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Intraplaque hemorrhage (IPH) is a characteristic of the vulnerable atherosclerotic plaque that has been associated with ischemic stroke. Not much is known about determinants of IPH. We studied whether blood pressure parameters are associated with presence of IPH. Within the framework of a prospective population-based cohort study, The Rotterdam Study, the carotid arteries of 1006 healthy participants ≥45 years and with intima-media thickening (≥2.5 mm) on ultrasound were imaged with a 1.5-T magnetic resonance imaging scanner. IPH was defined as a hyperintense signal on a 3D-T1w-GRE magnetic resonance sequence. Generalized estimation equation analysis, adjusted for age, sex, carotid wall thickness, and cardiovascular risk factors, was used to assess the association between blood pressure parameters and IPH. Magnetic resonance imaging of the carotid arteries revealed presence of IPH in 444 of 1860 plaques (24%). Systolic blood pressure and pulse pressure (PP) were significantly associated with IPH after adjustment for age and sex. In multivariate analysis, PP yielded the strongest association, with an odds ratio per SD increase in PP of 1.22 (95% CI, 1.07-1.40). The odds ratio per SD for systolic blood pressure was 1.13 (0.99-1.28). Only PP remained significant after additional adjustment for other blood pressure components. The combination of smoking and isolated systolic hypertension was associated with 2.5 times increased risk of IPH (1.2-5.2). In conclusion, PP was the strongest determinant of IPH independent of cardiovascular risk factors and other blood pressure components. The association between pulsatile flow and IPH may provide novel insights in the development of the vulnerable plaque. [ABSTRACT FROM AUTHOR]

Objectives: The purpose of this study was to investigate the role of shear stress (SS) in plaque regression. Background: A condition favorable to the development of atherosclerotic lesions is low oscillating SS. In the descending thoracic aorta, the relationship between plaque distribution and SS has never been characterized. The regression of plaque as the result of lipid-lowering therapy is associated with reverse atherogenic mechanisms. Therefore, we investigated the role of SS in plaque regression. Magnetic resonance imaging (MRI) provides a unique opportunity to noninvasively study morphology and hemodynamics. Methods: Cross-sectional images of atherosclerotic plaques in the descending thoracic aorta of 10 asymptomatic, hypercholesteremic patients were acquired at baseline and 24 months after starting lipid-lowering therapy by using a black-blood sequence on a 1.5-T clinical MRI system (5 mm x 780 microm x 780 microm). Average wall thickness (WT) was derived per quadrant. The aorta was subdivided in segments 2 cm in length starting 1 cm from the aortic arch. Results: Average WT decreased with increasing distance from the arch (3.0 +/- 0.7 mm vs. 2.5 +/- 0.3 mm; p < 0.05) and showed a helical pattern from the proximal to distal segments. Phase-contrast MRI was performed in the thoracic aorta of eight healthy volunteers to derive typical average SS distribution. Shear stress predicted the location of WT (r(2) = 0.29, p < 0.05) but did not predict plaque regression. The best predictor of plaque regression was baseline WT. Conclusions: Our data showing an association between WT and average low SS locations support the role of local hemodynamics in the development of atherosclerotic lesions in descending thoracic aorta. Furthermore, SS does not seem to be the major predictor for plaque regression by lipid-lowering interventions. Therefore, our data suggest that other mechanisms are involved in the lipid-reversal mechanism. [ABSTRACT FROM AUTHOR]

Background: The process of restenosis after a stenting procedure is related to local biomechanical environment. Arterial wall stresses caused by the interaction of the stent with the vascular wall and possibly stress induced stent strut fracture are two important parameters. The knowledge of these parameters after stent deployment in a patient derived 3D reconstruction of a diseased coronary artery might give insights in the understanding of the process of restenosis.Methods: 3D reconstruction of a mildly stenosed coronary artery was carried out based on a combination of biplane angiography and intravascular ultrasound. Finite element method computations were performed to simulate the deployment of a stent inside the reconstructed coronary artery model at inflation pressure of 1.0 MPa. Strut thickness of the stent was varied to investigate stresses in the stent and the vessel wall.Results: Deformed configurations, pressure-lumen area relationship and stress distribution in the arterial wall and stent struts were studied. The simulations show how the stent pushes the arterial wall towards the outside allowing the expansion of the occluded artery. Higher stresses in the arterial wall are present behind the stent struts and in regions where the arterial wall was thin. Values of 200 MPa for the peak stresses in the stent strut were detected near the connecting parts between the stent struts, and they were only just below the fatigue stress. Decreasing strut thickness might reduce arterial damage without increasing stresses in the struts significantly.Conclusion: The method presented in this paper can be used to predict stresses in the stent struts and the vessel wall, and thus evaluate whether a specific stent design is optimal for a specific patient. [ABSTRACT FROM AUTHOR]

Background: Aortic wall shear stress (WSS) is a known predictor of ascending aortic growth in patients with a bicuspid aortic valve (BAV). The aim of this study was to study regional WSS and changes over time in BAV patients., Methods: BAV patients and age-matched healthy controls underwent four-dimensional (4D) flow cardiovascular magnetic resonance (CMR). Regional, peak systolic ascending aortic WSS, aortic valve function, aortic stiffness measures, and aortic dimensions were assessed. In BAV patients, 4D flow CMR was repeated after 3 years of follow-up and both at baseline and follow-up computed tomography angiography (CTA) were acquired. Aortic growth (volume increase of ≥5%) was measured on CTA. Regional WSS differences within patients' aorta and WSS changes over time were analyzed using linear mixed-effect models and were associated with clinical parameters., Results: Thirty BAV patients (aged 34 years [interquartile range (IQR) 25-41]) were included in the follow-up analysis. Additionally, another 16 BAV patients and 32 healthy controls (aged 33 years [IQR 28-48]) were included for other regional analyses. Magnitude, axial, and circumferential WSS increased over time (all p < 0.001) irrespective of aortic growth. The percentage of regions exposed to a magnitude WSS >95th percentile of healthy controls increased from 21% (baseline 506/2400 regions) to 31% (follow-up 734/2400 regions) (p < 0.001). WSS angle, a measure of helicity near the aortic wall, decreased during follow-up. Magnitude WSS changes over time were associated with systolic blood pressure, peak aortic valve velocity, aortic valve regurgitation fraction, aortic stiffness indexes, and normalized flow displacement (all p < 0.05)., Conclusion: An increase in regional WSS over time was observed in BAV patients, irrespective of aortic growth. The increasing WSSs, comprising a larger area of the aorta, warrant further research to investigate the possible predictive value for aortic dissection., Competing Interests: Declaration of competing interests The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Alexander Hirsch reports financial support was provided by Thorax Foundation. Jolien Roos-Hesselink reports financial support was provided by Dutch Heart Foundation. Alexander Hirsch reports a relationship with GE Healthcare that includes consulting or advisory, funding grants, and speaking and lecture fees. Alexander Hirsch reports a relationship with Bayer AG that includes speaking and lecture fees. Alexander Hirsch reports a relationship with Medis Medical Imaging Systems BV that includes consulting or advisory. Alexander Hirsch reports a relationship with Cardialysis BV that includes board membership. Alexander Hirsch is the associate editor of the Journal of Cardiovascular Magnetic Resonance. The other 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 © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.)

Atherosclerosis manifests itself differently in men and women with respect to plaque initiation, progression and plaque composition. The observed delay in plaque progression in women is thought to be related to the hormonal status of women. Also features associated with the vulnerability of plaques to rupture seem to be less frequently present in women compared to men. Current invasive and non-invasive imaging modalities allow for visualization of plaque size, composition and high risk vulnerable plaque features. Moreover, image based modeling gives access to local shear stress and shear stress-related plaque growth. In this review, current knowledge on sex-related differences in plaque size, composition, high risk plaque features and shear stress related plaque growth in carotid and coronary arteries obtained from imaging are summarized., 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 © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)

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<0.001, wall surface area p=0.026, volume p=0.007). Patients had more aortic arch torsion (p<0.001) and a higher curvature (p<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., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: Plaque composition and wall shear stress (WSS) magnitude act as well-established players in coronary plaque progression. However, WSS magnitude per se does not completely capture the mechanical stimulus to which the endothelium is subjected, since endothelial cells experience changes in the WSS spatiotemporal configuration on the luminal surface. This study explores WSS profile and lipid content signatures of plaque progression to identify novel biomarkers of coronary atherosclerosis., Methods: Thirty-seven patients with acute coronary syndrome underwent coronary computed tomography angiography, near-infrared spectroscopy intravascular ultrasound, and optical coherence tomography of at least 1 nonculprit vessel at baseline and 1-year follow-up. Baseline coronary artery geometries were reconstructed from intravascular ultrasound and coronary computed tomography angiography and combined with flow information to perform computational fluid dynamics simulations to assess the time-averaged WSS magnitude (TAWSS) and the variability in the contraction/expansion action exerted by WSS on the endothelium, quantifiable in terms of topological shear variation index (TSVI). Plaque progression was measured as intravascular ultrasound-derived percentage plaque atheroma volume change at 1-year follow-up. Plaque composition information was extracted from near-infrared spectroscopy and optical coherence tomography., Results: Exposure to high TSVI and low TAWSS was associated with higher plaque progression (4.00±0.69% and 3.60±0.62%, respectively). Plaque composition acted synergistically with TSVI or TAWSS, resulting in the highest plaque progression (≥5.90%) at locations where lipid-rich plaque is exposed to high TSVI or low TAWSS., Conclusions: Luminal exposure to high TSVI, solely or combined with a lipid-rich plaque phenotype, is associated with enhanced plaque progression at 1-year follow-up. Where plaque progression occurred, low TAWSS was also observed. These findings suggest TSVI, in addition to low TAWSS, as a potential biomechanical predictor for plaque progression, showing promise for clinical translation to improve patient prognosis., Competing Interests: Disclosures None.

Background: Kidney disease is the most important predictor of death in patients with a Fontan circulation, yet its clinical and hemodynamic correlates have not been well established., Methods and Results: A total of 53 ambulatory patients with a Fontan circulation (median age, 16.2 years, 52.8% male patients) underwent advanced cardiovascular magnetic resonance assessment, including 4-dimensional flow imaging and computational fluid dynamics. Estimated glomerular filtration rate (eGFR) <90 mL/min per 1.73 m 2 was observed in 20.8% and albumin-to-creatinine ratio >3 mg/mmol in 39.6%. The average eGFR decline rate was -1.83 mL/min per 1.73 m 2 per year (95% CI, -2.67 to -0.99; P <0.001). Lower eGFR was associated with older age, larger body surface area at examination, longer time since Fontan procedure, and lower systemic ventricular ejection fraction. Higher albumin-to-creatinine ratio was associated with absence of fenestration at the Fontan operation, and older age and lower systemic ventricular ejection fraction at the assessment. Lower cross-sectional area of the Fontan conduit indexed to flow (r=0.32, P =0.038), higher inferior vena cava-conduit velocity mismatch factor (r=-0.35, P =0.022), higher kinetic energy indexed to flow in the total cavopulmonary connection (r=-0.59, P =0.005), and higher total cavopulmonary connection resistance (r=-0.42, P =0.005 at rest; r=-0.43, P =0.004 during exercise) were all associated with lower eGFR but not with albuminuria., Conclusions: Kidney dysfunction and albuminuria are common among clinically well adolescents and young adults with a Fontan circulation. Advanced cardiovascular magnetic resonance-derived metrics indicative of declining Fontan hemodynamics are associated with eGFR and might serve as targets to improve kidney health. Albuminuria might be driven by other factors that need further investigation.

Background: Optimal timing of pulmonary valve replacement (PVR) in Tetralogy of Fallot (TOF) patients remains challenging. Ventricular wall stress is considered to be an early marker of right ventricular (RV) dysfunction., Objectives: To investigate the association of RV wall stresses and their change over time with functional parameters in TOF patients., Methods: Ten TOF patients after surgical repair with moderate/severe pulmonary regurgitation were included. At two timepoints (median follow-up time 7.2 years), patient-specific computational biventricular models for wall stress assessment were created using CMR short-axis cine images and echocardiography-based RV pressures. RV ejection fraction (RVEF), NT-proBNP and cardiopulmonary exercise tests were used as outcome measures reflecting RV function. Associations between regional RV diastolic wall stress and RV function were investigated using linear mixed models., Results: Increased wall stress correlated with lower RV mass ( r rm  = -0.70, p  = 0.017) and lower RV mass-to-volume ( r rm  = -0.80, p  = 0.003) using repeated measures. Wall stress decreased significantly over time, especially in patients with a stable RVEF ( p  < 0.001). Higher wall stress was independently associated with lower RVEF, adjusted for left ventricular ejection fraction, RV end-diastolic volume and time since initial surgery (decrease of 1.27% RVEF per kPa increase in wall stress, p  = 0.029) using repeated measurements. No association was found between wall stress, NT-proBNP, and exercise capacity., Conclusions: Using a computational method to calculate wall stress locally in geometrically complex ventricles, we demonstrated that lower wall stress might be important to maintain ventricular function. RV wall stress assessment can be used in serial follow-up, and is potentially an early marker of impending RV dysfunction., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. The author(s) declared that they were an editorial board member of Frontiers, at the time of submission. This had no impact on the peer review process and the final decision., (© 2023 Minderhoud, Hirsch, Marin, Kardys, Rodríguez-Matas, Chiastra, Roos-Hesselink, Wentzel, Helbing and Akyildiz.)

Safety and efficacy of coronary drug-eluting stents (DES) are often preclinically tested using healthy or minimally diseased swine. These generally show significant fibrotic neointima at follow-up, while in patients, incomplete healing is often observed. The aim of this study was to investigate neointima responses to DES in swine with significant coronary atherosclerosis. Adult familial hypercholesterolemic swine (n = 6) received a high fat diet to develop atherosclerosis. Serial OCT was performed before, directly after, and 28 days after DES implantation (n = 14 stents). Lumen, stent and plaque area, uncovered struts, neointima thickness and neointima type were analyzed for each frame and averaged per stent. Histology was performed to show differences in coronary atherosclerosis. A range of plaque size and severity was found, from healthy segments to lipid-rich plaques. Accordingly, neointima responses ranged from uncovered struts, to minimal neointima, to fibrotic neointima. Lower plaque burden resulted in a fibrotic neointima at follow-up, reminiscent of minimally diseased swine coronary models. In contrast, higher plaque burden resulted in minimal neointima and more uncovered struts at follow-up, similarly to patients' responses. The presence of lipid-rich plaques resulted in more uncovered struts, which underscores the importance of advanced disease when performing safety and efficacy testing of DES., (© 2023. The Author(s).)

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., Competing Interests: Conflict of interest: None declared., (© The Author(s) 2022. Published by Oxford University Press on behalf of the European Society of Cardiology.)

Objectives: To date, it is not known if 16-20-mm extracardiac conduits are outgrown during somatic growth from childhood to adolescence. This study aims to determine total cavopulmonary connection (TCPC) haemodynamics in adolescent Fontan patients at rest and during simulated exercise and to assess the relationship between conduit size and haemodynamics., Methods: Patient-specific, magnetic resonance imaging-based computational fluid dynamic models of the TCPC were performed in 51 extracardiac Fontan patients with 16-20-mm conduits. Power loss, pressure gradient and normalized resistance were quantified in rest and during simulated exercise. The cross-sectional area (CSA) (mean and minimum) of the vessels of the TCPC was determined and normalized for flow rate (mm2/l/min). Peak (predicted) oxygen uptake was assessed., Results: The median age was 16.2 years (Q1-Q3 14.0-18.2). The normalized mean conduit CSA was 35-73% smaller compared to the inferior and superior vena cava, hepatic veins and left/right pulmonary artery (all P < 0.001). The median TCPC pressure gradient was 0.7 mmHg (Q1-Q3 0.5-0.8) and 2.0 (Q1-Q3 1.4-2.6) during rest and simulated exercise, respectively. A moderate-strong inverse non-linear relationship was present between normalized mean conduit CSA and TCPC haemodynamics in rest and exercise. TCPC pressure gradients of ≥1.0 at rest and ≥3.0 mmHg during simulated exercise were observed in patients with a conduit CSA ≤ 45 mm2/l/min and favourable haemodynamics (<1 mmHg during both rest and exercise) in conduits ≥125 mm2/l/min. Normalized TCPC resistance correlated with (predicted) peak oxygen uptake., Conclusions: Extracardiac conduits of 16-20 mm have become relatively undersized in most adolescent Fontan patients leading to suboptimal haemodynamics., (© The Author(s) 2022. Published by Oxford University Press on behalf of the European Association for Cardio-Thoracic Surgery.)

Aims: The influence haemodynamics have on vessel wall pathobiology in aortic disease is incomplete. This aim of this study was to develop a repeatable method for assessing the relationship between aortic wall shear stress (WSS) and disease activity by fusing 4D flow cardiovascular magnetic resonance (CMR) with hybrid positron emission tomography (PET)., Methods and Results: As part of an ongoing clinical trial, patients with bicuspid aortic valve (BAV) were prospectively imaged with both 18F-sodium fluoride (18F-NaF) PET, a marker of calcification activity, and 4D flow CMR. We developed novel software allowing accurate 3D co-registration and high-resolution comparison of aortic peak systolic WSS and 18F-NaF PET uptake (maximum tissue-to-background ratio). Intra-observer repeatability of both measurements was determined using Bland-Altman plots and intra-class correlation coefficients (ICCs). The relationship between localized WSS and 18F-NaF uptake was analysed using linear mixed-effect models. Twenty-three patients with BAV (median age 50 [44-55] years, 22% female) were included. Intra-observer repeatability for WSS (ICC = 0.92) and 18F-NaF (ICC = 0.91) measurements obtained within 1.4 ± 0.6 cm2 regions of interest was excellent. On multivariable analysis, 18F-NaF PET uptake was independently and negatively associated with WSS as well as diastolic blood pressure (both P < 0.05), adjusted for age., Conclusion: Fused assessment of WSS and 18F-NaF PET uptake is feasible and repeatable, demonstrating a clear association between these two factors. This high spatial resolution approach has major potential to advance our understanding of the relationship between vascular haemodynamics and disease activity., Competing Interests: Conflict of interest: The authors have no relationships relevant to the content of this paper to disclose. D.E.N. was supported by Toshiba, M.R.D. has received speaker fees from Pfizer and Novartis. He has received consultancy fees from Novartis, Jupiter Bioventures and Silence therapeutics. S.S. has received consultancy fee and research funding from GlaxoSmithKline. Siemens gave institutional support., (© The Author(s) 2022. Published by Oxford University Press on behalf of the European Society of Cardiology.)

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., Competing Interests: Conflict of interest: The authors have no relationships relevant to the content of this paper to disclose. A.H. received a research grant from GE Healthcare and is a member of the medical advisory board of Medis Medical Imaging Systems. Siemens and Heartflow gave institutional support. No personal compensation was given., (© The Author(s) 2022. Published by Oxford University Press on behalf of the European Society of Cardiology.)

Background and Objective: 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., Methods: 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., Results: 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., Conclusions: 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., Competing Interests: Declaration of Competing Interest The authors state no conflict of interest for the study object of the manuscript. The research was not supported financially by private companies. None of the authors has a financial agreement with peoples or organizations that could inappropriately influence their work., (Copyright © 2022 Elsevier B.V. All rights reserved.)

Background: Positive near-infrared spectroscopy (NIRS) signals might be encountered in areas without evident artery wall thickening, being typically perceived as artefacts., Aims: We aimed to evaluate the utility of NIRS to identify artery wall regions associated with an increase in wall thickness (WT) as assessed by serial intravascular ultrasound (IVUS) and optical coherence tomography (OCT)., Methods: In this prospective, single-centre study, patients presenting with acute coronary syndrome (ACS) underwent NIRS-IVUS and OCT assessment of a non-culprit artery at baseline and 12-month follow-up. For each vessel, 1.5 mm segments were identified, matched and divided into 45 sectors. The relationship between the change in IVUS-based WT (DWT) and the presence of NIRS-positive signals and OCT-detected lipid was evaluated using linear mixed models., Results: A total of 37 patients (38 vessels, 6,936 matched sectors) were analysed at baseline and 12 months. A total of 140/406 (34.5%) NIRS (+) sectors and 513/1,575 (32.6%) OCT-lipid (+) sectors were found to be located in thin (WT<0.5 mm) wall sectors. In the thin wall sectors, an increase in WT was significantly more pronounced in NIRS (+) vs NIRS (-) sectors (0.11 mm vs 0.06 mm, p<0.001). In the thick wall sectors, there was a decrease in WT observed that was less pronounced in the NIRS (+) versus NIRS (-) sectors (-0.08 mm vs -0.09 mm, p<0.001). Thin wall NIRS (+) OCT-lipid (+) sectors showed significant wall thickening (DWT=0.13 mm)., Conclusions: NIRS-positive signals in otherwise non-diseased arterial walls as assessed by IVUS could identify vessel wall regions prone to WT increase over 12-month follow-up. Our observations suggest that NIRS-positive signals in areas without evident wall thickening by IVUS should no longer be viewed as benign or imaging artefact.

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 Author(s) 2021. Published by Oxford University Press on behalf of the European Association for Cardio-Thoracic Surgery.)

Background and Aims: Clinical atherosclerosis manifestations are different in women compared to men. Since endothelial shear stress (ESS) is known to play a critical role in coronary atherosclerosis development, we investigated differences in anatomical characteristics and endothelial shear stress (ESS)-related plaque growth in human coronary arteries in men compared to women., Methods: 1183 coronary arteries (male/female: 944/239) from the PREDICTION study were studied for differences in artery/plaque and ESS characteristics, and ESS-related plaque progression (6-10 months follow-up) among men and women and after stratification for age. All characteristics were derived from IVUS-based vascular profiling and reported per 3 mm-segments (13,030 3-mm-segments (male/female: 10,465/2,565))., Results: Coronary arteries and plaques were significantly smaller in females compared to males; but no important differences were observed in plaque burden, ESS and rate of plaque progression. Change in plaque burden was inversely related to ESS (p<0.001) with no difference between women versus men (β: -0.62 ± 0.13 vs -0.68 ± 0.05, p=0.62). However, stratification for age demonstrated that ESS-related plaque growth was more marked in young women compared to men (<55 years, β: -2.02 ± 0.61 vs -0.33 ± 0.10, p=0.007), reducing in magnitude over the age-categories up till 75 years., Conclusions: Coronary artery and plaque size are smaller in women compared to men, but ESS and ESS- related plaque progression were similar. Sex-related differences in ESS-related plaque growth were evident after stratification for age. These observations suggest that although the fundamental processes of atherosclerosis progression are similar in men versus women, plaque progression may be influenced by age within gender., (Copyright © 2021. Published by Elsevier B.V.)

The role of wall shear stress (WSS) in atherosclerotic plaque development is evident, but the relation between WSS and plaque composition in advanced atherosclerosis, potentially resulting in plaque destabilization, is a topic of discussion. Using our previously developed image registration pipeline, we investigated the relation between two WSS metrics, time-averaged WSS (TAWSS) and the oscillatory shear index (OSI), and the local histologically determined plaque composition in a set of advanced human carotid plaques. Our dataset of 11 carotid endarterectomy samples yielded 87 histological cross-sections, which yielded 511 radial bins for analysis. Both TAWSS and OSI values were subdivided into patient-specific low, mid, and high tertiles. This cross-sectional study shows that necrotic core (NC) size and macrophage area are significantly larger in areas exposed to high TAWSS or low OSI. Local TAWSS and OSI tertile values were generally inversely related, as described in the literature, but other combinations were also found. Investigating the relation between plaque vulnerability features and different combinations of TAWSS and OSI tertile values revealed a significantly larger cap thickness in areas exposed to both low TAWSS and low OSI. In conclusion, our study confirmed previous findings, correlating high TAWSS to larger macrophage areas and necrotic core sizes. In addition, our study demonstrated new relations, correlating low OSI to larger macrophage areas, and a combination of low TAWSS and low OSI to larger cap thickness., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Moerman, Korteland, Dilba, van Gaalen, Poot, van Der Lugt, Verhagen, Wentzel, van Der Steen, Gijsen and Van der Heiden.)

Background and Purpose: Shear stress (WSS) is involved in the pathophysiology of atherosclerotic disease and might affect plaque ulceration. In this case-control study, we compared carotid plaques that developed a new ulcer during follow-up and plaques that remained silent for their exposure to time-dependent oscillatory shear stress parameters at baseline. Materials and Methods: Eighteen patients who underwent CTA and MRI of their carotid arteries at baseline and 2 years follow-up were included. These 18 patients consisted of six patients who demonstrated a new ulcer and 12 control patients selected from a larger cohort with similar MRI-based plaque characteristics as the ulcer group. (Oscillatory) WSS parameters [time average WSS, oscillatory shear index (OSI), and relative residence time (RRT)] were calculated using computational fluid dynamics applying the MRI-based geometry of the carotid arteries and compared among plaques (wall thickness>2 mm) with and without ulceration (Mann-Whitney U test) and ulcer-site vs. non-ulcer-site within the plaque (Wilcoxon signed rank test). More detailed analysis on ulcer cases was performed and the predictive value of oscillatory WSS parameters was calculated using linear and logistic mixed-effect regression models. Results: The ulcer group demonstrated no difference in maximum WSS [9.9 (6.6-18.5) vs. 13.6 (9.7-17.7) Pa, p = 0.349], a lower maximum OSI [0.04 (0.01-0.10) vs. 0.12 (0.06-0.20) p = 0.019] and lower maximum RRT [1.25 (0.78-2.03) Pa -1 vs. 2.93 (2.03-5.28) Pa -1 , p = 0.011] compared to controls. The location of the ulcer (ulcer-site) within the plaque was not always at the maximal WSS, but demonstrated higher average WSS, lower average RRT and OSI at the ulcer-site compared to the non-ulcer-sites. High WSS (WSS>4.3 Pa) and low RRT (RRT < 0.25 Pa) were associated with ulceration with an odds ratio of 3.6 [CI 2.1-6.3] and 2.6 [CI 1.54-4.44] respectively, which remained significant after adjustment for wall thickness. Conclusion: In this explorative study, ulcers were not exclusively located at plaque regions exposed to the highest WSS, OSI, or RRT, but high WSS and low RRT regions had a significantly higher odds to present ulceration within the plaque even after adjustment for wall thickness., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Dilba, van Dam-Nolen, Korteland, van der Kolk, Kassem, Bos, Koudstaal, Nederkoorn, Hendrikse, Kooi, Gijsen, van der Steen, van der Lugt and Wentzel.)

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., (© 2021. The Author(s).)

Significant portions of the world's forests have been impacted by severe and large-scale tree declines characterised by gradual but widespread loss of vigour and subsequent death of either single or several tree species. Tree deaths represent a threat for fauna that are dependent on forest habitats for their survival. Although tree declines have received considerable scientific attention, surprisingly, little is known about their impacts on fauna. In total, we calculated 631 effect sizes across 59 studies that quantified the impact of tree declines on animal abundance. Data representing 186 bird species indicated an overall increase in bird abundance in response to tree declines (meta-analysis mean ± estimation g = 0.172 ± 0.053 [CI 0.069 to 0.275], P = 0.001); however, there was substantial variability in responses (significant heterogeneity P < 0.001) with a strong influence of diet as well as nesting guild on bird responses. Granivores (especially ground-foraging species, e.g. Passerellidae species), bark-foraging insectivores (e.g. woodpeckers), as well as ground- and cavity-nesting species apparently benefitted from tree declines, while nectarivorous birds [and, although not significant, aerially foraging insectivores (e.g. flycatchers) and leaf-gleaning insectivores (canopy-feeding)] were less common in the presence of tree declines. Data representing 33 mammal species indicate a tendency for detrimental effects of tree declines on mammals that use trees as refuges, while aerial foragers (i.e. bats) may benefit from opening up the canopy. Overall the average effect for mammals was neutral (meta-analysis mean estimation g = -0.150 ± 0.145 [-0.433 to 0.134], P = 0.302). Data representing 20 reptile species showed an insufficient range of responses to determine any diet or foraging effect on their responses. Data for 28 arthropod taxa should be considered with caution, as we could not adequately separate taxa according to their specialisations and reliance on key habitat. The data broadly suggest a detrimental effect of tree declines (meta-analysis mean estimation g = -0.171 ± 0.072 [-0.311 to -0.031], P = 0.017) with ground-foraging arthropods (e.g. detritivores and predators such as spiders and centipedes) more likely to be detrimentally impacted by tree declines. The range of responses to tree declines signifies substantially altered animal communities. In many instances, altered ecosystem function due to loss of key animal services will represent a significant threat to forest health., (© 2021 Cambridge Philosophical Society.)

Although unphysiological wall shear stress (WSS) has become the consensus hemodynamic mechanism for coronary atherosclerosis, the complex biomechanical stimulus affecting atherosclerosis evolution is still undetermined. This has motivated the interest on the contraction/expansion action exerted by WSS on the endothelium, obtained through the WSS topological skeleton analysis. This study tests the ability of this WSS feature, alone or combined with WSS magnitude, to predict coronary wall thickness (WT) longitudinal changes. Nine coronary arteries of hypercholesterolemic minipigs underwent imaging with local WT measurement at three time points: baseline (T1), after 5.6 ± 0.9 (T2), and 7.6 ± 2.5 (T3) months. Individualized computational hemodynamic simulations were performed at T1 and T2. The variability of the WSS contraction/expansion action along the cardiac cycle was quantified using the WSS topological shear variation index (TSVI). Alone or combined, high TSVI and low WSS significantly co-localized with high WT at the same time points and were significant predictors of thickening at later time points. TSVI and WSS magnitude values in a physiological range appeared to play an atheroprotective role. Both the variability of the WSS contraction/expansion action and WSS magnitude, accounting for different hemodynamic effects on the endothelium, (1) are linked to WT changes and (2) concur to identify WSS features leading to coronary atherosclerosis., (© 2021. The Author(s).)

Background and Purpose: Dolichoarteriopathies of the extracranial part of the internal carotid artery (ICA) are associated with cerebrovascular events, yet information on their prevalence and risk factors remains limited. The aim of the present study therefore was to study the prevalence and risk factors of dolichoarteriopathies in a sample of patients with cerebrovascular symptoms from the Plaque At RISK (PARISK) study., Methods: In a random sample of 100 patients from the PARISK study, multidetector computed tomography angiography (MDCTA) was performed as part of clinical workup. On MDCTA, we evaluated the extracranial trajectory of the ICA by measuring the length (in millimeters), the tortuosity index (TI; defined as the ICA length divided by the shortest possible distance from bifurcation to skull base), and dolichoarteriopathy type (tortuosity, coiling or kinking). Next, we investigated the association between cardiovascular risk factors and these measurements using linear and logistic regression analyses., Results: The mean (standard deviation) length of the ICA was 93 (± 14) mm, with a median (interquartile range) TI of 1.2 (1.1-1.3). The overall prevalence of dolichoarteriopathies was 69%, with tortuosity being the most common (72%), followed by coiling (20%), and kinking (8%). We found that age and obesity were associated with a higher TI: difference per 10-year increase in age: 0.05 (95% confidence interval [CI] 0.02-0.08) and 0.16 (95% CI 0.07-0.25) for obesity. Obesity and hypercholesterolemia were associated with a more severe type of dolichoarteriopathy (odds ratio [OR] 2.07 [95% CI 1.04-4.12] and OR 2.17 [95% CI 1.02-4.63], respectively)., Conclusion: Dolichoarteriopathies in the extracranial ICA are common in patients with cerebrovascular symptoms, and age, obesity and hypercholesterolemia may play an important role in the pathophysiology of these abnormalities., (© 2021 The Authors. European Journal of Neurology published by John Wiley & Sons Ltd on behalf of European Academy of Neurology.)

Congenital heart disease is the most common birth defect and functionally univentricular heart defects represent the most severe end of this spectrum. The Fontan circulation provides an unique solution for single ventricle patients, by connecting both caval veins directly to the pulmonary arteries. As a result, the pulmonary circulation in Fontan palliated patients is characterized by a passive, low-energy circulation that depends on increased systemic venous pressure to drive blood toward the lungs. The absence of a subpulmonary ventricle led to the widely believed concept that respiration, by sucking blood to the pulmonary circulation during inspiration, is of great importance as a driving force for antegrade blood flow in Fontan patients. However, recent studies show that respiration influences pulsatility, but has a limited effect on net forward flow in the Fontan circulation. Importantly, since MRI examination is recommended every 2 years in Fontan patients, clinicians should be aware that most conventional MRI flow sequences do not capture the pulsatility of the blood flow as a result of the respiration. In this review, the unique flow dynamics influenced by the cardiac and respiratory cycle at multiple locations within the Fontan circulation is discussed. The impact of (not) incorporating respiration in different MRI flow sequences on the interpretation of clinical flow parameters will be covered. Finally, the influence of incorporating respiration in advanced computational fluid dynamic modeling will be outlined., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 van der Woude, Rijnberg, Hazekamp, Jongbloed, Kenjeres, Lamb, Westenberg, Roest and Wentzel.)

Coronary atherosclerosis is a leading cause of illness and death in Western World and its mechanisms are still non completely understood. Several animal models have been used to 1) study coronary atherosclerosis natural history and 2) propose predictive tools for this disease, that is asymptomatic for a long time, aiming for a direct translation of their findings to human coronary arteries. Among them, swine models are largely used due to the observed anatomical and pathophysiological similarities to humans. However, a direct comparison between swine and human models in terms of coronary hemodynamics, known to influence atherosclerotic onset/development, is still lacking. In this context, we performed a detailed comparative analysis between swine- and human-specific computational hemodynamic models of coronary arteries. The analysis involved several near-wall and intravascular flow descriptors, previously emerged as markers of coronary atherosclerosis initiation/progression, as well as anatomical features. To do that, non-culprit coronary arteries (18 right-RCA, 18 left anterior descending-LAD, 13 left circumflex-LCX coronary artery) from patients presenting with acute coronary syndrome were imaged by intravascular ultrasound and coronary computed tomography angiography. Similarly, the three main coronary arteries of ten adult mini-pigs were also imaged (10 RCA, 10 LAD, 10 LCX). The geometries of the imaged coronary arteries were reconstructed (49 human, 30 swine), and computational fluid dynamic simulations were performed by imposing individualized boundary conditions. Overall, no relevant differences in 1) wall shear stress-based quantities, 2) intravascular hemodynamics (in terms of helical flow features), and 3) anatomical features emerged between human- and swine-specific models. The findings of this study strongly support the use of swine-specific computational models to study and characterize the hemodynamic features linked to coronary atherosclerosis, sustaining the reliability of their translation to human vascular disease., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 De Nisco, Chiastra, Hartman, Hoogendoorn, Daemen, Calò, Gallo, Morbiducci and Wentzel.)

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. Graphical Abstract.

Coronary artery atherosclerosis is a local, multifactorial, complex disease, and the leading cause of death in the US. Complex interactions between biochemical transport and biomechanical forces influence disease growth. Wall shear stress (WSS) affects coronary artery atherosclerosis by inducing endothelial cell mechanotransduction and by controlling the near-wall transport processes involved in atherosclerosis. Each of these processes is controlled by WSS differently and therefore has complicated the interpretation of WSS in atherosclerosis. In this paper, we present a comprehensive theory for WSS in atherosclerosis. First, a short review of shear stress-mediated mechanotransduction in atherosclerosis was presented. Next, subject-specific computational fluid dynamics (CFD) simulations were performed in ten coronary artery models of diseased and healthy subjects. Biochemical-specific mass transport models were developed to study low-density lipoprotein, nitric oxide, adenosine triphosphate, oxygen, monocyte chemoattractant protein-1, and monocyte transport. The transport results were compared with WSS vectors and WSS Lagrangian coherent structures (WSS LCS). High WSS magnitude protected against atherosclerosis by increasing the production or flux of atheroprotective biochemicals and decreasing the near-wall localization of atherogenic biochemicals. Low WSS magnitude promoted atherosclerosis by increasing atherogenic biochemical localization. Finally, the attracting WSS LCS's role was more complex where it promoted or prevented atherosclerosis based on different biochemicals. We present a summary of the different pathways by which WSS influences coronary artery atherosclerosis and compare different mechanotransduction and biotransport mechanisms., (Copyright © 2021 by ASME.)

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.

Fontan patients require a balanced hepatic blood flow distribution (HFD) to prevent pulmonary arteriovenous malformations. Currently, HFD is quantified by tracking Fontan conduit flow, assuming hepatic venous (HV) flow to be uniformly distributed within the Fontan conduit. However, this assumption may be unvalid leading to inaccuracies in HFD quantification with potential clinical impact. The aim of this study was to (i) assess the mixing of HV flow and inferior vena caval (IVC) flow within the Fontan conduit and (ii) quantify HFD by directly tracking HV flow and quantitatively comparing results with the conventional approach. Patient-specific, time-resolved computational fluid dynamic models of 15 total cavopulmonary connections were generated, including the HV and subhepatic IVC. Mixing of HV and IVC flow, on a scale between 0 (no mixing) and 1 (perfect mixing), was assessed at the caudal and cranial Fontan conduit. HFD was quantified by tracking particles from the caudal (HFD caudal conduit ) and cranial (HFD cranial conduit ) conduit and from the hepatic veins (HFD HV ). HV flow was non-uniformly distributed at both the caudal (mean mixing 0.66 ± 0.13) and cranial (mean 0.79 ± 0.11) level within the Fontan conduit. On a cohort level, differences in HFD between methods were significant but small; HFD HV (51.0 ± 20.6%) versus HFD caudal conduit (48.2 ± 21.9%, p = 0.033) or HFD cranial conduit (48.0 ± 21.9%, p = 0.044). However, individual absolute differences of 8.2-14.9% in HFD were observed in 4/15 patients. HV flow is non-uniformly distributed within the Fontan conduit. Substantial individual inaccuracies in HFD quantification were observed in a subset of patients with potential clinical impact.

Introduction: Vascular remodeling is a compensatory enlargement of the vessel wall in response to atherosclerotic plaque growth. We aimed to investigate the association between intraplaque hemorrhage (IPH), vascular remodeling, and luminal dimensions in recently symptomatic patients with mild to moderate carotid artery stenosis in which the differences in plaque size were taken into account., Materials and Methods: We assessed vessel dimensions on MRI of the symptomatic carotid artery in 164 patients from the Plaque At RISK study. This study included patients with recent ischemic neurological event and ipsilateral carotid artery stenosis <70%. The cross section with the largest wall area (WA) in the internal carotid artery (ICA) was selected for analysis. On this cross section, the following parameters were determined: WA, total vessel area (TVA), and lumen area (LA). Vascular remodeling was quantified as the remodeling ratio (RR) and was calculated as TVA at this position divided by the TVA in an unaffected distal portion of the ipsilateral ICA. Adjustment for WA was performed to correct for plaque size., Results: Plaques with IPH had a larger WA (0.56 vs. 0.46 cm2; p < 0.001), a smaller LA (0.17 vs. 0.22 cm2; p = 0.03), and a higher RR (2.0 vs. 1.9; p = 0.03) than plaques without IPH. After adjustment for WA, plaques containing IPH had a smaller LA (B = -0.052, p = 0.01) than plaques without IPH, but the RR was not different., Conclusion: After correcting for plaque size, plaques containing IPH had a smaller LA than plaques without IPH. However, RR was not different., (© 2020 The Author(s)Published by S. Karger AG, Basel.)

Background and Purpose: Plaque ulceration is a marker of previous plaque rupture. We studied the association between atherosclerotic plaque composition at baseline and plaque ulceration at baseline and follow-up., Materials and Methods: We included symptomatic patients with a carotid stenosis of <70% who underwent MDCTA and MR imaging at baseline ( n  = 180). MDCTA was repeated at 2 years ( n  = 73). We assessed the presence of ulceration using MDCTA. Baseline MR imaging was used to assess the vessel wall volume and the presence and volume of plaque components (intraplaque hemorrhage, lipid-rich necrotic core, and calcifications) and the fibrous cap status. Associations at baseline were evaluated with binary logistic regression and reported with an OR and its 95% CI. Simple statistical testing was performed in the follow-up analysis., Results: At baseline, the prevalence of plaque ulceration was 27% (49/180). Increased wall volume (OR  = 12.1; 95% CI, 3.5-42.0), higher relative lipid-rich necrotic core (OR = 1.7; 95% CI, 1.3-2.2), higher relative intraplaque hemorrhage volume (OR = 1.7; 95% CI, 1.3-2.2), and a thin-or-ruptured fibrous cap (OR = 3.4; 95% CI, 1.7-6.7) were associated with the presence of ulcerations at baseline. In 8% (6/73) of the patients, a new ulcer developed. Plaques with a new ulceration at follow-up had at baseline a larger wall volume (1.04 cm 3 [IQR, 0.97-1.16 cm 3 ] versus 0.86 cm 3 [IQR, 0.73-1.00 cm 3 ]; P  = .029), a larger relative lipid-rich necrotic core volume (23% [IQR, 13-31%] versus 2% [IQR, 0-14%]; P  = .002), and a larger relative intraplaque hemorrhage volume (14% [IQR, 8-24%] versus 0% [IQR, 0-5%]; P  < .001)., Conclusions: Large atherosclerotic plaques and plaques with intraplaque hemorrhage and lipid-rich necrotic cores were associated with plaque ulcerations at baseline and follow-up., (© 2021 by American Journal of Neuroradiology.)

Improvements in spatial and temporal resolution now permit robust high quality characterization of presence, morphology and composition of coronary atherosclerosis in computed tomography (CT). These characteristics include high risk features such as large plaque volume, low CT attenuation, napkin-ring sign, spotty calcification and positive remodeling. Because of the high image quality, principles of patient-specific computational fluid dynamics modeling of blood flow through the coronary arteries can now be applied to CT and allow the calculation of local lesion-specific hemodynamics such as endothelial shear stress, fractional flow reserve and axial plaque stress. This review examines recent advances in coronary CT image-based computational modeling and discusses the opportunity to identify lesions at risk for rupture much earlier than today through the combination of anatomic and hemodynamic information.

Atherosclerosis at the early stage in coronary arteries has been associated with low cycle-average wall shear stress magnitude. However, parallel to the identification of an established active role for low wall shear stress in the onset/progression of the atherosclerotic disease, a weak association between lesions localization and low/oscillatory wall shear stress has been observed. In the attempt to fully identify the wall shear stress phenotype triggering early atherosclerosis in coronary arteries, this exploratory study aims at enriching the characterization of wall shear stress emerging features combining correlation-based analysis and complex networks theory with computational hemodynamics. The final goal is the characterization of the spatiotemporal and topological heterogeneity of wall shear stress waveforms along the cardiac cycle. In detail, here time-histories of wall shear stress magnitude and wall shear stress projection along the main flow direction and orthogonal to it (a measure of wall shear stress multidirectionality) are analyzed in a representative dataset of 10 left anterior descending pig coronary artery computational hemodynamics models. Among the main findings, we report that the proposed analysis quantitatively demonstrates that the model-specific inlet flow-rate shapes wall shear stress time-histories. Moreover, it emerges that a combined effect of low wall shear stress magnitude and of the shape of the wall shear stress-based descriptors time-histories could trigger atherosclerosis at its earliest stage. The findings of this work suggest for new experiments to provide a clearer determination of the wall shear stress phenotype which is at the basis of the so-called arterial hemodynamic risk hypothesis in coronary arteries.

Atherosclerotic plaques prone to rupture may cause acute myocardial infarction (MI) but can also heal without causing an event. Certain common histopathological features, including inflammation, a thin fibrous cap, positive remodelling, a large necrotic core, microcalcification, and plaque haemorrhage are commonly found in plaques causing an acute event. Recent advances in imaging techniques have made it possible to detect not only luminal stenosis and overall coronary atherosclerosis burden but also to identify such adverse plaque characteristics. However, the predictive value of identifying individual adverse atherosclerotic plaques for future events has remained poor. In this Position Paper, the relationship between vulnerable plaque imaging and MI is addressed, mainly for non-invasive assessments but also for invasive imaging of adverse plaques in patients undergoing invasive coronary angiography. Dynamic changes in atherosclerotic plaque development and composition may indicate that an adverse plaque phenotype should be considered at the patient level rather than for individual plaques. Imaging of adverse plaque burden throughout the coronary vascular tree, in combination with biomarkers and biomechanical parameters, therefore holds promise for identifying subjects at increased risk of MI and for guiding medical and invasive treatment., (Published on behalf of the European Society of Cardiology. All rights reserved. © The Author(s) 2020. For permissions, please email: journals.permissions@oup.com.)

Coronary calcification represents a challenge in the treatment of coronary artery disease by stent placement. It negatively affects stent expansion and has been related to future adverse cardiac events. Intravascular ultrasound (IVUS) is known for its high sensitivity in detecting coronary calcification. At present, automated quantification of calcium as detected by IVUS is not available. For this reason, we developed and validated an optimized framework for accurate automated detection and quantification of calcified plaque in coronary atherosclerosis as seen by IVUS. Calcified lesions were detected by training a supported vector classifier per IVUS A-line on manually annotated IVUS images, followed by post-processing using regional information. We applied our framework to 35 IVUS pullbacks from each of the three commonly used IVUS systems. Cross-validation accuracy for each system was >0.9, and the testing accuracy was 0.87, 0.89 and 0.89 for the three systems. Using the detection result, we propose an IVUS calcium score, based on the fraction of calcium-positive A-lines in a pullback segment, to quantify the extent of calcified plaque. The high accuracy of the proposed classifier suggests that it may provide a robust and accurate tool to assess the presence and amount of coronary calcification and, thus, may play a role in image-guided coronary interventions., (Copyright © 2020 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: Cardiovascular magnetic resonance (CMR) phase contrast (PC) flow measurements suffer from phase offset errors. Background subtraction based on stationary phantom measurements can most reliably be used to overcome this inaccuracy. Stationary tissue correction is an alternative and does not require additional phantom scanning. The aim of this study was 1) to compare measurements with and without stationary tissue correction to phantom corrected measurements on different GE Healthcare CMR scanners using different software packages and 2) to evaluate the clinical implications of these methods., Methods: CMR PC imaging of both the aortic and pulmonary artery flow was performed in patients on three different 1.5 T CMR scanners (GE Healthcare) using identical scan parameters. Uncorrected, first, second and third order stationary tissue corrected flow measurement were compared to phantom corrected flow measurements, our reference method, using Medis QFlow, Circle cvi42 and MASS software. The optimal (optimized) stationary tissue order was determined per scanner and software program. Velocity offsets, net flow, clinically significant difference (deviation > 10% net flow), and regurgitation severity were assessed., Results: Data from 175 patients (28 (17-38) years) were included, of which 84% had congenital heart disease. First, second and third order and optimized stationary tissue correction did not improve the velocity offsets and net flow measurements. Uncorrected measurements resulted in the least clinically significant differences in net flow compared to phantom corrected data. Optimized stationary tissue correction per scanner and software program resulted in net flow differences (> 10%) in 19% (MASS) and 30% (Circle cvi42) of all measurements compared to 18% (MASS) and 23% (Circle cvi42) with no correction. Compared to phantom correction, regurgitation reclassification was the least common using uncorrected data. One CMR scanner performed worse and significant net flow differences of > 10% were present both with and without stationary tissue correction in more than 30% of all measurements., Conclusion: Phase offset errors had a significant impact on net flow quantification, regurgitation assessment and varied greatly between CMR scanners. Background phase correction using stationary tissue correction worsened accuracy compared to no correction on three GE Healthcare CMR scanners. Therefore, careful assessment of phase offset errors at each individual scanner is essential to determine whether routine use of phantom correction is necessary., Trial Registration: Observational Study.