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Severe right heart failure, often overlooked and challenging to manage, has prompted a growing interest in innovative approaches to provide functional support. This study uses experimentation in large porcine models to introduce a novel prototype of a pulsatile mechanical circulatory support device and document its effects when deployed as a right ventricular assist device (RVAD). The pulsatile ventricular assist platform (pVAP), featuring a membrane pump driven by an intra-aortic balloon pump console, actively generates pulsatile flow to propel right ventricular blood into the pulmonary artery. This novel prototype demonstrates promising potential in addressing the challenges of right heart failure management. After preliminary in vitro assessments, the pVAP was tested on seven porcine models in a healthy state and after the induction of right ventricular failure. During the procedure, a set of standard ( ie , standard-of-care) hemodynamic measurements was obtained. Additionally, invasive pressure-volume loop analysis was employed to examine left ventricular hemodynamics. Results indicated that activation of the pVAP during right ventricular failure significantly improved systemic hemodynamics and enhanced left ventricular function. This study sheds light on the potential of the pVAP in managing right heart failure., Competing Interests: O.M. is the CEO of PulseCath BV. M.B. receives personal fees from PulseCath BV. The other authors have no conflicts of interest to report., (Copyright © ASAIO 2024.)

Blood pressure or flow measurements have been associated with vascular health and cognitive function. We proposed that energetic hemodynamic parameters may provide a more nuanced understanding and stronger correlation with cognitive function, in comparisons with conventional aortic and carotid pressure and flow parameters. The study comprised 1858 participants, in whom we assessed cognitive function via MoCA method, and measured central aortic and carotid pressure and flow waveforms. In addition to various pressure and flow parameters, we calculated energetic hemodynamic parameters through integration of pressure multiplying flow with respect to time. Energetic hemodynamic parameters, particularly aortic and carotid mean and pulsatile energy and pulsatility index (PI), were significantly associated with MoCA score more than any aortic and carotid pressure and flow parameters, after adjusting for age, sex, education, depression score, heart rate, BMI, HDL-cholesterol, and glucose levels. MoCA exhibited a strong positive relationship with carotid mean energy (standardized beta = 0.053, P = 0.0253) and a negative relationship with carotid energy PI (standardized beta = -0.093, P = 0.0002), exceeding the association with all traditional pressure- or flow-based parameters. Aortic pressure reflection coefficient at the aorto-carotid junction was positively correlated with mean carotid energy and negatively correlated with PI. Aortic characteristic impedance positively correlated with carotid energy PI but not mean energy. Our research indicates that energetic hemodynamic parameters, particularly carotid mean energy and carotid energy PI, have a stronger association with MoCA scores than traditional pressure- or flow-based metrics. This correlation with cognitive function is notably influenced by the properties of the aorto-carotid interface., (© 2024. The Author(s).)

Right ventricular assist devices (RVADs) have been extensively used to provide hemodynamic support for patients with end-stage right heart (RV) failure. However, conventional in-parallel RVADs can lead to an elevation of pulmonary artery (PA) pressure, consequently increasing the right ventricular (RV) afterload, which is unfavorable for the relaxation of cardiac muscles and reduction of valve complications. The aim of this study is to investigate the hemodynamic effects of the pulsatile frequency of the RVAD on pulmonary artery. Firstly, a mathematical model incorporating heart, systemic circulation, pulmonary circulation, and RVAD is developed to simulate the cardiovascular system. Subsequently, the frequency characteristics of the pulmonary circulation system are analyzed, and the calculated results demonstrate that the pulsatile frequency of the RVAD has a substantive impact on the pulmonary artery pressure. Finally, to verify the analysis results, the hemodynamic effects of the pulsatile frequency of the RVAD on pulmonary artery are compared under diffident support modes. It is found that the pulmonary artery pressure decreases by approximately 6% when the pulsatile frequency changes from 1 to 3 Hz. The increased pulsatile frequency of RA-PA support mode may facilitate the opening of the pulmonary valve, while the RV-PA support mode can more effectively reduce the load of RV. This work provides a useful method to decrease the pulmonary artery pressure during the RVAD supports and may be beneficial for improving myocardial function in patients with end-stage right heart failure, especially those with pulmonary hypertension., Competing Interests: Declarations Conflict of interest The authors declare no competing interests., (© 2024. International Federation for Medical and Biological Engineering.)

Neurovascular 4D-Flow MRI enables non-invasive evaluation of cerebral hemodynamics including measures of cerebral blood flow (CBF), vessel pulsatility index (PI), and cerebral pulse wave velocity (PWV). 4D-Flow measures have been linked to various neurovascular disorders including small vessel disease and Alzheimer's disease; however, physiological and technical sources of variability are not well established. Here, we characterized sources of diurnal physiological and technical variability in cerebral hemodynamics using 4D-Flow in a retrospective study of cognitively unimpaired older adults (N = 750) and a prospective study of younger adults (N = 10). Younger participants underwent repeated MRI sessions at 7am, 4 pm, and 10 pm. In the older cohort, having an MRI earlier on the day was significantly associated with higher CBF and lower PI. In prospective experiments, time of day significantly explained variability in CBF and PI; however, not in PWV. Test-retest experiments showed high CBF intra-session repeatability (repeatability coefficient (RPC) =7.2%), compared to lower diurnal repeatability (RPC = 40%). PI and PWV displayed similar intra-session and diurnal variability (PI intra-session RPC = 22%, RPC = 24% 7am vs 4 pm; PWV intra-session RPC = 17%, RPC = 21% 7am vs 4 pm). Overall, CBF measures showed low technical variability, supporting diurnal variability is from physiology. PI and PWV showed higher technical variability but less diurnal variability., Competing Interests: Declaration of conflicting interestsThe author(s) declared the following potential conflicts of interest with respect to the research, authorship, and/or publication of this article: S.C. Johnson served on an advisory board for Roche Diagnostics in 2018 for which he received an honorarium and is principal investigator of an equipment grant from Roche. He conducts tau imaging in NIH funded studies as well as a study funded by Cerveau Technologies using radioligand precursor material supplied by Cerveau Technologies.

Mechanisms behind the protective effects of aerobic exercise on brain health remain elusive but may be vascular in origin and relate to cerebral pulsatility. This pilot study investigated the effects of 12-wk aerobic exercise training on cerebral pulsatility and its vascular contributors (large artery stiffness, characteristic impedance) in at-risk middle-aged adults. Twenty-eight inactive middle-aged adults with elevated blood pressure or stage 1 hypertension were assigned to either moderate/vigorous aerobic exercise training (AET) for 3 days/wk or no-exercise control (CON) group. Middle cerebral artery (MCA) pulsatility index (PI), large artery (i.e., aorta, carotid) stiffness, and characteristic impedance were assessed via Doppler and tonometry at baseline, 6, and 12 wk, whereas cardiorespiratory fitness (V̇o 2peak ) was assessed via incremental exercise test and cognitive function via computerized battery at baseline and 12 wk. V̇o 2peak increased 6% in AET and decreased 4% in CON ( P < 0.05). Proximal aortic compliance increased ( P = 0.04, partial η 2 = 0.14) and aortic characteristic impedance decreased ( P = 0.02, partial η 2  = 0.17) with AET but not CON. Cerebral pulsatility showed a medium-to-large effect size increase with AET, although not statistically significant ( P = 0.07, partial η 2  = 0.11) compared with CON. Working memory reaction time improved with AET but not CON ( P = 0.02, partial η 2  = 0.20). Our data suggest 12-wk AET elicited improvements in central vascular hemodynamics (e.g., proximal aortic compliance and characteristic impedance) along with apparent, paradoxical increases in cerebral pulsatile hemodynamics. NEW & NOTEWORTHY We identify differential central versus cerebrovascular responses to 12 wk of aerobic exercise training in middle-aged adults. Although proximal aortic compliance and characteristic impedance improved after 12 wk of exercise, cerebral pulsatility tended to unexpectedly increase. These data suggest short-term aerobic exercise training may lead to more immediate benefits in the central vasculature, whereas longer duration exercise training may be required for beneficial changes in pulsatility within the cerebrovasculature.

To investigate flow conditions in a double-layered carotid artery stent, a bench-top in vitro flow setup including a bifurcation phantom was designed and fabricated. The geometry of the tissue-mimicking phantom was based on healthy individuals. Two identical phantoms were created using 3D-printing techniques and molding with PVA-gel. In one of them, a clinically available CGuard double-layer stent was inserted. Measurements were performed using both continuous and pulsatile flow conditions. Blood flow studies were performed using echoPIV: a novel ultrasound-based technique combined with particle image velocimetry. A maximum deviation of 3% was visible between desired and measured flow patterns. The echoPIV measurements showed promising results on visualization and quantification of blood flow in and downstream the stent. Further research could demonstrate the effects of a double-layered stent on blood flow patterns in a carotid bifurcation in detail., (© 2023. International Federation for Medical and Biological Engineering.)

In this study, we investigate the impact of aortic stenosis on the hemodynamics of pulsatile blood flow within a 3D aortic model. Employing a non-Newtonian Casson model with a hematocrit of 45%, our study introduces a preliminary hypothesis to simulate blood flow dynamics, incorporating both linear elastic and viscoelastic models to define the mechanical characteristics of the artery. Through simulations conducted with Ansys-Cfx (version 15), we utilize a 2-way fluid-structure interaction (FSI) approach, employing a Lagrangian-Eulerian formulation with second-order accuracy. We explore the influence of stenosis severity on variables including velocity profiles, pressure distribution, shear stress, wall displacement, and changes in the OSI parameter. Our investigation encompasses arteries with both elastic and viscoelastic walls. The key findings that arise from our results highlight the viscoelastic model's demonstration of reduced radial wall displacement when compared to the linear elastic model. Additionally, we observe that elevated arterial stenosis percentages lead to the elongation of vortex length, heightened wall shear stress, and increased slope of velocity profiles downstream of the stenosed region. Furthermore, bulky obstruction of viscoelastic arteries as opposed to elastic, resulted in a maximum 5 percent increase in velocity profile and a 29.6% decrease in radial displacement. The zenith of shear stress occurs concomitantly with the velocity's peak within the stenosed area. Viscoelastic arterial wall shear stress at the stenosis site escalates due to the rapid expansion of the stenosis. The viscoelastic wall, responding with a blend of viscous and elastic characteristics to applied stress, undergoes slight deformation in shape. Following stress reduction, the wall gradually reverts to its original form, thus alleviating some of the applied stress. In contrast, the elastic wall retains its altered shape due to stress preservation within the material. Additionally, we ascertain an augmentation in radial displacement corresponding with increased artery stenosis., (© 2023 IOP Publishing Ltd.)

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., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

Pulsatile hemodynamics analyses provide important information about the ventricular-arterial system which cannot be inferred by standard blood pressure measurements. Pulse wave analysis (PWA), wave separation analysis (WSA), and wave power analysis (WPA) characterize arterial hemodynamics with limited preclinical applications. Integrating these tools into preclinical testing may enhance understanding of disease or therapeutic effects on cardiovascular function. We used a canine rapid ventricular pacing (RVP) heart failure model to: (1) Characterize hemodynamics in response to RVP and (2) assess analyses from flow waveforms synthesized from pressure compared to those derived from measured flow. Female canines (n = 7) were instrumented with thoracic aortic pressure transducers, ventricular pacing leads, and an ascending aortic flow probe. Data were collected at baseline, 1 week, and 1 month after RVP onset. RVP progressively reduced stroke volume (SV), the PWA SV estimator, and WSA and WPA pulsatility and wave reflection indices. Indices derived from synthesized flow exhibited similar directional changes and high concordance with measured flow calculations. Our data demonstrate the value of analytical hemodynamic methods to gain deeper insight into cardiovascular function in preclinical models. These approaches can provide complementary value to standard endpoints in evaluating potential effects of pharmaceutical agents intended for human use., (© 2023 Merck Sharp & Dohme LLC and The Authors. Physiological Reports published by Wiley Periodicals LLC on behalf of The Physiological Society and the American Physiological Society.)

Background: Pulsatile perfusion during extracorporeal circulation is a promising concept to improve perfusion of critical organs. Clinical benefits are limited by the amount of pulsatile energy provided by standard pumps. The present study investigated the properties of a novel positive displacement blood pump in a mock circulation., Methods: The pump was attached to an aortic model with a human-like geometry and compliance as a pseudo patient. Hemodynamic data were recorded while the pump settings were adjusted systematically., Results: Using a regular oxygenator, maximum flow was 2.6 L/min at a pressure of 27 mm Hg and a frequency (F) of 90 bpm. Pulse pressure (PP; 28.9 mm Hg) and surplus hemodynamic energy (SHE; 26.1% of mean arterial pressure) were highest at F = 40 bpm. Flow and pressure profiles appeared sinusoid. Using a low-resistance membrane ventilator to assess the impact of back pressure, maximum flow was 4.0 L/min at a pressure of 58.6 mm Hg and F = 40 bpm. At F = 40 bpm, PP was 58.7 mm Hg with an SHE of 33.4%. SHE decreased with increasing flow, heart rate, and systolic percentage but surpassed 10% with reasonable settings., Conclusions: The present prototype achieved sufficient flow and pressure ranges only in the presence of a low-resistance membrane ventilator. It delivered supraphysiologic levels of pulse pressure and SHE. Further modifications are planned to establish this concept for adult pulsatile perfusion., (© 2022 The Authors. Artificial Organs published by International Center for Artificial Organ and Transplantation (ICAOT) and Wiley Periodicals LLC.)

Heterogeneous medium enhanced angiogr- ams are key diagnostic tools in clinical practice; the associated hemodynamic information is crucial for diagnosing cardiovascular diseases. However, the dynamics of such medium in physiological blood flow are poorly understood. Herein, we report a previously unnoticed dispersion pattern, which is a universal phenomenon, of a medium in pulsatile blood flow. We present a physical theory for studying the dispersion of a steadily injected heterogeneous medium into a thin tubular blood vessel in which the blood flow is pulsatile. In a thin tubular blood vessel, we demonstrate that variations of concentration associated with the heterogeneous medium obey a one-dimensional advection diffusion equation, and the diffusion has limited effect whenever a short vascular segment is considered. A distinct feature of the distribution of the medium in the axial distance-time plane is a "dilation-retraction" pattern. The time evolution signals at different axial positions exhibit distinct concentration waveforms. A numerical scheme is proposed for exploiting this information to estimate the pulsatile velocity. Artificial data are adopted to validate the scheme. Real X-ray angiography is also analyzed to support our theory and method. The theory is applicable whenever imaging protocols involve a heterogeneous medium in pulsatile flow.

The study of turbulence in physiologic blood flow is important due to its strong relevance to endothelial mechanobiology and vascular disease. Recently, Saqr et al. (Sci Rep 10, 15,492, 2020) discovered non-Kolmogorov turbulence in physiologic blood flow in vivo, traced its origins to the Navier-Stokes equation and demonstrated some of its properties using chaos and hydrodynamic-stability theories. The present work extends these findings and investigates some inherent characteristics of non-Kolmogorov turbulence in monoharmonic and multiharmonic pulsatile flow under ideal physiologic conditions. The purpose of this work is to propose a conjecture for the origins for picoNewton forces that are known to regulate endothelial cells' functions. The new conjecture relates these forces to physiologic momentum-viscous interactions in the near-wall region of the flow. Here, we used high-resolution large eddy simulation (HRLES) to study pulsatile incompressible flow in a straight pipe of [Formula: see text]. The simulations presented Newtonian and Carreau-Yasuda fluid flows, at [Formula: see text], each represented by one, two and three boundary harmonics. Comparison was established based on maintaining constant time-averaged mass flow rate in all simulations. First, we report the effect of primary harmonics on the global power budget using primitive variables in phase space. Second, we describe the non-Kolmogorov turbulence in frequency domain. Third, we investigate the near-wall coherent structures in time and space domains. Finally, we propose a new conjecture for the role of turbulence in endothelial cells' mechanobiology. The proposed conjecture correlates near-wall turbulence to a force field of picoNewton scale, suggesting possible relevance to endothelial cells mechanobiology., (© 2022. The Author(s).)

Background: The most common configuration for arteriovenous fistula is brachiocephalic which often develop cephalic arch stenosis leading to the need for numerous procedures to maintain access patency. The hemodynamics that contributes to the development of cephalic arch stenosis is incompletely understood given the inability to accurately determine shear stress in the cephalic arch. In the current investigation our aim was to determine pressure, velocity and wall shear stress profiles in the cephalic arch in 3D using computational modeling as tools to understand stenosis., Methods: Five subjects with brachiocephalic fistula access had protocol labs, Doppler, venogram and intravascular ultrasound imaging performed at 3 and 12 months. 3D reconstructions of the cephalic arch were generated by combining intravascular ultrasounds and venograms. Standard finite element analysis software was used to simulate time dependent blood flow in the cephalic arch with velocity, pressure and wall shear stress profiles generated., Results: Our models generated from imaging and flow measurements at 3 and 12 months offer snapshots of the patient's cephalic arch at a precise time point, although the remodeling of the vessel downstream of an arteriovenous fistula in patients undergoing regular dialysis is a dynamic process that persists over long periods of time (~ 5 years). The velocity and pressure increase at the cephalic bend cause abnormal hemodynamics most prominent along the inner wall of the terminal cephalic arch. The topology of the cephalic arch is highly variable between subjects and predictive of pathologic stenosis at later time points., Conclusions: Low flow velocity and wall pressure along the inner wall of the bend may provide possible nidus of endothelial activation that leads to stenosis and thrombosis. In addition, 3D modelling of the arch can indicate areas of stenosis that may be missed by venograms alone. Computational modeling reconstructed from 3D radiologic imaging and Doppler flow provides important insights into the hemodynamics of blood flow in arteriovenous fistula. This technique could be used in future studies to determine optimal flow to prevent endothelial damage for patients with arteriovenous fistula access., Competing Interests: The authors have read the journal’s policy and have the following competing interests: Anindita Basu is a paid consultant for Novartis Institutes for BioMedical Research. There are no patents, products in development or marketed products associated with this research to declare. This does not alter our adherence to PLOS ONE policies on sharing data and materials.

Background and Objectives: Hemodynamics plays a crucial role in the progression of atherosclerosis and the treatment of arterial diseases. Stroke is one of the arterial diseases and a leading cause of death worldwide. Hemodynamics in the carotid artery plays a vital role in the stroke. The common carotid artery bifurcates into the internal carotid artery and the external carotid artery. Carotid sinus, a slightly dilated area, exists in the internal carotid artery just after the bifurcation and acts as a pressure receptor and regulator. The location and size of the sinus can vary in different people; the change in sinus size and location may affect the hemodynamics. It is necessary to study the shift in hemodynamics due to changes in sinus size and position on atherosclerosis. The change in flow behavior may suggest the probable sites of backflow and low wall shear stress, and therefore the sites prone to atherosclerosis., Methods: The model of the carotid artery has been constructed using patient data. Transient computational fluid dynamics simulations have been performed using a finite volume method for the numerical solution in a three-dimensional computational domain using ANSYS Fluent 19.2. Pulsatile flow is specified at the inlet boundary. The coupled scheme is used for the pressure-velocity coupling. The second-order discretization scheme is used for pressure interpolation and second-order upwind scheme is used for the discretisation of momentum equation. The temporal term is discretized using the first-order implicit scheme., Results: The effect of sinus size and location on the overall flow behavior, wall shear stress, and secondary flow are presented. Results show that the outer wall of bifurcation has low wall shear stress and bigger recirculation as compared with that on the inner wall of bifurcation. Numerical results obtained for varying sinus size and position are shown in graphs and contours, including wall shear stress, secondary flow, and velocity streamlines., Conclusion: Numerical results reveal that sinus away from bifurcation, and larger diameter sinus has more recirculation and low wall shear stress. Therefore, the person having sinus away from bifurcation and larger sinus diameter are more susceptible to plaque formation., Competing Interests: Declaration of Competing Interest The authors declare that they do not have any conflict of interest., (Copyright © 2020. Published by Elsevier B.V.)

Continuous-flow ventricular-assist devices are widely used to support patients with advanced heart failure, because continuous-flow ventricular-assist devices are more durable, have smaller sizes and have better survival rates for patients compared to the pulsatile-flow ventricular-assist devices. Nevertheless, continuous-flow ventricular-assist devices often cause complications such as gastrointestinal bleeding, haemorrhagic stroke, and aortic insufficiency and have a negative impact on the microcirculation for both long-time implantable and short-time extracorporeal systems. The aim of this study is the evaluation of the pulsatile-flow generation method in continuous-flow ventricular-assist device without pump speed changes. The method may be used for short-time extracorporeal continuous-flow mechanical circulatory support and long-time implantable mechanical circulatory support. A shunt with a controlled adjustable valve, that clamps periodically, is connected in parallel to the continuous-flow ventricular-assist device. We compared the continuous-flow ventricular-assist device operating with and without the shunt on the mock circulation loop. The continuous-flow ventricular-assist device-shunt system was connected according to the left ventricle-aorta circuit and worked in phase with the ventricle. Heart failure was simulated on the mock circulation circuit. Rotaflow (Maquet Inc.) was used as the continuous-flow pump. Haemolysis studies of the system for generating a pulse flow were carried out at a flow rate of 5 L/min and a pressure drop of 100 mm Hg. To compare the haemodynamic efficiency, we used the aortic pulsation index I p , the equivalent energy pressure and the surplus haemodynamic energy. These indexes were higher in the pulsatile mode ( I p - 4 times, equivalent energy pressure by 7.36% and surplus haemodynamic energy - 10 times), while haemolysis was the same. The normalised index of haemolysis was 0.0015 ± 0.001. The results demonstrate the efficiency of the pulsatile-flow generation method for continuous-flow ventricular-assist devices without impeller rotation rate changes.

Arterial stiffness and impedance gradients are known to influence pressure wave propagation and macrovascular-microvascular interactions. We studied the association between the carotid-femoral arterial stiffness gradient and the systemic reflection coefficient (N=393); of this population, 246 also underwent assessment of forward/backward pressure wave propagation and microvascular pulsatile pressure transmission (MPPT). Hemodynamic parameters were measured noninvasively. From peripheral vascular resistance and characteristic impedance, we estimated the systemic reflection coefficient and MPPT on peripheral and cardiac microcirculation in age-matched, sex-matched and body mass index-matched individuals with (n=147) or without (n=98) hypertension. The arterial stiffness gradient, systemic reflection coefficient, and correlations between the arterial stiffness gradient and age or blood pressure were similar in both populations. MPPT was higher in hypertension ( P <0.0001), and the subendocardial viability (Buckberg) index lower ( P <0.0001). In both populations, the systemic reflection coefficient and arterial stiffness gradient were significantly associated with changes in MPPT and the subendocardial viability index. Despite similar systemic reflection coefficients, the carotid reflected pressure and MPPT were higher in hypertension. Maintaining the systemic reflection coefficient within normal ranges was, therefore, insufficient to compensate for higher carotid forward pressure waves which, in hypertension, were associated with increased aortic stiffness ( P <0.0001) and higher stroke volume ( P =0.0365). Independently of cardiovascular risk, hypertension-induced changes have a weighted effect on MPPT, although insufficient to compensate for increased forward pressure waves. In hypertension, elevated aortic stiffness negatively affects the arterial stiffness gradient and systemic reflection coefficient but positively affects forward pressure.

As the alternative treatment for heart failure, left ventricular assist devices (LVADs) have been widely applied to clinical practice. However, the effects of the support modes of LVADs on the biomechanical states of the aortic valve are still poorly understood. Hence, the present study investigates such effects and proposes a novel fluid-structure interaction (FSI) approach that combines the lattice Boltzmann method (LBM) and finite element (FE) method. Two support modes of LVADs, namely constant speed mode and constant flow mode, which have been widely applied to clinical practice, are also designed. Results demonstrate that the support modes of LVADs could significantly affect the biomechanical states of the aortic valve and the blood flow pattern of the ascending aorta. Compared with those in the constant flow mode, the leaflets in the constant speed mode could achieve better dynamic performance and lower stress during the systolic phase. The max radial displacement of the leaflets in the constant speed mode is at 8 mm, whereas that in the constant flow mode is at 0.8 mm. Furthermore, the outflow of LVADs directly impacts the aortic surfaces of the leaflets during the diastolic phase by increasing the level of wall shear stress of the leaflets. The leaflets in the constant speed mode receive less impact than those in the constant flow mode. The condition with such minimal impact is conducive to maintaining the normal structure of leaflets and benefits the reduction of the risk of valvular diseases. In sum, the support modes of LVADs exert a crucial effect on the biomechanical environment of the aortic valve. The constant speed mode is better than the constant flow mode in terms of providing a good hemodynamic environment for the aortic valve.

Aortic pulse wave velocity is a worldwide accepted index to evaluate aortic stiffness and can be assessed noninvasively by several methods. This study sought to determine if commonly used noninvasive devices can all accurately estimate aortic pulse wave velocity. Pulse wave velocity was estimated in 102 patients (aged 65±13 years) undergoing diagnostic coronary angiography with 7 noninvasive devices and compared with invasive aortic pulse wave velocity. Devices evaluating carotid-femoral pulse wave velocity (Complior Analyse, PulsePen ET, PulsePen ETT, and SphygmoCor) showed a strong agreement between each other ( r>0.83) and with invasive aortic pulse wave velocity. The mean difference ±SD with the invasive pulse wave velocity was -0.73±2.83 m/s ( r=0.64) for Complior-Analyse: 0.20±2.54 m/s ( r=0.71) for PulsePen-ETT: -0.04±2.33 m/s ( r=0.78) for PulsePen ET; and -0.61±2.57 m/s ( r=0.70) for SphygmoCor. The finger-toe pulse wave velocity, evaluated by pOpmètre, showed only a weak relationship with invasive aortic recording (mean difference ±SD =-0.44±4.44 m/s; r=0.41), and with noninvasive carotid-femoral pulse wave velocity measurements ( r<0.33). Pulse wave velocity estimated through a proprietary algorithm by BPLab (v.5.03 and v.6.02) and Mobil-O-Graph showed a weaker agreement with invasive pulse wave velocity compared with carotid-femoral pulse wave velocity (mean difference ±SD =-0.71±3.55 m/s, r=0.23; 1.04±2.27 m/s, r=0.77; and -1.01±2.54 m/s, r=0.71, respectively), revealing a negative proportional bias at Bland-Altman plot. Aortic pulse wave velocity values provided by BPLab and Mobil-O-Graph were entirely dependent on age-squared and peripheral systolic blood pressure (cumulative r 2 =0.98 and 0.99, respectively). Thus, among the methods evaluated, only those assessing carotid-femoral pulse wave velocity (Complior Analyse, PulsePen ETT, PulsePen ET, and SphygmoCor) appear to be reliable approaches for estimation of aortic stiffness.

Objective: To compare maternal hemodynamics and perinatal outcome, in pregnancies that do not develop pre-eclampsia (PE) or deliver a small-for-gestational-age (SGA) neonate, between those identified at 11-13 weeks' gestation as being screen positive or negative for preterm PE, by a combination of maternal factors, mean arterial pressure, uterine artery pulsatility index, serum placental growth factor and pregnancy associated plasma protein-A., Methods: This was a prospective longitudinal cohort study of maternal cardiovascular function, assessed using a bioreactance method, in women undergoing first-trimester screening for PE. Maternal hemodynamics and perinatal outcome were compared between screen-positive and screen-negative women who did not have a medical comorbidity, did not develop PE or pregnancy-induced hypertension and delivered at term a live neonate with birth weight between the 5 th and 95 th percentiles. A multilevel linear mixed-effects model was used to compare the repeated measures of cardiac variables, controlling for maternal characteristics., Results: The screen-negative group (n = 926) had normal cardiac function changes across gestation, whereas the screen-positive group (n = 170) demonstrated static or reduced cardiac output and stroke volume and higher mean arterial pressure and peripheral vascular resistance with advancing gestation. In the screen-positive group, compared with screen-negative women, birth-weight Z-score was shifted toward lower values, with prevalence of delivery of a neonate below the 35 th , 30 th or 25 th percentile being about 70% higher, and the rate of operative delivery for fetal distress in labor also being higher., Conclusion: Women who were screen positive for impaired placentation, even though they did not develop PE or deliver a SGA neonate, had pathological cardiac adaptation in pregnancy and increased risk of adverse perinatal outcome. Copyright © 2018 ISUOG. Published by John Wiley & Sons Ltd., (Copyright © 2018 ISUOG. Published by John Wiley & Sons Ltd.)

Pulsatile hemodynamics are associated with brain small perivascular spaces (SPVS). It is unknown whether the stiffness of intermediary arteries connecting the aorta and brain modifies this association. Participants from the Northern Manhattan Study were assessed for SPVS (defined as ≤3 mm T1 voids) and white matter hyperintensity volume (WMH) using MRI. Middle (MCA) and anterior cerebral arterial (ACA) diameters (measured on time-of-flight MRA) and CCA strain (assessed by ultrasound) were used as surrogates of stiffness. Brachial and aortic pulse pressure (PP) and aortic augmentation index (Aix, assessed by applanation tonometry) were used as markers of pulsatility. We tested whether stiffness in intermediary arteries modifies the association between extracranial pulsatility with SPVS and WMH. We found that among 941 participants (mean age 71 ± 9 years, 60% women, 66% Hispanic), the right MCA/ACA diameter was associated with right anterior SPVS (B = 0.177, P = 0.002). Brachial PP was associated with right anterior SPVS (B = 0.003, P = 0.02), and the effect size was bigger with right MCA/ACA diameter in the upper tertile (P = 0.001 for the interaction). The association between right CCA strain and ipsilateral SPVS was modified by MCA/ACA diameter, with the largest effect size in those with ipsilateral MCA/ACA diameter in the upper tertile (P = 0.001 for the interaction). Similar dose-effects and statistical interactions were replicated using aortic AIx or aortic PP. We found no evidence of effect modification between pulsatile measures and WMH by stiffness measures. In summary, pulsatile hemodynamics relate to brain SPVS, and the association is the strongest among individuals with dilated brain arteries.

Objective: Pregnancies affected by a hypertensive disorder (HDP) have increased uterine artery pulsatility index (UtA-PI) compared with that in healthy pregnancies. Women with HDP are also known to have lower cardiac output and increased systemic vascular resistance. The aim of this study was to investigate the relationship between central and uterine hemodynamics in HDP and uncomplicated pregnancy., Methods: This was a prospective study of HDP and normotensive control singleton pregnancies presenting at a tertiary referral hospital between January 2012 and December 2017. Paired measurements of maternal hemodynamics, using a non-invasive device (USCOM-1A®), and UtA-PI were performed in the third trimester. HDP pregnancies were divided into preterm (onset < 37 weeks' gestation) and term (onset ≥ 37 weeks). Spearman's rank coefficient was used to assess the correlation between the central and uteroplacental hemodynamics. Regression analysis was performed to assess the association of UtA-PI with independent variables., Results: We included 231 women with HDP (152 with preterm and 79 with term HDP) and 378 controls with normotensive pregnancy. Compared with controls, women with preterm HDP had significantly lower cardiac output (median (interquartile range (IQR)), 6.0 (5.1-7.2) vs 6.6 (5.8-7.5) L/min; P < 0.001) and significantly higher systemic vascular resistance (median (IQR), 1394 (1189-1670) vs 1063 (915-1222) dynes × s/cm 5 ; P < 0.001) and UtA-PI (median (IQR), 1.0 (0.75-1.4) vs 0.67 (0.58-0.83); P < 0.001). Conversely, in women with term HDP, there were no significant differences in heart rate, cardiac output or UtA-PI compared with controls (all P > 0.05), while systemic vascular resistance was significantly higher (median (IQR), 1315 (1099-1527) vs 1063 (915-1222) dynes × s/cm 5 ; P < 0.001). On multiple regression analysis, heart rate, mean arterial pressure and stroke volume were associated significantly with mean UtA-PI (all P < 0.001)., Conclusions: Differences observed between HDP and normotensive pregnancies in third-trimester UtA resistance are mirrored in the central maternal hemodynamic parameters. Late pregnancy differences in the uteroplacental circulation in preterm and term HDP are an index of maternal cardiovascular function rather than being related to inadequate spiral artery remodeling and impaired placentation. Copyright © 2018 ISUOG. Published by John Wiley & Sons Ltd., (Copyright © 2018 ISUOG. Published by John Wiley & Sons Ltd.)

Background: Complex and unstable flow patterns are reported to be associated with the rupture status of cerebral aneurysms, while their evaluation depends on qualitative analysis of streamlines of bloodflow. Oscillatory velocity index (OVI) is a hemodynamic parameter to quantify flow patterns. The aim of this study is to elucidate the associations between OVI and the rupture status of cerebral aneurysms., Methods: One hundred and twenty-nine ruptured and unruptured cerebral aneurysms were analyzed with computational fluid dynamics under pulsatile flow conditions. With the use of median value of OVI, all aneurysms were divided into high and low OVI groups. Statistical analysis was performed to compare rupture status, and morphological and hemodynamic parameters between the two groups., Results: The median value of OVI was 0.006. High OVI was more likely observed in ruptured aneurysms (P=0.028) and associated with irregular shape, complex flow patterns, and unstable flow patterns (P<0.001, respectively). In morphological parameters, maximum size, aspect, projection, size, and volume-to-ostium area ratios were significantly higher in the high OVI group (P<0.001, respectively). In hemodynamic parameters, wall shear stress and wall shear stress gradient were significantly lower, and oscillatory shear index and gradient oscillatory number were significantly higher in the high OVI group (P<0.001, respectively)., Conclusion: High OVI was associated with rupture status, and morphological and hemodynamic characteristics of ruptured aneurysms. These results indicate that OVI may serve as a valuable hemodynamic parameter for diagnosing rupture status and risks of aneurysms., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2019. No commercial re-use. See rights and permissions. Published by BMJ.)

Background and Purpose: Cerebral aneurysms have significantly different rupture rates depending on their size and location. The mechanisms underlying these differences are unclear. We examined whether anatomic rupture risks are dependent on the hemodynamic environment on the aneurysmal surface., Materials and Methods: Patient-specific geometries and flow rates of 84 cerebral aneurysms (42 anterior communicating artery and 42 MCA aneurysms) were acquired from our clinical study, the Computational Fluid Dynamics Analysis of Blood Flow in Cerebral Aneurysms: Prospective Observational Study. Pulsatile blood flow was simulated to calculate hemodynamic metrics with special attention to wall shear stress magnitude and temporal disturbance. Multivariate analyses were performed to identify associations between hemodynamic metrics and known rupture predictors (age, sex, hypertension, smoking history, location, and size)., Results: All the wall shear stress magnitude-based metrics showed a significant negative association with size and location ( P < .03), but not other risk factors. All the wall shear stress disturbance-based metrics were significantly related to size ( P < .001). Only normalized transverse wall shear stress, a metric for multidirectional wall shear stress disturbance, was related to location ( P = .03). The normalized transverse wall shear stress had the highest odds ratio for location and size among hemodynamic metrics (odds ratios, 1.275 and 1.579; 95% confidence intervals, 1.020-1.693 and 1.238-2.219, respectively). Among the arterial geometric parameters, the aspect ratio had the second strongest association with all hemodynamic metrics, after our newly proposed aspect ratio-asphericity index., Conclusions: The differences in aneurysm rupture rates according to size and location may reflect differences in hemodynamic environments in qualitatively different ways. An enhanced multidirectional wall shear stress disturbance may be especially associated with aneurysm rupture., (© 2019 by American Journal of Neuroradiology.)

Objectives: Forest fires in South Asia lead to widespread haze, where many healthy individuals develop psychosomatic symptoms. We investigated the effects of haze exposure on cerebral hemodynamics and new symptoms. We hypothesised that vasoactive substances present in the haze, would lead to vasodilation of cerebral vasculature, thereby altering cerebral hemodynamics, which in turn may account for new psychosomatic symptoms., Methods: Seventy-four healthy volunteers were recruited, and serial transcranial Doppler (TCD) ultrasonography was performed to record blood flow parameters of bilateral middle cerebral arteries (MCA). The first TCD was performed in an air-conditioned environment. It was repeated outdoors after the participants spent 30-minutes in the haze environment. The prevailing level of pollutant standards index (PSI) was recorded. Appropriate statistical analyses were performed to compare cerebral hemodynamics at baseline and after haze exposure in all participants. Subgroup analyses were then employed to compare the findings between symptomatic and asymptomatic participants., Results: Study participants' median age was 30 years (IQR 26-34), and new psychosomatic symptoms were reported by 35 (47.3%). There was a modest but significant decrease in pulsatility index (PI) and resistivity index (RI) in the left MCA after haze exposure (PI: p = 0.026; RI: p = 0.021). When compared to baseline parameters, haze exposure resulted in significantly lower mean PI (p = 0.001) and RI (p = 0.001) in symptomatic patients, but this difference was not present in asymptomatic patients (PI: p = 0.919; RI: p = 0.970)., Conclusion: Haze causes significant alterations in cerebral hemodynamics in susceptible individuals, probably responsible for various psychosomatic symptoms. The prognostic implications and health effects of haze require evaluation in a larger study., Competing Interests: The authors have declared that no competing interests exist.

Background and Purpose: Vertebrobasilar dolichoectatic and fusiform aneurysms (VBDAs) are known to have a poor natural history, with high rates of growth, rupture, and stroke. The purpose of this study was to identify hemodynamic characteristics that differ between VBDAs associated with growth, rupture, and stroke., Materials and Methods: VBDAs with CT angiography or MR angiography followed longitudinally without treatment were studied. Unstable aneurysms were defined as those that grew or ruptured during follow-up. Aneurysms associated with stroke were defined as those associated with posterior circulation infarct at follow-up. Baseline data, including demographics, comorbidities, and aneurysm morphology and size were collected. Image based computational fluid dynamics models were created and run under pulsatile flow conditions. Relevant hemodynamic and geometric variables were calculated and compared between groups (stable vs unstable and no stroke vs stroke) using the Wilcoxon test., Results: A total of 37 VBDAs were included (24 stable, 13 unstable; 30 no stroke, 7 stroke). Unstable aneurysms had lower shear rates (P=0.05), blood flow velocity (P=0.03), and lower vorticity (P=0.049) than stable aneurysms. In addition, unstable aneurysms had higher mean oscillatory shear indices (P=0.001). There were no differences in the hemodynamic characteristics of aneurysms in the stroke group compared with the non-stroke group., Conclusion: This small study suggests there may be hemodynamic differences between unstable and stable VBDAs. Unstable VBDAs appear to be under lower flow conditions with lower velocity, vorticity, and shear rates, and have more oscillatory flow. There was no difference in the hemodynamic characteristics of aneurysms in the stroke and no stroke group., Competing Interests: Competing interests: WB: CEO of Marblehead Medical LLC and patents pending in balloon catheter technologies; consultant for Johnson and Johnson. DFK: President of Marblehead Medical LLC and patents pending in balloon catheter technologies., (© Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2018. All rights reserved. No commercial use is permitted unless otherwise expressly granted.)

Although rotary blood pumps (RBPs) sustain life, blood exposure to continuous supra-physiological shear stress induces adverse effects (e.g., thromboembolism); thus, pulsatile flow in RBPs represents a potential solution. The present study introduced pulsatile flow to the HeartWare HVAD using a custom-built controller and compared hemocompatibility biomarkers (i.e., platelet aggregation, concentrations for ADAMTS13, von Willebrand factor (vWf), and free-hemoglobin in plasma (pfHb), red blood cell (RBC) deformability, and RBC-nitric oxide synthase (NOS) activity) between continuous and pulsatile flow in a blood circulation loop over 5 h. The HeartWare HVAD was operated using a custom-built controller, at continuous speed (3282 rev/min) or in a pulsatile mode (mean speed = 3273 rev/min, amplitude = 430 rev/min, frequency = 1 Hz) to generate a blood flow rate of 5.0 L/min, HVAD differential pressure of 90 mm Hg for continuous flow and 92 mm Hg for pulsatile flow, and systolic and diastolic pressures of 121/80 mm Hg. For both flow regimes, the current study found; (i) ADP- and collagen-induced platelet aggregation, and ADAMTS13 concentration significantly decreased after 5 h (P < 0.01; P < 0.05), (ii) ristocetin-induced platelet aggregation significantly increased after 45 min (P < 0.05), (iii) vWf concentration did not significantly differ at any time point, (iv) pfHb significantly increased after 5 h (P < 0.01), (v) RBC deformability improved during the continuous flow regime (P < 0.05) but not during pulsatile flow, and (vi) RBC-NOS activity significantly increased during continuous flow (15 min), and pulsatile flow (5 h; P < 0.05). The current study demonstrated: (i) speed modulation does not improve hemocompatibility of the HeartWare HVAD based on no observable differences being detected for routine biomarkers, and (ii) the time-course for increased RBC-NOS activity observed during continuous flow may have improved RBC deformability., (© 2018 International Center for Artificial Organs and Transplantation and Wiley Periodicals, Inc.)

The objective of this study was to evaluate a pulsatile extracorporeal membrane oxygenation (ECMO) system in terms of hemodynamic energy generation and transmission under various pulsatile amplitudes, flow rates, and pseudopatient pressures in a simulated adult ECMO circuit. Surplus hemodynamic energy (SHE), a measure of the quality of pulsatility, was used to quantify pulsatile flow. The circuit consisted of an i-cor diagonal pump, an adult XLung oxygenator, a 21 Fr Medtronic Biomedicus femoral arterial cannula, a 23/25 Fr Sorin RAP femoral venous cannula, and 3/8 in ID tubing for both arterial and venous lines. The circuit was primed with lactated Ringer's solution and then packed red blood cells (hematocrit 37%). Trials were conducted at 36°C with flow rates of 2-5 L/min (1 L/min increments) under nonpulsatile and pulsatile mode with pulsatile amplitudes of 1000-5000 rpm (1000 rpm increments). The pseudopatient pressure was maintained at 40-100 mm Hg (20 mm Hg increments). Real-time pressure and flow data were recorded for analysis using a custom-made data acquisition system. There was no SHE generated by the pump under nonpulsatile mode. Under pulsatile mode, SHE levels increased with increasing pulsatile amplitude and pseudopatient pressure (P < 0.01) but decreased with increasing flow rate. SHE levels were significantly higher at flow rates of 2-4 L/min. In addition, the XLung oxygenator had acceptable pressure drops (36.1-104.9 mm Hg) and percentages of total hemodynamic energy loss (19.6-43.9%) during all trials. The novel pulsatile ECMO system can create nonpulsatile and pulsatile flow in an adult ECMO model. However, pulsatility gradually weakened with increasing flow rates. Pulsatile amplitude settings were found to have a great impact on pulsatility., (© 2018 International Center for Artificial Organs and Transplantation and Wiley Periodicals, Inc.)

Objective: To use 4D-flow MRI to characterize hemodynamics of transverse and sigmoid sinus in venous pulsatile tinnitus (PT) patients and to investigate their differences vs healthy controls., Methods: A total of 21 patients with venous PT and 11 healthy controls were included in the retrospective study. All participants underwent 4D-flow and magnetic resonance venography scan in a 3.0T magnetic resonance scanner. All visualization, quantification, and analysis of 4D-flow data were performed using dedicated software. Two independent reviewers evaluated the existence of vortex or turbulence. Covariance analysis adjusted for age was used to compare average through-plane velocity (V tp&#95;avg ), maximum through-plane velocity (V tp&#95;max ), average velocity (V avg ), maximum velocity (V max ), average blood flow (Flow avg ), and pulsatility index (PI) between PT and control group., Results: There were hemodynamic differences between PT patients and healthy controls. Compared with the control group, the PT group showed significantly higher V tp&#95;avg , V tp&#95;max , V avg , V max , and Flow avg , and slightly higher PI. For the assessment of flow pattern, inter-reader reproducibility was excellent (κ = 1.00). Vortex or turbulence was observed in PT patients with good sensitivity (86.4%) and specificity (90.9%). Drainage dominance was more frequently observed in patients (15/21, 71.4%) than healthy controls (4/11, 36.4%)., Conclusions: Significant hemodynamic differences were found between venous PT patients and healthy controls with 4D-flow MRI. Hemodynamic conditions could serve as noninvasive biomarkers for diagnosis and treatment evaluation of venous PT., Classification of Evidence: This study provides Class III evidence that 4D-flow MRI accurately identifies patients with venous PT., (© 2018 American Academy of Neurology.)

Pulsatility seems to have a teleological role because evolutionary hierarchy favors higher ordered animals with more complex, multichamber circulatory systems that generate higher pulse pressure compared with lower ordered animals. Yet despite years of such natural selection, the modern generation of continuous-flow left ventricular assist devices (CF-LVADs) that have been increasingly used for the last decade have created a unique physiology characterized by a nonpulsatile, nonlaminar blood flow profile with the absence of the usual large elastic artery Windkessel effect during diastole. Although outcomes and durability have improved with CF-LVADs, patients supported with CF-LVADs have a high rate of complications that were not as frequently observed with older pulsatile devices, including gastrointestinal bleeding from arteriovenous malformations, pump thrombosis, and stroke. Given the apparent fundamental biological role of the pulse, the purpose of this review is to describe the normal physiology of ventricular-arterial coupling from pulsatile flow, the effects of heart failure on this physiology and the vasculature, and to examine the effects of nonpulsatile blood flow on the vascular system and potential role in complications seen with CF-LVAD therapy. Understanding these concomitant vascular changes with CF-LVADs may be a key step in improving patient outcomes as modulation of pulsatility and flow characteristics may serve as a novel, yet simple, therapy for reducing complications., (© 2018 American Heart Association, Inc.)

In this paper, we investigate pulsatile flow through a constricted tube with the aim of assessing the effect of stenosis morphology on hemodynamic parameters. The fluid-solid interaction of pulsatile flow through a compliant tube with elastic walls was simulated using an arbitrary Lagrangian-Eulerian (ALE) finite-element method. We consider blood flow through various mild stenoses of 25.8% severity in diameter with trapezoidal and bell-like morphologies at a fixed Womersley number of 7.75. The results show that the distribution of the time-averaged wall shear stress (TAWSS), which is the main factor affecting the hemodynamic parameters, strongly depends on the axial stretch of the stenosis; elongation of the stenotic region increases by 41.1% the maximum TAWSS for stenoses of trapezoidal morphology whereas the maximum TAWSS decreases by 14.8% for the corresponding stenoses of bell-like morphology. The present findings indicate that risk factors due to atherosclerosis may vary in a complicated manner as an atheromatous plaque gradually builds up and morphs with time.

Purpose: Intracranial artery calcification (IAC) has been demonstrated to be correlated with ischemic stroke, cognitive decline, and other vascular events by accumulating evidences from both Western and Asian populations. The proposed study aimed to investigate its potential mechanisms by evaluating the blood flow velocity and pulsatility index (PI) of cerebral arteries., Methods: Consecutive ischemic stroke patients admitted to the Prince of Wales Hospital were recruited after excluding those with atrial fibrillation or poor temporal window. Quantitative measurements of IAC severity were assessed on brain CT scans. Transcranial Doppler (TCD) ultrasonography was performed to evaluate the blood flow velocity of the middle cerebral artery (MCA) and vertebral-basilar artery (VBA)., Results: In total, 318 patients were analyzed. Spearman's correlation analysis demonstrated both high MCA systolic flow velocity and high MCA PI were correlated with IAC Agatston score, p < 0.001 individually. Similar correlation was also found between IAC Agatston score and high VBA velocity/high VBA PI, p ≤ 0.001 individually. Multiple logistic regression analysis showed IAC Agatston score was an independent risk factor for high MCA velocity (OR 1.533; 95% CI 1.235-1.903), high VBA velocity (OR 1.964; 95% CI 1.381-2.794), and high VBA PI (OR 1.200; 95% CI 1.016-1.418), respectively., Conclusion: Heavier IAC might cause generalized artery flow velocity changes and increased pulsatility index, which may indicate high resistance within cerebrovasculature.

Purpose of Review: Concepts of pulsatile arterial haemodynamics, including relationships between oscillatory blood pressure and flow in systemic arteries, arterial stiffness and wave propagation phenomena have provided basic understanding of underlying haemodynamic mechanisms associated with elevated arterial blood pressure as a major factor of cardiovascular risk, particularly the deleterious effects of isolated systolic hypertension in the elderly. This topical review assesses the effects of pulsatility of blood pressure and flow in the systemic arteries on the brain. The review builds on the emerging notion of the "pulsating brain", taking into account the high throughput of blood flow in the cerebral circulation in the presence of mechanisms involved in ensuring efficient and regulated cerebral perfusion., Recent Findings: Recent studies have provided evidence of the relevance of pulsatility and hypertension in the following areas: (i) pressure and flow pulsatility and regulation of cerebral blood flow, (ii) cerebral and systemic haemodynamics, hypertension and brain pathologies (cognitive impairment, dementia, Alzheimer's disease), (iii) stroke and cerebral small vessel disease, (iv) cerebral haemodynamics and noninvasive estimation of cerebral vascular impedance, (v) cerebral and systemic pulsatile haemodynamics and intracranial pressure, (iv) response of brain endothelial cells to cyclic mechanical stretch and increase in amyloid burden. Studies to date, producing increasing epidemiological, clinical and experimental evidence, suggest a potentially significant role of systemic haemodynamic pulsatility on structure and function of the brain.

Ventricular assist devices (LVADs) are increasingly recognized for supporting blood circulation in heart failure patients who are non-transplant eligible. Because of its volume, the traditional pulsatile device is not easy to implant intracorporeally. Continuous flow LVADs (CF-LVADs) reduce arterial pulsatility and only offer continuous flow, which is different from physiological flow, and may cause long-term complications in the cardiovascular system. The aim of this study was to design a new pulsatile assist device that overcomes this disadvantage, and to test this device in the cardiovascular system. Firstly, the input and output characteristics of the new device were tested in a simple cardiovascular mock system. A detailed mathematical model was established by fitting the experimental data. Secondly, the model was tested in four pathological cases, and was simulated and coupled with a fifth-order cardiovascular system and a new device model using Matlab software. Using assistance of the new device, we demonstrated that the left ventricle pressure, aortic pressure, and aortic flow of heart failure patients improved to the levels of a healthy individual. Especially, in state IV level heart failure patients, the systolic blood pressure increased from 81.34 mmHg to 132.1 mmHg, whereas the diastolic blood pressure increased from 54.28 mmHg to 78.7 mmHg. Cardiac output increased from 3.21 L/min to 5.16 L/min. The newly-developed assist device not only provided a physiological flow that was similar to healthy individuals, but also effectively improved the ability of the pathological ventricular volume. Finally, the effects of the new device on other hemodynamic parameters are discussed.

The use of left ventricular assist devices (LVADs) has increased significantly over the past few years, in part because heart transplant activity has plateaued, but also because of the improving clinical outcomes with contemporary continuous-flow LVAD. As such, there is now a growing population of patients with continuous-flow LVADs. Management of these patients is complicated by the altered circulatory physiology, because continuous-flow LVADs provide a parallel circulation from the heart to the aorta, which interacts with the native left heart (systemic) circulation with consequent effects on the right heart circulation. In addition, the displayed pump parameters can mislead the unwary clinician. An understanding of LVAD physiology can guide clinicians in the management of patients with LVADs. This review describes the basic design of axial and centrifugal continuous-flow LVADs, the functional anatomy and physiology of continuous-flow LVADs, and the interaction between the heart and the LVAD. leading to a discussion about the interpretation of the pump parameters in clinical practice., (Copyright © 2016 Elsevier Inc. All rights reserved.)

We hypothesized that increased aortic forward pressure wave amplitude (Pf), which is determined by characteristic impedance (Zc) in the proximal aorta, is the primary hemodynamic determinant of obesity-associated higher left ventricular (LV) mass in adolescents. Aortic pulsatile hemodynamics were measured noninvasively in 60 healthy adolescents (age 14-19 years; 42% male; 50% black) by sequential recordings of pulse waveforms via tonometry, brachial blood pressure, and pulsed Doppler and diameter of the LV outflow tract using 2-dimensional echocardiography. Adolescents who were overweight/obese (n=23; age 16.0±0.3 years; body mass index ≥85th percentile) had higher LV mass index, brachial and carotid systolic blood pressure and pulse pressure, normalized Zc and Pf compared with adolescents with healthy weight (n=37; 16.7±0.3 years; body mass index <85th percentile, all P<0.01). In contrast, there was no difference in mean or diastolic blood pressure, carotid-femoral pulse wave velocity, carotid augmentation index, or aortic backward wave amplitude (all P>0.05). Stepwise multiple linear regression analysis that included age, sex, race, normalized Zc, and brachial systolic blood pressure revealed that body mass index (B±SE; 0.49±0.20, P=0.02, R 2 =0.26), aortic Pf (0.22±0.07; P<0.02, R 2 change=0.11), and cardiac output (2.82±1.02, P<0.01; R 2 change=0.08) were significant correlates of LV mass index (total R 2 =0.44, P<0.01). These findings suggest that higher aortic Pf is a major hemodynamic determinant of increased LV mass in adolescents with elevated adiposity. Improper matching between aortic diameter and pulsatile flow during early systole potentially contributes to the early development of LV hypertrophy in childhood obesity., (© 2016 American Heart Association, Inc.)

Cerebral blood flow, arterial pulsation, and vasomotion play important roles in the transport of waste metabolites out of the brain. Impaired vasomotion results in reduced driving force for the perivascular/glymphatic clearance of beta-amyloid. Noninvasive cerebrovascular characteristic features that potentially assess these transport mechanisms are mean blood flow (MBF) and pulsatility index (PI). In this study, 4D flow MRI was used to measure intra-cranial flow features, particularly MBF, PI, resistive index (RI) and cross-sectional area in patients with Alzheimer's disease (AD), mild cognitive impairment and in age matched and younger cognitively healthy controls. Three-hundred fourteen subjects participated in this study. Volumetric, time-resolved phase contrast (PC) MRI data were used to quantify hemodynamic parameters from 11 vessel segments. Anatomical variants of the Circle of Willis were also cataloged. The AD population reported a statistically significant decrease in MBF and cross-sectional area, and also an increase in PI and RI compared to age matched cognitively healthy control subjects. The 4D flow MRI technique used in this study provides quantitative measurements of intracranial vessel geometry and the velocity of flow. Cerebrovascular characteristics features of vascular health such as pulsatility index can be extracted from the 4D flow MRI data., (© The Author(s) 2015.)

Background/aims: Cirrhosis causes a decrease in cerebral blood flow because of a hyperdynamic circulatory state. We aimed to study the cerebral hemodynamic parameters in patients with decompensated cirrhosis and their relationship to the Child-Pugh and Model for End-Stage Liver Disease (MELD) scores., Materials and Methods: We used transcranial Doppler to investigate the cerebral hemodynamic parameters, namely the mean flow velocity of the middle cerebral artery, pulsatility index (PI), and resistive index (RI), in 50 patients who had decompensated cirrhosis and in a control group of 50 healthy people. We also investigated their relationship to the Child-Pugh and MELD scores., Results: Patients with cirrhosis had a lower mean flow velocity than those in the control group. Further, patients with cirrhosis had higher PI and RI values. There was a positive correlation between PI and the Child-Pugh score. In addition, there was a positive correlation among PI, RI, and the MELD score. The RI values of patients with ascites were higher than those of patients without ascites., Conclusion: Cerebral autoregulation might be impaired in patients with cirrhosis. Cerebral resistance proportionally increases to disease severity. There was a positive correlation among PI, RI, and MELD scores, which means that transcranial Doppler might be useful not only in the follow-up of the severity of the disease but also in determining the survival of these patients.

It remains uncertain whether intensive antihypertensive therapy can normalize pulsatile hemodynamics resulting in minimized residual cardiovascular risks. In this study, office and 24-hour ambulatory systolic blood pressure (SBP), diastolic blood pressure (DBP), pulse pressure, carotid-femoral pulse wave velocity (PWV), and forward (Pf) and reflected (Pb) pressure wave from a decomposed carotid pressure wave were measured in hypertensive participants. Among them, 57 patients whose 24-hour SBP and DBP were normalized by three or more classes of antihypertensive medications were included. Another 57 age- and sex-matched normotensive participants were randomly selected from a community survey. The well-treated hypertensive patients had similar 24-hour SBP, lower DBP, and higher PP values. The treated patients had higher PWV (11.7±0.3 vs 8.3±0.2 m/s, P<.001), Pf, Pb, Pb/Pf, and left ventricular mass index values. After adjustment for age, sex, body mass index, and office SBP, the differences for PWV, Pb, and Pb/Pf remained significant. Hypertensive patients whose 24-hour SBP and DBP are normalized may still have markedly increased arterial stiffness and wave reflection., (© 2015 Wiley Periodicals, Inc.)

Implantation of a total artificial heart (TAH) is one of the therapeutic options for the treatment of patients with end-stage biventricular heart failure. There is no report on the hemodynamics of the functional centrifugal-flow TAH with functional atrial contraction (fCFTAH). We evaluated the effects of pulsatile flow by atrial contraction in acute animal models. The goats received fCFTAH that we created from two centrifugal-flow ventricular assist devices. Some hemodynamic parameters maintained acceptable levels: heart rate 115.5 ± 26.3 bpm, aortic pressure 83.5 ± 10.1 mmHg, left atrial pressure 18.0 ± 5.9 mmHg, pulmonary pressure 28.5 ± 9.7 mmHg, right atrial pressure 13.6 ± 5.2 mmHg, pump flow 4.0 ± 1.1 L/min (left) 3.9 ± 1.1 L/min (right), and cardiac index 2.13 ± 0.14 L/min/m(2). fCFTAH with atrial contraction was able to maintain the TAH circulation by forming a pulsatile flow in acute animal experiments. Taking the left and right flow rate balance using the low internal pressure loss of the VAD pumps may be easier than by other pumps having considerable internal pressure loss. We showed that the remnant atrial contraction effected the flow rate change of the centrifugal pump, and the atrial contraction waves reflected the heart rate. These results indicate that remnant atria had the possibility to preserve autonomic function in fCFTAH. We may control fCFTAH by reflecting the autonomic function, which is estimated with the flow rate change of the centrifugal pump.

Background: Current-generation left ventricular assist devices provide circulatory support that is minimally or entirely nonpulsatile and are associated with marked increases in muscle sympathetic nerve activity (MSNA), likely through a baroreceptor-mediated pathway. We sought to determine whether the restoration of pulsatile flow through modulations in pump speed would reduce MSNA through the arterial baroreceptor reflex., Methods and Results: Ten men and 3 women (54 ± 14 years) with Heartmate II continuous-flow left ventricular assist devices underwent hemodynamic and sympathetic neural assessment. Beat-to-beat blood pressure, carotid ultrasonography at the level of the arterial baroreceptors, and MSNA via microneurography were continuously recorded to determine steady-state responses to step changes (200-400 revolutions per minute) in continuous-flow left ventricular assist device pump speed from a maximum of 10,480 ± 315 revolutions per minute to a minimum of 8500 ± 380 revolutions per minute. Reductions in pump speed led to increases in pulse pressure (high versus low speed: 17 ± 7 versus 26 ± 12 mm Hg; P<0.01), distension of the carotid artery, and carotid arterial wall tension (P<0.05 for all measures). In addition, MSNA was reduced (high versus low speed: 41 ± 15 versus 33 ± 16 bursts per minute; P<0.01) despite a reduction in mean arterial pressure and was inversely related to pulse pressure (P=0.037)., Conclusions: Among subjects with continuous-flow left ventricular assist devices, the restoration of pulsatile flow through modulations in pump speed leads to increased distortion of the arterial baroreceptors with a subsequent decline in MSNA. Additional study is needed to determine whether reduction of MSNA in this setting leads to improved outcomes., (© 2015 American Heart Association, Inc.)

Normally, central elastic arteries (e.g., aorta and common carotid artery) effectively buffer cardiac pulsation-induced flow/pressure fluctuations. With advancing age, arterial stiffening deteriorates this function and produces the greater cerebral hemodynamic pulsatility that impacts vulnerable brain tissue. It is well known that the buffering function of the central artery is improved by regular aerobic exercise, but the influence of endurance training on the pulsatile component of cerebral hemodynamics remains poorly understood. To characterize the functional role of the central artery at the heart-brain hemodynamic connection comprehensively, we assessed relations among the endurance training-induced changes in the left ventricle (LV), carotid arterial compliance, and cerebral hemodynamics. Thirteen collegiate tennis players (20 ± 1 yr) underwent a 16-wk endurance training intervention designed for improving cardiovascular function. Expectedly, maximal oxygen uptake (V̇o2peak), LV ejection velocity (via Doppler ultrasound), and the maximal rate of pressure increase of estimated aortic pressure waveform (via general transfer function) improved after the training intervention, whereas middle cerebral arterial (MCA) hemodynamics (via transcranial Doppler), such as mean and pulsatile flow velocities, remained unchanged. Carotid arterial compliance (via ultrasound and applanation tonometry) increased after the training intervention, and a larger increase in carotid arterial compliance was significantly associated with the greater attenuations of pulsatile MCA velocity (r = -0.621) normalized by mean MCA velocity. These results suggest that the training-induced improvement of carotid artery Windkessel function might offset the expected increase in the pulsatile component of cerebral perfusion induced by the enhanced LV systolic function., (Copyright © 2015 the American Physiological Society.)

A powerful alternative means to study the hemodynamics of bileaflet mechanical heart valves is the computational fluid dynamics method. It is well recognized that computational fluid dynamics allows reliable physiological blood flow simulation and measurements of flow parameters. To date, in almost all of the modeling studies on the hemodynamics of bileaflet mechanical heart valves, a velocity (mass flow)-based boundary condition and an axisymmetric geometry for the aortic root have been assigned, which, to some extent, are erroneous. Also, there have been contradictory reports of the profile of velocity in downstream of leaflets, that is, in some studies, it is suggested that the maximum blood velocity occurs in the lateral orifice, and in some other studies, it is postulated that the maximum velocities in the main and lateral orifices are identical. The reported values for the peak velocities range from 1 to 3 m/s, which highly depend on the model assumptions. The objective of this study is to demonstrate the importance of the exact anatomical model of the aortic root and the realistic boundary conditions in the hemodynamics of the bileaflet mechanical heart valves. The model considered in this study is based on the St Jude Medical valve in a novel modeling platform. Through a more realistic geometrical model for the aortic root and the St Jude Medical valve, we have developed a new set of boundary conditions in order to be used for the assessment of the hemodynamics of aortic bileaflet mechanical heart valves. The results of this study are significant for the design improvement of conventional bileaflet mechanical heart valves and for the design of the next generation of prosthetic valves., (© IMechE 2015.)

Various clinical observations reported that swirling blood flow is a normal physiological flow pattern in various vasculatures. The swirling flow has beneficial effects on blood circulation through the blood vessels. It enhances oxygen transfer and reduces low-density lipoprotein concentration in the blood vessel by enhancing cross-plane mixing of the blood. However, the fluid-dynamic roles of the swirling flow are not yet fully understood. In this study, inhibition of material deposition at the post-stenosis region by the swirling flow was observed. To reveal the underlying fluid-dynamic characteristics, pathline flow visualization and time-resolved particle image velocimetry measurements were conducted. Results showed that the swirling inlet flow increased the development of vortices at near wall region of the post-stenosis, which can suppress further development of stenosis by enhancing transport and mixing of the blood flow. The fluid-dynamic characteristics obtained in this study would be useful for improving hemodynamic characteristics of vascular grafts and stents in which the stenosis frequently occurred. Moreover, the time-resolved particle image velocimetry measurement technique and vortex identification method employed in this study would be useful for investigating the fluid-dynamic effects of the swirling flow on various vascular environments., (© IMechE 2015.)

The objective of this study is to evaluate three different diameters of arterial tubing and three diameters of arterial cannulae in terms of pressure drop, and hemodynamic energy delivery in simulated neonatal/pediatric cardiopulmonary bypass (CPB) circuits. The CPB circuit consisted of a Terumo Capiox Baby FX05 oxygenator (Terumo Corporation, Tokyo, Japan), arterial tubing (1/4 in, 3/16 in, or 1/8 in × 150 cm), and a Medtronic Bio-Medicus arterial cannula (8, 10, or 12 Fr; Medtronic, Inc., Minneapolis, MN, USA). The pseudo patient's pressure was maintained at 50 mm Hg. The circuit was primed using lactated Ringer's solution and heparinized packed human red blood cells (hematocrit 30%). Trials were conducted at different flow rates and temperatures (35 and 28°C). Flow and pressure data were collected using a custom-based data acquisition system. Using 8 Fr arterial cannula at 500 mL/min, small diameter arterial tubing generated higher circuit pressure (294.6 ± 0.1 mm Hg [1/8 in], 213.5 ± 0.5 mm Hg [3/16 in], 208.4 ± 0.4 mm Hg [1/4 in] at 35°C) and arterial line pressure drop (158.3 ± 0.1 mm Hg [1/8 in], 79.6 ± 0.1 mm Hg [3/16 in], 62.1 ± 0.1 mm Hg [1/4 in] at 35°C). Using 10 Fr arterial cannula at 1000 mL/min, pre-oxygenator pressures were 266.8 ± 0.2 mm Hg (3/16 in) and 248.0 ± 0.3 mm Hg (1/4 in); arterial line pressure drops were 111.6 ± 0.0 mm Hg (3/16 in) and 74.0 ± 0.1 mm Hg (1/4 in) at 35°C. When using 12 Fr arterial cannula at 1500 mL/min, preoxygenator pressures reached 324.4 ± 0.3 mm Hg (3/16 in) and 302.5 ± 0.4 mm Hg (1/4 in); arterial line pressure drops were 154.0 ± 0.1 mm Hg (3/16 in) and 92.0 ± 0.2 mm Hg (1/4 in) at 35°C. Pressure drops across arterial line tubing were main CPB circuit pressure drops. High flow rate, hypothermia, small diameter arterial tubing. and arterial cannula created more hemodynamic energy at the preoxygenator site, but energy loss across CPB circuit also increased. Although small diameter (<1/4 in ID) arterial tubing may decrease total CPB priming volume, it also led to significantly higher circuit pressure, higher pressure drop, and more hemodynamic energy loss across CPB circuit. Larger diameter arterial cannula had less pressure drop and allowed more hemodynamic energy delivery to the patient., (Copyright © 2015 International Center for Artificial Organs and Transplantation and Wiley Periodicals, Inc.)

In the modern era, stroke remains a main cause of morbidity after cardiac surgery despite continuing improvements in the cardiopulmonary bypass (CPB) techniques. The aim of the current work was to numerically investigate the blood flow in aorta and epiaortic vessels during standard and pulsed CPB, obtained with the intra-aortic balloon pump (IABP). A multi-scale model, realized coupling a 3D computational fluid dynamics study with a 0D model, was developed and validated with in vivo data. The presence of IABP improved the flow pattern directed towards the epiaortic vessels with a mean flow increase of 6.3% and reduced flow vorticity.

Arrhythmias are a frequent complication during extracorporeal life support (ECLS). A new ECLS system can provide pulsatile flow synchronized to the patient's intrinsic cardiac cycle based upon the R wave of the electrocardiogram (ECG). It is unclear how the occurrence of arrhythmias may alter the hemodynamic performance of the system. This in vitro study evaluated the effect of simulated arrhythmias on hemodynamics during R wave-triggered pulsatile ECLS. The ECLS circuit with an i-cor diagonal pump and iLA membrane ventilator was primed with whole blood at room temperature. Flow and pressure data were collected at 2.5 and 4 L/min for each condition using a customized data acquisition system. Pulsatile ECLS flow was R wave synchronized to an ECG simulator using 1:1, 1:2, and 1:3 assist ratios. Conditions tested included sinus rhythm at 45 and 90 bpm, supraventricular tachycardia (SVT), ventricular tachycardia (VT), and irregular rhythms such as ventricular fibrillation. Pulsatile mode was successfully triggered by ECG signals of normal sinus rhythm, SVT, VT, atrial fibrillation, atrial flutter, and ventricular bigeminy with assist ratios 1:1, 1:2, and 1:3. Regular rhythm at 90 bpm generated the best surplus hemodynamic energy (SHE). For SVT and VT, an assist ratio of 1:2 resulted in maximum pulsatile flow waveforms with optimal SHE at 2.5 L/min flow rate. At 4 L/min, SHE declined and the pressure drop increased independent of arrhythmia condition. Irregular rhythms still produced adequate pulsatile wave forms at lower pulsatile frequency. This study demonstrated the feasibility of generating pulsatile ECLS flow with the novel ECG-synchronized i-cor system during various simulated rhythms. The optimal rate for pulsatile flow was 90 bpm. During irregular rhythms, the lower pulsatile frequency was the more reliable synchronization mode for generating pulsatile flow., (Copyright © 2015 International Center for Artificial Organs and Transplantation and Wiley Periodicals, Inc.)

The objective of this study is to investigate the impact of every component of extracorporeal life support (ECLS) circuit on hemodynamic energy transmission in terms of energy equivalent pressure (EEP), total hemodynamic energy (THE), and surplus hemodynamic energy (SHE) under nonpulsatile and pulsatile modes in a novel ECLS system. The ECLS circuit consisted of i-cor diagonal pump and console (Xenios AG, Heilbronn, Germany), an iLA membrane ventilator (Xenios AG), an 18 Fr femoral arterial cannula, a 23/25 Fr femoral venous cannula, and 3/8-in ID arterial and venous tubing. The circuit was primed with lactated Ringer's solution and human whole blood (hematocrit 33%). All trials were conducted under room temperature at the flow rates of 1-4 L/min (1 L/min increments). The pulsatile flow settings were set at pulsatile frequency of 75 beats per minute and differential speed values of 1000-4000 rpm (1000 rpm increments). Flow and pressure data were collected using a custom-based data acquisition system. EEP was significantly higher than mean arterial pressure in all experimental conditions under pulsatile flow (P < 0.01). THE was also increased under pulsatile flow compared with the nonpulsatile flow (P < 0.01). Under pulsatile flow conditions, SHE was significantly higher and increased differential rpm resulted in significantly higher SHE (P < 0.01). There was no SHE generated under nonpulsatile flow. Energy loss depending on the circuit components was almost similar in both perfusion modes at all different flow rates. The pressure drops across the oxygenator were 3.8-24.9 mm Hg, and the pressure drops across the arterial cannula were 19.3-172.6 mm Hg at the flow rates of 1-4 L/min. Depending on the pulsatility setting, i-cor ECLS system generates physiological quality pulsatile flow without increasing the mean circuit pressure. The iLA membrane ventilator is a low-resistance oxygenator, and allows more hemodynamic energy to be delivered to the patient under pulsatile mode. The 18 Fr femoral arterial cannula has acceptable pressure drops under nonpulsatile and pulsatile modes. Further in vivo studies are warranted to confirm these results., (Copyright © 2015 International Center for Artificial Organs and Transplantation and Wiley Periodicals, Inc.)