Acute myocardial infarction (AMI) is a leading cause of death in the United States and industrialized countries.1,2
Research conducted over the past 15 years has demonstrated that several types of minimally or modestly stenotic atherosclerotic plaques, termed vulnerable plaques, are precursors to coronary thrombosis, myocardial ischemia, and sudden cardiac death. Postmortem studies have identified one type of vulnerable plaque, the thin-cap fibroatheroma (TCFA), as the culprit lesion in approximately 80% of sudden cardiac deaths.3–7
Over 90% of TCFAs are found within the most proximal 5.0 cm segment of each of the main coronary arteries [left anterior descending (LAD); left circumflex (LCx); and right coronary artery (RCA)].3,5
The TCFA is typically a minimally occlusive plaque characterized histologically by the following features: (1) thin fibrous cap (<65 µm), (2) large lipid pool, and (3) activated macrophages near or within the fibrous cap.3,5,7–9
It is hypothesized that these features predispose TCFAs to rupture in response to biomechanical stresses.10,11
Following rupture and the release of procoagulant proteins, such as tissue factor, a substrate for thrombus formation is created, leading to an acute coronary event.12,13
While TCFAs are associated with the majority of AMIs, recent autopsy studies have shown that coronary plaques with erosions or superficial calcified nodules may also precipitate thrombosis and sudden occlusion of a coronary artery.3,5,14,15
Although autopsy studies have been valuable in determining features of culprit plaques, the retrospective nature of these studies limits their ability to quantify the risk of an individual plaque for causing acute coronary thrombosis. For instance, TCFAs are a frequent autopsy finding in asymptomatic or stable patients and are found with equal frequency in culprit and nonculprit arteries in acute coronary syndromes.16
Moreover, disrupted TCFAs have been found in 10% of non-cardiac deaths.16
Recent findings of multiple ruptured plaques17
and increased systemic inflammation in acute patients18–20
has challenged the notion of a single vulnerable plaque as the precursor for AMI.19,21,22
An improved understanding of the natural history and clinical significance of these lesions would accelerate progress in diagnosis, treatment, and prevention of coronary artery disease (CAD).
An attractive approach to studying the evolution of vulnerable plaques is noninvasive or intracoronary imaging of individual lesions at multiple time points. Unfortunately, the microscopic features that characterize vulnerable plaque are not reliably identified by conventional imaging technologies such as intravascular ultrasound (IVUS),23–28
While experimental intracoronary imaging modalities such as integrated backscatter IVUS,36,37
have been investigated for the detection of vulnerable plaque, no method to date has been shown to reliably identify all of the characteristic features of these lesions.