SAN FRANCISCO, Calif.—In ACS patients treated with stents and medical therapy, culprit and non-culprit lesions contribute equally to the risk of three-year adverse events. Identification of lesions can be enhanced by intravascular ultrasound (IVUS) and virtual histology (VH), according to the first prospective, natural history study of atherosclerosis using multimodality imaging to characterize the coronary tree.

TCT Course Director Gregg W. Stone, MD, of Columbia University Medical Center, New York, presented results from the PROSPECT study in a late-breaking session Thursday. “Most cases of sudden cardiac death and MI are believed to arise from plaque rupture with subsequent thrombotic coronary occlusion of angiographically mild lesions (so-called ‘vulnerable plaques’), the prospective detection of which has not been achieved,” Stone said, adding that the event rate attributed to progression of such lesions has never been prospectively studied.

The PROSPECT researchers therefore sought to “quantify the clinical event rate due to atherosclerotic progression and to identify those lesions which place patients at risk for unexpected adverse cardiovascular events,” Stone said.

Non-culprit lesions no worse

PROSPECT included 700 patients with ACS — either STEMI within 24 hours (30.3%), non-STEMI (65.6%) or unstable angina with ECG changes (4.2%) — who underwent successful PCI in one or two major coronary arteries at 37 centers in the United States and Europe. The investigators performed quantitative coronary angiography (QCA) of the entire coronary tree, IVUS and VH.

Over a median follow-up period of 3.4 years, the culprit and non-culprit lesions led to similar levels of MACE, a composite of cardiac death, cardiac arrest, MI, unstable angina and increasing angina. Half of the events occurred within one year and half between one and three years (see Figure 1).

The non-culprit lesions were not linked to any cases of cardiac death or arrest but were most commonly associated with increasing angina (8.5%), unstable angina (3.3%) and MI (1.0%). If all of the deaths that could not be definitively linked to either a culprit or non-culprit lesion were attributed to the non-culprit lesions, the worst-case scenario would be a combined cardiac death/cardiac arrest/MI rate of 3.3% in that group, Stone said.

Predictors identify risky lesions

Baseline clinical and angiographic factors were poor predictors of non-culprit lesion-related events. Insulin-dependent diabetes was the strongest risk factor (HR=4.07; 95% CI, 1.75-9.46).

IVUS characteristics and VH plaque type, however, were much more informative. Among them, multivariable analysis found five independent predictors of events (see Figure 2).

“The prospective identification of non-culprit lesions prone to develop MACE within three years can be enhanced by characterization of underlying plaque morphology with virtual histology, with virtual histology-thin-cap fibroatheromas (VH-TCFA) representing the highest-risk lesion type,” concluded Stone. “Specifically, the combination of large plaque burden detected by IVUS and a large necrotic core without a visible cap, that is, a VH-TCFA, identifies lesions which are at especially high risk for future adverse cardiovascular events.”

Questioning the role of imaging

Discussant John A. Ambrose, MD, of the University of California Fresno, Fresno, Calif., asked fellow panelists to discuss whether the data justify a more aggressive approach with IVUS and possibly VH imaging at baseline. In addition, he asked, “do these data support the ultimate goal of finding and locally treating a vulnerable plaque?”

Cindy L. Grines, MD, of William Beaumont Hospital, Royal Oak, Mich., replied that the latter question may not be possible to answer. “I’m struck by the fact that although we’ve been taught that non-culprit lesions are usually angiographically not severe, Gregg did a great job at showing that many of these lesions are severe, we’re just not very good at assessing them angiographically. This speaks toward more imaging . . . to determine more of the plaque burden and to characterize that plaque.”

“The next question is, how do you treat that?” Grines continued. “When you have the thin-cap fibroatheroma, those might be more prone to thrombosis or prone to no reflow or plaque shifting when we perform PCI. And clearly this speaks to the need for a randomized trial to determine that.”

Disclosures:

• Dr. Stone reports serving on the advisory boards of Abbott Vascular and Boston Scientific and being a consultant to InfraReDx.
• Dr. Ambrose reports no relevant conflicts of interest.
• Dr. Grines reports serving as a consultant to Abbott Vascular, Boston Scientific, InfraReDx and Possis Medical