LVAD) therapy alone is effective in many instances, up to 50% of LVAD recipients demonstrate clinically significant postoperative right ventricular failure and potentially need a biventricular assist device (BiVAD). In these cases, the BiVAD can effectively support both sides of the failing heart. This article presents a technical review of BiVADs, both clinically applied and under development. The BiVADs which have been used clinically are predominantly first generation, pulsatile, and paracorporeal systems that are bulky and prone to device failure, thrombus formation, and infection. While they have saved many lives, they generally necessitate a large external pneumatic driver which inhibits normal movement and quality of life for many patients. In an attempt to alleviate these issues, several smaller, implantable second and third generation devices that use either immersed mechanical blood bearings or hydrodynamic/magnetic levitation systems to support a rotating impeller are under development or in the early stages of clinical use. Although these rotary devices may offer a longer term, completely implantable option for patients with biventricular failure, their control strategies need to be refined to compete with the inherent volume balancing ability of the first generation devices. The BiVAD systems potentially offer an improved quality of life to patients with total heart failure, and thus a viable alternative to heart transplantation is anticipated with continued development.     

Prerequisites to salvage profound biventricular failure patients with ventricular assist devices

We conducted chronic experiments to determine how to treat profound biventricular failure systematically with ventricular assist devices (VADs) and to analyze the factors that affect prognoses for this condition. Anoxic arrest was induced in ten goats by aortic cross-clamping under normothermic conditions (38.5 degrees C) for 30 (n = 3), 45 (n = 1), and 60 (n = 6) minutes. A left ventricular assist device (LVAD) was implanted in eight animals, and a biventricular assist device (BVAD) was used in two. Three goats--two of which had undergone anoxic arrest for 30 minutes and one for 60 minutes--whose right atrial pressure (RAP) was approximately 18 mm Hg during the acute stage, recovered in two to three weeks, and the pumps were successfully removed. Pathological findings in these animals showed scattered areas of surviving myocardium, with connective tissue replacing the degenerated myocardium. The remaining five LVAD goats required higher RAPs to maintain circulation and died from various causes. Maintaining circulation without volume loading, even in the presence of arrhythmias, was easier with the BVAD. One BVAD animal that underwent 45 minutes of anoxic arrest recovered from right ventricular failure, and the right pump was removed. The second goat (anoxic arrest, 60 min) on the BVAD failed to recover. Autopsy of the myocardium revealed a thin ventricular wall. Our studies show that the use of VADs allows time for a failing heart to recover, but the potential for healing is affected by the severity of myocardial damage prior to VAD application.(ABSTRACT TRUNCATED AT 250 WORDS)     

Computational fluid dynamics and experimental validation of a microaxial blood pump

Intravascular application of microaxial blood pumps as heart assist devices requires a maximum in size reduction of the pump components. These limitations affect the design process in many ways and restrict the number of applicable experimental procedures, but a detailed knowledge of the hemodynamics of the pump is of great interest for efficiency enhancement and reduction of blood trauma and thrombus formation. Computational fluid dynamics (CFD) offers a convenient approach to this goal. In this study, the inlet, vane, and outlet regions of a microaxial blood pump used as an intraaortic left ventricular assist device are analyzed by CFD and 3-dimensional (3-D) particle tracking velocimetry (PTV). For this purpose, a mock loop is set up that facilitates 3-D flow visualization. Flow in the main part of this testing device is modeled and computed by means of CFD. Pump head/flow (HQ) characteristics, axial pressure distribution, and particle images are then compared with numerical flow data. Results show that the pump performance characteristics, as well as inlet and outlet swirl predicted by the CFD model, are quite accurate compared with measured data. Proper boundary condition definitions and spatial discretization topology requirements for satisfactory results are discussed.     

Arterial sound based noninvasive malrotation detection of rotary LVAD

A number of advanced cardiovascular assist devices have been developed recently with the capability to prolong the life expectancy of patients with cardiac disease. To allow long-term use, it is necessary to assemble these devices using as few accessories as possible; however, a sensor for mechanical disorder detection is typically included to ensure mechanical reliability. Although a rotary left ventricular assist device (LVAD) has a simple mechanism, a malrotation caused by thrombogenesis can occur at any time. This situation could cause fatal damage to the cardiovascular circulation of the patient. In this study, we propose a simple, noninvasive method based on Korotkoff sounds, which would be able to detect the pressure-flow state during circulation supported by a rotary LVAD. Korotkoff sounds provide a means to noninvasively measure blood pressure in auscultation. We have found that the sounds are directly influenced by the pressure-flow state. We measured the arterial sound generated by an occluded brachial artery, as well as the Korotkoff sound generated during rotary LVAD circulation. To verify the effectiveness of the system, a circulatory simulator, rather than a human subject, was used. The arterial sound of several abnormal pressure-flow conditions was investigated. The simulator consists of a pulsatile blood pump, a compliance chamber, flow valves, a venous reservoir, and a rotary LVAD. Abnormal pressure-flow states are generated by simply changing the rotational speed of the rotary LVAD. We established the relationship between an abnormal pressure-flow state and the characteristics of the arterial sound, thus demonstrating that a malrotation of the rotary LVAD can be detected by the change of the arterial sound.     

Artificial heart research and present status of clinical application in Japan

Japan has a long history of research and development of the artificial heart since Atsumi began studying artificial hearts at the University of Tokyo in 1959. Since that time, the University of Tokyo group has been developing different types of artificial hearts, as well as materials, blood pumps, driving mechanisms, and control methods. Other than the University of Tokyo, there are 12 institutes involved in artificial heart research and development in Japan. As for artificial heart clinical application in Japan, four devices were approved by the government; two are domestic, two are imported. Between 1980 and 2004, 697 cases of clinical application of a ventricular assist device (VAD) have been performed, including in 38 pediatric patients under 18 years. Recently, clinical use of percutaneous cardiopulmonary support has been increasing with 600 to 800 cases being performed every year, including in 40 to 60 patients under age 20 years. Although the requirement for clinical use of pediatric VADs is increasing, there is no device, domestic or imported, currently used in Japan; therefore, there is an urgent need for development of a pediatric VAD.     

The influence of surface micro-structure on endothelialization under supraphysiological wall shear stress

Interaction between platelets and artificial materials within cardiovascular devices triggers blood coagulation and represents a frequent adverse response to implant deployment. Avoidance of this interaction is obtained through the generation and sustenance under flow of a confluent and stable endothelial monolayer covering the luminal device surface, altogether defined as the process of endothelialization. Supraphysiological wall shear stress (WSS) levels generated within vascular assist devices (VADs) constitute a major challenge toward endothelialization. Here we report the experimental demonstration that stable endothelialization can be achieved at supraphysiological WSS levels by pure means of appropriate surface micro-structuring. Using a custom-designed flow bioreactor we exposed endothelial monolayers to physiological and supraphysiological WSS levels and investigated the resulting integrity of cell-to-cell junctions, the cell density and the cell polarization. At physiological WSS levels, optimal endothelialization was obtained independently from surface topography. However, at higher WSS levels, only monolayers grown on appropriately micro-structured surfaces preserved optimal integrity. Under these flow conditions, endothelial cells polarized by the contact with the micro-structure and, interestingly, oriented themselves in the direction perpendicular to flow. Such endothelial layers withstood WSS levels exceeding of 100% or more the thresholds detected on flat substrates.