TCT: Can new coronary imaging techniques help predict future events?
SAN FRANCISCO—In PROSPECT, the first prospective, natural history trial of atherosclerosis using multimodality imaging to characterize the coronary tree, researchers found that about 20 percent of patients with acute coronary syndromes (ACS) successfully treated with stents and medical therapy develop at least one major coronary event (MACE) within three years, with adverse events equally attributable to recurrence at originally treated culprit lesions and to previously untreated non-culprit coronary segments. The results of PROSPECT were revealed during the late breaking clinical trials on Thursday at the 2009 Transcatheter Cardiovascular Therapeutics (TCT) scientific meeting.

The first-of-its-kind trial was presented by Gregg W. Stone, MD, director of cardiovascular research and education at the Center for Interventional Vascular Therapy at New York-Presbyterian Hospital/Columbia University Medical Center in New York City, who called it the most complex trial he has ever worked on.

“In cath labs, we’re pretty good in treating symptoms and lesions that present with symptoms; however, we are not good at predicting which patients will have sudden death, MI or unexpected cardiovascular events,” Stone said. “Even a coronary angiogram is not a very good predictor of who is going to have events in the future.”

He explained that most cases of sudden cardiac death and MI are thought to arise from plaque rupture with subsequent thrombotic coronary occlusion of angiographically mild lesions, or so-called vulnerable plaques. However, the event rate attributable to the progression of vulnerable plaque has never been prospectively assessed.

To examine these questions, the researchers performed a prospective, multicenter natural history study on 700 ACS patients using three-vessel multimodality intracoronary imaging—angiography, intravascular ultrasound (IVUS) and virtual histology—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. Almost all patients were troponin positive.

After the patients underwent an angiogram, every millimeter of their lesions was imaged, equaling 310,000 millimeters of lesions imaged. IVUS and virtual histology imaged a proximal 6-8 cm of each coronary artery. Also, repeat imaging occurred in patients with events.

At three years of follow up, 20.4 percent had a major adverse cardiac event (MACE), which the investigators defined as either cardiac death, cardiac arrest, MI, unstable or increasing angina requiring hospitalization. Approximately 12 percent of patients developed MACE from non-culprit lesions (areas that were not previously treated) during three years of follow up.

Among many of the trial’s revelations are that most untreated plaques that cause unexpected MIs are not mild lesions, as previously thought, but actually have a large plaque burden and a small lumen area. According to Stone, these are characteristics that were not visible to the coronary angiogram, but are detectable by IVUS.

Only about half of new cardiac events due to non-culprit lesions exemplified the classic notion of vulnerable plaque (11.6 percent), while half were attributable to unrecognized and untreated severe disease with minimal change over time. Also, Stone noted that most of the patients in the trial presented to hospital with unstable angina, not a so-called hard event.

For the first time it was demonstrated that characterization of the underlying plaque composition (with virtual histology [VH]) was able to significantly improve the capability to predict future adverse events over standard imaging techniques.

Importantly, the trial identified three independent predictors of future events related to non-culprit lesions: VH-thin cap fibroatheroma (VH-TCFA), being present on virtual histology; a minimal luminal area of less than 4 mm on IVUS and a plaque burden of greater than 70 percent on IVUS. The VH-TCFA represented the highest risk lesion type.

The combination of large plaque burden and a large necrotic core without a visible cap (VH-TCFA) identifies lesions which are at especially high risk for future adverse cardiovascular events. Over a three-year period in this patient population, 15 percent of those lesions would be problematic. However, these types of lesions are only present in 11 percent of patients.

The trial speaks to the limitations of angiography, according to Stone. “Angiography does a very good job for severe lesions, but for borderline lesions or no lesions, we are often missing the complete picture,” he said.

Yet, he also noted that the event rate was not high enough to justify routine three-vessel invasive screening.

“As a result of the PROSPECT trial, we are closer to being able to predict—and therefore prevent—sudden and unexpected adverse cardiac events,” Stone said. “These results mean that using a combination of imaging modalities, including IVUS, to identify lesions with a large plaque burden or small lumen area, and virtual histology to identify a large necrotic core without a visible cap [a thin cap fibroatheroma] identifies the lesions that are at especially high risk of causing future adverse cardiovascular events.”