Circulatory efficiency in patients with severe aortic valve stenosis before and after aortic valve replacement.

BACKGROUND: Circulatory efficiency reflects the ratio between total left ventricular work and the work required for maintaining cardiovascular circulation. The effect of severe aortic valve stenosis (AS) and aortic valve replacement (AVR) on left ventricular/circulatory mechanical power and efficiency is not yet fully understood. We aimed to quantify left ventricular (LV) efficiency in patients with severe AS before and after surgical AVR. METHODS: Circulatory efficiency was computed from cardiovascular magnetic resonance (CMR) imaging derived volumetric data, echocardiographic and clinical data in patients with severe AS (n = 41) before and 4 months after AVR and in age and sex-matched healthy subjects (n = 10). RESULTS: In patients with AS circulatory efficiency was significantly decreased compared to healthy subjects (9 ± 3% vs 12 ± 2%; p = 0.004). There were significant negative correlations between circulatory efficiency and LV myocardial mass (r = - 0.591, p < 0.001), myocardial fibrosis volume (r = - 0.427, p = 0.015), end systolic volume (r = - 0.609, p < 0.001) and NT-proBNP (r = - 0.444, p = 0.009) and significant positive correlation between circulatory efficiency and LV ejection fraction (r = 0.704, p < 0.001). After AVR, circulatory efficiency increased significantly in the total cohort (9 ± 3 vs 13 ± 5%; p < 0.001). However, in 10/41 (24%) patients, circulatory efficiency remained below 10% after AVR and, thus, did not restore to normal values. These patients also showed less reduction in myocardial fibrosis volume compared to patients with restored circulatory efficiency after AVR. CONCLUSION: In our cohort, circulatory efficiency is reduced in patients with severe AS. In 76% of cases, AVR leads to normalization of circulatory efficiency. However, in 24% of patients, circulatory efficiency remained below normal values even after successful AVR. In these patients also less regression of myocardial fibrosis volume was seen. Trial Registration clinicaltrials.gov NCT03172338, June 1, 2017, retrospectively registered.

[Numerical flow simulation : A new method for assessing nasal breathing]. / Numerische Strömungssimulation : Eine neue Methode zur Beurteilung der Nasenatmung.

The current options for objective assessment of nasal breathing are limited. The maximum they can determine is the total nasal resistance. Possibilities to analyze the endonasal airstream are lacking. In contrast, numerical flow simulation is able to provide detailed information of the flow field within the nasal cavity. Thus, it has the potential to analyze the nasal airstream of an individual patient in a comprehensive manner and only a computed tomography (CT) scan of the paranasal sinuses is required. The clinical application is still limited due to the necessary technical and personnel resources. In particular, a statistically based referential characterization of normal nasal breathing does not yet exist in order to be able to compare and classify the simulation results.

Verification Study of In Silico Computed Intracardiac Blood Flow With 4D Flow MRI.

OBJECTIVE: Major challenges for clinical applications of in silico medicine are limitations in time and computational resources. Computational approaches should therefore be tailored to specific applications with relatively low complexity and must be verified and validated against clinical gold standards. METHODS: This study performed computational fluid dynamics simulations of left ventricular hemodynamics of different complexity based on shape reconstruction from steady state gradient echo magnetic resonance imaging (MRI) data. Computed flow results of a rigid wall model (RWM) and a prescribed motion fluid-structure interaction (PM-FSI) model were compared against phase-contrast MRI measurements for three healthy subjects. RESULTS: Extracted boundary conditions from the steady state MRI sequences as well as computed metrics, such as flow rate, valve velocities, and kinetic energy show good agreement with in vivo flow measurements. Regional flow analysis reveals larger differences. CONCLUSION: Basic flow structures are well captured with RWM and PM-FSI. For the computation of further biomarkers like washout or flow efficiency, usage of PM-FSI is required. Regarding boundary-near flow, more accurate anatomical models are inevitable. SIGNIFICANCE: These results delineate areas of application of both methods and lay a foundation for larger validation studies and sensitivity analysis for healthy and diseased cases, being an essential step upon clinical translations.

Synthetic Database of Aortic Morphometry and Hemodynamics: Overcoming Medical Imaging Data Availability.

Modeling of hemodynamics and artificial intelligence have great potential to support clinical diagnosis and decision making. While hemodynamics modeling is extremely time- and resource-consuming, machine learning (ML) typically requires large training data that are often unavailable. The aim of this study was to develop and evaluate a novel methodology generating a large database of synthetic cases with characteristics similar to clinical cohorts of patients with coarctation of the aorta (CoA), a congenital heart disease associated with abnormal hemodynamics. Synthetic data allows use of ML approaches to investigate aortic morphometric pathology and its influence on hemodynamics. Magnetic resonance imaging data (154 patients as well as of healthy subjects) of aortic shape and flow were used to statistically characterize the clinical cohort. The methodology generating the synthetic cohort combined statistical shape modeling of aortic morphometry and aorta inlet flow fields and numerical flow simulations. Hierarchical clustering and non-linear regression analysis were successfully used to investigate the relationship between morphometry and hemodynamics and to demonstrate credibility of the synthetic cohort by comparison with a clinical cohort. A database of 2652 synthetic cases with realistic shape and hemodynamic properties was generated. Three shape clusters and respective differences in hemodynamics were identified. The novel model predicts the CoA pressure gradient with a root mean square error of 4.6 mmHg. In conclusion, synthetic data for anatomy and hemodynamics is a suitable means to address the lack of large datasets and provide a powerful basis for ML to gain new insights into cardiovascular diseases.

Towards improving the accuracy of aortic transvalvular pressure gradients: rethinking Bernoulli.

The transvalvular pressure gradient (TPG) is commonly estimated using the Bernoulli equation. However, the method is known to be inaccurate. Therefore, an adjusted Bernoulli model for accurate TPG assessment was developed and evaluated. Numerical simulations were used to calculate TPGCFD in patient-specific geometries of aortic stenosis as ground truth. Geometries, aortic valve areas (AVA), and flow rates were derived from computed tomography scans. Simulations were divided in a training data set (135 cases) and a test data set (36 cases). The training data was used to fit an adjusted Bernoulli model as a function of AVA and flow rate. The model-predicted TPGModel was evaluated using the test data set and also compared against the common Bernoulli equation (TPGB). TPGB and TPGModel both correlated well with TPGCFD (r > 0.94), but significantly overestimated it. The average difference between TPGModel and TPGCFD was much lower: 3.3 mmHg vs. 17.3 mmHg between TPGB and TPGCFD. Also, the standard error of estimate was lower for the adjusted model: SEEModel = 5.3 mmHg vs. SEEB = 22.3 mmHg. The adjusted model's performance was more accurate than that of the conventional Bernoulli equation. The model might help to improve non-invasive assessment of TPG. Graphical abstract Processing pipeline for the definition of an adjusted Bernoulli model for the assessment of transvalvular pressure gradient. Using CT image data, the patient specific geometry of the stenosed AVs were reconstructed. Using this segmentation, the AVA as well as the volume flow rate was calculated and used for model definition. This novel model was compared against classical approaches on a test data set, which was not used for the model definition.

Publisher Correction: Model-Based Therapy Planning Allows Prediction of Haemodynamic Outcome after Aortic Valve Replacement.

A correction to this article has been published and is linked from the HTML and PDF versions of this paper. The error has been fixed in the paper.

Effect of daptomycin and vancomycin on Staphylococcus epidermidis biofilms: An in vitro assessment using fluorescence in situ hybridization.

Colonization of in-dwelling catheters by microbial biofilms is a major concern in patient health eventually leading to catheter-related blood stream infections. Biofilms are less susceptible to standard antibiotic therapies that are effective against planktonic bacteria. Standard procedure for the detection of microorganisms on the catheter tip is culture. However, viable but non-culturable cells (VBNCs) may be missed. The aim of this study was to evaluate the use of fluorescence in situ hybridization (FISH) as an indicator to visualize and quantify the effect of the antibiotics daptomycin and vancomycin on biofilms in situ. We established an in vitro catheter biofilm model of Staphylococcus epidermidis biofilms on polyurethane catheters. Biofilm activity was measured by FISH and correlated to colony forming units (CFU) data. Digital image analysis was used for quantification of total biofilm mass and the area of the FISH positive biofilm cells. FISH showed a pronounced effect of both antibiotics on the biofilms, with daptomycin having a significantly stronger effect in terms of both reduction of biofilm mass and number of FISH-positive cells. This supports the anti-biofilm capacity of daptomycin. Interestingly, neither antibiotic was able to eradicate all of the FISH-positive cells. In summary, FISH succeeded in visualization, quantification, and localization of antibiotic activity on biofilms. This technique adds a new tool to the arsenal of test systems for anti-biofilm compounds. FISH is a valuable complementary technique to CFU since it can be highly standardized and provides information on biofilm architecture and quantity and localization of survivor cells.

Particle image velocimetry of a flow at a vaulted wall.

The assessment of flow along a vaulted wall (with two main finite radii of curvature) is of general interest; in biofluid mechanics, it is of special interest. Unlike the geometry of flows in engineering, flow geometry in nature is often determined by vaulted walls. Specifically the flow adjacent to the wall of blood vessels is particularly interesting since this is where either thrombi are formed or atherosclerosis develops. Current measurement methods have problems assessing the flow along vaulted walls. In contrast with conventional particle image velocimetry (PIV), this new method, called wall PIV, allows the investigation of a flow adjacent to transparent flexible surfaces with two finite radii of curvature. Using an optical method which allows the observation of particles up to a predefined depth enables the visualization solely of the boundary layer flow. This is accomplished by adding a specific dye to the fluid which absorbs the monochromatic light used to illuminate the region of observation. The obtained images can be analysed with the methods of conventional PIV and result in a vector field of the velocities along the wall. With wall PIV, the steady flow adjacent to the vaulted wall of a blood pump was investigated and the resulting velocity field as well as the velocity fluctuations were assessed.

Model-Based Therapy Planning Allows Prediction of Haemodynamic Outcome after Aortic Valve Replacement.

Optimizing treatment planning is essential for advances in patient care and outcomes. Precisely tailored therapy for each patient remains a yearned-for goal. Cardiovascular modelling has the potential to simulate and predict the functional response before the actual intervention is performed. The objective of this study was to proof the validity of model-based prediction of haemodynamic outcome after aortic valve replacement. In a prospective study design virtual (model-based) treatment of the valve and the surrounding vasculature were performed alongside the actual surgical procedure (control group). The resulting predictions of anatomic and haemodynamic outcome based on information from magnetic resonance imaging before the procedure were compared to post-operative imaging assessment of the surgical control group in ten patients. Predicted vs. post-operative peak velocities across the valve were comparable (2.97 ± 1.12 vs. 2.68 ± 0.67 m/s; p = 0.362). In wall shear stress (17.3 ± 12.3 Pa vs. 16.7 ± 16.84 Pa; p = 0.803) and secondary flow degree (0.44 ± 0.32 vs. 0.49 ± 0.23; p = 0.277) significant linear correlations (p < 0.001) were found between predicted and post-operative outcomes. Between groups blood flow patterns showed good agreement (helicity p = 0.852, vorticity p = 0.185, eccentricity p = 0.333). Model-based therapy planning is able to accurately predict post-operative haemodynamics after aortic valve replacement. These validated virtual treatment procedures open up promising opportunities for individually targeted interventions.

Is MRI-based CFD able to improve clinical treatment of coarctations of aorta?

Pressure drop associated with coarctation of the aorta (CoA) can be successfully treated surgically or by stent placement. However, a decreased life expectancy associated with altered aortic hemodynamics was found in long-term studies. Image-based computational fluid dynamics (CFD) is intended to support particular diagnoses, to help in choosing between treatment options, and to improve performance of treatment procedures. This study aimed to prove the ability of CFD to improve aortic hemodynamics in CoA patients. In 13 patients (6 males, 7 females; mean age 25 ± 14 years), we compared pre- and post-treatment peak systole hemodynamics [pressure drops and wall shear stress (WSS)] vs. virtual treatment as proposed by biomedical engineers. Anatomy and flow data for CFD were based on MRI and angiography. Segmentation, geometry reconstruction and virtual treatment geometry were performed using the software ZIBAmira, whereas peak systole flow conditions were simulated with the software ANSYS(®) Fluent(®). Virtual treatment significantly reduced pressure drop compared to post-treatment values by a mean of 2.8 ± 3.15 mmHg, which significantly reduced mean WSS by 3.8 Pa. Thus, CFD has the potential to improve post-treatment hemodynamics associated with poor long-term prognosis of patients with coarctation of the aorta. MRI-based CFD has a huge potential to allow the slight reduction of post-treatment pressure drop, which causes significant improvement (reduction) of the WSS at the stenosis segment.

Geometry of the human common carotid artery. A vessel cast study of 86 specimens.

The carotid artery is of special interest for the pathologist because of its frequent depositions, and for the fluidmechanician because of its complex flow properties. However, there is a distinct lack in current knowledge of its geometry. Therefore, a vessel cast study was undertaken. At post mortem, the arteries are excised and filled with a special resin at the proper transmural pressure. Eighty-six vessel casts of the carotid artery were performed, and some etiological factors of atherosclerosis, such as age, sex and disease, were collected. The following selected geometric parameters of these vessel casts were measured in this study: the diameters of the main branches of carotid bifurcation (common, internal and external arteries), and the angles between internal, external and common carotid arteries. The averaged geometric parameters and their variability over 86 vessel casts of the carotid artery were investigated. Furthermore, the relationship between these measured parameters and the etiological factors age, sex and disease was analyzed. The geometric parameters varied considerably, presumably contributing to a corresponding variability in the local hemodynamic and distribution of the atherosclerotic lesions.

Atherosclerosis in the human common carotid artery. A morphometric study of 31 specimens.

The carotid artery bifurcation is of special interest to both the pathologist because of its frequent atherosclerotic depositions, and to the fluidmechanicist because of its complex flow properties. However, current knowledge is incomplete regarding the level and position of atherosclerotic plaques in the carotid bifurcation and their quantitative correlation with its geometry. The study presented here is intended to fill that knowledge gap and try to quantify the geometrical risk factors. During the post-mortem the arteries were excised and filled with a resin at the proper transmural pressure of 80 mm Hg. Thirty-one vessel casts of the carotid artery from twenty-three autopsied individuals were made. The vessel casts were used to measure several geometrical parameters. After fabrication of the vessel casts each artery was investigated according to pathomorphological procedure. An atherometric system (AS) indicating the level of atherosclerotic lesions was applied. The specimens were divided into three groups according to the level of atherosclerosis. The comparison was made between the level of wall alteration of the main branches of the carotid bifurcation (common, internal and external carotid branch), and between these three groups themselves. Further, we conducted a comparison of the averaged geometric parameters in different groups to define the correlations between atherosclerotic lesions and geometric parameters. The results show that the most advanced lesions (fibrous and severe plaques) with about 70% of all lesions were mainly found in the internal and the external carotid branches, compared with only 25% for the common carotid branch. The comparative analysis showed that a relatively high carotid sinus enlargement of > 1.2 of the common carotid branch diameter is a most significant geometric risk factor among those investigated, whereas there was no correlation between branch angles and atherosclerosis. In conclusion, the quantification of atherosclerotic risk factors is very important in the investigation of atherosclerotic disease development.

Variability of the geometry of the human common carotid artery. A vessel cast study of 31 specimens.

The carotid artery is of special interest both for the pathologist because of its frequent depositions and for the fluid mechanic because of its complex flow properties. However, current knowledge of its geometry is insufficient. Therefore, a vessel cast study was undertaken and a method to fabricate vessel casts was developed. At post mortem the arteries are excised and filled with a resin at the proper transmural pressure. Thirty-one vessel casts of the carotid artery were performed and the following selected geometric parameters of these vessel casts were measured: the diameters of the main branches of carotid bifurcation (common, internal and external arteries) and the angles between internal, external and common carotid arteries. The geometric parameters vary considerably and may contribute to a corresponding variability in local hemodynamics.

Novel cardiac assist valve with a purge flow in the valve sinus.

Clinical applications of cardiac assist systems continue to have a severe problem, that of thromboembolic complications. The problem originates mainly at the valves, which are usually made of a antithrombogenic material, such as bovine pericardium. However, the valve housing is made of a less suitable material, and wherever the blood flow is stagnant, a thrombus is likely to form. Such stagnant blood flow is found in the space between the housing of the valve and the leaflets, in the sinuses. Consequently, thrombi often are generated in the sinuses. The novel valve design presented in this article avoids the formation of the stagnation zone in the sinuses by a purge flow. This flow is taken from the main flow through the valve and is directed into each sinus of the res purges the sinuses. The purge flow effect is investigated with an experimental method in which the sinus is filled with dye, and washout during the valve action is observed and recorded on videotape, which is compared with washout in a valve without a purge flow. In addition, the purge flow effect is investigated by computational fluid dynamics. Both methods show that the purge flow effectively increases fluid exchange in the sinuses.

Experimental assessment of wall shear flow in models.

The blood flow immediately adjacent to the wall of a blood vessel or an artificial surface is of great interest. This flow defines the shear stress at the wall and is known to have a great physiological importance. The use of models is a viable method to investigate this flow. However, even in models the shear stress at the wall is difficult to assess. A new optical method is based on transparent models and uses particles in the model fluid, which are only visible near the wall. This is achieved with a model fluid having a defined opacity. This fluid obscures particles in the center of the models, but permits the observation and recording of particles close to the wall. The method has been applied for Hagen-Poiseuille flow and for the likewise well researched flow in a tube with a sudden expansion.

Atherosclerosis and flow in carotid arteries with authentic geometries.

The influence of blood flow on the depositions and development of atherosclerotic lesions have been observed and described since the 19th century. Observations have shown that depositions correlate with regions of low wall shear stress. However, the exact correlations between depositions, vessel geometry and flow parameters are not yet known. The purpose of this study was the quantification of atherosclerosis risk factors in carotid bifurcation. This artery has attracted particular interest because lesions are often found in this bifurcation. Post mortem, the arteries are excised and vessel casts are produced. Afterwards, the arteries are analyzed morphometrically. The vessel casts are used for the assessment of some geometrical parameters. 31 carotid bifurcations were analyzed in this study. Eight vessel casts were digitized and rendered three-dimensional mathematical models of the arteries. These data were imported by the computational fluid dynamics program FLUENT. Further, the blood flow was reconstructed in a computer model based on the individual vessel geometry. The flow parameters, such as velocity, pressure and wall shear stress were computed. At the same time the geometrical parameters and wall alterations are known. This permits the comparison of the anatomical shape and its flow with the distribution and level of the wall alterations.

Optimization and investigation of a novel cardiac assist valve with a purge flow.

Clinical applications of cardiac assist systems still suffer from thromboembolic complications due to thrombus formation behind the valve's leaflets. Wherever the flow is stagnant such as in the sinus, a thrombus is likely to form. The valve design in this study avoids stagnation zones behind the leaflets by a purge flow during systole. This purge flow is separated from the valve's main flow by a flow divider directing a part of the main flow into the sinus behind the leaflet. The optimization was performed on a monoleaflet valve because of its simple geometry. Relevant geometric parameters were systematically varied. Thirty-two models were designed and numerically investigated. The models with the best results were preselected and investigated in a computer-controlled valve tester. The washout of a dye filled in the sinus was digitally recorded and quantified. The results show that a sinus purge flow minimizes stagnation areas in the sinus and thus may avoid thrombus formation.

Estimation of wall shear stress in bypass grafts with computational fluid dynamics method.

Coronary artery bypass graft (CABG) operation for coronary artery disease with different types of grafts has a large clinical application world wide. Immediately after this operation patients are usually relieved of their chest pain and have improved cardiac function. However, after a while, these bypass grafts may fail due to for example, neointimal hyperplasia or thrombosis. One of the causes for this bypass graft failure is assumed to be the blood flow with low wall shear stress. The aim of this research is to estimate the wall shear stress in a graft and thus to locate areas were wall shear stress is low. This was done with the help of a blood flow computer model. Post-operative biplane angiograms of the graft were recorded, and from these the three-dimensional geometry of the graft was reconstructed and imported into the computational fluid dynamics (CFD) program FLUENT. The stationary diastolic flow through the grafts was calculated, and the wall shear stress distribution was estimated. This procedure was carried out for one native vessel and two different types of bypass grafts. One bypass graft was a saphenous vein and the other one was a varicose saphenous vein encased in a fine, flexible metal mesh. The mesh was attached to give the graft a defined diameter. The computational results show that each graft has distinct areas of low wall shear stress. The graft with the metal mesh has an area of low wall shear stress (< 1 Pa, stationary flow), which is four times smaller than the respective areas in the other graft and in the native vessel. This is thought to be caused by the smaller and more uniform diameter of the metal mesh-reinforced graft.

Mathematical model of platelet deposition under flow conditions.

Platelet deposition in resting blood is well researched and understood. However, the influence of hemodynamic parameters such as wall shear rate is less clear. Clinical experience and experiments show an interaction between flow and platelet deposition. But a complete understanding of the flow influence and hence a quantification has not yet been achieved. A well defined experiment of flow dependant platelet depositions is the stagnation point flow. This kind of flow is ubiquitous in the circulatory system, to be found in every bifurcation and recirculation region. These are the areas where thrombus formations are likely to occur if other conditions are also met. First, experiments were performed in a stagnation point flow chamber. A simplified blood model, platelet rich plasma, was used as a test fluid. With a microscope the platelet deposition was observed and recorded. Platelets deposit in a characteristic pattern showing the influence of the flow. An analysis of this pattern is the objective of this study and is achieved with the help of a numerical model, which is based on a convective diffusive transport. The model results in a platelet deposition pattern, which in its shape and temporal development is very similar to experimental results. Hence it is concluded that the assumed transport processes are causal for platelet depositions and thrombus formation.

[Flow through an improved ball valve for the heart assist device]. / Strömung durch eine neu entwickelte Kugelklappe für ein Herzunterstützungssystem.

Objective of the present study is the hemodynamic investigation of the fluidmechanics a ball valve developed for ventricular assist devices with improved parameters. The flow was investigated using Digital Particle Image Velocimetry with an enlarged model of the valve (2.8:1). The flow was recorded using a high speed video camera with 250 fps and analyzed by a cross-correlation method implemented in the software DaVis by LaVision. The results confirmed the improvement of the ball valve performed by a numerical study. The flow separations on the ball valve housing observed in the first design version was eliminated in the final design of the novel valve. Hence a valve of this design applied in ventricular assist devices can be expected to have a lower rate of thromboembolic complications.