Study of the Relationship between Pulmonary Artery Pressure and Heart Valve Vibration Sound Based on Mock Loop.

The vibration of the heart valves' closure is an important component of the heart sound and contains important information about the mechanical activity of a heart. Stenosis of the distal pulmonary artery can lead to pulmonary hypertension (PH). Therefore, in this paper, the relationship between the vibration sound of heart valves and the pulmonary artery blood pressure was investigated to contribute to the noninvasive detection of PH. In this paper, a lumped parameter circuit platform of pulmonary circulation was first set to guide the establishment of a mock loop of circulation. By adjusting the distal vascular resistance of the pulmonary artery, six different pulmonary arterial pressure states were achieved. In the experiment, pulmonary artery blood pressure, right ventricular blood pressure, and the vibration sound of the pulmonary valve and tricuspid valve were measured synchronously. Features of the time domain and frequency domain of two valves' vibration sound were extracted. By conducting a significance analysis of the inter-group features, it was found that the amplitude, energy and frequency features of vibration sounds changed significantly. Finally, the continuously varied pulmonary arterial blood pressure and valves' vibration sound were obtained by continuously adjusting the resistance of the distal pulmonary artery. A backward propagation neural network and deep learning model were used, respectively, to estimate the features of pulmonary arterial blood pressure, pulmonary artery systolic blood pressure, the maximum rising rate of pulmonary artery blood pressure and the maximum falling rate of pulmonary artery blood pressure by the vibration sound of the pulmonary and tricuspid valves. The results showed that the pulmonary artery pressure parameters can be well estimated by valve vibration sounds.

Oxygenation performance assessment of an artificial lung in different central anatomic configurations.

OBJECTIVES: Aim of this work was to characterize possible central anatomical configurations in which a future artificial lung (AL) could be connected, in terms of oxygenation performance. METHODS: Pulmonary and systemic circulations were simulated using a numerical and an in vitro approach. The in vitro simulation was carried out in a mock loop in three phases: (1) normal lung, (2) pulmonary shunt (50% and 100%), and (3) oxygenator support in three anatomical configurations: right atrium-pulmonary artery (RA-PA), pulmonary artery-left atrium (PA-LA), and aorta-left atrium (Ao-LA). The numerical simulation was performed for the oxygenator support phase. The oxygen saturation (SO2) of the arterial blood was plotted over time for two percentages of pulmonary shunt and three blood flow rates through the oxygenator. RESULTS: During the pulmonary shunt phase, SO2 reached a steady state value (of 68% for a 50% shunt and of nearly 0% for a 100% shunt) 20 min after the shunt was set. During the oxygenator support phase, physiological values of SO2 were reached for RA-PA and PA-LA, in case of a 50% pulmonary shunt. For the same conditions, Ao-LA could reach a maximum SO2 of nearly 60%. Numerical results were congruous to the in vitro simulation ones. CONCLUSIONS: Both in vitro and numerical simulations were able to properly characterize oxygenation properties of a future AL depending on its placement. Different anatomical configurations perform differently in terms of oxygenation. Right to right and right to left connections perform better than left to left ones.

Enhanced Drug Delivery for Cardiac Microvascular Obstruction with an Occlusion-Infusion-Catheter.

Microvascular Obstruction (MVO) is a common consequence of acute myocardial infarction. MVO is underdiagnosed and treatment is often nonspecific and ineffective. A multi-scale in-vitro benchtop model was established to investigate drug perfusion in MVO affected microcirculation. The central element of the benchtop model was a fluidic microchip containing channels with diameters between [Formula: see text] and 50 µm representing [Formula: see text] of the microvascular tree fed by the left anterior descending artery (LAD). The outlets of the chip could be closed to mimic MVO. Two methods for intracoronary infusion of pharmacologic agents (simulated by dye) to regions with MVO were investigated using an occlusion-infusion catheter. The first case was a simple, bolus-like infusion into the LAD, whereas the second case consisted of infusion with concomitant proximal occlusion of the LAD phantom with a balloon. Results show that local dye concentration maxima in the chip with MVO were 2.2-3.2 times higher for the case with proximal balloon occlusion than for the conventional infusion method. The cumulated dose could be raised by a factor 4.6-5.2. These results suggest that drug infusion by catheter is more effective if the blood supply to the treated vascular bed is temporarily blocked by a balloon catheter.

Particle Image Velocimetry to Evaluate Pulse Wave Velocity in Aorta Phantom with the lnD-U Method.

PURPOSE: Pulse wave velocity (PWV) is an indicator of arterial stiffness used in the prediction of cardiovascular disease such as atherosclerosis. Non-invasive methods performed with ultrasound probes allow one to compute PWV and aortic stiffness through the measurement of the aortic diameter (D) and blood flow velocity (U) with the lnD-U method. This technique based on in vivo acquisitions lacks validation since the aortic elasticity modulus cannot be verified with mechanical strength tests. METHOD: In the present study, an alternative validation is carried out on an aorta phantom hosted in an aortic flow simulator which mimics pulsatile inflow conditions. This in vitro setup included a Particle Image Velocimetry device to visualize flow in a 2D longitudinal section of the phantom, compute velocity fields (U), and track wall displacements in the aorta phantom to measure the apparent diameter (AD) variations throughout cycles. RESULTS: The lnD-U method was then applied to evaluate PWV (5.79 ± 0.33 m/s) and calculate the Young's modulus of the aorta phantom (0.56 ± 0.12 MPa). This last value was compared to the elasticity modulus (0.53 ± 0.07 MPa) evaluated with tensile strength tests on samples cut from the silicone phantom. CONCLUSION: The PIV technique PWV measurement showed good agreement with the direct tensile test method with a 5.6% difference in Young's modulus. Considering the uncertainties from the two methods, the measured elasticities are consistent and close to a 50-60 years old male aortic behavior. The choice of silicone for the phantom material is a relevant and promising option to mimic the human aorta on in vitro systems.

In vitro thrombogenicity evaluation of rotary blood pumps by thromboelastometry.

In vitro thrombogenicity tests for rotary blood pumps (RBPs) could benefit from assessing coagulation kinematics, as RBP design improves. In this feasibility study, we investigated if the method of thromboelastometry (TEM) is able to assess coagulation kinematics under the in vitro conditions of RBP tests. We conducted in vitro thrombogenicity tests (n=4) by placing Deltastream® DP3 pumps into test loops that were filled with 150 mL of slightly anti-coagulated porcine blood, adjusted to an activated clotting time (ACT) well below clinically recommended levels. Blood samples were taken at certain time points during the experiment until a continuous decrease in pump flow indicated major thrombus formation. Blood samples were analyzed for ACT, platelet count (PLT), and several TEM parameters. While visible thrombus formation was observed in three pumps, ACT indicated an ongoing activation of coagulation, PLT might have indicated platelet consumption. Unexpectedly, most TEM results gave no clear indications. Nonetheless, TEM clotting time obtained by non-anticoagulated and chemically non-activated whole blood (HEPNATEM-CT) appeared to be more sensitive for the activation of coagulation in vitro than ACT, which might be of interest for future pump tests. However, more research regarding standardization of thrombogenicity pump tests is urgently required.

Aortic valve opening in mock-loop with continuous-flow left ventricular assist device.

The appropriate opening of aortic valves is crucial for heart failure (HF) patients with left ventricular assist devices (LVADs). Nevertheless, up to the present time, aortic valve monitoring has not been performed in discharged patients. In this study, a mock-loop platform was developed to investigate the aortic valve performance in LVAD patients. An additional sluice valve was placed next to the aortic valve that when the sluice valve is manually closed, the aortic valve will remain closed; when the sluice valve is open, the aortic valve is opened or closed upon the pressures. The results showed that when the LVAD speed was below 2600 rpm, the aortic valve can be intermittently opened, while when the LVAD speed was over 2600 rpm, the aortic valve was persistently closed. The left ventricular end-systolic pressure (LVESP) was found to be an indicator of aortic valve closure that, upon the aortic valve closure LVESP suddenly decreased. The LVESP is suggested for future monitoring the status of the aortic valve for patients with implanted LVADs. The effects of heart failure (HF) degrees, circulation resistance, and aortic compliance on aortic valve closure were further studied. The results revealed that LVAD implantation in patients with early HF degrees will help to avoid persistent aortic valve closure.

Hemodynamic characterization of the Realheart® total artificial heart with a hybrid cardiovascular simulator.

BACKGROUND: Heart failure is a growing health problem worldwide. Due to the lack of donor hearts there is a need for alternative therapies, such as total artificial hearts (TAHs). The aim of this study is to evaluate the hemodynamic performance of the Realheart® TAH, a new 4-chamber cardiac prosthesis device. METHODS: The Realheart® TAH was connected to a hybrid cardiovascular simulator with inflow connections at the left/right atrium, and outflow connections at the ascending aorta/pulmonary artery. The Realheart® TAH was tested at different pumping rates and stroke volumes. Different systemic resistances (20.0-16.7-13.3-10.0 Wood units), pulmonary resistances (6.7-3.3-1.7 Wood units), and pulmonary/systemic arterial compliances (1.4-0.6 ml/mm Hg) were simulated. Tests were also conducted in static conditions, by imposing predefined values of preload-afterload across the artificial ventricle. RESULTS: The Realheart® TAH allows the operator to finely tune the delivered flow by regulating the pumping rate and stroke volume of the artificial ventricles. For a systemic resistance of 16.7 Wood units, the TAH flow ranges from 2.7 ± 0.1 to 6.9 ± 0.1 L/min. For a pulmonary resistance of 3.3 Wood units, the TAH flow ranges from 3.1 ± 0.0 to 8.2 ± 0.3 L/min. The Realheart® TAH delivered a pulse pressure ranging between ~25 mm Hg and ~50 mm Hg for the tested conditions. CONCLUSIONS: The Realheart® TAH offers great flexibility to adjust the output flow and delivers good pressure pulsatility in the vessels. Low sensitivity of device flow to the pressure drop across it was identified and a new version is under development to counteract this.

In vitro flow study in a compliant abdominal aorta phantom with a non-Newtonian blood-mimicking fluid.

In vitro aortic flow simulators allow studying hemodynamics with a wider range of flow visualization techniques compared to in vivo medical imaging and without the limitations of invasive examinations. This work aims to develop an experimental bench to emulate the pulsatile circulation in a realistic aortic phantom. To mimic the blood shear thinning behavior, a non-Newtonian aqueous solution is prepared with glycerin and xanthan gum polymer. The flow is compared to a reference flow of Newtonian fluid. Particle image velocimetry is carried out to visualize 2D velocity fields in a phantom section. The experimental loop accurately recreates flowrates and pressure conditions and preserves the shear-thinning properties of the non-Newtonian fluid. Velocity profiles, shear rate, and shear stress distribution maps show that the Newtonian fluid tends to dampen the observed velocities. Preferential asymmetrical flow paths are observed in a diameter narrowing region and amplified in the non-Newtonian case. Wall shear stresses are about twice higher in the non-Newtonian case. This study shows new insights on flow patterns, velocity and shear stress distributions compared to rigid and simplified geometry aorta phantom with Newtonian fluid flows studies. The use of a non-Newtonian blood analog shows clear differences in flows compared to the Newtonian one in this compliant patient-specific geometry. The development of this aortic simulator is a promising tool to better analyze and understand aortic hemodynamics and to aid in clinical decision-making.

Left atrial assist device to treat patients with heart failure with preserved ejection fraction: Initial in vitro study.

OBJECTIVES: Many patients with heart failure have preserved ejection fraction but also diastolic dysfunction, with no effective therapy. We are developing a new pump (left atrial assist device, LAAD) for implantation at the mitral position to pump blood from the left atrium to sufficiently fill the left ventricle. The purpose of the initial in vitro study was to demonstrate that the LAAD can reduce left atrial pressure (LAP) and increase cardiac output (CO) while maintaining arterial pulsatility and normal aortic valve function using a proof-of-concept device. METHODS: The LAAD concept was tested at 3 pump speeds on a pulsatile mock loop with a pneumatic pump that simulated the normal function of the native ventricle as well as 3 levels of diastolic heart failure (DHF 1, 2, and 3) by adjusting the diastolic drive pressure to limit diastolic filling of the ventricle. RESULTS: Without the LAAD, CO and aortic pressure (AoP) decreased dramatically from 3.8 L/min and 100 mm Hg at normal heart condition to 1.2 L/min and 35 mm Hg at DHF 3, respectively. With LAAD support, both CO and AoP recovered to normal heart values at 3200 rpm and surpassed normal heart values at 3800 rpm. Furthermore, with LAAD support, LAP recovered to almost that of the normal heart condition at 3800 rpm. CONCLUSIONS: These initial in vitro results support our hypothesis that use of the LAAD increases CO and AoP and decreases LAP under DHF conditions while maintaining arterial pulsatility and full function of the aortic valve.

A Valveless Pulsatile Pump for Heart Failure with Preserved Ejection Fraction: Hemo- and Fluid Dynamic Feasibility.

Treatment of heart failure with preserved ejection fraction (HFpEF) remains a major unmet medical need. An implantable valveless pulsatile pump with a single cannula-the CoPulse pump-may provide beneficial hemodynamic support for select HFpEF patients when connected to the failing ventricle. We aimed to demonstrate hemodynamic efficacy and hemocompatible design feasibility for this novel assist device. The hemodynamic effect of the pump was investigated with an in vitro circulatory mock loop and an ex vivo isolated porcine heart model. The hydraulic design was optimized using computational fluid dynamics (CFD), and validated by 4D-flow magnetic resonance imaging (MRI). The pump reduced left atrial pressure (> 27%) and increased cardiac output (> 14%) in vitro. Ex vivo experiments revealed elevated total stroke volume at increased end-systolic volume during pump support. Asymmetric cannula positioning indicated superior washout, decreased stagnation (8.06 mm2 vs. 31.42 mm2), and marginal blood trauma potential with moderate shear stresses (< 24 Pa) in silico. Good agreement in flow velocities was evident among CFD and 4D-flow MRI data (r > 0.76). The CoPulse pump proved hemodynamically effective. Hemocompatibility metrics were comparable to those of a previously reported, typical pulsatile pump with two cannulae. The encouraging in vitro, ex vivo, and hemocompatibility results substantiate further development of the CoPulse pump.

The design modification of advanced ventricular assist device to enhance pulse augmentation and regurgitant flow shut-off.

The new Advanced ventricular assist device (Advanced VAD) has many features such as improving pulsatility and preventing regurgitant flow during pump stoppage. The purpose of this study was to evaluate the effects of design modifications of the Advanced VAD on these features in vitro. Bench testing of four versions of the Advanced VAD was performed on a static or pulsatile mock loop with a pneumatic device. After pump performance was evaluated, each pump was run at 3000 rpm to evaluate pulse augmentation, then was stopped to assess regurgitant flow through the pump. There was no significant difference in pump performance between the pump models. The average pulse pressure in the pulsatile mock loop was 23.0, 34.0, 39.3, 33.8, and 37.3 mm Hg without pump, with AV010, AV020 3S, AV020 6S, and AV020 RC, respectively. The pulse augmentation factor was 48%, 71%, 47%, and 62% with AV010, AV020 3S, AV020 6S, and AV020 RC, respectively. In the pump stop test, regurgitant flow was -0.60 ± 0.70, -0.13 ± 0.57, -0.14 ± 0.09, and -0.18 ± 0.06 L/min in AV010, AV020 3S, AV020 6S, and AV020 RC, respectively. In conclusion, by modifying the design of the Advanced VAD, we successfully showed the improved pulsatility augmentation and regurgitant flow shut-off features.

A Hybrid Experimental-Computational Modeling Framework for Cardiovascular Device Testing.

Significant advances in biomedical science often leverage powerful computational and experimental modeling platforms. We present a framework named physiology simulation coupled experiment ("PSCOPE") that can capitalize on the strengths of both types of platforms in a single hybrid model. PSCOPE uses an iterative method to couple an in vitro mock circuit to a lumped-parameter numerical simulation of physiology, obtaining closed-loop feedback between the two. We first compared the results of Fontan graft obstruction scenarios modeled using both PSCOPE and an established multiscale computational fluid dynamics method; the normalized root-mean-square error values of important physiologic parameters were between 0.1% and 2.1%, confirming the fidelity of the PSCOPE framework. Next, we demonstrate an example application of PSCOPE to model a scenario beyond the current capabilities of multiscale computational methods-the implantation of a Jarvik 2000 blood pump for cavopulmonary support in the single-ventricle circulation; we found that the commercial Jarvik 2000 controller can be modified to produce a suitable rotor speed for augmenting cardiac output by approximately 20% while maintaining blood pressures within safe ranges. The unified modeling framework enables a testing environment which simultaneously operates a medical device and performs computational simulations of the resulting physiology, providing a tool for physically testing medical devices with simulated physiologic feedback.

In vitro comparison of the hemocompatibility of two centrifugal left ventricular assist devices.

OBJECTIVES: Shear stress from left ventricular assist devices induces von Willebrand factor degradation and platelet dysfunction, leading to nonsurgical bleeding. We characterized the hemostatic changes induced by 2 centrifugal left ventricular assist devices, the HeartMate 3 (Abbott Inc, Chicago, Ill) and the EVAHEART (Evaheart Inc, Houston, Tex), for comparison. METHODS: Whole blood from 8 healthy volunteers was used ex vivo. Blood from the same donor was used for 6 hours of circulation in a miniature mock-loop system consisting of 2 identical extracorporeal circuits to compare the following experimental settings: (1) optimal revolutions per minute (rpm) for the HeartMate 3 (n = 4; 5000 rpm) and the EVAHEART (n = 4; 2500 rpm) and (2) equal rpm (3000 rpm for the HeartMate 3 and EVAHEART, n = 4 vs n = 4). For both settings, blood flow was adjusted to 1 mock-loop filling volume per minute (HeartMate 3 = 82 mL/min, EVAHEART = 100 mL/min). A panel of coagulation markers was analyzed to investigate hemostatic changes. RESULTS: The free plasma hemoglobin concentration was significantly lower in the EVAHEART compared with the HeartMate 3 after 6 hours of mock-loop circulation under both settings (optimal: 37 ± 31 vs 503 ± 173 mg/dL, P < .0001; equal: 27 ± 4 vs 139 ± 135 mg/dL, P = .024). Loss of von Willebrand factor high-molecular-weight multimers occurred in both left ventricular assist devices and settings, but the von Willebrand factor:activity/von Willebrand factor:antigen ratio after 6 hours was significantly lower in optimal settings for the HeartMate 3 (P = .009). The thrombin-antithrombin complex level was significantly lower with the EVAHEART for both settings (P < .0001). CONCLUSIONS: The EVAHEART left ventricular assist device caused less hemolysis, resulted in lower coagulation activation, and provided better preservation of von Willebrand factor functional activity compared with the HeartMate 3 device. These findings prove that left ventricular assist device design plays a major role in minimizing blood damage during left ventricular assist device support.

Mechanism of Self-Regulation and In Vivo Performance of the Cleveland Clinic Continuous-Flow Total Artificial Heart.

Cleveland Clinic's continuous-flow total artificial heart (CFTAH) provides systemic and pulmonary circulations using one assembly (one motor, two impellers). The right pump hydraulic output to the pulmonary circulation is self-regulated by the rotating assembly's passive axial movement in response to atrial differential pressure to balance itself to the left pump output. This combination of features integrates a biocompatible, pressure-balancing regulator with a double-ended pump. The CFTAH requires no flow or pressure sensors. The only control parameter is pump speed, modulated at programmable rates (60-120 beats/min) and amplitudes (0 to ±25%) to provide flow pulses. In bench studies, passive self-regulation (range: -5 mm Hg ≤ [left atrial pressure - right atrial pressure] ≤ 10 mm Hg) was demonstrated over a systemic/vascular resistance ratio range of 2.0-20 and a flow range of 3-9 L/min. Performance of the most recent pump configuration was demonstrated in chronic studies, including three consecutive long-term experiments (30, 90, and 90 days). These experiments were performed at a constant postoperative mean speed with a ±15% speed modulation, demonstrating a totally self-regulating mode of operation, from 3 days after implant to explant, despite a weight gain of up to 40%. The mechanism of self-regulation functioned properly, continuously throughout the chronic in vivo experiments, demonstrating the performance goals.