Physiological severity of coronary artery stenosis.

THREE FUNDAMENTAL ADVANCES in our knowledge underlie the rapidly evolving long-term treatment of coronary artery disease (CAD), summarized briefly here for perspective on the paper by Marques and colleagues (17) in this issue of American Journal of Physiology-Heart and Circulatory Physiology, on quantifying severity of coronary artery stenoses by their pressure-flow velocity relation. The first of these advances identified sudden plaque rupture and thrombosis as the cause of most acute coronary syndromes associated with inflammation and wall stress of lipid-rich plaques with thin fibrous caps. Consequently, in randomized trials, revascularization procedures in chronic stable CAD do not decrease coronary events or improve long-term survival (13–15). Deferring revascularization based on physiological severity of coronary artery stenosis quantified by coronary flow reserve (CFR) or fractional flow reserve (FFR) improves management of CAD by reducing unnecessary procedures with better outcomes than routine revascularization based on visual stenosis severity on coronary arteriograms (1, 2, 22). Revascularization procedures may be appropriate for acute coronary syndromes or refractory symptoms due to myocardial ischemia but, even with advanced surgical techniques and coated stents, have not improved survival in chronic stable CAD (13–15). However, based on well-documented visual overestimates of stenosis severity, economic incentives, and the well-meaning urge to “do something now” by patients and physicians, these procedures are substantially overutilized without objective measures of ischemia or severity (21), particularly in view of comparable outcomes with deferring revascularization based on objective physiological severity (1, 2, 22). The second of the major advances was stabilization or regression of coronary atherosclerosis by intense pharmacological and/or lifestyle changes that improve coronary blood flow, reduce atherosclerotic burden, and decrease coronary events by over 90% compared with less intensively treated control subjects (3, 4, 19). Whereas statin monotherapy reduces coronary events and mortality by 30–50% compared with untreated controls, it does not adequately address the risks of low HDL and/or high triglycerides. Multidrug and/or intense combined pharmacological and lifestyle treatment further improve outcomes more than after revascularization procedures with parallel improvement in myocardial perfusion. The third major advance integrated the anatomic, pressure, and blood flow characteristics of the entire coronary artery tree that explain fundamental coronary artery branching structure, the interacting effects of single or multiple stenosis, and/or diffuse atherosclerosis as the basis for precisely quantifying disease severity in clinically relevant terms, both invasively and noninvasively (6, 7, 20). CFR was the first physiological measure of stenosis severity (8–12, 16). Relative CFR is the basis of noninvasive stress perfusion imaging. Absolute CFR is the basis of flow velocity measurements using intracoronary Doppler wires or arterial thermodilution catheters during maximum flow after intracoronary adenosine. Absolute or relative CFR is also measured by positron emission tomography (PET) perfusion imaging after intravenous adenosine or dipyridamole. Arteriographic stenosis flow reserve is a calculated flow reserve based on precise integrated stenosis dimensions objectively measured by automated arteriographic analysis using fluid dynamic equations. Coronary FFR is relative flow reserve determined from pressure wire recordings across a single stenosis at maximum flow after intracoronary adenosine (18). FFR is readily obtained during routine coronary arteriography, is reproducible, and, at a threshold of 0.75 (normal FFR being 1.0), correlates well with exertional ischemia. It serves as a guide for deferring revascularization procedures with better outcomes than visual estimates of severity as the basis for these procedures (1, 2, 22). However, FFR is not valid for multiple stenoses or diffuse disease (18). Neither FFR nor CFR indicates stenosis severity if small vessel disease or diffuse coronary atherosclerosis limits the flow response to pharmacological agents or exercise as commonly occurs in CAD. These three advances suggest that revascularization procedures are indicated at coronary arteriography only for stenoses that are physiologically severe enough to cause refractory ischemia by objective measurements since visual assessment of severity is grossly inadequate for moderate stenosis of intermediate severity. Stenoses not meeting preestablished thresholds of severity should not be instrumented but treated with intensive lifestyle and pharmacological agents for optimal outcomes. After appropriate noninvasive testing and/or a trial of medical treatment, the question then becomes, What is the best measure of physiological severity of a stenosis at coronary arteriography–automated quantitative arteriographic analysis, CFR, FFR, or dpv50?