Importance: Obstructive coronary lesions with reduced luminal dimensions may result in abnormal regional myocardial blood flow as assessed by stress-induced myocardial perfusion imaging or a significant fall in distal perfusion pressure with hyperemia-induced vasodilatation (fractional flow reserve [FFR] ≤0.80). An abnormal FFR has been demonstrated to identify high-risk lesions benefitting from percutaneous coronary intervention while safely allowing revascularization to be deferred in low-risk lesions, resulting in a decrease in the number of revascularization procedures as well as substantially reduced death and myocardial infarction. While FFR identifies hemodynamically significant lesions likely to produce ischemia-related symptoms, it remains less clear as to why it might predict the risk of acute coronary syndromes, which are usually due to plaque rupture and coronary thrombosis.
Observations: Although the atherosclerotic plaques with large necrotic cores (independent of the degree of luminal stenosis) are known to be associated with vulnerability to rupture and acute coronary syndromes, emerging evidence also suggests that they may induce greater rates of ischemia and reduced FFR compared with non-lipid-rich plaques also independent of the degree of luminal narrowing. It is proposed that the presence of large necrotic cores within the neointima may be associated with the inability of the vessel to dilate and may predispose to ischemia and abnormal FFR.
Conclusions and relevance: Having a normal FFR requires unimpaired vasoregulatory ability and significant luminal stenosis. Therefore, FFR should identify lesions that are unlikely to possess large necrotic core, rendering them safe for treatment with medical therapy alone. Further studies are warranted to determine whether revascularization decisions in patients with stable coronary artery disease could be improved by assessment of both plaque composition and ischemia.