In our Phase I project which was funded under special high-risk/high-impact applications program, a thrombogenicity predictive technology - Device Thrombogenicity Emulator (DTE) - a universal methodology for improving the thromboresistance of circulatory cardiovascular devices was successfully developed, and its application to design optimization for achieving improved performance was demonstrated. In this Quantum Phase II project an array of CVS devices from various manufacturers will be tested and optimized, with the ultimate goal to reduce their thrombogenicity to a level that will liberate the device recipients from the need for complex pharmacological anticoagulation therapy. During the Phase II of the proposed quantum project, the DTE will be utilized to optimize the design of various sub-groups of CVS devices: Prosthetic Heart Valves (PHV), Ventricular Assist Devices (VAD), bi-ventricular VAD, and the first FDA approved temporary Total Artificial Heart (TAHt). All these devices will be optimized in the numerical domain, using cutting edge numerical simulation techniques, and will be interfaced to a Hemodynamic Shearing Device (HSD) that emulates the hemodynamics within the device- in which the potential of the device to promote blood clotting is measured. The process is reiterated, and design modifications aimed at reducing the device thrombogenicity are optimized to a level that will eventually eliminate the use of risky and complex anticoagulation these devices require. Prototypes of optimized devices will be manufactured by the industrial partners in this proposal- among them some of the leading companies who have introduced to the market several break-through mechanical circulatory support (MCS) devices. The optimized prototypes will be tested by us in vitro to test whether the DTE optimization achieved its stated goals, and will be further tested in vivo in an extensive animal experiments series (performed at the renowned Sarver Heart Center, U. Arizona), as well as in the various participating device manufacturers facilities. We will further build DTE systems for each of the industrial partners and train them in this innovative methodology. We will interact with the FDA for establishing new guidelines for device thrombogenicity. Our industrial partners will further seek trial or study requirements from the FDA (PMA/IDE/HDE), as required for the type of device and the optimization modifications, to facilitate first human demonstration and introduction of the optimized devices to the market. It is envisioned that by the end of phase II some of the devices tested and optimized will demonstrate the potential for a quantum advance of eliminating anticoagulation. The technology offered will become an essential tool for manufacturers that seek to create, redesign and test a cardiovascular device.

Public Health Relevance

Over 5 million patients in the US suffer annually from heart failure. Of those a significant proportion will become candidates for longer-term mechanical circulatory support (MCS). Thromboembolism and the attendant risk for stroke remains the critical barrier to their use for long term destination therapy. The DTE technology will help in drastically reducing the R&D and escalating healthcare costs involved. Elimination of difficult and costly pharmacological management with anticoagulants is expected to pave the way for the use of these devices as long term destination therapy and save countless lives.

Agency
National Institute of Health (NIH)
Institute
National Institute of Biomedical Imaging and Bioengineering (NIBIB)
Type
Research Project--Cooperative Agreements (U01)
Project #
5U01EB012487-02
Application #
8149932
Study Section
Special Emphasis Panel (ZEB1-OSR-E (A1))
Program Officer
Peng, Grace
Project Start
2010-09-30
Project End
2015-08-31
Budget Start
2011-09-01
Budget End
2012-08-31
Support Year
2
Fiscal Year
2011
Total Cost
$1,414,610
Indirect Cost
Name
State University New York Stony Brook
Department
Biomedical Engineering
Type
Schools of Engineering
DUNS #
804878247
City
Stony Brook
State
NY
Country
United States
Zip Code
11794
Crosby, Jessica R; DeCook, Katrina J; Tran, Phat L et al. (2017) A Physical Heart Failure Simulation System Utilizing the Total Artificial Heart and Modified Donovan Mock Circulation. Artif Organs 41:E52-E65
Zhang, Peng; Zhang, Li; Slepian, Marvin J et al. (2017) A multiscale biomechanical model of platelets: Correlating with in-vitro results. J Biomech 50:26-33
Chiu, Wei-Che; Alemu, Yared; McLarty, Allison J et al. (2017) Ventricular Assist Device Implantation Configurations Impact Overall Mechanical Circulatory Support System Thrombogenic Potential. ASAIO J 63:285-292
Dimasi, Annalisa; Rasponi, Marco; Consolo, Filippo et al. (2017) Microfludic platforms for the evaluation of anti-platelet agent efficacy under hyper-shear conditions associated with ventricular assist devices. Med Eng Phys 48:31-38
Slepian, Marvin J; Sheriff, Jawaad; Hutchinson, Marcus et al. (2017) Shear-mediated platelet activation in the free flow: Perspectives on the emerging spectrum of cell mechanobiological mechanisms mediating cardiovascular implant thrombosis. J Biomech 50:20-25
Consolo, Filippo; Sheriff, Jawaad; Gorla, Silvia et al. (2017) High Frequency Components of Hemodynamic Shear Stress Profiles are a Major Determinant of Shear-Mediated Platelet Activation in Therapeutic Blood Recirculating Devices. Sci Rep 7:4994
Bluestein, Danny (2017) Utilizing Computational Fluid Dynamics in Cardiovascular Engineering and Medicine-What You Need to Know. Its Translation to the Clinic/Bedside. Artif Organs 41:117-121
Tran, Phat L; Pietropaolo, Maria-Grazia; Valerio, Lorenzo et al. (2016) Hemolysate-mediated platelet aggregation: an additional risk mechanism contributing to thrombosis of continuous flow ventricular assist devices. Perfusion 31:401-8
Valerio, Lorenzo; Tran, Phat L; Sheriff, Jawaad et al. (2016) Aspirin has limited ability to modulate shear-mediated platelet activation associated with elevated shear stress of ventricular assist devices. Thromb Res 140:110-117
Sheriff, Jawaad; Tran, Phat L; Hutchinson, Marcus et al. (2016) Repetitive Hypershear Activates and Sensitizes Platelets in a Dose-Dependent Manner. Artif Organs 40:586-95

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