Sodium bicarbonate as a local adjunctive agent for limiting platelet activation, aggregation, and adhesion within cardiovascular therapeutic devices.

Cardiovascular therapeutic devices (CTDs) remain limited by thrombotic adverse events. Current antithrombotic agents limit thrombosis partially, often adding to bleeding. The Impella® blood pump utilizes heparin in 5% dextrose (D5W) as an internal purge to limit thrombosis. While effective, exogenous heparin often complicates overall anticoagulation management, increasing bleeding tendency. Recent clinical studies suggest sodium bicarbonate (bicarb) may be an effective alternative to heparin for local anti-thrombosis. We examined the effect of sodium bicarbonate on human platelet morphology and function to better understand its translational utility. Human platelets were incubated (60:40) with D5W + 25 mEq/L, 50 mEq/L, or 100 mEq/L sodium bicarbonate versus D5W or D5W + Heparin 50 U/mL as controls. pH of platelet-bicarbonate solutions mixtures was measured. Platelet morphology was examined via transmission electron microscopy; activation assessed via P-selectin expression, phosphatidylserine exposure and thrombin generation; and aggregation with TRAP-6, calcium ionophore, ADP and collagen quantified; adhesion to glass measured via fluorescence microscopy. Sodium bicarbonate did not alter platelet morphology but did significantly inhibit activation, aggregation, and adhesion. Phosphatidylserine exposure and thrombin generation were both reduced in a concentration-dependent manner-between 26.6 ± 8.2% (p = 0.01) and 70.7 ± 5.6% (p < 0.0001); and 14.0 ± 6.2% (p = 0.15) and 41.7 ± 6.8% (p = 0.03), respectively, compared to D5W control. Platelet aggregation via all agonists was also reduced, particularly at higher concentrations of bicarb. Platelet adhesion to glass was similarly reduced, between 0.04 ± 0.03% (p = 0.61) and 0.11 ± 0.04% (p = 0.05). Sodium bicarbonate has direct, local, dose-dependent effects limiting platelet activation and adhesion. Our results highlight the potential utility of sodium bicarbonate as a locally acting agent to limit device thrombosis.

Sodium bicarbonate alters protein stability and blood coagulability in a simulated Impella purge gap model.

BACKGROUND: The Impella® microaxial blood pumps utilize purge fluid containing heparin to prevent biofouling of internal surfaces. Purge fluid interfaces with blood or blood components at two notable internal locations: (1) 5-8 µm radial gap ("Radial Gap" or "Gap 1") between the motor shaft and bearing, a site accessible by blood proteins or small molecules; and (2) 100 µm axial gap ("Axial Gap" or "Gap 2") between the impeller rotor and bearing, the site of mixing with larger circulating blood components. Despite its efficacy, heparin in the purge fluid complicates overall patient anticoagulation management. Here, we investigate sodium bicarbonate as an alternative to heparin in the purge fluid in a simulated purge gap micro-environment. METHODS: To assess protein stability simulated at Gap 1, human serum albumin (HSA; 40 mg/ml) species were quantified utilizing size exclusion liquid chromatography (SEC-HPLC) after stirring with purge fluid (5% dextrose in water (D5W) with heparin (25 U/ml) or sodium bicarbonate (25 or 50 mEq/L)) over a 24-h period. pH measurements were taken immediately prior to stirring. Mixing between blood and purge fluid at Gap 2 was mimicked in vitro utilizing a 60:40 blood: purge fluid ratio. Purge fluid consisted of D5W with or without sodium bicarbonate (25 or 50 mEq/L). Human citrated blood samples were freshly collected with or without the addition of heparin (5 U/ml). Coagulability was determined via thromboelastography (TEG). pH measurements of blood mixtures were taken immediately before and after TEG analysis. RESULTS: Sodium bicarbonate alone or synergistically with heparin was effective in increasing protein stability, increasing pH, and reducing coagulability. In the Gap 1 model, sodium bicarbonate led to preservation of HSA monomer after 24 h mixing, with monomer composing 88.3 ± 2.3% and 88.6 ± 0.9% of total HSA species for 25 or 50 mEq/L sodium bicarbonate, respectively. Only 60.4 ± 4.3% monomer was observed with D5W alone (p < 0.005). HSA aggregates and fragments were evident in heparin and D5W purge mixtures, but absent in sodium bicarbonate (25 and 50 mEq/L). pH of HSA mixtures significantly increased in the presence of sodium bicarbonate. In the Gap 2 model, combined heparin (5 U/ml) and sodium bicarbonate prolonged clotting time (TEG-ACT), leading to an average increase of 795 ± 275 s (p = 0.04) and 846 243 s (p = 0.03). This trend of reduced coagulability was similarly observed in clot initiation time (R time), clot formation time (K time), and clotting rate (α angle). Blood mixture pH measurements increased with addition of sodium bicarbonate in both heparinized and non-heparinized blood samples. CONCLUSION: Sodium bicarbonate in the purge fluid has the potential to significantly increase protein stability and reduce protein denaturation at the Impella® radial gap (Gap 1), while reducing blood coagulation at the Impella® axial gap (Gap 2). The influence of sodium bicarbonate on the biochemical environment of the purge fluid may ensure stable purge flow resistance and play a synergistic or supportive role in the purge gap micro-environment when used with systemic anticoagulation.

Shear-Mediated Platelet Microparticles Demonstrate Phenotypic Heterogeneity as to Morphology, Receptor Distribution, and Hemostatic Function.

Implantable Cardiovascular Therapeutic Devices (CTD), while lifesaving, impart supraphysiologic shear stress to platelets, resulting in thrombotic and bleeding coagulopathy. We previously demonstrated that shear-mediated platelet dysfunction is associated with downregulation of platelet GPIb-IX-V and αIIbß3 receptors via generation of Platelet-Derived MicroParticles (PDMPs). Here, we test the hypothesis that sheared PDMPs manifest phenotypical heterogeneity of morphology and receptor surface expression and modulate platelet hemostatic function. Human gel-filtered platelets were exposed to continuous shear stress. Alterations of platelet morphology were visualized using transmission electron microscopy. Surface expression of platelet receptors and PDMP generation were quantified by flow cytometry. Thrombin generation was quantified spectrophotometrically, and platelet aggregation was measured by optical aggregometry. Shear stress promotes notable alterations in platelet morphology and ejection of distinctive types of PDMPs. Shear-mediated microvesiculation is associated with the remodeling of platelet receptors, with PDMPs expressing significantly higher levels of adhesion receptors (αIIbß3, GPIX, PECAM-1, P-selectin, and PSGL-1) and agonist receptors (P2Y12 and PAR1). Sheared PDMPs promote thrombin generation and inhibit platelet aggregation induced by collagen and ADP. Sheared PDMPs demonstrate phenotypic heterogeneity as to morphology and defined patterns of surface receptors and impose a bidirectional effect on platelet hemostatic function. PDMP heterogeneity suggests that a range of mechanisms are operative in the microvesiculation process, contributing to CTD coagulopathy and posing opportunities for therapeutic manipulation.

DNA Origami-Platelet Adducts: Nanoconstruct Binding without Platelet Activation.

Objective. Platelets are small, mechanosensitive blood cells responsible for maintaining vascular integrity and activatable on demand to limit bleeding and facilitate thrombosis. While circulating in the blood, platelets are exposed to a range of mechanical and chemical stimuli, with the platelet membrane being the primary interface and transducer of outside-in signaling. Sensing and modulating these interface signals would be useful to study mechanochemical interactions; yet, to date, no methods have been defined to attach adducts for sensor fabrication to platelets without triggering platelet activation. We hypothesized that DNA origami, and methods for its attachment, could be optimized to enable nonactivating instrumentation of the platelet membrane. Approach and Results. We designed and fabricated multivalent DNA origami nanotile constructs to investigate nanotile hybridization to membrane-embedded single-stranded DNA-tetraethylene glycol cholesteryl linkers. Two hybridization protocols were developed and validated (Methods I and II) for rendering high-density binding of DNA origami nanotiles to human platelets. Using quantitative flow cytometry, we showed that DNA origami binding efficacy was significantly improved when the number of binding overhangs was increased from two to six. However, no additional binding benefit was observed when increasing the number of nanotile overhangs further to 12. Using flow cytometry and transmission electron microscopy, we verified that hybridization with DNA origami constructs did not cause alterations in the platelet morphology, activation, aggregation, or generation of platelet-derived microparticles. Conclusions. Herein, we demonstrate that platelets can be successfully instrumented with DNA origami constructs with no or minimal effect on the platelet morphology and function. Our protocol allows for efficient high-density binding of DNA origami to platelets using low quantities of the DNA material to label a large number of platelets in a timely manner. Nonactivating platelet-nanotile adducts afford a path for advancing the development of DNA origami nanoconstructs for cell-adherent mechanosensing and therapeutic agent delivery.

Platelet Dysfunction During Mechanical Circulatory Support: Elevated Shear Stress Promotes Downregulation of αIIbß3 and GPIb via Microparticle Shedding Decreasing Platelet Aggregability.

[Figure: see text].

Vascular endothelial and smooth muscle cell galvanotactic response and differential migratory behavior.

Chronic disease or injury of the vasculature impairs the functionality of vascular wall cells particularly in their ability to migrate and repair vascular surfaces. Under pathologic conditions, vascular endothelial cells (ECs) lose their non-thrombogenic properties and decrease their motility. Alternatively, vascular smooth muscle cells (SMCs) may increase motility and proliferation, leading to blood vessel luminal invasion. Current therapies to prevent subsequent blood vessel occlusion commonly mechanically injure vascular cells leading to endothelial denudation and smooth muscle cell luminal migration. Due to this dichotomous migratory behavior, a need exists for modulating vascular cell growth and migration in a more targeted manner. Here, we examine the efficacy of utilizing small direct current electric fields to influence vascular cell-specific migration ("galvanotaxis"). We designed, fabricated, and implemented an in vitro chamber for tracking vascular cell migration direction, distance, and displacement under galvanotactic influence of varying magnitude. Our results indicate that vascular ECs and SMCs have differing responses to galvanotaxis; ECs exhibit a positive correlation of anodal migration while SMCs exhibit minimal change in directional migration in relation to the electric field direction. SMCs exhibit less motility response (i.e. distance traveled in 4 h) compared to ECs, but SMCs show a significantly higher motility at low electric potentials (80 mV/cm). With further investigation and translation, galvanotaxis may be an effective solution for modulation of vascular cell-specific migration, leading to enhanced endothelialization, with coordinate reduced smooth muscle in-migration.

A computational framework for post-TAVR cardiac conduction abnormality (CCA) risk assessment in patient-specific anatomy.

BACKGROUND: Cardiac conduction abnormality (CCA)- one of the major persistent complications associated with transcatheter aortic valve replacement (TAVR) may lead to permanent pacemaker implantation. Localized stresses exerted by the device frame on the membranous septum (MS) which lies between the aortic annulus and the bundle of His, may disturb the cardiac conduction and cause the resultant CCA. We hypothesize that the area-weighted average maximum principal logarithmic strain (AMPLS) in the MS region can predict the risk of CCA following TAVR. METHODS: Rigorous finite element-based analysis was conducted in two patients (Balloon expandable TAVR recipients) to assess post-TAVR CCA risk. Following the procedure one of the patients required permanent pacemaker (PPM) implantation while the other did not (control case). Patient-specific aortic root was modeled, MS was identified from the CT image, and the TAVR deployment was simulated. Mechanical factors in the MS region such as logarithmic strain, contact force, contact pressure, contact pressure index (CPI) and their time history during the TAVR deployment; and anatomical factors such as MS length, implantation depth, were analyzed. RESULTS: Maximum AMPLS (0.47 and 0.37, respectively), contact force (0.92 N and 0.72 N, respectively), and CPI (3.99 and 2.86, respectively) in the MS region were significantly elevated in the PPM patient as compared to control patient. CONCLUSION: Elevated stresses generated by TAVR devices during deployment appear to correlate with CCA risk, with AMPLS in the MS region emerging as a strong predictor that could be used for preprocedural planning in order to minimize CCA risk.

Visions of TAVR Future: Development and Optimization of a Second Generation Novel Polymeric TAVR.

Tissue-based transcatheter aortic valve (AV) replacement (TAVR) devices have been a breakthrough approach for treating aortic valve stenosis. However, with the expansion of TAVR to younger and lower risk patients, issues of long-term durability and thrombosis persist. Recent advances in polymeric valve technology facilitate designing more durable valves with minimal in vivo adverse reactions. We introduce our second-generation polymeric transcatheter aortic valve (TAV) device, designed and optimized to address these issues. We present the optimization process of the device, wherein each aspect of device deployment and functionality was optimized for performance, including unique considerations of polymeric technologies for reducing the volume of the polymer material for lower crimped delivery profiles. The stent frame was optimized to generate larger radial forces with lower material volumes, securing robust deployment and anchoring. The leaflet shape, combined with varying leaflets thickness, was optimized for reducing the flexural cyclic stresses and the valve's hydrodynamics. Our first-generation polymeric device already demonstrated that its hydrodynamic performance meets and exceeds tissue devices for both ISO standard and patient-specific in vitro scenarios. The valve already reached 900 × 106 cycles of accelerated durability testing, equivalent to over 20 years in a patient. The optimization framework and technology led to the second generation of polymeric TAV design- currently undergoing in vitro hydrodynamic testing and following in vivo animal trials. As TAVR use is rapidly expanding, our rigorous bio-engineering optimization methodology and advanced polymer technology serve to establish polymeric TAV technology as a viable alternative to the challenges facing existing tissue-based TAV technology.

Patient-specific in vitro testing for evaluating TAVR clinical performance-A complementary approach to current ISO standard testing.

Following in vitro tests established for surgical prosthetic heart valves, transcatheter aortic valves (TAV) are similarly tested in idealized geometries-excluding effects that may hamper TAVR performance in situ. Testing in vitro in pulse duplicator systems that incorporated patient-specific replicas would enhance the testing veracity by bringing it closer to the clinical scenario. To that end we compare TAV hemodynamic performance tested in idealized geometries according to the ISO standard (baseline performance) to that obtained by testing the TAVs following deployment in patient-specific replicas. Balloon-expandable (n = 2) and self-expandable (n = 3) TAVs were tested in an idealized geometry in mock-circulation system (following ISO 5840-3 guidelines) and compared to the measurements in a dedicated mock-circulation system adapted for the five patient-specific replicas. Patient-specific deployments resulted in a decline in performance as compared to the baseline idealized testing, as well as a variation in performance that depended on the design features of each device that was further correlated with the radial expansion and eccentricity of the deployed TAV stent (obtained with CT-scans of the deployed valves). By excluding the deployment effects in irregular geometries, the current idealized ISO testing is limited to characterize the baseline device performance. Utilizing patient-specific anatomic contours provides performance indicators under more stringent conditions likely encountered in vivo. It has the potential to enhance testing and development complementary to the ISO standard, for improved TAV safety and effectiveness.

Relation between blood pressure and pulse wave velocity for human arteries.

Continuous monitoring of blood pressure, an essential measure of health status, typically requires complex, costly, and invasive techniques that can expose patients to risks of complications. Continuous, cuffless, and noninvasive blood pressure monitoring methods that correlate measured pulse wave velocity (PWV) to the blood pressure via the Moens-Korteweg (MK) and Hughes Equations, offer promising alternatives. The MK Equation, however, involves two assumptions that do not hold for human arteries, and the Hughes Equation is empirical, without any theoretical basis. The results presented here establish a relation between the blood pressure P and PWV that does not rely on the Hughes Equation nor on the assumptions used in the MK Equation. This relation degenerates to the MK Equation under extremely low blood pressures, and it accurately captures the results of in vitro experiments using artificial blood vessels at comparatively high pressures. For human arteries, which are well characterized by the Fung hyperelastic model, a simple formula between P and PWV is established within the range of human blood pressures. This formula is validated by literature data as well as by experiments on human subjects, with applicability in the determination of blood pressure from PWV in continuous, cuffless, and noninvasive blood pressure monitoring systems.

Identification and quantitation of clinically relevant microbes in patient samples: Comparison of three k-mer based classifiers for speed, accuracy, and sensitivity.

Infections are a serious health concern worldwide, particularly in vulnerable populations such as the immunocompromised, elderly, and young. Advances in metagenomic sequencing availability, speed, and decreased cost offer the opportunity to supplement or even replace culture-based identification of pathogens with DNA sequence-based diagnostics. Adopting metagenomic analysis for clinical use requires that all aspects of the workflow are optimized and tested, including data analysis and computational time and resources. We tested the accuracy, sensitivity, and resource requirements of three top metagenomic taxonomic classifiers that use fast k-mer based algorithms: Centrifuge, CLARK, and KrakenUniq. Binary mixtures of bacteria showed all three reliably identified organisms down to 1% relative abundance, while only the relative abundance estimates of Centrifuge and CLARK were accurate. All three classifiers identified the organisms present in their default databases from a mock bacterial community of 20 organisms, but only Centrifuge had no false positives. In addition, Centrifuge required far less computational resources and time for analysis. Centrifuge analysis of metagenomes obtained from samples of VAP, infected DFUs, and FN showed Centrifuge identified pathogenic bacteria and one virus that were corroborated by culture or a clinical PCR assay. Importantly, in both diabetic foot ulcer patients, metagenomic sequencing identified pathogens 4-6 weeks before culture. Finally, we show that Centrifuge results were minimally affected by elimination of time-consuming read quality control and host screening steps.

Migration versus proliferation as contributor to in vitro wound healing of vascular endothelial and smooth muscle cells.

Wound closure, as a result of collective cell growth, is an essential biological response to injury. In the field of vascular biology, the response of vascular smooth muscle cells (SMCs) and endothelial cells (ECs) to injury and substrate surface is important in therapeutic clinical treatment interventions such as angioplasty and atherectomy. Specifically, the mechanism by which cells close wounds (i.e. proliferation versus migration) in response to injury stimuli is of interest to better modulate recurrent vascular stenosis, prevent thrombus formation, occlusion, and life-threatening cardiovascular events. Here, we examine growth extent and temporal sequence of events following wound or gap introduction to a confluent monolayer of vascular SMCs or ECs. Significant differences in the preferred mechanisms of these cells to close wounds or gaps were observed; after 48 h, 73% of SMC wound closure was observed to be due to proliferation, while 75% of EC wound closure resulted from migration. These mechanisms were further modulated via addition or removal of extracellular matrix substrate and injury, with ECs more responsive to substrate composition and less to injury, in comparison to SMCs. Our results indicate that ECs and SMCs heal wounds differently, and that the time and mode of injury and associated substrate surface all impact this response.

Circulatory loop design and components introduce artifacts impacting in vitro evaluation of ventricular assist device thrombogenicity: A call for caution.

Mechanical circulatory support (MCS) devices continue to be hampered by thrombotic adverse events (AEs), a consequence of device-imparted supraphysiologic shear stresses, leading to shear-mediated platelet activation (SMPA). In advancing MCS devices from design to clinical use, in vitro circulatory loops containing the device under development and testing are utilized as a means of assessing device thrombogenicity. Physical characteristics of these test circulatory loops may also contribute to inadvertent platelet activation through imparted shear stress, adding inadvertent error in evaluating MCS device thrombogenicity. While investigators normally control for the effect of a loop, inadvertent addition of what are considered innocuous connectors may impact test results. Here, we tested the effect of common, additive components of in vitro circulatory test loops, that is, connectors and loop geometry, as to their additive contribution to shear stress via both in silico and in vitro models. A series of test circulatory loops containing a ventricular assist device (VAD) with differing constituent components, were established in silico including: loops with 0~5 Luer connectors, a loop with a T-connector creating 90° angulation, and a loop with 90° angulation. Computational fluid dynamics (CFD) simulations were performed using a k - ω shear stress transport turbulence model to platelet activation index (PAI) based on a power law model. VAD-operated loops replicating in silico designs were assembled in vitro and gel-filtered human platelets were recirculated within (1 hour) and SMPA was determined. CFD simulations demonstrated high shear being introduced at non-smooth regions such as edge-connector boundaries, tubing, and at Luer holes. Noticeable peaks' shifts of scalar shear stress (sss) distributions toward high shear-region existed with increasing loop complexity. Platelet activation also increased with increasing shear exposure time, being statistically higher when platelets were exposed to connector-employed loop designs. The extent of platelet activation in vitro could be successfully predicted by CFD simulations. Loops employing additional components (non-physiological flow pattern connectors) resulted in higher PAI. Loops with more components (5-connector loop and 90° T-connector) showed 63% and 128% higher platelet activation levels, respectively, versus those with fewer (0-connector (P = .023) and a 90° heat-bend loop (P = .0041). Our results underscore the importance of careful consideration of all component elements, and suggest the need for standardization in designing in vitro circulatory loops for MCS device evaluation to avoid inadvertent additive SMPA during device evaluation, confounding overall results. Specifically, we caution on the use and inadvertent introduction of additional connectors, ports, and other shear-generating elements which introduce artifact, clouding primary device evaluation via introduction of additive SMPA.

Bond Graph Modeling of Mechanical Circulatory Support Device-Cardiovascular System Interactions.

Though mechanical circulatory support (MCS) devices, such as ventricular assist devices and total artificial hearts (TAH), provide heart failure patients with bridges to heart transplantation or are alternatives to transplantation, device performance, and corresponding control strategies are often difficult to evaluate. Difficulties arise due to the complex interaction of multiple domains-i.e., biological, hydraulic, hemodynamics, electromechanical, system dynamics, and controls. In an attempt to organize, integrate and clarify these interactions, a technique often used in hydraulic pump design and robotics, called "bond graph modeling," is applied to describe the performance and functionality of MCS devices and the interaction between the cardiovascular (CV) system and the MCS device. This technical brief demonstrates the advantages of this tool in formulating a model for the systemic circulation interacting with the left side of a TAH, adopting the fundamental structure of either a hydraulic mechanism (i.e., AbioCor/Carmat) or a pneumatic mechanism (i.e., SynCardia), combined with a systemic circulation loop. The model captures the dynamics of the membrane, the hydraulic source or pneumatic source, and the systemic circulation. This multidisciplinary cross-pollination of an analytical tool from the field of dynamic systems may provide important insight to further aid and improve the design and control of future MCS systems.

The MICELI (MICrofluidic, ELectrical, Impedance): Prototyping a Point-of-Care Impedance Platelet Aggregometer.

As key cellular elements of hemostasis, platelets represent a primary target for thrombosis and bleeding management. Currently, therapeutic manipulations of platelet function (antithrombotic drugs) and count (platelet transfusion) are performed with limited or no real-time monitoring of the desired outcome at the point-of-care. To address the need, we have designed and fabricated an easy-to-use, accurate, and portable impedance aggregometer called "MICELI" (MICrofluidic, ELectrical, Impedance). It improves on current platelet aggregation technology by decreasing footprint, assay complexity, and time to obtain results. The current study aimed to optimize the MICELI protocol; validate sensitivity to aggregation agonists and key blood parameters, i.e., platelet count and hematocrit; and verify the MICELI operational performance as compared to commercial impedance aggregometry. We demonstrated that the MICELI aggregometer could detect platelet aggregation in 250 µL of whole blood or platelet-rich plasma, stimulated by ADP, TRAP-6, collagen, epinephrine, and calcium ionophore. Using hirudin as blood anticoagulant allowed higher aggregation values. Aggregation values obtained by the MICELI strongly correlated with platelet count and were not affected by hematocrit. The operational performance comparison of the MICELI and the Multiplate® Analyzer demonstrated strong correlation and similar interdonor distribution of aggregation values obtained between these devices. With the proven reliability of the data obtained by the MICELI aggregometer, it can be further translated into a point-of-care diagnostic device aimed at monitoring platelet function in order to guide pharmacological hemostasis management and platelet transfusions.

Design Effect of Metallic (Durable) and Polymeric (Resorbable) Stents on Blood Flow and Platelet Activation.

Bioresorbable vascular scaffolds (BVS) provide transient vessel support for occluded coronary arteries while resorbing over time, potentially allowing vessel restoration approximating the native, healthy state. Clinical trials indicate that the Absorb BVS (Abbott Vascular, Santa Clara, CA) performance was similar to that of the Xience metallic drug-eluting stent (DES), with low long-term complications rates. However, when under-deployed in very small vessels (diameter < 2.25 mm), the thrombosis rate of BVS was higher, possibly due to the effect of strut thickness on the hemodynamics (157 µm BVS vs. 81 µm DES). This study aims to determine the influence of BVS design in vessels of varying diameter on the potential platelet activation. Sixteen computational fluid dynamics models of vessels of varying diameter (1.8-3.0 mm), strut thickness (81-157 µm), and BVS/DES designs were compared. Platelet stress accumulation (SA), a metric for the activation potential, was calculated along platelet flow trajectories and their probability distribution was compared. The models were consistent with clinical observations, indicating that devices deployed in very small vessels exhibited increased probability for platelet activity as compared to the same devices deployed in nominal sized vessels. Deployment, although with residual stenosis, increased probability for higher SA than in similar diameter straight vessels. Reducing BVS struts thickness while maintaining their pattern improved performance closer to that of DES. Our findings highlight the importance of appropriate vessel sizing and deployment technique for BVS, and may help designing future BVS with thinner struts, ultimately improving performance in very small vessels.

Comparative Fluid-Structure Interaction Analysis of Polymeric Transcatheter and Surgical Aortic Valves' Hemodynamics and Structural Mechanics.

Transcatheter aortic valve replacement (TAVR) has emerged as an effective alternative to conventional surgical aortic valve replacement (SAVR) in high-risk elderly patients with calcified aortic valve disease. All currently FDA-approved TAVR devices use tissue valves that were adapted to but not specifically designed for TAVR use. Emerging clinical evidence indicates that these valves may get damaged during crimping and deployment- leading to valvular calcification, thrombotic complications, and limited durability. This impedes the expected expansion of TAVR to lower-risk and younger patients. Viable polymeric valves have the potential to overcome such limitations. We have developed a polymeric SAVR valve, which was optimized to reduce leaflet stresses and offer a thromboresistance profile similar to that of a tissue valve. This study compares the polymeric SAVR valve's hemodynamic performance and mechanical stresses to a new version of the valve- specifically designed for TAVR. Fluid-structure interaction (FSI) models were utilized and the valves' hemodynamics, flexural stresses, strains, orifice area, and wall shear stresses were compared. The TAVR valve had 42% larger opening area and 27% higher flow rate versus the SAVR valve, while wall shear stress distribution and mechanical stress magnitudes were of the same order, demonstrating the enhanced performance of the TAVR valve prototype. The TAVR valve FSI simulation and Vivitro pulse duplicator experiments were compared in terms of the leaflets' kinematics and the effective orifice area. The numerical methodology presented can be further used as a predictive tool for valve design optimization for enhanced hemodynamics and durability.

Peripheral VA-ECMO with direct biventricular decompression for refractory cardiogenic shock.

Cardiogenic shock and cardiac arrest are life-threatening emergencies that result in high mortality rates. Veno-arterial extracorporeal membrane oxygenation (VA-ECMO) via peripheral cannulation is an option for patients who do not respond to conventional therapies. Left ventricular (LV) distention is a major limitation with peripheral VA-ECMO and is thought to contribute to poor recovery and the inability to wean off VA-ECMO. We report on a novel technique that combines peripheral VA-ECMO with off-pump insertion of a trans-apical LV venting cannula and a right ventricular decompression cannula.

A Physical Heart Failure Simulation System Utilizing the Total Artificial Heart and Modified Donovan Mock Circulation.

With the growth and diversity of mechanical circulatory support (MCS) systems entering clinical use, a need exists for a robust mock circulation system capable of reliably emulating and reproducing physiologic as well as pathophysiologic states for use in MCS training and inter-device comparison. We report on the development of such a platform utilizing the SynCardia Total Artificial Heart and a modified Donovan Mock Circulation System, capable of being driven at normal and reduced output. With this platform, clinically relevant heart failure hemodynamics could be reliably reproduced as evidenced by elevated left atrial pressure (+112%), reduced aortic flow (-12.6%), blunted Starling-like behavior, and increased afterload sensitivity when compared with normal function. Similarly, pressure-volume relationships demonstrated enhanced sensitivity to afterload and decreased Starling-like behavior in the heart failure model. Lastly, the platform was configured to allow the easy addition of a left ventricular assist device (HeartMate II at 9600 RPM), which upon insertion resulted in improvement of hemodynamics. The present configuration has the potential to serve as a viable system for training and research, aimed at fostering safe and effective MCS device use.