Functional Approach for Coronary Artery Disease: Filling the Gap Between Evidence and Practice

Abstract

The presence of myocardial ischemia is the most important prognostic factor in patients with coronary artery disease, and ischemia-directed revascularization has been a standard of care. Fractional flow reserve (FFR) is an invasive method used to detect the functionally significant epicardial coronary stenosis, and FFR-guided revascularization strategy has been proven to be superior to angiography-guided strategy. Recently, a hyperemia-free index, instantaneous wave free ratio (iFR), was developed and showed its non-inferiority for clinical outcomes compared with FFR-guided strategy. While evidence supporting the benefit of pressure wire assessment exists, there remain several unresolved issues, such as the mechanism of discordance between resting and hyperemic physiologic indices, clinical outcomes of patient/lesions with discordant results among the physiologic indices, role of physiologic indices beyond per-vessel decision tool, and the role of microvascular dysfunction in patient prognosis. The current article will review the recent studies performed to address these questions.

Keywords: Coronary artery stenosis; Coronary physiology; Invasive physiologic assessment; Ischemic heart disease.

Figure 1

Resting and hyperemic pressure-derived invasive physiologic indices. Resting Pd/Pa is measured during the entire cardiac cycle and iFR is measured during “wave-free period” at resting status. Conversely, FFR is measured during the entire cardiac cycle at maximal hyperemia. FFR = fractional flow reserve; iFR = instantaneous wave-free ratio; Pa = aortic pressure; Pd = distal coronary pressure; Resting Pd/Pa = resting distal to aortic coronary pressure.

Figure 2

Changes of FFR and iFR according to anatomical and hemodynamic stenosis severity. Regardless of (A) anatomical or (B) hemodynamic epicardial stenosis severity indices, the iFR threshold for separating normal from abnormal values matches with a more severe stenosis level than that for FFR. This figure was modified from the original version. FFR = fractional flow reserve; iFR = instantaneous wave-free ratio.

Figure 3

Association of FFR and iFR with clinical outcomes and the variability in estimated event rates due to intrinsic measurement variability. (A) Both FFR and iFR showed significant association with the estimated 2-year event rates. (B) FFR and iFR showed differences in the variability of the estimated event rates according to the approximate measurement variability. FFR showed lower maximum variability compared with that of iFR. This figure was modified from the original version. CI = confidence interval; FFR = fractional flow reserve; HR = hazard ratio; iFR = instantaneous wave-free ratio.

Figure 4

Risk of clinical events in medically treated and revascularized vessels according to FFR. The 2-year MACE rates were plotted according to pre-intervention native vessel FFR in medically treated vessels and stented vessels. The relationship between native vessel FFR and clinical outcome was different between medically treated vessels and stented vessels. In medically treated vessels with FFR<0.75, the risk of 2-year MACE was exponentially increased. In stented vessels with pre-intervention FFR>0.75, the MACE risk was higher than medically treated vessels. This figure was adapted from the authors' original work under permission of the publisher. FFR = fractional flow reserve; MACE = major adverse cardiac events; MT = medical treatment; PCI = percutaneous coronary intervention.

Figure 5

Concept of coronary flow reserve and IMR. (A) Using thermodilution technique, Tmn, which is the surrogate marker of coronary flow, can be measured in both resting and hyperemic conditions. CFR is calculated by resting Tmn/hyperaemic Tmn. IMR is calculated by Pd×Tmn during hyperaemia. (B) The patient presented with typical chest pain on exertion and a positive exercise stress test. Coronary angiography showed no obstructive epicardial coronary artery disease and FFR was insignificant in both LAD and LCX. However, CFR was low and IMR was high in both LAD and LCX, suggesting the presence of overt microvascular disease. CAD = coronary artery disease; CFR = coronary flow reserve; FFR = fractional flow reserve; IMR = index of microcirculatory resistance; LAD = left anterior descending artery; LCX = left circumflex artery; Tmn = mean transit time; TMT = treadmill test.