•WSS-based quantities represent convenient surrogates of LDL uptake.•WSS contraction regions co-localize with LDL concentration polarization profiles.•WSS contraction regions can be identified by the ...normalized WSS divergence.•A trade-off between cost and accuracy is achieved using the normalized WSS divergence.
Near-wall transport of low-density lipoproteins (LDL) in arteries plays a relevant role in the initiation of atherosclerosis. Although it can be modelled in silico by coupling the Navier–Stokes equations with the 3D advection-diffusion (AD) equation, the associated computational cost is high. As wall shear stress (WSS) represents a first-order approximation of the near-wall velocity in arteries, we aimed at identifying computationally convenient WSS-based quantities to infer LDL near-wall transport based on the underlying near-wall hemodynamics in five models of three human arterial districts (aorta, carotid bifurcations, coronary arteries). The simulated LDL transport and its WSS-based surrogates were qualitatively compared with in vivo longitudinal measurements of wall thickness growth on the coronary artery models.
Numerical simulations of blood flow coupled with AD equations for LDL transport and blood-wall transfer were performed. The co-localization of the simulated LDL concentration polarization patterns with luminal surface areas characterized by low cycle-average WSS, near-wall flow stagnation and WSS attracting patterns was quantitatively assessed by the similarity index (SI). In detail, the latter two represent features of the WSS topological skeleton, obtained respectively through the Lagrangian tracking of surface-born particles, and the Eulerian analysis of the divergence of the normalized cycle-average WSS vector field.
Convergence of the solution of the AD problem required the simulation of 3 (coronary artery) to 10 (aorta) additional cardiac cycles with respect to the Navier-Stokes problem. Co-localization results underlined that WSS topological skeleton features indicating near-wall flow stagnation and WSS attracting patterns identified LDL concentration polarization profiles more effectively than low WSS, as indicated by higher SI values (SI range: 0.17–0.50 for low WSS; 0.24–0.57 for WSS topological skeleton features). Moreover, the correspondence between the simulated LDL uptake and WSS-based quantities profiles with the in vivo measured wall thickness growth in coronary arteries appears promising.
The recently introduced Eulerian approach for identifying WSS attracting patterns from the divergence of normalized WSS provides a computationally affordable template of the LDL polarization at the arterial blood-wall interface without simulating the AD problem. It thus candidates as an effective biomechanical tool for elucidating the mechanistic link amongst LDL transfer at the arterial blood-wall interface, WSS and atherogenesis.
Aortic wall shear stress (WSS) distributions in bicuspid aortic valve (BAV) patients have been associated with aortic dilatation, but prospective, longitudinal data are missing. This study assessed ...differences in aortic WSS distributions between BAV patients and healthy controls and determined the association of WSS with aortic growth in patients.
Sixty subjects underwent four-dimensional (4D) flow cardiovascular magnetic resonance of the thoracic aorta (32 BAV patients and 28 healthy controls). Peak velocity, pulse wave velocity, aortic distensibility, peak systolic WSS (magnitude, axial, and circumferential), and WSS angle were assessed. WSS angle is defined as the angle between the WSSmagnitude and WSSaxial component. In BAV patients, three-year computed tomography angiography-based aortic volumetric growth was determined in the proximal and entire ascending aorta. WSSaxial was significantly lower in BAV patients compared with controls (0.93 vs. 0.72 Pa, P = 0.047) and WSScircumferential and WSS angle were significantly higher (0.29 vs. 0.64 Pa and 18° vs. 40°, both P < 0.001). Significant volumetric growth of the proximal ascending aorta occurred in BAV patients (from 49.1 to 52.5 cm3, P = 0.003). In multivariable analysis corrected for baseline aortic volume and diastolic blood pressure, WSS angle was the only parameter independently associated with proximal aortic growth (P = 0.031). In the entire ascending aorta, besides the WSS angle, the WSSmagnitude was also independently associated with growth.
Increased WSScircumferential and especially WSS angle are typical in BAV patients. WSS angle was found to predict aortic growth. These findings highlight the potential role of WSS measurements in BAV patients to stratify patients at risk for aortic dilation.
Statins represent a key treatment for cardiovascular disease. Nevertheless, the direct effects of statin treatment on the composition of atherosclerotic plaques remain elusive.
We aimed to ...investigate the association of statin treatment with the presence of different plaque components located in the carotid arteries within a population-based setting.
From the population-based Rotterdam Study, 1740 participants with carotid atherosclerosis (mean age 72.9 years, 46% women) underwent MRI of the carotid arteries to determine the presence of calcification, lipid core, and intraplaque hemorrhage. Information for the duration and dosage of statin use was obtained from pharmacy records for all participants. We used logistic regression models to study the association of statin use with the presence of plaque components.
Statin treatment was associated with a higher presence of calcification (OR: 1.73 95% CI: 1.22–2.44). Longer duration of use strengthened this association (OR: 1.82 95% CI: 1.00–3.33 for 10 to 48 months, and OR 1.74 95% CI: 1.09–2.77 for >48 months, compared to OR: 1.65 95% CI: 0.94–2.89 for ≤10 months). Current statin treatment was also associated with a lower presence of lipid core (OR: 0.66 95% CI: 0.42–1.04), but only when using statins for 10 months or less. Any dosage of statins was associated with a higher presence of calcification, whilst only high dosages (DDD > 1.33) were associated with a lower presence of lipid core.
Active, high-dosage statin use seems to beneficially influence the composition of carotid atherosclerosis by shifting the composition from vulnerable plaque with a lipid core to more stable calcified plaque.
•How the use of statins is associated with atherosclerotic plaque composition in the carotid artery, is unknown.•The statin use was associated with a higher presence of calcification and lower presence of lipid core.•Duration and daily dosage of statin use play an important role in the plaque remodeling process and plaque morphology•Statins produce observable changes in the plaque and can alter plaque morphology into a stable plaque phenotype.
Abstract
OBJECTIVES
Adequacy of 16–20mm extracardiac conduits for adolescent Fontan patients remains unknown. This study aims to evaluate conduit adequacy using the inferior vena cava (IVC)–conduit ...velocity mismatch factor along the respiratory cycle.
METHODS
Real-time 2D flow MRI was prospectively acquired in 50 extracardiac (16–20mm conduits) Fontan patients (mean age 16.9 ± 4.5 years) at the subhepatic IVC, conduit and superior vena cava. Hepatic venous flow was determined by subtracting IVC flow from conduit flow. The cross-sectional area (CSA) was reported for each vessel. Mean flow and velocity was calculated during the average respiratory cycle, inspiration and expiration. The IVC–conduit velocity mismatch factor was determined as follows: Vconduit/VIVC, where V is the mean velocity.
RESULTS
Median conduit CSA and IVC CSA were 221 mm2 (Q1–Q3 201–255) and 244 mm2 (Q1–Q3 203–265), respectively. From the IVC towards the conduit, flow rates increased significantly due to the entry of hepatic venous flow (IVC 1.9, Q1–Q3 1.5–2.2) versus conduit (3.3, Q1–Q3 2.5–4.0 l/min, P < 0.001). Consequently, mean velocity significantly increased (IVC 12 (Q1–Q3 11–14 cm/s) versus conduit 25 (Q1–Q3 17–31 cm/s), P < 0.001), resulting in a median IVC–conduit velocity mismatch of 1.8 (Q1–Q3 1.5–2.4), further augmenting during inspiration (median 2.3, Q1–Q3 1.8–3.0). IVC–conduit mismatch was inversely related to measured conduit size and positively correlated with conduit flow. The normalized IVC–conduit velocity mismatch factor during expiration and the entire respiratory cycle correlated with peak VO2 (r = –0.37, P = 0.014 and r = –0.31, P = 0.04, respectively).
CONCLUSIONS
Important blood flow accelerations are observed from the IVC towards the conduit in adolescent Fontan patients, which is related to peak VO2. This study, therefore, raises concerns that implanted 16–20mm conduits have become undersized for older Fontan patients and future studies should clarify its effect on long-term outcome.
The Fontan procedure provides a palliative solution for single-ventricle patients, by connecting both the superior vena cava (SVC) and inferior vena cava (IVC) directly to the pulmonary arteries i.e.
Abstract Wall shear stress (WSS), the frictional force between blood and endothelium, is an important determinant of vascular function. It is generally assumed that WSS remains constant at a ...reference value of 15 dyn/cm2 . In a study of small rodents, we realized that this assumption could not be valid. This review presents an overview of recent studies in large and small animals where shear stress was measured, derived from velocity measurements or otherwise, in large vessels. The data show that large variations exist within a single species (human: variation of 2–16 N/m2 ). Moreover, when we compared different species at the same location within the arterial tree, an inverse relationship between animal size and wall shear stress was noted. When we related WSS to diameter, a unique relationship was derived for all species studied. This relationship could not be described by the well-known r3 law of Murray, but by the r2 law introduced by Zamir et al. in 1972. In summary, by comparing data from the literature, we have shown that: (i) the assumption of a physiological WSS level of ∼15 dyn/cm2 for all straight vessels in the arterial tree is incorrect; (ii) WSS is not constant throughout the vascular tree; (iii) WSS varies between species; (iv) WSS is inversely related to the vessel diameter. These data support an “ r2 law” rather than Murray's r3 law for the larger vessels in the arterial tree.
Abstract
Aims
Low wall shear stress (WSS) is acknowledged to play a role in plaque development through its influence on local endothelial function. Also, lipid-rich plaques (LRPs) are associated with ...endothelial dysfunction. However, little is known about the interplay between WSS and the presence of lipids with respect to plaque progression. Therefore, we aimed to study the differences in WSS-related plaque progression between LRPs, non-LRPs, or plaque-free regions in human coronary arteries.
Methods and results
In the present single-centre, prospective study, 40 patients who presented with an acute coronary syndrome successfully underwent near-infrared spectroscopy intravascular ultrasound (NIRS-IVUS) and optical coherence tomography (OCT) of at least one non-culprit vessel at baseline and completed a 1-year follow-up. WSS was computed applying computational fluid dynamics to a three-dimensional reconstruction of the coronary artery based on the fusion of the IVUS-segmented lumen with a CT-derived centreline, using invasive flow measurements as boundary conditions. For data analysis, each artery was divided into 1.5 mm/45° sectors. Plaque growth based on IVUS-derived percentage atheroma volume change was compared between LRPs, non-LRPs, and plaque-free wall segments, as assessed by both OCT and NIRS. Both NIRS- and OCT-detected lipid-rich sectors showed a significantly higher plaque progression than non-LRPs or plaque-free regions. Exposure to low WSS was associated with a higher plaque progression than exposure to mid or high WSS, even in the regions classified as a plaque-free wall. Furthermore, low WSS and the presence of lipids had a synergistic effect on plaque growth, resulting in the highest plaque progression in lipid-rich regions exposed to low shear stress.
Conclusion
This study demonstrates that NIRS- and OCT-detected lipid-rich regions exposed to low WSS are subject to enhanced plaque growth over a 1-year follow-up. The presence of lipids and low WSS proves to have a synergistic effect on plaque growth.
Graphical Abstract
Graphical Abstract
Endothelial shear stress (ESS) identifies coronary plaques at high risk for progression and/or rupture leading to a future acute coronary syndrome. In this study an optimized methodology was ...developed to derive ESS, pressure drop and oscillatory shear index using computational fluid dynamics (CFD) in 3D models of coronary arteries derived from non-invasive coronary computed tomography angiography (CTA). These CTA-based ESS calculations were compared to the ESS calculations using the gold standard with fusion of invasive imaging and CTA. In 14 patients paired patient-specific CFD models based on invasive and non-invasive imaging of the left anterior descending (LAD) coronary arteries were created. Ten patients were used to optimize the methodology, and four patients to test this methodology. Time-averaged ESS (TAESS) was calculated for both coronary models applying patient-specific physiological data available at the time of imaging. For data analysis, each 3D reconstructed coronary artery was divided into 2 mm segments and each segment was subdivided into 8 arcs (45°).TAESS and other hemodynamic parameters were averaged per segment as well as per arc. Furthermore, the paired segment- and arc-averaged TAESS were categorized into patient-specific tertiles (low, medium and high). In the ten LADs, used for optimization of the methodology, we found high correlations between invasively-derived and non-invasively-derived TAESS averaged over segments (
n
= 263,
r
= 0.86) as well as arcs (
n
= 2104,
r
= 0.85,
p
< 0.001). The correlation was also strong in the four testing-patients with
r
= 0.95 (
n
= 117 segments,
p
= 0.001) and
r
= 0.93 (
n
= 936 arcs,
p
= 0.001).There was an overall high concordance of 78% of the three TAESS categories comparing both methodologies using the segment- and 76% for the arc-averages in the first ten patients. This concordance was lower in the four testing patients (64 and 64% in segment- and arc-averaged TAESS). Although the correlation and concordance were high for both patient groups, the absolute TAESS values averaged per segment and arc were overestimated using non-invasive vs. invasive imaging testing patients: TAESS segment: 30.1(17.1–83.8) vs. 15.8(8.8–63.4) and TAESS arc: 29.4(16.2–74.7) vs 15.0(8.9–57.4)
p
< 0.001. We showed that our methodology can accurately assess the TAESS distribution non-invasively from CTA and demonstrated a good correlation with TAESS calculated using IVUS/OCT 3D reconstructed models.
Treatment of coronary bifurcation lesions remains an ongoing challenge for interventional cardiologists. Stenting of coronary bifurcations carries higher risk for in-stent restenosis, stent ...thrombosis, and recurrent clinical events. This review summarizes the current evidence regarding application and use of biomechanical modeling in the study of stent properties, local flow dynamics, and outcomes after percutaneous coronary interventions in bifurcation lesions. Biomechanical modeling of bifurcation stenting involves computational simulations and in vitro bench testing using subject-specific arterial geometries obtained from in vivo imaging. Biomechanical modeling has the potential to optimize stenting strategies and stent design, thereby reducing adverse outcomes. Large-scale clinical studies are needed to establish the translation of pre-clinical findings to the clinical arena.
In an adult porcine model of familial hypercholesterolemia (FH), coronary plaque development was characterized. To elucidate the underlying mechanisms of the observed inter-individual variation in ...disease severity, detailed lipoprotein profiles were determined. Approach and Results: FH pigs (3 years old, homozygous
R84C mutation) received an atherogenic diet for 12 months. Coronary atherosclerosis development was monitored using serial invasive imaging and histology. A pronounced difference was observed between mildly diseased pigs which exclusively developed early lesions (maximal plaque burden, 25% 23%-34%; n=5) and advanced-diseased pigs (n=5) which developed human-like, lumen intruding plaques (maximal plaque burden, 69% 57%-77%) with large necrotic cores, intraplaque hemorrhage, and calcifications. Advanced-diseased pigs and mildly diseased pigs displayed no differences in conventional risk factors. Additional plasma lipoprotein profiling by size-exclusion chromatography revealed 2 different LDL (low-density lipoprotein) subtypes: regular and larger LDL. Cholesterol, sphingosine-1-phosphate, ceramide, and sphingomyelin levels were determined in these LDL-subfractions using standard laboratory techniques and high-pressure liquid chromatography mass-spectrometry analyses, respectively. At 3 months of diet, regular LDL of advanced-diseased pigs contained relatively more cholesterol (LDL-C; regular/larger LDL-C ratio 1.7 1.3-1.9 versus 0.8 0.6-0.9;
=0.008) than mildly diseased pigs, while larger LDL contained more sphingosine-1-phosphate, ceramides, and sphingomyelins. Larger and regular LDL was also found in plasma of 3 patients with homozygous FH with varying LDL-C ratios.
In our adult FH pig model, inter-individual differences in atherosclerotic disease severity were directly related to the distribution of cholesterol and sphingolipids over a distinct LDL profile with regular and larger LDL shortly after the diet start. A similar LDL profile was detected in patients with homozygous FH.
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