The definition of low wall shear stress and its effect on plaque progression estimation in human coronary arteries

Wall shear stress (WSS), the frictional force of the blood on the vessel wall, plays a crucial role in atherosclerotic plaque development. Low WSS has been associated with plaque growth, however previous research used different approaches to define low WSS to investigate its effect on plaque progression. In this study, we used four methodologies to allocate low, mid and high WSS in one dataset of human coronary arteries and investigated the predictive power of low WSS for plaque progression. Coronary reconstructions were based on multimodality imaging, using intravascular ultrasound and CT-imaging. Vessel-specific flow was measured using Doppler wire and computational fluid dynamics was performed to calculate WSS. The absolute WSS range varied greatly between the coronary arteries. On the population level, the established pattern of most plaque progression at low WSS was apparent in all methodologies defining the WSS categories. However, for the individual patient, when using measured flow to determine WSS, the absolute WSS values range so widely, that the use of absolute thresholds to determine low WSS was not appropriate to identify regions at high risk for plaque progression

Aortic geometry and long-term outcome in patients with a repaired coarctation

Objective This study aims to compare aortic morphology between repaired coarctation patients and controls, and to identify aortic morphological risk factors for hypertension and cardiovascular events (CVEs) in coarctation patients. Methods Repaired coarctation patients with computed tomography angiography (CTA) or magnetic resonance angiography (MRA) were included, followed-up and compared with sex-matched and age-matched controls. Three-dimensional aortic shape was reconstructed using patients' CTA or MRA, or four-dimensional flow cardiovascular magnetic resonance in controls, and advanced geometrical characteristics were calculated and visualised using statistical shape modelling. In patients, we examined the association of geometrical characteristics with (1) baseline hypertension, using multivariable logistic regression; and (2) cardiovascular events (CVE, composite of aortic complications, coronary artery disease, ventricular arrhythmias, heart failure hospitalisation, stroke, transient ischaemic attacks and cardiovascular death), using multivariable Cox regression. The least absolute shrinkage and selection operator (LASSO) method selected the most informative multivariable model. Results Sixty-five repaired coarctation patients (23 years (IQR 19-38)) were included, of which 44 (68%) patients were hypertensive at baseline. After a median follow-up of 8.7 years (IQR 4.8-15.4), 27 CVEs occurred in 20 patients. Aortic arch dimensions were smaller in patients compared with controls (diameter p&lt;0.001, wall surface area p=0.026, volume p=0.007). Patients had more aortic arch torsion (p&lt;0.001) and a higher curvature (p&lt;0.001). No geometrical characteristics were associated with hypertension. LASSO selected left ventricular mass, male sex, tortuosity and age for the multivariable model. Left ventricular mass (p=0.014) was independently associated with CVE, and aortic tortuosity showed a trend towards significance (p=0.070). Conclusion Repaired coarctation patients have a smaller aortic arch and a more tortuous course of the aorta compared with controls. Besides left ventricular mass index, geometrical features might be of importance in long-term risk assessment in coarctation patients.</p

Aortic geometry and long-term outcome in patients with a repaired coarctation

Objective This study aims to compare aortic morphology between repaired coarctation patients and controls, and to identify aortic morphological risk factors for hypertension and cardiovascular events (CVEs) in coarctation patients. Methods Repaired coarctation patients with computed tomography angiography (CTA) or magnetic resonance angiography (MRA) were included, followed-up and compared with sex-matched and age-matched controls. Three-dimensional aortic shape was reconstructed using patients' CTA or MRA, or four-dimensional flow cardiovascular magnetic resonance in controls, and advanced geometrical characteristics were calculated and visualised using statistical shape modelling. In patients, we examined the association of geometrical characteristics with (1) baseline hypertension, using multivariable logistic regression; and (2) cardiovascular events (CVE, composite of aortic complications, coronary artery disease, ventricular arrhythmias, heart failure hospitalisation, stroke, transient ischaemic attacks and cardiovascular death), using multivariable Cox regression. The least absolute shrinkage and selection operator (LASSO) method selected the most informative multivariable model. Results Sixty-five repaired coarctation patients (23 years (IQR 19-38)) were included, of which 44 (68%) patients were hypertensive at baseline. After a median follow-up of 8.7 years (IQR 4.8-15.4), 27 CVEs occurred in 20 patients. Aortic arch dimensions were smaller in patients compared with controls (diameter p&lt;0.001, wall surface area p=0.026, volume p=0.007). Patients had more aortic arch torsion (p&lt;0.001) and a higher curvature (p&lt;0.001). No geometrical characteristics were associated with hypertension. LASSO selected left ventricular mass, male sex, tortuosity and age for the multivariable model. Left ventricular mass (p=0.014) was independently associated with CVE, and aortic tortuosity showed a trend towards significance (p=0.070). Conclusion Repaired coarctation patients have a smaller aortic arch and a more tortuous course of the aorta compared with controls. Besides left ventricular mass index, geometrical features might be of importance in long-term risk assessment in coarctation patients.</p

Identifying lipid traces of atherogenic mechanisms in human carotid plaque

Background and aims: Lipids play an important role in atherosclerotic plaque development and are interesting candidate predictive biomarkers. However, the link between circulating lipids, accumulating lipids in the vessel wall, and plaque destabilization processes in humans remains largely unknown. This study aims to provide new insights into the role of lipids in atherosclerosis using lipidomics and mass spectrometry imaging to investigate lipid signatures in advanced human carotid plaque and plasma samples. Methods: We used lipidomics and desorption electrospray ionization mass spectrometry imaging (DESI-MSI) to investigate lipid signatures of advanced human carotid plaque and plasma obtained from patients who underwent carotid endarterectomy (n = 14 out of 17 whose plaque samples were analyzed by DESI-MSI). Multivariate data analysis and unsupervised clustering were applied to identify lipids that were the most discriminative species between different patterns in plaque and plasma. These patterns were interpreted by quantitative comparison with conventional histology. Results: Lipidomics detected more than 300 lipid species in plasma and plaque, with markedly different relative abundances. DESI-MSI visualized the spatial distribution of 611 lipid-related m/z features in plaques, of which 330 m/z features could be assigned based on exact mass, comparison to the lipidomic data, and high mass resolution MSI. Matching spatial lipid patterns to histological areas of interest revealed several molecular species that were colocalized with pertinent disease processes in plaque including specific sphingomyelin and ceramide species with calcification, phospholipids and free fatty acids with inflammation, and triacylglycerols and phosphatidylinositols with fibrin-rich areas.Conclusions: By comparing lipid species in plaque and plasma, we identified those circulating species that were also prominently present in plaque. Quantitative comparison of lipid spectral patterns with histology revealed the presence of specific lipid species in destabilized plaque areas, corroborating previous in vitro and animal studies.</p

Mechanical wall stress and wall shear stress are associated with atherosclerosis development in non-calcified coronary segments

Background and aims: Atherosclerotic plaque onset and progression are known to be affected by local biomechanical factors. While the role of wall shear stress (WSS) has been studied, the impact of another biomechanical factor, namely mechanical wall stress (MWS), remains poorly understood. In this study, we investigated the association of MWS, independently and combined with WSS, towards atherosclerosis in coronary arteries. Methods: Thirty-four human coronary arteries were analyzed using near-infrared spectroscopy intravascular ultrasound (NIRS-IVUS) and optical coherence tomography (OCT) at baseline and after 12 months. Baseline WSS and MWS were calculated using computational models, and wall thickness (ΔWT) and lipid-rich necrotic core size (ΔLRNC) change were measured in non-calcified coronary segments. The arteries were further divided into 1.5 mm/45° sectors and categorized as plaque-free or plaque sectors. For each category, associations between biomechanical factors (WSS &amp; MWS) and changes in coronary wall (ΔWT &amp; ΔLRNC) were studied using linear mixed models. Results: In plaque-free sectors, higher MWS (p &lt; 0.001) was associated with greater vessel wall growth. Plaque sectors demonstrated wall thickness reduction over time, likely due to medical therapy, where higher levels of WSS and WMS, individually and combined, (p &lt; 0.05) were associated with a greater reduction. Sectors with low MWS combined with high WSS demonstrated the highest LRNC increase (p &lt; 0.01). Conclusions:In this study, we investigated the association of the (largely-overlooked) biomechanical factor MWS with coronary atherosclerosis, individually and combined with WSS. Our results demonstrated that both MWS and WSS significantly correlate with atherosclerotic plaque initiation and development.</p

Micro Spectroscopic Photoacoustic (μsPA) imaging of advanced carotid atherosclerosis

Atherosclerosis is a lipid-driven and an inflammatory disease of the artery walls. The composition of atherosclerotic plaque stratifies the risk of a specific plaque to cause a cardiovascular event. In an optical resolution photoacoustic microscopy setup, of 45 μm resolution, we extracted plaque lipid photoacoustic (PA) spectral signatures of human endarterectomy samples in the range of 1150–1240 nm, using matrix assisted laser desorption ionization mass spectrometry imaging as a reference. We found plaque PA signals to correlate best with sphingomyelins and cholesteryl esters. PA signal spectral variations within the plaque area were compared to reference molecular patterns and absorption spectra of lipid laboratory standards. Variability in the lipid spectroscopic features extracted by principal component analysis of all samples revealed three distinct components with peaks at: 1164, 1188, 1196 and 1210 nm. This result will guide the development of PA-based atherosclerosis disease staging capitalizing on lipidomics of atherosclerotic tissue

Wall shear stress angle is associated with aortic growth in bicuspid aortic valve patients

Aims 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. Methods and results 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. Conclusion 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

Spatial lipidomics of coronary atherosclerotic plaque development in a familial hypercholesterolemia swine model

Coronary atherosclerosis is caused by plaque build-up, with lipids playing a pivotal role in its progression. However, lipid composition and distribution within coronary atherosclerosis remain unknown. This study aims to characterize lipids and investigate differences in lipid composition across disease stages to aid in the understanding of disease progression. Matrix-assisted laser desorption/ionization mass spectrometry imaging (MALDI-MSI) was used to visualize lipid distributions in coronary artery sections (n = 17) from hypercholesterolemic swine. We performed histology on consecutive sections to classify the artery segments and to investigate colocalization between lipids and histological regions of interest in advanced plaque, including necrotic core and inflammatory cells. Segments were classified as healthy (n = 6), mild (n = 6), and advanced disease (n = 5) artery segments. Multivariate data analysis was employed to find differences in lipid composition between the segment types, and the lipids' spatial distribution was investigated using non-negative matrix factorization (NMF). Through this process, MALDI-MSI detected 473 lipid-related features. NMF clustering described three components in positive ionization mode: triacylglycerides (TAG), phosphatidylcholines (PC), and cholesterol species. In negative ionization mode, two components were identified: one driven by phosphatidylinositol(PI)(38:4), and one driven by ceramide-phosphoethanolamine(36:1). Multivariate data analysis showed the association between advanced disease and specific lipid signatures like PC(O-40:5) and cholesterylester(CE)(18:2). Ether-linked phospholipids and LysoPC species were found to colocalize with necrotic core, and mostly CE, ceramide, and PI species colocalized with inflammatory cells. This study, therefore, uncovers distinct lipid signatures correlated with plaque development and their colocalization with necrotic core and inflammatory cells, enhancing our understanding of coronary atherosclerosis progression

Mechanical wall stress and wall shear stress are associated with atherosclerosis development in non-calcified coronary segments

Background and aims: Atherosclerotic plaque onset and progression are known to be affected by local biomechanical factors. While the role of wall shear stress (WSS) has been studied, the impact of another biomechanical factor, namely mechanical wall stress (MWS), remains poorly understood. In this study, we investigated the association of MWS, independently and combined with WSS, towards atherosclerosis in coronary arteries. Methods: Thirty-four human coronary arteries were analyzed using near-infrared spectroscopy intravascular ultrasound (NIRS-IVUS) and optical coherence tomography (OCT) at baseline and after 12 months. Baseline WSS and MWS were calculated using computational models, and wall thickness (ΔWT) and lipid-rich necrotic core size (ΔLRNC) change were measured in non-calcified coronary segments. The arteries were further divided into 1.5 mm/45° sectors and categorized as plaque-free or plaque sectors. For each category, associations between biomechanical factors (WSS &amp; MWS) and changes in coronary wall (ΔWT &amp; ΔLRNC) were studied using linear mixed models. Results: In plaque-free sectors, higher MWS (p &lt; 0.001) was associated with greater vessel wall growth. Plaque sectors demonstrated wall thickness reduction over time, likely due to medical therapy, where higher levels of WSS and WMS, individually and combined, (p &lt; 0.05) were associated with a greater reduction. Sectors with low MWS combined with high WSS demonstrated the highest LRNC increase (p &lt; 0.01). Conclusions: In this study, we investigated the association of the (largely-overlooked) biomechanical factor MWS with coronary atherosclerosis, individually and combined with WSS. Our results demonstrated that both MWS and WSS significantly correlate with atherosclerotic plaque initiation and development.Medical Instruments & Bio-Inspired Technolog

Lipid-rich Plaques Detected by Near-infrared Spectroscopy Are More Frequently Exposed to High Shear Stress

High wall shear stress (WSS) and near-infrared spectroscopy (NIRS) detected lipid-rich plaque (LRP) are both known to be associated with plaque destabilization and future adverse cardiovascular events. However, knowledge of spatial co-localization of LRP and high WSS is lacking. This study investigated the co-localization of LRP based on NIRS and high WSS. Fifty-three patients presenting acute coronary syndrome underwent NIRS-intravascular-ultrasound (NIRS-IVUS) imaging of a non-culprit coronary artery. WSS was obtained using WSS profiling in 3D-reconstructions of the coronary arteries based on fusion of IVUS-segmented lumen and CT-derived 3D-centerline. Thirty-eight vessels were available for final analysis and divided into 0.5 mm/45° sectors. LRP sectors, as identified by NIRS, were more often colocalized with high WSS than sectors without LRP. Moreover, there was a dose-dependent relationship between lipid content and high WSS exposure. This study is a first step in understanding the evolution of LRPs to vulnerable plaques. [Figure not available: see fulltext.