Historically, coronary angiography has been the workhorse invasive imaging tool for coronary diagnostic and invasive procedures. As a luminogram, coronary angiography has intrinsic limitations in cases of vessel foreshortening and overlapping and does not provide information regarding plaque composition and vessel morphology. Intravascular ultrasound (IVUS) provides real-time tomographic crosssectional images of the coronary vessel wall, allowing for quantification of luminal and vessel dimensions, as well as identification of plaque type, location, distribution, size, and burden.

IVUS has been of fundamental importance in the development of interventional cardiology, providing unique insights into the understanding of coronary atherosclerosis and refinements on percutaneous interventional procedures, being considered the gold standard intravascular imaging method to guide percutaneous coronary interventions (PCI) and investigate vascular responses to coronary stents. However, IVUS has limited axial resolution (100–150 μm),1 which can affect its ability to detect acute effects of PCI and vascular response to drug-eluting stents (DES).

Intravascular optical coherence tomography (OCT) is a recently developed light-based imaging modality that uses near-infrared light as its energy source. OCT provides cross-sectional tomographic images of the internal vascular environment, with high axial (10–15 μm) and lateral (20–90 μm) resolutions, by measuring the echo time delay and magnitude of backscattered light.1,2 To date, OCT has been mostly used in the research field, providing new insights into the pathophysiology of atherosclerosis and vascular response to coronary stents. In this article, we discuss the potential clinical applications of OCT.

PREINTERVENTION USE OF OCT

Atherosclerosis Characterization and Plaque Morphology
OCT has proven to be accurate in visualizing all three arterial layers in a normal coronary artery and in detecting even small degrees of intimal thickening. OCT has also demonstrated high sensitivities and specificities for discrimination of different components of atherosclerotic disease, such as fibrotic, fibrocalcific, and lipid-rich plaques.3-5 It also showed high accuracy and sensitivity in identifying and quantifying different features of the so-called vulnerable plaques prone to rupture, such as lipid content, fibrous cap thickness,6,7 and macrophage infiltration.8,9 In comparison to angioscopy and IVUS, OCT demonstrated a superior ability to detect plaque rupture, fibrous cap erosion, and intraluminal thrombus in acute coronary syndrome (ACS) patients.10 High sensitivity and specificity in differentiating red (erythrocyterich) from white (platelet-rich) thrombus has also been demonstrated.11

These features make OCT an invaluable imaging tool for in vivo characterization of atherosclerosis and investigation of plaque morphologies (Figure 1), which may provide useful insights into the mechanisms leading to ACS and help to identify vulnerable lesions that might be at high risk of a future adverse event. Furthermore, accurate plaque characterization may aid in deciding the best landing zone for intracoronary stenting and selecting adjunctive devices and therapies, such as rotational atherectomy, thrombectomy, dedicated devices, and medications.

Assessment of Stenosis Severity
OCT provides accurate information regarding lumen dimensions and quantification of target stenosis, which are important in clinical decision making and planning interventional procedures. Due to a very clear interface between the vascular lumen and the intima layer of the vessel, accurate, automated, and reproducible measurements of lumen area have been accomplished with OCT both in vitro and in vivo.12-14 It is important to note that OCT usually underestimates lumen area in comparison to IVUS measurements.

In an in vivo study, IVUS demonstrated larger lumen areas in comparison to the first-generation time-domain OCT measurements of coregistered vessel segments when OCT images were acquired with a proximal balloon occlusion technique (the lumen area, as determined by IVUS, was 33.7% larger than by OCT). In addition, some preliminary studies suggest this may also be the case with nonocclusive techniques (the lumen area, as determined by IVUS, was 21.5% larger than that determined by time-domain OCT).15 At this point, such differences between methods have to be taken into account when using previously established IVUS criteria during OCT examination for clinical decision making, but new studies with new-generation OCT systems are currently ongoing to better assess this issue.

A variety of observational studies validated IVUSderived parameters against invasive and noninvasive tests for the assessment of lesion severity. An absolute minimal lumen area (MLA) < 4 mm2 correlated strongly with a coronary flow reserve < 2,16 a fractional flow reserve (FFR) < 0.75,17 and perfusion defects on single-photon emission computed tomography.18 In a recent validation study with a total of 236 lesions in 201 patients, an MLA < 2.4 mm2 was identified as the best cutoff to predict an FFR < 0.8, with a diagnostic accuracy of 68% and a sensitivity of 90%. However, poor specificity (60%) limited the value of the anatomical IVUS MLA cutoff to predict physiological significance of coronary lesions.19

More recently, Gonzalo et al20 assessed the diagnostic efficiency of OCT and IVUS in identifying hemodynamically hemodynamically significant coronary stenosis as determined by FFR. Both OCT and IVUS presented moderate diagnostic accuracy for identifying physiologically significant stenosis. The best cutoff values of OCTderived measurements to identify stenosis with an FFR ≤ 0.8 were 1.95 mm2 for MLA (82% sensitivity and 63% specificity) and 1.34 mm for minimal lumen diameter (82% sensitivity and 67% specificity). Optimal cut-off values for IVUS-derived parameters were 2.36 mm2 for MLA (67% sensitivity and 65% specificity) and 1.59 mm for minimal lumen diameter (67% sensitivity and 65% specificity). This study reinforces the low specificities of intravascular anatomic metrics to predict functionally significant stenosis, precluding the routine use of OCT and IVUS as substitutes for FFR regarding the decision making of intermediate angiographic stenosis. However, although FFR is more suitable for assessing the functional significance of angiographically ambiguous lesions, OCT demonstrated a valuable complementary role in identifying the culprit sites and presence of potentially unstable lesions in cases with ACS and an FFR > 0.8.21

OCT USE DURING PCI PROCEDURES

Safety
The introduction of Fourier (or frequency)-domain OCT (FD-OCT), with more A-lines per frame, faster frame rates, and faster pullback speeds, enabled quicker image acquisition (a scan of 54 mm takes < 3 seconds) without the need of coronary blood flow occlusion. These characteristics made OCT procedures simpler, faster, and safer than the first-generation time-domain OCT, particularly with fewer complications, such as chest discomfort, transient arrhythmias, and electrocardiographic changes, increasing the interest for clinical application of OCT.22,23 In fact, use of FD-OCT for PCI guidance was associated with a favorable safety profile.24 In a large series of 297 FD-OCT acquisitions performed in 155 vessels in 150 all-comers patients, no procedure-related adverse events were recorded.25

Selection of PCI Strategy
Before PCI, OCT provides valuable information about plaque composition and extension, which may help in planning and guiding the interventional procedure and the use of adjunctive therapies. In cases of heavy calcification, OCT can accurately assess calcium circumferential extension and distance from the lumen,26 contributing to decisions on avoiding direct stenting, performing lesion predilatation, and the use of adjunctive devices such as scoring balloons and rotational atherectomy.27 Plaque composition at stent edges has been associated with the occurrence of stent-edge dissections.28 Avoiding stent placement over calcified or lipid-rich plaques might potentially reduce the occurrence of stent-edge dissections. Furthermore, placing stents over thin-capped fibroatheromas has been independently associated with the occurrence of periprocedural myocardial infarction (MI),29 and possible disruption of such areas may lead to increased risk of late stent thrombosis (LST), as suggested by pathologic studies.30

OCT can also help to identify suitable normal (or “less diseased”) vessel references for stent placement—the so-called stent landing zone. Because of limited tissue penetration, the adventitia is not always visualized, and quantification of the plaque burden is not an available option. Therefore, determination of stenosis severity and lesion length relies entirely upon proper lumen identification and may be cumbersome for less-experienced operators. Sites with the largest lumen proximal and distal to a stenosis and in the same arterial segment (usually within 10 mm of the stenosis with no major intervening side branches) have been used to define the proximal and distal references of a stenosis (Figure 2).31 Importantly, this is not necessarily the site with the least amount of plaque. Accurate quantification of vascular lumen dimensions can also optimize the selection of balloon and stent sizes.

Assessment of Stent Expansion, Apposition, and Sizing
Stent underexpansion and malapposition have been linked to DES restenosis32,33 and acute/subacute thrombosis. 34 To date, the use of intravascular imaging to define stent and/or balloon sizing has relied on distal vessel reference or average reference vessel sizes. Likewise, stent expansion is usually assessed by comparison of the minimum in-stent cross-section area (frequently by using single cross-section information to represent the whole stented segment) against predefined reference areas, which can be the proximal, distal, largest, or average reference area.35 Current semiautomatic algorithms can easily and reproducibly quantify lumen and stent dimensions during OCT procedures in the catheterization laboratory, allowing quick recognition of minimal stent area and the estimation of stent expansion against the vascular references.

Stent strut apposition is part of most IVUS-guided PCI criteria for optimal stent implantation. Due to its high resolution, OCT is more sensitive than IVUS in detecting incomplete stent apposition (ISA), tissue prolapse, and in-stent thrombus formation.36 Although acute ISA in the modern PCI era has not been associated with an increased occurrence of late adverse events,37-39 it has been related to delayed vascular healing and incomplete endothelialization of stent struts at follow-up40,41—one of the most powerful pathological predictors for stent thrombosis.30,42 The clinical and prognostic impact of frequent and usually small-sized stent malapposition as seen by OCT has yet to be defined. In a recent study, acute ISA size was an independent predictor of persistent ISA and grossly delayed coverage after 6-month follow-up.43

Assessing Acute Effects of PCI
Coronary stenting promotes differing degrees of vessel injury. Pathologic studies have indicated the association of implantation characteristics with late events after stent implantation.44 Furthermore, IVUS studies have demonstrated that stent expansion, tissue protrusion, and edge dissections are associated with increased rates of early stent thrombosis.39,45 Due to its high resolution, OCT can accurately assess the acute vascular response after coronary stent implantation (Figure 3). In a study of 80 vessels in 73 patients, OCT allowed a detailed visualization of vessel injury after stent implantation. Tissue prolapse within the stented segment was present in nearly all patients (97.5%) after stenting. In-stent dissections are also very frequent (86.3%), whereas stent-edge dissections were identified in 25% of the cases. A detailed quantification of the morphometric characteristics of such findings was also possible by OCT.46 Still, because of its higher resolution, OCT clearly allows a much more detailed and frequent visualization of such phenomenon than IVUS, but the clinical impact of these findings is yet to be determined.

OCT-Guided PCI
To date, there are no randomized, prospective studies assessing the role of OCT-guided PCI. In a small study, OCT was performed after stent implantation in 74 patients to assess the need for further intervention. In 24 patients (32.4%), additional interventions were performed based on the OCT findings (15 patients underwent additional balloon dilatation, and nine patients underwent additional stenting). In the remaining 50 patients, the PCI results were deemed satisfactory, and no further interventions were performed, resulting in a 6-month event-free survival rate of 98%.24

Stefano et al25 reported a series including unrestricted use of OCT in 150 consecutive patients (155 vessels) for pre-PCI evaluation or poststenting optimization. In this series, pre-PCI OCT imaging prompted changes in the initial angiography-based PCI strategy in 81.8% of the cases. Almost half of the angiographically planned stent lengths, one-quarter of stent diameters, and more than half of the postdilatation balloon diameters were altered based on OCT imaging. The use of OCT after PCI led to further interventions in 54.8% of the target vessels, mostly by inducing additional balloon dilatations to correct stent malappositions or implanting additional stents to treat edge dissections.

In the study by Viceconte et al,47 OCT was used to guide coronary stenting in 108 patients. Sixty-eight OCT pullbacks were performed before PCI, leading to deferral of the procedure in 13 (19.1%) and use of adjunctive devices in 23 (33.8%). Out of 207 pullbacks performed after stenting, 29 (14%) led to additional stent implantation either because of edge dissection or residual stenosis, and further stent optimization with a high-pressure/ larger-sized balloon was suggested in 64 (30.9%). In another small case series study, OCT measurements safely allowed upsizing of the cutting balloon, resulting in an acceptable lumen increase before deployment of another DES for in-stent restenosis.48

Lastly, Prati et al49 compared the 1-year clinical outcomes of 335 patients undergoing PCI with angiographic plus OCT guidance against a matched group of another 335 patients undergoing PCI with angiographic guidance alone. Per protocol, some recommendations were advised when signs of acute vascular injury were detected by OCT: (1) edge dissections and reference lumen narrowing had to be treated with an additional stent; (2) stent underexpansion (in-stent MLA ≥ 90% of the average reference lumen area or ≥ 100% of lumen area of the reference segment with the lowest lumen area) required further dilatation of the implanted stent with a noncompliant balloon of the same size at ≥ 18 atm or with a semicompliant balloon having a diameter ≥ 0.25 mm larger than the previously used balloon at ≥ 14 atm; (3) stent malapposition required further dilatation of the implanted stent with a noncompliant or semicompliant balloon having a diameter ≥ 0.25 mm larger than the previously used balloon at ≥ 14 atm; and (4) intraluminal thrombus required further dilatation of the stent with a noncompliant or semicompliant balloon of the same diameter at 8 to 14 atm for 60 seconds. OCT discovered adverse features requiring interventions in 34.7% of the cases. Unadjusted analysis revealed that the OCT group had a significantly lower 1-year risk of cardiac death (1.2% vs 4.5%; P = .01), cardiac death or MI (6.6% vs 13%; P = .006), and the composite of cardiac death, MI, or repeat revascularization (9.6% vs 14.8%; P = .044). After extensive adjustments by multivariate analysis and propensity score–adjusted analysis, angiographic plus OCT guidance was still associated with a significantly lower risk of cardiac death or MI (odds ratio, 0.49; 95% confidence interval, 0.25–0.96; P = .037).

Despite these favorable results, the magnitude of OCTdetected vascular injury that deserves further interventions is still controversial. Whether OCT-guided stent optimization will lead to improved clinical outcomes in the contemporary era of new-generation DES and potent adjunct pharmacology has yet to be determined in large, prospective, randomized trials.

ASSESSMENT OF LONG-TERM RESULTS AFTER PCI

The extent of endothelialization has been suggested by pathologic studies as one of the strongest predictors for late DES thrombosis, hence introducing the need for detailed, in vivo assessment of stent strut coverage. For many years, IVUS has been considered the gold standard imaging modality to assess long-term results of coronary stenting. Although IVUS was the standard tool for neointimal hyperplasia quantification at follow-up, it lacks the axial resolution to resolve the thin neointimal coverage in the DES era, when the average late loss of modern secondgeneration DES is as low as 0.1 to 0.2 mm. OCT has 10-fold greater resolution than IVUS and demonstrated a high correlation with histology for the evaluation of neointimal area and neointimal thickness,50,51 providing detailed in vivo assessment of stent coverage as a surrogate marker for stent safety.52 Nevertheless, the correlation of OCT evaluation of stent coverage and late adverse clinical events has yet to be determined.

A recent study by Guagliumi et al53 was the first attempt to investigate, in vivo, the role of uncovered struts in patients with definite LST after DES implantation. In this study, 18 patients experiencing DES LST (median, 615 days after implantation) undergoing emergent PCI were compared with 36 matched DES control subjects undergoing routine repeat OCT and IVUS who did not experience LST for a period of ≥ 3 years. By OCT, patients with LST had a higher percentage of uncovered (median [interquartile range]; 12.27 [5.5–23.33] vs 4.14 [3–6.22]; P < .001) and malapposed struts (4.6 [1.85–7.19] vs 1.81 [0–2.99]; P < .001) in comparison to the control group. By IVUS, positive vascular remodeling was increased in patients with LST (mean vessel cross-section area, 19.4 ± 5.8 mm2 vs 15.1 ± 4.6 mm2; P = .003). By multivariate analysis, the length of segments with uncovered stent struts by OCT and the remodeling index by IVUS were independent predictors of LST.

OCT can also be used for elucidating other mechanisms of late stent failures. Different patterns of neointimal hyperplasia can be easily characterized by OCT,54,55 allowing for the identification of areas consistent with the presence of peristrut fibrinoid and proteoglycan deposition,56 as well as the occurrence of in-stent neoatherosclerosis (Figure 4),57,58 which has been recently linked to late restenosis and LST.58-62

Furthermore, although IVUS is more sensitive in detecting stent fracture than angiography,63 limited resolution along with the frequent occurrence of acoustic and heart motion artifacts may affect its ability to detect small strut fractures. By providing fewer artifacts, faster pullback speeds, and higher axial resolution, intravascular OCT can be an important adjunctive tool for the clinical diagnosis of this complication.64-66 Moreover, investigation of structural integrity is of particular importance for the acute and late success of new polymeric bioresorbable scaffold technologies.

PERSPECTIVES FOR THE FUTURE

A great amount of effort has been dedicated toward automating the segmentation process of acquired OCT images. Automatic lumen segmentation will provide operators with a fast and accurate quantification of vascular dimensions, making it very easy and intuitive to estimate the degree of lesion stenosis and select the size of intracoronary stents. Algorithms enabling automated tissue characterization will allow for a more objective assessment of plaque morphology and composition.67,68 The same is true for automated stent strut detection and segmentation algorithms,69 which will provide fast quantification of stent dimensions and identification of sites of stent underexpansion and malapposition.

Three-dimensional volumetric OCT datasets are capable of providing a large amount of data in a very intuitive and comprehensive way, aiding the interpretation and analysis of atherosclerosis and vessel/stent interaction. 70,71 Automation of lumen and stent segmentation will serve as the basis for faster three-dimensional OCT reconstruction software, available online in the cath lab, with the potential to add information regarding vascular and stent geometries, as well as stent expansion and its relation to surrounding structures. Algorithms providing fusion of intravascular OCT images and angiography carry the potential to improve the interpretation of coronary artery disease and the guidance of coronary intervention.72,73

Despite all the potential for clinical use of OCT images, there are still no clear indications for the clinical application of OCT. Ongoing and future studies validating the clinical use of OCT in all-comers and selected population subgroups will determine the role of OCT in procedural guidance.

CONCLUSION

OCT is a recently introduced high-resolution imaging modality with unique features that provide detailed information regarding the vascular biology. OCT has established itself in the research scenario as an invaluable tool for atherosclerosis characterization, especially in the detection of vulnerable plaques, and assessment of vascular response to intracoronary devices. The large amount of detailed structural information along with great potential for technology and software development makes OCT a promising intravascular tool for clinical decision making and guiding and optimizing interventional procedures. Whether these beneficial advantages will translate to an improvement in patientrelated outcomes is an issue to be determined in large prospective studies and registries.

Daniel Chamié, MD, is with the Department of Invasive Cardiology, Instituto Dante Pazzanese de Cardiologia in São Paulo, Brazil. He has disclosed that he has no financial interests related to this article.

Ricardo A. Costa, MD, PhD, is with the Department of Invasive Cardiology, Instituto Dante Pazzanese de Cardiologia in São Paulo, Brazil. He has disclosed that he has no financial interests related to this article. Dr. Costa may be reached at +55 (11) 5085-6000; rcosta@dantepazzanese.org.br.

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