Aortic valve replacement (AVR) does not usually restore physiological flow profiles. Complex flow profiles are associated with aorta dilatation, ventricle remodeling, aneurysms, and development of atherosclerosis. All these affect long-term morbidity and often require reoperations. In this pilot study, we aim to investigate an ability to optimize the real surgical AVR procedure toward flow profile associated with healthy persons. Four cases of surgical AVR (two with biological and two with mechanical valve prosthesis) with available post-treatment cardiac magnetic resonance imaging (MRI), including four-dimensional flow MRI and showing abnormal complex post-treatment hemodynamics, were investigated. All cases feature complex hemodynamic outcomes associated with valve-jet eccentricity and strong secondary flow characterized by helical flow and recirculation regions. A commercial computational fluid dynamics solver was used to simulate peak systolic hemodynamics of the real post-treatment outcome using patient-specific MRI measured boundary conditions. Then, an attempt to optimize hemodynamic outcome by modifying valve size and orientation as well as ascending aorta size reduction was made. Pressure drop, wall shear stress, secondary flow degree, helicity, maximal velocity, and turbulent kinetic energy were evaluated to characterize the AVR hemodynamic outcome. The proposed optimization strategy was successful in three of four cases investigated. Although no single parameter was identified as the sole predictor for a successful flow optimization, downsizing of the ascending aorta in combination with the valve orientation was the most effective optimization approach. Simulations promise to become an effective tool to predict hemodynamic outcome. The translation of these tools requires, however, studies with a larger cohort of patients followed by a prospective clinical validation study.

As the first section of a multi-part review series, this section provides an overview of the ongoing research and development aimed at fabricating novel heart valve replacements beyond what is currently available for patients. Here we discuss heart valve replacement options that involve a biological component or process for creation, either in vitro or in vivo (tissue-engineered heart valves), and heart valves that are fabricated from polymeric material that are considered permanent inert materials that may suffice for adults where growth is not required. Polymeric materials provide opportunities for cost-effective heart valves that can be more easily manufactured and can be easily integrated with artificial heart and ventricular assist device technologies. Tissue engineered heart valves show promise as a regenerative patient specific model that could be the future of all valve replacement. Because tissue-engineered heart valves depend on cells for their creation, understanding how cells sense and respond to chemical and physical stimuli in their microenvironment is critical and therefore, is also reviewed.

OBJECTIVES: The aim of this study was to assess the influence of amount and distribution of calcifications of the aortic valve and the left ventricular outflow tract on the acute procedural outcome of patients undergoing transcatheter aortic valve implantation (TAVI). BACKGROUND: Transcatheter aortic valve implantation is a new percutaneous technique especially for elderly, high-risk patients with significant aortic valve stenosis (AS). After TAVI, post-interventional paravalvular aortic regurgitations (PAR) can occur, which is believed to be related partially to valve calcifications. METHODS: We prospectively analyzed 100 symptomatic patients with severe AS scheduled for TAVI with the CoreValve ReValving (Medtronic, Minneapolis, Minnesota) prosthesis. In all patients, a native and contrast-enhanced multislice cardiac computed tomography was performed pre-interventionally. Calcification load of the valve and the adjacent outflow tract was estimated by the Agatston Score (AgS), and the amount and distribution of calcification was semi-quantitatively assessed and graded on a 1 to 4 scale (device

Prosthesis positioning in transcatheter aortic valve implantation procedures represents a crucial aspect for procedure success as demonstrated by many recent studies on this topic. Possible complications, device performance, and, consequently, also long-term durability are highly affected by the adopted prosthesis placement strategy. In the present work, we develop a computational finite element model able to predict device-specific and patient-specific replacement procedure outcomes, which may help medical operators to plan and choose the optimal implantation strategy. We focus in particular on the effects of prosthesis implantation depth and release angle. We start from a real clinical case undergoing Corevalve self-expanding device implantation. Our study confirms the crucial role of positioning in determining valve anchoring, replacement failure due to intra or para-valvular regurgitation, and post-operative device deformation.

BACKGROUND AND AIM OF THE STUDY: Aortic hemodynamics influence the integrity of the vessel wall and cardiac afterload. The aim of this study was to compare hemodynamics distal to biological (BV) and mechanical aortic valve (MV) replacements by in vitro 4D Flow MRI excluding confounding factors of in-vivo testing potentially influencing hemodynamics. METHODS: Two BV (Perimount MagnaEase [Carpentier-Edwards], Trifecta [Abbott]) and two MV (On-X [CryoLife], prototype trileaflet valve) were scanned in a flexible aortic phantom at 3T using a recommended 4D Flow MR sequence. A triphasic aortic flow profile with blood-mimicking fluid was established. Using GTFlow (Gyrotools), area and velocity of the ejection jet were measured. Presence and extent of sinus vortices and secondary flow patterns were graded on a 0 to 3 scale. RESULTS: A narrow, accelerated central ejection jet (Area = 27 +/- 7% of vessel area, Velocity = 166 +/- 13 cm/s; measured at sinotubular junction) was observed in BV as compared to MV (Area = 53 +/- 13%, Velocity = 109 +/- 21 cm/s). As opposed to MV, the jet distal to BV impacted the outer curvature of the ascending aorta and resulted in large secondary flow patterns (BV: n = 4, grades 3, 3, 2, 1; MV: n = 1, grade 1). Sinus vortices only formed distal to MV. Although physiologically configured, they were larger than normal (grade 3). CONCLUSIONS: In contrast to mechanical valves, biological valve replacements induced accelerated and increased flow patterns deviating from physiological ones. While it remains speculative whether this increases the risk of aneurysm formation through wall shear stress changes, findings are contrasted by almost no secondary flow patterns and typical, near-physiological sinus vortex formation distal to mechanical valves.

Aortic stenosis caused by valve calcification is a major cause of death around the world. Hemodynamic factors have been suggested to be major players in the development of valve calcification, yet a detailed knowledge of the blood flow dynamics as experienced by endothelial cells on valve surfaces is still lacking. In this study we carry out high-resolution numerical simulations of the blood flow through a polymeric trileaflet valve in order to elucidate the differential flow dynamics on the aortic and ventricular sides of the valve leaflets. Limiting streamlines and surface shear stress contours are used to probe and quantify the blood flows on its side. Complicated flow patterns were only observed on the aortic side of the valve near the region where focalized distribution of valve calcification is typically observed.

Transcatheter aortic valve implantation is a novel treatment for severe aortic valve stenosis. Due to the recent use of this technology and the procedural variability, there is very little data that quantify the hemodynamic consequences of variations in valve placement. Changes in aortic wall stresses and fluid retention in the sinuses of Valsalva can have a significant effect on the clinical response a patient has to the procedure. By comprehensively characterizing complex flow in the sinuses of Valsalva using digital particle image velocimetry and an advanced heart-flow simulator, various positions of a deployed transcatheter valve with respect to a bioprosthetic aortic valve (valve-in-valve) were tested in vitro. Displacements of the transcatheter valve were axial and directed below the simulated native valve annulus. It was determined that for both blood residence time and aortic Reynolds stresses, it is optimal to have the annulus of the transcatheter valve deployed as close to the aortic valve annulus as possible.

PURPOSE: The physiological flow dynamics within the Valsalva sinuses, in terms of global and local parameters, are still not fully understood. This study attempts to identify the physiological conditions as closely as possible, and to give an explanation of the different and sometime contradictory results in literature. METHODS: An in vitro approach was implemented for testing porcine bio-prosthetic valves operating within different aortic root configurations. All tests were performed on a pulse duplicator, under physiological pressure and flow conditions. The fluid dynamics established in the various cases were analysed by means of 2D Particle Image Velocimetry, and related with the achieved hydrodynamic performance. RESULTS: Each configuration is associated with substantially different flow dynamics, which significantly affects the valve performance. The configuration most closely replicating healthy native anatomy was characterised by the best hemodynamic performance, and any mismatch in size and position between the valve and the root produced substantial modification of the fluid dynamics downstream of the valve, hindering the hydrodynamic performance of the system. The worst conditions were observed for a configuration characterised by the total absence of the Valsalva sinuses. CONCLUSION: This study provides an explanation for the different vortical structures described in the literature downstream of bioprosthetic valves, enlightening the experimental complications in valve testing. Most importantly, the results clearly identify the fluid mechanisms promoted by the Valsalva sinuses to enhance the ejection and closing phases, and this study exposes the importance of an optimal integration of the valve and root, to operate as a single system.

/= 50, the likelihood of occurrence of significant AR could be predicted with a sensitivity of 85% and a specificity of 87%. CONCLUSIONS: The occurrence of significant AR after TAVI can be predicted by anatomic and procedural variables. A model such as that presented can be used to select suitable patients for this procedure and guide operators during implantation of the device.]]>

Restenosis and thrombosis are potentially fatal complications of coronary stenting with a recognized multifactorial etiology. The effect of documented risk factors, however, cannot explain the preponderance of certain lesion types, stent designs, and implantation configurations for the development of these complications. Local hemodynamic factors, low endothelial shear stress (ESS) in particular, are long known to critically affect the natural history of atherosclerosis. Increasing evidence now suggests that ESS may also contribute to the development of restenosis and thrombosis upon stenting of atherosclerotic plaques, in conjunction with well-appreciated risk factors. In this review, we present in vivo and mechanistic evidence associating ESS with the localization and progression of neointimal hyperplasia and in-stent clotting. Clinical studies have associated stent design features with the risk of restenosis. Importantly, computational simulations extend these observations by directly linking specific stent geometry and positioning characteristics with the post-stenting hemodynamic milieu and with the stent's thrombogenicity and pro-restenotic potential, thereby indicating ways to clinical translation. An enhanced understanding of the pathophysiologic role of ESS in restenosis and thrombosis might dictate hemodynamically favorable stent designs and deployment configurations to reduce the potential for late lumen loss and thrombotic obstruction. Recent methodologies for in vivo ESS profiling at a clinical level might allow for early identification of patients at high risk for the development of restenosis or thrombosis and might thereby guide individualized, risk-tailored treatment strategies to prevent devastating complications of endovascular interventions.

6,000 s(-1) (P

Flow fields in the distal end-to-side anastomosis of coronary artery bypass graft are associated with intimal hyperplasia and bypass failure. This work aims to demonstrate the effect of anastomotic angle and diameter ratio on flow field of coronary artery bypass graft. The flow fields inside polydimethylsiloxane models of coronary artery bypass graft with various anastomotic angles (alpha = 30 degrees , 45 degrees , 60 degrees and 75 degrees ) and different diameter ratios (Phi = 0.78 and 1.11) are investigated using particle image velocimetry and computational fluid dynamics method under pulsatile flow condition. The results show that the anastomotic angle is positively correlated with the number and area of the recirculation zone, and the flow field disturbance at the anastomosis will develop in the same direction. Compared with that of Phi = 0.78, when Phi = 1.11, the flow fields at the anastomosis are relatively smoother with less turbulence.

INTRODUCTION: Blood flow induced shear stress plays an important role in platelet and endothelial cell functions. The goal of this study was to investigate the effect of physiologically relevant dynamic shear stress on platelet and endothelial cells. MATERIALS AND METHODS: Pulsatile shear stress waveforms mimicking the flow in a normal left coronary artery (0.1-1 Pa), at a 60% stenosis (0.2 - 6 Pa) and in the recirculation zone (0.01 - 0.5 Pa) behind a stenosis were used to stimulate platelets and endothelial cells in a cone and plate shearing device. Platelet activation was measured by CD62P expression and thrombogenicity. Meanwhile, endothelial cell activation and damage was measured by cell surface ICAM-1 and tissue factor expression using fluorescence microscopy. Endothelial tissue factor activity was measured using a commercial kit. RESULTS: Results showed that for platelets, a short exposure to elevated shear stress at the stenosis throat did not induce significant increase in platelet activation or thrombogenicity. While the low pulsatile shear stress had a potential for enhanced thrombosis. Both low and high pulsatile shear stress led to a significant increase in ICAM-1 expression on endothelial cell surface, but only low shear stress caused tissue factor over expression and enhanced tissue factor activity. CONCLUSION: These results suggest that low pulsatile shear stress may be more atherogenic, compared to elevated shear stress induced by stenosis.

Impairment of coronary artery flow, in either acute or chronic conditions, is a severe complication of transcatheter aortic valve (TAV) implantation, which can arise due to improper TAV positioning. However, little work has been done to quantify the effects of the TAV positioning on the coronary flow. In this study, a realistic in vitro model of coronary artery flow was developed and used to investigate the impact of TAV deployed orientations on coronary flow. The coronary hemodynamics was first replicated mathematically using a lumped parameter model with time-varying myocardial resistance. Based on the analytical model, two stepper motor controlled stopcock valves were integrated in a left heart simulator to represent the variable myocardial resistance in the experimental setup. The coronary flow and pressure waveforms obtained from the in vitro system were consistent with published data. With a TAV deployed in different orientations, the measured results demonstrated that TAV orientation does not have a significant impact on the coronary flow. The developed in vitro model can be further utilized to simulate coronary flow under various pathological conditions.

The regulation of valvular endothelial phenotypes by the hemodynamic environments of the human aortic valve is poorly understood. The nodular lesions of calcific aortic stenosis (CAS) develop predominantly beneath the aortic surface of the valve leaflets in the valvular fibrosa layer. However, the mechanisms of this regional localization remain poorly characterized. In this study, we combine numerical simulation with in vitro experimentation to investigate the hypothesis that the previously documented differences between valve endothelial phenotypes are linked to distinct hemodynamic environments characteristic of these individual anatomical locations. A finite-element model of the aortic valve was created, describing the dynamic motion of the valve cusps and blood in the valve throughout the cardiac cycle. A fluid mesh with high resolution on the fluid boundary was used to allow accurate computation of the wall shear stresses. This model was used to compute two distinct shear stress waveforms, one for the ventricular surface and one for the aortic surface. These waveforms were then applied experimentally to cultured human endothelial cells and the expression of several pathophysiological relevant genes was assessed. Compared to endothelial cells subjected to shear stress waveforms representative of the aortic face, the endothelial cells subjected to the ventricular waveform showed significantly increased expression of the

OBJECTIVE: Valve-in-valve procedures using transcatheter aortic valves are increasingly performed to treat degenerated bioprosthetic surgical aortic valves because they are less invasive than redo aortic valve replacement. The objective of this study is to quantify the changes in aortic sinus blood flow dynamics before and after a valve-in-valve procedure to gain insight into mechanisms for clinical and subclinical thrombosis of leaflets. METHODS: A detailed description of the sinus hemodynamics for valve-in-valve implantation was performed in vitro. A Medtronic Hancock II (Medtronic Inc, Minneapolis, Minn) porcine bioprosthesis was modeled as a surgical aortic valve, and Medtronic CoreValve and Edwards Sapien (Edwards Lifesciences, Irvine, Calif) valves were used as the transcatheter aortic valves. High-resolution particle image velocimetry was used to compare the flow patterns from these 2 valves within both the left coronary and noncoronary sinuses in vitro. RESULTS: Velocity and vorticity within the surgical valve sinuses reached peak values of 0.7 m/s and 1000 s(-1), with a 70% decrease in peak fluid shear stress near the aortic side of the leaflet in the noncoronary sinus. With the introduction of transcatheter aortic valves, peak velocity and vorticity were reduced to approximately 0.4 m/s and 550 s(-1) and 0.58 m/s and 653 s(-1) without coronary flow and 0.60 m/s and 631 s(-1) and 0.81 m/s and 669 s(-1) with coronary flow for the CoreValve and Sapien valve-in-valve implantations, respectively. Peak shear stress was approximately 38% higher along the aortic side of the coronary versus noncoronary transcatheter aortic valve leaflet. CONCLUSIONS: Decreased flow and shear stress in valve-in-valve procedures indicate a higher risk of leaflet thrombosis secondary to flow stasis, perhaps more so in the noncoronary sinus.

The bicuspid aortic valve (BAV) is a common congenital malformation of the aortic valve (AV) affecting 1% to 2% of the population. The BAV is predisposed to early degenerative calcification of valve leaflets, and BAV patients constitute 50% of AV stenosis patients. Although evidence shows that genetic defects can play a role in calcification of the BAV leaflets, we hypothesize that drastic changes in the mechanical environment of the BAV elicit pathological responses from the valve and might be concurrently responsible for early calcification. An in vitro model of the BAV was constructed by surgically manipulating a native trileaflet porcine AV. The BAV valve model and a trileaflet AV (TAV) model were tested in an in vitro pulsatile flow loop mimicking physiological hemodynamics. Laser Doppler velocimetry was used to make measurements of fluid shear stresses on the leaflet of the valve models using previously established methodologies. Furthermore, particle image velocimetry was used to visualize the flow fields downstream of the valves and in the sinuses. In the BAV model, flow near the leaflets and fluid shear stresses on the leaflets were much more unsteady than for the TAV model, most likely due to the moderate stenosis in the BAV and the skewed forward flow jet that collided with the aorta wall. This additional unsteadiness occurred during mid- to late-systole and was composed of cycle-to-cycle magnitude variability as well as high-frequency fluctuations about the mean shear stress. It has been demonstrated that the BAV geometry can lead to unsteady shear stresses under physiological flow and pressure conditions. Such altered shear stresses could play a role in accelerated calcification in BAVs.

Patients with aortic stenosis present with calcium deposits on the native aortic valve, which can result in non-concentric expansion of Transcatheter Aortic Valve Replacement (TAVR) stents. The objective of this study is to evaluate whether eccentric deployment of TAVRs lead to turbulent blood flow and blood cell damage. Particle Image Velocimetry was used to quantitatively characterize fluid velocity fields, shear stress and turbulent kinetic energy downstream of TAVRs deployed in circular and eccentric orifices representative of deployed TAVRs in vivo. Effective orifice area (EOA) and mean transvalvular pressure gradient (TVG) values did not differ substantially in circular and eccentric deployed valves, with only a minor decrease in EOA observed in the eccentric valve (2.0 cm(2) for circular, 1.9 cm(2) for eccentric). Eccentric deployed TAVR lead to asymmetric systolic jet formation, with increased shear stresses (circular = 97 N/m(2) vs. eccentric = 119 N/m(2)) and regions of turbulence intensity (circular = 180 N/m(2) vs. eccentric = 230 N/m(2)) downstream that was not present in the circular deployed TAVR. The results of this study indicate that eccentric deployment of TAVRs can lead to altered flow characteristics and may potentially increase the hemolytic potential of the valve, which were not captured through hemodynamic evaluation alone.