Prosthetic Heart Valves
Mechanical heart valves
Mechanical heart valves can be very effective replacements for diseased or failing native valves. These biomedical devices can be implanted directly into patients or as components within larger cardiovascular assist devices. Tilting disc valves (Bjork-Shiley, MedHall, etc.) and bileaflet valves (St. Jude Medical, Carbomedics, etc.) are the most studied valves in our labs. Very slight design modifications can have significant effects on the flow structures generated by the closure of these valves. Thus, much of the research conducted in the Artificial Heart Lab involves exploring means by which to minimize hemolysis and valve failure. The strength of vortices and regurgitant jets produced by valve closure are visualized using high speed videography and quantified through optical flow techniques such as PIV and LDV.
Mechanical heart valve induced cavitation is also investigated in our lab. Cavitation formed due to the rapid pressure drop on the upstream side of the leaflet following impact with the housing can be detected acoustically with a hydrophone. Various signal isolation techniques, some of which implement wavelets, are being explored in order to completely extract the cavitation signal from the statistically transient mechanical closure signal. It is important to quantify the amount of cavitation produced by valves under physiologic loading conditions, because the collapse of the bubbles can be very damaging locally to red blood cells. Cavitation has also been linked to stable bubble formation. Once these stable bubbles have been introduced into the bloodstream, they can make their way into the cranial circulation, which increases the risk of stroke in mechanical heart valve patients.
While mechanical heart valves (MHVs) remain the most widely implanted prosthetic valves, polymeric valves have inherent advantages. These include their unobstructed orifice and lower leaflet closing velocities which minimize their hemolytic, platelet activating and cavitation potential, relative to MHVs. Currently, most polymeric valves are used as part of left ventricular assist devices and total artificial hearts. There is interest to implant these valves clinically, and characterizing the fluid dynamics of polymeric heart valves will help achieve this goal. An in vitro laser Doppler velocimetry study was conducted on a 25 mm polymeric trileaflet heart valve in the aortic position. The valve is housed in an acrylic conduit with aortic sinuses that allows for optical access upstream and downstream of the valve. A sodium/iodide/glycerin fluid that matches the kinematic viscosity of blood and the index of refraction of the model is used as a blood analog.
In this project, a mock circulatory flow loop, which includes an acrylic model that mimics the anatomy of the sinus region around the aortic valve, is used to assess the viability of aortic valve replacements. Living bovine aortic valve leaflets are sewn into a testing ring and inserted into the acrylic model. The flow loop; consisting of tubing, a pulsatile pump, compliance chambers, and a resistive element; produces physiologically relevant pressures and flow rates, similar to what an aortic valve experiences in vivo. Using a non-toxic blood analog fluid, the velocity fields near, and downstream of, the tissue valve are quantified with particle image velocimetry. A range of heart beat rates is used in this study to investigate valve performance.
Artificial Heart and Ventricular Assist Devices
Pediatric ventricular assist device (PVAD)
While heart transplantation has become a viable option for children, there is continual concern for organ availability, especially in infants under 1 year of age. As a result, there has been an increased movement to aid pediatric patients during the “bridge-to-transplant” period. Ventricular assist devices (VADs) have been successfully used in adult patients for several years; however, there have been limited options for pediatrics due to their smaller blood volume, the possible growth of the patient during the support period, and the size range of pediatric patients (from infant to adolescent). Therefore, in 2004 the National Institutes of Health initiated The National Heart, Lung and Blood Institute (NHLBI) Pediatric Circulatory Support Program. As part of this program, Penn State has been developing 12 and 25 cc devices for use in pediatric patients, based on the successful, pneumatic Pierce-Donachy adult device.
The 12 cc pulsatile pediatric ventricular assist device (PVAD) is a collaboration between the Departments of Bioengineering and Surgery at Hershey Medical Center and the Artificial Heart Lab at University Park. As part of this project the Artificial Heart Lab uses 2D particle image velocimetry (PIV) to observe the fluid dynamics within these devices including flow patterns and wall shear rates. This is important to the design since certain flow characteristics have shown a decrease in thrombus deposition within the device, an issue many VADs currently face. The desired properties include a strong rotation during diastole, low blood residence time, and no areas of stasis within the device. Several design considerations are currently being studied including valve selection orientation and position as well as possible weaning applications including changes in inflow timing and flow reduction.
Rotary Ventricular Assist Device (VAD)
Patients who have received a HeartMate II (HMII) left ventricular assist device are at an elevated risk for Acquired von Willebrand Syndrome, which occurs when a glycoprotein in the coagulation cascade is cleaved by high shear stresses. In this project, a laser Doppler velocimetry (LDV) system is used to quantify the three-dimensional flow field in the outlet cannula of a HMII so the Reynolds stresses can be calculated. LDV utilizes the Doppler effect to calculate the velocities of tiny glass particles that are seeded in the test fluid, which is a non-Newtonian blood analog in this case. The HMII is incorporated into a flow loop which includes tubing, a compliance chamber, a resistive element, and a pulsatile pump. A range of physiologically relevant pressures and flow rates are used to analyze the potential blood damage caused by the HMII at numerous levels of left ventricular function.
Pulsatile Ventricular Assist Device (VAD)
The Penn State 50 cc left ventricular assist device (LVAD) is a blood pump designed for smaller patients as a follow on to the clinically successful 70 cc Arrow LionHeart (TM) also developed at Penn State. In vitro fluid mechanic studies are performed on the device at University Park using particle image velocimetry and high speed video techniques. Flow field characteristics such as velocity and wall shear are measured, with the goal of reducing the hemolytic and thrombogenic potential of the pump. This research is used to accelerate the design process in conjunction with in vivo studies at the the Penn State Milton S. Hershey Medical Center.
The usefulness of cardiovascular prosthetics is limited by thromboembolic events. Even after many attempts to reduce thrombogencity by changing prosthetic design and modifying the surfaces of the blood contacting materials, it is estimated that ventricular assist devices still have a thromboembolic event rate of approximately 50%. Preventing thrombosis often involves an anticoagulation regime with its own related problems.
There is a need to predict thrombogencity of cardiovascular devices, both when in development and once they are implanted, but it is difficult to assess with existing assays. There are a variety of clinical markers to measure platelet function or thrombin level in response to the vascular implant, but they can be influenced by other existing pathologies and no marker specifically indicates actual thrombus formation. In the ventricular assist device, for example, the oscillatory stress field about artificial heart valves is known to activate platelets, but it is the subsequent exposure to low blood-flow that permits clot formation.
The goal of this research project is to develop techniques to better determine thrombogencity of cardiovascular prosthetics. An in vitro flow loop is being developed to simulate the complex flow patterns that are caused by cardiovascular prosthetics. Circulating whole blood through the loop, clinical measures of thrombogencity are used to assess platelet function and aggregation. Measures of platelet function and activation will be used to correlate thrombosis with flow stresses. Cross-correlating the assays may be a better indicator of thrombosis than any single assay. These studies will provide fundamental information necessary to develop tools for both cardiovascular implant development and patient monitoring devices.
In this project, bovine blood is circulated through a flow loop containing a backward-facing step (i.e. an asymmetric sudden expansion) for varying lengths of time. A recirculation region, which is physiologically relevant in the context of some cardiac devices, forms downstream of the step and facilitates thrombus (blood clot) formation. The resulting thrombi are analyzed both with histology sectioning and magnetic resonance imaging. Histology sectioning allows the cellular components of the thrombus to be visualized, while the MRI data allows computational fluid dynamics simulations to be performed on realistic thrombus geometries to investigate velocity patterns near, and shear stresses on, the thrombi surfaces. This project will aid in our understanding of how fluid mechanics affects both the composition and size of thrombi formed in recirculation regions.
Magnetic resonance imaging (MRI) flow visualization
MRI is used to characterize blood flow in a simple known geometry, specifically flow past a step. The formation and growth of thrombi are also imaged, along with the thrombi embolizing, in order to form a relationship between the flow patterns of the blood and thrombi growth/shearing. Unlike LDV and PIV techniques, MRI can characterize the flow of whole blood because it uses the magnetic resonance of hydrogen atoms in the blood, compared to light scattering, which does not work with opaque fluids. The MRI measurements also allow for a time history of the thrombi, so the formation, growth and detachment can be characterized according to the blood flow velocity.
Blood is a suspension consisting of primarily red blood cells, along with other formed elements. This gives blood viscoelastic behavior, with properties that are characteristic of both fluids and solids. The concentration, aggregation and deformability of red blood cells as well as plasma viscosity and plasma protein concentration influence the viscosity and elasticity of whole blood. Blood behaves as a Newtonian fluid at shear rates above 500 s-1. At shear rates lower than 50 s-1 the viscosity of blood increases exponentially, due to the formation of large aggregates of erythrocytes. As shear rate increases, the erythrocytes are dispersed and aligned in the direction of flow. These parameters affect the flow properties, especially at low shear rates (< 50 s-1). Newtonian blood analogs are often used for in vitro experiments, but it has been shown that these fluids produce higher values of wall shear stress and Reynolds stresses than non-Newtonian fluids. The lower stresses seen in viscoelastic fluids are more conducive to thrombus formation. When conducting in vitro testing to measure the fluid mechanics in cardiac devices, it is important to use a fluid that mimics properties of blood. Shown below are viscoelastic blood analogs that we have developed to mimic blood at different values of hematocrit.