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 #
5U01EB012487-04
Application #
8538814
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
2013-09-01
Budget End
2014-08-31
Support Year
4
Fiscal Year
2013
Total Cost
$2,590,748
Indirect Cost
$644,168
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
Xenos, Michalis; Labropoulos, Nicos; Rambhia, Suraj et al. (2015) Progression of abdominal aortic aneurysm towards rupture: refining clinical risk assessment using a fully coupled fluid-structure interaction method. Ann Biomed Eng 43:139-53
Dagdeviren, Canan; Yang, Byung Duk; Su, Yewang et al. (2014) Conformal piezoelectric energy harvesting and storage from motions of the heart, lung, and diaphragm. Proc Natl Acad Sci U S A 111:1927-32
Marom, Gil; Chiu, Wei-Che; Crosby, Jessica R et al. (2014) Numerical model of full-cardiac cycle hemodynamics in a total artificial heart and the effect of its size on platelet activation. J Cardiovasc Transl Res 7:788-96
Zhang, Na; Zhang, Peng; Kang, Wei et al. (2014) Parameterizing the Morse Potential for Coarse-Grained Modeling of Blood Plasma. J Comput Phys 257:726-736
Chiu, Wei-Che; Girdhar, Gaurav; Xenos, Michalis et al. (2014) Thromboresistance comparison of the HeartMate II ventricular assist device with the device thrombogenicity emulation- optimized HeartAssist 5 VAD. J Biomech Eng 136:021014
Zhang, Peng; Gao, Chao; Zhang, Na et al. (2014) Multiscale Particle-Based Modeling of Flowing Platelets in Blood Plasma Using Dissipative Particle Dynamics and Coarse Grained Molecular Dynamics. Cell Mol Bioeng 7:552-574
Chiu, Wei-Che; Slepian, Marvin J; Bluestein, Danny (2014) Thrombus formation patterns in the HeartMate II ventricular assist device: clinical observations can be predicted by numerical simulations. ASAIO J 60:237-40
Sheriff, Jawaad; Girdhar, Gaurav; Chiu, Wei-Che et al. (2014) Comparative efficacy of in vitro and in vivo metabolized aspirin in the DeBakey ventricular assist device. J Thromb Thrombolysis 37:499-506
Claiborne, Thomas E; Sheriff, Jawaad; Kuetting, Maximilian et al. (2013) In vitro evaluation of a novel hemodynamically optimized trileaflet polymeric prosthetic heart valve. J Biomech Eng 135:021021
Soares, Joao S; Gao, Chao; Alemu, Yared et al. (2013) Simulation of platelets suspension flowing through a stenosis model using a dissipative particle dynamics approach. Ann Biomed Eng 41:2318-33

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