Personalized Numerical Cardiovascular Model with Weight Growth for Evaluating Pediatric Left Ventricular Assist Devices: Derivation from an Experimental Mock Circulatory Loop.

Pediatric patients with heart failure have limited treatment options because of a shortage of donor hearts and compatible left ventricular assist devices (LVADs). To address this issue, our group is developing an implantable pediatric LVAD for patients weighing 5-20 kg, capable of accommodating different physiological hemodynamic conditions as patients grow. To evaluate LVAD prototypes across a wide range of conditions, we developed a numerical cardiovascular model, using data from a mock circulatory loop (MCL) and patient-specific elastance functions. The numerical MCL was validated against experimental MCL results, showing good agreement, with differences ranging from 0 to 11%. The numerical model was also tested under left heart failure conditions and showed a worst-case difference of 16%. In an MCL study with a pediatric LVAD, a pediatric dataset was obtained from the experimental MCL and used to tune the numerical MCL. Then, the numerical model simulated LVAD flow by using an HQ curve obtained from the LVAD's impeller. When the numerical MCL was validated against the experimental MCL, hemodynamic differences ranged between 0 and 9%. These findings suggest that the numerical model can replicate various physiological conditions and impeller designs, indicating its potential as a tool for developing and optimizing pediatric LVADs.

Blood-contacting magnetic levitation bearing design using computational fluid dynamics for haemocompatibility.

The Hemocompatibility Assessment Platform (HAP) is a testing rig that will allow for the evaluation of blood trauma caused by individual components of rotary blood pumps including the NeoVAD - a proposed paediatric Left Ventricular Assist Device (LVAD). It is important that the HAP itself is only minimally haemolytic such that the plasma free haemoglobin measured can be assumed to come from the test component. In this study, Computational Fluid Dynamics simulations have been carried out to inform the design of a magnetically levitated motor bearing gap. Simulations show that issues with the original design, namely stagnation regions and large recirculation zones can be mitigated with the introduction of a pipe that introduces blood-flow to the centre of the bearing and disrupts the secondary flow patterns that cause these issues.Clinical relevance- The consequent reduction in shear exposure time will reduce heamolsyis from the HAP. The redesign of the bearing will result in reduced baseline blood trauma from the HAP, thus allowing quantification of test component haemolysis and will therefore aid the design of future paediatric LVADs.

Numerical and Experimental Analysis for a Magnetic Levitation System in a Hemocompatibility Assessment Platform.

Development of pediatric left ventricular assist devices (LVADs) has lagged behind that of adult LVADs, primarily due to the size and hemocompatibility constraints of pediatric anatomy. To quantify sources of blood trauma during LVAD development, we proposed a hemocompatibility assessment platform (HAP) that can evaluate the hemocompatibility of individual components of LVADs. To eliminate the hemolysis induced by the HAP itself, we incorporated passive magnetic (PM) bearings to suspend the rotor radially and an active magnetic bearing (AMB) to control the axial position. In this study, we numerically evaluated AMB forces of 2 geometries and validated the model by comparing its predictions with experimental results. The magnetic forces generated by the AMB were evaluated by increasing the rotor-stator gap from 0.1 mm to 0.5 mm with a 0.1 mm increment and by varying the coil current from -2 A to 2 A with a 1 A increment. The average error of the numerical models was 8.8% and 7.0% for the two geometries, respectively. Higher errors were found at smaller (<0.2mm) rotor-stator gaps. For both biasing ring sizes, the AMB exhibits high magnetic stiffness from -1 A to 1 A, though it saturates for currents of -2 A and 2 A. This region of high current stiffness was identified as the optimal control region. In future work, this function will be used to tune a control algorithm to modulate current supplied to the AMB, ultimately stabilizing the rotor axially. Clinical Relevance- This work furthers the development of a hemocompatibility assessment platform that will enhance and accelerate the development of adult and pediatric LVADs.

Physiological Control Algorithm for a Pulsatile-flow 3D Printed Circulatory Model to Simulate Human Cardiovascular System.

The human heart is responsible for maintaining constant, pulsatile blood flow in the human body. Mock circulatory loops (MCLs) have long been used as the mechanical representations of the human cardiovascular system and as test beds for mechanical circulatory support (MCS) devices and other interventional medical devices. This technology could also be used as a training and educational tool for surgeons/clinicians. To ensure the MCL can accurately simulate the pulsatile human cardiovascular system, it is essential that the MCL can reproduce human physiological responses, e.g., the Frank-Starling Mechanism, in a controllable operating environment. In this study, by using an elastance function template to control the simulated left ventricle, we created controllable pulsatile physiological flow in a 3D printed silicone vascular structure to successfully simulate the hemodynamic environment of the human cardiovascular system. Clinical Relevance- This work will provide an in vitro test platform to simulate the human cardiovascular system. The accurate simulation of human cardiovascular anatomy and hemodynamic environment will allow this device to be an ideal training/educational tool for surgeons/clinicians to recreate various physiological conditions that cannot be created in vivo in animal or cadaver models.

An algorithm mimicking pancreas pulsatile behavior improves artificial pancreas performance.

BACKGROUND: Artificial pancreas design using subcutaneous insulin infusion without pre-meal feed-forward boluses often induces an over-response leading to hypoglycemia due to the increase of blood insulin concentration sustained in time. The objective of this work was to create an algorithm for controlling the function of insulin pumps in closed-loop systems to improve blood glucose management in type 1 diabetic patients by mimicking the pulsatile behaviour of the pancreas. METHODS: A controller tuned in a pulsatile way promotes damped oscillations of blood insulin concentration injected through an insulin pump. We tested it in a simulated environment, using nine 'in silica' subjects. The control algorithm is founded on feedback linearization where through a change of variables, the nonlinear system turns into an equivalent linear system, suitable for implementing through a PID controller. We compared the results obtained 'in silica' with the volume injected by an insulin pump controlled by this algorithm. RESULTS: The use of this algorithm resulted in a pulsatile control of postprandial blood glucose concentration, avoiding hypoglycaemic episodes. The results obtained 'in silica' were replicated in a real pump 'in vitro'. CONCLUSIONS: With this proposed linear system, an appropriate control input can be designed. The controller works with a damped pulsatile pattern making the insulin infusion from the pump and blood insulin concentration pulsatile. This operational would improve the performance of an artificial pancreas.

Biomarkers for Predicting Cytokine Release Syndrome following CD19-Targeted CAR T Cell Therapy.

Chimeric Ag receptor (CAR) T cell therapy has shown astonishing potency in treating a variety of hematological malignancies in recent years. Along with this lifesaving potential comes the life-threatening toxicities of cytokine release syndrome (CRS) and neurotoxicity. This work seeks to consolidate biomarker candidates with the potential to predict the severity of CRS and neurotoxicity in patients receiving CD19-targeted CAR T cell therapy. In this systematic review, 33 clinical trials were evaluated for biomarkers that can predict the severity of posttreatment CRS and neurotoxicity. CRS and neurotoxicity occurred in 73.4 and 37% of the reviewed patients, respectively. Identified biomarker candidates included tumor burden, platelet count, C-reactive protein, ferritin, IFN-γ, IL-2, IL-6, IL-8, IL-10, IL-15, and TGF-ß. Combinatorial algorithms based on cytokine levels and clinical parameters show excellent promise in predicting CAR-T-cell-therapy-associated toxicities, with improved accuracy over the component biomarkers.

Pledget Induced Cardiogenic Shock Following a Minimally Invasive Aortic Valve Replacement.

Within the last decade, minimally invasive valve replacements have become exceedingly popular, and as a result, so has the rise of technology aimed at refining and simplifying these techniques. With new technology, new complications are inevitable. We present a routine Minimally invasive aortic valve replacement through a right anterior minithoracotomy complicated by pledget impaction in a coronary artery.