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

2021 ◽  
Vol 8 ◽  
Author(s):  
Kristine Dilba ◽  
Dianne H. K. van Dam-Nolen ◽  
Suze-Anne Korteland ◽  
Anja G. van der Kolk ◽  
Mohamed Kassem ◽  
...  

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.

1996 ◽  
Vol 10 ◽  
pp. 20
Author(s):  
J.T. Salonen ◽  
K. Nyyssönen ◽  
K. Seppänen ◽  
R. Salonen ◽  
J. Lynch ◽  
...  

2019 ◽  
Vol 40 (Supplement_1) ◽  
Author(s):  
A Hoogendoorn ◽  
A M Kok ◽  
E M J Hartman ◽  
C Chiastra ◽  
L Casadonte ◽  
...  

Abstract Aim Wall shear stress (WSS) has been widely associated with plaque development and destabilization. However, the multidirectionality of WSS, induced by the pulsatile nature of blood flow in combination with the arterial geometry, is rarely taken into account. The purpose of this study was to investigate the influence and predictive value of five (multidirectional) WSS parameters for coronary plaque progression and composition. Methods Familial hypercholesterolemic pigs (n=10, castrated male, 3 years old) were put on a high-fat diet and underwent imaging (near infrared spectroscopy-intravascular ultrasound (NIRS-IVUS), optical coherence tomography (OCT) and CT) of the three main coronary arteries at baseline and 10/12 months follow-up. IVUS-based lumen contours were combined with the centerline of artery as extracted from CT to obtain a 3D reconstruction of the coronary artery. Local flow velocity measurements were combined with the 3D-geometry of the coronary arterial lumen to calculate five multidirectional WSS parameters including: time average wall shear stress (TAWSS), oscilatory shear index (OSI), relative residence time (RRT), trans wall shear stress (TransWSS), cross flow index (CFI). For the analysis, arteries were divided into 3mm/45° sectors (n=3627). Per vessel each segment was classified as low, mid or high for each WSS metric based on the average value in the sector. Changes in wall thickness (WT) and plaque composition were assessed with NIRS-IVUS and OCT, and histology and related to the local (multidirectional) WSS. Results Half of the pigs developed lumen intruding, complex, lipid-rich plaques. In these pigs, coronary segments exposed to low baseline levels of TAWSS exhibited a significantly larger plaque growth per month compared to regions with either mid or high TAWSS (p<0.05, see figure). Furthermore, plaque growth correlated positively with the multidirectional WSS metrics OSI, RRT and CFI, with high multidirectionality resulting in the largest plaque growth (see figure). The positive predictive values (PPV) of the WSS metrics for plaque presence (WT>0.5mm) at follow up were 50% (low TAWSS), 48% (high OSI), 49% (high RRT), 47% (high CFI) and 43% (high transWSS). The PPVs for the presence of a fibroatheroma observed with histology were 61% (low TAWSS), 58% (high OSI), 61% (high RRT), 59% (high CFI) and 49% (high transWSS). Plaque growth vs. multidirectional WSS Conclusions This study shows that both low and multidirectional WSS promote the development of large and complex coronary atherosclerotic plaques with vulnerable characteristics. The high predictive values for fibrous cap atheroma development demonstrate the potential of multidirectional WSS metrics as a predictive clinical marker for vulnerable disease. Acknowledgement/Funding ERC- starter grant (grant agreement 310457)


Author(s):  
Dalin Tang ◽  
Chun Yang ◽  
Joseph D. Petruccelli ◽  
Jie Zheng ◽  
Richard Bach ◽  
...  

Atherosclerotic plaque progression is believed to be associated with low and oscillating flow shear stress conditions [1–3]. In vivo image-based coronary plaque modeling papers are relatively rare because clinical recognition of vulnerable coronary plaques has remained challenging [3–4]. Samady et al. [3] published their seminal patient follow-up coronary plaque progression study and indicated that flow shear stress (FSS) was associated with plaque progression and remodeling. We have published results based on follow-up studies showing that advanced carotid plaque had positive correlation with flow shear stress and negative correlation with plaque wall stress (PWS) [4]. In this paper, patient-specific intravascular ultrasound (IVUS)-based coronary plaque models with fluid-structure interaction (FSI), on-site pressure and ex vivo biaxial mechanical testing of human coronary plaque material properties were constructed to obtain flow shear stress and plaque wall stress data from six patients to investigate possible associations between vessel wall thickness and both flow shear stress and plaque wall stress conditions.


2021 ◽  
Vol 23 (2) ◽  
Author(s):  
Zhongyou Li ◽  
Chong Chen ◽  
Yu Chen ◽  
Zhenze Wang ◽  
Wentao Jiang ◽  
...  

Purpose: As the factors affecting the efficacy of the bare-metal stent in the treatment of aneurysm with a visceral vessel attached were not fully understood, we aimed to discuss the effects of different characteristics of the stent on the hemodynamics and flexibility in the treatment of the aneurysm. Methods: Single-layer (with different strut widths) and multi-layer (with a different number of struts) stent models divided into three porosity groups, with porosities of 72.3, 60.5, and 52.4%, were modeled for a comparison of their hemodynamic isolation and flexibility performance via computational fluid dynamics and finite element methods. Results: The velocity and timeaveraged wall shear stress decreased more noticeably with multi-layer stent interventions. A higher oscillatory shear index and relative residence time occurred at the aneurysmal sac wall after multi-layer stents were employed. Time-averaged wall shear stress on the aneurysmal wall decreased with an increase in the number of struts or a decrease in pore size, but oscillatory shear index and relative residence time increased as the number of struts increased or the pore size decreased. Besides, all stents affect the branch patency slightly. In the bending test, when the porosity exceeded 60.5%, multi-layer stents were more flexible. Conclusion: The number of struts or pore size of stent dominated the isolation in the management of the aneurysm and affected the flexibility significantly when the porosity was below 60.5%. These findings may contribute to the special design of the stent in the treatment of such types of aneurysms.


2021 ◽  
Vol 39 (6_suppl) ◽  
pp. 11-11
Author(s):  
Kim N. Chi ◽  
Simon Chowdhury ◽  
Anders Bjartell ◽  
Byung Ha Chung ◽  
Andrea Juliana Pereira de Santana Gomes ◽  
...  

11 Background: TITAN evaluated APA or PBO added to ADT in pts with mCSPC. Pts with high- and low-volume disease, prior docetaxel, prior treatment for localized disease, and prior ADT (≤ 6 mos) were eligible. At the first interim analysis, with 22.7 mos median follow-up, APA significantly improved dual primary end points of overall survival (OS) (hazard ratio [HR] 0.67) and radiographic progression-free survival (rPFS) (HR 0.48) compared with PBO (Chi et al. NEJM. 2019). At that time, OS analysis was first planned interim while rPFS was final. TITAN was unblinded, allowing pts without progression who were still receiving PBO to cross over to APA. Herein, we report the final analysis of efficacy and safety results from TITAN. Methods: 1052 mCSPC pts were randomized 1:1 to receive APA (240 mg QD) or PBO plus ADT. Time-to-event end points were analyzed by Kaplan-Meier method and Cox proportional hazards model. A preplanned sensitivity analysis for OS, accounting for crossover using inverse probability censoring weighted (IPCW) log-rank test, was conducted. No formal statistical retesting was performed; nominal p values were reported without multiplicity adjustment. Change from baseline in Functional Assessment of Cancer Therapy-Prostate (FACT-P) total score was assessed using a mixed-effect repeated-measures model. Results: With 44 mos median follow-up, 405 OS events had occurred. After unblinding, 208 PBO pts (39.5%) crossed over to APA. Median treatment duration was 39.3 mos for the APA group, 20.2 mos for the entire PBO group, and 15.4 mos for the PBO→APA crossover group. OS was superior in the APA group compared with the PBO group despite crossover (Table). 48-mo survival rates were 65% (APA) vs 52% (PBO). Other end points also favored APA vs PBO (Table). Health-related quality of life (HRQoL), per total FACT-P, was maintained in the APA group through the study and was not different from the PBO group. Safety was consistent with previous reports. Conclusions: With close to 4 yrs of follow-up, the final analysis of TITAN demonstrated that in a broad population of pts with mCSPC, APA plus ADT provides an improvement in OS with a 35% reduction in risk of death, which increased to 48% reduction after adjusting for pts who crossed over from PBO to APA. In addition, there was consistent benefit with APA in other end points, including delaying castration resistance, and HRQoL continued to be maintained with an acceptable safety profile. Clinical trial information: NCT02489318. [Table: see text]


2016 ◽  
Vol 2016 ◽  
pp. 1-8 ◽  
Author(s):  
Xiao-qing Cao ◽  
Xin-xin Liu ◽  
Meng-meng Li ◽  
Yu Zhang ◽  
Liang Chen ◽  
...  

The rupture and erosion of atherosclerotic plaque can induce coronary thrombosis. Prolyl-4-hydroxylase (P4H) plays a central role in the synthesis of all known types of collagens, which are the most abundant constituent of the extracellular matrix in atherosclerotic plaque. The pathogenesis of atherosclerosis is thought to be in part caused by shear stress. In this study, we aimed to investigate a relationship between P4Hα1 and shear stress-induced atherosclerotic plaque. Carotid arteries of ApoE−/− mice were exposed to low and oscillatory shear stress conditions by the placement of a shear stress cast for 2 weeks; we divided 60 male ApoE−/− mice into three groups for treatments with saline (mock) (n=20), empty lentivirus (lenti-EGFP) (n=20), and lentivirus-P4Hα1 (lenti-P4Hα1) (n=20). Our results reveal that after 2 weeks of lenti-P4Hα1 treatment both low and oscillatory shear stress-induced plaques increased collagen and the thickness of fibrous cap and decreased macrophage accumulation but no change in lipid accumulation. We also observed that overexpression of P4Ha1 increased plaque size. Our study suggests that P4Hα1 overexpression might be a potential therapeutic target in stabilizing vulnerable plaques.


Stroke ◽  
2020 ◽  
Vol 51 (Suppl_1) ◽  
Author(s):  
Yun-Ju Lai ◽  
Diego Morales-Scheihing ◽  
Frank W Blixt ◽  
Yashasvee Munshi ◽  
Brina V Bui ◽  
...  

Introduction: Post-stroke inflammation is detrimental to the brain and leads to impaired recovery. Optimism has been associated with lower inflammation and better health outcomes among people with medical conditions, but no studies have assessed this association in stroke population. The overall goals were to examine the relationship between optimism, stroke severity, physical disability, and inflammation during hospitalization and to evaluate this relationship over the three-month post-stroke period. Hypothesis: Patients with higher levels of optimism have lower stroke severity on presentation, less physical disability, decreased inflammation, and better recovery during the first three months after stroke compared to those with lower levels of optimism. Methods: This pilot study is a secondary analysis of data prospectively collected from the BioRepository of Neurological Diseases biobank. Outcomes included optimism level measured by the revised Life Orientation Test (LOT-R), stroke severity evaluated via the NIHSS, physical recovery defined by the mRS, and levels of inflammatory markers (IL-6, TNFα, and CRP) assessed by ELISA. Spearman’s correlation, Wilcoxon signed-rank test, multiple linear regression, and mixed-effect regression model were used to determine the relationship among the variables. Results: The sample consisted of 49 subjects at baseline and 13 subjects at 3-month follow-up. LOT-R scores were negatively correlated with NIHSS (ρ= -.41, p=.003), mRS (ρ= -.30, p=.05), and inflammatory markers IL-6 (ρ= -.44, p=.008) and CRP (ρ= -.40, p=.02), but not with TNFα. After adjusting for potential confounders, NIHSS and CRP remained negatively correlated with the optimism level. For every unit increase of LOT-R, subject’s NIHSS scores decreased by .27 point (p=.001), mRS decreased by .11 point (p=.03), and level of CRP decreased 148.6 ng/ml (p=.02). However, LOT-R was not correlated with mRS the three-month follow-up. Conclusion: Optimistic stroke survivors showed lower inflammation, less stroke severity, and less physical disability. Although the number of patients was low in this initial cohort, understanding this relationship may provide a scientific framework whereby new strategies for stroke recovery can be developed.


Swiss Surgery ◽  
2000 ◽  
Vol 6 (1) ◽  
pp. 6-10
Author(s):  
Knoefel ◽  
Brunken ◽  
Neumann ◽  
Gundlach ◽  
Rogiers ◽  
...  

Die komplette chirurgische Entfernung von Lebermetastasen bietet Patienten nach kolorektalem Karzinom die einzige kurative Chance. Es gibt jedoch eine, anscheinend unbegrenzte, Anzahl an Parametern, die die Prognose dieser Patienten bestimmen und damit den Sinn dieser Therapie vorhersagen können. Zu den am häufigsten diskutierten und am einfachsten zu bestimmenden Parametern gehört die Anzahl der Metastasen. Ziel dieser Studie war es daher die Wertigkeit dieses Parameters in der Literatur zu reflektieren und unsere eigenen Patientendaten zu evaluieren. Insgesamt konnte von 302 Patienten ein komplettes Follow-up erhoben werden. Die gebildeten Patientengruppen wurden mit Hilfe einer Kaplan Meier Analyse und konsekutivem log rank Test untersucht. Die Literatur wurde bis Dezember 1998 revidiert. Die Anzahl der Metastasen bestätigte sich als ein prognostisches Kriterium. Lagen drei oder mehr Metastasen vor, so war nicht nur die Wahrscheinlichkeit einer R0 Resektion deutlich geringer (17.8% versus 67.2%) sondern auch das Überleben der Patienten nach einer R0 Resektion tendenziell unwahrscheinlicher. Das 5-Jahres Überleben betrug bei > 2 Metastasen 9% bei > 2 Metastasen 36%. Das 10-Jahres Überleben beträgt bislang bei > 2 Metastasen 0% bei > 2 Metastasen 18% (p < 0.07). Die Anzahl der Metastasen spielt in der Prognose der Patienten mit kolorektalen Lebermetastasen eine Rolle. Selbst bei mehr als vier Metastasen ist jedoch gelegentlich eine R0 Resektion möglich. In diesen Fällen kann der Patient auch langfristig von einer Operation profitieren. Das wichtigere Kriterium einer onkologisch sinnvollen Resektabilität ist die Frage ob technisch und funktionell eine R0 Resektion durchführbar ist. Ist das der Fall, so sollte auch einem Patienten mit mehreren Metastasen die einzige kurative Chance einer Resektion nicht vorenthalten bleiben.


1996 ◽  
Vol 35 (05) ◽  
pp. 146-152 ◽  
Author(s):  
A. Kögler ◽  
H.-A. Schmitt ◽  
D. Emrich ◽  
H. Kreuzer ◽  
D. L. Munz ◽  
...  

SummaryThis prospective study assessed myocardial viability in 30 patients with coronary heart disease and persistent defects despite reinjection on TI-201 single-photon computed tomography (SPECT). In each patient, three observers graded TI-201 uptake in 7 left ventricular wall segments. Gradient-echo magnetic resonance imaging in the region of the persistent defect generated 12 to 16 short axis views representing a cardiac cycle. A total of 120 segments were analyzed. Mean end-diastolic wall thickness and systolic wall thickening (± SD) was 11.5 ± 2.7 mm and 5.8 ± 3.9 mm in 48 segments with normal TI-201 uptake, 10.1 ± 3.4 mm and 3.7 ± 3.1 mm in 31 with reversible lesions, 11.3 ± 2.8 mm and 3.3 ± 1.9 mm in 10 with mild persistent defects, 9.2 ± 2.9 mm and 3.2 ±2.2 mm in 15 with moderate persistent defects, 5.8 ± 1.7 mm and 1.3 ± 1.4 mm in 16 with severe persistent defects, respectively. Significant differences in mean end-diastolic wall thickness (p <0.0005) and systolic wall thickening (p <0.005) were found only between segments with severe persistent defects and all other groups, but not among the other groups. On follow-up in 11 patients after revascularization, 6 segments with mild-to-moderate persistent defects showed improvement in mean systolic wall thickening that was not seen in 6 other segments with severe persistent defects. These data indicate that most myocardial segments with mild and moderate persistent TI-201 defects after reinjection still contain viable tissue. Segments with severe persistent defects, however, represent predominantly nonviable myocardium without contractile function.


2021 ◽  
Vol 80 (Suppl 1) ◽  
pp. 1132.3-1133
Author(s):  
G. Jurado Quijano ◽  
L. Fernández de la Fuente Bursón ◽  
B. Hernández-Cruz ◽  
P. Muñoz Reinoso ◽  
V. Merino Bohóquez ◽  
...  

Background:Rituximab (RTX) is a monoclonal antibody against the CD20 B cell antigen that has been used successfully in recent years for the treatment of rheumatoid arthritis (RA). It is an effective drug that reaches survival rates of 60% at 5 years of treatment as reflected in the British experience. However, survival in Spanish patients is unknown.Objectives:To study the survival of RTX treatment and the characteristics of patients with RA treated with the drug since its commercialization in Spain.Methods:Observational, retrospective and analytical study of a cohort of patients with RA treated with at least one dose of RTX. We reviewed the medical records of all patients with RA from January 2007 to June 2017. A total of 178 previous defined variables were collected, highlighting data about treatment (use of RTX, associated conventional synthetic disease modifying drugs [FAMEsc], doses of corticosteroids [GC] used) and activity indices. Descriptive statistics were performed (median and the 25th and 75th percentiles are shown). The comparative analysis was done with χ2 and U of Mann Whitney for categorical variables and paired sign rank test or Student’s t for continuous. Survival Kaplan Mayer curves were constructed. The study was carried out in accordance with the standards of our Clinical Research Ethics Committee.Results:A total of 54 patients were analyzed. 74% (n = 40) of them were women, the age was 61.2 years (51.0 - 67.4). 74% (n = 40) presented some type of relevant comorbidity. Its RA was FR + in 96% (n = 52) and ACCP + in 78% (n = 42) of the cases, with an evolution time of 9.3 years (3.5-19, 2), and with radiographic erosions in up to 63% (n = 34). At the time of the start of the RTX, 100% of the patients (n = 54) received some FAMEsc, and 33 (61%) were treated with prednisone; the daily dose of prednisone was 9 (6-12) mg. The baseline DAS28-VSG was 5 (4.1 - 6.0). The duration of the follow-up was 56.6 (29.3-92.1) months. Patients received a mean of 5 (1-6) cycles of RTX at a dose of 1000 mg on days 0 and 15 in most cases. The final DAS28-VSG was 2.6 (2.1 - 4.0), p = 0.00001 compared to baseline. The delta between baseline and final DAS was -2.36 (-0.55 - -3.1). At the end of the RTX treatment, the EULAR response rate was good in 64% (n = 25), reaching remission in 17 (31%) of the patients, and moderate response in 21% (n = 8) of them (Figure 1). Only 2 (4%) patients were treated with GCC at the end of the follow-up, p<0,00001 compared to baseline. The daily dose of PDN at the end of follow-up was 6 mg in a case and 12 mg in the other, p=00001 compared to baseline. At the end of the follow-up 24%of the patients (n = 13) changed or discontinued the drug: 9 changed due to secondary failure, 2 suspended due to adverse events, 1 due to death due to prior neoplastic process and 1 due to complete disease remission. Survival at 1, 2, 3, 4, 5, 6 and 7 years was 92%, 92%, 82% 78%, 75%, 75% and 65% respectively; with a mean survival rate of 90 months (Figure 1).Conclusion:The results of our analysis show that patients with RA undergoing RTX treatment have adequate control of disease activity and drug survival rates, like published data. RTX treatment allowed stopped GCC treatment in 31 cases (90%).References:[1]Oldroyd AGS, et al. Rheumatology (Oxford). 2018 Jun 1;57(6):1089-1096.Disclosure of Interests:Gonzalo Jurado Quijano: None declared, Lola Fernández de la Fuente Bursón: None declared, Blanca Hernández-Cruz Speakers bureau: Sociedad Española de Reumatología, Abbvie, Roche, Bristol, MSD, Lilly, Pfizer, Amgen, Sanofi, Consultant of: Abbvie, Lilly, Sanofi, STADA, UCB, Amgen, Grant/research support from: Fundación para la Investigación Sevilla, Junta de Andalucía, Fundación Andaluza de Reumatología, Paloma Muñoz Reinoso: None declared, Vicente Merino Bohóquez: None declared, José Javier Pérez Venegas: None declared


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