Fractional flow reserve (FFR; the ratio of distal to proximal pressure at maximum hyperemia) is the standard method for assessing the physiologic significance of a non-left main coronary artery (LMCA) lesion. IVUS has been corrected for vessel size, but IVUS has not been able to factor in the amount of subtended viable myocardium. IVUS minimal lumen area (MLA) in predicting hemodynamic significance in non-LMCA lesions is that the functional effects of a lesion are dependent on additional factors besides dimension. These include lesion location in the coronary tree, lesion length, eccentricity, entrance and exit angles, shear forces, reference vessel dimensions, and the amount of viable myocardium subtended by the lesion [3].

Therefore, in non-LMCA lesions there is only moderate correlation between anatomic dimensions by IVUS and ischemia by physiological assessment. Many studies have attempted to identify invasive IVUS minimum lumen area (MLA) criteria that are equivalent to FFR, reported IVUS MLA cut-off thresholds range from 2.3 to 3.9 mm² (Table 6.2) [4–14].

In earlier study IVUS MLA < 4.0 mm² correlates with ischemia on single-photon emission computed tomography and also correlates moderately well with an FFR < 0.75. Importantly, low event rates are observed in intermediate lesions when intervention is deferred with an IVUS MLA ≥ 4 mm² [15–17]. In the largest study to date, IVUS was compared with FFR in 544 lesions [13]. The optimal cut-off value for predicting an FFR ≤ 0.80 was an MLA = 2.9 mm² by IVUS, but the overall accuracy was only 66%. Moreover, of the 240 lesions that had an MLA < 2.9 mm², only 47% was hemodynamically significant by FFR. Similarly concerning, 19% of lesions with an MLA > 2.9 mm² had an FFR < 0.80, limiting the utility of IVUS for lesion assessment. Kang et al. [7, 8] evaluated 236 angiographically intermediate coronary lesions in which both IVUS and FFR measurements were performed. An IVUS MLA_2.4 mm² had the maximum accuracy for predicting FFR < 0.80. However, the overall diagnostic accuracy was 68% with a confidence interval ranging from 1.8 to 2.6 mm². FIRST was a multicenter prospective registry of patients who underwent elective coronary angiography and had intermediate coronary stenosis (40–80%) [12]. An IVUS-measured MLA < 3.07 mm² had the best sensitivity and specificity (64% and 64.9%, respectively) for correlating with FFR < 0.80.

So, FFR should be considered the standard for assessing the hemodynamic significance of intermediate non-LMCA lesions and better validated than IVUS as a physiologic assessment. An MLA < 4.0 mm² has reasonable accuracy in identifying non-significant lesions for which percutaneous coronary intervention (PCI) can be safely deferred [18]. However, an MLA < 4.0 mm² does not accurately predict a hemodynamically significant lesion and should not be used in the absence of supporting functional data (such as DEFER, FAME-I, or FAME-II with FFR) to recommend revascularization [3]. An MLA < 3.0 mm² is most likely a significant stenosis, but due to its only modest sensitivity and specificity, physiologic testing is desirable before proceeding with revascularization. It may be acceptable to defer an intervention in selected situations based on MLA size, IVUS should never be used to justify an intervention.

Left main coronary artery (LMCA) lesion has greatest angiographic assessment variability. Small real-world analysis showed that less than half of intermediate LMCA had significant stenosis by IVUS assessment, especially for lesions located at the left main ostium [19].

IVUS evaluation for LMCA stenosis can be valuable when coronary angiography gives equivocal or ambiguous images. Both IVUS and FFR have theoretical and practical limitations for LMCA lesion, proximal LAD and/or LCX disease can impact FFR of LMCA stenosis. With IVUS, distal LMCA lesions can be difficult to accurately image, and often require pullback from both the LCX and LAD. But limited variability in LMCA length, diameter, and amount of supplied myocardium explains the better correlation in LMCA with FFR than non-LMCA stenosis, the most widely used parameter is MLA in LMCA stenosis.

Jasti et al. [20] showed good correlation between FFR and IVUS, with good sensitivities and specificities >0.90. In a study of 55 intermediate LMCA lesions (reference diameter 4.2 mm), an MLA <5.9 mm² and an MLD <2.8 mm correlated well with FFR < 0.75.

A prospective application of these criteria was tested in the LITRO study [21]. LMCA revascularization was performed in 90.5% of patients with an MLA < 6 mm² and was deferred in 96% of patients with an MLA > 6 mm². In a 2-year follow-up period, cardiac death-free survival was 97.7% in the deferred group versus 94.5% in the revascularized group (P = ns), and event-free survival was 87.3% versus 80.6%, respectively (P = ns). At 2-year follow-up, only eight (4.4%) patients in the deferred group required subsequent LMCA revascularization, none of who had an MI. Thus, it is safe to defer LMCA revascularization with MLA > 6 mm². Additionally, the data confirms that MLA < 6.0 mm² is clinically significant, correlates with FFR < 0.75 (Tables 6.3 and 6.4).

More recently study with Asian populations with smaller normal coronary diameters, an MLA cut-off < 4.8 mm² correlates with reduced FFR < 0.8 and <4.1 mm² with FFR < 0.75 [22, 23].

Calcium is under-recognized angiographically. In IVUS study, most of visible calcification by angiogram is correlated with arc of calcium involved, length of calcium involved, and where calcium is located [24]. So visible calcified lesion in angiography means significant calcification nearly encircled the vessel wall and spread along the vessel.

Coronary calcification has been considered a stable coronary lesion. But recent studies, however, it is not really stable because lots of microcalcification and calcified nodule had observed in unstable plaque. Patients with moderate or severe target lesion calcification (TLC) were older, had more renal insufficiency, had lower ejection fractions, and were more likely to have had a STEMI compared with patients with no or mild TLC. On the other hand, lesions with moderate or severe TLC also have other characteristics that are unfavorable, including longer lesion length, more total occlusions, more visible thrombi, and more triple-vessel disease [25].

Calcification may prevent complete expansion of the stent or interfere with stent delivery, resulting in damage either to the structure of the stent or to the polymer in the case of drug-eluting stent (DES). A malapposed, incompletely expanded, or damaged stent increases the risks for stent thrombosis of target lesion. There is general agreement that the greater the arc and length of IVUS-associated lesion calcium the greater the likelihood of underexpansion, but published or agreed criteria for recommending lesion modification prior to stent implantation does not exist. And IVUS has limitation for measure calcium thickness because of acoustic shadow, which may be an important limit to stent expansion ([26], http://​www.​acc.​org/​latest-in-cardiology/​articles/​2016/​06/​13/​10/​01/​ivus-in-pci-guidance).

On the other hand, and most of the time, iterative IVUS imaging in conjunction with preparation and debulking of the lesion with rotational atherectomy, special balloons such as cutting or scoring and wire-cutting technique and repeated high-pressure adjunctive balloon inflations can be used to correct post-procedure stent underexpansion even in the setting of significant calcification (Fig. 6.1). Nevertheless, it is easier to prevent stent underexpansion than it is to struggle to correct it such as stent ablation procedure. IVUS studies have shown that localized calcium deposits or the transition from calcified to non-calcified plaque (or to normal vessel wall) are foci for PCI-associated dissections. More extensive dissections occur in segments of arteries that are heavily calcified, and stent implantation into calcified lesions is more often associated with stent fracture.

Coronary bifurcation PCI represents 10–15% of PCI procedures. Bifurcation lesions may show dynamic changes during PCI, with plaque/carina shift or dissection leading to side branch compromise and requiring adjustment to the interventional approach. Therefore, accurate anatomic characterization of bifurcation lesions may improve stent sizing and deployment techniques. The most important role of IVUS is correct measurement of reference vessel size of both main and side branch (SB), if operator decided to use two stent technique with proximal optimization technique.

Also IVUS can detect the distribution of plaques not only in the main branch but also in the ostium of the SB. One study revealed that SB occlusion occurred in 35% of the plaque-containing lesions at the SB ostium after PCI as compared to the 8.2% occlusion rate of plaque-free lesions at the SB ostium [27]. Therefore, wiring the SB to protect it before PCI should be considered if IVUS reveals plaque involvement at the SB ostium, but there do not appear to be reliable IVUS predictors of functional SB compromise after crossover stenting.

In IVUS study [28] regarding complex bifurcation lesions (nearly 90% of the lesions were medina class 1, 1, 1), the number of implanted stents was significantly lower in the IVUS-guided PCI group. Also, the rate of TLR was significantly lower in the IVUS-guided PCI group (6% vs 21%, P = 0.001). In this regard, the role of IVUS in decreasing the TLR rate may become more important, a decrease in the number of stents in the IVUS-guided PCI group may contribute to reduce the TLR rate. So, liberal and active use of IVUS in bifurcation PCI is encouraged.

To Identify thrombosis or embolization-prone “vulnerable” plaques before they rupture, catheter-based intravascular imaging modalities are being developed to visualize pathologies in coronary arteries in vivo. Mounting evidences have shown three distinctive histopathological features—the presence of a thin fibrous cap (<65 μm), a lipid-rich necrotic core (>40% of total lesion area), and numerous infiltrating macrophages in the fibrous cap—are key markers of increased vulnerability in atherosclerotic plaques [29].

In the early days of coronary intervention, many coronary angiographic predictors for no-reflow or CK-MB elevation after and during PCI were identified (Table 6.5). After that to visualize these changes, the majority of catheter-based imaging modalities used IVUS with integrated tissue characterization techniques and OCT to enhance the characterization of vulnerable plaques.