Fractional Flow Reserve: Setting Criteria and Changing Clinical Practice References Fractional flow reserve (FFR) is the ratio of distal to proximal pressure on either side of a stenosis during maximum hyperemia.[5] The pressure sensor is located at the junction of the radio-opaque and radiolucent segments of an intracoronary guidewire, 3 cm proximal to the tip. Normal FFR is 1.0. Provocable ischemia occurs with an FFR <0.75. Rest ischemia is present with an FFR <0.2. While an FFR >0.75 typically correlates with a negative stress test (exercise, thallium scintigraphy, or dobutamine echocardiography), Dr. DeBruyne noted that there is a gray area when the FFR measures 0.72-0.82. DEFER Study FFR may be especially useful in patients with angiographic stenoses and atypical symptoms and/or in those with no, nondiagnostic, or negative noninvasive test findings. In the DEFER Study, 325 patients were enrolled. Those with an FFR <0.75 underwent intervention. Those with an FFR >0.75 were randomly assigned to intervention or no intervention. At 1 year, the event-free survival rates in the 3 groups were 81%, 75%, and 89%, respectively. FFR may also be useful in patients with ambiguous left main disease. In one study, 30 patients had an FFR <0.75 and underwent surgery; 24 had an FFR >0.75. At 29 months' follow-up, event-free survival was 83% and 79%, respectively. Thus, FFR is stenosis-specific, takes collaterals into account, is applicable in multivessel disease, and is independent of prevailing hemodynamics. Assessment of Endothelial Function: Relieving Angina Without PCI The normal coronary artery responds to acetylcholine with vasodilation. Early atherosclerosis, as well as the presence of diabetes mellitus, hypertension, and hyperlipidemia cause vasoconstriction.[6] This is not just a laboratory finding; the frequency of coronary events varies with the presence of endothelial dysfunction. When patients are separated into thirds according to endothelial function, those with the worst endothelial function have the highest event rate (14%). Hyperlipidemia is an important cause of endothelial dysfunction. Oxidized low-density lipoprotein (LDL -- especially small, dense LDL particles) activates macrophages, causes inflammation, increases the adhesiveness of monocytes, and upregulates procoagulant markers. These pathophysiologic findings are reversed with lipid-lowering agents, especially in combination with antioxidants. These pathophysiologic findings are even acutely reversible with lipopheresis. While routine assessment of coronary endothelial dysfunction is not practical, brachial reactivity (B-mode ultrasound assessment of brachial diameter artery response to cuff occlusion) is a useful noninvasive surrogate. In the presence of normal coronary endothelial function, the brachial artery diameter should increase by 14%. In the presence of angiographically normal coronary arteries but coronary endothelial dysfunction, the brachial artery diameter increases by 9%. It falls to 4% in the presence of angiographic CAD. Brachial reactivity is also abnormal in the presence of increasing numbers of risk factors. The failure of endothelial-dependent vasodilation as well as the presence of procoagulants, macrophage infiltration, inflammation, and proliferation can be reversed by aggressive risk factor modification -- especially reducing LDL to <100 mg/dL and systolic blood pressure to <138 mm Hg. This should be the goal in all patients with CAD, including those undergoing intervention.