Intracoronary Optical Coherence Tomography 2018...cular optical coherence tomography-based...

15
STATE-OF-THE-ART REVIEW Intracoronary Optical Coherence Tomography 2018 Current Status and Future Directions Ziad A. Ali, MD, DPHIL, a,c Keyvan Karimi Galougahi, MD, PHD, a Akiko Maehara, MD, a,c Richard A. Shlofmitz, MD, b Ori Ben-Yehuda, MD, a,c Gary S. Mintz, MD, c Gregg W. Stone, MD a,c ABSTRACT The advent of intravascular imaging has been a signicant advancement in visualization of coronary arteries, particularly with optical coherence tomography (OCT) that allows for high-resolution imaging of intraluminal and transmural coronary structures. Accumulating data support a clinical role for OCT in a multitude of clinical scenarios, including assessing the natural history of atherosclerosis and modulating effects of therapies, mechanisms of acute coronary syndromes, mechanistic insights into the effects of novel interventional devices, and optimization of percuta- neous coronary intervention. In this state-of-the-art review, we provide an overview of the published data on the clinical utility of OCT, highlighting the areas that need further investigation and the current barriers for further adoption of OCT in interventional cardiology practice. (J Am Coll Cardiol Intv 2017;10:247387) © 2017 by the American College of Cardiology Foundation. S ince its introduction more than 2 decades ago, optical coherence tomography (OCT) has been increasingly used in biomedical research and clinical practice, including recently in cardiovascular medicine. Despite the diagnostic use of OCT in vascular pathology, the impact of intracoronary OCT on clinical practice has been limited. Large- registry data in percutaneous coronary intervention (PCI) (1) have raised questions regarding the clinical signicance of the detailed ndings on high- resolution imaging by OCT (2), highlighting the paucity of data from prospective clinical trials. Here- in we provide an up-do-date overview of the use of OCT in coronary artery disease and highlight areas in which more denitive data on clinical application of intracoronary OCT are needed. LIMITATIONS OF CORONARY ANGIOGRAPHY AND INCREMENTAL DIAGNOSTIC VALUE OF INTRAVASCULAR IMAGING Coronary angiography provides a real-time lume- nogramof the coronary anatomy and remains the most widely used invasive imaging technique for diagnosing coronary artery disease and guiding PCI. However, angiography has a number of inherent limitations, including those arising from its 2-dimensional projection of the 3-dimensional coro- nary tree, as well as limitations in assessing the vessel wall, plaque composition, and extent and distribution of atherosclerosis (3). Angiography is associated with high interobserver variability in visual estimation of degree of stenosis, even among experienced From the a Center for Interventional Vascular Therapy, Division of Cardiology, Presbyterian Hospital and Columbia University, New York, New York; b Department of Cardiology, St. Francis Hospital, Roslyn, New York; and the c Cardiovascular Research Foundation, New York, New York. Dr. Shlofmitz has served as a member of the Speakers Bureau for Cardiovascular Systems. Dr. Maehara has received grant support from Boston Scientic; has received consulting honoraria from Boston Scientic and ACIST Medical Systems; and is a member of the Speakers Bureau for St. Jude Medical. Dr. Mintz has received grants from Boston Scientic, Volcano, and St. Jude Medical; and consulting honoraria from Volcano Corporation, Boston Scientic, and ACIST Medical Systems. Dr. Ali is a consultant for and has received grant support from St. Jude Medical and Cardiovascular Systems Inc. to Columbia University. All other authors have reported that they have no relationships relevant to contents of this paper to disclose. Manuscript received August 7, 2017; accepted September 13, 2017. JACC: CARDIOVASCULAR INTERVENTIONS VOL. 10, NO. 24, 2017 ª 2017 BY THE AMERICAN COLLEGE OF CARDIOLOGY FOUNDATION PUBLISHED BY ELSEVIER ISSN 1936-8798/$36.00 https://doi.org/10.1016/j.jcin.2017.09.042

Transcript of Intracoronary Optical Coherence Tomography 2018...cular optical coherence tomography-based...

J A C C : C A R D I O V A S C U L A R I N T E R V E N T I O N S VO L . 1 0 , N O . 2 4 , 2 0 1 7

ª 2 0 1 7 B Y T H E AM E R I C A N C O L L E G E O F C A R D I O L O G Y F O U N D A T I O N

P U B L I S H E D B Y E L S E V I E R

I S S N 1 9 3 6 - 8 7 9 8 / $ 3 6 . 0 0

h t t p s : / / d o i . o r g / 1 0 . 1 0 1 6 / j . j c i n . 2 0 1 7 . 0 9 . 0 4 2

STATE-OF-THE-ART REVIEW

Intracoronary Optical CoherenceTomography 2018Current Status and Future Directions

Ziad A. Ali, MD, DPHIL,a,c Keyvan Karimi Galougahi, MD, PHD,a Akiko Maehara, MD,a,c Richard A. Shlofmitz, MD,b

Ori Ben-Yehuda, MD,a,c Gary S. Mintz, MD,c Gregg W. Stone, MDa,c

ABSTRACT

Fro

Ne

Fo

Dr

AC

Sci

Me

Co

Ma

The advent of intravascular imaging has been a significant advancement in visualization of coronary arteries,

particularly with optical coherence tomography (OCT) that allows for high-resolution imaging of intraluminal

and transmural coronary structures. Accumulating data support a clinical role for OCT in a multitude of clinical scenarios,

including assessing the natural history of atherosclerosis and modulating effects of therapies, mechanisms of acute

coronary syndromes, mechanistic insights into the effects of novel interventional devices, and optimization of percuta-

neous coronary intervention. In this state-of-the-art review, we provide an overview of the published data on the clinical

utility of OCT, highlighting the areas that need further investigation and the current barriers for further adoption of OCT

in interventional cardiology practice. (J Am Coll Cardiol Intv 2017;10:2473–87)

© 2017 by the American College of Cardiology Foundation.

S ince its introduction more than 2 decades ago,optical coherence tomography (OCT) has beenincreasingly used in biomedical research and

clinical practice, including recently in cardiovascularmedicine. Despite the diagnostic use of OCT invascular pathology, the impact of intracoronaryOCT on clinical practice has been limited. Large-registry data in percutaneous coronary intervention(PCI) (1) have raised questions regarding the clinicalsignificance of the detailed findings on high-resolution imaging by OCT (2), highlighting thepaucity of data from prospective clinical trials. Here-in we provide an up-do-date overview of the use ofOCT in coronary artery disease and highlight areasin which more definitive data on clinical applicationof intracoronary OCT are needed.

m the aCenter for Interventional Vascular Therapy, Division of Cardiolo

w York, New York; bDepartment of Cardiology, St. Francis Hospital, Ro

undation, New York, New York. Dr. Shlofmitz has served as a member o

. Maehara has received grant support from Boston Scientific; has receiv

IST Medical Systems; and is a member of the Speakers Bureau for St. Jude

entific, Volcano, and St. Jude Medical; and consulting honoraria from

dical Systems. Dr. Ali is a consultant for and has received grant support from

lumbia University. All other authors have reported that they have no relati

nuscript received August 7, 2017; accepted September 13, 2017.

LIMITATIONS OF CORONARY ANGIOGRAPHY

AND INCREMENTAL DIAGNOSTIC VALUE OF

INTRAVASCULAR IMAGING

Coronary angiography provides a real-time “lume-nogram” of the coronary anatomy and remains themost widely used invasive imaging technique fordiagnosing coronary artery disease and guiding PCI.However, angiography has a number of inherentlimitations, including those arising from its2-dimensional projection of the 3-dimensional coro-nary tree, as well as limitations in assessing the vesselwall, plaque composition, and extent and distributionof atherosclerosis (3). Angiography is associated withhigh interobserver variability in visual estimationof degree of stenosis, even among experienced

gy, Presbyterian Hospital and Columbia University,

slyn, New York; and the cCardiovascular Research

f the Speakers Bureau for Cardiovascular Systems.

ed consulting honoraria from Boston Scientific and

Medical. Dr. Mintz has received grants from Boston

Volcano Corporation, Boston Scientific, and ACIST

St. JudeMedical and Cardiovascular Systems Inc. to

onships relevant to contents of this paper to disclose.

ABBR EV I A T I ON S

AND ACRONYMS

ACS = acute coronary

syndrome(s)

DES = drug-eluting stent(s)

EEL = external elastic laminae

FFR = fractional flow reserve

HR = hazard ratio

IFC = intact fibrous cap

IVUS = intravascular

ultrasound

MI = myocardial infarction

MLA = minimal luminal area

MSA = minimum stent area

NA = neoatherosclerosis

OCT = optical coherence

tomography

PCI = percutaneous coronary

intervention

RFC = ruptured fibrous cap

ScT = scaffold thrombosis

ST = stent thrombosis

STEMI = ST-segment elevation

myocardial infarction

TCFA = thin-cap fibroatheroma

Ali et al. J A C C : C A R D I O V A S C U L A R I N T E R V E N T I O N S V O L . 1 0 , N O . 2 4 , 2 0 1 7

State-of-the-Art OCT 2018 D E C E M B E R 2 6 , 2 0 1 7 : 2 4 7 3 – 8 7

2474

operators (3–5); computer-assisted quantita-tive coronary angiography only marginallyimproves diagnostic accuracy and estimationof functional significance (6). Furthermore,coronary artery segments that appear normalon angiography may harbor a significantburden of atherosclerosis (7). The diseasedbut angiographically nonstenotic segmentsundergo compensatory changes in responseto accumulation of plaques by outwardexpansion of the external elastic laminae(EEL) to maintain normal luminal area(i.e., positive remodeling) (8).

Intravascular imaging by intravascular ul-trasound (IVUS) or OCT provides detailedvisualization of intraluminal and transmuralcoronary anatomy, overcoming many of thelimitations of angiography (9). Comparedwith grayscale IVUS, image acquisition byOCT is faster with higher resolution but haslower depth of tissue penetration. The higherspatial resolution of OCT offers better ex-amination of fine details in the near fieldcompared with IVUS, including more specificdetermination of tissue characteristics (e.g.,calcium, thrombus, neointimal tissue) and

more accurate assessment of stent parameters such asvessel wall apposition, strut coverage, tissue pro-lapse, and edge dissection (9). Because of its greaterdepth of penetration, IVUS is better suited forassessment of larger vessels such as the left maincoronary artery and more reliably images aorto-ostiallesions, because image acquisition by IVUS does notrequire blood clearance, unlike OCT (9). Despite thesedifferences, both techniques provide value fordiagnostic and procedural guidance by providingadditional information that is complementary toangiography (10). Acknowledging that OCT is a rela-tively new imaging modality, with fewer data on itsuse in PCI compared with IVUS (11–13), in this reviewwe describe the potential use of OCT in guiding PCI,including qualitative and quantitative assessmentof atherosclerotic plaques, plaque-specific lesionpreparation, selection of appropriate interventionaldevices, and optimization of PCI.

ASSESSMENT OF ATHEROSCLEROTIC LESIONS:

MORPHOLOGY, FUNCTIONAL SIGNIFICANCE,

ANDVULNERABILITY

OCT is useful in morphologic assessment of coronaryatherosclerosis. Detailed description of normal anddiseased coronary arteries by OCT is feasible by un-derstanding the optical attenuation characteristics of

vascular tissue layers. Although the trilaminarappearance represents the light scattering reflectedfrom the layers of the normal vessel, loss of this ar-chitecture generates appearances that correlate withdifferent types of atherosclerotic lesions (14). Asimplified algorithm for OCT image interpretation innative coronary arteries is shown in Figure 1. Thisalgorithm is useful in describing the most frequentpathological morphologies in the vessel wall thatinclude low-attenuating, signal-rich lesions (fibrousplaques), high-attenuating, signal-poor regionscovered with fibrous cap (lipid-rich plaques), andlow-attenuating, sharply delineated, signal-poor re-gions (calcific plaques), and those inside the lumenincluding the low-attenuating white thrombus orhigh-attenuating red thrombus that casts a shadow onthe vessel wall (14) (Figure 2).

Similar to IVUS, OCT has limited use in deter-mining the functional significance of coronary le-sions. Minimal luminal area (MLA) on OCT modestlycorrelates with fractional flow reserve (FFR) in ves-sels other than the left main coronary artery (15),reflecting additional factors beyond the degree ofstenosis that determine functional significance, suchas the amount of subtended viable myocardium. OCT-derived cutoff values for MLA that correlate withischemic threshold on FFR (16–22) are summarized inTable 1. The OCT-derived MLA thresholds are smallerthan IVUS-derived MLAs (median OCT-derived MLA1.96 mm2 [1.85 to 1.98 mm2] vs. IVUS-derived MLA 2.8mm2 [2.7 to 2.9 mm2]) (15). Like IVUS, OCT-derivedMLA thresholds have reasonably high positive pre-dictive value (80% to 92%) but lower negative pre-dictive value for physiological significance (66% to89%) (Table 1); thus, the decision whether to performPCI on the basis of OCT-derived MLA alone can beerroneous in up to one-third of cases and is notroutinely recommended. Precise delineation of the3-dimensional vessel geometry on OCT has been usedin computational models to calculate FFR in inter-mediate coronary stenoses, with good correlationwith invasively measured FFR <0.80 (R ¼ 0.72;p < 0.001) (23). Unlike IVUS, few studies have corre-lated clinical outcomes after OCT-determined lesionseverity versus FFR, particularly in the left maincoronary artery (9).

OCT has been used to define plaques with high-riskfeatures (i.e., “vulnerable plaque”) that are associ-ated with acute coronary syndromes (ACS), includingthin-cap fibroatheromas (TCFAs) and inflammation(macrophage infiltration). The ability to measure capthickness on OCT may improve detection of TCFAscompared with IVUS-based modalities, which havebeen validated in prospective studies on the natural

FIGURE 1 Simplified Algorithm for Interpretation of Optical Coherence Tomographic Images in the Native Coronary Arteries

This algorithm is useful in describing native coronary lesions, with the understanding that many lesions have a mixed appearance and contain

more than 1 pathological morphology mentioned in the schematic. For a comprehensive description of lesions by optical coherence

tomography (OCT), including recognition of the artifacts that may affect image interpretation, readers are referred to the consensus standard

OCT document (17).

J A C C : C A R D I O V A S C U L A R I N T E R V E N T I O N S V O L . 1 0 , N O . 2 4 , 2 0 1 7 Ali et al.D E C E M B E R 2 6 , 2 0 1 7 : 2 4 7 3 – 8 7 State-of-the-Art OCT 2018

2475

history of atherosclerosis (24–26). Nevertheless,several issues regarding the detection of vulnerableplaques by OCT, particularly TCFA (27,28), remainunresolved, including modest interobserver agree-ment (29), artifacts mimicking lipid (30), and lack ofprospective studies validating a cutoff value forfibrous cap thickness or the use of plaquemorphology to predict or exclude future clinicalevents. Future studies are required to establishwhether OCT alone or in combination with other im-aging modalities (31) has clinical value in identifyingvulnerable plaques.

GUIDANCE OF PCI

LESION PREPARATION. A potential application ofOCT is to guide strategies for “lesion preparation”on the basis of the baseline plaque morphology(Central Illustration). For example, pre-dilatation withan undersized balloon or a direct stenting approachmay be appropriate in the presence of largely fibrousor lipid-rich plaques on OCT, whereas in calcified le-sions, aggressive noncompliant balloon pre-dilatation, use of a cutting or scoring balloon, orrotational or orbital atherectomy can be considered.In calcified lesions, IVUS delineates the calcificationarc but not its thickness, because of reflection of ul-trasound waves off calcium. In contrast, OCT allowsthe determination of both calcification arc andthickness in most cases (32,33) (Figure 2C). This dif-ference may be of clinical significance because calci-fication area on OCT (determined by arc and

thickness) correlates with stent underexpansion (32),a critical determinant of stent-related outcomes (9).Furthermore, detailed OCT characterization may beuseful in guiding calcific plaque preparation. Forinstance, balloon inflation in plaques with widearc and low thickness on OCT (with cutoff valuesof 227� and 0.67 mm, respectively [34]) results incalcium fracture, which is associated with greaterstent expansion (33,34). Last, the presence ofOCT-determined large lipid burden and TCFA hasbeen associated with peri-PCI myocardial infarc-tion (MI) (35–41). In the ILUMIEN I (ObservationalStudy of Optical Coherence Tomography [OCT] inPatients Undergoing Fractional Flow Reserve [FFR]and Percutaneous Coronary Intervention) study,optical coherence tomographic guidance comparedwith angiography only was associated with lowerperi-PCI MI (0% vs. 8.8%) (42). Prospective studiesare needed to determine whether OCT-derivedquantification of calcification severity to directprimary atheroablation versus balloon dilatationonly for preparation of calcified plaques orperhaps to avoid aggressive pre-dilatation in lipid-rich lesions improves periprocedural and clinicaloutcomes.

MEASUREMENT OF VESSEL DIMENSIONS AND

SELECTION OF DEVICES. OCT can be used tomeasurevessel dimensions to select balloon and stent di-ameters (Central Illustration). The high resolution ofOCT coupled with blood clearance required for imageacquisition provide sharp border definition between

FIGURE 2 Common Morphologies Detected on Intracoronary Optical Coherence Tomography

*

A B C

D

* Intima

Media

Adventitia

*

Media

E F

*

(A) Normal artery: the bright-dark-bright 3-layered appearance corresponding to intima, media, and adventitia is visualized in the entirety of

the vessel circumference. (B) Fibrous plaque: note homogeneous, signal-rich regions (asterisk). (C) Calcific plaque: characterized as a

signal-poor region with sharply delineated borders (arrowheads). Analysis of calcification depth (double arrows) and arc (measured at 348�) is

feasible in most cases with optical coherence tomography. (D) Lipid-rich plaque: characterized as a signal-poor region with poorly defined

borders (asterisk). Note that because of light attenuation, the media is not visible beyond the lipid content of the plaque. (E) White

thrombus: mass floating within the lumen (arrows) that is platelet and white blood cell rich with minimal optical coherence tomographic

signal attenuation. (F) Red thrombus: mass floating/attached to the luminal surface (arrows) that is rich in red blood cells and therefore highly

attenuates the optical coherence tomographic signal, casting a shadow on the vessel wall behind the mass (asterisk).

Ali et al. J A C C : C A R D I O V A S C U L A R I N T E R V E N T I O N S V O L . 1 0 , N O . 2 4 , 2 0 1 7

State-of-the-Art OCT 2018 D E C E M B E R 2 6 , 2 0 1 7 : 2 4 7 3 – 8 7

2476

the lumen and the vessel wall, allowing automatedmeasurements of vessel dimensions. In phantommodels, linear dimensions are overestimated by IVUSby about 10%, whereas optical coherence tomographicmeasurements are close to the actual values (12).Moreover, measurements of vessel dimensions in vivoare more reproducible by OCT than IVUS (43,44).However, unlike IVUS, there are no establishedmethods for stent sizing by OCT during PCI. Thelimited depth of penetration of light at the athero-sclerotic lesion site results in the loss of EEL visibilityin lesions with large plaque burden (whereas thegreater depth of penetration of IVUS allows EEL visi-bility in all but severely calcific or lipidic lesions).Because of this difference, in a small randomizedstudy of 70 patients, luminal dimensions weremore frequently used for measurement of referencevessel diameters and selection of stent size, likelycontributing to smaller minimum stent areas (MSA)

(6.1 � 2.2 mm2 vs. 7.1 � 2.1 mm2; p ¼ 0.04) and lowerstent expansion defined as the MSA divided by meanluminal cross-sectional area (84 � 16% vs. 99 � 17%;p ¼ 0.003), compared with “more aggressive” EEL-based sizing with IVUS 5.37 mm2 (interquartile range[IQR]: 3.82 to 6.02) vs. 5.77 mm2 (IQR: 5.19 to 7.61);p ¼ 0.024) (11) (Table 2). In a post hoc propensity-matched retrospective analysis of the outcomes ofOCT-guided stent implantation in the ILUMIEN I studycompared with IVUS-guided PCI in the ADAPT-DES(Assessment of Dual Antiplatelet Therapy With Drug-Eluting Stents) study (i.e., ILUMIEN II) (45), opticalcoherence tomographic guidance resulted in similarstent expansion but a smaller finalMSA comparedwithIVUS guidance (Table 2). The randomized OPINION(Optical Frequency Domain Imaging vs. IntravascularUltrasound in Percutaneous Coronary Intervention)trial comparing OCT- versus IVUS-guided PCIshowed smaller stent diameters (2.92 � 0.39 mm2 vs.

TABLE 1 Relationship Between Optical Coherence Tomographic Minimal Luminal Area

and Fractional Flow Reserve

First Author (Ref. #) Lesions

FFRPositive

(<0.80) (%)

OCT MLACutoff(mm2) AUC

Sensitivity(%)

Specificity(%)

NPV(%)

PPV(%)

Shiono et al. (16)* 62 50* 1.91 0.90 93 77 81 92

Gonzalo et al. (17) 61 46 1.95 0.73 82 63 66 80

Pawlowski et al. (18) 71 23 2.05 0.91 75 90 — —

Reith et al. (19) 62 53 1.59 0.81 76 79 74 81

Pyxaras et al. (20) 55 26 2.43 0.89 — — — —

Zafar et al. (21) 41 22 1.62 0.80 70 97 89 91

Reith et al. (22) 142 — 1.64 0.84 79 76 — —

*FFR cutoff <0.75.

AUC ¼ area under curve; FFR¼ fractional flow reserve; MLA¼minimal luminal area; NPV ¼ negative predictivevalue; OCT ¼ optical coherence tomographic; PPV ¼ positive predictive value.

CENTRAL ILLUSTRATION PCI Guidance and Optimizationby OCT

Intracoronary OCT in PCI

Pre-Interven�onAssessment

Lesion Prepara�on and Stent Deployment

Complica�on and Post Procedural

Assessments

• Assess plaque morphology• Iden�fy reference segments• Choose stent size

• Confirm landing zones• Determine stent expansion

• Iden�fy edge dissec�on• Determine apposi�on• Iden�fy �ssue protrusion

Ali, Z.A. et al. J Am Coll Cardiol Intv. 2017;10(24):2473–87.

Intracoronary optical coherence tomography (OCT) provides detailed characterization of

the arterial wall complimentary to angiography. Pre-percutaneous coronary interven-

tion (pre-PCT) OCT can precisely determine plaque morphology, reference segments, and

stent size. During lesion preparation and stent deployment, OCT may aid in minimizing

geographical miss, in particular with angiographic co-registration, for both lesion

preparation and stent deployment. OCT allows automated assessment of stent

expansion. Post-PCI, OCT identifies with the greatest sensitivity edge dissections, mal-

apposition and tissue protrusion due to its superior resolution

J A C C : C A R D I O V A S C U L A R I N T E R V E N T I O N S V O L . 1 0 , N O . 2 4 , 2 0 1 7 Ali et al.D E C E M B E R 2 6 , 2 0 1 7 : 2 4 7 3 – 8 7 State-of-the-Art OCT 2018

2477

2.99 � 0.39 mm2; p ¼ 0.005), maximum balloon di-ameters (3.1 � 0.8 mm vs. 3.3 � 1.2 mm; p ¼ 0.058)and acute post-procedural minimal stent areas(5.17 mm2 [IQR: 4.06 to 6.29] vs. 5.63 mm2 [IQR: 4.76to 7.52]; p ¼ 0.088) in the OCT-guided arm withno difference in the acute in-stent angiographicminimum lumen diameter (2.57 � 0.43 mm vs. 2.61 �0.46 mm; p ¼ 0.23) (46,47). Follow-up OCT fromthe OPINION study at 8 months showed a largerMSA with IVUS compared with optical coherencetomographic guidance (Table 2) (47).

In this context, the prospective, multicenterrandomized ILUMIEN III: OPTIMIZE PCI study wasrecently conducted with 1:1:1 randomization of 450patients undergoing PCI to optical coherence tomo-graphic, IVUS, or angiographic guidance. A blindedpost-PCI OCT run was performed in the angiographyand IVUS groups to allow comparison of OCT-derivedMSA across all groups as the primary endpoint of thestudy. In ILUMIEN III, an EEL-based OCT-guidedsizing strategy was used in an attempt to achievelarger stent diameters compared with luminal refer-ence measurements, accommodating for IVUS over-sizing (Figure 3) (48). Operators were able to identifyEEL at >180� of the reference segments in 84% ofcases (vs. 83% by IVUS; p ¼ 0.78), whereas in the corelaboratory, these rates were 95% and 100%, respec-tively (p ¼ 0.02). The final median MSA was 5.79 mm2

(IQR: 4.54 to 7.34 mm2) with optical coherencetomographic guidance, 5.89 mm2 (IQR: 4.67 to 7.80mm2) with IVUS guidance, and 5.49 mm2 (IQR: 4.39 to6.59 mm2) with angiographic guidance. Opticalcoherence tomographic guidance was noninferior toIVUS guidance (p ¼ 0.001), achieving the primaryendpoint of the trial, but not superior to either IVUS(p ¼ 0.42) or angiographic guidance (p ¼ 0.12) (48).Whether optical coherence tomographic guidance ofPCI results in improved clinical outcomes comparedwith angiographic guidance alone will be addressedin the large-scale multicenter randomized ILUMIENIV trial, using the same algorithm for OCT-guided PCI,with 1:1 randomization of more than 2,500 patientswith high-risk clinical (medically treated diabetesmellitus) or high-risk angiographic (biomarkerpositive ACS, stented segment $28mm, 2-stentbifurcation, severe calcification, CTO, ISR) features.The primary clinical outcome will be target vesselfailure.

OPTIMIZATION OF STENT DEPLOYMENT. The auto-mated OCT-angiography coregistration feature canhelp in identifying the stent edge landing zonesand determining the optimal stent length, thereforeeliminating the ambiguity of visually selecting

the “normal-appearing” reference segments on angi-ography where plaque burden may be extensive (7)(Figure 3, Central Illustration). In a recentlycompleted randomized study, OCT-angiography cor-egistration aided in more precise stent deploymentand resulted in a trend toward reducing major stentedge dissection compared with angiographic guid-ance (49). Future studies are needed to compare theOCT-based anatomic lesion length with the proposed“physiological” lesion length, determined by FFRpull-back or automated instantaneous wave-freeratio maps (50), in serial or diffuse stenoses andto examine the impact of the combined opticalcoherence tomographic imaging and physiologic

TABLE 2 Studies Comparing Procedural Results With Optical Coherence Tomography–Guided Versus Intravascular Ultrasound–Guided

Percutaneous Coronary Intervention

First Author (Ref. #)

PatientsReference Diameter

Measurement MSA (mm2) Stent Expansion (%)

OCT IVUS OCT IVUS OCT IVUS OCT IVUS

Habara et al. (11) 35 35 EEL: 63% EEL: 100% 6.1 � 2.2 7.1 � 2.1 84 � 16 99 � 17

p < 0.001 p ¼ 0.04 p ¼ 0.003

Maehara et al. (45) 286 286 Lumen EEL 5.0 (3.9–6.4) 5.5 (4.4–7.0) 73 (63–81) 71 (62–79)

p < 0.0001 p ¼ 0.29

Otake (47) 50 50 Lumen EEL 5.17 (4.06–6.29) 5.63 (4.76–7.52) 0.82 (0.71–0.94) 0.89 (0.81–0.99)

p ¼ 0.088 p ¼ 0.17

Ali et al. (48) 158 146 EEL: 95% EEL: 100% 5.79 (4.54–7.34) 5.89 (4.67–7.80) 88 � 17 87 � 16

p ¼ 0.02 p ¼ 0.42 p ¼ 0.63

Values are mean � SD or median (interquartile range).

EEL ¼ external elastic lamina; IVUS ¼ intravascular ultrasound; MSA ¼ minimum sent area; OCT ¼ optical coherence tomography.

Ali et al. J A C C : C A R D I O V A S C U L A R I N T E R V E N T I O N S V O L . 1 0 , N O . 2 4 , 2 0 1 7

State-of-the-Art OCT 2018 D E C E M B E R 2 6 , 2 0 1 7 : 2 4 7 3 – 8 7

2478

guidance in optimizing PCI in such lesions. OCT-angiography coregistration can also aid in quickidentification and targeted post-dilatation of under-expanded stent segments (Central Illustration), thusavoiding unnecessary post-dilatation, especially nearstent edges, where post-dilatation may result in edgedissection (51). It may be feasible to use a combina-tion of intracoronary visualization by OCT usingnoncontrast flush media and OCT-fluoroscopy cor-egistration together with coronary physiology in lieuof angiographic guidance under specific circum-stances. An example of this concept is shown by thefeasibility and safety of OCT- and physiology-guided“zero-contrast” PCI in advanced chronic kidneydisease (52).

The implications of post-stent deployment find-ings, such as edge dissection, tissue protrusion,thrombus, and malapposition (Central Illustration),have been the subject of studies from registries(1,42,53–55). The relationship of these findings tosubsequent adverse events and how they should bemanaged remains uncertain (2). ILUMIEN IV will helpdetermine whether correction of post-deploymentfindings such as major edge dissection and malap-position, which were more frequently detected byOCT compared with angiography in ILUMIEN III (48),will translate to lower stent-related adverse events.On the basis of the available data, acute stent–vesselwall malapposition without underexpansion (56),intrastent plaque or thrombus protrusion, or proximaledge dissection (not affecting effective luminal areaas extrapolated from IVUS studies [57]) may not needcorrection, as they have not been associated withhigher rates of major adverse cardiovascular events(1). OCT-detected in-stent tissue protrusion has beencategorized into 3 groups: smooth protrusion (signi-fying minimal vessel injury), disrupted fibrous tissue

protrusion (mild vessel injury), and irregular protru-sion (moderate to severe vessel injury with a highlikelihood of medial disruption and lipid core pene-tration) (58). Of these patterns, irregular protrusionwas an independent predictor of device-orientedclinical events and target lesion revascularization ina large cohort (58). Moreover, small in-stent MLA(<4.5 mm2 [1] or <5.0 mm2 in drug-eluting stents[DES] and <5.6 mm2 in bare-metal stent [58]),dissection >200 mm at the distal stent edge, andreference luminal area <4.5 mm2 at either the distalor proximal stent edges (1) were predictors of majoradverse cardiovascular events, driven largely bytarget lesion revascularization and hence may requirecorrection (Table 3).

ASSESSMENT OF CULPRIT LESIONS AND

GUIDANCE OF PRIMARY PCI IN ACS

By identifying thrombus and delineating plaquerupture or erosion, OCT is useful in identifying culpritlesions and the underlying mechanisms in ACS, espe-cially when the culprit lesion(s) are ambiguous onangiography (59). Most culprit lesions in ST-segmentelevation myocardial infarction (STEMI) are due toacute thrombosis overlying or adjacent to a rupturedfibrous cap (RFC). Overall, optical coherence tomo-graphic studies have identified plaques with RFCs in50% (Figure 4A) and plaques with intact fibrous caps(IFCs) (Figure 4B) in 37% of all underlying culprit le-sions in ACS (60–65) (Table 4). Compared with plaqueswith RFCs, plaques with IFCs tend to have less severediameter stenosis, lower lipid content, thicker fibrouscaps, and smaller lipid arcs and more often occur inyounger patients, especially women, without tradi-tional cardiovascular risk factors with the exception ofsmoking (66). ACS with an RFC portends a worse

FIGURE 3 Optical Coherence Tomography–Guided Percutaneous Coronary Intervention Strategy Tested in the ILUMIEN III Study

A B C D

E

F G H I J

K

Coregistration of angiography and optical coherence tomography (OCT) (A), including longitudinal (E) and cross-sectional optical coherence tomographic frames (B–D),

along with longitudinal luminal automated measures that provides minimal, mean, and reference diameter measurements as well as area and diameter stenosis along

the pull-back. An example of OCT-guided percutaneous coronary intervention (PCI) in a patient with angina is illustrated on the coregistered angiographic (A) and

optical coherence tomographic (B to E) images. On the basis of the external elastic lamina–based measurements of the distal (B, 2.91 mm) and proximal (D, 3.10 mm)

reference segments, and the distance on optical coherence tomographic automation (24.4 mm) (E), a 3.0 � 24 mm drug-eluting stent was directly deployed without

pre-dilatation because of the presence of fibroatheromatous plaque without calcification. On post-PCI OCT (F to K), the minimum stent area (MSA) in both the distal

(G,H) and proximal (I,J) halves of the stent met protocol criteria for adequate expansion (7.90 > 90% � 6.67 mm2 distally and 8.28 > 90% � 8.66 mm2 proximally);

thus, post-dilatation was deemed unnecessary. This case highlights the potential use of plaque characterization on OCT to determine the need for pre-dilatation and

post-dilatation, although ensuring optimal stent sizing and deployment. The ILUMIEN (Observational Study of Optical Coherence Tomography [OCT] in Patients

Undergoing Fractional Flow Reserve [FFR] and Percutaneous Coronary Intervention) IV study will investigate whether stent implantation with this algorithm for stent

sizing and optimization improves clinical outcomes compared with angiography guidance alone. AS ¼ area stenosis; dist ¼ distal; DS ¼ diameter stenosis;

MLA ¼ minimal luminal area; prox ¼ proximal.

J A C C : C A R D I O V A S C U L A R I N T E R V E N T I O N S V O L . 1 0 , N O . 2 4 , 2 0 1 7 Ali et al.D E C E M B E R 2 6 , 2 0 1 7 : 2 4 7 3 – 8 7 State-of-the-Art OCT 2018

2479

prognosis compared with an IFC (67). TCFA is the mostlikely lesion precursor for ACS due to an RFC (60–65).Whereas OCT is useful in identifying culprit plaques inIFC ACS, OCT cannot presently identify a non-thrombotic vulnerable plaque phenotype that un-derlies future IFC ACS. Finally, aggressive antiplatelettherapy alone without stenting has been applied inselected patients with IFC ACS in registry studies withgood results (68), although larger, prospective studiesare required before routine stenting is deferred inpatients with OCT-identified IFC-ACS.

OCT has also been useful in ascertaining lesscommon causes of ACS, such as calcified nodules orspontaneous coronary dissection (detected in 3% and2% of cases, respectively [Table 4]) and in specificpatient populations (e.g., diabetes and end-stage

renal disease). Similar to IVUS (69), atheroscleroticplaques demonstrating luminal irregularities withoutthrombus, intimal tears, erosion, or intraluminalthrombi have been identified by OCT in the culpritsegments of spasm-induced ACS (70). On rarer occa-sions, OCT may be useful in identifying STEMI due tocoronary thromboemboli (e.g., secondary to atrialfibrillation or hypercoagulable states) wherein eitherno underlying plaque or plaque without erosion ordisruption is evident following thrombectomy (71,72).

The ability of OCT to determine the site of plaquerupture (vs. erosion), thrombus burden, and the lon-gitudinal extent of underlying plaque, as well as toaccurately measure reference lumen and vesseldiameters, underlies the potential utility of OCT toguide PCI in STEMI. In a 2:1 propensity-matched

TABLE 3 Independent Optical Coherence Tomography Predictors of Post-Stenting Events

First Author (Ref. #)Patients(Lesions) Endpoints Clinical Outcomes OCT Predictors of Events

Prati et al. (1) 832 (984) MACE (12 months) OCT suboptimal vs. optimal:HR: 4.41 (95% CI: 2.9–6.8;p ¼ 0.001)

In-stent MLA <4.5 mm2: HR: 1.64 (95% CI: 1.1–2.6; p ¼ 0.04)Dist dissection >200 mm: HR: 2.54 (95% CI: 1.3–4.8; p ¼ 0.004)Dist reference luminal area <4.5 mm2: HR: 4.65 (95% CI: 2.5–8.8; p < 0.001)Prox reference luminal area <4.5 mm2: HR: 5.73 (95% CI: 2.2–14.6; p < 0.001)

Wijns et al. (42) 409 (458) MACE (1 months) No optimization vs. pre- vs.post- vs. pre- andpost-OCT optimization:

Device oriented: p ¼ 0.12Patient oriented: p ¼ 0.07

Chamie et al. (54) 230 (249) MACE (12 months) With vs. without acute edgedissection: p ¼ 0.58

OCT predictors of stent edge dissections:Plaque at stent edges: HR: 6.15 (95% CI: 2.09–18.1; p ¼ 0.001)Angle of calcification: HR: 1.02 (95% CI: 1.00–1.03; p ¼ 0.017)TCFAs: HR: 6.16 (95% CI: 1.42–26.69; p ¼ 0.016)Stent eccentricity: HR: 1.06 (95% CI: 1.01–1.12; p ¼ 0.02)Luminal eccentricity: HR: 1.10 (95% CI: 1.06–1.15; p < 0.01)Stent-to-lumen diameter: HR: 1.22 (95% CI: 1.13–1.15; p < 0.01)

Soeda et al. (58) 900 (786) MACE/TLR(12 months)

Irregular protrusion: HR: 2.64 (95% CI: 1.40–5.010; p ¼ 0.003) for MACE; HR: 2.66(95% CI: 1.40–5.05; p ¼ 0.003) for TLR

MSA <5.0 mm2 in BMS or <5.6 mm2 in DES: HR: 2.54 (95% CI: 1.23–5.25; p ¼ 0.012)for MACE; HR: 2.54 (95% CI: 1.24–5.21; p ¼ 0.011) for TLR

Prati et al. (78)* 507 (588) MACE (18 months) OCT suboptimal vs. optimalstenting: p < 0.01

In-stent MLA <4.5 mm2: HR: 2.72 (p < 0.001)Intrastent plaque/thrombus protrusion >500 mm: HR: 2.3 (p ¼ 0.002)Dist dissection >200 mm: HR: 3.84 (p < 0.001)Dist reference luminal area <4.5 mm2: HR: 8.50 (p < 0.001)

Im et al. (92) 351 (356) MACE (28 months) No malapposition vs. acute vs.late persistent vs. lateacquired malapposition:p ¼ 1.00

OCT predictors of acute malapposition:Diameter stenosis >70%: HR: 2.45 (95% CI: 1.19–5.06; p ¼ 0.015)Calcified lesion: HR: 11.19 (95% CI: 3.52–35.63; p < 0.001)Stent length >25 mm: HR: 3.80 (95% CI: 1.11–13.03; p ¼ 0.033)OCT predictors of late persistent malapposition:Acute malapposition within stent edges: HR: 6.31 (95% CI: 2.03–19.60; p ¼ 0.001)Acute malapposition volume >2.56 mm3: HR: 1.17 (95% CI: 1.01–1.35; p ¼ 0.044)OCT predictors of late acquired malapposition:Plaque/thrombus prolapse 70% vs. 42% in no malapposition (p < 0.001)

*Performed in patients with acute coronary syndromes.

BMS ¼ bare-metal stent(s); CI ¼ confidence interval; DES ¼ drug-eluting stent(s); dist ¼ distal; HR ¼ hazard ratio; MACE ¼ major adverse cardiac event(s) (composite of death, myocardial infarction, andtarget lesion revascularization); MLA ¼ minimal luminal area; MSA ¼ minimum stent area; OCT ¼ optical coherence tomographic; prox ¼ proximal; TCFA ¼ thin-cap fibroatheroma; TLR ¼ target lesionrevascularization.

Ali et al. J A C C : C A R D I O V A S C U L A R I N T E R V E N T I O N S V O L . 1 0 , N O . 2 4 , 2 0 1 7

State-of-the-Art OCT 2018 D E C E M B E R 2 6 , 2 0 1 7 : 2 4 7 3 – 8 7

2480

prospective cohort study, pre- and post-stenting op-tical coherence tomographic guidance in 214 patientswith STEMI resulted in larger final minimum lumendiameter compared with angiographic guidance in 428patients with STEMI (2.99 � 0.48 mm vs. 2.79 � 0.47mm; p < 0.0001), potentially because of further dila-tation of suboptimal stent results in the OCT arm (73).In the randomized DOCTORS (Does Optical CoherenceTomography Optimize Results of Stenting) study,higher post-PCI FFR values were achieved with opticalcoherence tomographic guidance versus angiographyguidance in 240 patients with non-STEMI (0.94 � 0.04vs. 0.92 � 0.05; p ¼ 0.005) (74). By OCT assessment inTROFI (Randomized study to Assess the Effect ofThrombus Aspiration on Flow Area in Patients WithSTEMI), in 141 patients, manual thrombectomy did notincrease the effective flow area or MSA (75). In the214-patient OCT substudy of the TOTAL (Thrombec-tomy Versus PCI Alone) trial, manual thrombectomydid not reduce thrombus burden at the STEMI lesionsite compared with PCI alone (76). Although routine

aspiration thrombectomy in STEMI is not warranted,a recent retrospective OCT-based study reported acorrelation between post-thrombectomy residualthrombus and the extent of microvascular dysfunc-tion and myocardial damage, suggesting potentialuse of thrombectomy in lesions with high thrombusburden to reduce distal embolization and preservemicrocirculatory function (77). This approachrequires prospective validation before adoption inclinical practice. Last, in a retrospective analysis of588 lesions in 507 patients in CLI-OPCI ACS(Centro per la Lotta Contro L’Infarto-Optimizationof Percutaneous Coronary Intervention DatabaseUndergoing PCI for ACS), optical coherence tomo-graphic predictors of stent-related events were similarto the elective setting: underexpansion (in-stentMLA <4.5 mm2 [hazard ratio (HR): 2.72; p < 0.01]),stent inflow/outflow disease (reference luminalarea <4.5 mm2 at the distal [HR: 6.07; p < 0.01] orproximal (HR: 8.50; p < 0.001] stent edges), anddissection at the distal stent edge >200 mm (HR: 3.84;

FIGURE 4 ST-Segment Elevation Myocardial Infarction Caused by Plaque

Rupture and Erosion

A

B

C D E F

G

H

H

G

FEDC

B

A

ST-segment elevation myocardial infarction (STEMI) with plaque rupture (top).

Angiography in a patient presenting with STEMI showed stenosis in the left

anterior descending coronary artery (inset). Serial optical coherence tomographic

cross-sectional imaging with coregistration from proximal to distal of the culprit

lesion following aspiration thrombectomy (A to H) identified the minimal luminal

area (MLA) (A) in an area of necrotic core, adherent white thrombus (B,C), empty

crater from plaque rupture (D,E), thin-cap fibroatheroma (TCFA) rupture (arrows)

(F), intact TCFA (arrow) (G), and lipidic plaque (H). STEMI without plaque rupture

(bottom). Angiography in a patient presenting with STEMI showed stenosis in the

left anterior descending coronary artery (inset). Serial optical coherence tomo-

graphic cross-sectional imaging with coregistration from proximal to distal of the

culprit lesion (A to H) identified thrombus (mostly white thrombus, arrows)

without ruptured fibrous cap, indicating plaque erosion. Figure courtesy of Drs.

Kakuta and Lee, Tsuchiura Kyodo Hospital, Japan.

J A C C : C A R D I O V A S C U L A R I N T E R V E N T I O N S V O L . 1 0 , N O . 2 4 , 2 0 1 7 Ali et al.D E C E M B E R 2 6 , 2 0 1 7 : 2 4 7 3 – 8 7 State-of-the-Art OCT 2018

2481

p < 0.001) (78). Additionally, intrastent plaqueor thrombus protrusion (HR: 2.35; p < 0.01) wasan independent predictor of adverse outcomes(Table 3) (78).

SURVEILLANCE OF METAL STENTS AND

BIORESORBABLE SCAFFOLDS

DURING FOLLOW-UP

OCT may have use in long-term surveillance of stentsand scaffolds including visualization of neointimalproliferation, neoatherosclerosis (NA) and mecha-nisms of stent thrombosis (ST) or scaffold thrombosis(ScT). Strut coverage has been frequently used as asurrogate for safety and efficacy of new stents,assuming that it represents re-endothelialization.However, studies in experimental models (79) andfibrin-targeted near-infrared fluoroscopy combinedwith OCT have shown that strut coverage canbe composed of fibrin rather than the assumedphysiological neointima, especially in DES (80).Moreover, a relationship between strut coverage andendothelium-dependent vasorelaxation has not beenestablished (81). Although a density-based analysis ofstrut coverage on OCT has been able to differentiatefibrin from physiological neointimal tissue (82), it isunclear whether this approach could be easily andreliably used in the clinical setting. Neointimal pat-terns on OCT do not always agree with specific his-topathologic tissue types. The “homogenous pattern”often correlates with smooth muscle cells withincollagenous/proteoglycan matrix, the “layeredpattern” with healed neointimal rupture or erosion,and “high intensity with high attenuation” with su-perficial macrophage accumulation, but each patternmay also correlate with other histological findings(83). It is important to note that inhomogeneousneointimal patterns, especially in neointimal tissue>1 to 2 mm in thickness, may also occur because ofartifacts secondary to limited penetration of light.Combining OCT with a second imaging modalityholds promise to determine the cellular componentsof neointima and may prove useful for assessment ofpost-stenting healing (31,84).

Chronic inflammation and impaired endothelialfunction with increased lipid uptake contribute tolate NA developing inside stents, which may be animportant mechanism for stent restenosis and lateand very late ST (85). NA is more common, occursearlier, and is more diffuse in DES compared withbare-metal stents (84). The axial length of NA andpresence of thin-cap NA (86), in particular with DES

TABLE 4 Underlying Culprits for Acute Coronary Syndromes on Optical

Coherence Tomography

First Author (Ref. #) LesionsRupturedPlaque

PlaqueErosion

CalcifiedNodule SCAD

Other Causesor Undetermined

Nishiguchi et al. (60) 326 160 153* — 13 —

Jia et al. (61) 126 55 39 10 3 19†

Guagliumi et al. (62) 128 63 32* — 2 31

Wang et al. (63) 80 37 25* 2 — 16

Higuma et al. (64) 112 72 30 9 1 —

Kajander et al. (65) 70 34 31* 5 — —

Total 842 421 (50) 310 (37) 26 (3) 19 (2) 66 (8%)

Values are n (%). *Included all plaques with intact fibrous caps. †Eight lesions with tight stenosis, 2 with coronaryspasm, 1 with fissure, 1 with takotsubo cardiomyopathy, and the remaining 7 showing absence of any afore-mentioned characteristics.

SCAD ¼ spontaneous coronary artery dissection.

Ali et al. J A C C : C A R D I O V A S C U L A R I N T E R V E N T I O N S V O L . 1 0 , N O . 2 4 , 2 0 1 7

State-of-the-Art OCT 2018 D E C E M B E R 2 6 , 2 0 1 7 : 2 4 7 3 – 8 7

2482

(84), has been associated with higher rates of peri-PCIMI. In the randomized TRANSFORM OCT (TripleAssessment of Neointima Stent Formation to Reab-sorbable Polymer With OCT) study, the NA burdenwas similar in a DES with bioresorbable polymercompared with a DES with permanent polymer (87),suggesting comparable biocompatibility of biode-gradable versus permanent polymer coatings used inthe latest generations of DES.

Optical coherence tomographic findings in patientswith metallic DES thrombosis may be mechanisticallyrelated but causality cannot be declared from registrydata. In the prospective PESTO (Morphological Pa-rameters Explaining Stent Thrombosis Assessed byOCT) registry of 120 patients with definite ST aftermetallic DES placement, strut malapposition (48%)and underexpansion (26%) were associated withacute ST (<24 h post-PCI) and subacute ST (1 to 30days), whereas malapposition (31%) and NA (28%)were associated with late ST (>30 days) and very lateST (>12 months) (88). In the CLI-THRO (Centro per laLotta Contro L’Infarto) registry, subacute ST wasassociated with suboptimal stent deployment (stentunderexpansion and edge dissection) (89). Late andvery late ST were associated with malapposition in aretrospective study (90), whereas very late ST wasassociated with strut malapposition (35%), NA (28%),uncovered struts (12%), and stent underexpansion(7%) in a prospective registry (91). Among factors thathave been associated with ST, the role of malap-position remains unclear. Malapposition at the timeof stent implantation is a common finding on OCT(48), usually occurring because of stent/vessel size orcontour mismatch, and may not require correction ifnot associated with stent underexpansion (56). Mal-apposition may persist (late persistent malapposition)or subsequently develop because of stent-relatedinflammation with positive vascular remodeling

(late-acquired malapposition) (88,92). Malapposition,regardless of type, was not shown in a large serialoptical coherence tomographic follow-up study to beof clinical consequence (92) (Table 3).

By OCT, suboptimal implantation with incompletelesion coverage, underexpansion, and malappositionhave been associated with both early and late AbsorbBioresorbable Vascular Scaffold ScT, whereas discon-tinuation of dual-antiplatelet therapy may contributeto late events (93). In a study summarizing all thepublished cases of early (n ¼ 17), late (n ¼ 10), and verylate (n ¼ 16) ScT assessed by OCT, findings associatedwith early ScT were malapposition (24%), incompletelesion coverage (18%), and device underexpansion(12%). Findings in late and very late ScT consisted ofmalapposition (35%), scaffold discontinuity (31%),peristrut low-intensity area (19%), uncovered struts(15%), scaffold underexpansion (15%), incompletelesion coverage (12%), scaffold recoil (12%), andrestenosis (8%) (94). Late Absorb ScT has also beenassociated with preserved box-shaped appearance onOCT (which has been detected at up to 44 monthspost-deployment [95]) and intraluminal scaffolddismantling (95,96). If scaffold dismantling is me-chanically restrained by neointimal tissue and doesnot abut into the lumen, it may be of no clinicalconsequence (97). Scaffold structures protruding intothe lumenmay occur either at the time of implantationby excessive polymer stretching with fracture or lateor very late during bioresorption due to excessivebiomechanical cyclic stress or iatrogenic causes(disruption by interventional catheters) (98). Cautionis thus warranted when passing interventional or im-aging devices through the Absorb BioresorbableVascular Scaffold within several years after implan-tation, and prolonged dual-antiplatelet therapy maybe considered, especially if intraluminal scaffolddismantling is visualized (98).

LIMITATIONS OF OCT

It is important to be aware of several limitations ofthe current optical coherence tomographic technol-ogy. Because of lower penetration depth (1 to 2 mm)compared with IVUS (8 to 10 mm), assessment ofplaque volume or visualization of plaques in the deeplayers of the vessel wall may not always be feasible byOCT. Differentiating calcium from lipid, especially inthe presence of large plaque burden, may be chal-lenging. As mentioned, signal attenuation by lipidicplaques can obscure EEL and preclude EEL-baseddiameter measurement in some cases.

Moreover, interpretation of the structures under-neath the red thrombus is limited by the high signal

TABLE 5 Applications of Optical Coherence Tomography in Interventional Cardiology Based on Current Evidence

Level of Evidence forClinical Application Atherosclerosis ACS PCI and Stent Surveillance

Good evidence supportingclinical application

Morphologic plaquedescription:

Fibrous, fibrocalcific,lipid-rich plaquesAccurate dimensional

measurements

Identification of thrombus andunderlying culprit lesionphenotype:

� RFC� IFC� Calcified nodules� ThromboembolismIdentification of culprit lesions inangiographically obscure cases

Accurate dimensional measurements

Some evidence supportingclinical application

Identification of underlyinglesions in vasospastic ACS

Selection of stent/scaffold diameter/length(minimizing geographic miss and residual edge

disease)Stent/scaffold optimization (avoiding

underexpansion, major edge dissection,irregular protrusion, acute malappostion(scaffolds only)

Identification of treatable mechanisms of stent/scaffold thrombosis (e.g., underexpansion orfracture)

More evidence needed toestablish application

Identification ofinflammationand vulnerableplaques (TCFA)

Guidance of lesion preparation strategy and directstenting

Healing post-stenting (neointimal coverage)Treatment of IFC in ACS

ACS ¼ acute coronary syndrome; IFC ¼ intact fibrous cap; RFC ¼ ruptured fibrous cap; TCFA ¼ thin-cap fibroatheroma.

J A C C : C A R D I O V A S C U L A R I N T E R V E N T I O N S V O L . 1 0 , N O . 2 4 , 2 0 1 7 Ali et al.D E C E M B E R 2 6 , 2 0 1 7 : 2 4 7 3 – 8 7 State-of-the-Art OCT 2018

2483

attenuation that casts a shadow on the vessel wall.Although thrombectomy can aid in recognition ofthe underlying RFC or IFC, it may also remove partsof the fibrous cap and modify the underlying plaque,leading to misinterpretation of the substrate for ACS.Thrombectomy may also remove the thin neointimallayer in ST, leaving “uncovered struts” as theapparent mechanism of ST. Although some opticalcoherence tomographic criteria, including shape andsize, have been suggested to distinguish tissue fromthrombus protrusion post-stent deployment (14),this distinction may not always be feasible. Simi-larly, subtle changes due to the presence of macro-phages in inflamed plaques may not be readilyappreciated (14). Recognition of various artifactsoriginating from light propagation, optical coherencetomographic catheter location, and movement andartifacts associated with stents is essential in correctinterpretation of optical coherence tomographic im-ages (14). Last, 2-dimensional optical coherencetomographic imaging has limitations, particularly inPCI on bifurcation lesions or assessment of stentdeformation and fracture. Online 3-dimensionalreconstruction is promising in mitigating these lim-itations (99,100).

BARRIERS TO ADOPTION OF OCT

Although accumulating evidence supports the clin-ical use of intravascular imaging (e.g., a reduction inmajor adverse cardiovascular events by IVUS- vs.

angiography-guided DES implantation in meta-analysis of numerous randomized trials [101]) IVUSremains markedly underused in the United Statesand Europe, and the newer technique of OCT evenmore so. There are practical barriers to widespreaduptake of OCT. The amount of imaging data acquiredby OCT can be overwhelming, and training in properoptical coherence tomographic image interpretationhas been suboptimal. New-generation opticalcoherence tomographic systems have software thatreduce manual processing burden by automatingsome tasks. For example, the automated luminalprofile measurements in the Ilumien Optis I System(St. Jude Medical, St. Paul, Minnesota) facilitatesselection of stent diameter and length and combinedwith tracking-based angiography coregistration aidsin the real-time assessment of stent deployment(Figure 3). However, tissue characterization is timeconsuming and labor intensive, and automated pla-que characterization with OCT is not yet available.Progress is promising, however, for the developmentof algorithms for automated tissue classification us-ing texture, attenuation, or other tissue characteris-tics on OCT (102–105). Blood clearance needed forimage acquisition increases the radio-contrastburden, which is particularly undesirable in pa-tients with renal disease. Alternative noncontrastflush media with proven biocompatibility andadequate optical transparency are needed to addressthis concern (52). Last, the additional cost of intra-vascular imaging is prohibitive in many countries

Ali et al. J A C C : C A R D I O V A S C U L A R I N T E R V E N T I O N S V O L . 1 0 , N O . 2 4 , 2 0 1 7

State-of-the-Art OCT 2018 D E C E M B E R 2 6 , 2 0 1 7 : 2 4 7 3 – 8 7

2484

because of inadequate or restricted reimbursement.Nonetheless, although intravascular imaging isroutine in Japan, where the costs of both IVUS andOCT are reimbursed (106), demonstration of cost-effectiveness is essential for OCT to become widelyintegrated into routine PCI.

CONCLUSIONS

A summary of clinical uses of intracoronary OCT onthe basis of current data is provided in Table 5. OCTprovides a wealth of data on coronary structure andpathology with an as yet unrealized potential for

application in the diagnosis and treatment of coro-nary artery disease. Systematic efforts on educatingthe interventional cardiology community on appro-priate use of OCT and demonstration of improvedclinical outcomes from randomized trials are requiredto further integrate this novel modality into clinicalpractice.

ADDRESS FOR CORRESPONDENCE: Dr. Ziad A. Ali,Center for Interventional Vascular Therapy, Divisionof Cardiology, New York Presbyterian Hospital andColumbia University, New York, New York 10032.E-mail: [email protected].

RE F E RENCE S

1. Prati F, Romagnoli E, Burzotta F, et al. Clinicalimpact of OCT findings during PCI: the CLI-OPCI IIstudy. J Am Coll Cardiol Img 2015;8:1297–305.

2. Chandrashekhar Y, Narula J. A picture is worth athousand questions: is OCT ready for routineclinical use? J Am Coll Cardiol Img 2015;8:1347–9.

3. Topol EJ, Nissen SE. Our preoccupation withcoronary luminology. The dissociation betweenclinical and angiographic findings in ischemic heartdisease. Circulation 1995;92:2333–42.

4. Zir LM, Miller SW, Dinsmore RE, Gilbert JP,Harthorne JW. Interobserver variability in coronaryangiography. Circulation 1976;53:627–32.

5. White CW, Wright CB, Doty DB, et al. Does vi-sual interpretation of the coronary arteriogrampredict the physiologic importance of a coronarystenosis? N Engl J Med 1984;310:819–24.

6. Yong AS, Ng AC, Brieger D, Lowe HC, Ng MK,Kritharides L. Three-dimensional and two-dimensional quantitative coronary angiography,and their prediction of reduced fractional flowreserve. Eur Heart J 2011;32:345–53.

7. Mintz GS, Painter JA, Pichard AD, et al.Atherosclerosis in angiographically “normal” cor-onary artery reference segments: an intravascularultrasound study with clinical correlations. J AmColl Cardiol 1995;25:1479–85.

8. Glagov S, Weisenberg E, Zarins CK,Stankunavicius R, Kolettis GJ. Compensatoryenlargement of human atherosclerotic coronaryarteries. N Engl J Med 1987;316:1371–5.

9. Mintz GS. Clinical utility of intravascular imag-ing and physiology in coronary artery disease.J Am Coll Cardiol 2014;64:207–22.

10. Prati F, Di Vito L, Biondi-Zoccai G, et al.Angiography alone versus angiography plusoptical coherence tomography to guidedecision-making during percutaneous coronaryintervention: the Centro per la Lotta control’Infarto-Optimisation of Percutaneous CoronaryIntervention (CLI-OPCI) study. EuroIntervention2012;8:823–9.

11. Habara M, Nasu K, Terashima M, et al. Impactof frequency-domain optical coherence tomogra-phy guidance for optimal coronary stent

implantation in comparison with intravascular ul-trasound guidance. Circ Cardiovasc Interv 2012;5:193–201.

12. Kubo T, Akasaka T, Shite J, et al. OCTcompared with IVUS in a coronary lesion assess-ment: the OPUS-CLASS study. J Am Coll CardiolImg 2013;6:1095–104.

13. Fujino Y, Bezerra HG, Attizzani GF, et al. Fre-quency-domain optical coherence tomographyassessment of unprotected left main coronary ar-tery disease-a comparison with intravascular ul-trasound. Catheter Cardiovasc Interv 2013;82:E173–83.

14. Tearney GJ, Regar E, Akasaka T, et al.Consensus standards for acquisition, measure-ment, and reporting of intravascular opticalcoherence tomography studies: a report from theInternational Working Group for IntravascularOptical Coherence Tomography Standardizationand Validation. J Am Coll Cardiol 2012;59:1058–72.

15. D’Ascenzo F, Barbero U, Cerrato E, et al. Ac-curacy of intravascular ultrasound and opticalcoherence tomography in identifying functionallysignificant coronary stenosis according to vesseldiameter: a meta-analysis of 2,581 patients and 2,807 lesions. Am Heart J 2015;169:663–73.

16. Shiono Y, Kitabata H, Kubo T, et al. Opticalcoherence tomography-derived anatomical criteriafor functionally significant coronary stenosisassessed by fractional flow reserve. Circ J 2012;76:2218–25.

17. Gonzalo N, Escaned J, Alfonso F, et al.Morphometric assessment of coronary stenosisrelevance with optical coherence tomography: acomparison with fractional flow reserve andintravascular ultrasound. J Am Coll Cardiol 2012;59:1080–9.

18. Pawlowski T, Prati F, Kulawik T, Ficarra E, Bil J,Gil R. Optical coherence tomography criteria fordefining functional severity of intermediate le-sions: a comparative study with FFR. Int J Car-diovasc Imaging 2013;29:1685–91.

19. Reith S, Battermann S, Jaskolka A, et al.Relationship between optical coherence tomog-raphy derived intraluminal and intramural criteriaand haemodynamic relevance as determined by

fractional flow reserve in intermediate coronarystenoses of patients with type 2 diabetes. Heart2013;99:700–7.

20. Pyxaras SA, Tu S, Barbato E, et al. Quantitativeangiography and optical coherence tomographyfor the functional assessment of nonobstructivecoronary stenoses: comparison with fractionalflow reserve. Am Heart J 2013;166:1010–8.e1.

21. Zafar H, Ullah I, Dinneen K, et al. Evaluation ofhemodynamically severe coronary stenosis asdetermined by fractional flow reserve with fre-quency domain optical coherence tomographymeasured anatomical parameters. J Cardiol 2014;64:19–24.

22. Reith S, Battermann S, Hellmich M, Marx N,Burgmaier M. Correlation between optical coher-ence tomography-derived intraluminal parametersand fractional flow reserve measurements in in-termediate grade coronary lesions: a comparisonbetween diabetic and non-diabetic patients. ClinRes Cardiol 2015;104:59–70.

23. Ha J, Kim JS, Lim J, et al. Assessing compu-tational fractional flow reserve from opticalcoherence tomography in patients with interme-diate coronary stenosis in the left anteriordescending artery. Circ Cardiovasc Interv 2016;9:e003613.

24. Stone GW, Maehara A, Lansky AJ, et al.A prospective natural-history study of coronaryatherosclerosis. N Engl J Med 2011;364:226–35.

25. Calvert PA, Obaid DR, O’Sullivan M, et al. As-sociation between IVUS findings and adverseoutcomes in patients with coronary artery disease:the VIVA (VH-IVUS in Vulnerable Atherosclerosis)study. J Am Coll Cardiol Img 2011;4:894–901.

26. Cheng JM, Garcia-Garcia HM, de Boer SP, et al.In vivo detection of high-risk coronary plaques byradiofrequency intravascular ultrasound and car-diovascular outcome: results of theATHEROREMO-IVUS study. Eur Heart J 2014;35:639–47.

27. Mintz GS. Vulnerable plaque detection: whenOCT is not enough. J Am Coll Cardiol Img 2016;9:173–5.

28. Sinclair H, Bourantas C, Bagnall A, Mintz GS,Kunadian V. OCT for the identification of

J A C C : C A R D I O V A S C U L A R I N T E R V E N T I O N S V O L . 1 0 , N O . 2 4 , 2 0 1 7 Ali et al.D E C E M B E R 2 6 , 2 0 1 7 : 2 4 7 3 – 8 7 State-of-the-Art OCT 2018

2485

vulnerable plaque in acute coronary syndrome.J Am Coll Cardiol Img 2015;8:198–209.

29. Kim SJ, Lee H, Kato K, et al. Reproducibility ofin vivo measurements for fibrous cap thicknessand lipid arc by OCT. J Am Coll Cardiol Img 2012;5:1072–4.

30. Phipps JE, Hoyt T, Vela D, et al. Diagnosis ofthin-capped fibroatheromas in intravascular opti-cal coherence tomography images: effects of lightscattering. Circ Cardiovasc Interv 2016;9:e003163.

31. Bourantas CV, Jaffer FA, Gijsen FJ, et al. Hybridintravascular imaging: recent advances, technicalconsiderations, and current applications in thestudy of plaque pathophysiology. Eur Heart J2017;38:400–12.

32. Kobayashi Y, Okura H, Kume T, et al. Impact oftarget lesion coronary calcification on stentexpansion. Circ J 2014;78:2209–14.

33. Karimi Galougahi K, Shlofmitz RA, Ben-Yehuda O, et al. Guiding light: insights into athe-rectomy by optical coherence tomography. J AmColl Cardiol Intv 2016;9:2362–3.

34. Maejima N, Hibi K, Saka K, et al. Relationshipbetween thickness of calcium on optical coherencetomography and crack formation after balloondilatation in calcified plaque requiring rotationalatherectomy. Circ J 2016;25:1413–9.

35. Tanaka A, Imanishi T, Kitabata H, et al. Lipid-rich plaque and myocardial perfusion after suc-cessful stenting in patients with non-ST-segmentelevation acute coronary syndrome: an opticalcoherence tomography study. Eur Heart J 2009;30:1348–55.

36. Yonetsu T, Kakuta T, Lee T, et al. Impact ofplaque morphology on creatine kinase-MB eleva-tion in patients with elective stent implantation.Int J Cardiol 2011;146:80–5.

37. Lee T, Yonetsu T, Koura K, et al. Impact ofcoronary plaque morphology assessed by opticalcoherence tomography on cardiac troponinelevation in patients with elective stent implan-tation. Circ Cardiovasc Interv 2011;4:378–86.

38. Porto I, Di Vito L, Burzotta F, et al. Predictorsof periprocedural (type IVa) myocardial infarction,as assessed by frequency-domain optical coher-ence tomography. Circ Cardiovasc Interv 2012;5:89–96.

39. Imola F, Occhipinti M, Biondi-Zoccai G, et al.Association between proximal stent edge posi-tioning on atherosclerotic plaques containing lipidpools and postprocedural myocardial infarction(from the CLI-POOL Study). Am J Cardiol 2013;111:526–31.

40. Ikenaga H, Ishihara M, Inoue I, et al. Longi-tudinal extent of lipid pool assessed by opticalcoherence tomography predicts microvascular no-reflow after primary percutaneous coronaryintervention for ST-segment elevation myocardialinfarction. J Cardiol 2013;62:71–6.

41. Kini AS, Motoyama S, Vengrenyuk Y, et al.Multimodality Intravascular Imaging to PredictPeriprocedural Myocardial Infarction DuringPercutaneous Coronary Intervention. J Am CollCardiol Intv 2015;8:937–45.

42. Wijns W, Shite J, Jones MR, et al. Opticalcoherence tomography imaging during percuta-neous coronary intervention impacts physiciandecision-making: ILUMIEN I study. Eur Heart J2015;36:3346–55.

43. Gerbaud E, Weisz G, Tanaka A, et al. Multi-laboratory inter-institute reproducibility study ofIVOCT and IVUS assessments using publishedconsensus document definitions. Eur Heart J Car-diovasc Imaging 2015;17:756–64.

44. Kim IC, Nam CW, Cho YK, et al. Discrepancybetween frequency domain optical coherence to-mography and intravascular ultrasound in humancoronary arteries and in a phantom in vitro coro-nary model. Int J Cardiol 2016;221:860–6.

45. Maehara A, Ben-Yehuda O, Ali Z, et al. Com-parison of stent expansion guided by opticalcoherence tomography versus intravascular ultra-sound: the ILUMIEN II study (Observational Studyof Optical Coherence Tomography [OCT] in Pa-tients Undergoing Fractional Flow Reserve [FFR]and Percutaneous Coronary Intervention). J AmColl Cardiol Intv 2015;8:1704–14.

46. Kubo T, Shinke T, Okamura T, et al. Opticalfrequency domain imaging vs. intravascular ultra-sound in percutaneous coronary intervention(OPINION trial): one-year angiographic and clinicalresults. Eur Heart J 2017;38:3139–47.

47. Otake H, Kubo T, Takahashi H, et al. OpticalFrequency Domain Imaging Versus IntravascularUltrasound in Percutaneous Coronary Intervention(OPINION Trial): Results From the OPINIONImaging Study. J Am Coll Cardiol Img 2017 Sep 9[E-pub ahead of print].

48. Ali ZA, Maehara A, Genereux P, et al. Opticalcoherence tomography compared with intravas-cular ultrasound and with angiography to guidecoronary stent implantation (ILUMIEN III: OPTI-MIZE PCI): a randomised controlled trial. Lancet2016;388:2618–28.

49. Koyama K. A prospective, single-center, ran-domized study to assess whether co-registrationof OCT and angiography can reduce geographicmiss. Available at: https://www.tctmd.com/slide/prospective-single-center-randomized-study-assess-whether-co-registration-oct-and-angiography.Accessed November 17, 2017.

50. Nijjer SS, Sen S, Petraco R, Mayet J,Francis DP, Davies JE. The instantaneous wave-free ratio (iFR) pullback: a novel innovation usingbaseline physiology to optimise coronary angio-plasty in tandem lesions. Cardiovasc Revasc Med2015;16:167–71.

51. Romagnoli E, Sangiorgi GM, Cosgrave J,Guillet E, Colombo A. Drug-eluting stenting: thecase for post-dilation. J Am Coll Cardiol Intv2008;1:22–31.

52. Karimi Galougahi K, Zalewski A, Leon MB,Karmpaliotis D, Ali ZA. Optical coherencetomography-guided percutaneous coronary inter-vention in pre-terminal chronic kidney diseasewith no radio-contrast administration. Eur Heart J2015;37:1059.

53. Kume T, Okura H, Miyamoto Y, et al. Naturalhistory of stent edge dissection, tissue protrusionand incomplete stent apposition detectable onlyon optical coherence tomography after stent

implantation—preliminary observation. Circ J2012;76:698–703.

54. Chamie D, Bezerra HG, Attizzani GF, et al.Incidence, predictors, morphological characteris-tics, and clinical outcomes of stent edge dissec-tions detected by optical coherence tomography.J Am Coll Cardiol Intv 2013;6:800–13.

55. Kawamori H, Shite J, Shinke T, et al. Naturalconsequence of post-intervention stent malap-position, thrombus, tissue prolapse, and dissectionassessed by optical coherence tomography at mid-term follow-up. Eur Heart J Cardiovasc Imaging2013;14:865–75.

56. Mintz GS. Why are we so concerned with acuteincomplete stent apposition? Eur Heart J Car-diovasc Imaging 2015;16:110–1.

57. Kobayashi N, Mintz GS, Witzenbichler B, et al.Prevalence, features, and prognostic importanceof edge dissection after drug-eluting stent im-plantation: an ADAPT-DES intravascular ultra-sound substudy. Circ Cardiovasc Interv 2016;9:e003553.

58. Soeda T, Uemura S, Park SJ, et al. Incidenceand clinical significance of poststent opticalcoherence tomography findings: one-year follow-up study from a multicenter registry. Circulation2015;132:1020–9.

59. Kerensky RA, Wade M, Deedwania P,Boden WE, Pepine CJ, for the Veterans AffairsNon-Q-Wave Infarction Strategies in-Hospital(VANQWISH) Trial Investigators. Revisiting theculprit lesion in non-Q-wave myocardial infarction.Results from the VANQWISH trial angiographiccore laboratory. J Am Coll Cardiol 2002;39:1456–63.

60. Nishiguchi T, Tanaka A, Ozaki Y, et al. Preva-lence of spontaneous coronary artery dissection inpatients with acute coronary syndrome. Eur HeartJ Acute Cardiovasc Care 2016;5:263–70.

61. Jia H, Abtahian F, Aguirre AD, et al. In vivodiagnosis of plaque erosion and calcified nodule inpatients with acute coronary syndrome by intra-vascular optical coherence tomography. J Am CollCardiol 2013;62:1748–58.

62. Guagliumi G, Capodanno D, Saia F, et al.Mechanisms of atherothrombosis and vascularresponse to primary percutaneous coronary inter-vention in women versus men with acutemyocardial infarction: results of the OCTAVIAstudy. J Am Coll Cardiol Intv 2014;7:958–68.

63. Wang L, Parodi G, Maehara A, et al. Variableunderlying morphology of culprit plaques associ-ated with ST-elevation myocardial infarction: anoptical coherence tomography analysis from theSMART trial. Eur Heart J Cardiovasc Imaging 2015;16:1381–9.

64. Higuma T, Soeda T, Abe N, et al. A combinedoptical coherence tomography and intravascularultrasound study on plaque rupture, plaqueerosion, and calcified nodule in patients with ST-segment elevation myocardial infarction: inci-dence, morphologic characteristics, and outcomesafter percutaneous coronary intervention. J AmColl Cardiol Intv 2015;8:1166–76.

65. Kajander OA, Pinilla-Echeverri N, Jolly SS,et al. Culprit plaque morphology in STEMI—anoptical coherence tomography study: insights

Ali et al. J A C C : C A R D I O V A S C U L A R I N T E R V E N T I O N S V O L . 1 0 , N O . 2 4 , 2 0 1 7

State-of-the-Art OCT 2018 D E C E M B E R 2 6 , 2 0 1 7 : 2 4 7 3 – 8 7

2486

from the TOTAL-OCT substudy. EuroIntervention2016;12:716–23.

66. Kanwar SS, Stone GW, Singh M, et al. Acutecoronary syndromes without coronary plaquerupture. Nat Rev Cardiol 2016;13:257–65.

67. Niccoli G, Montone RA, Di Vito L, et al. Plaquerupture and intact fibrous cap assessed by opticalcoherence tomography portend different out-comes in patients with acute coronary syndrome.Eur Heart J 2015;36:1377–84.

68. Jia H, Dai J, Hou J, et al. Effective anti-thrombotic therapy without stenting: intravas-cular optical coherence tomography-basedmanagement in plaque erosion (the EROSIONstudy). Eur Heart J 2017;38:792–800.

69. Hong YJ, Jeong MH, Choi YH, et al. Plaquecomponents at coronary sites with focal spasm inpatients with variant angina: virtual histology-intravascular ultrasound analysis. Int J Cardiol2010;144:367–72.

70. Park HC, Shin JH, Jeong WK, Choi SI, Kim SG.Comparison of morphologic findings obtained byoptical coherence tomography in acute coronarysyndrome caused by vasospasm and chronic stablevariant angina. Int J Cardiovasc Imaging 2015;31:229–37.

71. Shibata T, Kawakami S, Noguchi T, et al.Prevalence, clinical features, and prognosis ofacute myocardial infarction attributable to coro-nary artery embolism. Circulation 2015;132:241–50.

72. Soverow J, Hastings R, Ali Z. OCT-guidedmanagement of a pregnant woman with ST-elevation myocardial infarction. Int J Cardiol2016;215:135–7.

73. Sheth TN, Kajander OA, Lavi S, et al. Opticalcoherence tomography-guided percutaneous cor-onary intervention in ST-segment-elevationmyocardial infarction: a prospective propensity-matched cohort of the Thrombectomy VersusPercutaneous Coronary Intervention Alone trial.Circ Cardiovasc Interv 2016;9:e003414.

74. Meneveau N, Souteyrand G, Motreff P, et al.Optical coherence tomography to optimize resultsof percutaneous coronary intervention in patientswith non-ST-elevation acute coronary syndrome:results of the multicenter, randomized DOCTORSstudy (Does Optical Coherence TomographyOptimize Results of Stenting). Circulation 2016;134:906–17.

75. Sabate M, Windecker S, Iniguez A, et al.Everolimus-eluting bioresorbable stent vs. durablepolymer everolimus-eluting metallic stent in pa-tients with ST-segment elevation myocardialinfarction: results of the randomized ABSORB ST-segment elevation myocardial infarction—TROFI IItrial. Eur Heart J 2016;37:229–40.

76. Bhindi R, Kajander OA, Jolly SS, et al. Culpritlesion thrombus burden after manual thrombec-tomy or percutaneous coronary intervention-alonein ST-segment elevation myocardial infarction: theoptical coherence tomography sub-study of theTOTAL (Thrombectomy Versus PCI Alone) trial. EurHeart J 2015;36:1892–900.

77. Higuma T, Soeda T, Yamada M, et al. Doesresidual thrombus after aspiration thrombectomyaffect the outcome of primary PCI in patients withST-segment elevation myocardial infarction? Anoptical coherence tomography study. J Am CollCardiol Intv 2016;9:2002–11.

78. Prati F, Romagnoli E, Gatto L, et al. Clinicalimpact of suboptimal stenting and residual intra-stent plaque/thrombus protrusion in patients withacute coronary syndrome: the CLI-OPCI ACSsubstudy (Centro per la Lotta Contro L’Infarto-Optimization of Percutaneous Coronary Interven-tion in Acute Coronary Syndrome). Circ CardiovascInterv 2016;9:e00372.

79. Ali ZA, de Jesus Perez V, Yuan K, et al. Oxido-reductive regulation of vascular remodeling byreceptor tyrosine kinase ROS1. J Clin Invest 2014;124:5159–74.

80. Hara T, Ughi GJ, McCarthy JR, et al. Intra-vascular fibrin molecular imaging improves thedetection of unhealed stents assessed by opticalcoherence tomography in vivo. Eur Heart J 2017;38:447–55.

81. Nakata T, Fujii K, Fukunaga M, et al. Morpho-logical, functional, and biological vascular healingresponse 6 months after drug-eluting stent im-plantation: a randomized comparison of threedrug-eluting stents. Catheter Cardiovasc Interv2015;88:350–7.

82. Templin C, Meyer M, Muller MF, et al. Coro-nary optical frequency domain imaging (OFDI) forin vivo evaluation of stent healing: comparisonwith light and electron microscopy. Eur Heart J2010;31:1792–801.

83. Lutter C, Mori H, Yahagi K, et al. Histopatho-logical differential diagnosis of optical coherencetomographic image interpretation after stenting.J Am Coll Cardiol Intv 2016;9:2511–23.

84. Ali ZA, Roleder T, Narula J, et al. Increasedthin-cap neoatheroma and periproceduralmyocardial infarction in drug-eluting stent reste-nosis: multimodality intravascular imaging ofdrug-eluting and bare-metal stents. Circ Car-diovasc Interv 2013;6:507–17.

85. Otsuka F, Byrne RA, Yahagi K, et al. Neo-atherosclerosis: overview of histopathologic find-ings and implications for intravascular imagingassessment. Eur Heart J 2015;36:2147–59.

86. Lee SY, Hong MK, Shin DH, et al. Opticalcoherence tomography-based predictors for cre-atine kinase-myocardial band elevation afterelective percutaneous coronary intervention forin-stent restenosis. Catheter Cardiovasc Interv2015;85:564–72.

87. Guagliumi G. TRANSFORM-OCT: a prospective,randomized trial using OCT imaging to evaluatestrut coverage at three months andneoatherosclerosis at eighteen months in bio-resorbable polymer-based and durable polymer-based drug-eluting stents. Available at: https://www.tctmd.com/slide/transform-oct-prospective-randomized-trial-using-oct-imaging-evaluate-strut-coverage-three. Accessed November 17, 2017.

88. Souteyrand G, Amabile N, Mangin L, et al.Mechanisms of stent thrombosis analysed by op-tical coherence tomography: insights from thenational PESTO French registry. Eur Heart J 2016;37:1208–16.

89. Prati F, Kodama T, Romagnoli E, et al.Suboptimal stent deployment is associatedwith subacute stent thrombosis: opticalcoherence tomography insights from a multi-center matched study. From the CLI Founda-tion Investigators: the CLI-THRO study. AmHeart J 2015;169:249–56.

90. Jones CR, Khandhar SJ, Ramratnam M, et al.Identification of intrastent pathology associ-ated with late stent thrombosis using opticalcoherence tomography. J Interv Cardiol 2015;28:439–48.

91. Taniwaki M, Radu MD, Zaugg S, et al. Mecha-nisms of very late drug-eluting stent thrombosisassessed by optical coherence tomography. Cir-culation 2016;133:650–60.

92. Im E, Kim BK, Ko YG, et al. Incidences, pre-dictors, and clinical outcomes of acute and latestent malapposition detected by optical coherencetomography after drug-eluting stent implantation.Circ Cardiovasc Interv 2014;7:88–96.

93. Karanasos A, Simsek C, Gnanadesigan M, et al.OCT assessment of the long-term vascular healingresponse 5 years after everolimus-eluting bio-resorbable vascular scaffold. J Am Coll Cardiol2014;64:2343–56.

94. Sotomi Y, Suwannasom P, Serruys PW,Onuma Y. Possible mechanical causes of scaffoldthrombosis: insights from case reports withintracoronary imaging. EuroIntervention 2017;12:1747–56.

95. Raber L, Brugaletta S, Yamaji K, et al. Very latescaffold thrombosis: intracoronary imaging andhistopathological and spectroscopic findings. J AmColl Cardiol 2015;66:1901–14.

96. Patel A, Nazif T, Stone GW, Ali ZA. Intra-luminal bioresorbable vascular scaffold disman-tling with aneurysm formation leading to very latethrombosis. Catheter Cardiovasc Interv 2017;89:876–9.

97. Onuma Y, Serruys PW, Muramatsu T, et al.Incidence and imaging outcomes of acute scaffolddisruption and late structural discontinuity afterimplantation of the absorb Everolimus-Elutingfully bioresorbable vascular scaffold: opticalcoherence tomography assessment in the ABSORBcohort B trial (A Clinical Evaluation of the Bio-absorbable Everolimus Eluting Coronary StentSystem in the Treatment of Patients With De NovoNative Coronary Artery Lesions). J Am Coll CardiolIntv 2014;7:1400–11.

98. Stone GW, Granada JF. Very late thrombosisafter bioresorbable scaffolds: cause for concern?J Am Coll Cardiol 2015;66:1915–7.

99. Okamura T, Onuma Y, Yamada J, et al. 3Doptical coherence tomography: new insights intothe process of optimal rewiring of side branchesduring bifurcational stenting. EuroIntervention2014;10:907–15.

J A C C : C A R D I O V A S C U L A R I N T E R V E N T I O N S V O L . 1 0 , N O . 2 4 , 2 0 1 7 Ali et al.D E C E M B E R 2 6 , 2 0 1 7 : 2 4 7 3 – 8 7 State-of-the-Art OCT 2018

2487

100. Francaviglia B, Capranzano P, Gargiulo G,et al. Usefulness of 3D OCT to diagnose a non-circumferential open-cell stent fracture. J Am CollCardiol Img 2016;9:210–1.

101. Bavishi C, Sardar P, Chatterjee S, et al. Intra-vascular ultrasound-guided vs angiography-guided drug-eluting stent implantation incomplex coronary lesions: meta-analysis ofrandomized trials. Am Heart J 2017;185:26–34.

102. van Soest G, Goderie T, Regar E, et al.Atherosclerotic tissue characterization in vivo byoptical coherence tomography attenuation imag-ing. J Biomed Opt 2010;15:011105.

103. Wang Z, Kyono H, Bezerra HG, et al. Semi-automatic segmentation and quantification ofcalcified plaques in intracoronary optical coher-ence tomography images. J Biomed Opt 2010;15:061711.

104. Ughi GJ, Adriaenssens T, Sinnaeve P,Desmet W, D’Hooge J. Automated tissuecharacterization of in vivo atherosclerotic pla-ques by intravascular optical coherence to-mography images. Biomed Opt Express 2013;4:1014–30.

105. Rico-Jimenez JJ, Campos-Delgado DU,Villiger M, Otsuka K, Bouma BE, Jo JA. Automatic

classification of atherosclerotic plaques imagedwith intravascular OCT. Biomed Opt Express 2016;7:4069–85.

106. Wijns W, Pyxaras SA. Optical coherencetomography guidance for percutaneous inter-vention: the French “doctors” are seeing light atthe end of the tunnel. Circulation 2016;134:918–22.

KEY WORDS angioplasty, drug-elutingstent(s), intravascular imaging, IVUS, OCT,PCI