Acute right ventricular failure (ARVF) is a life-threatening condition commonly encountered in the intensive care unit. The treatment of ARVF profoundly changed in the last years, with a growing number of mechanical circulatory support (MCS) devices that have been deployed in clinical practice to support patients with severe forms of ARVF. However, comparative clinical data addressing the superiority of the different MCS strategies are lacking. Several animal models addressing ARVF have been proposed in the literature, and they have been crucial to increase the knowledge on right ventricular (RV) pathophysiology and response to different stressors. Nevertheless, models that reliably mimic acute RV severe failure, ventricular–pulmonary artery uncoupling, and cardiogenic shock are comparatively scarce. Furthermore, only a limited number of experimental studies have incorporated MCS devices in this setting, and direct head-to-head comparisons between different support strategies are largely lacking. This gap in preclinical experiences significantly limits the development of evidence-based algorithms for right-sided MCS deployment. In this review, we summarize currently available animal models of ARVF, critically highlighting their methodological strengths and limitations, and examining the evidence supporting the use of MCS within these frameworks. By highlighting the translational limitations of the existing preclinical experiences, we underscore the urgent need for standardized, reproducible, and clinically relevant ARVF models. Such efforts are essential to improve the current treatment of ARVF, and they could be particularly relevant in developing and optimizing MCS devices and their selection, ultimately enhancing outcomes in patients with ARVF.

Elastic interfaces with varying levels of permeability are widely encountered in nature. Red blood cells, for example, are characterized by an area-incompressible membrane that is permeable to the diffusion of oxygen and carbon dioxide. Artificial capsules, on the other hand, are often engineered to remain impermeable until they reach a designated location or time, whereby they release their internal contents into the surrounding medium. A common approach to numerical simulations of elastic capsules in flow involves discretizing the membrane surface to facilitate the calculation of shear strains and area changes. Recently, level-set-based methods that rely on advection of the reference map between the deformed and reference configurations have proven to be a promising alternative. This approach offers several advantages, including ease of implementation and parallelization. In the present work, we adapt the level-set-based formulation to a diffuse interface framework to overcome the intrinsic limitation of the level-set to conserve mass. We show that by adding a variational term to the reference map advection equation, consistency between the interface location (defined using a reference map) and the diffused interface can be ensured. Through a number of validation cases, we show the accuracy and robustness of the present approach. In addition, we extend the framework to multi-capsule simulations, demonstrating the ability of handling hundreds of discrete capsules with minimal additional computational cost.

Background: While current antiplatelets protect against thrombosis, their clinical utility is limited by an elevated risk of bleeding. Objectives: To understand how structure-function relations in the hemostatic system may be leveraged into improve risk/benefit ratios of antiplatelet therapies. Methods: We developed a deep learning-based framework to track the activities of large numbers of platelets in vivo, enabling a detailed comparative assessment of the effects of therapeutic interventions on the evolving structural hierarchy of the hemostatic response. Results: Unlike conventional antiplatelets targeting paracrine signaling, selective pharmaceutical inhibition of platelet mechanosensory signaling via PI3KC2 alpha preserved the initial build-up of thrombi following vascular injury to high-flow mesenteric veins. However, as this burst of hemostatic activity subsided, inhibition of platelet mechanosensory signaling caused localized reductions of platelet intracellular calcium ion levels ([Ca2+]i) in shear-exposed peripheral thrombus subregions, inhibiting the formation of platelet clusters capable of withstanding the drag forces of the blood flow. As a consequence, platelets in these subregions detached, became elongated, and/or slid along the thrombus surface. On a macrostructural level, this selective destabilization prevented sustained physical expansion of thrombi outside the perimeters of vascular injuries while preserving platelet packing density in thrombus subregions close to vascular injuries. Conclusion: Collectively, our results highlight platelet mechanosensory signaling as a significant driver of sustained platelet population growth after the initial agonistdriven phase of thrombus expansion. We show that pharmaceutical targeting of this pathway enforced the convergence of thrombus growth trajectories toward a rheologically favorable setpoint without compromising the structural integrity of thrombus subregions that are critical for hemostasis.

Venovenous extracorporeal membrane oxygenation (VV ECMO) can be performed with different cannulation approaches: femoro-femoral (FF), femoro-jugular (FJ), or jugulo-femoral (JF), all characterized by one drainage cannula. Dual drainage cannulation (JFF, with two drainage cannulae) may be considered in refractory hypoxemia. This work compared single vs. dual drainage concerning the impact on hemodynamics and oxygenation performance by studying the drainage ratio between the jugular and femoral cannulae, their type and position. Computational fluid dynamics was used in a patient-averaged model of the right atrium (RA) and central veins to estimate recirculation fraction (R f), arterial oxygen saturation (SaO 2), caval pressures, shear rates, time-averaged wall shear stress (TAWSS), and stagnation volume in each cannulation configuration. An ECMO flow rate of 4 L/min and cardiac output of 6 L/min were considered. JF showed the highest R f (22%) and the lowest SaO 2 (80%). The lowest R f (0.03%) and the highest SaO 2 (90%) were obtained in JFF with a multistage jugular cannula draining at a flow rate lower than the native venous inflow. FF presented the lowest pressure in the inferior vena cava (IVC, -10 mmHg), but the highest in the superior vena cava (SVC, 32 mmHg) when the return cannula tip was placed at the superior cavo-atrial junction. The stagnation volume was highest in JFF at femoral drainage ≤2 L/min. In most configurations the maximum TAWSS in the RA and SVC were more than 5 times higher than no ECMO (baseline). Adding an additional drainage cannula may in some cases improve oxygenation compared to standard single drainage configurations. The efficiency of JFF was mainly influenced by the jugular/femoral drainage ratio, cannula type and position in the SVC. Significant differences in caval pressures and TAWSS were observed between the configurations. The optimal choice of cannulation would be patient-tailored, considering specific needs and complication risks.

Needling of arteriovenous fistulas is a critical aspect of vascular access in haemodialysis, where a particular concern is the venous return needle strongly perturbing local haemodynamics. To isolate and characterise these effects, controlled experiments are performed in an idealised geometry representing venous return, using clinically relevant vessel and needle dimensions with Reynolds-number similarity. Scalar transport and mixing are quantified using planar laser-induced fluorescence, while velocity field and shear stress are obtained from particle image velocimetry. The results demonstrate that needle angle and the vein-to-needle flow-rate ratio jointly govern the development of primary and secondary flow structures. Lower needle angles and higher flow-rate ratios delay mixing, whereas higher angles and lower ratios promote rapid mixing and sustain localised stagnation regions. Complete mixing, when achieved, occurs within approximately 15 needle diameters downstream, although the velocity field remains undeveloped and influenced by the needle jet up to 25 diameters downstream. Viscous shear stresses are found to be highly unsteady (root-mean-square of fluctuation/mean value varying between 0.21 and 0.48 at the location of maximum shear stress), with instantaneous values frequently exceeding physiologically relevant levels. These findings provide fundamental fluid-mechanical insight for clinically informed optimisation of cannulation strategies.

In cases of severe cardiopulmonary failure, extracorporeal membrane oxygenation (ECMO) may be temporarily used as a life-saving support for cardiac and/or lung function. Operating under non-physiological flow conditions, characterized by elevated shear rates and stagnant flow zones, there is an increased risk of inducing thrombosis, bleeding and hemolysis. Pinpointing the underlying mechanism triggering the onset of thrombus formation may aid development of device design, as well as management of anti-coagulation, benefiting patient outcome. Here we present a combined methodology enabling a multiscale understanding of thrombus development. Two thrombi collected from different ECMO circuits were analyzed by computational fluid dynamics (CFD), ultra small angle X-ray scattering (USAXS) and scanning electron microscopy (SEM). USAXS quantified the density and bulk alignment of fibrin, building the thrombus scaffold structure. SEM provided information on cellular morphology and surface fibrin structure, and CFD identified regions in the ECMO circuit with high thrombotic potential. Together, this combined approach was able to link local flow conditions and the structural growth of thrombi in ECMO circuits.

Background: A vascular closure device (VCD) may be employed to close arteriotomy of the femoral artery following endovascular surgery, catheterization, and extracorporeal life support cannulation. Such devices aim to reduce the time to hemostasis and avoid the need for manual compression. Despite ubiquity of VCDs in clinical practice, limited research on the hemodynamic impact of these devices has been published. Methodology: Four commonly-used VCDs were applied on a 10 mm longitudinal incision in a 3/8 inch diameter polyvinylchloride tubing for geometry. Each sample was imaged with micro-computed tomography and reconstructed into a 3-dimensional model. Using computational fluid dynamics, blood flow over the 4 VCDs was simulated in a straight cylinder. In addition, 1 sample was simulated in a patient-specific femoral artery geometry. Time-averaged wall shear stress (TAWSS), oscillatory shear index (OSI), and endothelial cell activation potential were used to assess the impact of each device on vessel hemodynamics. Results and Conclusions: The results suggest that anchor-based devices, resulted in larger flow disturbances, decreasing TAWSS and increasing OSI in their wake, compared with suture-based devices. Such conditions are likely to be pro-thrombotic. While the choice of VCD may be multifactorial, the present study offers new comparative data on their hemodynamic impact. Clinical Impact: The results from the present study offer unique comparative data on the hemodynamic impact of 4 vascular closure devices. These findings may help in the selection of devices. The pro-thrombotic nature of anchor-based devices may make these less suitable for certain clinical scenarios where there is a high risk of thrombosis and vessel occlusion.

Thrombosis in extracorporeal membrane oxygenation (ECMO) circuit components remains a challenge. Besides blood state and surface properties, flow plays a critical role in hemostasis. In this work, we aimed to study the fluid dynamics of a membrane lung (ML) outlet due to its complex design with pins protruding into the blood flow stream (temperature sensor and cap of purge line), with respect to the potential risk of flow-induced coagulation activation. Large eddy simulations were carried out for blood flow of 1 and 4 L/min. Recirculation bubbles and strong vortical structures developed in this geometry. These flow structures were similar to characteristics of flow past bluff bodies, which facilitate entrapment of platelets that may be activated by the elongational shear rates (> 2,000 s−1), observed near the surface of the temperature sensor for the 4 L/min case. Moreover, a thrombus, extracted from an ECMO circuit, was analyzed by scanning electron microscopy. It is concluded that a review of devices used for ECMO with auxiliary objects protruding into the bloodstream is warranted for improvement of design to reduce the risk of blood trauma and coagulation activation.

Extracorporeal life support (ECLS) technology has witnessed remarkable advancements during the last decades. However, further research and development of devices are required to increase, for example, performance-efficiency, hemocompatibility, and long-term stability. All novel devices, even in early research stages, must undergo rigorous testing and evaluation. Yet, these early evaluations are often conducted under nonstandardized conditions, resulting in data difficult to compare, interpret, or translate into clinical practice. Establishing well-defined, standardized in-vitro testing protocols for all ECLS components and devices would represent a major step forward. Such protocols would improve methodological consistency and ensure reproducibility across research groups. This document, developed by an international group of ECLS experts from all disciplines in which such components are designed, developed, and applied, provides clear recommendations and standardized criteria for device testing according to international norms. Adoption of these criteria including the ways of reporting results will foster a unified approach among scientists, engineers, clinicians, and the medical device industry. Ultimately, this common framework will facilitate data interpretation, improve comparability of study results between different groups, making the review of studies more straightforward, as not every aspect of testing requires additional review and discussion, certainly favoring decision-making in the development and application of ECLS technologies.

Extracorporeal life support (ECLS) technology has witnessed remarkable advancements during the last decades. However, further research and development of devices are required to increase, for example, performance-efficiency, hemocompatibility, and long-term stability. All novel devices, even in early research stages, must undergo rigorous testing and evaluation. Yet, these early evaluations are often conducted under nonstandardized conditions, resulting in data difficult to compare, interpret, or translate into clinical practice. Establishing well-defined, standardized in-vitro testing protocols for all ECLS components and devices would represent a major step forward. Such protocols would improve methodological consistency and ensure reproducibility across research groups. This document, developed by an international group of ECLS experts from all disciplines in which such components are designed, developed, and applied, provides clear recommendations and standardized criteria for device testing according to international norms. Adoption of these criteria including the ways of reporting results will foster a unified approach among scientists, engineers, clinicians, and the medical device industry. Ultimately, this common framework will facilitate data interpretation, improve comparability of study results between different groups, making the review of studies more straightforward, as not every aspect of testing requires additional review and discussion, certainly favoring decision-making in the development and application of ECLS technologies.