Dynamic Shear Stress Induced Platelet Activation in Blood Recirculation Devices: Implications for Thrombogenicity Minimization

Author(s):  
Gaurav Girdhar ◽  
Jawaad Sheriff ◽  
Michalis Xenos ◽  
Yared Alemu ◽  
Thomas Claiborne ◽  
...  

Implantable blood recirculation devices such as ventricular assist devices (VADs) and more recently the temporary total artificial heart (TAH-t) are promising bridge-to-transplant (BTT) solutions for patients with end-stage cardiovascular disease. However, blood flow in and around certain non-physiological geometries, mostly associated with pathological flow around mechanical heart valves (MHVs) of these devices, enhances shear stress-induced platelet activation, thereby significantly promoting flow induced thrombogenicity and subsequent complications such as stroke, despite a regimen of post-implant antithrombotic agents. Careful characterization of such localized high shear stress trajectories in these devices by numerical techniques and corresponding experimental measurements of their accentuated effects on platelet activation and sensitization, is therefore critical for effective design optimization of these devices (reducing the occurrence of pathological flow patterns formation) for minimizing thrombogenicity [1].

Author(s):  
Jawaad Sheriff ◽  
Michalis Xenos ◽  
João S. Soares ◽  
Jolyon Jesty ◽  
Danny Bluestein

Blood recirculating devices, which include ventricular assist devices and prosthetic heart valves, are necessary for some patients suffering from end-stage heart failure and valvular diseases. However, disturbed flow patterns in these devices cause shear-induced platelet activation and aggregation. Thromboembolic complications resulting from this platelet behavior necessitates lifelong anticoagulant therapy for patients implanted with such devices. In addition, blood recirculating device manufacturers mostly test and optimize their products for hemolysis, which occurs at shear stresses ten-fold higher than required for platelet activation. The relative paucity of optimization for flow-induced thrombogenicity is further exacerbated by the fact that there are few predictive shear-induced platelet activation models.


Author(s):  
Jawaad Sheriff ◽  
Gaurav Girdhar ◽  
Sheela George ◽  
Wei-Che Chiu ◽  
Bryan E. Lynch ◽  
...  

Mechanical circulatory support (MCS) devices, which include ventricular assist devices (VADs), offer an attractive solution to approximately 35,000 end-stage heart failure patients eligible for transplants, of which only 2,000–2,300 are performed annually [1]. These devices are employed to augment the function of the ailing left and/or right ventricle and serve as bridge-to-transplant or destination therapy, but are often accompanied by thrombotic complications. Pathologic flow patterns are characteristic of VADs and increase susceptibility to shear-induced platelet activation, which leads to thrombus formation [2]. Patients implanted with such devices are routinely prescribed antiplatelets to tackle these complications. Despite this concurrent therapy, thromboembolic incident rates of 0.9–13% are reported for the widely-implanted Thoratec HeartMate II and MicroMed DeBakey VADs [3, 4]. This has spurred the development of design optimization techniques to lower or eliminate the incidence of thrombosis and reduce the dependence on pharmacotherapy management.


2016 ◽  
Vol 140 ◽  
pp. 110-117 ◽  
Author(s):  
Lorenzo Valerio ◽  
Phat L. Tran ◽  
Jawaad Sheriff ◽  
William Brengle ◽  
Ram Ghosh ◽  
...  

Author(s):  
Isabella E. Valenti ◽  
Breigh N. Roszelle ◽  
Michael V. Perone ◽  
Steven Deutsch ◽  
Keefe B. Manning

Congenital cardiovascular defects are the leading cause of death among live births [1]. These defects involve the interior walls of the heart, valves, arteries, and veins and change the normal flow of blood through the heart and into the systemic system. Fortunately, several options exist for the more than 35,000 children born with congenital heart disease. Ventricular assist devices (VADs) currently hold the most promise for bridge-to-transplant treatment; however, a major problem for these devices is thrombus formation and deposition.


Author(s):  
Gaurav Girdhar ◽  
Michalis Xenos ◽  
Wei-Che Chiu ◽  
Yared Alemu ◽  
Bryan Lynch ◽  
...  

Mechanical circulatory support (MCS) devices such as the ventricular assist devices (VADs) provide life saving short-term bridge-to-transplant solutions (1) to a large proportion of patients who suffer from chronic heart failure. Although hemodynamically efficient, such devices are burdened with high incidence of thromboembolic events due to non-physiological flow past constricted geometries where platelets (the principal cellular clotting elements in blood) are exposed to elevated shear stresses and exposure times (2) — requiring mandatory anticoagulation. We recently developed an optimization methodology — Device Thrombogenicity Emulator (DTE)(3) — that integrates device specific hemodynamic stresses (from numerical simulations) with experimental measurements of platelet activation. The DTE was successfully applied by our group to measure / optimize the thromboresistance of mechanical heart valves (MHV) (3, 4).


Author(s):  
Thomas E. Claiborne ◽  
Gaurav Girdhar ◽  
Jawaad Sheriff ◽  
Jolyon Jesty ◽  
Marvin J. Slepian ◽  
...  

Mechanical circulatory support (MCS) devices developed for end-stage heart failure or as a bridge-to-transplant include total artificial hearts (TAH) and ventricular assist devices (VAD) and utilize prosthetic heart valves (PHV) or rotary impellers to control blood recirculation [1]. These devices are currently not optimized to reduce the incidence of pathological flow patterns that cause elevated stresses leading to platelet activation and thrombosis. Although the latter is partially mitigated by lifelong anticoagulation therapy, it dramatically increases the risk of uncontrolled bleeding. For instance thromboembolic stroke-related complications (∼2%) were relatively less with the TAH-t compared to uncontrolled bleeding due to anticoagulation use (∼20%) [2]. Platelet activation should therefore be quantified and optimized based on patient-specific cardiac outputs in device prototypes before clinical use.


Author(s):  
J. Hanker ◽  
B. Giammara ◽  
J. Dobbins ◽  
W. DeVries

Implantation of the total artificial heart and its associated systems, such as the pneumatic driving system, or other cardiovascular prostheses such as ventricular assist devices, intravenous catheters, ventriculo-atrial shunts, pacemaker electrodes and prosthetic heart valves can be complicated by the problem of bacterial infection. Staphylococcus epidermidis. a ubiquitous commensal of human skin and mucous membranes normally does not cause disease in man. It is now recognized, however, as an opportunistic pathogen of biomaterial implants especially cardiovascular protheses. This is due to its ability to undergo transformation to produce mucoid or polysaccharide extracellular coating substances which promote its adherence to biomaterial surfaces and protect the bacteria against antibiotics and host defense mechanisms; this results in increased virulence of the slime-producing strains.


2008 ◽  
Vol 130 (4) ◽  
Author(s):  
Benjamin T. Cooper ◽  
Breigh N. Roszelle ◽  
Tobias C. Long ◽  
Steven Deutsch ◽  
Keefe B. Manning

The mortality rate for infants awaiting a heart transplant is 40% because of the extremely limited number of donor organs. Ventricular assist devices (VADs), a common bridge-to-transplant solution in adults, are becoming a viable option for pediatric patients. A major obstacle faced by VAD designers is thromboembolism. Previous studies have shown that the interrelated flow characteristics necessary for the prevention of thrombosis in a pulsatile VAD are a strong inlet jet, a late diastolic recirculating flow, and a wall shear rate greater than 500s−1. Particle image velocimetry was used to compare the flow fields in the chamber of the 12cc Penn State pediatric pulsatile VAD using two mechanical heart valves: Björk–Shiley monostrut (BSM) tilting disk valves and CarboMedics (CM) bileaflet valves. In conjunction with the flow evaluation, wall shear data were calculated and analyzed to help quantify wall washing. The major orifice inlet jet of the device containing BSM valves was more intense, which led to better recirculation and wall washing than the three jets produced by the CM valves. Regurgitation through the CM valve served as a significant hindrance to the development of the rotational flow.


2012 ◽  
Vol 6 (4) ◽  
Author(s):  
Charles E. Taylor ◽  
Gerald E. Miller

Accurate peripheral resistance simulation in a mock circulatory loop is critical to the evaluation of ventricular assist devices and heart valves. Implementation of an automated device that is capable of accurate resistance settings and precise reproduction of cardiovascular parameters allows for improved construction of experimental conditions within a mock circulatory loop. A mock circulatory loop resistor that employs a proportional valve design is proposed; a piston extending into the flow path to produce a resistance to flow. Real-time position feedback of the piston is used to determine orifice size, providing resolution in the change of resistance over time. Characterization of the physical system with The MathWorks SIMULINK™ SIMSCAPE™ block set allowed the determination of objective device parameters; the discharge coefficient and critical Reynolds number. The determination of these values was achieved utilizing the SIMULINK™ Parameter Estimation™ tool, experimental data, and a computational plant model of the experimental setup. With this information, an accurate computational model of the resistance device is presented for use in determining resistance settings in silico prior to implementation in the mock circulatory loop. Experimental in vitro trials verified the repeatability of the automated resistor performance by means of a staircase testing of piston position during several different continuous flow rates of a glycerin/water solution.


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