Blood vessels are exposed to multiple mechanical forces that are exerted on the vessel wall (radial, circumferential and longitudinal forces) or on the endothelial surface (shear stress). The ...stresses and strains experienced by arteries influence the initiation of atherosclerotic lesions, which develop at regions of arteries that are exposed to complex blood flow. In addition, plaque progression and eventually plaque rupture is influenced by a complex interaction between biological and mechanical factors-mechanical forces regulate the cellular and molecular composition of plaques and, conversely, the composition of plaques determines their ability to withstand mechanical load. A deeper understanding of these interactions is essential for designing new therapeutic strategies to prevent lesion development and promote plaque stabilization. Moreover, integrating clinical imaging techniques with finite element modelling techniques allows for detailed examination of local morphological and biomechanical characteristics of atherosclerotic lesions that may be of help in prediction of future events. In this ESC Position Paper on biomechanical factors in atherosclerosis, we summarize the current 'state of the art' on the interface between mechanical forces and atherosclerotic plaque biology and identify potential clinical applications and key questions for future research.
Atherosclerotic plaques are found at distinct locations in the arterial system, despite the exposure to systemic risk factors of the entire vascular tree. From the study of arterial bifurcation ...regions, emerges ample evidence that haemodynamics are involved in the local onset and progression of the atherosclerotic disease. This observed co-localisation of disturbed flow regions and lesion prevalence at geometrically predisposed districts such as arterial bifurcations has led to the formulation of a 'haemodynamic hypothesis', that in this review is grounded to the most current research concerning localising factors of vascular disease. In particular, this review focuses on carotid and coronary bifurcations because of their primary relevance to stroke and heart attack. We highlight reported relationships between atherosclerotic plaque location, progression and composition, and fluid forces at vessel's wall, in particular shear stress and its 'easier-to-measure' surrogates, i.e. vascular geometric attributes (because geometry shapes the flow) and intravascular flow features (because they mediate disturbed shear stress), in order to give more insight in plaque initiation and destabilisation. Analogous to Virchow's triad for thrombosis, atherosclerosis must be thought of as subject to a triad of, and especially interactions among, haemodynamic forces, systemic risk factors, and the biological response of the wall.
Wall shear stress (WSS) and oscillatory shear index (OSI) are associated with atherosclerotic disease. Both parameters are derived from blood velocities, which can be measured with phase-contrast MRI ...(PC-MRI). Limitations in spatiotemporal resolution of PC-MRI are known to affect these measurements. Our aim was to investigate the effect of spatiotemporal resolution using a carotid artery phantom.
A carotid artery phantom was connected to a flow set-up supplying pulsatile flow. MRI measurement planes were placed at the common carotid artery (CCA) and internal carotid artery (ICA). Two-dimensional PC-MRI measurements were performed with thirty different spatiotemporal resolution settings. The MRI flow measurement was validated with ultrasound probe measurements. Mean flow, peak flow, flow waveform, WSS and OSI were compared for these spatiotemporal resolutions using regression analysis. The slopes of the regression lines were reported in %/mm and %/100ms. The distribution of low and high WSS and OSI was compared between different spatiotemporal resolutions.
The mean PC-MRI CCA flow (2.5±0.2mL/s) agreed with the ultrasound probe measurements (2.7±0.02mL/s). Mean flow (mL/s) depended only on spatial resolution (CCA:-13%/mm, ICA:-49%/mm). Peak flow (mL/s) depended on both spatial (CCA:-13%/mm, ICA:-17%/mm) and temporal resolution (CCA:-19%/100ms, ICA:-24%/100ms). Mean WSS (Pa) was in inverse relationship only with spatial resolution (CCA:-19%/mm, ICA:-33%/mm). OSI was dependent on spatial resolution for CCA (-26%/mm) and temporal resolution for ICA (-16%/100ms). The regions of low and high WSS and OSI matched for most of the spatiotemporal resolutions (CCA:30/30, ICA:28/30 cases for WSS; CCA:23/30, ICA:29/30 cases for OSI).
We show that both mean flow and mean WSS are independent of temporal resolution. Peak flow and OSI are dependent on both spatial and temporal resolution. However, the magnitude of mean and peak flow, WSS and OSI, and the spatial distribution of OSI and WSS did not exhibit a strong dependency on spatiotemporal resolution.
Abstract
Aims
Atherosclerotic plaque development has been associated with wall shear stress (WSS). However, the multidirectionality of blood flow, and thus of WSS, is rarely taken into account. The ...purpose of this study was to comprehensively compare five metrics that describe (multidirectional) WSS behaviour and assess how WSS multidirectionality affects coronary plaque initiation and progression.
Methods and results
Adult familial hypercholesterolaemic pigs (n = 10) that were fed a high-fat diet, underwent imaging of the three main coronary arteries at three-time points 3 (T1), 9 (T2), and 10–12 (T3) months. Three-dimensional geometry of the arterial lumen, in combination with local flow velocity measurements, was used to calculate WSS at T1 and T2. For analysis, arteries were divided into 3 mm/45° sectors (n = 3648). Changes in wall thickness and final plaque composition were assessed with near-infrared spectroscopy–intravascular ultrasound, optical coherence tomography imaging, and histology. Both in pigs with advanced and mild disease, the highest plaque progression rate was exclusively found at low time-averaged WSS (TAWSS) or high multidirectional WSS regions at both T1 and T2. However, the eventually largest plaque growth was located in regions with initial low TAWSS or high multidirectional WSS that, over time, became exposed to high TAWSS or low multidirectional WSS at T2. Besides plaque size, also the presence of vulnerable plaque components at the last time point was related to low and multidirectional WSS. Almost all WSS metrics had good predictive values for the development of plaque (47–50%) and advanced fibrous cap atheroma (FCA) development (59–61%).
Conclusion
This study demonstrates that low and multidirectional WSS promote both initiation and progression of coronary atherosclerotic plaques. The high-predictive values of the multidirectional WSS metrics for FCA development indicate their potential as an additional clinical marker for the vulnerable disease.
Graphical Abstract
Graphical Abstract
Abstract Local hemodynamics has been identified as one main determinant in the onset and progression of atherosclerotic lesions at coronary bifurcations. Starting from the observation that ...atherosensitive hemodynamic conditions in arterial bifurcation are majorly determined by the underlying anatomy, the aim of the present study is to investigate how peculiar coronary bifurcation anatomical features influence near-wall and intravascular flow patterns. Different bifurcation angles and cardiac curvatures were varied in population-based, idealized models of both stenosed and unstenosed bifurcations, representing the left anterior descending (LAD) coronary artery with its diagonal branch. Local hemodynamics was analyzed in terms of helical flow and exposure to low/oscillatory shear stress by performing computational fluid dynamics simulations. Results show that bifurcation angle impacts lowly hemodynamics in both stenosed and unstenosed cases. Instead, curvature radius influences the generation and transport of helical flow structures, with smaller cardiac curvature radius associated to higher helicity intensity. Stenosed bifurcation models exhibit helicity intensity values one order of magnitude higher than the corresponding unstenosed cases. Cardiac curvature radius moderately affects near-wall hemodynamics of the stenosed cases, with smaller curvature radius leading to higher exposure to low shear stress and lower exposure to oscillatory shear stress. In conclusion, the proposed controlled benchmark allows to investigate the effect of various geometrical features on local hemodynamics at the LAD/diagonal bifurcation, highlighting that cardiac curvature influences near wall and intravascular hemodynamics, while bifurcation angle has a minor effect.
Arterial hemodynamics is markedly characterized by the presence of helical flow patterns. Previous observations suggest that arterial helical blood flow is of physiological significance, and that its ...quantitative analysis holds promise for clinical applications. In particular, it has been reported that distinguishable helical flow patterns are potentially atheroprotective in the carotid bifurcation as they suppress flow disturbances. In this context, there is a knowledge gap about the physiological significance of helical flow in coronary arteries, a prominent site of atherosclerotic plaque formation. This study aimed at the quantitative assessment of helical blood flow in coronary arteries, and to investigate its possible associations with vascular geometry and with atherogenic wall shear stress (WSS) phenotypes in a representative sample of 30 swine coronary arteries. This study demonstrates that in coronary arteries: (1) the hemodynamics is characterized by counter-rotating bi-helical flow structures; (2) unfavorable conditions of WSS are strongly and inversely associated with helicity intensity (
r
= − 0.91;
p
< 0.001), suggesting an atheroprotective role for helical flow in the coronary tree; (3) vascular torsion dictates helical flow features (
r
= 0.64;
p
< 0.001). The findings of this work support future studies on the role of helical flow in atherogenesis in coronary arteries.
The heterogeneity of plaque formation, the vascular remodelling response to plaque formation, and the consequent phenotype of plaque instability attest to the extraordinarily complex pathobiology of ...plaque development and progression, culminating in different clinical coronary syndromes. Atherosclerotic plaques predominantly form in regions of low endothelial shear stress (ESS), whereas regions of moderate/physiological and high ESS are generally protected. Low ESS-induced compensatory expansive remodelling plays an important role in preserving lumen dimensions during plaque progression, but when the expansive remodelling becomes excessive promotes continued influx of lipids into the vessel wall, vulnerable plaque formation and potential precipitation of an acute coronary syndrome. Advanced plaques which start to encroach into the lumen experience high ESS at their most stenotic region, which appears to promote plaque destabilization. This review describes the role of ESS from early atherogenesis to early plaque formation, plaque progression to advanced high-risk stenotic or non-stenotic plaque, and plaque destabilization. The critical implication of the vascular remodelling response to plaque growth is also discussed. Current developments in technology to characterize local ESS and vascular remodelling in vivo may provide a rationale for innovative diagnostic and therapeutic strategies for coronary patients that aim to prevent clinical coronary syndromes.
Atherosclerosis has been associated with near-wall hemodynamics and wall shear stress (WSS). However, the role of coronary intravascular hemodynamics, in particular of the helical flow (HF) patterns ...that physiologically develop in those arteries, is rarely considered.
The purpose of this study was to assess how HF affects coronary plaque initiation and progression, definitively demonstrating its atheroprotective nature.
The three main coronary arteries of five adult hypercholesterolemic mini-pigs on a high fat diet were imaged by computed coronary tomography angiography (CCTA) and intravascular ultrasound (IVUS) at 3 (T1, baseline) and 9.4 ± 1.9 (T2) months follow-up. The baseline geometries of imaged coronary arteries (n = 15) were reconstructed, and combined with pig-specific boundary conditions (based on in vivo Doppler blood flow measurements) to perform computational fluid dynamic simulations. Local wall thickness (WT) was measured on IVUS images at T1 and T2, and its temporal changes were assessed. Descriptors of HF and WSS nature were computed for each model, and statistically compared to WT data.
HF intensity was strongly positively associated with WSS magnitude (p < 0.001). Overall, coronary segments exposed to high baseline levels of HF intensity exhibited a significantly lower WT growth (p < 0.05), compared to regions with either mid or low HF intensity.
This study confirms the physiological significance of HF in coronary arteries, revealing its protective role against atherosclerotic WT growth and its potential in predicting regions undergoing WT development. These findings support future in vivo measurement of coronary HF as atherosclerotic risk marker, overcoming current limitations of in vivo WSS assessment.
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•In coronaries, blood flow helicity is strongly associated with wall shear stress.•Exposure to high helicity intensity levels resulted in low wall thickness growth.•Helical blood flow has a protective role against coronary atherosclerosis.
Stent deployment following balloon angioplasty is used routinely to treat coronary artery disease. These interventions cause damage and loss of endothelial cells (EC), and thus promote in-stent ...thrombosis and restenosis. Injured arteries are repaired (intrinsically) by locally derived EC and by circulating endothelial progenitor cells which migrate and proliferate to re-populate denuded regions. However, re-endothelialization is not always complete and often dysfunctional. Moreover, the molecular and biomechanical mechanisms that control EC repair and function in stented segments are poorly understood. Here, we propose that stents modify endothelial repair processes, in part, by altering fluid shear stress, a mechanical force that influences EC migration and proliferation. A more detailed understanding of the biomechanical processes that control endothelial healing would provide a platform for the development of novel therapeutic approaches to minimize damage and promote vascular repair in stented arteries.
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