The Experts below are selected from a list of 285 Experts worldwide ranked by ideXlab platform
Danny Bluestein - One of the best experts on this subject based on the ideXlab platform.
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device Thrombogenicity emulation an in silico predictor of in vitro and in vivo ventricular assist device Thrombogenicity
Scientific Reports, 2019Co-Authors: Wei Che Chiu, Marvin J Slepian, Phat L Tran, Zain I Khalpey, Danny BluesteinAbstract:: Ventricular assist devices (VAD), a mainstay of therapy for advanced and end-stage heart failure, remain plagued by device Thrombogenicity. Combining advanced in silico and in vitro methods, Device Thrombogenicity Emulation (DTE) is a device design approach for enhancing VAD thromboresistance. Here we tested DTE efficacy in experimental VAD designs. DTE incorporates iterative design modifications with advanced CFD to compute the propensity of large populations of platelets to activate by flow-induced stresses (statistically representing the VAD 'Thrombogenic Footprint'). The DTE approach was applied to a VAD (MINDTE) design with a favorable thromboresistance profile and compared against a design (MAXDTE) that generated an intentionally poor thromboresistance profile. DTE predictions were confirmed by testing physical prototypes in vitro by measuring VAD Thrombogenicity using the modified prothrombinase assay. Chronic in vivo studies in VAD implanted calves, revealed MINDTE calf surviving well with low platelet activation, whereas the MAXDTE animal sustained thromboembolic strokes. DTE predictions were confirmed, correlating with in vitro and in vivo Thrombogenicity, supporting utility in guiding device development, potentially reducing the need for animal studies.
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device Thrombogenicity emulation a novel methodology for optimizing the thromboresistance of cardiovascular devices
Journal of Biomechanics, 2013Co-Authors: Danny Bluestein, Marvin J Slepian, Shmuel EinavAbstract:Thrombotic complications with mechanical circulatory support (MCS) devices remain a critical limitation to their long-term use. Device-induced shear forces may enhance the thrombotic potential of MCS devices through chronic activation of platelets, with a known dose–time response of the platelets to the accumulated stress experienced while flowing through the device–mandating complex, lifelong anticoagulation therapy. To enhance the thromboresistance of these devices for facilitating their long-term use, a universal predictive methodology entitled device Thrombogenicity emulation (DTE) was developed. DTE is aimed at optimizing the thromboresistance of any MCS device. It is designed to test device-mediated Thrombogenicity, coupled with virtual design modifications, in an iterative approach. This disruptive technology combines in silico numerical simulations with in vitro measurements, by correlating device hemodynamics with platelet activity coagulation markers—before and after iterative design modifications aimed at achieving optimized thrombogenic performance. The design changes are first tested in the numerical domain, and the resultant device conditions are then emulated in a hemodynamic shearing device (HSD) in which platelet activity is measured under device emulated conditions. As such, DTE can be easily incorporated during the device research and development phase—achieving minimization of the device Thrombogenicity before prototypes are built and tested thereby reducing the ultimate cost of preclinical and clinical trials. The robust capability of this predictive technology is demonstrated here in various MCS devices. The presented examples indicate the potential of DTE for reducing device Thrombogenicity to a level that may obviate or significantly reduce the extent of anticoagulation currently mandated for patients implanted with MCS devices for safe long-term clinical use.
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device Thrombogenicity emulation a novel method for optimizing mechanical circulatory support device thromboresistance
PLOS ONE, 2012Co-Authors: Gaurav Girdhar, Michalis Xenos, Yared Alemu, Jolyon Jesty, Marvin J Slepian, Shmuel Einav, Wei Che Chiu, Bryan Lynch, Danny BluesteinAbstract:Mechanical circulatory support (MCS) devices provide both short and long term hemodynamic support for advanced heart failure patients. Unfortunately these devices remain plagued by thromboembolic complications associated with chronic platelet activation – mandating complex, lifelong anticoagulation therapy. To address the unmet need for enhancing the thromboresistance of these devices to extend their long term use, we developed a universal predictive methodology entitled Device Thrombogenicity Emulation (DTE) that facilitates optimizing the thrombogenic performance of any MCS device – ideally to a level that may obviate the need for mandatory anticoagulation. DTE combines in silico numerical simulations with in vitro measurements by correlating device hemodynamics with platelet activity coagulation markers – before and after iterative design modifications aimed at achieving optimized thrombogenic performance. DTE proof-of-concept is demonstrated by comparing two rotary Left Ventricular Assist Devices (LVADs) (DeBakey vs HeartAssist 5, Micromed Houston, TX), the latter a version of the former following optimization of geometrical features implicated in device Thrombogenicity. Cumulative stresses that may drive platelets beyond their activation threshold were calculated along multiple flow trajectories and collapsed into probability density functions (PDFs) representing the device ‘thrombogenic footprint’, indicating significantly reduced Thrombogenicity for the optimized design. Platelet activity measurements performed in the actual pump prototypes operating under clinical conditions in circulation flow loops – before and after the optimization with the DTE methodology, show an order of magnitude lower platelet activity rate for the optimized device. The robust capability of this predictive technology – demonstrated here for attaining safe and cost-effective pre-clinical MCS thrombo-optimization – indicates its potential for reducing device Thrombogenicity to a level that may significantly limit the extent of concomitant antithrombotic pharmacotherapy needed for safe clinical device use.
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design optimization of a mechanical heart valve for reducing valve Thrombogenicity a case study with ats valve
Asaio Journal, 2010Co-Authors: Yared Alemu, Michalis Xenos, Gaurav Girdhar, Jolyon Jesty, Shmuel Einav, Jawaad Sheriff, Danny BluesteinAbstract:: Patients implanted with mechanical heart valves (MHV) or with ventricular assist devices that use MHV require mandatory lifelong anticoagulation for secondary stroke prevention. We recently developed a novel Device Thrombogenicity Emulator (DTE) methodology that interfaces numerical and experimental approaches to optimize the thrombogenic performance of the device and reduce the bleeding risk associated with anticoagulation therapy. Device Thrombogenicity Emulator uses stress-loading waveforms in pertinent platelet flow trajectories that are extracted from highly resolved numerical simulations and emulates these flow conditions in a programmable hemodynamic shearing device (HSD) by which platelet activity is measured. We have previously compared two MHV, ATS and the St. Jude Medical, and demonstrated that owing to its nonrecessed hinge design, the ATS valve offers improved thrombogenic performance. In this study, we further optimize the ATS valve thrombogenic performance, by modifying various design features of the valve, intended to achieve reduced Thrombogenicity: 1) optimizing the leaflet-housing gap clearance; 2) increasing the effective maximum opening angle of the valve; and 3) introducing a streamlined channel between the leaflet stops of the valve that increases the effective flow area. We have demonstrated that the DTE optimization methodology can be used as test bed for developing devices with significantly improved thombogenic performance.
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design optimization of a mechanical heart valve for reducing valve Thrombogenicity a case study with ats valve
Asaio Journal, 2010Co-Authors: Yared Alemu, Michalis Xenos, Gaurav Girdhar, Jolyon Jesty, Shmuel Einav, Jawaad Sheriff, Danny BluesteinAbstract:Patients implanted with mechanical heart valves (MHV) or with ventricular assist devices that use MHV require mandatory lifelong anticoagulation for secondary stroke prevention. We recently developed a novel Device Thrombogenicity Emulator (DTE) methodology that interfaces numerical and experimental approaches to optimize the thrombogenic performance of the device and reduce the bleeding risk associated with anticoagulation therapy. Device Thrombogenicity Emulator uses stress-loading waveforms in pertinent platelet flow trajectories that are extracted from highly resolved numerical simulations and emulates these flow conditions in a programmable hemodynamic shearing device (HSD) by which platelet activity is measured. We have previously compared two MHV, ATS and the St. Jude Medical, and demonstrated that owing to its nonrecessed hinge design, the ATS valve offers improved thrombogenic performance. In this study, we further optimize the ATS valve thrombogenic performance, by modifying various design features of the valve, intended to achieve reduced Thrombogenicity: 1) optimizing the leaflet-housing gap clearance; 2) increasing the effective maximum opening angle of the valve; and 3) introducing a streamlined channel between the leaflet stops of the valve that increases the effective flow area. We have demonstrated that the DTE optimization methodology can be used as test bed for developing devices with significantly improved thombogenic performance. ASAIO Journal 2010; 56:389 –396. Flow past mechanical heart valves (MHV) in mechanical circulatory support devices, including total artificial hearts and ventricular assist devices (VADs), is primarily implicated in thromboembolism.1 The newer valve designs, although more
Frank D Kolodgie - One of the best experts on this subject based on the ideXlab platform.
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tct 486 acute Thrombogenicity and inflammation in response to a durable fluoropolymer everolimus eluting stent relative to a durable biolinx polymer zotarolimus eluting stent
Journal of the American College of Cardiology, 2017Co-Authors: Sho Torii, Syed Hossainy, Qi Cheng, Frank D Kolodgie, Eduardo Acampado, Laura Perkins, Stephen D Pacetti, Aloke V Finn, Renu VirmaniAbstract:Clinical data indicate differences in acute thrombosis among different drug-eluting stents (DES), which may relate to properties of DES polymer coatings and stent design. We sought to investigate stent Thrombogenicity between a durable fluoropolymer coated DES (Xience Alpine, X-EES, Abbott Vascular
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acute Thrombogenicity of a durable polymer everolimus eluting stent relative to contemporary drug eluting stents with biodegradable polymer coatings assessed ex vivo in a swine shunt model
Jacc-cardiovascular Interventions, 2015Co-Authors: Fumiyuki Otsuka, Qi Cheng, Kazuyuki Yahagi, Eduardo Acampado, Alexander Sheehy, Kenichi Sakakura, Laura Perkins, Saami K Yazdani, Kristina Euller, Frank D KolodgieAbstract:Abstract Objectives This study sought to evaluate whether the permanent fluoropolymer-coated Xience Xpedition everolimus-eluting stent (Xience-EES) exhibits lower acute Thrombogenicity compared with contemporary drug-eluting stents (DES) with biodegradable polymer coatings in an acute swine shunt model. Background Previous pre-clinical and clinical experience suggests that several factors may influence the predisposition for acute thrombus formation of polymer-coated DES, including stent design and the polymer coating technology. It remains unclear whether relevant differences exist with respect to acute Thrombogenicity, particularly between current commercial stent designs using permanent polymers and those using biodegradable polymers. Methods An ex vivo carotid to jugular arteriovenous porcine shunt model involving a test circuit of 3 in-line stents, was used to test acute Thrombogenicity, where Xience-EES (n = 24) was compared with 4 CE-marked DES with biodegradable polymer coatings (BioMatrix Flex, Synergy, Nobori, and Orsiro [n = 6 each]). After 1 h of circulation, platelet aggregation in whole mount stents was evaluated by confocal microscopy with immunofluorescent staining against dual platelet markers (CD61/CD42b) along with scanning electron microscopy. Results Xience-EES showed the least percentage of thrombus-occupied area as compared with the biodegradable polymer-coated DES, with a significant difference compared with BioMatrix Flex and Synergy (mean differences: [BioMatrix Flex: 15.54, 95% confidence interval [CI]: 11.34 to 19.75, p Conclusions Xience-EES’s overall design confers acute thromboresistance relative to contemporary DES with biodegradable coatings, with less platelet aggregation versus BioMatrix Flex and Synergy, and less inflammatory cell attachment versus BioMatrix Flex, Nobori, and Orsiro, in an ex vivo swine shunt model, which lends support to reported clinical findings of lower early stent thrombosis.
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Thrombogenicity and early vascular healing response in metallic biodegradable polymer based and fully bioabsorbable drug eluting stents
Circulation-cardiovascular Interventions, 2015Co-Authors: Tobias Koppara, Qi Cheng, Kazuyuki Yahagi, Hiroyoshi Mori, Oscar D Sanchez, Julia Feygin, Eric Wittchow, Frank D Kolodgie, Renu Virmani, Michael JonerAbstract:Background— Acute Thrombogenicity and re-endothelialization represent clinically relevant end points pertaining to the safety of coronary stents, which have not been compared among biodegradable polymer-based drug-eluting metallic stents and fully bioabsorbable scaffolds to date. Methods and Results— We investigated comparative outcomes with respect to acute Thrombogenicity and re-endothelialization among thin-strut biodegradable polymer metallic everolimus eluting stents (EES), thick-strut fully bioabsorbable EES, thick-strut biodegradable polymer metallic biolimus-eluting stents and control bare metal stents. An ex-vivo porcine arterio-venous shunt model was used to assess platelet aggregation, whereas a healthy rabbit model of iliofemoral stent implantation was used to assess re-endothelialization and inflammation. Confocal microscopy was used to detect fluorescently labeled antibody staining directed against CD61/CD42b for the identification of aggregated thrombocytes, CD14/PM-1, and RAM-11 for identification of neutrophils and monocytes/macrophages. Endothelial recovery was assessed by scanning electron microscopy, whereas CD31/PECAM-1 was used to confirm endothelial maturity. EES demonstrated significantly less acute Thrombogenicity compared with bioabsorbable EES and biolimus-eluting stents. EES showed greater re-endothelialization at 28 days and reduced inflammatory cell adhesion of monocytes/macrophages at 14 days compared with bioabsorbable EES. Only bare metal stents showed complete re-endothelialization at 28 days. Conclusions— These outcomes indicate differential trends in Thrombogenicity and vascular healing among contemporary stents used in clinical practice and suggest a need for long-term adjunct antithrombotic pharmacotherapy for bioabsorbable EES.
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tct 436 ex vivo shunt Thrombogenicity a comparison of xience everolimus eluting stents to contemporary biodegradable polymer coated drug eluting stents
Journal of the American College of Cardiology, 2014Co-Authors: Fumiyuki Otsuka, Qi Cheng, Kazuyuki Yahagi, Michael Joner, Alexander Sheehy, Kenichi Sakakura, Robert Kutys, Laura E Perkins, Elena Ladich, Frank D KolodgieAbstract:Previous preclinical experience showed that polymer-coatings of drug eluting stents (DES) lower the predisposition for stent thrombosis compared to bare metal stents. It remains unclear whether relevant differences exist in acute Thrombogenicity particularly between current permanent and
Qi Cheng - One of the best experts on this subject based on the ideXlab platform.
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tct 486 acute Thrombogenicity and inflammation in response to a durable fluoropolymer everolimus eluting stent relative to a durable biolinx polymer zotarolimus eluting stent
Journal of the American College of Cardiology, 2017Co-Authors: Sho Torii, Syed Hossainy, Qi Cheng, Frank D Kolodgie, Eduardo Acampado, Laura Perkins, Stephen D Pacetti, Aloke V Finn, Renu VirmaniAbstract:Clinical data indicate differences in acute thrombosis among different drug-eluting stents (DES), which may relate to properties of DES polymer coatings and stent design. We sought to investigate stent Thrombogenicity between a durable fluoropolymer coated DES (Xience Alpine, X-EES, Abbott Vascular
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comparison of acute Thrombogenicity for metallic and polymeric bioabsorbable scaffolds magmaris versus absorb in a porcine arteriovenous shunt model
Circulation-cardiovascular Interventions, 2017Co-Authors: Ron Waksman, Qi Cheng, Michael J Lipinski, Eduardo Acampado, Lila Adams, Sho Torii, Rebecca Torguson, David M Hellinga, Peter C Westman, Michael D JonerAbstract:Background—A comparison in acute Thrombogenicity between the Magmaris sirolimus-eluting bioabsorbable magnesium scaffold and the Absorb bioresorbable vascular scaffold has not been performed. This ...
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acute Thrombogenicity of a durable polymer everolimus eluting stent relative to contemporary drug eluting stents with biodegradable polymer coatings assessed ex vivo in a swine shunt model
Jacc-cardiovascular Interventions, 2015Co-Authors: Fumiyuki Otsuka, Qi Cheng, Kazuyuki Yahagi, Eduardo Acampado, Alexander Sheehy, Kenichi Sakakura, Laura Perkins, Saami K Yazdani, Kristina Euller, Frank D KolodgieAbstract:Abstract Objectives This study sought to evaluate whether the permanent fluoropolymer-coated Xience Xpedition everolimus-eluting stent (Xience-EES) exhibits lower acute Thrombogenicity compared with contemporary drug-eluting stents (DES) with biodegradable polymer coatings in an acute swine shunt model. Background Previous pre-clinical and clinical experience suggests that several factors may influence the predisposition for acute thrombus formation of polymer-coated DES, including stent design and the polymer coating technology. It remains unclear whether relevant differences exist with respect to acute Thrombogenicity, particularly between current commercial stent designs using permanent polymers and those using biodegradable polymers. Methods An ex vivo carotid to jugular arteriovenous porcine shunt model involving a test circuit of 3 in-line stents, was used to test acute Thrombogenicity, where Xience-EES (n = 24) was compared with 4 CE-marked DES with biodegradable polymer coatings (BioMatrix Flex, Synergy, Nobori, and Orsiro [n = 6 each]). After 1 h of circulation, platelet aggregation in whole mount stents was evaluated by confocal microscopy with immunofluorescent staining against dual platelet markers (CD61/CD42b) along with scanning electron microscopy. Results Xience-EES showed the least percentage of thrombus-occupied area as compared with the biodegradable polymer-coated DES, with a significant difference compared with BioMatrix Flex and Synergy (mean differences: [BioMatrix Flex: 15.54, 95% confidence interval [CI]: 11.34 to 19.75, p Conclusions Xience-EES’s overall design confers acute thromboresistance relative to contemporary DES with biodegradable coatings, with less platelet aggregation versus BioMatrix Flex and Synergy, and less inflammatory cell attachment versus BioMatrix Flex, Nobori, and Orsiro, in an ex vivo swine shunt model, which lends support to reported clinical findings of lower early stent thrombosis.
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Thrombogenicity and early vascular healing response in metallic biodegradable polymer based and fully bioabsorbable drug eluting stents
Circulation-cardiovascular Interventions, 2015Co-Authors: Tobias Koppara, Qi Cheng, Kazuyuki Yahagi, Hiroyoshi Mori, Oscar D Sanchez, Julia Feygin, Eric Wittchow, Frank D Kolodgie, Renu Virmani, Michael JonerAbstract:Background— Acute Thrombogenicity and re-endothelialization represent clinically relevant end points pertaining to the safety of coronary stents, which have not been compared among biodegradable polymer-based drug-eluting metallic stents and fully bioabsorbable scaffolds to date. Methods and Results— We investigated comparative outcomes with respect to acute Thrombogenicity and re-endothelialization among thin-strut biodegradable polymer metallic everolimus eluting stents (EES), thick-strut fully bioabsorbable EES, thick-strut biodegradable polymer metallic biolimus-eluting stents and control bare metal stents. An ex-vivo porcine arterio-venous shunt model was used to assess platelet aggregation, whereas a healthy rabbit model of iliofemoral stent implantation was used to assess re-endothelialization and inflammation. Confocal microscopy was used to detect fluorescently labeled antibody staining directed against CD61/CD42b for the identification of aggregated thrombocytes, CD14/PM-1, and RAM-11 for identification of neutrophils and monocytes/macrophages. Endothelial recovery was assessed by scanning electron microscopy, whereas CD31/PECAM-1 was used to confirm endothelial maturity. EES demonstrated significantly less acute Thrombogenicity compared with bioabsorbable EES and biolimus-eluting stents. EES showed greater re-endothelialization at 28 days and reduced inflammatory cell adhesion of monocytes/macrophages at 14 days compared with bioabsorbable EES. Only bare metal stents showed complete re-endothelialization at 28 days. Conclusions— These outcomes indicate differential trends in Thrombogenicity and vascular healing among contemporary stents used in clinical practice and suggest a need for long-term adjunct antithrombotic pharmacotherapy for bioabsorbable EES.
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tct 436 ex vivo shunt Thrombogenicity a comparison of xience everolimus eluting stents to contemporary biodegradable polymer coated drug eluting stents
Journal of the American College of Cardiology, 2014Co-Authors: Fumiyuki Otsuka, Qi Cheng, Kazuyuki Yahagi, Michael Joner, Alexander Sheehy, Kenichi Sakakura, Robert Kutys, Laura E Perkins, Elena Ladich, Frank D KolodgieAbstract:Previous preclinical experience showed that polymer-coatings of drug eluting stents (DES) lower the predisposition for stent thrombosis compared to bare metal stents. It remains unclear whether relevant differences exist in acute Thrombogenicity particularly between current permanent and
Elazer R Edelman - One of the best experts on this subject based on the ideXlab platform.
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response to letter regarding article stent Thrombogenicity early in high risk interventional settings is driven by stent design and deployment and protected by polymer drug coatings
Circulation, 2011Co-Authors: Kumaran Kolandaivelu, Rajesh V Swaminathan, William J Gibson, Vijaya B Kolachalama, Kimlien Nguyenehrenreich, Virginia L Giddings, Leslie Coleman, Gee K Wong, Elazer R EdelmanAbstract:Vorphal and Kelm raise an intriguing nuance regarding vascular repair after drug-eluting stent implantation. Their insightful letter and pioneering work suggest limited thrombosis may be important for optimal healing, and complete elimination of clot may adversely affect repair. Interestingly, early studies of drug-free stent coatings reported reduced Thrombogenicity compared with bare metal devices without effecting intimal hyperplasia.1 …
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stent Thrombogenicity early in high risk interventional settings is driven by stent design and deployment and protected by polymer drug coatings
Circulation, 2011Co-Authors: Kumaran Kolandaivelu, Rajesh V Swaminathan, William J Gibson, Vijaya B Kolachalama, Kimlien Nguyenehrenreich, Virginia L Giddings, Leslie Coleman, Gee K Wong, Elazer R EdelmanAbstract:Background—Stent thrombosis is a lethal complication of endovascular intervention. Concern has been raised about the inherent risk associated with specific stent designs and drug-eluting coatings, yet clinical and animal support is equivocal. Methods and Results—We examined whether drug-eluting coatings are inherently thrombogenic and if the response to these materials was determined to a greater degree by stent design and deployment with custom-built stents. Drug/polymer coatings uniformly reduce rather than increase Thrombogenicity relative to matched bare metal counterparts (0.65-fold; P=0.011). Thick-strutted (162 μm) stents were 1.5-fold more thrombogenic than otherwise identical thin-strutted (81 μm) devices in ex vivo flow loops (P<0.001), commensurate with 1.6-fold greater thrombus coverage 3 days after implantation in porcine coronary arteries (P=0.004). When bare metal stents were deployed in malapposed or overlapping configurations, Thrombogenicity increased compared with apposed, length-matche...
Marvin J Slepian - One of the best experts on this subject based on the ideXlab platform.
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device Thrombogenicity emulation an in silico predictor of in vitro and in vivo ventricular assist device Thrombogenicity
Scientific Reports, 2019Co-Authors: Wei Che Chiu, Marvin J Slepian, Phat L Tran, Zain I Khalpey, Danny BluesteinAbstract:: Ventricular assist devices (VAD), a mainstay of therapy for advanced and end-stage heart failure, remain plagued by device Thrombogenicity. Combining advanced in silico and in vitro methods, Device Thrombogenicity Emulation (DTE) is a device design approach for enhancing VAD thromboresistance. Here we tested DTE efficacy in experimental VAD designs. DTE incorporates iterative design modifications with advanced CFD to compute the propensity of large populations of platelets to activate by flow-induced stresses (statistically representing the VAD 'Thrombogenic Footprint'). The DTE approach was applied to a VAD (MINDTE) design with a favorable thromboresistance profile and compared against a design (MAXDTE) that generated an intentionally poor thromboresistance profile. DTE predictions were confirmed by testing physical prototypes in vitro by measuring VAD Thrombogenicity using the modified prothrombinase assay. Chronic in vivo studies in VAD implanted calves, revealed MINDTE calf surviving well with low platelet activation, whereas the MAXDTE animal sustained thromboembolic strokes. DTE predictions were confirmed, correlating with in vitro and in vivo Thrombogenicity, supporting utility in guiding device development, potentially reducing the need for animal studies.
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device Thrombogenicity emulation a novel methodology for optimizing the thromboresistance of cardiovascular devices
Journal of Biomechanics, 2013Co-Authors: Danny Bluestein, Marvin J Slepian, Shmuel EinavAbstract:Thrombotic complications with mechanical circulatory support (MCS) devices remain a critical limitation to their long-term use. Device-induced shear forces may enhance the thrombotic potential of MCS devices through chronic activation of platelets, with a known dose–time response of the platelets to the accumulated stress experienced while flowing through the device–mandating complex, lifelong anticoagulation therapy. To enhance the thromboresistance of these devices for facilitating their long-term use, a universal predictive methodology entitled device Thrombogenicity emulation (DTE) was developed. DTE is aimed at optimizing the thromboresistance of any MCS device. It is designed to test device-mediated Thrombogenicity, coupled with virtual design modifications, in an iterative approach. This disruptive technology combines in silico numerical simulations with in vitro measurements, by correlating device hemodynamics with platelet activity coagulation markers—before and after iterative design modifications aimed at achieving optimized thrombogenic performance. The design changes are first tested in the numerical domain, and the resultant device conditions are then emulated in a hemodynamic shearing device (HSD) in which platelet activity is measured under device emulated conditions. As such, DTE can be easily incorporated during the device research and development phase—achieving minimization of the device Thrombogenicity before prototypes are built and tested thereby reducing the ultimate cost of preclinical and clinical trials. The robust capability of this predictive technology is demonstrated here in various MCS devices. The presented examples indicate the potential of DTE for reducing device Thrombogenicity to a level that may obviate or significantly reduce the extent of anticoagulation currently mandated for patients implanted with MCS devices for safe long-term clinical use.
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device Thrombogenicity emulation a novel method for optimizing mechanical circulatory support device thromboresistance
PLOS ONE, 2012Co-Authors: Gaurav Girdhar, Michalis Xenos, Yared Alemu, Jolyon Jesty, Marvin J Slepian, Shmuel Einav, Wei Che Chiu, Bryan Lynch, Danny BluesteinAbstract:Mechanical circulatory support (MCS) devices provide both short and long term hemodynamic support for advanced heart failure patients. Unfortunately these devices remain plagued by thromboembolic complications associated with chronic platelet activation – mandating complex, lifelong anticoagulation therapy. To address the unmet need for enhancing the thromboresistance of these devices to extend their long term use, we developed a universal predictive methodology entitled Device Thrombogenicity Emulation (DTE) that facilitates optimizing the thrombogenic performance of any MCS device – ideally to a level that may obviate the need for mandatory anticoagulation. DTE combines in silico numerical simulations with in vitro measurements by correlating device hemodynamics with platelet activity coagulation markers – before and after iterative design modifications aimed at achieving optimized thrombogenic performance. DTE proof-of-concept is demonstrated by comparing two rotary Left Ventricular Assist Devices (LVADs) (DeBakey vs HeartAssist 5, Micromed Houston, TX), the latter a version of the former following optimization of geometrical features implicated in device Thrombogenicity. Cumulative stresses that may drive platelets beyond their activation threshold were calculated along multiple flow trajectories and collapsed into probability density functions (PDFs) representing the device ‘thrombogenic footprint’, indicating significantly reduced Thrombogenicity for the optimized design. Platelet activity measurements performed in the actual pump prototypes operating under clinical conditions in circulation flow loops – before and after the optimization with the DTE methodology, show an order of magnitude lower platelet activity rate for the optimized device. The robust capability of this predictive technology – demonstrated here for attaining safe and cost-effective pre-clinical MCS thrombo-optimization – indicates its potential for reducing device Thrombogenicity to a level that may significantly limit the extent of concomitant antithrombotic pharmacotherapy needed for safe clinical device use.
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device Thrombogenicity emulator dte design optimization methodology for cardiovascular devices a study in two bileaflet mhv designs
Journal of Biomechanics, 2010Co-Authors: Michalis Xenos, Gaurav Girdhar, Yared Alemu, Jolyon Jesty, Marvin J Slepian, Shmuel Einav, Danny BluesteinAbstract:Patients who receive prosthetic heart valve (PHV) implants require mandatory anticoagulation medication after implantation due to the thrombogenic potential of the valve. Optimization of PHV designs may facilitate reduction of flow-induced Thrombogenicity and reduce or eliminate the need for post-implant anticoagulants. We present a methodology entitled Device Thrombogenicty Emulator (DTE) for optimizing the thrombo-resistance performance of PHV by combining numerical and experimental approaches. Two bileaflet mechanical heart valves (MHV) designs, St. Jude Medical (SJM) and ATS, were investigated by studying the effect of distinct flow phases on platelet activation. Transient turbulent and direct numerical simulations (DNS) were conducted, and stress loading histories experienced by the platelets were calculated along flow trajectories. The numerical simulations indicated distinct design dependent differences between the two valves. The stress loading waveforms extracted from the numerical simulations were programmed into a hemodynamic shearing device (HSD), emulating the flow conditions past the valves in distinct ‘hot-spot’ flow regions that are implicated in MHV Thrombogenicity. The resultant platelet activity was measured with a modified prothrombinase assay, and was found to be significantly higher in the SJM valve, mostly during the regurgitation phase. The experimental results were in excellent agreement with the calculated platelet activation potential. This establishes the utility of the DTE methodology for serving as a test bed for evaluating design modifications for achieving better thrombogenic performance for such devices.
