Validation of a Miniaturized Test Loop for the Assessment of Human Blood Damage by Continuous-Flow Left-Ventricular Assist Devices.

Despite improved hemocompatibility of left-ventricular assist devices (LVADs), assessment of blood damage remains mandatory in preclinical testing as standardized by ASTM-F1841. The most relevant test fluid is fresh, non-pooled human blood, but the limited volume of a standard donation requires significantly smaller loops than those commonly used with animal blood. In a recent study with porcine blood, we verified a miniaturized test loop with only 160 mL for the ASTM-conform paired testing of at least two LVADs and a static reference. Here, we validated this mini test loop for standardized assessment of blood damage with one 450-mL single donation of fresh human blood. Blood damage was assessed for HeartMate 3 and BPX-80 in 9 experiments with heparinized human blood for 6 hours. We analyzed plasma free hemoglobin, von Willebrand factor (vWF) concentration and collagen-binding functionality and calculated indices of hemolysis and vWF-ratios. Overall, we observed less blood damage compared to our previous study; however, the differences in mean indices of hemolysis and in mean normalized vWF-ratio between BPX-80 and HeartMate 3 were consistent for human blood. Thus, our mini test loop proved to be valid for preclinical standardized assessment of blood damage with only 450 mL of fresh human blood.

Miniaturized Test Loop for the Assessment of Blood Damage by Continuous-Flow Left-Ventricular Assist Devices.

Although the hemocompatibility of left-ventricular assist devices (LVADs) has continuously improved, assessment of hemolysis remains mandatory in pre-clinical testing. The ASTM-F1841 has standardized this assessment since 1997. However, the recommended usage of fresh, non-pooled human blood is hardly feasible with the test loop volume specified therein, when testing the device under test versus a predicate device as required by the international standard 10993-4. In this study, we compared ASTM-conforming (ASTM) and downscaled (mini) test loops with a one-third priming volume for the assessment of blood damage at the ASTM operating point. Blood damage was assessed for HeartMate 3 and BPX-80 in 6 experiments with heparinized porcine slaughterhouse blood for 6 h. We analyzed plasma free hemoglobin (pfHb), von Willebrand factor (vWF) concentration and collagen-binding functionality and calculated indices of hemolysis and vWF-ratios. The mini test loops provided significantly higher pfHb increase and consistently stronger vWF-ratio decrease and yielded a significantly better differentiation of the pumps. Interestingly, indices of hemolysis were generally lower in the mini set-up, indicating less adverse effects by the mini loop itself. Thus, we propose our mini test loop as suitable tool for clinically relevant standardized assessment of blood damage by future LVADs with single-donation human blood.

Low-flow assessment of current ECMO/ECCO2R rotary blood pumps and the potential effect on hemocompatibility.

BACKGROUND: Extracorporeal carbon dioxide removal (ECCO2R) uses an extracorporeal circuit to directly remove carbon dioxide from the blood either in lieu of mechanical ventilation or in combination with it. While the potential benefits of the technology are leading to increasing use, there are very real risks associated with it. Several studies demonstrated major bleeding and clotting complications, often associated with hemolysis and poorer outcomes in patients receiving ECCO2R. A better understanding of the risks originating specifically from the rotary blood pump component of the circuit is urgently needed. METHODS: High-resolution computational fluid dynamics was used to calculate the hemodynamics and hemocompatibility of three current rotary blood pumps for various pump flow rates. RESULTS: The hydraulic efficiency dramatically decreases to 5-10% if operating at blood flow rates below 1 L/min, the pump internal flow recirculation rate increases 6-12-fold in these flow ranges, and adverse effects are increased due to multiple exposures to high shear stress. The deleterious consequences include a steep increase in hemolysis and destruction of platelets. CONCLUSIONS: The role of blood pumps in contributing to adverse effects at the lower blood flow rates used during ECCO2R is shown here to be significant. Current rotary blood pumps should be used with caution if operated at blood flow rates below 2 L/min, because of significant and high recirculation, shear stress, and hemolysis. There is a clear and urgent need to design dedicated blood pumps which are optimized for blood flow rates in the range of 0.5-1.5 L/min.

Mesh Sensitivity Analysis for Quantitative Shear Stress Assessment in Blood Pumps Using Computational Fluid Dynamics.

The reduction of excessive, nonphysiologic shear stresses leading to blood trauma can be the key to overcome many of the associated complications in blood recirculating devices. In that regard, computational fluid dynamics (CFD) are gaining in importance for the hydraulic and hemocompatibility assessment. Still, direct hemolysis assessments with CFD remain inaccurate and limited to qualitative comparisons rather than quantitative predictions. An underestimated quantity for improved blood damage prediction accuracy is the influence of near-wall mesh resolution on shear stress quantification in regions of complex flows. This study investigated the necessary mesh refinement to quantify shear stress for two selected, meshing sensitive hotspots within a rotary centrifugal blood pump (the blade leading edge and tip clearance gap). The shear stress in these regions is elevated due to presence of stagnation points and the flow around a sharp edge. The nondimensional mesh characteristic number y+, which is known in the context of turbulence modeling, underestimated the maximum wall shear stress by 60% on average with the recommended value of 1, but was found to be exact below 0.1. To evaluate the meshing related error on the numerical hemolysis prediction, three-dimensional simulations of a generic centrifugal pump were performed with mesh sizes from 3 × 106 to 30 × 106 elements. The respective hemolysis was calculated using an Eulerian scalar transport model. Mesh insensitivity was found below a maximum y+ of 0.2 necessitating 18 × 106 mesh elements. A meshing related error of up to 25% was found for the coarser meshes. Further investigations need to address: (1) the transferability to other geometries and (2) potential adaptions on blood damage estimation models to allow better quantitative predictions.

Multivariate Assessment of the Effect of Pump Design and Pump Gap Design Parameters on Blood Trauma.

Pump gaps are the most critical regions in a rotary blood pump when it comes to blood trauma in the form of hemolysis, protein destruction, and platelet activation. This study investigated six pump design parameters affecting the flow in a radial pump gap. A multivariate approach was employed to determine individual and quantitative parameter effects on blood trauma as well as parameter interactions. To consider the effect of shear stress and blood cell residence time, a validated numerical Lagrangian particle tracking approach was used. Based on the results, small-diameter pumps can be as blood compatible, if not more blood compatible, as large-diameter pumps as long as identical circumferential velocities and clearance gaps are maintained. Furthermore, the results indicate that an eccentric rotor position in the casing is not harmful and that a pressure difference generating washout flow and thereby reducing the cell residence time is of significant importance.

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.

In vitro assessment of the influence of aortic annulus ovality on the hydrodynamic performance of self-expanding transcatheter heart valve prostheses.

BACKGROUND: Although CT-studies as well as intraoperative analyses have described broad anatomic variations of the aortic annulus, which is predominantly found non-circular, commercially available transcatheter aortic heart valve prostheses are circular. In this study, we hypothesize that the in vitro hydrodynamic function of a self-expanding transcatheter heart valve (Medtronic CoreValve) assessed in an oval compartment representing the aortic annulus will differ from the conventionally used circular compartment. METHODS: Medtronic CoreValve prostheses were tested in specifically designed and fabricated silicone compartments with three degrees of defined ovalities. The measurements were performed in a left heart simulator at three different flow rates. In this setting, regurgitation flow, effective orifice area, and systolic pressure gradient across the valve were determined. In addition, high speed video recordings were taken to investigate leaflet kinematics. RESULTS: The pressure difference across the prosthesis increased with rising ovality. The effective orifice areas were only slightly impacted. The analyses of the regurgitation showed minor changes and partially lower regurgitation when switching from round to slightly oval settings, followed by strong increases for further ovalization. The high speed videos show minor central leakage and impaired leaflet apposition for strong ovalities, but no leaflet/stentframe contact in any setting. CONCLUSION: This study quantifies the influence of oval expansion of transcatheter heart valve prostheses on their hydrodynamic performance. While slight ovalities were well tolerated by a self-expanding prosthesis, more significant ovality led to worsening of prosthesis function and regurgitation.

Combined computational and experimental approach to improve the assessment of mitral regurgitation by echocardiography.

Mitral regurgitation (MR) is one of the most frequent valvular heart diseases. To assess MR severity, color Doppler imaging (CDI) is the clinical standard. However, inadequate reliability, poor reproducibility and heavy user-dependence are known limitations. A novel approach combining computational and experimental methods is currently under development aiming to improve the quantification. A flow chamber for a circulatory flow loop was developed. Three different orifices were used to mimic variations of MR. The flow field was recorded simultaneously by a 2D Doppler ultrasound transducer and Particle Image Velocimetry (PIV). Computational Fluid Dynamics (CFD) simulations were conducted using the same geometry and boundary conditions. The resulting computed velocity field was used to simulate synthetic Doppler signals. Comparison between PIV and CFD shows a high level of agreement. The simulated CDI exhibits the same characteristics as the recorded color Doppler images. The feasibility of the proposed combination of experimental and computational methods for the investigation of MR is shown and the numerical methods are successfully validated against the experiments. Furthermore, it is discussed how the approach can be used in the long run as a platform to improve the assessment of MR quantification.

In vitro assessment of prosthesis type and pressure recovery characteristics: Doppler echocardiography overestimation of bileaflet mechanical and bioprosthetic aortic valve gradients.

OBJECTIVE: Pressure recovery results in Doppler gradients greater than catheter gradients and is well established in association with bileaflet mechanical aortic valves. Because pressure recovery is influenced by orifice geometry, it might manifest differently with various valve prostheses. If true, then the reliability of Doppler echocardiography for the estimation of aortic valve gradients might be different with different prostheses. The purpose of the present study was to test, in an in vitro setting, the degree to which pressure recovery results in Doppler overestimation of gradients for three commonly used aortic valve prostheses. METHODS: Carpentier Edwards Perimount, Medtronic Mosaic, and St. Jude Medical bileaflet prostheses were tested under various flow conditions in a pulsatile mock flow loop with a normal aorta size. Mean pressure gradient was assessed with transducers 1 cm and 10 cm distal to the valve and with Doppler echocardiography. Pressure recovery was defined as the difference between the Doppler gradient and a 10-cm gradient. The percentage of the maximum pressure gradient composed of pressure recovery and the percentage of pressure recovery complete 1 cm distal to the valve were calculated. RESULTS: There was substantial pressure recovery for all valves in all flow states. Pressure recovery was responsible for 50% or more of the Doppler gradients for almost all conditions and was more than 70% complete within 1 cm for almost all conditions. Multivariate analysis found that flow and valve area (but not valve type) were predictors of pressure recovery; that flow was the major predictor of the percentage of Doppler gradient composed of pressure recovery (with minor contributions from the aorta size and prosthesis type); and that valve type and aorta size were the major predictors of the percentage of pressure recovery complete at 1 cm. CONCLUSIONS: In an in vitro model with a normal aorta size, substantial pressure recovery occurred with all three aortic valve prostheses. Although statistically significant differences were found between valve types in the percentage of pressure recovery and percentage of pressure recovery complete at 1 cm, the differences were small and clinically unimportant. Clinically, among patients with an ascending aorta diameter less than 3.0 cm, Doppler echocardiography likely substantially overestimates aortic valve mean gradient, regardless of prosthesis type.

Assessment of right pump outflow banding and speed changes on pulmonary hemodynamics during biventricular support with two rotary left ventricular assist devices.

The absence of an effective, easily implantable right ventricular assist device (RVAD) significantly diminishes long-term treatment options for patients with biventricular heart failure. The implantation of a second rotary left ventricular assist device (LVAD) for right heart support is therefore being considered; however, this approach exhibits technical challenges when adapting current devices to produce the lower pressures required of the pulmonary circulation. Hemodynamic adaptation may be achieved by either reducing the rotational speed of the right pump impeller or reducing the diameter of the right outflow cannula by the placement of a restricting band; however, the optimal value and influence of changes to each parameter are not well understood. Hemodynamics were therefore investigated using different banding diameters of the right outflow cannula (3-6.5 mm) and pump speeds (500-4500 rpm), using two identical rotary blood pumps coupled to a pulsatile mock circulation loop. Reducing the speed of the right pump from 4900 rpm (for left ventricle support) to 3500 rpm, or banding the Ø10 mm (area 78.5 mm²) right outflow graft to Ø5.4 mm (22.9 mm²) produced suitable hemodynamics. Pulmonary pressures were most sensitive to banding diameters, especially when RVAD flow exceeded LVAD flow. This occurred between Ø5.3 and Ø6.5 mm (22.05-38.5 mm²) and speeds between 3200 and 4400 rpm, with the flow imbalance potentially leading to pulmonary congestion. Total flow was not affected by banding diameters and speeds below this range, and only increased slightly at higher values. Both right outflow banding or right pump speed reduction were found to be effective techniques to allow a rotary LVAD to be used directly for right heart support. However, the observed sensitivity to diameter and speed indicate that challenges may be presented when setting appropriate values for each patient, and control over these parameters is desirable.