Trileaflet Polymeric Valves and their uses for Transcatheter Delivery and in the Total Artificial Heart Funded by a Special Quantum Award from the NIH Thomas Claiborne, M.Sc. 1 , Michalis Xenos, Ph.D. 1 , Yared Alemu, Ph.D. 1 , Jawaad Sheriff, Ph.D. 1 , Leonard Pinchuk, Ph.D. 2 , Marvin Slepian, M.D. 3 , Stefan Judex, Ph.D. 1 , Shmuel Einav, Ph.D. 1 , Jolyon Jesty, Ph.D. 4 , Danny Bluestein, Ph.D. 1 1 Stony Brook University, Department of Biomedical Engineering, Stony Brook, NY 11794, 2 Innovia LLC, Miami, FL 33186, 3 University of Arizona, Department of Medicine and SynCardia, Tuscon, AZ 85724 , 4 Stony Brook University, School of Medicine, Division of Hematology, Stony Brook, NY 11794 Clinical Problem ● Cardiovascular disease is the #1 cause of death in America and costs $500 billion annually 1,2 ● The final common pathway of all cardiovascular dis- ease is congestive heart failure (CHF) affecting 6 mil- lion Americans at a cost of $38 billion per year 1 ● 3,100 people in the United States are waiting for heart transplant on any given day 1 ● Only 2,200 donor hearts are available each year 1 ● 1-2% of Americans suffer from valvular heart disease (VHD) 2 ● VHD is treated with open-heart surgery to implant pros- thetic heart valve 2 ● 33% of VHD patients in need do not qualify for surgery 2 Fig. 1: Human heart anatomy. Solutions ● SynCardia Total Artificial Heart (TAH) ● The only device that eliminates the symptoms and source of end-stage CHF 5 (Figs. 2&3) ● Polymer Valves ● Combine low blood clotting risk of tissue (Fig. 4) and high durability of mechanical (Fig. 5) valves into one (Figs. 6&7) 3 ● Transcatheter Valves ● Minimally invasive valve replacement for people who cannot tolerate surgery 4 (Figs. 8&9) Fig. 2: SynCardia Total Artificial Heart (TAH). Fig. 3: TAH shown with monoleaflet mechani- cal valves (A) and trileaflet polymer valves (B). Fig. 4: Carpentier-Ed- wards Perimount Magna Bioprosthetic Valve the 'gold standard'. Fig. 5: St. Jude Med- ical Bileaflet Me- chanical Valve; 80% of the market. Fig. 6: Aortech Elast- Eon polymer valve Fig. 7: Innovia SIBS polymer valve. Fig. 8: Our Tran- scatheter Poly- mer Valve. Fig. 9: Our Tran- scatheter De- livery System. Research Objectives ● Reduce or eliminate the need for anticoagulant drugs ● Reduce risk of blood clots and stroke ● Reduce R&D costs ● Speed time to market Methods Polymer Characterization ● Prepare poly(Styrene-block-IsoButylene-block-Styrene) or SIBS (Innovia LLC, Miami, FL, Fig. 10) ● Tensile Testing: stress vs. strain behavior Fig. 10: Chemical structure of Innovia's SIBS. There are no reactive pendant groups making it oxida- tively, enzymatically, and hydrolytically stable. Numerical Simulations ● Advanced numerical simulations to study the blood flow patterns through the valves and quantify their po- tential to induce blood clotting ● Fluid structure interaction (FSI) ● Computational fluid dynamics (CFD) 6 ● Probability Density Function (PDF) of Stress Accumu- lation (SA) 6 ● 'Thombogenic Footprint' Prototype Design, Fabrication, Hydrodynamic Testing ● Computer Aided Design (CAD) Prototypes ● Fabricated in-house using compression molding (Figs. 11&12) ● Hydrodynamics in Vivitro Left Heart Simulator (LHS) 4 ● Accelerated durability testing in Vivitro Hi-Cycle System Fig. 11: Polymer Valve compression mold. Fig. 12: Compliance tubing mold. Platelet Activation Studies ● Platelet Activity State (PAS) assay 8 (Fig. 13) ● Pulsatile Berlin left ventricular assist device (LVAD) (Fig. 14) 7 ● Hemodynamic Shearing Device (HSD) emulates dy- namic stress waveforms extracted from CFD for com- parison to PDFs 6 (Fig. 15) Fig. 13: Platelet Activity State (PAS) As- say to measure thrombin gerneration. Fig. 14: Berlin pulsatile LVAD for bulk flow platelet activation studies. Fig. 15: Programmable Hemodynamic Shearing Device (HSD) to em- ulate dynamic stress waveforms extracted from CFD simulations. Results FSI-Innovia SIBS Valve ● Peak velocity was 1.45 m/s (Fig. 16) ● Max. stress 81 kPa (Fig. 17) Fig. 16: FSI fluid phase side view Innovia polymer valve Fig. 17: FSI solid phase top view Innovia polymer valve CFD-Innovia vs. Aortech ● Slight advantage to the Innovia valve over the Aortech (Figs. 18-20) Fig. 18: Regurgitant flow par- ticle trajectories: Innovia. Fig. 19: Reguritant flow par- ticle trajectories: Aortech Fig. 20: Thrombogenic footprints of Innovia vs. Aortech polymer valves LVAD-Innovia vs. Tissue ● PAS results: Innovia valve 5-fold lower platelet activa- tion rate (PAR) vs. 'gold-standard' Tissue valve (Fig. 21) ● P-selectin results: agreed with PAS (Fig. 22) Fig. 21: PAS results show- ing 5-fold difference between Innovia and Magna valves. Fig. 22: P-selectin results show- ing 4-fold difference between Innovia and Magna valves. Discussion ● Innovative combination of state-of-the-art numerical and experimental methods ● Design, fabrication, evaluation, and optimization capa- bilities ● Reduce or eliminate the need for anticoagulant drugs ● May be adapted by industry and regulatory agencies ● Developing novel technology ● Successful partnership of Academia & Industry Funding ● This study is supported by the National Institutes of Health-NIBIB ● Quantum Award Phase I R01, EB008004-01, DB ● $2 million ● Quantum Award Implementation Phase II, 1U01EB012487-0, DB ● $7.5 million References 1. American Heart Association 2. W. Rosamond et al. Circulation, 115 (2007) e69-171. 3. H. Ghanbari et al. Trends Biotechnol, 27 (2009) 359-367. 4. T.E. Claiborne et al. Int J Artif Organs, 32 (2009) 262-271. 5. D. Bluestein et al. Ann Biomed Eng, 38 (2010) 1236-1256. 6. M. Xenos et al. J Biomech, 43 (2010) 2400-2409. 7. T.E. Claiborne et al. ASAIO J, 57 (2011) 26-31. 8. J. Jesty, D. Bluestein, Anal Biochem, 272 (1999) 64-70.