The pathophysiologic factors underlying the transition from a stable lesion to a vulnerable plaque that subsequently undergoes disruption are not fully delineated. Likely mechanisms include local coronary and systemic inflammation, local coronary shear stress, alterations in lipid chemistry, status of blood thrombogenicity, and other factors (1). Regardless of the factors involved, disease transition may be reasonably considered analogous to the clinical “flares” characteristic of chronic inflammatory disorders (e.g., inflammatory bowel disease) in which a quiescent process smolders and then “flares.” The concept that such disease “flares” characterize ACS patients is supported by observations that demonstrate that, in comparison with those with chronic stable angina, unstable patients manifest evidence of multifocal plaque instability and multiple TCFAs, local and systemic inflammation, that persistent systemic inflammation predicts recurrent events and that in ACS cases are at higher risk for recurrent clinical instability arising from nonculprit lesions (3, 4, 5, 6, 7, 8, 9, 10, 11 and 12). In aggregate, these observations support the concept that plaque vulnerability and instability reflect pan-coronary destabilization processes associated with greater “disease activity.”

However, it must be emphasized that asymptomatic “stable” patients also are at risk for ACS events. Moreover, clinical symptomatic status does not necessarily reflect underlying plaque pathophysiology. The traditional view of “stable angina” is that this clinical entity typically reflects stable flow-limiting stenosis resulting from indolent, steady accretion of plaque. However, observations from pathologic and direct coronary imaging studies now document that some patients with clinically “stable” angina manifest evidence of plaque disruption (1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11 and 12). Such events could underlie the transition from an asymptomatic state to the onset of exertional angina, as plaque disruption facilitates rapid lesion progression, from a hemodynamically insignificant lesion to a flow-limiting stenosis. Thus, all patients with atherosclerosis are at risk for VP that may result in catastrophic complications, thereby offering a future opportunity to identify lesions at risk and potentially preempt disruption and its complications.

First, it is essential to consider plaque characterization terminology and technology (14). The following definition of terms is offered: (a) “Unstable plaque,” the proximate cause of ACS characterized pathologically by a ruptured inflamed plaque with superimposed thrombus; (b) “Complex lesions,” the invasive angiographic hallmark of a frankly unstable plaque, characterized by haziness, fissuring, ulceration, filling defect, and impaired flow; (c) VP, a rupture-prone precursor of unstable plaque, linked pathologically to thin-capped fibroatheroma (TCFA); (d) “Culprit lesion,” the unstable plaque responsible for ACS; and (e) “Target” lesion, that plaque designated for revascularization. Unfortunately, although these definitions are widely accepted, these terms are often applied imprecisely or misused interchangeably.

An appreciation of the information necessary to precisely characterize plaques and fundamental data provided by plaque imaging technologies is essential. The ideal invasive tool for characterization of coronary plaque would provide a complete roadmap of atherosclerotic burden throughout the coronary tree and provide comprehensive per plaque analysis (Table 9-1, (6)).