Impact of continuous-flow mechanical circulatory support on cerebrospinal fluid motility.

BACKGROUND: Mechanical circulatory support (MCS), including ventricular assist devices (VADs), have emerged as promising therapeutic alternatives for end-stage congestive heart failure (CHF). The latest generation of these devices are continuous flow (CF) blood pumps. While there have been demonstrated benefits to patient outcomes due to CF-MCS, there continue to be significant clinical challenges. Research to-date has concentrated on mitigating thromboembolic risk (stroke), while the downstream impact of CF-MCS on the cerebrospinal fluid (CSF) flow has not been well investigated. Disturbances in the CSF pressure and flow patterns are known to be associated with neurologic impairment and diseased states. Thus, here we seek to develop an understanding of the pathophysiologic consequences of CF-MCS on CSF dynamics. METHODS: We built and validated a computational framework using lumped parameter modeling of cardiovascular, cerebrovascular physics, CSF dynamics, and autoregulation. A sensitivity analysis was performed to confirm robustness of the modeling framework. Then, we characterized the impact of CF-MCS on the CSF and investigated cardiovascular conditions of healthy and end-stage heart failure. RESULTS: Modeling results demonstrated appropriate hemodynamics and indicated that CSF pressure depends on blood flow pulsatility more than CSF flow. An acute equilibrium between CSF production and absorption was observed in the CF-MCS case, characterized by CSF pressure remaining elevated, and CSF flow rates remaining below healthy, but higher than CHF states. CONCLUSION: This research has advanced our understanding of the impact of CF-MCS on CSF dynamics and cerebral hemodynamics.

Channel impeller design for centrifugal blood pump in hybrid pediatric total artificial heart: Modeling, magnet integration, and hydraulic experiments.

BACKGROUND: The purpose of this research is to address ongoing device shortfalls for pediatric patients by developing a novel pediatric hybrid total artificial heart (TAH). The valveless magnetically-levitated MCS device (Dragon Heart) has only two moving parts, integrates an axial and centrifugal blood pump into a single device, and will occupy a compact footprint within the chest for the pediatric patient population. METHODS: Prior work on the Dragon Heart focused on the development of pump designs to achieve hemodynamic requirements. The impeller of these pumps was shaft-driven and thus could not be integrated for testing. The presented research leverages an existing magnetically levitated axial flow pump and focuses on centrifugal pump development. Using the axial pump diameter as a geometric constraint, a shaftless, magnetically supported centrifugal pump was designed for placement circumferentially around the axial pump domain. The new design process included the computational analysis of more than 50 potential centrifugal impeller geometries. The resulting centrifugal pump designs were prototyped and tested for levitation and no-load rotation, followed by in vitro testing using a blood analog. To meet physiologic demands, target performance goals were pressure rises exceeding 90 mm Hg for flow rates of 1-5 L/min with operating speeds of less than 5000 RPM. RESULTS: Three puck-shaped, channel impellers for the centrifugal blood pump were selected based on achieving performance and space requirements for magnetic integration. A quasi-steady flow analysis revealed that the impeller rotational position led to a pulsatile component in the pressure generation. After prototyping, the centrifugal prototypes (3, 4, and 5 channeled designs) demonstrated levitation and no-load rotation. Hydraulic experiments established pressure generation capabilities beyond target requirements. The pressure-flow performance of the prototypes followed expected trends with a dependence on rotational speed. Pulsatile blood flow was observed without pump-speed modulation due to rotating channel passage frequency. CONCLUSION: The results are promising in the advancement of this pediatric TAH. The channeled impeller design creates pressure-flow curves that are decoupled from the flow rate, a benefit that could reduce the required controller inputs and improve treatment of hypertensive patients.

Technology landscape of pediatric mechanical circulatory support devices: A systematic review 2010-2021.

BACKGROUND: Mechanical circulatory support (MCS) devices, such as ventricular assist devices (VADs) and total artificial hearts (TAHs), have become a vital therapeutic option in the treatment of end-stage heart failure for adult patients. Such therapeutic options continue to be limited for pediatric patients. Clinicians initially adapted or scaled existing adult devices for pediatric patients; however, these adult devices are not designed to support the anatomical structure and varying flow capacities required for this population and are generally operated "off-design," which risks complications such as hemolysis and thrombosis. Devices designed specifically for the pediatric population which seek to address these shortcomings are now emerging and gaining FDA approval. METHODS: To analyze the competitive landscape of pediatric MCS devices, we conducted a systematic literature review. Approximately 27 devices were studied in detail: 8 were established or previously approved designs, and 19 were under development (11 VADs, 5 Fontan assist devices, and 3 TAHs). RESULTS: Despite significant progress, there is still no pediatric pump technology that satisfies the unique and distinct design constraints and requirements to support pediatric patients, including the wide range of patient sizes, increased cardiovascular demand with growth, and anatomic and physiologic heterogeneity of congenital heart disease. CONCLUSIONS: Forward-thinking design solutions are required to overcome these challenges and to ensure the translation of new therapeutic MCS devices for pediatric patients.

Invited commentary: Total anomalous pulmonary venous connection remains a challenging pediatric disease.

Cervantes-Salazar and colleagues report the long-term surgical outcomes of 414 patients with total anomalous pulmonary venous connection (TAPVC) from January 2003 to June 2019. With an overall survival rate of 87.2% from 2003 to 2019, the authors found that an increased mortality risk was associated with infracardiac TAPVC, pulmonary venous obstruction, and postoperative mechanical ventilation. Their comprehensive study with a large sample size of varying age groups, and patients with late referrals for surgery, provide valuable insight into TAPVC surgical outcomes. Improved survival for these patients continues to be a major goal of clinical teams striving to transform treatment paradigms. The promising result of the study reported by Cervantes-Salazar and colleagues gives our field hope for a better future for these patients.

Novel hybrid total artificial heart with integrated oxygenator.

There continues to be an unmet therapeutic need for an alternative treatment strategy for respiratory distress and lung disease. We are developing a portable cardiopulmonary support system that integrates an implantable oxygenator with a hybrid, dual-support, continuous-flow total artificial heart (TAH). The TAH has a centrifugal flow pump that is rotating about an axial flow pump. By attaching the hollow fiber bundle of the oxygenator to the base of the TAH, we establish a new cardiopulmonary support technology that permits a patient to be ambulatory during usage. In this study, we investigated the design and improvement of the blood flow pathway from the inflow-to-outflow of four oxygenators using a mathematical model and computational fluid dynamics (CFD). Pressure loss and gas transport through diffusion were examined to assess oxygenator design. The oxygenator designs led to a resistance-driven pressure loss range of less than 35 mmHg for flow rates of 1-7 L/min. All of the designs met requirements. The configuration having an outside-to-inside blood flow direction was found to have higher oxygen transport. Based on this advantageous flow direction, two designs (Model 1 and 3) were then integrated with the axial-flow impeller of the TAH for simulation. Flow rates of 1-7 L/min and speeds of 10,000-16,000 RPM were analyzed. Blood damage studies were performed, and Model 1 demonstrated the lowest potential for hemolysis. Future work will focus on developing and testing a physical prototype for integration into the new cardiopulmonary assist system.

The newly emerging field of pediatric engineering: Innovation for our next generation.

Neonates, infants, and children have unique physiology and body surface areas that dramatically change during growth and development, and the substantial diversity of complicated pediatric illnesses and rare childhood diseases are distinct from the adult sphere. Unfortunately, medical innovation is generally constrained to retrofitting adult treatment strategies for this heterogeneous population. This conventional, but limited, approach ignores the dynamic biopsychosocial, growth, and developmental complexities that abound, as one progresses through this life cycle from newborn onward toward early adulthood. Forward-thinking solutions are essential to advance the state-of-the-art to address the challenges and unmet clinical needs that are uniquely presented by the pediatric population, and it has become obvious that newly trained engineers are essential for success. These unmet clinical needs and the necessity of new technical skills and expertise give rise to the emergence of an entirely new field of engineering and applied science: Pediatric Engineering. The field of Pediatric Engineering flips conventional wisdom that adult therapies can simply be scaled or successfully modified for children. It commandeers design to suit the specific needs of the child, while anticipating the dynamic growth and development into adulthood. We are growing a new pipeline of educated scientists and engineers who will have developed a unique toolbox of skills that they can use to tackle unmet clinical needs in global pediatric healthcare for years to come.

Fluid-structure interaction analysis of a collapsible axial flow blood pump impeller and protective cage for Fontan patients.

Limited donor organs and alternative therapies have led to a growing interest in the use of blood pumps as a treatment strategy for patients with single functional ventricle. The present study examines the use of collapsible and flexible impeller, cage, and diffuser designs of an axial blood pump for Fontan patients. Using one-way fluid-structure interaction (FSI) studies, the impact of blade deformation on blood damage and pump performance was investigated for flexible impellers. We evaluated biocompatible materials, including Nitinol, Bionate 80A polyurethane, and silicone for flow rates between 2.0-4.0 L/min and rotational speeds of 3000-9000 rpm. The level of deformation experienced by a cage and diffuser made of surgical stainless steel (control), Nitinol, and Bionate 80A polyurethane was also predicted using one-way FSI. The fluid pressure on the surface of the impeller, cage, and diffuser was determined using computational fluid dynamics (CFD), and then, the surface pressure was exported and used to investigate the impeller, cage, and diffuser deformation using finite element analysis. Finally, deformed impeller geometries were imported into the CFD software to determine the implication of deformation on pressure generation, blood damage index, and fluid streamlines. It was found that rotational speed, and not flow rate, is the largest determinant of impeller deformation, occurring at the blade trailing edges. The models predicted the maximum impeller deformation for Nitinol to be 40 nm, Bionate 80A polyurethane to be 106 µm, and silicone to be 2.8 mm, all occurring at 9000 rpm. The effects of silicone deformation on performance were significant, particularly at speeds above 5000 rpm where a decrease in pressure generation of more than 10% was observed. Despite this loss, the pressure generation at 5000 rpm exceeded the level required to alleviate Fontan complications. A blood damage estimation was performed and levels remained low. The effect of significant impeller deformation on blood damage was inconsistent and requires additional investigation. Cage and diffuser geometries made of steel and Nitinol deformed minimally but Bionate 80A experienced unacceptable levels of deformation, particularly in the free-flow case without a spinning impeller. These results support the continued evaluation of a flexible, pitch-adjusting, axial-flow, mechanical assist device as a clinical therapeutic option for patients with dysfunctional Fontan physiology.

Clinical implications of LDH isoenzymes in hemolysis and continuous-flow left ventricular assist device-induced thrombosis.

Pump-induced thrombosis continues to be a major complication of continuous-flow left ventricular assist devices (CF-LVADs), which increases the risks of thromboembolic stroke, peripheral thromboembolism, reduced pump flow, pump failure, cardiogenic shock, and death. This is confounded by the fact that there is currently no direct measure for a proper diagnosis during pump support. Given the severity of this complication and its required treatment, the ability to accurately differentiate CF-LVAD pump thrombosis from other complications is vital. Hemolysis measured by elevated lactate dehydrogenase (LDH) enzyme levels, when there is clinical suspicion of pump-induced thrombosis, is currently accepted as an important metric used by clinicians for diagnosis; however, LDH is a relatively nonspecific finding. LDH exists as five isoenzymes in the body, each with a unique tissue distribution. CF-LVAD pump thrombosis has been associated with elevated serum LDH-1 and LDH-2, as well as decreased LDH-4 and LDH-5. Herein, we review the various isoenzymes of LDH and their utility in differentiating hemolysis seen in CF-LVAD pump thrombosis from other physiologic and pathologic conditions as reported in the literature.

Mechanical Circulatory Support Devices for Pediatric Patients With Congenital Heart Disease.

The use of mechanical circulatory support (MCS) devices is a viable therapeutic treatment option for patients with congestive heart failure. Ventricular assist devices, cavopulmonary assist devices, and total artificial heart pumps continue to gain acceptance as viable treatment strategies for both adults and pediatric patients as bridge-to-transplant, bridge-to-recovery, and longer-term circulatory support alternatives. We present a review of the current and future MCS devices for patients having congenital heart disease (CHD) with biventricular or univentricular circulations. Several devices that are specifically designed for patients with complex CHD are in the development pipeline undergoing rigorous animal testing as readiness experiments in preparation for future clinical trials. These advances in the development of new blood pumps for patients with CHD will address a significant unmet clinical need, as well as generally improve innovation of the current state of the art in MCS technology.

Beyond the VAD: Human Factors Engineering for Mechanically Assisted Circulation in the 21st Century.

Thousands of ventricular assist devices (VADs) currently provide circulatory support to patients worldwide, and dozens of heart pump designs for adults and pediatric patients are under various stages of development in preparation for translation to clinical use. The successful bench-to-bedside development of a VAD involves a structured evaluation of possible system states, including human interaction with the device and auxiliary component usage in the hospital or home environment. In this study, we review the literature and present the current landscape of preclinical design and assessment, decision support tools and procedures, and patient-centered therapy. Gaps of knowledge are identified. The study findings support the need for more attention to user-centered design approaches for medical devices, such as mechanical circulatory assist systems, that specifically involve detailed qualitative and quantitative assessments of human-device interaction to mitigate risk and failure.

Pressure-Flow Experimental Performance of New Intravascular Blood Pump Designs for Fontan Patients.

An intravascular axial flow pump is being developed as a mechanical cavopulmonary assist device for adolescent and adult patients with dysfunctional Fontan physiology. Coupling computational modeling with experimental evaluation of prototypic designs, this study examined the hydraulic performance of 11 impeller prototypes with blade stagger or twist angles varying from 100 to 600 degrees. A refined range of twisted blade angles between 300 and 400 degrees with 20-degree increments was then selected, and four additional geometries were constructed and hydraulically evaluated. The prototypes met performance expectations and produced 3-31 mm Hg for flow rates of 1-5 L/min for 6000-8000 rpm. A regression analysis was completed with all characteristic coefficients contributing significantly (P < 0.0001). This analysis revealed that the impeller with 400 degrees of blade twist outperformed the other designs. The findings of the numerical model for 300-degree twisted case and the experimental results deviated within approximately 20%. In an effort to simplify the impeller geometry, this work advanced the design of this intravascular cavopulmonary assist device closer to preclinical animal testing.

Three-dimensional laser flow measurements of a patient-specific fontan physiology with mechanical circulatory assistance.

Mechanical assistance of the Fontan circulation is hypothesized to enhance ventricular preload and improve cardiac output; however, little is known about the fluid dynamics. This study is the first to investigate the three-dimensional flow conditions of a blood pump in an anatomic Fontan. Laser measurements were conducted having an axial flow impeller in the inferior vena cava. Experiments were performed for a physiologic cardiac output, pulmonary arterial flows, and pump speeds of 1000-4000 rpm. The impeller had a modest effect on the flow conditions entering the total cavopulmonary connection at low pump speeds, but a substantial impact on the velocity at higher speeds. The higher speeds of the pump disrupted the recirculation region in the center of the anastomosis, which could be advantageous for washout purposes. No retrograde velocities in the superior vena cava were measured. These findings indicate that mechanical assistance is a viable therapeutic option for patients having dysfunctional single ventricle physiology.

Stereo-particle image velocimetry measurements of a patient-specific Fontan physiology utilizing novel pressure augmentation stents.

Single ventricle anomalies are a challenging set of congenital heart defects that require lifelong clinical management due to progressive decline of cardiovascular function. Few therapeutic devices are available for these patients, and conventional blood pumps are not designed for the unique anatomy of the single ventricle physiology. To address this unmet need, we are developing an axial flow blood pump with a protective cage or stent for Fontan patients. This study investigates the 3-D particle image velocimetry measurements of two cage designs being deployed in a patient-specific Fontan anatomy. We considered a control case without a pump, impeller placed in the inferior vena cava, and two cases where the impeller has two protective stents with unique geometric characteristics. The experiments were evaluated at a cardiac output of 3 L/min, a fixed vena caval flow split of 40%/60%, a fixed pulmonary arterial flow split of 50%/50%, and for operating speeds of 1000-4000 rpm. The introduction of the cardiovascular stents had a substantial impact on the flow conditions leaving the pump and entering the cavopulmonary circulation. The findings indicated that rotational speeds above 4000 rpm for this pump could result in irregular flows in this specific circulatory condition. Although retrograde flow into the superior vena cava was not measured, the risk of this occurrence increases with higher pump speeds. The against-with stent geometry outperformed the other configurations by generating higher pressures and more energetic flows. These results provide further support for the viability of mechanical cavopulmonary assistance as a therapeutic treatment strategy for Fontan patients.

Design of axial blood pumps for patients with dysfunctional fontan physiology: computational studies and performance testing.

Limited treatment options for patients having dysfunctional single ventricle physiology motivate the necessity for alternative therapeutic options. To address this unmet need, we are developing a collapsible axial flow blood pump. This study investigated the impact of geometric simplicity to facilitate percutaneous placement and maintain optimal performance. Three new pump designs were numerically evaluated. A transient simulation explored the impact of respiration on blood flow conditions over the entire respiratory cycle. Prototype testing of the top performing pump design was completed. The top performing Rec design generated the highest pressure rise range of 2-38 mm Hg for flow rates of 1-4 L/min at 4000-7000 RPM, exceeding the performance of the other two configurations by more than 26%. The blood damage indices for the new pump designs were determined to be below 0.5% and predicted hemolysis levels remained low at less than 7 × 10(-5) g/100 L. Prototype testing of the Rec design confirmed numerical predictions to within an average of approximately 22%. These findings demonstrate that the pumps are reasonably versatile in operational ability, meet pressure-flow requirements to support Fontan patients, and are expected to have low levels of blood trauma.

Total Artificial Hearts-Past, Current, and Future.

We present a review of the evolution of total artificial hearts (TAHs) and new directions in development, including the coupling of VADs as biventricular TAH support.

Experimental measurements of energy augmentation for mechanical circulatory assistance in a patient-specific Fontan model.

A mechanical blood pump specifically designed to increase pressure in the great veins would improve hemodynamic stability in adolescent and adult Fontan patients having dysfunctional cavopulmonary circulation. This study investigates the impact of axial-flow blood pumps on pressure, flow rate, and energy augmentation in the total cavopulmonary circulation (TCPC) using a patient-specific Fontan model. The experiments were conducted for three mechanical support configurations, which included an axial-flow impeller alone in the inferior vena cava (IVC) and an impeller with one of two different protective stent designs. All of the pump configurations led to an increase in pressure generation and flow in the Fontan circuit. The increase in IVC flow was found to augment pulmonary arterial flow, having only a small impact on the pressure and flow in the superior vena cava (SVC). Retrograde flow was neither observed nor measured from the TCPC junction into the SVC. All of the pump configurations enhanced the rate of power gain of the cavopulmonary circulation by adding energy and rotational force to the fluid flow. We measured an enhancement of forward flow into the TCPC junction, reduction in IVC pressure, and only minimally increased pulmonary arterial pressure under conditions of pump support.

Dual-pump support in the inferior and superior vena cavae of a patient-specific fontan physiology.

The implementation of simultaneous mechanical cavopulmonary assistance having blood pumps located in both of the vena cavae is investigated as an approach to treating patients with an ailing Fontan physiology. Identical intravascular blood pumps are employed to model the hemodynamic support of a patient-specific Fontan. Pressure flow characteristics, energy gain calculations, and blood damage analyses are assessed for each model. The performance of the dual-support scenario is compared to conditions of mechanical support in the inferior vena cava only and to a nonsupported cavopulmonary circuit. The blood pump in the superior vena cava generates pressures ranging from 1 to 22 mm Hg for flow rates of 1-4 L/min at operating speeds of 1250-2500 rpm. The blood pump in the inferior vena cava produces pressures at levels approximately 20% lower. The blood pumps positively augment the hydraulic energy in the total cavopulmonary connection circuit as a function of flow rate and rotational speed. Scalar stress levels and fluid residence times are at acceptable levels. Damage indices for the dual-support case, however, are elevated slightly above 3.5%. These results suggest that concurrent, mechanical assistance of the inferior vena cava and superior vena cava in Fontan patients has the potential to be beneficial, but additional studies are needed to further explore this approach.

A viable therapeutic option: mechanical circulatory support of the failing Fontan physiology.

A blood pump specifically designed to augment flow from the great veins through the lungs would ameliorate the poor physiology of the failing univentricular circulation and result in a paradigm shift in the treatment strategy for Fontan patients. This study is the first to examine mechanical cavopulmonary assistance with a blood pump in the inferior vena cava (IVC) and hepatic blood flow. Five numerical models of mechanical cavopulmonary assistance were investigated using a three-dimensional, reconstructed, patient-specific Fontan circulation from magnetic resonance imaging data. Pressure flow characteristics of the axial blood pump, energy augmentation calculations for the cavopulmonary circulation with and without pump support, and hemolysis estimations were determined. In all of the pump-supported scenarios, a pressure increase of 7-9.5 mm Hg was achieved. The fluid power of the cavopulmonary circulation was also positive over the range of flow rates. No retrograde flow from the IVC into the hepatic circulation was evident during support cases. Vessel suction risk, however, was found for greater operating rotational speeds. Fluid shear stresses and hemolysis predictions remained at acceptable levels with normalized index of hemolysis estimations at 0.0001 g/100 L. The findings of this study support the continued design and development of this blood pump technology for Fontan patients with progressive cardiovascular insufficiency. Validation of these flow and performance predictions will be completed in the next round of experimental testing with blood bag evaluation.

Next Generation Development of Hybrid Continuous Flow Pediatric Total Artificial Heart Technology: Design-Build-Test.

To address the unmet clinical need for pediatric circulatory support, we are developing an operationally versatile, hybrid, continuous-flow, total artificial heart ("Dragon Heart"). This device integrates a magnetically levitated axial and centrifugal blood pump. Here, we utilized a validated axial flow pump, and we focused on the development of the centrifugal pump. A motor was integrated to drive the centrifugal pump, achieving 50% size reduction. The motor design was simulated by finite element analysis, and pump design improvement was attained by computational fluid dynamics. A prototype centrifugal pump was constructed from biocompatible 3D printed parts for the housing and machined metal parts for the drive system. Centrifugal prototype testing was conducted using water and then bovine blood. The fully combined device ( i.e. , axial pump nested inside of the centrifugal pump) was tested to ensure proper operation. We demonstrated the hydraulic performance of the two pumps operating in tandem, and we found that the centrifugal blood pump performance was not adversely impacted by the simultaneous operation of the axial blood pump. The current iteration of this design achieved a range of operation overlapping our target range. Future design iterations will further reduce size and incorporate complete and active magnetic levitation.