In January of 1812, the first ever published article in the New England Journal of Medicine (then known as New England Journal of Medicine and Surgery and the Collateral Branches of Science) was Dr. John Warren’s “Remarks on Angina Pectoris.” In this essay, Dr. Warren carefully speculated on the possible correlation between chest pain, its patterns of exacerbation, and the possible relation to autopsy findings of “ossification of coronary arteries.” Fast forward almost 200 years: we are still researching the same topic, but now using sophisticated technology of angiography, ultrasound, and histopathology to directly visualize and identify high risk coronary lesions.
Pathological studies have been the basis of the widely accepted theory that the most common cause of myocardial infarction and cardiac death is from the rupture of lipid-rich, thin cap fibroatheromas. There has also been anecdotal evidence that in patients with acute coronary syndrome (ACS), subsequent cardiovascular events often occur from non-culprit lesions that do not cause an extensive degree of angiographic stenosis.
In the January 20, 2011, issue of NEJM, Greg Stone, et al presents a prospective, multicenter, natural history study of coronary atherosclerosis. Using several imaging modalities, angiography, gray-scale intravascular ultrasonography, and radiofrequency intravascular ultrasonography, the authors attempt to identify clinical and intravascular lesion related factors that place ACS patients at risk for subsequent adverse cardiac events.
When I asked Dr. John Jarcho, NEJM deputy editor and cardiologist, why this publication was important, he replied, “This is one of the first systematic in vivo evaluations for identifying predictors of high-risk coronary lesions. It provides confirmation of two concepts. The first is the principle that many acute coronary syndromes occur, not at sites of critical angiographic stenosis, but in parts of the coronary tree with angiographically mild disease. The second is the idea that certain histologic features of atheromas are predictive of the risk of coronary events.”
In 697 patients with ACS who underwent successful percutaneous coronary intervention, there was 20.4% cumulative rate of subsequent major adverse cardiovascular events. Approximately half of these events were due to non-culprit lesions that were angiographically mild. These “high risk” non-culprit lesions, were found to instead be characterized by a either a plaque burden of 70% or greater seen on grey-scale ultrasound, a minimal luminal area of 4.0mm2 or less, or by classification of a thin cap fibroatheroma on the basis of radiofrequency intravascular ultransonography.
Does this study mean that ultrasound will now replace angiography or histopathology in determining which coronary lesions will lead to additional cardiovascular events? In short, no. Ultrasound adds insight to the characteristics of high risk lesions, but there is still not enough information to predict which of the high risk lesions will ultimately lead to clinical consequence. The results, though not ready for clinical application, do reaffirm the hypothesis of the high risk nature of thin cap fibroatheromas. As Dr. Warren noted in 1812, “In our inquiries into any particular subject of Medicine, our labours will generally be shortened and directed to their proper objects, by a knowledge of preceding discoveries.” Being able to risk stratify lesions non-invasively via ultransonography provides a stepping stone for further research.