Anatomic and physiologic measures of stenosis severity have evolved in parallel over the past 40 years. Stenosis severity and their pressure or flow effects have been integrated into fluid dynamic equations and validated in experimental models. Based on animal stenosis models, the concept that a 70% diameter narrowing identifies a “critical stenosis ” which reduces coronary flow capacity [8] persists as an anatomic threshold for revascularization. However, the limitations of percent stenosis are well established, particularly with documentation of diffuse disease, multiple stenoses, heterogeneous remodeling, and endothelial dysfunction which all have complex cumulative effects on coronary flow and pressure not accounted for by a single percent diameter narrowing [9]. Evidence over the intervening years has proven that percent diameter stenosis is an inadequate measure of severity for guiding management.

Anatomic measures such as diameter stenosis and location, coronary plaque volume, and the overall extent of disease substantially contribute to individual cardiovascular risk. The number of vessels with a stenosis of ≥50% was the most robust predictor of outcomes, beyond that provided by traditional risk factors and left ventricular ejection fraction [10] (Fig. 25.3a). Because atherosclerosis is the substrate of most myocardial infarctions, sudden deaths, and strokes, even commonly identified nonobstructive lesions (<50% diameter stenosis) portend additional risk when compared with the excellent prognosis known to be associated with the absence of coronary atherosclerosis on coronary computerized tomographic angiography (CCTA) [11] (Fig. 25.3b).

Given the robust prognostic power of coronary anatomy in determining future events, a simplistic and straightforward approach would be to treat all patients with stable CAD with either elective PCI or coronary artery bypass graft (CABG) , as appropriate. However, the COURAGE trial revealed that an initial approach of OMT was equally as effective as PCI plus OMT in preventing death or myocardial infarction (MI) and that revascularization could be safely deferred in approximately two-thirds of patients with stable CAD. No current randomized trial data support the concept that coronary anatomy alone should dictate therapeutic strategy in stable CAD. An exception may be patients with ischemic cardiomyopathy in whom improved survival with CABG compared with OMT alone was recently reported from the 10-year extension of the NHLBI-sponsored Surgical Treatment for Ischemic Heart Failure (STICH) trial [12].

Overall, coronary anatomy provides prognostic utility beyond traditional risk factors and risk estimate scores. However, in most cases anatomy alone does not help guide revascularization decisions when improving survival and freedom from MI are the major goals.

Numerous stress imaging studies have demonstrated a gradient between the extent and the severity of ischemia and subsequent risk of cardiac events [13]. Thus, enrollment of patients with lower levels of ischemia in published trials of stable CAD may explain why revascularization did not improve prognosis. In the COURAGE nuclear sub-study, the average amount of left ventricle ischemia was only 8.2% (with 10% usually accepted as representing moderate ischemia). In several reports from the Cedars-Sinai registry , patients with ≈10% or more (i.e., moderate to severe) ischemic myocardium had a nearly doubling of mortality when treated medically as compared with a demonstrable reduction in death among patients undergoing coronary revascularization [2, 14].

To date, definitive data that revascularization improves the prognosis of patients with stable CAD and noninvasively detected ischemia are absent. Although progressive narrowing of a canine coronary artery produced a predictable decline in coronary flow reserve, in clinical studies, the relationship between anatomy (including intravascular ultrasound (IVUS) and optical coherence tomography (OCT)) and physiology has been far from perfect (Fig. 25.4) [15].

To overcome the fundamental limitations of anatomical imaging, sensor guide wires have been developed to enable intracoronary measurements of pressure and flow. The physiological impact of a stenosis may be characterized by its effect on post-stenotic pressure (and flow) transmission. The post-stenotic pressure is a function of stenosis flow and resistance specific to unique morphological features that include minimal lumen area (MLA) , lesion length, the stenosis entrance and exit orifice configurations, and the shape and size of the normal reference vessel segment (Fig. 25.5) [16].

Early studies suggested that intracoronary Doppler flow velocity measurements could determine the significance of a coronary lesion [17]. However, these approaches were never adopted into clinical practice because of difficulty in obtaining a valid flow velocity signal and the unknown status of the microcirculation in interpreting an abnormal coronary flow reserve. However, FFR, the ratio of post-stenotic pressure/aortic pressure obtained at maximal pharmacologically induced hyperemia, closely correlates to indices of ischemia to a greater degree than the resting trans-stenotic pressure gradient. Because its derivation was based on pressure at maximal flow and excluded the microcirculatory resistance, FFR was largely independent of changes in basal flow, systemic hemodynamics, or contractility [18], although an intact microcirculation is required for the hemodynamic effects of full hyperemia to be established. FFR thresholds for hemodynamic significance were established by comparisons with ischemic stress testing modalities and subsequently validated in numerous clinical outcome studies. Compared with traditional angiographic PCI guidance, FFR-guided decisions have demonstrated clinical and economic superiority in numerous single- and multicenter interventional trials. In the FAME trial , an FFR-guided PCI strategy was superior to an angiography-guided PCI therapy in reducing both stent use and the rates of future urgent revascularization because of unstable angina and MI [1]. In the FAME 2 trial, FFR-guided revascularization resulted in lower rates of progressive ischemic symptoms and the need for urgent or elective revascularization within 2 years, compared with OMT alone. Notably, these trials were not blinded, and rates of death or MI were not significantly reduced with revascularization. Nonetheless, the totality of the evidence supports the strong guideline-based recommendations for the use of FFR to guide PCI revascularization decisions.