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...th Unsteady Reynolds Averaged Navier-Stokes (URANS) CFD. Highly resolved computational grids (currently up to 20 million elements) are generated as required for the two equation k-o turbulence model (=-=Wilcox, 1994-=-). This simulation approach is further described in detail in our previous publications (Alemu et al., 2010; Xenos et al., 2010). Typical platelet trajectories in the flow field of a VAD and their cor...

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...latelet activity, the iterations are stopped and an optimized prototypThe numerical simulations of blood flow through the devices (modeled as a two-phase fluid with the platelets suspended in plasma (=-=Gosman and Ioannides, 1983-=-) combine fluid structure interaction (FSI) with Unsteady Reynolds Averaged Navier-Stokes (URANS) CFD. Highly resolved computational grids (currently up to 20 million elements) are generated as requir...

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...g hemolysis and platelet lysis indices along trajectories in the flow field of MHV (Goubergrits and Affeld, 2004). Several models examined the interaction of activated platelets with the blood field (=-=Kuharsky and Fogelson, 2001-=-; Sorensen et al., 1999a), and platelet deposition (Reininger et al., 1999; Worth Longest and Kleinstreuer, 2003). Such modeling efforts provide insight into the areas where platelets have a high prob...

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...tly available (Charron et al., 1994). Several approaches for studying device-induced thrombogenicity were developed by a few groups (Paul et al., 1998; Travis et al., 2002; Jesty and Bluestein, 1999; =-=Jesty et al., 2003-=-). Jesty and Bluestein developed an innovative platelet activity state (PAS) assay, facilitating measurements of the thrombogenic potential induced by flow in devices. This technique was applied to in...

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... activation (SIPA). In prosthetic devices the pathological blood flow patterns related to pulsatility, eddy formation, and turbulence, may predominate the platelets response (Alveriadou et al., 1993; =-=Folie and McIntire, 1989-=-). The cumulative effect of varying flow stresses and exposure times along platelet trajectories was studied in stenoses and past MHV (Bluestein, 2004; Bluestein et al., 1997, 2000, 2002, 2004; Cao an...

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...emonstrated to have a significant effect on platelet damage (Travis et al., 2001).the wake dynamics and complex behavior of vortex shedding (Huang et al., 1994; Kelly et al., 1999; King et al., 1997; =-=Krafczyk et al., 1998-=-). First unsteady turbulent Reynolds Averaged (URANS) simulations using the transient turbulence Wilcox k-o model (Bluestein et al., 2000, 2002) quantified stress histories of platelets along pertinen...

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...0; Xenos et al., 2010). Typical platelet trajectories in the flow field of a VAD and their corresponding stress-loading histories (computed with the combined effect of shear stress and exposure time (=-=Alemu and Bluestein, 2007-=-; Apel et al., 2001; Hellums, 1994) are shown (Fig. 1a and b)). Currently up to 65,000 such histories are collapsed into a quantitative probability density function (PDF) which serves as the ‘thrombog...

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...mbogenic aspects are currently available (Charron et al., 1994). Several approaches for studying device-induced thrombogenicity were developed by a few groups (Paul et al., 1998; Travis et al., 2002; =-=Jesty and Bluestein, 1999-=-; Jesty et al., 2003). Jesty and Bluestein developed an innovative platelet activity state (PAS) assay, facilitating measurements of the thrombogenic potential induced by flow in devices. This techniq...

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...facilitating measurements of the thrombogenic potential induced by flow in devices. This technique was applied to in vitro measurements of flow-induced platelet activation in MHVs mounted in an LVAD (=-=Yin et al., 2004-=-), and in bioprosthetic and polymer valves (Yin et al., 2005), which are targeted for minimally invasive, percutaneous valve delivery (Feldman, 2006; Mesana, 2006)—the breakthrough technique with a hu...

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...ont et al., 2007). Few models for hemolysis have been developed over the years, e.g., as a function of mechanical energy dissipation (Bluestein and Mockros, 1969), or shear stress (Apel et al., 2001; =-=Bludszuweit, 1995-=-; Burgreen et al., 2001). In these predictive phenomenological models, that are adaptable to platelets, the normalized internal damage accumulates until a critical value of damage is reached, either a...

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...ctories in the flow field of a VAD and their corresponding stress-loading histories (computed with the combined effect of shear stress and exposure time (Alemu and Bluestein, 2007; Apel et al., 2001; =-=Hellums, 1994-=-) are shown (Fig. 1a and b)). Currently up to 65,000 such histories are collapsed into a quantitative probability density function (PDF) which serves as the ‘thrombogenic footprint’ of the device (Ale...

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...e Medical MHVs (Dumont et al., 2007). Few models for hemolysis have been developed over the years, e.g., as a function of mechanical energy dissipation (Bluestein and Mockros, 1969), or shear stress (=-=Apel et al., 2001-=-; Bludszuweit, 1995; Burgreen et al., 2001). In these predictive phenomenological models, that are adaptable to platelets, the normalized internal damage accumulates until a critical value of damage i...

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...lveriadou et al., 1993; Folie and McIntire, 1989). The cumulative effect of varying flow stresses and exposure times along platelet trajectories was studied in stenoses and past MHV (Bluestein, 2004; =-=Bluestein et al., 1997-=-, 2000, 2002, 2004; Cao and Rittgers, 1998). In PHV and CVS devices portions of the flow cycle may become turbulent, (Bluestein et al., 1994, 2000), with elevated stresses within MHV hinges (Yoganatha...

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...merically over 3D device domains for the purpose of design optimization (Garon and Farinas, 2004), and by integrating hemolysis and platelet lysis indices along trajectories in the flow field of MHV (=-=Goubergrits and Affeld, 2004-=-). Several models examined the interaction of activated platelets with the blood field (Kuharsky and Fogelson, 2001; Sorensen et al., 1999a), and platelet deposition (Reininger et al., 1999; Worth Lon...

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...elets response (Alveriadou et al., 1993; Folie and McIntire, 1989). The cumulative effect of varying flow stresses and exposure times along platelet trajectories was studied in stenoses and past MHV (=-=Bluestein, 2004-=-; Bluestein et al., 1997, 2000, 2002, 2004; Cao and Rittgers, 1998). In PHV and CVS devices portions of the flow cycle may become turbulent, (Bluestein et al., 1994, 2000), with elevated stresses with...

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...for shearinduced platelet activation (SIPA). In prosthetic devices the pathological blood flow patterns related to pulsatility, eddy formation, and turbulence, may predominate the platelets response (=-=Alveriadou et al., 1993-=-; Folie and McIntire, 1989). The cumulative effect of varying flow stresses and exposure times along platelet trajectories was studied in stenoses and past MHV (Bluestein, 2004; Bluestein et al., 1997...

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...mage history, or as weight average damage accumulation over a number of cycles. In vitro hemolysis indices were investigated numerically over 3D device domains for the purpose of design optimization (=-=Garon and Farinas, 2004-=-), and by integrating hemolysis and platelet lysis indices along trajectories in the flow field of MHV (Goubergrits and Affeld, 2004). Several models examined the interaction of activated platelets wi...

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...et MHV pivots was demonstrated to have a significant effect on platelet damage (Travis et al., 2001).the wake dynamics and complex behavior of vortex shedding (Huang et al., 1994; Kelly et al., 1999; =-=King et al., 1997-=-; Krafczyk et al., 1998). First unsteady turbulent Reynolds Averaged (URANS) simulations using the transient turbulence Wilcox k-o model (Bluestein et al., 2000, 2002) quantified stress histories of p...

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...ulations of the blood flow through the redesignedThrombus formation was investigated in blood flow through orifices simulating these MHV hinges region using a thrombin– antithrombin -llI (TAT) assay (=-=Fallon et al., 2006-=-). Vortex shedding was observed experimentally and computed numerically in the wake of MHV leaflets and in various MCS devices. Shed vortices were studied in the wake of MHVs (Bluestein et al., 2001, ...

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...me response characteristics of equivalent chemical agonists (O’Brien and Salmon, 1990). A commonly used threshold for platelet activation under constant shear level was established by Hellums et al.,(=-=Hellums et al., 1987-=-), forming the foundation for shearinduced platelet activation (SIPA). In prosthetic devices the pathological blood flow patterns related to pulsatility, eddy formation, and turbulence, may predominat...

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...e www.Jel methodology for iovascular devices n a,b y of Arizona, Tucson, AZ, USA iv 69978, Israel vier.com/locate/jbiomech omech.com mechanics several folds, resulting in an increased collision rate (=-=Wurzinger et al., 1985-=-). Numerical simulation in the wake of a MHV depicted D. Bluestein et al. / Journal of Biomechanics 46 (2013) 338–344 339The non-physiologic flow patterns generated in a device are considered as one o...

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...ries was studied in stenoses and past MHV (Bluestein, 2004; Bluestein et al., 1997, 2000, 2002, 2004; Cao and Rittgers, 1998). In PHV and CVS devices portions of the flow cycle may become turbulent, (=-=Bluestein et al., 1994-=-, 2000), with elevated stresses within MHV hinges (Yoganathan et al., 1998). VADs induce changes to coagulation through activation of platelets (Rothenburger et al., 2002; Wilhelm et al., 2001) despit...

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... platelet activation in MHVs mounted in an LVAD (Yin et al., 2004), and in bioprosthetic and polymer valves (Yin et al., 2005), which are targeted for minimally invasive, percutaneous valve delivery (=-=Feldman, 2006-=-; Mesana, 2006)—the breakthrough technique with a huge promise for patients who cannot tolerate cardiothoracic surgery. The goal is for polymer valves, which are better suited for catheter-based stent...

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...herapy. Leakage gap width within bileaflet MHV pivots was demonstrated to have a significant effect on platelet damage (Travis et al., 2001).the wake dynamics and complex behavior of vortex shedding (=-=Huang et al., 1994-=-; Kelly et al., 1999; King et al., 1997; Krafczyk et al., 1998). First unsteady turbulent Reynolds Averaged (URANS) simulations using the transient turbulence Wilcox k-o model (Bluestein et al., 2000,...

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...say (Fallon et al., 2006). Vortex shedding was observed experimentally and computed numerically in the wake of MHV leaflets and in various MCS devices. Shed vortices were studied in the wake of MHVs (=-=Bluestein et al., 2001-=-, 2002; Reif et al., 1990) which promote hemostatic reaction by providing optimal mixing for platelet aggregation, increasing the procoagulant surfaces needed for the coagulation reactions to proceed,...

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...to activate). The HSD (Fig. 1c) combines features of cone and plate, and Couette viscometers to dynamically expose a population of platelets to a uniform shear stress field of rapidly varying levels (=-=Girdhar and Bluestein, 2008-=-), which are programmed into the device according to the loading waveforms extracted from advanced numerical simulations of blood flow through a device (Fig. 1b). The PAS assay employs a modified prot...

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...elements) are generated as required for the two equation k-o turbulence model (Wilcox, 1994). This simulation approach is further described in detail in our previous publications (Alemu et al., 2010; =-=Xenos et al., 2010-=-). Typical platelet trajectories in the flow field of a VAD and their corresponding stress-loading histories (computed with the combined effect of shear stress and exposure time (Alemu and Bluestein, ...

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...y applied the DTE methodology for optimizing the thrombogenic performance of various MCS and prosthetic heart valves, e.g., MHV (Xenos et al., 2010), polymer valves (Claiborne et al., 2011) and VADs (=-=Girdhar et al., 2012-=-). In the following section an example of utilizing DTE for achieving optimal thromboresistance in a VAD is demonstrated and also compared in vitro to the equivalent effect achieved by the anti-thromb...

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...s and thrombo-emboli generated in cardiovascular devices are composed primarily of platelets, with less fibrin involvement than one would encounter in situations associated with low-shear thrombosis (=-=Harker and Slichter, 1970-=-). Flow-induced shear platelet activation causes both aggregation and thrombin generation, showing consistent ‘dose’ and time response characteristics of equivalent chemical agonists (O’Brien and Salm...

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...ugh activation of platelets (Rothenburger et al., 2002; Wilhelm et al., 2001) despite aggressive anticoagulant therapy, with flow patterns implicated in the underlying risk for their thromboembolism (=-=Jin and Clark, 1993-=-), especially cerebral embolism (e.g., rates ranging from 7.4% for the Heartmate I VAD to approx. 50% for the Novacor VAD system) (El-Banayosy et al., 2001). Platelet aggregates are the source of micr...

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...16/j.jbiomech.2012.11.033 n Correspondence to: Department of Biomedical Engineering, Stony Brook University, HSC T15-090, Stony Brook, NY 11794-8151, USA. Tel.: þ1 631 444 2156; fax: þ1 631 444 6646.(=-=Portner et al., 2001-=-), and strokes (Lazar et al., 2004). Second and third generation continuous-flow VADs that have emerged complications at a rate of 0.7–6.4% per patient year (Butchart et al., 2001, 2003). In these pat...

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... on flow-induced thrombogenic aspects are currently available (Charron et al., 1994). Several approaches for studying device-induced thrombogenicity were developed by a few groups (Paul et al., 1998; =-=Travis et al., 2002-=-; Jesty and Bluestein, 1999; Jesty et al., 2003). Jesty and Bluestein developed an innovative platelet activity state (PAS) assay, facilitating measurements of the thrombogenic potential induced by fl...

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...00, 2002) quantified stress histories of platelets along pertinent trajectories. Advanced URANS and direct numerical simulations (DNS) included a damage accumulation in repeated passages past valves (=-=Alemu et al., 2010-=-), and FSI simulation comparing the thrombogenic potential of ATS and St. Jude Medical MHVs (Dumont et al., 2007). Few models for hemolysis have been developed over the years, e.g., as a function of m...

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...he MCS arm demonstrated significant limitations with unacceptable complication rates et al., 2009), attributed to the increased shear st possibility that improved VAD design could prev in the future (=-=Geisen et al., 2008-=-). The AbioCor ar developed as a possible solution to the chro availability of human hearts for transplantation. of the AbioCor TAH (ABIOMED, Inc.), a high rate bolic complications made the clinical o...

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...rom 7.4% for the Heartmate I VAD to approx. 50% for the Novacor VAD system) (El-Banayosy et al., 2001). Platelet aggregates are the source of microembolic signals (MES) measured in patients with PHV (=-=Grosset et al., 1996-=-). A significant effect of valve hemodynamics on platelet activation for two differing valve designs (bileaflet. vs. monoleaflet) was also observed in patients (Laas et al., 2003). The AbioCor TAH stu...

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...tex shedding was observed experimentally and computed numerically in the wake of MHV leaflets and in various MCS devices. Shed vortices were studied in the wake of MHVs (Bluestein et al., 2001, 2002; =-=Reif et al., 1990-=-) which promote hemostatic reaction by providing optimal mixing for platelet aggregation, increasing the procoagulant surfaces needed for the coagulation reactions to proceed, and dispersing the clott...

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...low cycle may become turbulent, (Bluestein et al., 1994, 2000), with elevated stresses within MHV hinges (Yoganathan et al., 1998). VADs induce changes to coagulation through activation of platelets (=-=Rothenburger et al., 2002-=-; Wilhelm et al., 2001) despite aggressive anticoagulant therapy, with flow patterns implicated in the underlying risk for their thromboembolism (Jin and Clark, 1993), especially cerebral embolism (e....

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...In these patients, platelets are chronicallyThe advent of mechanical circulatory support devices has provided life-saving solutions to patients with severe cardiovascular diseases. The REMATCH trial (=-=Stevenson et al., 2004-=-) was one of the first major studies to demonstrate that left ventricular assist devices (LVAD) are superior to drug therapy for advanced heart failure, paving the way for their use as long-term heart...

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...al., 1997, 2000, 2002, 2004; Cao and Rittgers, 1998). In PHV and CVS devices portions of the flow cycle may become turbulent, (Bluestein et al., 1994, 2000), with elevated stresses within MHV hinges (=-=Yoganathan et al., 1998-=-). VADs induce changes to coagulation through activation of platelets (Rothenburger et al., 2002; Wilhelm et al., 2001) despite aggressive anticoagulant therapy, with flow patterns implicated in the u...

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.... vs. monoleaflet) was also observed in patients (Laas et al., 2003). The AbioCor TAH study indicated that while no evidence of significant hemolysis was observed in animal or human patients studies (=-=Dowling et al., 2004-=-; Samuels et al., 2005), the majority of patients died of stroke related complications. Regretfully, very few data on flow-induced thrombogenic aspects are currently available (Charron et al., 1994). ...

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...in the underlying risk for their thromboembolism (Jin and Clark, 1993), especially cerebral embolism (e.g., rates ranging from 7.4% for the Heartmate I VAD to approx. 50% for the Novacor VAD system) (=-=El-Banayosy et al., 2001-=-). Platelet aggregates are the source of microembolic signals (MES) measured in patients with PHV (Grosset et al., 1996). A significant effect of valve hemodynamics on platelet activation for two diff...

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...AbioCor ar developed as a possible solution to the chro availability of human hearts for transplantation. of the AbioCor TAH (ABIOMED, Inc.), a high rate bolic complications made the clinical outcom (=-=Frazier et al., 2004-=-) stemming from design and mechanical heart valve (MHV) patients develop1. Introduction However, in the recent HeartMate II VAD Destination-Therapy Trial patients still suffered 11% disabling stroke r...

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...patients with PHV (Grosset et al., 1996). A significant effect of valve hemodynamics on platelet activation for two differing valve designs (bileaflet. vs. monoleaflet) was also observed in patients (=-=Laas et al., 2003-=-). The AbioCor TAH study indicated that while no evidence of significant hemolysis was observed in animal or human patients studies (Dowling et al., 2004; Samuels et al., 2005), the majority of patien...

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...ndence to: Department of Biomedical Engineering, Stony Brook University, HSC T15-090, Stony Brook, NY 11794-8151, USA. Tel.: þ1 631 444 2156; fax: þ1 631 444 6646.(Portner et al., 2001), and strokes (=-=Lazar et al., 2004-=-). Second and third generation continuous-flow VADs that have emerged complications at a rate of 0.7–6.4% per patient year (Butchart et al., 2001, 2003). In these patients, platelets are chronicallyTh...

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...ation in MHVs mounted in an LVAD (Yin et al., 2004), and in bioprosthetic and polymer valves (Yin et al., 2005), which are targeted for minimally invasive, percutaneous valve delivery (Feldman, 2006; =-=Mesana, 2006-=-)—the breakthrough technique with a huge promise for patients who cannot tolerate cardiothoracic surgery. The goal is for polymer valves, which are better suited for catheter-based stented delivery, t...

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...ully, very few data on flow-induced thrombogenic aspects are currently available (Charron et al., 1994). Several approaches for studying device-induced thrombogenicity were developed by a few groups (=-=Paul et al., 1998-=-; Travis et al., 2002; Jesty and Bluestein, 1999; Jesty et al., 2003). Jesty and Bluestein developed an innovative platelet activity state (PAS) assay, facilitating measurements of the thrombogenic po...

Citation Context

...MHV (Goubergrits and Affeld, 2004). Several models examined the interaction of activated platelets with the blood field (Kuharsky and Fogelson, 2001; Sorensen et al., 1999a), and platelet deposition (=-=Reininger et al., 1999-=-; Worth Longest and Kleinstreuer, 2003). Such modeling efforts provide insight into the areas where platelets have a high probability for activation, leading to thrombus formation and thromboembolism....

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...parable to the latter thereby obviating the need for mandatory anticoagulation therapy. Leakage gap width within bileaflet MHV pivots was demonstrated to have a significant effect on platelet damage (=-=Travis et al., 2001-=-).the wake dynamics and complex behavior of vortex shedding (Huang et al., 1994; Kelly et al., 1999; King et al., 1997; Krafczyk et al., 1998). First unsteady turbulent Reynolds Averaged (URANS) simul...

Citation Context

...ent, (Bluestein et al., 1994, 2000), with elevated stresses within MHV hinges (Yoganathan et al., 1998). VADs induce changes to coagulation through activation of platelets (Rothenburger et al., 2002; =-=Wilhelm et al., 2001-=-) despite aggressive anticoagulant therapy, with flow patterns implicated in the underlying risk for their thromboembolism (Jin and Clark, 1993), especially cerebral embolism (e.g., rates ranging from...

Citation Context

...ced by flow in devices. This technique was applied to in vitro measurements of flow-induced platelet activation in MHVs mounted in an LVAD (Yin et al., 2004), and in bioprosthetic and polymer valves (=-=Yin et al., 2005-=-), which are targeted for minimally invasive, percutaneous valve delivery (Feldman, 2006; Mesana, 2006)—the breakthrough technique with a huge promise for patients who cannot tolerate cardiothoracic s...