Detection of Vulnerable Plaque With Intravascular Imaging: Case Closed

Abstract and Introduction

Introduction

Coronary artery lesions that result in myocardial ischemia are responsible for angina and anginal-equivalent symptoms such as exertional dyspnea; revascularization of these lesions improves functional capacity and quality of life, but in most patients does not prevent cardiac death or myocardial infarction (MI).^[1] In contrast, lesions that are prone to thrombose and place patients at risk for future major adverse cardiac events (MACE) are known as vulnerable plaques, many of which are angiographically mild and are difficult to detect. Pathologic studies have shown that most of these lesions are thin-cap fibroatheromas (TCFAs), characterized by a lipid-rich necrotic core consisting of free and esterified cholesterol with a thin (typically ≤55 μm) metabolically active inflamed fibrous cap that is prone to rupture and thrombosis.^[2] These TCFAs are typically positively remodeled and have a large plaque burden, but do not severely encroach the arterial lumen (Glagov phenomenon), and are thus not flow limiting.

PROSPECT (Providing Regional Observations to Study Predictors of Events in the Coronary Tree) was the first prospective, multicenter study to determine whether "stable" angiographically nonobstructive high-risk plaques could be identified with multimodality imaging before their causing clinical events. A total of 697 patients with recent acute coronary syndromes (ACS) underwent 3-vessel imaging with radiofrequency intravascular ultrasound (RF-IVUS). A total of 3,160 untreated IVUS-defined "nonculprit lesions" (NCLs) were characterized at a core laboratory at baseline, coregistered to the angiogram, and followed for a median of 3.4 years.^[3] Lesions from which future MACE arose during follow-up were at baseline angiographically benign (mean diameter stenosis 32%) but were often severe by IVUS (plaque burden ≥70%) and were frequently classified as a TCFA by RF imaging. The prospective, multicenter PROSPECT-II study validated these findings by using a combination near-infrared spectroscopy (NIRS)-IVUS catheter to image all 3 coronary arteries of 898 patients with recent MI. A total of 3,629 untreated NCLs were characterized at baseline. NIRS is a highly precise discriminator of lipid-rich plaque, and in this study a maxLCBI_4mm (maximum lipid core burden index over the worst 4 mm segment of a lesion) ≥325 (~32.5% lipid) and plaque burden ≥70% were independent predictors of lesion-level and patient-level events (both MI and new ACS requiring unplanned revascularization) during median 3.7-year follow-up.^[4] A small minimal luminal area (≤4.0 mm²) by IVUS was also an independent predictor of NCL-related future MACE in PROSPECT but not in PROSPECT-II. Other single-center and multicenter prospective and retrospective studies have since confirmed the ability of RF-IVUS and NIRS-IVUS to identify quiescent vulnerable plaques before they become clinically unstable.

Compared with IVUS, optical coherence tomography (OCT) has 10 to 20 times greater resolution and is the only imaging modality capable of truly assessing the thin fibrous cap. OCT also more accurately measures luminal dimensions than IVUS. However, OCT has limited depth penetration (especially in lipidic lesions) and thus typically cannot assess plaque burden. Several studies in which a limited portion of the coronary tree was imaged by OCT in patients with stable and unstable coronary syndromes have suggested that a thin fibrous cap (≤65 μm to 75 μm) or a large circumferential lipid arc (≥180°) identifies high-risk untreated NCLs prone to future MACE.^[5–8] However, 3-vessel imaging was not performed in these studies, and median follow-up was limited to 1 to 2 years.

In this issue of the Journal of the American College of Cardiology, these limitations have been addressed by Jiang et al,^[9] who report the results from a single-center retrospective study from Harbin, China, in which 3-vessel OCT was performed in 1,118 patients with recent MIs. After excluding 235 patients mainly for suboptimal imaging, massive thrombus, or previous revascularization, the study cohort comprised 883 patients in whom OCT identified 3,757 untreated NCLs, 515 (13.7%) of which were TCFAs (defined in this study as a lipidic plaque with both fibrous cap thickness <65 μm and lipid arc >180°). With median follow-up of 3.3 years, 34 events (5 MIs and 29 unplanned revascularization procedures) were attributed to NCLs. Both an OCT-defined TCFA and OCT-minimal lumen area (MLA) ≤3.5 mm² were independent predictors of events during follow-up. Of note, a small MLA may denote ischemia, which may have driven some of the revascularization events (lesions were not required to be proven nonflow limiting as in other studies^[4,5]). However, the majority (65%) of NCL-related events were associated with angiographic rapid lesion progression, suggesting that most were vulnerable plaque related. In this regard a small MLA is a surrogate for large plaque burden, which is itself a surrogate for pathologic TCFA.

J Am Coll Cardiol. 2023;81(13):1231-1234. © 2023 American College of Cardiology Foundation