Multitarget Vulnerable Plaque Imaging.

The search for the vulnerable plaque has been a prolonged, circuitous journey that despite considerable investment and resource expenditure has hitherto failed to alter clinical practice. The rationale remains enticing. We have known for some time that plaques at risk of rupture and precipitating myocardial infarction and stroke have certain characteristics that extend beyond simple stenosis severity. These include inflammation, microcalcification, angiogenesis, positive remodeling, a thin fibrous cap, a large necrotic core, and plaque hemorrhage. Rapid recent advances now allow us to detect such features using both invasive and noninvasive imaging technologies. The hope has been that such technology might allow us to predict with accuracy the plaques and, more importantly, the patients at risk of rupture-related events. However, recent data have been somewhat disappointing, at least at the plaque level. The PROSPECT trial (Providing Regional Observations to Study Predictors of Events in the Coronary Tree) used virtual histology intravascular ultrasound to identify high-risk lesions (the virtual histology intravascular ultrasound defined thin capped fibroatheroma), demonstrating that such plaques were a predictor of events and offered good negative predictive value. However, of a total of 595 such lesions, only 26 caused an event and most of these were not myocardial infarctions. Although this, in part, may reflect the limitations of virtual histology intravascular ultrasound, it is increasingly being appreciated that high-risk plaques are in fact relatively common and only rarely go on to cause a clinical event. The positive predictive value is currently so low that questions have been raised about whether treatment to individual plaques will ever be justified. Faced with this fundamental issue, what then is the future of high-risk plaque imaging?