Optical Coherence Tomography and Other Emerging Diagnostic Procedures for Vulnerable Plaque

Introduction

Outcomes after percutaneous coronary intervention (PCI) have improved significantly over the past few decades, in large part because of newer stent platforms, better implantation techniques, and improved adjunctive medical therapy. However, the risk of recurrent cardiac events after successful PCI remains high, and the culprit site for these events often differs from that of the index procedure. Traditional clinical risk models, such as the Framingham risk score, are useful for predicting overall risk of atherosclerosis and coronary events. However, clinical risk indicators do not provide anatomic information, and angiographic parameters have poor predictive accuracy in identifying the specific high-risk lesions responsible for future coronary events. Early angiographic studies suggested that the culprit lesions for these recurrent events were often only mildly stenotic at the time of index angiography, whereas pathological studies of patients with fatal cardiac events found that most acute occlusive thromboses occurred at sites with a large plaque burden and severe luminal narrowing. Therefore, a significant amount of research has been devoted to exploring the risk factors for individual plaque progression and thrombosis. In this chapter, we explore the concept of plaque vulnerability as introduced by pathological studies (see Chapter 3 ), and the contribution of intravascular imaging, in particular, optical coherence tomography (OCT), toward extending our understanding of vulnerable plaques and facilitating their identification in vivo. The use of cardiac computed tomography and magnetic resonance imaging to characterize plaque composition in large arteries is discussed in Chapter 9 and Chapter 33 . Molecular imaging applications are addressed in Chapter 32 .

Definition of Vulnerable Plaque

Vulnerable plaques have been defined as those at high risk for evolving into culprit lesions, including both plaques that are prone to provoking thrombosis and plaques at risk for rapid progression. The framework for studying vulnerable plaque features was established by data from autopsy studies that examined the culprit lesions of patients with sudden coronary death (see also Chapter 3 ). These studies revealed three main patterns observed in thrombotic culprit lesions: plaque rupture, plaque erosion, and calcified nodules. Ruptured plaques are the most common, accounting for approximately 60% of cases, and are characterized by fibrous cap disruption with overlying thrombus that is in continuity with an underlying necrotic core. In contrast, eroded plaques are found in approximately 35% of cases and are characterized pathologically by coronary thrombus with an intact fibrous cap. The endothelial lining is commonly absent, exposing the intima, which is primarily composed of smooth muscle cells and proteoglycan. Calcified nodules include approximately 5% of cases and are identified pathologically by fibrous cap disruption and thrombus overlying a fractured calcified plate.

Pathological studies are limited to the retrospective identification of features prevalent in culprit plaques, which are assumed to contribute to plaque vulnerability. However, the introduction and development of intravascular imaging modalities has enabled the study of these same features in vivo and prospectively, and multiple studies have sought to validate and extend the vulnerable plaque hypotheses generated by pathological studies. Although each of the intravascular imaging modalities has unique advantages and disadvantages, they can be broadly grouped into modalities that provide primarily anatomic or compositional information, such as OCT, intravascular ultrasound (IVUS), near-infrared spectroscopy (NIRS), and intravascular magnetic resonance imaging (IV-MRI), and modalities that provide functional or biomechanical information, such as thermography, elastography and/or palpography, and near-infrared fluorescence (NIRF) imaging. In addition, some modalities that provide primarily anatomic information may also indirectly facilitate functional assessment; for example, the identification of macrophages may serve as a marker of local inflammation. However, none of these imaging modalities independently provides physiologic information on coronary hemodynamics, which is better evaluated with techniques such as fractional flow reserve (see Chapter 17 ).

Intravascular Assessment of Coronary Plaque Anatomy or Composition

Optical Coherence Tomography

OCT is a high-resolution intravascular imaging modality that enables the detailed characterization of plaque morphology in vivo. In a manner analogous to the use of sound waves in ultrasonography, OCT technology measures the magnitude and time delay of backscattered light waves to produce images resembling an “optical biopsy,” with 15- to 20-μm resolution. This represents a 10-fold improvement in resolution compared with IVUS and has allowed for the in vivo differentiation of fibrous, lipid, and calcific plaques ( Figure 10-1 ). In addition, OCT can be used in the detection of intraluminal thrombus and the identification of plaque rupture, plaque erosion, and calcified nodules ( Figure 10-2 ). The OCT definitions for these thrombosis mechanisms are based on the pathological definitions, with slight modifications to account for the possibility that luminal thrombus may dissolve or embolize distally, precluding its identification on in vivo imaging. Plaque rupture is identified on OCT imaging as lipid plaque with fibrous cap discontinuity and cavity formation inside the plaque. Because the coronary endothelial lining remains below the resolution of OCT imaging, OCT-defined plaque erosion is confirmed by the presence of attached thrombus overlying an intact and visualized plaque. Probable plaque erosion is identified by attached thrombus in the absence of underlying plaque or neighboring superficial lipid or calcium, or if there is culprit site luminal irregularity without an attached thrombus. Calcified nodules appear on OCT imaging as sites with fibrous cap disruption and underlying plaque characterized by protruding calcification, superficial calcium, and significant calcium adjacent to the lesion.

The high resolution of OCT imaging has enabled the identification of many features suggested by pathological studies to be associated with plaque vulnerability. Because of the high prevalence of plaque rupture as the underlying mechanism for coronary thrombus formation, the features and risk factors associated with plaque vulnerability for rupture are the most commonly studied, and therefore, are the best understood. These features include large extracellular lipid pools, thin fibrous caps, small calcifications, macrophage accumulation, microchannels, and cholesterol crystals ( Figure 10-3 ). However, these characteristics may differ from the features and risk factors associated with plaque erosion and calcified nodules.

Extracellular Lipid Pools

Autopsy studies have identified large lipid cores as a common feature of culprit plaques in patients with sudden coronary death. On OCT imaging, lipid appears as a homogeneous area with low-signal intensity (dark) and high-signal attenuation (significant shadowing) in contrast to fibrous tissue that appears as a homogeneous area with high-signal intensity (bright) and low-signal attenuation (no significant shadowing). Lipid-rich plaques are defined as those with a lipid arc of more than 90 degrees on cross-sectional imaging (see Figure 10-3A ). OCT studies have shown that lipid-rich plaques are more prevalent in the culprit lesions of patients with acute unstable presentations such as ST-elevation myocardial infarction (STEMI) or non–ST-elevation MI (NSTEMI) compared with those presenting with stable angina pectoris (SAP). Furthermore, lipid pools are associated with plaque progression. In a study of 53 patients with 69 nonculprit plaques (<50% luminal stenosis on angiography), OCT-identified lipid pools were significantly more prevalent in lesions that progressed on angiographic follow-up performed between 6 and 9 months later compared with lesions that did not progress (100% vs. 61%; P = .02).

Thin-Cap Fibroatheroma

Thin-cap fibroatheroma (TCFA) are postulated to represent the vulnerable precursor lesion for plaque rupture because of their morphological similarity (see also Chapter 3 ). On pathological examination, most ruptured coronary plaques have fibrous caps measuring less than 65 μm, and therefore, this threshold has been used to define thick- versus thin-cap fibroatheroma. The sharp contrast in appearance between lipid and fibrous tissue on OCT imaging, coupled with its high resolution, make it an ideal intravascular imaging modality for measuring fibrous cap thickness, thereby identifying TCFA (see Figure 10-3B ). Multiple OCT studies have shown a higher prevalence of TCFA at culprit sites in patients with acute or unstable clinical presentations compared with those with SAP. Initially, nonculprit plaques with TCFA are more likely to show progression on angiographic follow-up than those without TCFA. Moreover, statin therapy has been shown to increase fibrous cap thickness, suggesting that one of the mechanisms underlying the clinical benefit of statins is the stabilization of vulnerable TCFA plaques ( Figure 10-4 ).

Calcifications

Coronary artery calcium score, as assessed using cardiac computed tomography, has been shown to correlate with total atherosclerotic burden and risk for future events. However, biomechanical models and pathological studies suggest that the pattern of vascular calcification may be a more important determinant of local plaque vulnerability than the total burden of calcium. On OCT imaging, calcium deposits appear as heterogeneous areas of high- and low-signal intensity with low-signal attenuation and a sharp demarcating border. Spotty calcium deposits are defined as small calcifications with an arc ≤90 degrees on cross-sectional imaging (see Figure 10-3C ). In contrast to ultrasound signals, which are highly attenuated by calcium, the light waves used in OCT imaging are able to penetrate calcium, thereby allowing for more detailed characterization of calcium deposits and better visualization of structures deep to those deposits than is possible with IVUS. In a study of 189 patients with coronary artery disease who underwent OCT imaging of culprit lesions, the number of spotty calcium deposits was significantly greater in patients presenting with acute MI and unstable angina (UA) compared with those presenting with SAP. In addition, these calcium deposits were more superficial in location in the MI and UA groups than in the SAP groups. Although all imaged lesions in this study were culprit lesions, plaque rupture as an underlying mechanism correlated positively with the number of spotty calcium deposits and inversely with the number of large calcium deposits. Taken together, these results support the mechanistic hypothesis that small calcifications can increase plaque vulnerability for rupture.

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