Validation of a Suprasystolic Cuff System for Static and Dynamic Representation of the Central Pressure Waveform.

BACKGROUND: Noninvasive pulse waveform analysis is valuable for central cardiovascular assessment, yet controversies persist over its validity in peripheral measurements. Our objective was to compare waveform features from a cuff system with suprasystolic blood pressure hold with an invasive aortic measurement. METHODS AND RESULTS: This study analyzed data from 88 subjects undergoing concurrent aortic catheterization and brachial pulse waveform acquisition using a suprasystolic blood pressure cuff system. Oscillometric blood pressure (BP) was compared with invasive aortic systolic BP and diastolic BP. Association between cuff and catheter waveform features was performed on a set of 15 parameters inclusive of magnitudes, time intervals, pressure-time integrals, and slopes of the pulsations. The evaluation covered both static (subject-averaged values) and dynamic (breathing-induced fluctuations) behaviors. Peripheral BP values from the cuff device were higher than catheter values (systolic BP-residual, 6.5 mm Hg; diastolic BP-residual, 12.4 mm Hg). Physiological correction for pressure amplification in the arterial system improved systolic BP prediction (r2=0.83). Dynamic calibration generated noninvasive BP fluctuations that reflect those invasively measured (systolic BP Pearson R=0.73, P<0.001; diastolic BP Pearson R=0.53, P<0.001). Static and dynamic analyses revealed a set of parameters with strong associations between catheter and cuff (Pearson R>0.5, P<0.001), encompassing magnitudes, timings, and pressure-time integrals but not slope-based parameters. CONCLUSIONS: This study demonstrated that the device and methods for peripheral waveform measurements presented here can be used for noninvasive estimation of central BP and a subset of aortic waveform features. These results serve as a benchmark for central cardiovascular assessment using suprasystolic BP cuff-based devices and contribute to preserving system dynamics in noninvasive measurements.

Smoothed particle hydrodynamics based FSI simulation of the native and mechanical heart valves in a patient-specific aortic model.

The failure of the aortic heart valve is common, resulting in deterioration of the pumping function of the heart. For the end stage valve failure, bi-leaflet mechanical valve (most popular artificial valve) is implanted. However, due to its non-physiological behaviour, a significant alteration is observed in the normal haemodynamics of the aorta. While in-vivo experimentation of a human heart valve (native and artificial) is a formidable task, in-silico study using computational fluid dynamics (CFD) with fluid structure interaction (FSI) is an effective and economic tool for investigating the haemodynamics of natural and artificial heart valves. In the present work, a haemodynamic model of a natural and mechanical heart valve has been developed using meshless particle-based smoothed particle hydrodynamics (SPH). In order to further enhance its clinical relevance, this study employs a patient-specific vascular geometry and presents a successful validation against traditional finite volume method and 4D magnetic resonance imaging (MRI) data. The results have demonstrated that SPH is ideally suited to simulate the heart valve function due to its Lagrangian description of motion, which is a favourable feature for FSI. In addition, a novel methodology for the estimation of the wall shear stress (WSS) and other related haemodynamic parameters have been proposed from the SPH perspective. Finally, a detailed comparison of the haemodynamic parameters has been carried out for both native and mechanical aortic valve, with a particular emphasis on the clinical risks associated with the mechanical valve.

Novel theory and potential applications of central diastolic pressure decay time constant.

Central aortic diastolic pressure decay time constant ( τ ) is according to the two-element Windkessel model equal to the product of total peripheral resistance ( R ) times total arterial compliance ( C ). As such, it is related to arterial stiffness, which has considerable pathophysiological relevance in the assessment of vascular health. This study aimed to investigate the relationship of the constant τ with the product T MBP cPP , given by heart period ( T ) times the ratio of mean blood pressure (MBP) to central pulse pressure ( cPP ). The relationship was derived by performing linear fitting on an in silico population of n1 = 3818 virtual subjects, and was subsequently evaluated on in vivo data (n2 = 2263) from the large Asklepios study. The resulted expression was found to be τ = k ' T MBP cPP , with k ' = 0.7 (R2 = 0.9). The evaluation of the equation on the in vivo human data reported high agreement between the estimated and reference τ values, with a correlation coefficient equal to 0.94 and a normalized RMSE equal to 5.5%. Moreover, the analysis provided evidence that the coefficient k ' is age- and gender-independent. The proposed formula provides novel theoretical insights in the relationship between τ and central blood pressure features. In addition, it may allow for the evaluation of τ without the need for acquiring the entire central blood pressure wave, especially when an approximation of the cPP is feasible. This study adds to the current literature by contributing to the accessibility of an additional biomarker, such as the central diastolic pressure decay time constant, for the improved assessment of vascular ageing.

Optimization and validation of a suprasystolic brachial cuff-based method for noninvasively estimating central aortic blood pressure.

Clinical studies have extensively demonstrated that central aortic blood pressure (CABP) has greater clinical significance in comparison with peripheral blood pressure. Despite the existence of various techniques for noninvasively measuring CABP, the clinical applications of most techniques are hampered by the unsatisfactory accuracy or large variability in measurement errors. In this study, we proposed a new method for noninvasively estimating CABP with improved accuracy and reduced uncertain errors. The main idea was to optimize the estimation of the pulse wave transit time from the aorta to the occluded lumen of the brachial artery under a suprasystolic cuff by identifying and utilizing the characteristic information of the cuff oscillation wave, thereby improving the accuracy and stability of the CABP estimation algorithms under various physiological conditions. The method was firstly developed and verified based on large-scale virtual subject data (n = 800) generated by a computational model of the cardiovascular system coupled to a brachial cuff, and then validated with small-scale in vivo data (n = 34). The estimation errors for the aortic systolic pressure were -0.05 ± 0.63 mmHg in the test group of the virtual subjects and -1.09 ± 3.70 mmHg in the test group of the patients, both demonstrating a good performance. In particular, the estimation errors were found to be insensitive to variations in hemodynamic conditions and cardiovascular properties, manifesting the high robustness of the method. The method may have promising clinical applicability, although further validation studies with larger-scale clinical data remain necessary.

Hemodynamic effects of a dielectric elastomer augmented aorta on aortic wave intensity: An in-vivo study.

Dielectric elastomer actuator augmented aorta (DEA) represents a novel approach with high potential for assisting a failing heart. The soft tubular device replaces a section of the aorta and increases its diameter when activated. The hemodynamic interaction between the DEA and the left ventricle (LV) has not been investigated with wave intensity (WI) analysis before. The objective of this study is to investigate the hemodynamic effects of the DEA on the aortic WI pattern. WI was calculated from aortic pressure and flow measured in-vivo in the descending aorta of two pigs implanted with DEAs. The DEAs were tested for different actuation phase shifts (PS). The DEA generated two decompression waves (traveling upstream and downstream of the device) at activation followed by two compression waves at deactivation. Depending on the PS, the end-diastolic pressure (EDP) decreased by 7% (or increased by 5-6%). The average early diastolic pressure augmentation (Pdia¯) increased by 2% (or decreased by 2-3%). The hydraulic work (WH) measured in the aorta decreased by 2% (or increased by 5%). The DEA-generated waves interfered with the LV-generated waves, and the timing of the waves affected the hemodynamic effect of the device. For the best actuation timing the upstream decompression wave arrived just before aortic valve opening and the upstream compression wave arrived just before aortic valve closure leading to a decreased EDP, an increased Pdia¯ and a reduced.WH.

Evaluation of Aortic Elasticity Parameters Measured by Transthoracic Echocardiography in a Normotensive Population: A Single-Center Study.

OBJECTIVE: Impaired arterial elastic features is one of the earliest manifestations of atherosclerosis in the vessel wall and is associated with the development of cardiovascular disease and increased mortality and morbidity. In this study, we aimed to investigate the mean values of aortic elasticity parameters in a normotensive population with transthoracic echocardiography and to evaluate these values in different age groups and their relationship with other risk factors. METHODS: This retrospective study included 405 subjects who met the inclusion criteria among 2880 individuals screened between 2020 and 2022. The study population was divided into 5 groups according to their age. Aortic elasticity parameters (aortic strain, aortic stiffness index, and aortic distensibility) were calculated from the associated formulas by measurements made from the ascending aorta in the parasternal long axis. RESULTS: In 405 subjects (mean age 42.18 ± 10.39, 54.3% female), the mean aortic strain value was 15.14 ± 3.56%, the mean aortic stiffness index was 3.24 ± 1.05, and the mean aortic distensibility was 7.48 ± 2.36 cm2/dyn1/103. It was observed that aortic strain and distensibility values significantly decreased with increasing age groups, while aortic stiffness significantly increased. All 3 aortic elasticity parameters were strongly correlated to age. In the multivariate linear regression analysis, age was found to be an independent factor for all aortic elasticity parameters. CONCLUSION: Aortic elasticity parameters can be evaluated with transthoracic echocardiography in daily practice. Comparing these measurements with normal values in similar age groups may help to detect patients with increased cardiovascular risk in the early period, regardless of the other risk factors.

Simulating Subject-Specific Aortic Hemodynamic Effects of Valvular Lesions in Rheumatic Heart Disease.

Rheumatic heart disease (RHD) is a neglected tropical disease despite the substantial global health burden. In this study, we aimed to develop a lower cost method of modeling aortic blood flow using subject-specific velocity profiles, aiding our understanding of RHD's consequences on the structure and function of the ascending aorta. Echocardiography and cardiovascular magnetic resonance (CMR) are often used for diagnosis, including valve dysfunction assessments. However, there is a need to further characterize aortic valve lesions to improve treatment options and timing for patients, while using accessible and affordable imaging strategies. Here, we simulated effects of RHD aortic valve lesions on the aorta using computational fluid dynamics (CFD). We hypothesized that inlet velocity distribution and wall shear stress (WSS) will differ between RHD and non-RHD individuals, as well as between subject-specific and standard Womersley velocity profiles. Phase-contrast CMR data from South Africa of six RHD subjects with aortic stenosis and/or regurgitation and six matched controls were used to estimate subject-specific velocity inlet profiles and the mean velocity for Womersley profiles. Our findings were twofold. First, we found WSS in subject-specific RHD was significantly higher (p < 0.05) than control subject simulations, while Womersley simulation groups did not differ. Second, evaluating spatial velocity differences (ΔSV) between simulation types revealed that simulations of RHD had significantly higher ΔSV than non-RHD (p < 0.05), these results highlight the need for implementing subject-specific input into RHD CFD, which we demonstrate how to accomplish through accessible methods.

Jacketed elastomeric tubes for passive self-regulation of pulsatile flow.

Regulating pulsatile flow is important to achieve optimal separation and mixing and enhanced heat transfer in microfluidic devices, as well as maintaining homeostasis in biological systems. The human aorta, a composite and layered tube made (among others) of elastin and collagen, is an inspiration for researchers who seek an engineering solution for a self-regulation of pulsatile flow. Here, we present a bio-inspired approach showing that fabric-jacketed elastomeric tubes, manufactured using commercially available silicone rubber and knitted textiles, can be used to regulate pulsatile flow. Our tubes are evaluated via incorporation into a mock-circulatory 'flow loop' that replicates the pulsatile fluid flow conditions of an ex-vivo heart perfusion (EVHP) device, a machine used in heart transplants. Pressure waveforms measured near the elastomeric tubing clearly indicated an effective flow regulation. The 'dynamic stiffening' behavior of the tubes during deformation is analyzed quantitatively. Broadly, the fabric jackets allow for the tubes to experience greater magnitudes of pressure and distension without risk of asymmetric aneurysm within the expected operating time of an EVHP. Owing to its highly tunable nature, our design may serve as a basis for tubing systems that require passive self-regulation of pulsatile flow.

A Vector Fitting Approach for the Automated Estimation of Lumped Boundary Conditions of 1D Circulation Models.

PURPOSE: The choice of appropriate boundary conditions is a crucial step in the development of cardiovascular models for blood flow simulations. The three-element Windkessel model is usually employed as a lumped boundary condition, providing a reduced order representation of the peripheral circulation. However, the systematic estimation of the Windkessel parameters remains an open problem. Moreover, the Windkessel model is not always adequate to model blood flow dynamics, which often require more elaborate boundary conditions. In this study, we propose a method for the estimation of the parameters of high order boundary conditions, including the Windkessel model, from pressure and flow rate waveforms at the truncation point. Moreover, we investigate the effect of adopting higher order boundary conditions, corresponding to equivalent circuits with more than one storage element, on the accuracy of the model. METHOD: The proposed technique is based on Time-Domain Vector Fitting, a modeling algorithm that, given samples of the input and output of a system, such as pressure and flow waveforms, can derive a differential equation approximating their relation. RESULTS: The capabilities of the proposed method are tested on a 1D circulation model consisting of the 55 largest human systemic arteries, to demonstrate its accuracy and its usefulness to estimate boundary conditions with order higher than the traditional Windkessel models. The proposed method is compared to other common estimation techniques, and its robustness in parameter estimation is verified in presence of noisy data and of physiological changes of aortic flow rate induced by mental stress. CONCLUSION: Results suggest that the proposed method is able to accurately estimate boundary conditions of arbitrary order. Higher order boundary conditions can improve the accuracy of cardiovascular simulations, and Time-Domain Vector Fitting can automatically estimate them.

The contribution of upper and lower body arterial vessels to the aortic root reflections: A one-dimensional computational study.

BACKGROUND AND OBJECTIVES: Reflections measured at the aortic root are of physiological and clinical interest and thought to be composed of the superimposed reflections arriving from the upper and lower parts of the circulatory system. However, the specific contribution of each region to the overall reflection measurement has not been thoroughly examined. This study aims to elucidate the relative contribution of reflected waves arising from the upper and lower human body vasculature to those observed at the aortic root. METHODS: We utilised a one-dimensional (1D) computational model of wave propagation to study reflections in an arterial model that included 37 largest arteries. A narrow Gaussian-shaped pulse was introduced to the arterial model from five distal locations: carotid, brachial, radial, renal, and anterior tibial. The propagation of each pulse towards the ascending aorta was computationally tracked. We calculated the reflected pressure and wave intensity at the ascending aorta in each case. The results are presented as a ratio of the initial pulse. RESULTS: The findings of this study indicates that pressure pulses originated at the lower body can hardly be observed, while those originated from the upper body account for the largest portion of reflected waves seen at the ascending aorta. CONCLUSIONS: Our study validates the findings of earlier studies, which demonstrated that human arterial bifurcations have a significantly lower reflection coefficient in the forward direction as compared to the backward direction. The results of this study underscore the need for further in-vivo investigations to provide a deeper understanding of the nature and characteristics of reflections observed in the ascending aorta, which can inform the development of effective strategies for the management of arterial diseases.

Impact of wall displacements on the large-scale flow coherence in ascending aorta.

In the context of aortic hemodynamics, uncertainties affecting blood flow simulations hamper their translational potential as supportive technology in clinics. Computational fluid dynamics (CFD) simulations under rigid-walls assumption are largely adopted, even though the aorta contributes markedly to the systemic compliance and is characterized by a complex motion. To account for personalized wall displacements in aortic hemodynamics simulations, the moving-boundary method (MBM) has been recently proposed as a computationally convenient strategy, although its implementation requires dynamic imaging acquisitions not always available in clinics. In this study we aim to clarify the real need for introducing aortic wall displacements in CFD simulations to accurately capture the large-scale flow structures in the healthy human ascending aorta (AAo). To do that, the impact of wall displacements is analyzed using subject-specific models where two CFD simulations are performed imposing (1) rigid walls, and (2) personalized wall displacements adopting a MBM, integrating dynamic CT imaging and a mesh morphing technique based on radial basis functions. The impact of wall displacements on AAo hemodynamics is analyzed in terms of large-scale flow patterns of physiological significance, namely axial blood flow coherence (quantified applying the Complex Networks theory), secondary flows, helical flow and wall shear stress (WSS). From the comparison with rigid-wall simulations, it emerges that wall displacements have a minor impact on the AAo large-scale axial flow, but they can affect secondary flows and WSS directional changes. Overall, helical flow topology is moderately affected by aortic wall displacements, whereas helicity intensity remains almost unchanged. We conclude that CFD simulations with rigid-wall assumption can be a valid approach to study large-scale aortic flows of physiological significance.

Data-driven generation of 4D velocity profiles in the aneurysmal ascending aorta.

BACKGROUND AND OBJECTIVE: Numerical simulations of blood flow are a valuable tool to investigate the pathophysiology of ascending thoratic aortic aneurysms (ATAA). To accurately reproduce in vivo hemodynamics, computational fluid dynamics (CFD) models must employ realistic inflow boundary conditions (BCs). However, the limited availability of in vivo velocity measurements, still makes researchers resort to idealized BCs. The aim of this study was to generate and thoroughly characterize a large dataset of synthetic 4D aortic velocity profiles sampled on a 2D cross-section along the ascending aorta with features similar to clinical cohorts of patients with ATAA. METHODS: Time-resolved 3D phase contrast magnetic resonance (4D flow MRI) scans of 30 subjects with ATAA were processed through in-house code to extract anatomically consistent cross-sectional planes along the ascending aorta, ensuring spatial alignment among all planes and interpolating all velocity fields to a reference configuration. Velocity profiles of the clinical cohort were extensively characterized by computing flow morphology descriptors of both spatial and temporal features. By exploiting principal component analysis (PCA), a statistical shape model (SSM) of 4D aortic velocity profiles was built and a dataset of 437 synthetic cases with realistic properties was generated. RESULTS: Comparison between clinical and synthetic datasets showed that the synthetic data presented similar characteristics as the clinical population in terms of key morphological parameters. The average velocity profile qualitatively resembled a parabolic-shaped profile, but was quantitatively characterized by more complex flow patterns which an idealized profile would not replicate. Statistically significant correlations were found between PCA principal modes of variation and flow descriptors. CONCLUSIONS: We built a data-driven generative model of 4D aortic inlet velocity profiles, suitable to be used in computational studies of blood flow. The proposed software system also allows to map any of the generated velocity profiles to the inlet plane of any virtual subject given its coordinate set.

Nondestructive Evaluation of Mechanical and Histological Properties of the Human Aorta With Near-Infrared Spectroscopy.

INTRODUCTION: Ascending aortic dilatation is a well-known risk factor for aortic rupture. Indications for aortic replacement in its dilatation concomitant to other open-heart surgery exist; however, cut-off values based solely on aortic diameter may fail to identify patients with weakened aortic tissue. We introduce near-infrared spectroscopy (NIRS) as a diagnostic tool to nondestructively evaluate the structural and compositional properties of the human ascending aorta during open-heart surgeries. During open-heart surgery, NIRS could provide information regarding tissue viability in situ and thus contribute to the decision of optimal surgical repair. MATERIALS AND METHODS: Samples were collected from patients with ascending aortic aneurysm (n = 23) undergoing elective aortic reconstruction surgery and from healthy subjects (n = 4). The samples were subjected to spectroscopic measurements, biomechanical testing, and histological analysis. The relationship between the near-infrared spectra and biomechanical and histological properties was investigated by adapting partial least squares regression. RESULTS: Moderate prediction performance was achieved with biomechanical properties (r = 0.681, normalized root-mean-square error of cross-validation = 17.9%) and histological properties (r = 0.602, normalized root-mean-square error of cross-validation = 22.2%). Especially the performance with parameters describing the aorta's ultimate strength, for example, failure strain (r = 0.658), and elasticity (phase difference, r = 0.875) were promising and could, therefore, provide quantitative information on the rupture sensitivity of the aorta. For the estimation of histological properties, the results with α-smooth muscle actin (r = 0.581), elastin density (r = 0.973), mucoid extracellular matrix accumulation(r = 0.708), and media thickness (r = 0.866) were promising. CONCLUSIONS: NIRS could be a potential technique for in situ evaluation of biomechanical and histological properties of human aorta and therefore useful in patient-specific treatment planning.

Pulse wave velocity: A clinical measure to aid material parameter estimation in computational arterial biomechanics.

Determining proper material parameters from clinical data remains a large, though unavoidable, challenge in patient-specific computational cardiovascular modeling. In an attempt to couple the clinical and modelling practice, this study investigated whether pulse wave velocity (PWV), a clinical arterial stiffness measure, can guide in determining appropriate parameter values for the Gasser-Ogden-Holzapfel (GOH) constitutive model. The reduction and uncertainty analysis was demonstrated on a cylindrical descending thoracic aorta model. Starting from discretized ranges of GOH parameters and using a full factorial design, the parameter sets yielding a physiological PWV (3.5-12.5 m/s) at diastolic pressure (80 mmHg; PWV80) were selected and their PWV at dicrotic notch pressure (110 mmHg; PWV110) was determined. These PWV measures were applied to determine the reduction of the 7D GOH parameter space, the 2D subspaces and the remaining uncertainty in case only PWV80 or both measurements are available. The resulting 12,032 parameter sets lead to a 7D parameter space reduction of ≥ 82.5 % using PWV80, which increased to 96.0 % when including PWV110, in particular at 3.5-8.5 m/s. A similar trend was observed for the remaining uncertainty and the 2D subspaces comprised of medial collagen fiber parameters, while scarce reductions were found for the adventitial and elastin parameters. In conclusion, PWV80 and PWV110 are complementary measures with the potential to reduce the GOH parameter space in arterial models, in particular for media- and collagen-related parameters. Moreover, this approach has the advantage that it allows the estimation of the remaining uncertainty after parameter space reduction.

Fitting mechanical properties of the aortic wall and individual layers to experimental tensile tests including residual stresses.

The authors have observed that a stress-strain curve for uniaxial tension of an aortic intact wall cannot be simply obtained by combining the strain energy functions of the three individual aortic layers - intima, media and adventitia - even taking into account the interaction among the three layers; the strain energy functions of the three layers are obtained fitting tensile tests on strips from the individual layers. Due to the layer separation, the residual stresses are released and thus they do not affect the stress-strain curves of the individual layers. The present study shows that it is instead possible to fit the intact wall experimental curves with the combination of the strain energy functions of the three individual layers if residual strains are added. The residual strains are used as optimization parameters with specific constraints and allowing for the buckling (wrinkling) of the intima under unpressurized condition of the aortic wall, as experimentally observed. By varying these parameters in the experimentally observed range of values, it is possible to find a solution with the combined responses of the individual layers matching the experimental stress-strain curves of the intact wall.

Direct 0D-3D coupling of a lattice Boltzmann methodology for fluid-structure aortic flow simulations.

This work introduces a numerical approach and implementation for the direct coupling of arbitrary complex ordinary differential equation- (ODE-)governed zero-dimensional (0D) boundary conditions to three-dimensional (3D) lattice Boltzmann-based fluid-structure systems for hemodynamics studies. In particular, a most complex configuration is treated by considering a dynamic left ventricle- (LV-)elastance heart model which is governed by (and applied as) a nonlinear, non-stationary hybrid ODE-Dirichlet system. Other ODE-based boundary conditions, such as lumped parameter Windkessel models for truncated vasculature, are also considered. Performance studies of the complete 0D-3D solver, including its treatment of the lattice Boltzmann fluid equations and elastodynamics equations as well as their interactions, is conducted through a variety of benchmark and convergence studies that demonstrate the ability of the coupled 0D-3D methodology in generating physiological pressure and flow waveforms-ultimately enabling the exploration of various physical and physiological parameters for hemodynamics studies of the coupled LV-arterial system. The methods proposed in this paper can be easily applied to other ODE-based boundary conditions as well as to other fluid problems that are modeled by 3D lattice Boltzmann equations and that require direct coupling of dynamic 0D boundary conditions.

Central arterial pressure and patient-specific model parameter estimation based on radial pressure measurements.

One-dimensional arterial flow simulations are suitable to estimate the aortic pressure from peripheral measurements in a patient-specific arterial network. This study introduces a reduction of the system parameters, and a novel calculation method to estimate the patient-specific set and the aortic curve based on radial applanation tonometry. Peripheral and aortic pressure curves were measured in patients, optimization were carried out. The aortic pressure curves were reproduced well, with an overestimation of the measured Systolic and Mean Blood Pressures on average by 0.6 and 0.5 mmHg respectively, and the Root Mean Square Difference of the curves was 3 mmHg on average.

Single measurement estimation of central blood pressure using an arterial transfer function.

BACKGROUND: Central blood pressure (BP) better reflects the loading conditions on the major organs and is more closely correlated with future cardiovascular events. The increased invasiveness and risk of infection prevents the routine measurement of central BP. Arterial transfer functions can provide central BP estimates from clinically available peripheral measurements. However, current methods are either generalized, potentially lacking the ability to adapt to inter and intra subject variability, or individualized based on additional, clinically unavailable, pulse transit time measurements. This work proposes a novel, self-contained method for individualizing an arterial transfer function from a single peripheral pressure measurement, capable of accurately estimating central BP in a range of hemodynamic conditions. METHODS: Pulse wave analysis of femoral BP waves was employed to formulate initial approximations of central BP and arterial inlet flow waveforms, to serve as objective functions for the identification of all model parameters. Root mean squared error (RMSE), and systolic and pulse pressure errors were assessed with respect to invasive aortic BP measurements in a seven (7) porcine endotoxin experiments. Systolic and pulse pressure errors were analysed using Bland-Altman analysis. Method accuracy is also compared with an idealized transfer function, derived using the measured aortic-femoral pulse transit time and minimizing the RMSE of model output pressure with respect to reference aortic pressure, a generalized transfer function model, and invasive femoral pressure measurements. RESULTS: Mean bias and limits of agreement (95% CI) for the proposed method were 1.0(-4.6, 6.7)mmHg and -1.0(-6.6, 4.6)mmHg for systolic and pulse pressure, respectively, compared to 3.6(-0.9, 8.2)mmHg and 2.7(-1.8, 7.3)mmHg for the generalized transfer function model. Mean bias and limits of agreement for femoral pressure measurements were -6.4(-15.0, 2.3)mmHg and -9.4(-18.1, -0.8)mmHg, for systolic and pulse pressure, respectively. The pooled mean and standard deviation of the RMSE produced by the single measurement method, relative to reference aortic pressure, was 4.3(1.1)mmHg, consistent with estimates produced by the idealized transfer function, 3.9(1.2)mmHg, and improving of the generalized transfer function, 4.6(1.4)mmHg. CONCLUSIONS: The proposed single measurement method provides accurate central BP estimates from routinely available peripheral pressure measurements, and nothing else. The method allows for the individualization of transfer functions on a per patient basis to better capture changes in patient condition during the progression of disease and subsequent treatment, at no additional clinical cost.

A coupled atrioventricular-aortic setup for in-vitro hemodynamic study of the systemic circulation: Design, fabrication, and physiological relevancy.

In-vitro models of the systemic circulation have gained a lot of interest for fundamental understanding of cardiovascular dynamics and for applied hemodynamic research. In this study, we introduce a physiologically accurate in-vitro hydraulic setup that models the hemodynamics of the coupled atrioventricular-aortic system. This unique experimental simulator has three major components: 1) an arterial system consisting of a human-scale artificial aorta along with the main branches, 2) an artificial left ventricle (LV) sac connected to a programmable piston-in-cylinder pump for simulating cardiac contraction and relaxation, and 3) an artificial left atrium (LA). The setup is designed in such a way that the basal LV is directly connected to the aortic root via an aortic valve, and to the LA via an artificial mitral valve. As a result, two-way hemodynamic couplings can be achieved for studying the effects that the LV, aorta, and LA have on each other. The collected pressure and flow measurements from this setup demonstrate a remarkable correspondence to clinical hemodynamics. We also investigate the physiological relevancies of isolated effects on cardiovascular hemodynamics of various major global parameters found in the circulatory system, including LV contractility, LV preload, heart rate, aortic compliance, and peripheral resistance. Subsequent control over such parameters ultimately captures physiological hemodynamic effects of LV systolic dysfunction, preload (cardiac) diseases, and afterload (arterial) diseases. The detailed design and fabrication of the proposed setup is also provided.

Non-intrusive PODI-ROM for patient-specific aortic blood flow in presence of a LVAD device.

Left ventricular assist devices (LVADs) are used to provide haemodynamic support to patients with critical cardiac failure. Severe complications can occur because of the modifications of the blood flow in the aortic region. In this work, the effect of a continuous flow LVAD device on the aortic flow is investigated by means of a non-intrusive reduced order model (ROM) built using the proper orthogonal decomposition with interpolation (PODI) method based on radial basis functions (RBF). The full order model (FOM) is represented by the incompressible Navier-Stokes equations discretized by using a Finite Volume (FV) technique, coupled with three-element Windkessel models to enforce outlet boundary conditions in a multi-scale approach. A patient-specific framework is proposed: a personalized geometry reconstructed from Computed Tomography (CT) images is used and the individualization of the coefficients of the three-element Windkessel models is based on experimental data provided by the Right Heart Catheterization (RHC) and Echocardiography (ECHO) tests. At FOM level, we also consider the pre-surgery configuration in order to further validate the predictive capabilities of the model in several contexts. The ROM has been tested by considering a parametric setting with respect to the LVAD flow, which is a crucial parameter of the problem. We consider a parameter range that covers typical clinical values. The accuracy of the ROM is assessed against results obtained with the FOM both for primal, velocity and pressure, and derived quantities, wall shear stress (WSS). Finally, we briefly discuss the efficiency of our ROM approach.