Role of Low Endothelial Shear Stress and Plaque Characteristics in the Prediction of Nonculprit Major Adverse Cardiac Events: The PROSPECT Study.

Objectives: This study sought to determine whether low endothelial shear stress (ESS) adds independent prognostication for future major adverse cardiac events (MACE) in coronary lesions in patients with high-risk acute coronary syndrome (ACS) from the United States and Europe.

Background: Low ESS is a proinflammatory, proatherogenic stimulus associated with coronary plaque development, progression, and destabilization in human-like animal models and in humans. Previous natural history studies including baseline ESS characterization investigated low-risk patients.

Intravascular hemodynamics and coronary artery disease: New insights and clinical implications.

Intracoronary hemodynamics play a pivotal role in the initiation and progression of the atherosclerotic process. Low pro-inflammatory endothelial shear stress impacts vascular physiology and leads to the occurrence of coronary artery disease and its implications.

Heterogeneity of Coronary Plaque Morphology and Natural History: Current Understanding and Clinical Significance.

Purpose Of Review: Despite the important progress in identifying high-risk atherosclerotic plaques, many key elements are elusive. Advanced imaging modalities provide valuable information about the anatomic and functional plaque characteristics and underscore the presence of multiple plaque morphologies. However, how the heterogeneity of atherosclerotic plaque can alter our current understanding of coronary artery disease is not fully understood.

Effects of Low Endothelial Shear Stress After Stent Implantation on Subsequent Neointimal Hyperplasia and Clinical Outcomes in Humans.

Background: In-stent hyperplasia (ISH) may develop in regions of low endothelial shear stress (ESS), but the relationship between the magnitude of low ESS, the extent of ISH, and subsequent clinical events has not been investigated.

Methods And Results: We assessed the association of poststent ESS with neointimal ISH and clinical outcomes in patients treated with percutaneous coronary interventions (PCI). Three-dimensional coronary reconstruction was performed in 374 post-PCI patients at baseline and 6 to 10 months follow-up as part of the PREDICTION Study.

Atherosclerotic plaque behind the stent changes after bare-metal and drug-eluting stent implantation in humans: Implications for late stent failure?

Background And Aims: The natural history and the role of atherosclerotic plaque located behind the stent (PBS) are still poorly understood. We evaluated the serial changes in PBS following bare-metal (BMS) compared to first-generation drug-eluting stent (DES) implantation and the impact of these changes on in-stent neointimal hyperplasia (NIH).

Methods: Three-dimensional coronary reconstruction by angiography and intravascular ultrasound was performed after intervention and at 6-10-month follow-up in 157 patients with 188 lesions treated with BMS (n = 89) and DES (n = 99).

Effect of the local hemodynamic environment on the de novo development and progression of eccentric coronary atherosclerosis in humans: insights from PREDICTION.

Background: Eccentric distribution of atheroma has been associated with plaques likely to rupture and cause an acute coronary syndrome, but the factors responsible for the development of eccentricity remain unknown. Endothelial shear stress (ESS) drives plaque formation. We aimed to investigate the role of the local ESS characteristics in the de novo development and progressive worsening of plaque eccentricity in humans.

How do we prevent the vulnerable atherosclerotic plaque from rupturing? Insights from in vivo assessments of plaque, vascular remodeling, and local endothelial shear stress.

Coronary atherosclerosis progresses both as slow, gradual enlargement of focal plaque and also as a more dynamic process with periodic abrupt changes in plaque geometry, size, and morphology. Systemic vasculoprotective therapies such as statins, angiotensin-converting enzyme inhibitors, and antiplatelet agents are the cornerstone of prevention of plaque rupture and new adverse clinical outcomes, but such systemic therapies are insufficient to prevent the majority of new cardiac events. Invasive imaging methods have been able to identify both the anatomic features of high-risk plaque and the ongoing pathobiological stimuli responsible for progressive plaque inflammation and instability and may provide sufficient information to formulate preventive local mechanical strategies (eg, preemptive percutaneous coronary interventions) to avert cardiac events.

Endothelial shear stress and coronary plaque characteristics in humans: combined frequency-domain optical coherence tomography and computational fluid dynamics study.

Background: Despite the exposure of the entire vasculature to the atherogenic effects of systemic risk factors, atherosclerotic plaques preferentially develop at sites with disturbed flow. This study aimed at exploring in vivo the relationship between local endothelial shear stress (ESS) and coronary plaque characteristics in humans using computational fluid dynamics and frequency-domain optical coherence tomography.

Methods And Results: Three-dimensional coronary artery reconstruction was performed in 21 patients (24 arteries) presenting with acute coronary syndrome using frequency-domain optical coherence tomography and coronary angiography.

Anatomically correct three-dimensional coronary artery reconstruction using frequency domain optical coherence tomographic and angiographic data: head-to-head comparison with intravascular ultrasound for endothelial shear stress assessment in humans.

Aims: To develop a methodology that permits accurate 3-dimensional (3D) reconstruction from FD-OCT and angiographic data enabling reliable evaluation of the ESS distribution, and to compare the FD-OCT-derived models against the established models based on angiography/IVUS.

Methods And Results: Fifteen patients (17 coronary arteries) who underwent angiography, FD-OCT and IVUS examination during the same procedure were studied. The FD-OCT and IVUS lumen borders were placed onto the 3D luminal centreline derived from angiographic data.

Synergistic effect of local endothelial shear stress and systemic hypercholesterolemia on coronary atherosclerotic plaque progression and composition in pigs.

Background: Systemic risk factors and local hemodynamic factors both contribute to coronary atherosclerosis, but their possibly synergistic inter-relationship remains unknown. The purpose of this natural history study was to investigate the combined in-vivo effect of varying levels of systemic hypercholesterolemia and local endothelial shear stress (ESS) on subsequent plaque progression and histological composition.

Methods: Diabetic, hyperlipidemic swine with higher systemic total cholesterol (TC) (n=4) and relatively lower TC levels (n=5) underwent three-vessel intravascular ultrasound (IVUS) at 3-5 consecutive time-points in-vivo.

Thin-capped atheromata with reduced collagen content in pigs develop in coronary arterial regions exposed to persistently low endothelial shear stress.

Objective: The mechanisms promoting the focal formation of rupture-prone coronary plaques in vivo remain incompletely understood. This study tested the hypothesis that coronary regions exposed to low endothelial shear stress (ESS) favor subsequent development of collagen-poor, thin-capped plaques.

Approach And Results: Coronary angiography and 3-vessel intravascular ultrasound were serially performed at 5 consecutive time points in vivo in 5 diabetic, hypercholesterolemic pigs.

A new methodology for accurate 3-dimensional coronary artery reconstruction using routine intravascular ultrasound and angiographic data: implications for widespread assessment of endothelial shear stress in humans.

Aims: To develop and validate a new methodology that allows accurate 3-dimensional (3-D) coronary artery reconstruction using standard, simple angiographic and intravascular ultrasound (IVUS) data acquired during routine catheterisation enabling reliable assessment of the endothelial shear stress (ESS) distribution.

Methods And Results: Twenty-two patients (22 arteries: 7 LAD; 7 LCx; 8 RCA) who underwent angiography and IVUS examination were included. The acquired data were used for 3-D reconstruction using a conventional method and a new methodology that utilised the luminal 3-D centreline to place the detected IVUS borders and anatomical landmarks to estimate their orientation.

Relation of distribution of coronary blood flow volume to coronary artery dominance.

Coronary artery dominance influences the amount and anatomic location of myocardium that is perfused by the left or right coronary circulation. However, it is unknown whether coronary artery dominance also influences the distribution of coronary blood flow volume. The aim of this study was to evaluate volumetric coronary blood flow in 1,322 vessels from 496 patients in the Prediction of Progression of Coronary Artery Disease and Clinical Outcomes Using Vascular Profiling of Endothelial Shear Stress and Arterial Wall Morphology (PREDICTION) study.

Shear-activated nanotherapeutics for drug targeting to obstructed blood vessels.

Obstruction of critical blood vessels due to thrombosis or embolism is a leading cause of death worldwide. Here, we describe a biomimetic strategy that uses high shear stress caused by vascular narrowing as a targeting mechanism--in the same way platelets do--to deliver drugs to obstructed blood vessels. Microscale aggregates of nanoparticles were fabricated to break up into nanoscale components when exposed to abnormally high fluid shear stress.

Endothelial shear stress in the evolution of coronary atherosclerotic plaque and vascular remodelling: current understanding and remaining questions.

The heterogeneity of plaque formation, the vascular remodelling response to plaque formation, and the consequent phenotype of plaque instability attest to the extraordinarily complex pathobiology of plaque development and progression, culminating in different clinical coronary syndromes. Atherosclerotic plaques predominantly form in regions of low endothelial shear stress (ESS), whereas regions of moderate/physiological and high ESS are generally protected. Low ESS-induced compensatory expansive remodelling plays an important role in preserving lumen dimensions during plaque progression, but when the expansive remodelling becomes excessive promotes continued influx of lipids into the vessel wall, vulnerable plaque formation and potential precipitation of an acute coronary syndrome.

Prediction of progression of coronary artery disease and clinical outcomes using vascular profiling of endothelial shear stress and arterial plaque characteristics: the PREDICTION Study.

Background: Atherosclerotic plaques progress in a highly individual manner. The purposes of the Prediction of Progression of Coronary Artery Disease and Clinical Outcome Using Vascular Profiling of Shear Stress and Wall Morphology (PREDICTION) Study were to determine the role of local hemodynamic and vascular characteristics in coronary plaque progression and to relate plaque changes to clinical events.

Methods And Results: Vascular profiling, using coronary angiography and intravascular ultrasound, was used to reconstruct each artery and calculate endothelial shear stress and plaque/remodeling characteristics in vivo.

Evaluation of artery visualizations for heart disease diagnosis.

Heart disease is the number one killer in the United States, and finding indicators of the disease at an early stage is critical for treatment and prevention. In this paper we evaluate visualization techniques that enable the diagnosis of coronary artery disease. A key physical quantity of medical interest is endothelial shear stress (ESS).

The effect of statins on high-risk atherosclerotic plaque associated with low endothelial shear stress.

Purpose Of Review: Low endothelial shear stress (ESS) plays an important role in the progression and severity of atherosclerotic lesions. As 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors (statins) appear to stabilize plaque, it would be valuable to understand how statins affect the nature of lesions in the proatherogenic and proinflammatory environment of low ESS and the effect of statins on that atherosclerotic process. The purpose of this review is to summarize the relationship among low ESS, high-risk plaque and statins.

Augmented expression and activity of extracellular matrix-degrading enzymes in regions of low endothelial shear stress colocalize with coronary atheromata with thin fibrous caps in pigs.

Background- The molecular mechanisms that determine the localized formation of thin-capped atheromata in the coronary arteries remain unknown. This study tested the hypothesis that low endothelial shear stress augments the expression of matrix-degrading proteases and thereby promotes the formation of thin-capped atheromata. Methods and Results- Intravascular ultrasound-based, geometrically correct 3-dimensional reconstruction of the coronary arteries of 12 swine was performed in vivo 23 weeks after initiation of diabetes mellitus and a hyperlipidemic diet.

Regulation of heparanase expression in coronary artery disease in diabetic, hyperlipidemic swine.

Objective: Enzymatic degradation of the extracellular matrix is known to be powerful regulator of atherosclerosis. However, little is known about the enzymatic regulation of heparan sulfate proteoglycans (HSPGs) during the formation and progression of atherosclerotic plaques.

Methods And Results: Swine were rendered diabetic through streptozotocin injection and hyperlipidemic through a high fat diet.