Optimal morphometric and functional assessment of intermediate coronary lesions

Coronary lesions of intermediate severity, defined as 50%-70% luminal diameter narrowing by visual estimation at angiography, are frequently encountered in patients with stable or unstable coronary artery disease. Clinical decision making for patients with intermediate coronary stenosis is still challenging, but may be facilitated by assessing the morphology and physiological significance of these lesions.1 It is clear that angiographic stenosis is a highly unreliable surrogate for myocardial ischemia, as a significant proportion of anatomically high-grade lesions do not cause ischemia. Conversely, even for anatomically mild coronary lesions, a non-negligible rate of myocardial ischemia is consistently noted. Because the physiological significance of a lesion is mainly determined by both the severity of a stenosis and the amount of myocardium supplied, coronary angiography alone does not accurately predict the functional significance of intermediate coronary lesions.2,3 Compared with angiography, intravascular ultrasound (IVUS) has greater advantages in assessing the geometry of the vessel including minimum lumen area (MLA), plaque burden and composition, and arterial remodeling.4 Likewise, optical coherence tomography (OCT) with a 10-fold higher spatial resolution than IVUS has been used to even more clearly identify the lumen border, depict the lipid core, and measure the thickness of the fibrous cap, which should be valuable for risk stratification and therapeutic intervention.5,6 Nevertheless, the application of both IVUS and OCT in evaluating the hemodynamic significance of a stenosis remains ill-defined. Fractional flow reserve (FFR) represents the degree by which the maximum blood flow is limited in the presence of a stenosis, and can be calculated as the ratio of distal pressure over aortic pressure obtained during maximum hyperemia.3 As a standard tool for lesion-specific physiologic assessment, FFR is a robust method that has been well approved to be an effective functional index of epicardial stenosis severity.3,7 Current evidence suggests that a stenosis with FFR <0.80 virtually always reflects potentially inducible ischemia and that an FFR >0.80 with few exceptions excluded ischemia related to that lesion.1,7,8 In this issue of Chinese Medical Journal, Cui et al9 integrated anatomical and physiological measurements in 141 patients with intermediate coronary lesions located at a vessel with luminal diameter ≥2.50 mm. MLA and plaque burden obtained by IVUS showed a moderate correlation with FFR values. The best threshold value of MLA for FFR <0.80 was <3.15 mm2, with diagnostic accuracy of 73.6%. However, poor specificity limits its value for physiological assessment of lesions with MLA <3.15 mm2. When MLA (3.15 mm2) and plaque burden (65.45%) were considered, both negative and positive predictive values for functional ischemia were increased. It is obvious that assessment of the functional significance of an intermediate lesion using MLA is influenced by multiple factors, including vessel size, lesion location and length, and anatomical variations of coronary artery, as well as imaging techniques used.8,10–14 IVUS studies have shown that the MLA cutoff for predicting FFR <0.80 was <4.8 mm2 for isolated left main disease,12 2.4 mm2 for left anterior descending artery (LAD), 1.6 mm2 for left circumflex artery, and 2.4 mm2 for right coronary artery.10 Correlation between MLA and FFR was better for larger-diameter vessels, and the best threshold values for FFR <0.80 of MLA varied greatly in lesions with different reference vessel diameters.8,10 Furthermore, it seems to be more appropriate to propose different IVUS criteria according to the lesion location than the size of a vessel.13 Koo et al1 revealed a greater cutoff value of MLA to best define the functional significance for proximal LAD stenoses than that for mid-LAD lesions before the second diagonal branch. However, the optimal MLA to predict the functional significance of lesions could not be found in other segments.1 Lesion length has a physiologically significant impact on intermediate-grade coronary lesions.14 Similarly, the presence of a collateralized chronic total occlusion was associated with significantly lower FFR values, and a larger amount of jeopardized or perfused myocardium subtended by a stenosis - irrespective of the methodology used to demonstrate its presence - is associated with a higher probability that an angiographically intermediate coronary stenosis is functionally significant. The same stenosis would be associated with a different FFR value in the presence of viable or scarred myocardium.3,11 OCT is an established technique that provides a great deal of anatomical information, but its application in assessing the hemodynamic significance of an intermediate coronary lesion is limited.5 The MLA measured by frequency-domain OCT correlated significantly with FFR values; the best cutoff value to identify stenoses with FFR <0.80 was 1.95 mm2,5 which is smaller than that previously reported for IVUS.1 For intermediate lesions at small coronary arteries (reference diameter <3 mm), OCT showed a significantly better diagnostic efficiency than IVUS to identify functionally significant stenoses.5 However, similar to IVUS method, the specificity and positive predictive value were lower, precluding the use of OCT-derived MLA <1.95 mm2 as a substitute of direct assessment of functional stenosis.5,6,15 In general, there is no one-size-fits-all. It is unlikely to completely and accurately predict the functional severity from one IVUS- or OCT-derived index for anatomical observations.10 Based on the available evidence, appropriate use of multiple modalities of direct functional assessment is therefore essential in guiding treatment for intermediate coronary lesions.10 FFR is the intracoronary physiology standard to evaluate functional relevance of coronary stenosis and traditionally measured with a pressure wire in the catheterization laboratory.1–3 Recently, noninvase assessment of FFR using coronary computed tomographic angiograms (CTA) has yielded great interest.16–19 In patients who had an angiographic intermediate coronary stenosis, at FFR <0.80 cutoff for lesion-specific ischemia, accuracy, sensitivity, specificity, positive and negative predictive values of CTA-computed FFR were high, with good correlation to pressure wire-measured FFR.16 These observations substantiate a notion that noninvasive FFR derived from coronary CTA may serve as a valuable method for detection and exclusion of coronary lesions that nevertheless cause ischemia.17 Previous studies have shown that angiographic complete revascularization with drug-eluting stent implantation or coronary artery bypass grafting may not improve long-term clinical outcomes in patients with multivessel disease,20 but survival benefit with revascularization is related to ischemic risk.21 These findings strongly support the strategy of ischemia-guided revascularization. Accordingly, an algorithm is proposed how to tailor the management strategy to each patient's individual situation. Although morphometric assessment of intermediate coronary stenoses by combined use of IVUS, virtual histology and OCT has been successful for characterizing coronary plaques,22,23 which is essentially different from the functional significance of these lesions. Because FFR-guided revascularization for intermediate coronary lesions is safe and cost-effective not only to avoid unnecessary invasive procedures provoked by physiologically irrelevant lesions, but also to predict the outcome of the patients after percutaneous coronary intervention,24–27 this approach has been upgraded to class IA recommendation for management of multivessel disease.28 In this regard, it is an interesting endeavor to apply FFR either measured directly by a pressure wire or derived from noninvasive coronary CTA to intermediate coronary lesions, which may identify patients whose lesions fall below an anatomic threshold of “severe” but who experienced ischemic symptoms and require intervention.