BACKGROUND: Non-alcoholic fatty liver disease (NAFLD) is estimated to affect approximately 25% of the global population. Both, coronary artery disease and NAFLD are linked to underlying insulin resistance and inflammation as drivers of the disease. Coronary flow reserve parameters, including coronary flow reserve velocity (CFRV), baseline diastolic peak flow velocity (DPFV), and hyperemic DPFV, are noninvasive markers of coronary microvascular circulation. The existing literature contains conflicting findings regarding these parameters in NAFLD patients.
METHODS: A comprehensive systematic search was conducted on major electronic databases from inception until May 8, 2024, to identify relevant studies. We pooled the standardized mean differences (SMD) with 95% confidence intervals (CI) using the inverse-variance random-effects model. Statistical significance was set at P < .05.
RESULTS: Four studies with 1139 participants (226 with NAFLD and 913 as controls) were included. NAFLD was associated with a significantly lower CFRV (SMD: -0.77; 95% CI: -1.19, -0.36; P < .0002) and hyperemic DPFV (SMD: -0.73; 95% CI: -1.03, -0.44; P < .00001) than the controls. NAFLD demonstrated a statistically insignificant trend toward a reduction in baseline DPFV (SMD: -0.09; 95% CI: -0.38, 0.19; P = .52) compared to healthy controls.
CONCLUSIONS: Patients with NAFLD are at a higher risk of coronary microvascular dysfunction, as demonstrated by reduced CFRV and hyperemic DPFV. The presence of abnormal coronary flow reserve in patients with NAFLD provides insights into the higher rates of cardiovascular disease in these patients. Early aggressive targeted interventions for impaired coronary flow reserve in subjects with NAFLD may lead to improvement in clinical outcomes.

Previous studies report contradicting age-related neurovascular coupling (NVC). Few studies assess postural effects, but less investigate relationships between age and NVC within different postures. Therefore, this study investigated the effect of age on NVC in different postures with varying cognitive stimuli. Beat-to-beat blood pressure, heart rate and end-tidal carbon dioxide were assessed alongside middle and posterior cerebral artery velocities (MCAv and PCAv, respectively) using transcranial Doppler ultrasonography in 78 participants (31 young-, 23 middle- and 24 older-aged) with visuospatial (VST) and attention tasks (AT) in various postures at two timepoints (T2 and T3). Between-group significance testing utilized one-way analysis-of-variance (ANOVA) (Tukey post-hoc). Mixed three-way/one-way ANOVAs explored task, posture, and age interactions. Significant effects of posture on NVC were driven by a 3.8% increase from seated to supine. For AT, mean supine %MCAv increase was greatest in younger (5.44%) versus middle (0.12%) and older-age (0.09%) at T3 (p = 0.005). For VST, mean supine %PCAv increase was greatest at T2 and T3 in middle (10.99%/10.12%) and older-age (17.36%/17.26%) versus younger (9.44%/8.89%) (p = 0.004/p = 0.002). We identified significant age-related NVC effects with VST-induced hyperactivation. This may reflect age-related compensatory processes in supine. Further work is required, using complex stimuli while standing/walking, examining NVC, aging and falls.

Numerical simulation of blood flow is a challenging topic due to the multiphase nature of this biological fluid. The choice of a specific method among the ones available in literature is often motivated by the physical scale of interest. Single-phase approximation allows for lower computational time, but does not consider this multiphase nature. Cell-level simulation, on the other hand, requires high computational resources and is limited to small scales. This work proposes a scale-up approach for cell-level simulation of blood flow, in the framework of unresolved CFD-DEM technique. This method offers the possibility to simulate hundreds of thousands of particles with limited computational effort, but requires specific models for fluid-particle interactions. Regarding blood flow, drag and lift force acting on the red blood cells (RBCs) are responsible for several macroscopic blood characteristics. Despite several correlations available for drag and lift force acting on rigid particles, specific force models for the simulation of deformable particles compatible with RBCs physics are missing. This study employs data obtained from cell-level simulations to derive equations then used in unresolved simulation of RBCs. The strategy followed during the modeling phase is presented, together with the model verification and validation. This approach returns satisfying results when used to simulate blood flow in large-scale channels. Up to half a million RBCs are considered, and computational effort is reported to allow a comparison with other existing methods. Future perspectives include further improvement of the model, such as a deeper understanding of particle-particle interactions.

Flow fluctuations have emerged as a promising hemodynamic metric for understanding of hemodynamics in intracranial aneurysms. Several investigations have reported flow instabilities using numerical tools. In this study, the occurrence of flow fluctuations is investigated using either Newtonian or non-Newtonian fluid models in five patient-specific intracranial aneurysms using high-resolution lattice Boltzmann simulation methods. Flow instabilities are quantified by computing power spectral density, proper orthogonal decomposition, and fluctuating kinetic energy of velocity fluctuations. Our simulations reveal substantial flow instabilities in two of the ruptured aneurysms, where the pulsatile inflow through the neck leads to hydrodynamic instability, particularly around the rupture position, throughout the entire cardiac cycle. In other monitoring points, the flow instability is primarily observed during the deceleration phase; typically, the fluctuations begin just after peak systole, gradually decay, and the flow returns to its original, laminar pulsatile state during diastole. Additionally, we assess the rheological impact on flow dynamics. The disparity between Newtonian and non-Newtonian outcomes remains minimal in unruptured aneurysms, with less than a 5% difference in key metrics. However, in ruptured cases, adopting a non-Newtonian model yields a substantial increase in the fluctuations within the aneurysm sac, with up to a 30% higher fluctuating kinetic energy compared to the Newtonian model. The study highlights the importance of using appropriate high-resolution simulations and non-Newtonian models to capture flow fluctuation characteristics that may be critical for assessing aneurysm rupture risk.

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Blood flow reconstruction in the vasculature is important for many clinical applications. However, in clinical settings, the available data are often quite limited. For instance, transcranial Doppler ultrasound is a non-invasive clinical tool that is commonly used in clinical settings to measure blood velocity waveforms at several locations. This amount of data is grossly insufficient for training machine learning surrogate models, such as deep neural networks or Gaussian process regression. In this work, we propose a Gaussian process regression approach based on empirical kernels constructed by data generated from physics-based simulations-enabling near-real-time reconstruction of blood flow in data-poor regimes. We introduce a novel methodology to reconstruct the kernel within the vascular network. The proposed kernel encodes both spatiotemporal and vessel-to-vessel correlations, thus enabling blood flow reconstruction in vessels that lack direct measurements. We demonstrate that any prediction made with the proposed kernel satisfies the conservation of mass principle. The kernel is constructed by running stochastic one-dimensional blood flow simulations, where the stochasticity captures the epistemic uncertainties, such as lack of knowledge about boundary conditions and uncertainties in vasculature geometries. We demonstrate the performance of the model on three test cases, namely, a simple Y-shaped bifurcation, abdominal aorta and the circle of Willis in the brain.

BACKGROUND: Aortic conduit and reservoir functions can be directly measured by four-dimensional flow (4D flow) cardiovascular magnetic resonance (CMR).
METHODS: Twenty healthy controls (10 young and 10 age-gender-matched old controls) and 20 patients with heart failure with preserved ejection fraction (HFpEF) were recruited. All had 4D flow CMR. Flow was quantified at the ascending and descending aorta levels. In addition, at the ascending aorta level, we quantified systolic flow displacement (FDs) and systolic flow reversal ratio (sFRR). The aortic conduit function was defined as the relative drop in systolic flow from the ascending to the descending aorta (∆Fs). Aortic reservoir function was defined as descending aortic diastolic stroke volume (DAo SVd).
RESULTS: Both ∆Fs (R=0.51, p=0.001) and DAo SVd (R=-0.68, p=0.001) were significantly associated with ageing. Native T1 (R=0.51, p=0.001) and extracellular volume (R=0.51, p=0.001) showed maximum association with ∆Fs. ∆Fs significantly increased in HFpEF versus age-gender-matched controls (41±8% vs 52±12%, p=0.02). In multiple regression, only ∆Fs and DAo SVd were independent predictors of the estimated glomerular filtration rate (model R=0.77, p=0.0001). FDs was significantly associated with ∆Fs (R=0.4, p=0.01) and DAo SVd (R=-0.48, p=0.002), whereas sFRR was mainly associated with DAo SVd (R=-0.46, p=0.003).
CONCLUSIONS: Both aortic conduit and reservoir function decline with age and this decline in aortic function is also independently associated with renal functional decline. Ascending aortic turbulent flow signatures are associated with loss of aortic conduit and reservoir functions. Finally, in HFpEF, aortic conduit and reservoir function demonstrate progressive decline.
BACKGROUND: NCT05114785.

Platelet aggregation is a dynamic process that can obstruct blood flow, leading to cardiovascular diseases. While many studies have demonstrated clear connections between shear rate and platelet aggregation, the impact of flow-derived mechanical signals on this process is not fully understood. The objective of this work is to investigate the role of flow conditions on platelet aggregation dynamics, including effects on growth, shape, density composition, and their potential correlation with binding processes that are characterised by longer (e.g., via αIIbβ3 integrin) and shorter (e.g., via VWF) initial binding times. In vitro blood perfusion experiments were conducted at wall shear rates of 800, 1600 and 4000 s-1. Detailed analysis of two modalities of experimental images was performed to offer insights into the morphology of platelet aggregates. A consistent structural pattern was observed across all samples: a high-density core enveloped by a low-density outer shell. An image-based 3D computational blood flow model was subsequently employed to study the local flow conditions, including binding availability time and flow-derived mechanical signals via shear rate and rate of elongation. The results show substantial dependence of the aggregation dynamics on these flow parameters. We found that the different binding mechanisms that prefer different flow regimes do not have a monotonic cross-over in efficiency as the flow increases. There is a significant dip in the cumulative aggregation potential in-between the preferred regimes. The results suggest that treatments targeting the biomechanical pathways could benefit from creating conditions that exploit these low-efficiency zones of aggregation.

OBJECTIVE: Our study aimed to investigate the effects of different extracorporeal membrane oxygenation (ECMO) blood flow rates on lung perfusion assessment using the saline bolus-based electrical impedance tomography (EIT) technique in patients on veno-venous (VV) ECMO.
METHODS: In this single-centered prospective physiological study, patients on VV ECMO who met the ECMO weaning criteria were assessed for lung perfusion using saline bolus-based EIT at various ECMO blood flow rates (gradually decreased from 4.5 L/min to 3.5 L/min, 2.5 L/min, 1.5 L/min, and finally to 0 L/min). Lung perfusion distribution, dead space, shunt, ventilation/perfusion matching, and recirculation fraction at different flow rates were compared.
RESULTS: Fifteen patients were included. As the ECMO blood flow rate decreased from 4.5 L/min to 0 L/min, the recirculation fraction decreased significantly. The main EIT-based findings were as follows. (1) Median lung perfusion significantly increased in region-of-interest (ROI) 2 and the ventral region [38.21 (34.93-42.16)% to 41.29 (35.32-43.75)%, p = 0.003, and 48.86 (45.53-58.96)% to 54.12 (45.07-61.16)%, p = 0.037, respectively], whereas it significantly decreased in ROI 4 and the dorsal region [7.87 (5.42-9.78)% to 6.08 (5.27-9.34)%, p = 0.049, and 51.14 (41.04-54.47)% to 45.88 (38.84-54.93)%, p = 0.037, respectively]. (2) Dead space significantly decreased, and ventilation/perfusion matching significantly increased in both the ventral and global regions. (3) No significant variations were observed in regional and global shunt.
CONCLUSIONS: During VV ECMO, the ECMO blood flow rate, closely linked to recirculation fraction, could affect the accuracy of lung perfusion assessment using hypertonic saline bolus-based EIT.

Vascular diseases are greatly influenced by the hemodynamic parameters and the accuracy of determining these parameters depends on the use of correct boundary conditions. The present work carries out a two-way fluid-structure interaction (FSI) simulation to investigate the effects of outlet pressure boundary conditions on the hemodynamics through the left coronary artery bifurcation with moderate stenosis (50%) in the left anterior descending (LAD) branch. The Carreau viscosity model is employed to characterise the shear-thinning behaviour of blood. The results of the study reveal that the employment of zero pressure at the outlet boundaries significantly overestimates the values of hemodynamic variables like wall shear stress (WSS), and time-averaged wall shear stress (TAWSS) compared with human healthy and pulsatile pressure outlet conditions. However, the difference between these variables is marginally low for human healthy and pulsatile pressure outlets. The oscillatory shear index (OSI) remains the same across all scenarios, indicating independence from the outlet boundary condition. Furthermore, the magnitude of negative axial velocity and pressure drop across the plaque are found to be higher at the zero pressure outlet boundary condition.