LOCATION OF POTENTIAL PLAQUE DESTABILIZING FEATURES IN HIGH-RISK PLAQUES WITH ABNORMAL RFR: SPATIAL HETEROGENEITY AMONG ENDOTHELIAL SHEAR STRESS (ESS) AND SHEAR STRESS GRADIENTS (ESSG)

Background: High risk plaque accounts for the majority of acute coronary events. Low endothelial shear stress (ESS) is a key factor of the natural history of atherosclerosis. The role of ESS in high risk plaque formation is not well studied in man. Hypothesis: To explore the association of low ESS with high risk plaque and to identify the ESS milieu and vascular remodeling response in high risk vs. non high risk plaque. Methods: 35 coronary arteries from 30 patients were 3D reconstructed with fusion of coronary angiography and optical coherence tomography (Fig A-D) . ESS was calculated in the 3D reconstructed arteries using computational fluid dynamics (Fig E) and classified into low, moderate and high in 3 mm long segments. In each segment: i) fibroatheromas were classified into high risk and non high risk based on fibrous cap thickness and lipid pool size ii) vascular remodeling was classified into constrictive, compensatory and expansive. Results: Fibroatheromas in low ESS segments had significantly thinner fibrous cap compared to high ESS segments (89±84 vs.138±83 μm, p<0.05). Lipid pool size was comparable across all ESS categories. The majority of low ESS segments co-localized with high risk plaques (29 vs. 9%, p<0.05), whereas the majority of high ESS co-localized with non high risk plaques (24 vs. 9%, p<0.05, Fig F ). Compensatory and expansive remodeling was the predominant remodeling response in low ESS segments containing high risk plaques. In non-stenotic fibroatheromas (expansive or compensatory remodeling) low ESS was predominantly associated with high risk plaques (29 vs. 3%, p<0.05) whereas high ESS was associated with non high risk plaques (Fig F) . Conclusions: Novel combined anatomic and functional imaging with 3D OCT showed that low ESS and non-constrictive remodeling are associated with high risk plaque in man. Further studies are needed to assess the role of ESS and vascular remodeling in high risk plaque rupture and precipitation of clinical outcomes.

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P869Predictive value of the endothelial shear stress distribution in three-dimensional quantitative coronary angiography models in detecting vulnerable plaques

European Heart Journal ◽

10.1093/eurheartj/ehz747.0466 ◽

2019 ◽

Vol 40 (Supplement_1) ◽

Author(s):

T Zanchin ◽

C Bourantas ◽

R Torii ◽

P W S Serruys ◽

A Karagiannis ◽

...

Keyword(s):

Shear Stress ◽

High Risk ◽

Coronary Angiography ◽

Intravascular Ultrasound ◽

Three Dimensional ◽

Quantitative Coronary Angiography ◽

Low Risk ◽

Plaque Burden ◽

Vulnerable Plaques ◽

Endothelial Shear Stress

Abstract Background Low Endothelial shear stress (ESS) is a well-known instigator of coronary atherosclerosis. Prospective intravascular ultrasound (IVUS)-based imaging studies with computational fluid dynamic analysis revealed its predictive merit in-vivo. However, whether coronary modelling derived from quantitative coronary angiography (QCA) is equally effective in detecting high-risk plaques remains to be established. Purpose To examine the value of endothelial shear stress (ESS) estimated in three-dimensional (3D) QCA models in detecting plaques that are likely to progress and cause events. Method We analysed the baseline intravascular ultrasound virtual histology (IVUS-VH) and angiographic data from 28 non-culprit lesions with a vulnerable phenotype (i.e., fibroatheroma or thin cap fibroatheroma) that caused major adverse cardiac events or required revascularization (nc-MACE-R) at 5-year follow-up and from a control group of 119 vulnerable plaques that remained quiescent. The segments studied by IVUS-VH at baseline were reconstructed using 3D-QCA software and in the obtained geometries blood flow simulation was performed and we estimated the resting Pd/Pa across the vulnerable plaque and the mean ESS values in 3mm sub-segments. A propensity score was built by the baseline plaque characteristics and the hemodynamic indices and its efficacy in detecting nc-MACE-R lesions was examined. Results Nc-MACE-R lesions were longer (32.5mm [18.0, 41.6], vs. 19.6mm [12.7, 31.3], p=0.03), had smaller minimum lumen area (MLA) (3.65mm2 [3.26, 4.36] vs. 5.03mm2 [3.98, 6.66], p<0.01), increased plaque burden (PB) (69.4% [63.5, 72.0] vs. 60.8% [53.7, 66.5], p<0.01), were exposed to higher ESS (9.40Pa [6.3, 12.5] vs. 4.1Pa [3.0, 6.9], p<0.01), and exhibited a lower resting Pd/Pa (0.97 [0.95, 0.98] vs. 0.98 [0.97, 0.99], p<0.01]. In multivariable analysis the only independent predictor of nc-MACE-R was the maximum 3mm ESS value (hazard ratio: 1.08 [1.02, 1.16], P=0.016). Lesions exposed to high ESS (>4.95Pa) with a high-risk anatomy (MLA<4mm2and PB>70%) had a higher nc-MACE-R rate (53.8%) than those with a low-risk anatomy exposed to high ESS (31.6%) or those exposed to low ESS that had high (20.0%) or low-risk anatomy (7.1%, P<0.001). Conclusion In the present study, 3D-QCA-derived local hemodynamic variables provided useful prognostic information and in combination with lesion anatomy enabled more accurate identification of nc-MACE-R lesions. Further research in a larger number of patients is need to confirm these findings before the conduction of large scale prospective studies that will combine intravascular imaging and 3D-QCA modelling to more accurately detect vulnerable plaques.

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Prediction of the Localization of High-Risk Coronary Atherosclerotic Plaques on the Basis of Low Endothelial Shear Stress

Circulation ◽

10.1161/circulationaha.107.695254 ◽

2008 ◽

Vol 117 (8) ◽

pp. 993-1002 ◽

Cited By ~ 263

Author(s):

Yiannis S. Chatzizisis ◽

Michael Jonas ◽

Ahmet U. Coskun ◽

Roy Beigel ◽

Benjamin V. Stone ◽

...

Keyword(s):

Shear Stress ◽

High Risk ◽

Atherosclerotic Plaques ◽

Endothelial Shear Stress

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Low Endothelial Shear Stress Is Associated With High-Risk Coronary Plaque Features and Microcalcification Activity

JACC Cardiovascular Imaging ◽

10.1016/j.jcmg.2021.06.016 ◽

2021 ◽

Author(s):

Lachlan J. Kelsey ◽

Jamie W. Bellinge ◽

Kamran Majeed ◽

Louis P. Parker ◽

Samantha Richards ◽

...

Keyword(s):

Shear Stress ◽

High Risk ◽

Coronary Plaque ◽

Endothelial Shear Stress

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P3468Coronary microvascular endothelial dysfunction is associated with low endothelial shear stress and high-risk coronary plaque characteristics in patients with early coronary atherosclerosis

European Heart Journal ◽

10.1093/eurheartj/ehx504.p3468 ◽

2017 ◽

Vol 38 (suppl_1) ◽

Author(s):

G. Siasos ◽

J. Sara ◽

M. Zaromytidou ◽

K.H. Park ◽

S.W. Yang ◽

...

Keyword(s):

Shear Stress ◽

High Risk ◽

Endothelial Dysfunction ◽

Coronary Atherosclerosis ◽

Coronary Plaque ◽

Endothelial Shear Stress ◽

Microvascular Endothelial

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Low endothelial shear stress, microcalcification activity and high-risk plaque features: merging computational flow modelling, OCT and 18F-NaF PET/CT

European Heart Journal ◽

10.1093/eurheartj/ehab724.0272 ◽

2021 ◽

Vol 42 (Supplement_1) ◽

Author(s):

B J Doyle ◽

L J Kelsey ◽

K Majeed ◽

J Bellinge ◽

L P Parker ◽

...

Keyword(s):

Shear Stress ◽

Acute Coronary Syndrome ◽

High Risk ◽

Critical Role ◽

Biologically Active ◽

Coronary Syndrome ◽

Funding Sources ◽

Positron Emission ◽

Arterial Plaque ◽

Endothelial Shear Stress

Abstract Background Endothelial shear stress (ESS) has a critical role in endothelial function. Abnormal shear stress leads to endothelial dysfunction, which contributes to arterial plaque initiation and development. Four dimensional magnetic resonance can determine shear stress in the larger arteries but cannot resolve the detail needed to calculate shear stress in the coronary arteries and thus methods such as computational fluid dynamics (CFD) are required. Additionally, a key feature of biologically active plaques is microcalcification activity, and this can be detected using 18F-sodium fluoride (18F-NaF) positron emission tomography (PET). Furthermore, using high resolution optical coherence tomography (OCT), the high-risk features plaques can be visualized and quantified. We aimed to merge these three techniques to investigate if low ESS is associated with high-risk plaque features and active microcalcifications in acute coronary syndrome. Methods We began by merging OCT images with CTCA images to obtain detailed 3D reconstructions of the target vessel. We then simulated blood flow and calculated the ESS, from which we extracted the area of low ESS (<0.4 Pa). We quantified plaque features using OCT and measured the maximum 18F-NaF uptake, and compared data at both the coronary segment and whole artery level (Figure 1). Results We investigated 20 arteries from 18 patients which we obtained 38 coronary segments according to the SCCT guidelines. We found that areas of low ESS were were significantly and positively associated with high-risk plaque features: macrophage infiltration (segment, rs=0.33, p=0.043; artery, rs=0.46, p=0.041) and presence of cholesterol crystals (segment, rs=0.45, p=0.005; artery, rs=0.58, p=0.007). Vessel segments with thin-capped fibroatheroma had greater area of low ESS (20 vs 4%). The uptake of 18F-NaF was positively associated with the area of low ESS (segment, rs=0.52, p=0.001; artery, rs=0.64, p=0.002). We found that there were typically more plaque features found in regions of low ESS (Table 1). Conclusion Here we provide the first data associating low ESS with both high-risk plaque features and active microcalcifications in patients with acute coronary syndrome. Although our sample size is small, these data are encouraging and could lead to better understanding of how best to deem a plaque “high risk”. FUNDunding Acknowledgement Type of funding sources: Public hospital(s). Main funding source(s): Royal Perth Hospital Medical Research Foundation Figure 1 Table 1

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