The early indications suggested vulnerable plaque imaging should have become the natural next step in coronary artery disease (CAD) diagnosis. Cardiologist James E. Muller, MD, was the first person to recognize in 1989 that there was something wrong about the commonly held belief about arterial narrowing and MI.
He offered a new view with vulnerable plaque as the cause. Researchers would soon appreciate that an infarction is actually a cascade of catastrophic events beginning with the rupture of the plaque’s thin fibrous cap and the release of its lipid core into the coronary blood stream. Clotting blood produces a thrombus blocking the artery. Within minutes, myocardial muscle cells become ischemic and start to die.
Revelations about the actual cause of MI led researchers to seek out new ways to diagnose, evaluate, treat and prevent coronary heart disease, stroke and other lethal forms of atherosclerosis. The effort capitalized on contemporary discoveries in immunology, angiogenesis, genomics and proteomics. It became an important part of the new scientific disciplines of molecular medicine and molecular imaging. New intravascular ultrasound (IVUS), optical coherence tomography (OCT) and noninvasive PET, SPECT, MRI, multidetector CT technologies generated images and data elucidating plaque behavior.
But bridging the gap between bench science and clinical practice has not been easy, according to Zahi A. Fayad, MD, director of cardiovascular imaging research at the Mount Sinai Medical Center in New York City. “We first had to understand the biology, which was not simple,” he says. “Finding the right tool is not obvious. It’s a long road, but we are getting closer.”
In the meantime, the diagnosis of CAD has not changed appreciably. Invasive x-ray coronary angiography remains the gold standard. Cardiac catheterization reliably assists to diagnose the location and severity of CAD, but it is an anatomic test, largely divorced from the actual cause of infarction. It rates the severity of disease and the likelihood of infarction on the old notion of arterial narrowing.
Fayad noted the imperfections of cardiac catheterization at the 2011 Radiological Society of North America meeting. “Non-significant luminal stenosis of less than 50 percent is really the main culprit in acute MI,” he said. “And there’s more and more evidence that it’s the non-stenotic lesions that lead to stroke.”
Vulnerable plaque imaging has not yet proven to be an effective alternative to cardiac catheterization, either. The prospective, multicenter PROSPECT trial demonstrated in 2011 that high-resolution virtual-histology IVUS (VH-IVUS) was not up to the task. The study, involving 697 patients with acute coronary syndrome (ACS), aimed at identifying the clinical and lesion-related factors that place patients at risk for MI and other adverse cardiac events. Both three-vessel coronary angiography and VH-IVUS for plaque characterization were performed after a percutaneous coronary intervention.
During three-year follow-up, 11.6 percent of patients had major adverse cardiovascular events that were associated with untreated coronary segments. Most showed no evidence of severe stenosis on conventional angiography, but a small luminal area, a large plaque burden, and the presence of a thin-cap fibroatheroma (TCFA) were consistently observed with VH-IVUS.
However, lead author Gregg W. Stone, MD, concluded the VH-IVUS was not ready to play a diagnostic role. The presence of TCFA correlated well with the subsequent risk of a major event, but only 26 of 595 plaques with TCFA were the culprit sites of a major CV event in the three years following initial assessment.
The trial demonstrated the impracticality of using imaging to predict which plaque will rupture, says Marco Costa, MD, PhD, director of the Vascular Research Institute at Case Western Medical School in Cleveland. “It is very difficult to study the topic because of the incidence of rupture is very small. Most patients develop stable progression,” he adds.
The low specificity of VH-IVUS also raised questions about its value for plaque assessment, says David Vancraeynest, MD, PhD, a professor of cardiovascular imaging science at the Catholic University of Louvain in Brussels. “Virtual histology also has limited spatial resolution, which precludes assessment of the most prominent feature of TCFAs: the fibrous cap thickness,” he says.
Moving along molecular pathways
Due to molecular imaging research,