30-day in vivo study of a fully maglev extracorporeal ventricular assist device.

OBJECTIVE: Cardiogenic shock (CS) often occurs in patients suffering from rapidly progressing end-stage heart failure or acute myocardial infarction. Mechanical circulatory support may be used for patients who do not respond to medication or revascularization to stabilize hemodynamics. Extracorporeal ventricular assist device (Extra-VAD) has been reported to be successful for patients with cardiogenic shock. This study aimed to evaluate the 30-day in-vivo performance and safety of a newly developed Extra-VAD with maglev centrifugal pump technology, MoyoAssist®. METHOD: The study was conducted with 6 healthy ovine models, weighing 43.2 ~ 59.6 kg. Cannulation was performed with a 34 Fr venous cannula surgically connected to the left arterial appendage and a 24 Fr arterial cannula inserted into descending aorta. The pump flow rate was maintained at 2 ~ 3 L/min to provide sufficient cardiac support without suction. Activated clotting time was maintained within the range of 150 ~ 250 s. RESULTS: No device-related adverse events occurred throughout the study. Plasma-free hemoglobin results were within the acceptable range of ventricular assist device therapy (<40 mg/dl). MGS01 had an anticoagulation management related bleeding event and was terminated on day 29. All other sheep's biochemical test results were stable. The autopsy showed no embolism or thrombus formation and no end-organ damage. CONCLUSION: This study demonstrated that the MoyoAssist® Extra-VAD is able to provide cardiac support effectively and safely and may provide a new alternative choice for patients with CS in China.

On the Accuracy of Hemolysis Models in Couette-Type Blood Shearing Devices.

Hemolysis is one of the most challenging issues faced by blood contacting devices. Empirical hemolysis models often relate hemolysis to shear stress and exposure time. These models were generally derived from the experimental results of Couette-type blood shearing devices, with assumption of uniform exposure time and shear stress. This assumption is not strictly valid since neither exposure time nor shear stress is uniform. Hence, this study evaluated the influence of the nonuniform exposure time and rotor eccentricity or run-out on the accuracy of power-law hemolysis models, using both theoretical and CFD analysis. This work first provided a systematic analysis of the flow regime in a typical Couette shearing device, and showed the axial flow component can be regarded as fully developed laminar plane Poiseuille flow. It was found that the influence of nonuniform exposure time is within 4% for several widely used power-law models, which were validated by steady CFD simulations. A theoretical relationship was then built between the rotor run-out and hemolysis. We noticed that the influence of rotor run-out on hemolysis is within 5% for a moderate rotor run-out ratio of 0.2. Next, transient CFD simulations were performed to investigate the influence of rotor run-out on hemolysis with run-out ratios of 0.1 and 0.2. The results showed negligible effects for a moderate run-out ratio of 0.1. However, a run-out ratio of 0.2 led to a significant increase of hemolysis, resulting from back flows induced by the run-out of the rotor. These findings will be of great importance for the improvement of the hemolysis estimation and blood compatibility design.

Systematic Design of a Magnetically Levitated Brushless DC Motor for a Reversible Rotary Intra-Aortic Blood Pump.

The IntraVAD is a miniature intra-aortic ventricular assist device (VAD) designed to work in series with the compromised left ventricle. A reverse-rotation control (RRc) mode has been developed to increase myocardial perfusion and reduce ventricular volume. The RRc mode includes forward rotation in systole and reverse rotation in diastole, which requires the IntraVAD to periodically reverse its rotational direction in synchrony with the cardiac cycle. This periodic reversal leads to changes in pressure force over the impeller, which makes the entire system less stable. To eliminate the mechanical wear of a contact bearing and provide active control over the axial position of the rotor, a miniature magnetically levitated bearing (i.e., the PM-Coil module) composed of two concentric permanent magnetic (PM) rings and a pair of coils-one on each side-was proposed to provide passive radial and active axial rotor stabilization. In the early design stage, the numerical finite element method (FEM) was used to optimize the geometry of the brushless DC (BLDC) motor and the maglev module, but constructing a new model each time certain design parameters were adjusted required substantial computation time. Because the design criteria for the module had to be modified to account for the magnetic force produced by the motor and for the hemodynamic changes associated with pump operation, a simplified analytic expression was derived for the expected magnetic forces. Suitable bearings could then be designed capable of overcoming these forces without repeating the complicated FEM simulation for the motor. Using this method at the initial design stage can inform the design of the miniature maglev BLDC motor for the proposed pulsatile axial-flow VAD.

In Vitro Evaluation of the Dual-Diffuser Design for a Reversible Rotary Intra-Aortic Ventricular Assist Device.

The intra-aortic ventricular assist device (IntraVAD) is a miniature intra-aortic axial-flow ventricular assist device (VAD) that works in series with the left ventricle (LV) to assist the compromised heart. Previous in vitro results have shown that the IntraVAD can successfully increase coronary perfusion and offload ventricular volume by operating in reverse-rotation control (RRc) mode. The RRc mode includes forward rotation in systole and reverse rotation (RR) in diastole. It is necessary to derive a new diffuser design that can be used for the bi-directional rotation of the IntraVAD. In this work, a dual-diffuser set (DDS) was proposed to replace the conventional inducer and diffuser upstream and downstream of the pump. The DDS comprised two diffusers, located on both sides of the impeller, omitting the conventional inducer and diffuser. Different configurations of the DDS were designed and manufactured with various combinations of curved and straight blades. All configurations were initially tested in continuous flow, then in a pulsatile mock circulatory loop. A weighted normalized scalar (WNS) was proposed to comprehensively evaluate the hemodynamic effect of the DDS with different configurations. The results show that the maximum of WNS occurred when the upstream diffuser had equal numbers of curved and straight blades and the downstream diffuser had only curved blades. This indicates such a dual-diffuser design for the IntraVAD can give an optimal cardiac assistance potentially improving ventricular contractility, thereby restoring heart function.

In-Series Versus In-Parallel Mechanical Circulatory Support for the Right Heart: A Simulation Study.

Right heart failure (RHF) is a serious health issue with increasing incidence and high mortality. Right ventricular assist devices (RVADs) have been used to support the end-stage failing right ventricle (RV). Current RVADs operate in parallel with native RV, which alter blood flow pattern and increase RV afterload, associated with high tension in cardiac muscles and long-term valve complications. We are developing an in-series RVAD for better RV unloading. This article presents a mathematical model to compare the effects of RV unloading and hemodynamic restoration on an overloaded or failing RV. The model was used to simulate both in-series (sRVAD) and in-parallel (pRVAD) (right atrium-pulmonary artery cannulation) support for severe RHF. The results demonstrated that sRVAD more effectively unloads the RV and restores the balance between RV oxygen supply and demand in RHF patients. In comparison to simulated pRVAD and published clinical and in silico studies, the sRVAD was able to provide comparable restoration of key hemodynamic parameters and demonstrated superior afterload and volume reduction. This study concluded that in-series support was able to produce effective afterload reduction and preserve the valve functionality and native blood flow pattern, eliminating complications associated with in-parallel support.

Design method of a foldable ventricular assist device for minimally invasive implantation.

To date, ventricular assist devices (VADs) have become accepted as a therapeutic solution for end-stage heart failure patients when a donor heart is not available. Newer generation VADs allow for a significant reduction in size and an improvement in reliability. However, the invasive implantation still limits this technology to critically ill patients. Recently, expandable/deployable devices have been investigated as a potential solution for minimally invasive insertion. Such a device can be inserted percutaneously via peripheral vessels in a collapsed form and operated in an expanded form at the desired location. A common structure of such foldable pumps comprises a memory alloy skeleton covered by flexible polyurethane material. The material properties allow elastic deformation to achieve the folded position and withstand the hydrodynamic forces during operation; however, determining the optimal geometry for such a structure is a complex challenge. The numerical finite element method (FEM) is widely used and provides accurate structural analysis, but computation time is considerably high during the initial design stage where various geometries need to be examined. This article details a simplified two-dimensional analytical method to estimate the mechanical stress and deformation of memory alloy skeletons. The method was applied in design examples including two popular types of blade skeletons of a foldable VAD. Furthermore, three force distributions were simulated to evaluate the strength of the structures under different loading conditions experienced during pump operation. The results were verified with FEM simulations. The proposed two-dimensional method gives a close stress and deformation estimation compared with three-dimensional FEM simulations. The results confirm the feasibility of such a simplified analytical approach to reveal priorities for structural optimization before time-consuming FEM simulations, providing an effective tool in the initial structural design stage of foldable minimally invasive VADs.

Experimental and analytical performance evaluation of short circular hydrodynamic journal bearings used in rotary blood pumps.

Rotary blood pumps (RBPs) have demonstrated considerable promise while treating heart failure patients, such that they are being placed at an earlier stage of the disease. These devices may therefore be required to operate for prolonged durations which yields the need for RBPs exhibiting high durability, reliability, and blood compatibility. Noncontacting bearings, utilizing magnetic and/or hydrodynamic suspension techniques, appear to provide a suitable solution to these challenges. Hydrodynamic suspension has the advantage that it does not need feedback control systems. Among various hydrodynamic bearing types, the circular journal bearing has the particular benefit of easy manufacturing. This study presents methods to evaluate the performance of short (length to diameter ratio <1) circular hydrodynamic journal bearings (HJBs) for RBPs. Analytical calculations with specific boundary conditions are presented to predict the rotor's eccentricity under equilibrium states and thus the related performance parameters such as load capacity, power loss, and shear rates. These results and boundary conditions were confirmed experimentally in a specially designed test set-up. The bearing performance was found to correlate to analytical solutions using the full Sommerfeld boundary condition instead of the half Sommerfeld condition conventionally used for such applications. Geometrical and operational parameter variations showed that HJB designs with a short Sommerfeld Number SS >0.02 can provide sufficient fluid film thicknesses and low shear rates. The measurements were further used to evaluate the bearings' stability. The estimation of the stability threshold drawn in relation to a modified stability index and the equilibrium eccentricity of the rotor allows the prediction of stability for short circular HJB designs under full Sommerfeld condition.

Case report: Successful percutaneous extracorporeal magnetic levitation ventricular assist device support in a patient with left heart failure due to dilated cardiomyopathy.

Introduction: Mechanical circulatory support (MCS) can help to maintain hemodynamic stability, improve cardiac function, reduce cardiac load, and is an important method for the treatment of advanced heart failure. However, traditional MCS systems [IABP, Impella, TandemHerat, veno-arterial extracorporeal membrane oxygenation (VA-ECMO)] are associated with limitations including trauma, a high rate of complications (hemolysis, bleeding) and require complex care from nurses. Case summary: We report a case of left heart failure resulting from dilated cardiomyopathy in a 24 years-old man. A catheter was placed through the right jugular vein and a drainage tube was positioned under ultrasound guidance through the superior vena cava, right atrium, atrial septum, to the left atrium, and returned to the axillary artery using an extracorporeal magnetic levitation ventricular assist device (VAD). The patient was successfully supported for 10 days and bridged to heart transplant. Discussion: To the best of our knowledge, this is the first report of the use of an extracorporeal magnetic levitation VAD for MCS via a percutaneous approach. Our findings support the wider use of this strategy for patients awaiting myocardial recovery or who require heart bridging or transplantation.

A comprehensive comparison of the in vitro hemocompatibility of extracorporeal centrifugal blood pumps.

Purpose: Blood damage has been associated with patients under temporary continuous-flow mechanical circulatory support. To evaluate the side effects caused by transit blood pumping, in vitro hemocompatibility testing for blood damage in pumps is considered a necessary reference before clinical trials. Methods: The hemocompatibility of five extracorporeal centrifugal blood pumps was investigated comprehensively, including four commercial pumps (the Abbott CentriMag, the Terumo Capiox, the Medos DP3, and the Medtronic BPX-80) and a pump in development (the magAssist MoyoAssist®). In vitro, hemolysis was tested with heparinized porcine blood at nominal operating conditions (5 L/min, 160 mmHg) and extreme operating conditions (1 L/min, 290 mmHg) using a circulation flow loop. Hematology analyses concerning the blood cell counts and the degradation of high-molecular-weight von Willebrand factor (VWF) during 6-h circulation were also evaluated. Results: Comparing the in vitro hemocompatibility of blood pumps at different operations, the blood damage was significantly more severe at extreme operating conditions than that at nominal operating conditions. The performance of the five blood pumps was arranged in different orders at these two operating conditions. The results also demonstrated superior hemocompatibility of CentriMag and MoyoAssist® at two operating conditions, with overall low blood damage at hemolysis level, blood cell counts, and degradation of high-molecular-weight VWF. It suggested that magnetic bearings have an advantage in hemocompatibility compared to the mechanical bearing of blood pumps. Conclusion: Involving multiple operating conditions of blood pumps in in vitro hemocompatibility evaluation will be helpful for clinical application. In addition, the magnetically levitated centrifugal blood pump MoyoAssist® shows great potential in the future as it demonstrated good in vitro hemocompatibility.

Mechanical circulatory support for right heart failure: current technology and future outlook.

The increasing global prevalence of congestive heart failure is a major healthcare concern, accounting for a high morbidity rate worldwide. In particular, isolated right heart dysfunction after cardiotomy has a poor prognosis and is associated with a high mortality rate. The occurrence of postoperative right heart failure may develop in more than 40% of patients undergoing implantation of a left ventricular assist device (LVAD) and cardiac transplantation. To date, mechanical cardiac assistance in the form of VADs has become accepted as a therapeutic solution for end-stage patients when a donor heart is not available. However, right ventricular (RV) assistance is still in the early phase of development when compared with LVAD technology. State-of-the-art RVADs, both in clinical use and under development, are reviewed in this manuscript. Clinical RVADs include the extracorporeal pulsatile Abiomed BVS 5000 and AB5000, Thoratec PVAD, MEDOS VAD, BerlinHeart Excor, the percutaneous continuous flow CentriMag and TandemHeart systems, and the implantable Thoratec IVAD. Devices on the horizon, including the wear-free implantable DexAide and the minimally invasive Impella RD, are additionally reviewed. In addition to the current status of RV assistance, as well as the device categorization, the outlook and considerations for successful development of future RVADs were discussed.

A controller for a miniature intra-aortic ventricular assist device.

Two control algorithms have been developed for a minimally invasive axial-flow ventricular assist device (VAD) for placement in the descending aorta. The purpose of the device is to offload the left ventricle and to augment lower body perfusion in patients with moderate congestive heart failure. The VAD consists of an intra-aortic impeller with a built-in permanent magnet rotor and an extra-aortic stator. The control algorithms, which use pressure readings upstream and downstream of the VAD to determine the pump status, have been tested in a mock circulatory system under two conditions, namely with or without afterload sensitivity. The results give an insight into controller design for an intra-aortic blood pump working in series with the heart.

Evaluation of hydraulic radial forces on the impeller by the volute in a centrifugal rotary blood pump.

In many state-of-the-art rotary blood pumps for long-term ventricular assistance, the impeller is suspended within the casing by magnetic or hydrodynamic means. For the design of such suspension systems, profound knowledge of the acting forces on the impeller is crucial. Hydrodynamic bearings running at low clearance gaps can yield increased blood damage and magnetic bearings counteracting high forces consume excessive power. Most current rotary blood pump devices with contactless bearings are centrifugal pumps that incorporate a radial diffuser volute where hydraulic forces on the impeller develop. The yielding radial forces are highly dependent on impeller design, operating point and volute design. There are three basic types of volute design--singular, circular, and double volute. In this study, the hydraulic radial forces on the impeller created by the volute in an investigational centrifugal blood pump are evaluated and discussed with regard to the choice of contactless suspension systems. Each volute type was tested experimentally in a centrifugal pump test setup at various rotational speeds and flow rates. For the pump's design point at 5 L/min and 2500 rpm, the single volute had the lowest radial force (∼0 N), the circular volute yielded the highest force (∼2 N), and the double volute possessed a force of approx. 0.5 N. Results of radial force magnitude and direction were obtained and compared with a previously performed computational fluid dynamics (CFD) study.

Evaluation method and platform of vibrational disturbance test for ventricular assist devices.

OBJECTIVE: For ventricular assist devices utilizing levitation bearing technology, collision and wear of the rotor would occur if the bearing cannot resist disturbances from patient activities and vibration/shock impacts. The reliability of ventricular assist devices can be seriously affected, potentially impairing blood compatibility (e.g. thrombus generation) and threatening patient safety. In this article, we proposed a vibrational disturbance test protocol for ventricular assist devices. METHODS: Two kinds of vibrational disturbances-translational and rotational-were defined and the disturbance levels determined as 6G and 10 rad/s per possible patient activity impact. A test platform was built according to the disturbance level requirements. RESULTS: The test platform successfully generated the required disturbance. The vibration test evaluation criteria for ventricular assist device assistance (characterized by the pressure head, flow rate, and driving current waveform) were well verified. CONCLUSION: Compared with translational vibration, rotational vibration had a greater impact on the rotor. Accurate control of high-speed rotor is difficult because of the gyroscopic effect. As conventional random vibration tests cannot cover all risk situations, it is recommended that translational and rotational disturbance tests are carried out for levitation ventricular assist devices. We recommend that researchers and manufacturers pay attention to the vibrational impact of rotor-levitated ventricular assist devices.

Mock circulatory loops used for testing cardiac assist devices: A review of computational and experimental models.

Heart failure is a major health risk, and with limited availability of donor organs, there is an increasing need for developing cardiac assist devices (CADs). Mock circulatory loops (MCL) are an important in-vitro test platform for CAD's performance assessment and optimisation. The MCL is a lumped parameter model constructed out of hydraulic and mechanical components aiming to simulate the native cardiovascular system (CVS) as closely as possible. Further development merged MCLs and numerical circulatory models to improve flexibility and accuracy of the system; commonly known as hybrid MCLs. A total of 128 MCLs were identified in a literature research until 25 September 2020. It was found that the complexity of the MCLs rose over the years, recent MCLs are not only capable of mimicking the healthy and pathological conditions, but also implemented cerebral, renal and coronary circulations and autoregulatory responses. Moreover, the development of anatomical models made flow visualisation studies possible. Mechanical MCLs showed excellent controllability and repeatability, however, often the CVS was overly simplified or lacked autoregulatory responses. In numerical MCLs the CVS is represented with a higher order of lumped parameters compared to mechanical test rigs, however, complex physiological aspects are often simplified. In hybrid MCLs complex physiological aspects are implemented in the hydraulic part of the system, whilst the numerical model represents parts of the CVS that are too difficult to represent by mechanical components per se. This review aims to describe the advances, limitations and future directions of the three types of MCLs.

Atrial versus ventricular cannulation for a rotary ventricular assist device.

The ventricular assist device inflow cannulation site is the primary interface between the device and the patient. Connecting these cannulae to either atria or ventricles induces major changes in flow dynamics; however, there are little data available on precise quantification of these changes. The objective of this investigation was to quantify the difference in ventricular/vascular hemodynamics during a range of left heart failure conditions with either atrial (AC) or ventricular (VC) inflow cannulation in a mock circulation loop with a rotary left VAD. Ventricular ejection fraction (EF), stroke work, and pump flow rates were found to be consistently lower with AC compared with VC over all simulated heart failure conditions. Adequate ventricular ejection remained with AC under low levels of mechanical support; however, the reduced EF in cases of severe heart failure may increase the risk of thromboembolic events. AC is therefore more suitable for class III, bridge to recovery patients, while VC is appropriate for class IV, bridge to transplant/destination patients.

An energy-dissipation-based power-law formulation for estimating hemolysis.

Hemolysis is a major concern in blood-circulating devices, which arises due to non-physiological stresses on red blood cells from ambient flow environment or moving mechanical structures. Computational fluid dynamics (CFD) and empirical hemolysis prediction models have been increasingly used for the design and optimization of blood-circulating devices. The commonly used power-law models for hemolysis prediction often use Reynolds stress to represent effective stress, tend to over-predict hemolysis and fail to capture trends of flow-related hemolysis. This study proposed a new power-law formulation for the numerical hemolysis prediction. The new formulation related hemolysis to the energy dissipation rate, which could be readily obtained from CFD simulations. The model constants were regressed from existing hemolysis data. The new formulation was tested for three benchmark cases and compared to conventional power-law models. The results showed that the new formulation improved prediction of hemolysis for a broad range of flow regimes. The deviations of the predicted hemolysis from experimental results were within one order, and better correlated with experimental results. This study confirmed that Reynolds stress is the main cause of over-prediction of hemolysis for conventional power-law models. Proportionally, the blood damage predicted with Reynolds stresses is more than one order higher than viscous stress, in terms of energy dissipation.

Study on in vitro performance verification protocol for left ventricular assist device.

OBJECTIVE: In vitro performance verification of ventricular assist devices using a mock circulatory loop is a prominent step to guarantee the system responses and the device performance and safety before the in vivo tests and ultimately clinical trials. METHODS: In this article, we performed a comprehensive literature research to establish a verification matrix consisting of 12 test cases, defined by a set of physiological parameters which are commonly used to characterize a physiological condition. The clinical hemodynamic indicators for defining successful mechanical support were used as the acceptance criteria. A mock circulatory loop was customized to simulate the test cases, and a full verification protocol was described in details. An example left ventricular assist device was incorporated in the loop to accomplish a standard ventricular assist device performance verification. RESULT: The test cases based on clinical data with sufficient safety margin represent our understanding in defining the extremes of operation. The mock circulatory loop was capable of generating the test conditions in the verification matrix and reproducing the Frank-Starling law of the native heart. The effect of the left ventricular assist device assistance (characterized by the total systemic flow, mean aortic pressure, and left atrial pressure) was well verified by the proposed protocol and acceptance criteria. CONCLUSION: To date, all left ventricular assist devices made in China have been evaluated according this protocol and some of them have entered the clinical trial stage. We are closely observing the clinical data in order to further improve the performance of the platform and encourage more advances in mechanical circulatory assist devices.

Dielectrophoresis-Based Method for Measuring the Multiangle Mechanical Properties of Biological Cells.

The mechanical properties of cells are closely related to their physiological functions and states. Analyzing and measuring these properties are beneficial to understanding cell mechanisms. However, most measurement methods only involve the unidirectional analysis of cellular mechanical properties and thus result in the incomplete measurement of these properties. In this study, a microfluidic platform was established, and an innovative microfluidic chip was designed to measure the multiangle cellular mechanical properties by using dielectrophoresis (DEP) force. Three unsymmetrical indium tin oxide (ITO) microelectrodes were designed and combined with the microfluidic chip, which were utilized to generate DEP force and stretch cell from different angles. A series of experiments was performed to measure and analyze the multiangle mechanical properties of red blood cells of mice. This work provided a new tool for the comprehensive and accurate measurement of multiangle cellular mechanical properties. The results may contribute to the exploration of the internal physiological structures of cells and the building of accurate cell models.

Hemodynamic performance of a compact centrifugal left ventricular assist device with fully magnetic levitation under pulsatile operation: An in vitro study.

Long-term using continuous flow ventricular assist devices could trigger complications associated with diminished pulsatility, such as valve insufficiency and gastrointestinal bleeding. One feasible solution is to produce pulsatile flow assist with speed regulation in continuous flow ventricular assist devices. A third-generation blood pump with pulsatile operation control algorithm was first characterized alone under pulsatile mode at various speeds, amplitudes, and waveforms. The pump was then incorporated in a Mock circulation system to evaluate in vitro hemodynamic effects when using continuous and different pulsatile operations. Pulsatility was evaluated by surplus hemodynamic energy. Results showed that pulsatile operations provided sufficient hemodynamic assistance and increased pulsatility of the circulatory system (53% increment), the mean aortic pressure (65% increment), and cardiac output (27% increment). The pulsatility of the system under pulsatile operation support was increased 147% compared with continuous operation support. The hemodynamic performance of pulsatile operations is susceptible to phase shifts, which could be a tacking angle for physiological control optimization. This study found third-generation blood pumps using different pulsatile operations for ventricular assistance promising.

A review of implantable pulsatile blood pumps: Engineering perspectives.

It has been reported that long-term use of continuous-flow mechanical circulatory support devices (CF-MCSDs) may induce complications associated with diminished pulsatility. Pulsatile-flow mechanical circulatory support devices (PF-MCSDs) have the potential of overcoming these shortcomings with the advance of technology. In order to promote in-depth understanding of PF-MCSD technology and thus encourage future mechanical circulatory support device innovations, engineering perspectives of PF-MCSD systems, including mechanical designs, drive mechanisms, working principles, and implantation strategies, are reviewed in this article. Some emerging designs of PF-MCSDs are introduced, and possible elements for next-generation PF-MCSDs are identified.