In Vivo Assessment of the Risk Profile of Evolving Individual Coronary Plaques

Abstract

T he natural history of coronary plaques within an individual patient with coronary disease is highly heterogeneous. Over time, each plaque may exhibit a different temporal pattern of progression, quiescence, or regression, as well as a variable rate of change. The trajectory of the natural history of a particular plaque depends on the level of systemic risk factors and patient-specific genetics, as well as local phenomena, such as the detailed local blood flow patterns, arterial wall characteristics, including plaque size and shape, and arterial remodeling characteristics. Local endothelial shear stress (ESS) is one of the most fundamental factors influencing endothelial structure and function, and it is the central factor responsible for the localization of coronary atherosclerotic plaque formation and progression. 1 Recent methodological innovations allow detailed in vivo characterization of local ESS and remodeling behavior of the artery based on biplane angiography, intravascular ultrasound (IVUS), reconstruction of the artery in 3-dimensional space, and computational fluid dynamics calculations. 2,3 Analysis of the radiofrequency patterns from the IVUS signal has also been used to estimate plaque composition. 4 These methodologies not only allow detailed characterization of plaque at a single point in time but, if studied in a serial manner, now allow prognostic insight into how plaques change over time and what antecedent features predict the future behavior of that plaque. Article see p 779Animal models have been extremely helpful in identifying the anatomic natural history of coronary plaque because in vivo serial studies can be performed over time and histological validation of the in vivo IVUS studies can be performed at the end of an animal's course of study. Such investigations have demonstrated that the formation of plaque and the remodeling response of the arterial wall to that plaque are highly variable and change dramatically over time. 5 Focal areas of low ESS, located at the inner surface of curved sections of the epicardial coronary arteries, at bifurcations and branch points, and downstream from an existing luminal obstruction, consistently lead to increased expression of proatherogenic and proinflammatory genes, which result in the formation and progression of focal plaque, culminating in highly inflamed atheromata with intense accumulation of lipids and activated inflammatory cells, augmented expression and activity of matrix-degrading enzymes, and disruption of supporting matrix, associated with subsequent excessive expansive remodeling and thinning of the fibrous cap overlying the plaque. 6 -8 Areas of moderate or physiological shear stress are generally vasculoprotective, with increased expression of atheroprotective molecules, such as nitric oxide and decreased expression of degrading enzymes. 8,9 Areas of high ESS may be associated with atrophy of smooth muscle cells, increased macrophages, matrix degradation, increased thrombogenicity, and high mechanical strain. 10 -14 Pilot seria...

Wall shear stress and evolution of coronary atherosclerosis: an emerging intravascular imaging modality

“…A large-scale natural history study (506 patients with 1-year follow-up), PREDICTION, evaluating the role of coronary WSS in patients with CAD has recently been completed. Preliminary results of the PREDICTION study are largely in keeping with our findings and show that low WSS is an independent predictor of worsening lumen narrowing, the need for percutaneous coronary intervention and is indicitaive of major adverse cardiac events at follow-up [15,16].…”

Evolution of intracranial atherosclerotic disease under modern medical therapy

“…46 From a broader perspective, apart from controlling conventional atherosclerotic risks, in vivo studies of coronary artery disease have revealed the importance of other factors in plaque remodeling; patient-specific genetics, local hemodynamics and endothelial shear stress, arterial wall and remodeling characteristics, and plaque size and shape also played determining roles. 47,48 The diverging clinical and angiographic outcomes in our patients amid a relatively uniform risk factor control might reflect an intricate interplay of these factors. Although remodeling of intracranial plaques remains largely unknown, further studies of the natural history of ICAD are crucial for defining the indication and time window of any forthcoming treatment that aims to improve stenosis.…”

A novel framework for fluid/structure interaction in rapid subject specific simulations of blood flow in coronary artery bifurcations

“…Thanks to rapid modeling, this methodology not only allows characterization of arterial plaque at a single point in time but, also allows prognostic insight into how plaques evolve over time 38 . If it were possible to recognize in vivo plaques that were expected to develop features of rupture prone lesions, specific interventions could be performed to avoid adverse cardiac event.…”