Predicting Lipid-Rich Plaque Progression in Coronary Arteries Using Multimodal Imaging and Wall Shear Stress Signatures.

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.

Noninvasive Advanced Cardiovascular Magnetic Resonance-Derived Fontan Hemodynamics Are Associated With Reduced Kidney Function But Not Albuminuria.

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 m2 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 m2 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.

Serial RV wall stress measurements: association with right ventricular function in repaired Tetralogy of Fallot patients.

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 (rrm = -0.70, p = 0.017) and lower RV mass-to-volume (rrm = -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.

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 & MWS) and changes in coronary wall (ΔWT & ΔLRNC) were studied using linear mixed models. RESULTS: In plaque-free sectors, higher MWS (p < 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 < 0.05) were associated with a greater reduction. Sectors with low MWS combined with high WSS demonstrated the highest LRNC increase (p < 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.

Plaque burden is associated with minimal intimal coverage following drug-eluting stent implantation in an adult familial hypercholesterolemia swine model.

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.

Virtual surgery to predict optimized conduit size for adult Fontan patients with 16-mm conduits.

OBJECTIVES: Recent evidence suggests that conduits implanted in Fontan patients at the age of 2-4 years become undersized for adulthood. The objective of this study is to use computational fluid dynamic models to evaluate the effect of virtual expansion of the Fontan conduit on haemodynamics and energetics of the total cavopulmonary connection (TCPC) under resting conditions and increased flow conditions. METHODS: Patient-specific, magnetic resonance imaging-based simulation models of the TCPC were performed during resting and increased flow conditions. The original 16-mm conduits were virtually enlarged to 3 new sizes. The proposed conduit sizes were defined based on magnetic resonance imaging-derived conduit flow in each patient. Flow efficiency was evaluated based on power loss, pressure drop and resistance and thrombosis risk was based on flow stagnation volume and relative residence time (RRT). RESULTS: Models of 5 adult patients with a 16-mm extracardiac Fontan connection were simulated and subsequently virtually expanded to 24-32 mm depending on patient-specific conduit flow. Virtual expansion led to a 40-65% decrease in pressure gradient across the TCPC depending on virtual conduit size. Despite improved energetics of the entire TCPC, the pulmonary arteries remained a significant contributor to energy loss (60-73% of total loss) even after virtual surgery. Flow stagnation volume inside the virtual conduit and surface area in case of elevated RRT (>20/Pa) increased after conduit enlargement but remained negligible (flow stagnation <2% of conduit volume in rest, <0.5% with exercise and elevated RRT <3% in rest, <1% with exercise). CONCLUSIONS: Virtual expansion of 16-mm conduits to 24-32 mm, depending on patient-specific conduit flow, in Fontan patients significantly improves TCPC efficiency while thrombosis risk presumably remains low.

Wall shear stress-related plaque growth of lipid-rich plaques in human coronary arteries: an near-infrared spectroscopy and optical coherence tomography study.

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.

Haemodynamic performance of 16-20-mm extracardiac Goretex conduits in adolescent Fontan patients at rest and during simulated exercise.

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.

Divergence of the normalized wall shear stress as an effective computational template of low-density lipoprotein polarization at the arterial blood-vessel wall interface.

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.

Erratum: Spectroscopic thermo-elastic optical coherence tomography for tissue characterization: publisher's note.

[This corrects the article on p. 1430 in vol. 13, PMID: 35414978.].

Vascular biomechanics and molecular disease activity in the thoracic aorta: a novel imaging method.

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.

Spectroscopic thermo-elastic optical coherence tomography for tissue characterization.

Optical imaging techniques that provide free space, label free imaging are powerful tools in obtaining structural and biochemical information in biological samples. To date, most of the optical imaging technologies create images with a specific contrast and require multimodality integration to add additional contrast. In this study, we demonstrate spectroscopic Thermo-elastic Optical Coherence Tomography (TE-OCT) as a potential tool in tissue identification. TE-OCT creates images based on two different forms of contrast: optical reflectance and thermo-elastic deformation. TE-OCT uses short laser pulses to induce thermo-elastic tissue deformation and measures the resulting surface displacement using phase-sensitive OCT. In this work we characterized the relation between thermo-elastic displacement and optical absorption, excitation, fluence and illumination area. The experimental results were validated with a 2-dimensional analytical model. Using spectroscopic TE-OCT, the thermo-elastic spectra of elastic phantoms and tissue components in coronary arteries were extracted. Specific tissue components, particularly lipid, an important biomarker for identifying atherosclerotic lesions, can be identified in the TE-OCT spectral response. As a label-free, free-space, dual-contrast, all-optical imaging technique, spectroscopic TE-OCT holds promise for biomedical research and clinical pathology diagnosis.

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.

Sex-related differences in plaque characteristics and endothelial shear stress related plaque-progression in human coronary arteries.

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 (ß: -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, ß: -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.

Extracardiac conduit adequacy along the respiratory cycle in adolescent Fontan patients.

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.

Near-infrared spectroscopy to predict plaque progression in plaque-free artery regions.

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.

The Association Between Time-Varying Wall Shear Stress and the Development of Plaque Ulcerations in Carotid Arteries From the Plaque at Risk Study.

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.

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.