IVUS overcomes limitations of angiography in terms of vessel imaging, stent optimization and clinical outcomes of drug-eluting stent (DES) implantation and it is superior to angiography alone in simple and complex lesions.

In the DES era, intravascular imaging plays a crucial role in the context of coronary angioplasty. To the best of our knowledge, the largest meta-analysis comparing IVUS-guided with angiography-guided DES implantation included 4724 patients from 9 randomized trials, including the ULTIMATE trial [29]. It demonstrated that IVUS guidance was associated with lower risk of major adverse cardiovascular events (MACE) (5.4% vs. 9.0%, p 0.001), cardiac death (0.6% vs. 1.2%, p = 0.03), target vessel revascularization (TVR) (3.5% vs. 6.1%, p = 0.001), target lesion revascularization (TLR) (3.1% vs. 5.2%, p = 0.001) and stent thrombosis (0.5% vs. 1.1%, p = 0.02) in a mean follow-up of 16.7 months. No difference was detected between the two groups regarding the incidence of all-cause death and myocardial infarction.

A previous meta-analysis enrolled 3 randomized and 14 observational trials with 26,503 patients and reported similar clinical outcomes [30]. Patients who had undergone IVUS-guided PCI had lower risk of having TLR (OR = 0.81, p = 0.046), death (OR = 0.61, p 0.001), myocardial infarction (OR = 0.57, p 0.001) and stent thrombosis (OR = 0.59, p 0.001) compared to those who had undergone angiography-guided PCI. Moreover, the improved outcomes in the IVUS group are obvious in the meta-analysis of Elgendy et al. [31], which included 7 randomized trials and 3192 patients who underwent DES PCI. IVUS guidance was associated with lower risk of MACE (6.5% vs. 10.3%, p 0.0001), cardiovascular death (0.5% vs. 1.2%, p = 0.05) and stent thrombosis (0.6% vs. 1.3%, p = 0.04). With this level of evidence, the superiority of IVUS over angiography in PCI guidance is unquestionable. Worth mentioning is that IVUS is, so far, the intravascular modality in which a decreased rate of death has been showed in meta-analyses.

Numerous studies have shown the benefits of OCT in catheterization procedures and its advantages in PCI guidance in contrast with plain angiography guidance [3, 4, 32]. The Centro per la Lotta contro l’Infarto-Optimisation of Percutaneous Coronary Intervention (CLI-OPCI) study was the first study to introduce OCT guidance in PCI [3]. Compared to angiographic guidance alone, angiography plus OCT demonstrated improved clinical outcomes in 1-year follow up, regarding MACE. Moreover, the use of OCT was not associated with major complications and led to additional interventions regarding management in almost 35% of patients.

Interestingly, OCT guidance has a significant impact in the procedural strategy of PCI. ILUMIEN I study was the first to demonstrate the influence of OCT on operators’ clinical decisions [32]. Operators’ decision-making was affected by pre- and post-PCI OCT images in 66% of cases, especially in more complex lesions. Pre-PCI OCT led to changes in stent length and diameter, whereas factors standing out by post-PCI OCT, as stent malapposition, stent underexpansion and edge dissection, resulted in additional in-stent post-dilation and/or new stent deployment. Moreover, OCT guidance seemed to improve clinical outcomes during and after the procedure -low 1 -month MACE rate.

Similarly, in the DOCTORS study, which is the first study to enroll patients with non-ST elevation acute coronary syndromes, the decision-making was affected by the OCT in half of the cases in the OCT-guided group [4]. OCT guidance succeeded superior hemodynamic parameters. Fractional flow reserve (FFR) values were higher in the OCT-guided group compared to the angiography guided group (0.94 $\pm$ 0.04 vs. 0.92 $\pm$ 0.05, p = 0.005). Despite the longer duration of the procedure and higher amount of contrast, OCT was not associated with increased incidence of complications during the procedure (i.e., MI, renal dysfunction). The main strength of the study is the optimization of stent expansion with the use of OCT.

One major concern is which approach would be the optimal treatment for cases with complex lesions and high-risk patients with several comorbidities. The ongoing ILUMIEN IV trial is sought to investigate the superiority of OCT-guided PCI compared to angiography-guided PCI in patients with complex lesions and/or diabetes mellitus [33]. Primary endpoints are the mean stent area (MSA) after revascularization and target vessel failure, which comprises cardiac death, target vessel myocardial infarction and ischemia-driven target vessel revascularization. The properties of OCT could improve acute PCI results and, thus, clinical outcomes in the future.

The first in vivo evaluation of optical frequency domain imaging (OFDI)—in comparison with IVUS was conducted by Okamura et al. [23]. OFDI imaging proved to be feasible and safe, with high reproducibility for both pre- and post-stenting areas. Unlike IVUS, OFDI systematically detected smaller minimal lumen diameter pre-stenting, which has been repeatedly described in literature, and detected vessel complications (thrombus, tissue prolapse, dissection, strut malapposition) at significantly higher rate.

One year later, Habara et al. [5] performed the first direct comparison of FD-OCT and IVUS in PCI guidance [5]. Interestingly, two major factors associated with stent thrombosis and restenosis, the minimal stent area (6.1 $\pm$ 2.2 mm vs. 7.1 $\pm$ 2.1 mm) and the MSA (7.5 $\pm$ 2.5 mm vs. 8.7 $\pm$ 2.4 mm) were constantly smaller with OCT than with IVUS (p 0.05). Device and success rates were similar in the two groups, however, IVUS showed an advantage over OCT regarding vessel border visualization, stent expansion and the decrease in stent-edge plaque burden. Residual stenosis was detected more frequently with OCT but only at the proximal edge of the reference segment. No significant difference was detected between the two groups regarding stent apposition. In this study it was shown that FD-OCT emerges as a novel technique but there are still limitations in stent optimization.

A comparison of stent expansion (defined as the MSA divided by the mean of the proximal and distal reference lumen areas) with OCT or IVUS was attempted in the ILUMIEN II study, an observational study including 940 patients [6]. The results revealed comparable stent expansion in OCT and IVUS group (72.8% vs. 70.6%, p = 0.29). The detection of major stent malapposition, tissue protrusion or stent edge dissection was higher in the OCT group, but the difference was small. Nevertheless, further randomized trials are needed to compare IVUS and OCT in stent optimization.

The OPINION trial was a multicenter, non-inferiority trial comparing acute and mid-term outcomes of OCT-guided and IVUS-guided PCI [7]. The primary endpoint was target vessel failure defined as a composite of cardiac death, target-vessel related myocardial infarction, and ischemia-driven target vessel revascularization until 12 months after the PCI. The major secondary endpoint was angiographic binary restenosis at 8 months. There was a significantly smaller post-PCI MSA in the OFDI than the IVUS group, but the minimum lumen area (MLA) was comparable in both groups (p = 0.18). OFDI-guided stent implantation was associated with fewer proximal stent-edge hematomas, suggesting that it might be attributed to increased physiological stress through the stent expansion technique with IVUS. Moreover, fewer irregular protrusions were detected in the OFDI group. In the 8-month follow-up OFDI seemed to be related to lower neointimal proliferation—probably because of the less aggressive stent sizing—and higher percentage of uncovered struts, although there was no difference in the minimum lumen area between the two groups. OCT proved to be non-inferior to IVUS in the 12-month follow-up.

The first comparison of IVUS-guided versus OCT-guided versus angiography-guided PCI was attempted in the ILUMIEN III trial [8]. For the OCT-guidance an external elastic membrane (EEM)-based strategy in the proximal and distal reference segments was followed, to assess luminal diameter and lesion coverage. The EEM-based approach was defined as the smallest EEM area in the reference segment. Regarding MSA measurement, OCT was non-inferior to IVUS. Precisely, OCT guidance led to better stent expansion than IVUS guidance and to higher detection of edge dissection and stent malapposition than IVUS or angiography guidance.

The EEM-based strategy proved to be a safe method for stent sizing and provided several advantages over a lumen-guided approach, because it leads to the deployment of a larger stent size (~0.5 mm) and, subsequently, a larger luminal diameter without increasing the risk for post-procedural complications [12, 31]. OCT was superior in detection of suboptimal acute post-PCI outcomes compared to IVUS, except for cases of LM and ostial right coronary artery (RCA) lesions.

The most recent data by the iSIGHT (Optical Coherence Tomography Versus Intravascular Ultrasound and Angiography to Guide Percutaneous Coronary Interventions) trial elaborated the utility of OCT in PCI guidance [9]. In accordance with the ILUMIEN III, 151 patients were randomized to OCT-guided, IVUS-guided or angiography-guided-PCI. For both types of intravascular imaging an EEM-based protocol was applied for stent sizing, provided that EEM was visible in $\ge$180° of the vessel circumference. Otherwise, the maximal lumen diameter was used. OCT proved non inferior to IVUS (91.69 $\pm$ 15.75%, p 0.001) and superior to angiography (90.53 $\pm$ 14.84%, p = 0.041), regarding stent expansion. The EEM-based sizing was delineated as of great importance in stent optimization.

Both intravascular imaging modalities have given new perspectives in PCI guidance. Both demonstrate a great potential in pre- and post-PCI clinical setting, with OCT emerging as a valuable tool in the assessment of PCI short- and long-term results with more precision than IVUS. On the other hand, IVUS is, so far, the intravascular modality most studied and with meta-analyses including death as a factor. Until today, OCT has proven to be non-inferior to IVUS, hence more data from future studies are needed to establish the one over the other in each clinical setting. Studies comparing OCT with IVUS and angiography in PCI guidance as well as ongoing studies are presented in Tables 1,3.

The anatomical location of LM lesions poses difficulties to the accurate evaluation with plain angiography [34]. This is particularly challenging in the presence of intermediate LM stenosis, which is not an uncommon phenomenon and where angiographic measurements cannot be so reliable. Certain pre-specified criteria for the cut-off lumen diameter both before and after PCI have been proposed. Park et al. [35] presented an IVUS-derived MLA of $\le$4.5 mm${}^2$ as a useful index of an FFR $\le$0.80 in functionally significant LM lesions. Fassa et al. [36] showed that deferral of PCI in 131 patients with an IVUS- measured MLA of $\ge$7.5 mm${}^2$ is a safe option with favorable clinical outcomes. Results from the LITRO study revealed that an MLA of 6 mm${}^2$ as a safe cut-off point for deferring PCI with favorable outcomes in 2-year follou-up.

Kang et al. [37] used IVUS to assess post-PCI MSA in LM lesions. 11.4% of patients demonstrated in-stent restenosis (ISR) in the 9-month follow up. The small MSA, defined by certain criteria on segmental basis and considering all areas of the bifurcation, including the polygon of confluence (POC), was a predictive factor of ISR. This segmental evaluation of the four parts, in which the LM was divided, was the novelty of this study. ISR was detected in almost half of the cases with stent under-expansion. This was accompanied with significantly higher rate of MACE in 2 years (90.2 $\pm$ 2.6% vs. 98.1 $\pm$ 0.9% at 2 years, p 0.001). Stent malapposition was not related to increased rate of ISR and/or MACE. Similarly, the EXCEL trial provided a post-PCI MSA cut-off in LM lesions for Caucasians showed a strong correlation of an MSA of 4.4–8.7 mm${}^2$ with adverse events in 3-year follow up [38].

As addressed in the meta-analysis of Wang et al. [34], which included 4592 patients and compared IVUS-guided with angiography-guided drug-eluting stenting of LM coronary artery, IVUS demonstrated a clear benefit regarding hard endpoints: IVUS-guided LM coronary artery stenting reduced the risk of MACE, all-cause death, cardiac death, MI and stent thrombosis. As limitations of this meta-analysis could be considered the fact that the great majority of the included studies were observational and that IVUS guidance did not reduce TVR and TLR. In the latest ACC/AHA and ESC/EACS guidelines IVUS has a class IIa recommendation in the assessment of LM lesions [27, 28].

On the other side, OCT has not yet been incorporated in the ESC/EACS guidelines for LM angioplasty, whereas it is considered as a reasonable alternative of IVUS in the ACC/AHA guidelines, except of cases with ostial lesions. Because of the large diameter of LM coronary artery and the need for complete blood transposition, OCT is thought to be unsuitable for the assessment of LM lesions. Burzotta et al. [39] showed that FD-OCT may be a feasible and effective imaging modality for non-ostial LM lesions. Images can be obtained by applying special manipulation [39]. FD-OCT seems unsuitable for lesions of the proximal segment of the LM due to artifacts, but it effectively demonstrates the other LM segments and, thus, the bifurcation, which is the most commonly diseased site.

The LEMON study was a recent pilot study, that investigated whether patients with mid-LM coronary artery or distal-LM coronary artery disease will benefit from OCT-guided PCI based on a pre-specified protocol [40]. Stent sizing was based on external elastic lamina (EEL). OCT proved to be a safe and feasible method for PCI-guidance in 86% of cases and led to modification in operator’s strategy in 26% of cases, despite the adequate results in angiography. Exceptionally noticeable are the benefits of intracoronary imaging in more complex and high-risk lesions. However, the LEMON criteria did not include vessel anatomical characteristics and a specific analysis of the POC, which might influence stent expansion estimations. The percentage of optimal stent expansion was higher than in ILUMIEN III and DOCTORS trials, in which stent expansion was, also, high. OCT proved to be an effective modality for mid- or distal but not ostial lesions [39, 40, 41]. Nevertheless, the Telescope®(Medtronic Cardiovascular, Santa Rosa, CA, USA)-guiding extension catheter with its special technical characteristics demonstrated good visualization of aorto-ostial lesions, which remain a challenge in OCT-guided PCI [42].

Bifurcation lesions account for 15–20% lesions in PCI procedures [43]. They comprise a demanding group of lesions, because of their complex morphological and physiological features and IVUS is considered as a useful tool for the invasive cardiologist. The latest ESC/EACTS guidelines on myocardial revascularization recommend IVUS-guided revascularization with class IIa for patients with coronary bifurcation lesions [28].

IVUS has demonstrated good results in bifurcation PCI procedures. In the meta-analysis of Yang et al. [43] IVUS-guided revascularization was associated with better short- and long-term clinical outcomes compared to angiography-guided revascularization. The risk for myocardial infarction and TLR or TVR was lower in the IVUS than in the angiography group (2.7% vs. 15.5% and 1.9% vs. 3.7%, respectively), which explains the lower risk of MACE in the IVUS group during the short-term follow-up and the risk for cardiac death in the long-term follow-up.

The important elements in decision-making regarding bifurcation lesions include anatomical and plaque characteristics, the presence of side branch ostial stenosis, the bifurcation angle, the length of the proximal side branch lesion and the distal side branch lesion diameter [44]. OCT is an excellent method for evaluating plaque features and can effectively assess the rest elements as well. Whereas all bifurcation segments can be adequately evaluated by OCT, the low penetration of light through lipid-rich plaque poses obstacles in visualization of the true lumen size, defined by the EEM. This has led to the general use of the media-to media diameter approach instead.

For each OCT round, about 10–15 mL of contrast are required, so the common practice for the visualization of the side branch is to perform one OCT examination before stent implantation and one after stent optimization, which is based on pre-stenting OCT images [44]. When 2 stents are required, the assessment of the side branch is of utmost importance but the angiographic assessment alone or the assessment only of the mother vessel by OCT is insufficient. OCT (especially 3D-OCT) is particularly useful for the guidance and optimization of side branch rewiring, and the evaluation of devices in bifurcation lesions and PCI results.

Ongoing studies are awaited to elaborate the role of intracoronary imaging in PCI guidance of bifurcations. Studies of OCT are about to drastically change our clinical practice. The OCTOBER trial (NCT03171311) aims to evaluate the clinical outcomes of OCT-guided PCI in bifurcations. Similarly, ILUMIEN IV trial is a large, multicenter, superiority trial which compares short- and long-term clinical outcomes of OCT-guided PCI versus angiography-guided PCI in high-risk patients and lesions, including bifurcations [4]. Regarding stent optimization, not only comparison but, also, combination has been studied: the BOOM (Bifurcation and Ostial Optical coherence Mapping) technique is a novel method, currently being evaluated for the precise mapping of the ostial side-branch segment, using OCT and angiography co-registration [45]. On the other hand, the IMPROVE trial (NCT04221815) is sought to evaluate the clinical outcomes and cost-effectiveness of IVUS-guided PCI in complex lesions.

Intracoronary visualization should be considered for the optimization during the implantation of bioresorbable scaffolds (BRS), because of their thick and wide struts. Nevertheless, limited data are available regarding the use of IVUS and OCT in PCI using BRS. Studies so far have demonstrated a rather favorable effect of OCT in PCI guidance with BRS. In their registry Caiazzo et al. [46] reported that there was a need for changing strategy in almost half of the patients treated with OCT-guided bioresorbable scaffolds implantation. Moreover, the examination of 45 patients included in the ABSORB trial with 20 MHz IVUS and OCT showed a clear advantage of OCT both in qualitative and quantitative parameters [47]. The two modalities had low agreement in terms of lesion, frame and strut assessment. OCT demonstrated superior ability to detect incomplete scaffold apposition, side branch struts, dissections and protrusions and an excellent overall reproducibility compared to 20 MHz IVUS.

Later investigations of BRS with IVUS with even higher resolution did not manage to establish it as a preferable method for PCI guidance in this setting. In a comparative study of 361 struts, as referenced to OCT assessments, the novel 60 MHz IVUS (axial resolution 40 $\mu$m) showed superiority over 40 MHz IVUS in terms of strut evaluation [48]. Still, the novel 60 MHz IVUS did not prove to perform better than OCT [49].

In treatment with BRS the so-called PSP (prepare the lesion, sizing appropriately, and post-dilation) criteria have been proposed for stent optimization and the avoidance of adverse cardiac events [50]. In the context of PSP criteria, OCT has a great potential in stent optimization [51]. But since there are no randomized trials with intravascular techniques in BRS implantation and bioresorbable scaffolds are only recommended for clinical trials, more studies are needed to shed light on the differential impact of IVUS and OCT in stent optimization, and their acute and future outcomes.

Intracoronary imaging could play an important role in prediction of slow flow and no-reflow phenomena and, thus, perioperative complications [52, 53, 54]. A pre-PCI IVUS examination of 687 atherosclerotic coronary plaques revealed, that lesion with echo signal attenuation and higher lipid core or microcalcification were strongly associated with post-PCI no-reflow [55]. Ultrasound attenuation with longitudinal length $\ge$5 mm has been associated with higher incidence of no-reflow in ST-Elevation Myocardial Infarction (STEMI) patients [53]. Predictive factors of these phenomena seem to be lesions characterized by large necrotic core or in acute plaque rupture, or Thin-Cap Fibroatheroma (TCFA) [53, 55]. Yamamoto et al. [56] delineated the possibly important role of IVUS in detecting high risk patients for slow-flow with LM-acute coronary syndrome (ACS). Factors predicting slow flow were the vessel diameter and the vessel area (defined as the EEM area).

Patients with ACS caused by plaque rupture are in greater risk for slow-flow and no-reflow phenomena. A retrospective analysis of 145 STEMI patients both with OCT and IVUS revealed occurrence of no-reflow in 40% of them [57]. The combination of OCT and IVUS highlighted the OCT-measured lipid index and the IVUS-measured plaque burden as two key factors for predicting no reflow in this group of patients. To the best of our knowledge, there is no other trial combining these two intravascular imaging modalities. Similarly, there are no randomized trials comparing OCT and IVUS in terms of slow-flow and no-reflow phenomena, which offers a broad field of investigation for risk factors associated with these phenomena.

IVUS has an established role in CTO PCI. The most frequent cause of failure in CTO recanalization is inability of the guide wire to cross the lesion [58]. In a single center series of IVUS-guided stumpless wiring of CTOs, Ryan et al. [58] reported a success rate of 77% of cases and no major complications requiring intervention. IVUS has been proposed as a safe and effective tool in guiding the reverse CART approach. Dai et al. [59] examined the role of IVUS in reverse CART technique: IVUS successfully determined the appropriate balloon size and calcium-free zones with a success rate of 95.9%. 10.2% of cases presented major adverse events but without significant clinical outcome.

Although the IVUS guidance has not been proven superior to the conventional angiography guidance in CTO PCI in reducing MACE, it is associated with a lower risk of TLR, especially in long lesions, MI and stent thrombosis [60, 61]. On the other hand, OCT is currently being studied in the assessment of post-PCI procedural and anatomical results (stent apposition, coverage and endothelization) [62, 63].

Intracoronary imaging is useful in determining predictors of long-term adverse events. Stent expansion and size, calcification and/or attenuation of a plaque are independent predictors of stent edge dissection [64]. Since geographical miss—defined as a significantly diseased segment or (balloon) injured segment not treated by stent—is linked to major adverse effects (TVR, MI, stent failure), intracoronary imaging could be of importance in detecting complications [64, 65, 66]. In an IVUS study, dissections associated with lumen diameter 5 mm${}^2$, with a length $>$3 mm and an arc $>$60° were related to greater risk for TLR [64]. Smaller luminal diameter and inflow/outflow disease (residual stenosis, dissection) were associated with early stent thrombosis after PCI for acute MI [67].

Favorable effects of IVUS guidance in PCI were, also, documented in more complex clinical settings. In the meta-analysis of Shin et al. [66], which included 3 randomized trials and 2345 patients with long lesions or chronic total occlusions (CTO), there was lower risk of MACE in the IVUS-guidance group compared to the angiography-guidance group in a mean follow-up of 1.4 years (0.4% vs. 1.2%, p = 0.040). Similarly, in the meta-analysis of Bavishi et al. [68] with 8 randomized trials and 3276 patients being included, a significant reduction of MACE (RR: 0.64, p = 0.0001), TLR (RR: 0.62, p = 0.004) and TVR (RR: 0.60, p = 0.007) rates was documented in the group of IVUS-guided PCI in 1 year. Of exceptional importance was the IVUS-guided PCI in long lesions, in diabetic patients and in patients suffering acute coronary syndrome.

On the other hand, OCT-guidance seems to positively affect decision-making—and, consequently, results—in PCI [3, 32]. It can effectively detect stent underexpansion, uncovered or malapposed struts, neointimal proliferation and major evaginations [69, 70]. Stent-related MI is associated with stent thrombosis, with or without restenosis [71]. Even though the in-stent thrombotic process after bare metal stent (BMS) and DES implantation is different, OCT proved to be a useful modality for definition of the special characteristics of each process and for the study of stent-related clinical events. Interestingly, MLA 4.5 mm${}^2$and distal edge dissection $>$200 $\mu$m are high-risk characteristics for adverse events [72].

There are limited data from direct comparison of IVUS and OCT with respect to clinical endpoints. The currently running OCTIVUS trial (NCT03394079) is sought to compare safety and efficacy of IVUS-guided and OCT-guided revascularization in terms of target vessel failure (cardiac death, target-vessel myocardial infarction, or ischemia-driven target-vessel revascularization) at 1 year. A broad spectrum of PCI population was enrolled in this study which has already completed recruitment. Both non-inferiority and superiority of OCT will be evaluated. ILUMIEN III and OPINION trial proved non-inferiority of OCT, but they did not have the power to compare relevant clinical outcomes. OCT has more benefits compared to IVUS because of its higher resolution, however, more data are needed. In the context of further optimization there should be a careful consideration of potential benefits (i.e., in avoiding stent underexpansion) and risks (i.e., perforation).