Circulation: Cardiovascular Interventions

ORIGINAL ARTICLE

Optical Coherence Tomography Versus

Intravascular Ultrasound and Angiography to
Guide Percutaneous Coronary Interventions
The iSIGHT Randomized Trial
Daniel Chamié , MD, PhD; J. Ribamar Costa, Jr, MD, PhD; Lucas P. Damiani , MSc; Dimytri Siqueira, MD, PhD;
Sérgio Braga, MD, PhD; Ricardo Costa, MD, PhD; Henry Seligman , MBBS; Freddy Brito , MD; Guilherme Barreto, MD;
Rodolfo Staico, MD, PhD; Fausto Feres, MD, PhD; Ricardo Petraco, MD, PhD; Alexandre Abizaid, MD, PhD

BACKGROUND: Specific algorithms for use of optical coherence tomography (OCT) to guide percutaneous coronary
intervention (PCI) are scarce. Also, the relative benefits of intravascular imaging guidance have not been tested against an
optimized angiography-guided PCI strategy. In iSIGHT (Optical Coherence Tomography Versus Intravascular Ultrasound and
Angiography to Guide Percutaneous Coronary Interventions), we aimed to investigate whether OCT-guided PCI achieves
noninferior stent expansion compared with intravascular ultrasound (IVUS) guidance and if both imaging modalities lead to
superior stent expansion compared with an optimized angiography-based strategy.

METHODS: Patients ≥18 years old undergoing PCI for ≥1 lesion in native coronaries of 2.25 to 4.00 mm in diameter were
randomized 1:1:1 to OCT-, IVUS-, or angiography-guided PCI. Predetermined guidance protocols were applied in all groups.
An external elastic membrane–based protocol was used for stent sizing by OCT and IVUS. The primary end point was
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noninferiority of stent expansion (minimum stent area ≥90% of the average reference lumen area), measured by post-PCI
OCT, in OCT-guided versus IVUS-guided PCI (noninferiority margin, 6.5%).

RESULTS: One hundred fifty-one patients (156 lesions) were randomly allocated to OCT (51 lesions [32.7%]), IVUS (52
lesions [33.3%]), or angiography (53 lesions [34.0%]). Stent expansion with OCT guidance (98.01±16.14%) was noninferior
to IVUS (91.69±15.75%; 1-sided lower 95% CI, 0.55 mm2; Pnon-inferiority<0.001) and superior to angiography (90.53±14.84%,
P=0.041). IVUS and angiography obtained similar stent expansions (P=0.921). Stent edge dissection and periprocedural
complication rates were not significantly different among the groups.

CONCLUSIONS: Stent expansion with OCT guidance using a dedicated external elastic membrane–based sizing strategy was
noninferior to that achieved with IVUS and superior to an optimized angiographic strategy.

REGISTRATION: URL: plataformabrasil.saude.gov.br; Unique identifier: 69968417.8.0000.5462.

GRAPHIC ABSTRACT: A graphic abstract is available for this article.

Key Words: angiography ◼ coronary artery disease ◼ myocardial infarction ◼ percutaneous coronary intervention ◼ optical coherence tomography

See Editorial by Maehara

 
Correspondence to: Daniel Chamié, MD, PhD, Interventional Cardiology Department, Dante Pazzanese Institute of Cardiology, 500 Dr Dante Pazzanese Ave, Ibirapuera,
Sao Paulo, SP, Brazil 04012-180. Email daniel.chamie@gmail.com
The Data Supplement is available at https://www.ahajournals.org/doi/suppl/10.1161/CIRCINTERVENTIONS.120.009452.
For Sources of Funding and Disclosures, see page 335.
© 2021 American Heart Association, Inc.
Circulation: Cardiovascular Interventions is available at www.ahajournals.org/journal/circinterventions

Circ Cardiovasc Interv. 2021;14:e009452. DOI: 10.1161/CIRCINTERVENTIONS.120.009452 March 2021 326

 Chamié et al
WHAT IS KNOWN
• By leading to larger minimal stent area and lower
rates of geographic miss, intravascular ultrasound-
guided percutaneous coronary intervention pro-
vides better short-term procedural and long-term
clinical outcomes when compared with percutane-
ous coronary intervention guided by angiography
alone.
• Intravascular optical coherence tomography is an
established high-resolution imaging modality. How-
ever, dedicated algorithms for optimized percuta-
neous coronary intervention guidance with optical
coherence tomography are largely underreported.
• The relative merits of intravascular imaging com-
pared with an optimized angiographic guidance
strategy that applies concepts learned from intra-
vascular imaging have not been tested.
WHAT THE STUDY ADDS
• The iSIGHT study (Optical Coherence Tomography
Versus Intravascular Ultrasound and Angiography
to Guide Percutaneous Coronary Interventions)
introduced a step-by-step approach for optimized
percutaneous coronary intervention with optical
coherence tomography guidance that provided
stent expansions noninferior to those achieved with
a classical intravascular ultrasound guidance pro-
tocol, and superior to an optimized angiography-
based approach, without increasing periprocedural
risks and adding a nonsignificant amount of con-
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trast to the procedures.
• An optimized angiography-guided approach with
systematic stent oversizing and high-pressure post
dilatation provided excellent stent expansions, simi-
lar to those achieved with intravascular ultrasound.
This practice may be applied in cases where intra-
vascular imaging is not available.
Nonstandard Abbreviations and Acronyms
EEM external elastic membrane
iSIGHT Optical Coherence Tomography Versus
Intravascular Ultrasound and Angiogra-
phy to Guide Percutaneous Coronary
Interventions
IVUS intravascular ultrasound
MI myocardial infarction
MSA minimum stent area
OCT optical coherence tomography
PCI percutaneous coronary intervention
E
vidence from observational studies, randomized trials,
and meta-analyses suggests that intravascular ultra-
sound (IVUS) guidance of percutaneous coronary
intervention (PCI) leads to better procedural results and
Circ Cardiovasc Interv. 2021;14:e009452. DOI: 10.1161/CIRCINTERVENTIONS.120.009452
iSIGHT: PCI Guided by OCT, IVUS, and Angiography
superior long-term clinical outcomes when compared
with PCI guided by angiography alone.1,2
The mechanism via which IVUS leads to superior out-
comes is believed to be centered around accurate ves-
sel sizing with a higher frequency of stent postdilatation,
leading to larger minimal stent area (MSA) and lower
rates of geographic miss.1,2 Nonetheless, IVUS adoption
in clinical practice remains limited.3
Optical coherence tomography (OCT) produces high-
resolution images of coronary arteries with accurate
automated quantification of vessel lumen dimensions
and higher sensitivity in identifying plaque characteristics
and morphology, and post-PCI findings.4,5
Early OCT experience used reference lumen dimen-
sions to size stent diameters. This led operators choose
smaller devices and obtain smaller post-PCI MSA as com-
pared to stents sized by the external elastic membrane
(EEM) with IVUS.6,7 Limited OCT penetration at the lesion
site was credited as the impossibility to size stents to the
EEM by OCT. To this date, ILUMIEN III (OPTIMIZE PCI
Optical Coherence Tomography Compared to Intravascu-
lar Ultrasound and Angiography to Guide Coronary Stent
Implantation: A Multicenter Randomized Trial in Percutane-
ous Coronary Intervention)8 is the only study to offer a ded-
icated algorithm for the use of OCT to guide PCI according
to The EEM. In the present study, we present a stepwise
OCT guidance algorithm based on the EEM diameter at
the reference segments that consider vessel tapering. We
test the noninferiority of this approach against a predefined
IVUS-guided strategy of stent expansion. Additionally, we
evaluate the superiority of both imaging modalities against
an optimized strategy based on angiography that applies
concepts learned from intravascular imaging.
METHODS
Study Design and Patient Population
iSIGHT (Optical Coherence Tomography Versus Intravascular
Ultrasound and Angiography to Guide Percutaneous Coronary
Interventions) is a prospective, randomized, active-controlled,
noninferiority trial performed in a single-center, compar-
ing PCI results after guidance by OCT, IVUS, and angiogra-
phy. iSIGHT is a physician’s initiative study with no external
sources of funding or any involvement from industry. An
independent contract research organization (Cardiovascular
Research Center, Sao Paulo, Brazil) performed core labora-
tory analyzes of all angiograms, IVUS, and OCT images, data
management, clinical events adjudication, and statistics. The
Institution’s ethics committee approved the study protocol,
and all subjects gave informed consent. The data that support
the findings of this study are available from the corresponding
author upon reasonable request.
Patients ≥18 years old scheduled for PCI of native coro-
nary arteries were eligible for inclusion. We enrolled patients
with stable angina, non–ST-segment–elevation acute coro-
nary syndromes, or ST-segment–elevation myocardial infarc-
tion (MI) with ≥48 hours from the initial presentation. Eligible
March 2021 327
 Chamié et al
patients could have ≥1 target lesion in ≥1 native coronary
with a reference diameter ranging from 2.25 to 4.0 mm by
visual estimation. The use of ≥1 stent was allowed for com-
plete lesion coverage. We excluded patients in cardiogenic
shock or with signs of congestive heart failure, chronic kid-
ney disease with an estimated glomerular filtration rate ≤45
mL/(min·1.73 m2), significant (≥50%) stenosis in the left main
stem, aorto-ostial lesions, chronic total occlusions, bifurcation
lesions in which 2-stent strategy was anticipated, and lesions
in arterial or venous grafts.
Bias Proof Strategies
Enrolled patients were randomly allocated, in a 1:1:1 ratio, to
OCT-, IVUS-, or angiography-guided PCI. For patients allocated
in the angiography arm, blinded IVUS and OCT images were
acquired at the end of the procedure. For patients allocated to
the IVUS and OCT arms, the opposite imaging modality was
blindly acquired at the end of each procedure (Figure I in the
Data Supplement).
The randomization sequence was electronically gener-
ated in block sizes of 9 and secured in opaque sealed enve-
lopes. Envelopes were opened when the 0.014” angioplasty
wire had been successfully positioned in the distal bed of
the target vessel.
To minimize bias in favor of a particular imaging method,
cases were operated by all catheterization laboratory physi-
cians regardless of their personal preference for stent guid-
ance modality. To maintain unbiased decisions and adherence
to the protocol, all procedural strategies were decided collec-
tively by the first operator and an imaging expert.
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Figure 1. Imaging guidance protocols.
EEM indicates external elastic membrane; IVUS, intravascular ultrasound; NC, non-compliant; OCT, optical coherence tomography; and PCI,
percutaneous coronary intervention.
Circ Cardiovasc Interv. 2021;14:e009452. DOI: 10.1161/CIRCINTERVENTIONS.120.009452
iSIGHT: PCI Guided by OCT, IVUS, and Angiography
At the end of each procedure, all images were deidenti-
fied and transferred to the core laboratories, where all analysts
were blinded to the randomization groups.
Procedures
A stepwise protocol for PCI guidance was created for all imag-
ing modalities (Figure 1).
In the angiography group, operators should cover the entire
stenosis targeting the most normal-looking segments proximal
and distal to the stenosis. The maximum reference diameters
were visually determined.
In the IVUS group, the distal and proximal landing zones
were the regions with the largest lumen areas with <50%
plaque burden (wherever possible). In each reference, diam-
eters were determined to the mean EEM diameter if the EEM
was visible in ≥180° of the vessel circumference. Otherwise,
the largest lumen diameter was measured.
In the OCT group, use of the proprietary lumen profile was
recommended for selection of the distal and proximal landing
zones. These were the regions with the largest lumen areas at
the most normal-looking sites, irrespective of the plaque bur-
den. Lipid-rich plaques should be avoided in the landing zones
to minimize the risks of edge dissection9 or periprocedural MI.10
When the EEM was visible in ≥180° of the vessel circumfer-
ence, the reference was sized to the mean EEM diameter.
Otherwise, the largest lumen diameter was used.
In all groups, operators sought for discrepancies between
both references to adjust for vessel tapering. If the proximal
and distal references differed ≥0.5 mm in diameter, the stent
was sized to the smaller reference; postdilatation balloons
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 Chamié et al
sized to each reference were used. Otherwise, the stent and
postdilatation balloon were sized to the largest reference. The
distance between the distal and proximal references deter-
mined the stent length.
High-pressure (>18 atm) postdilatation with noncompliant
balloons was strongly recommended in all groups. The use
of angiographic enhancement tools for assessment of stent
expansion was recommended in the angiography arm. Residual
in-stent diameter stenosis <10% in the angiography group and
an MSA ≥90% of the average reference lumen areas in the
IVUS and OCT groups were the stent expansion criteria.
Examples of PCI guidance in all groups are presented in the
Figures II through VI in the Data Supplement.
End Points and Definitions
The primary end point was the noninferiority of postprocedure
stent expansion (defined as MSA divided by the average lumen
area of the distal and proximal references) in the OCT versus
IVUS groups. As an exploratory analysis, prespecified second-
ary end points comprised superiority testing of stent expansion
among the groups and comparison of mean and minimum stent
areas, mean and minimum in-stent lumen areas, stent eccen-
tricity, mean and minimum stent diameters, plaque prolapse
area, incomplete stent apposition, stent edge dissections, and
the circumferential arc of visible EEM at the vessel references.
Stent edge dissections were defined and quantified, as pre-
viously described.9
Major adverse cardiac events were the composite of car-
diac death, nonfatal MI, and target lesion revascularization. MI
and stent thrombosis were defined according to the Society for
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Cardiovascular Angiography and Interventions11 and Academic
Research Consortium12 definitions, respectively.
Statistical Analysis
The noninferiority margin for stent expansion of OCT- versus
IVUS-guided PCI was set at 6.85%. This represents 50% of
the average standard deviations (13.7%) of stent expansions
described in the only randomized study comparing OCT- and
IVUS-guided PCI available when iSIGHT was designed.6
Assuming equal means for stent expansion, with a 1-sided
significance level of 0.05, a total of 150 patients (50 in each
group) provided 80% power to detect the noninferiority of
OCT- to IVUS-guided PCI. If OCT was noninferior to IVUS,
superiority testing for stent expansion was performed as fol-
lows: (1) OCT-guided versus IVUS-guided PCI; (2) OCT-guided
versus angiography-guided PCI, and (3) IVUS-guided versus
angiography-guided PCI.
All patients received the imaging modality assigned by ran-
dom allocation. Thus, the primary analysis was performed in
the per-protocol population considering 2 by 2 comparisons
according to the hierarchical procedure described in the 1-way
ANOVA model. Categorical data are presented as numbers
and percentages and were compared with Fisher exact test
or χ2 test. Continuous data are presented as mean (±SD) and
were compared with the ANOVA model or Kruskal-Wallis test
when measures were at the lesion level. To adjust for clus-
ter effects of OCT data when comparing variables in frame
and strut levels, we used generalized linear mixed models with
random intercept by lesion assuming the distribution that bet-
ter fit the data. All 2 by 2 comparisons were carried out with
Circ Cardiovasc Interv. 2021;14:e009452. DOI: 10.1161/CIRCINTERVENTIONS.120.009452
iSIGHT: PCI Guided by OCT, IVUS, and Angiography
2-sided tests, a 5% significance level, and Holm-Bonferroni
adjustments. The occurrence of clinical outcomes was tested
with Cox proportional hazard models. All analyses were per-
formed with the R software, version 3.5.2 (R Core Team, 2019,
Vienna, Austria).
RESULTS
Between January 2015 and December 2016, a total of
151 patients (156 lesions) were randomly allocated to
OCT-guided (51 patients [33.8%]; 51 lesions [32.7%]),
IVUS-guided (51 patients [33.8%]; 52 lesions [33.3%]),
or angiography-guided PCI (49 patients [32.4%]; 53
lesions [34.0%]; Figure 2).
Baseline Clinical, Angiographic, and Procedural
Characteristics
Baseline clinical, angiographic and procedural character-
istics are presented in Table 1 and Table I in the Data
Supplement. The majority (70.6%) of patients were male,
and the mean age was 59.2 years. Acute coronary syn-
drome was the most common indication for PCI (59.3%).
Lesion predilatation was more often performed in pro-
cedures guided by intravascular imaging than by angiog-
raphy (70.6% versus 39.6%, P=0.002). Lesions guided
by IVUS received significantly longer stents (32.5±14.0
mm) than those guided by angiography (25.8±10.4 mm,
P=0.016) but not to lesions guided by OCT (28.6±11.9
mm, P=0.235). Stent postdilatation was performed in
all cases in the IVUS and OCT groups and in 96.2%
of the angiography group. Maximum postdilatation bal-
loon diameter was comparable across the groups, but
higher pressures were applied in the angiography group
(P=0.035).
The total contrast volume used in the OCT group
(94.10±40.54 mL [27.63±7.39 mL due to OCT]) was
significantly higher than the volumes used in the angiog-
raphy (72.3±35.8 mL, P=0.018) but not significantly dif-
ferent than in the IVUS group (82.1±41.3 mL, P=0.277).
A mean of 12.85±3.05 mL of contrast was used
per OCT run in all 227 OCT acquisitions in all groups;
no significant differences were seen between pre-
stent (12.44±2.81 mL) and poststent (13.0±3.11 mL,
P=0.218) acquisitions. OCT runs in right coronaries
required less contrast than in left coronaries (10.62±2.21
versus 14.45±2.52, P<0.001).
Imaging Outcomes
Results of the postprocedure OCT analyses are pre-
sented in Table 2. The final MSA was not significantly
different among the groups (OCT, 7.18±2.66 mm2; IVUS,
6.97±2.09 mm2; angiography, 7.26±2.48 mm2, P=0.820).
Adjusting the MSA to the mean reference lumen
areas, stent expansion (primary end point) with OCT
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 Chamié et al
Figure 2. Study flowchart.
IVUS indicates intravascular ultrasound; NURD, nonuniform rotational distortions; OCT, optical coherence tomography; and PCI, percutaneous
coronary intervention.
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guidance (98.01±16.14%) was noninferior to that
obtained with IVUS (91.69±15.75%; 1-sided lower
95% CI, 0.55 mm2; Pnon-inferiority<0.001; Figure 3). In the
subsequent superiority analysis, OCT guidance resulted
in significantly greater expansions than angiography
(90.53±14.84%, P=0.041) but not significantly different
than IVUS (P=0.067). Stent expansion were similar with
IVUS and angiography (P=0.921; Figure 3). Noteworthy,
stent expansion ≥90% was achieved in a significantly
higher proportion of lesions guided by OCT (74.5%) than
by angiography (50.9%, P=0.015) and IVUS (49.0%,
P=0.014; Figure 4).
Any degree of incomplete stent apposition was
more prevalent after procedures guided by angi-
ography (81.1%) and IVUS (92.2%) than by OCT
(70.6%, P=0.016). When present, incomplete stent
apposition segments were shorter (OCT, 1.38±1.68
mm versus IVUS, 1.63±2.11 mm versus angiogra-
phy, 2.74±4.21 mm, P=0.032), and the proportion
of malapposed struts was lower after OCT guidance
(OCT, 1.59±2.14% versus IVUS, 3.07±3.92% versus
angiography, 4.14±6.92%, P=0.045; Table II in the
Data Supplement).
The frequency of stent edge dissection (OCT, 15.7%
versus IVUS, 11.7% versus angiography, 18.9%;
P=0.623) and the magnitude and depth of injury at stent
edges were comparable among the groups (Table II in
the Data Supplement).
Circ Cardiovasc Interv. 2021;14:e009452. DOI: 10.1161/CIRCINTERVENTIONS.120.009452
iSIGHT: PCI Guided by OCT, IVUS, and Angiography
Visibility of ≥180° of the EEM was similar between
OCT and IVUS (92.2% versus 100%, P=0.117) in the
distal but not in the proximal reference (80.4% versus
100%, P=0.001). Nonetheless, the mean EEM diameter
was more frequently used for distal reference sizing in
the OCT group (92.2% versus 64.7%, P=0.001) and
similarly used for the proximal reference sizing (80.4%
versus 70.6%, P=0.357) when compared with IVUS
(Table III in the Data Supplement).
The amount of untreated plaque burden on the final
IVUS images was similar across all groups in the dis-
tal (42.0±11% [OCT] versus 42.0±14% [IVUS] versus
44.0±12% [angiography], P=0.726) and proximal refer-
ences (48.0±11% [OCT] versus 45.0±11% [IVUS] ver-
sus 45.0±11% [angiography], P=0.224).
In-Hospital and Late Clinical Outcomes
Rates of periprocedural complications (Table IV in the
Data Supplement) and long-term major adverse cardiac
events (median of 2.5 years; Table V in the Data Sup-
plement) were low and not significantly different among
the groups.
DISCUSSION
In the iSIGHT trial, stent expansions with OCT guidance
were noninferior to IVUS and superior to angiography
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 Chamié et al iSIGHT: PCI Guided by OCT, IVUS, and Angiography

Table 1.  Baseline Clinical, Angiographic, and Procedural Characteristics

OCT (n=51 patients|51 IVUS (n=50 patients|51 Angiography (n=49

lesions) lesions) patients|53 lesions) P value
Baseline clinical characteristics
  Age, y 59.92±8.92 59.32±10.37 58.59±10.20 0.795
  Male sex 31 (60.8%) 36 (72.0%) 38 (77.5%) 0.177
 Hypertension 46 (90.2%) 42 (84.0%) 39 (79.6%) 0.334
 Diabetes 17 (33.3%) 20 (40.0%) 22 (44.9%) 0.675
 Dyslipidemia 36 (70.6%) 30 (60.0%) 28 (57.2%) 0.340
  Current smoker 17 (33.3%) 14 (28.0%) 14 (28.6%) 0.814
  Serum creatinine, mg/dL 0.98±0.28 0.94±0.18 0.95±0.22 0.219
Clinical presentation 0.446
  Silent ischemia/stable angina 22 (43.1%) 18 (36.0%) 21 (42.9%)
  Unstable Angina/NSTEMI 20 (39.2%) 22 (44.0%) 16 (32.6%)
  Recent MI 9 (17.7%) 10 (20.0%) 12 (24.5%)
Baseline angiographic characteristics
  Target vessel 0.602
   Left anterior descending 19 (37.3%) 22 (43.1%) 20 (37.7%)
  Left circumflex 12 (23.5%) 10 (19.6%) 7 (13.2%)
   Right coronary artery 20 (39.2%) 19 (37.3%) 26 (49.1%)
   Reference vessel diameter, mm 2.82±0.69 2.85±0.61 2.85±0.59 0.948
  Minimum lumen diameter, mm 0.76±0.35 0.80±0.39 0.83±0.39 0.573
  Diameter stenosis, % 73.00±10.99 71.49±12.91 71.32±10.61 0.948
  Lesion length, mm 21.61±10.28 23.10±9.40 20.20±8.54 0.720
Procedure characteristics
  Lesion predilatation 38 (75.4%) 34 (66.6%) 21 (39.6%) 0.002*†
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   Maximum balloon diameter, mm 2.43±0.35 2.45±0.38 2.52±0.37 0.753

  Stents per lesion 1.12±0.33 1.22±0.46 1.06±0.23 0.091
  Stent diameter, mm 3.26±0.49 3.31±0.48 3.24±0.45 0.820
  Stent length, mm 28.57±11.95 32.51±14.00 25.81±10.41 0.022†
  Postdilatation 51 (100%) 51 (100%) 51 (96.2%) 0.329
   Balloons used per lesion 1.29±0.46 1.24±0.43 1.13±0.52 0.089
   Maximum balloon diameter, mm 3.5 [3.1–4.0] 3.5 [3.1–4.0] 3.5 [3.0–4.0] 0.678
   Maximum inflation pressure, atm 20 [20–24] 20 [18.0–25.5] 24 [20–27] 0.035†
  Fluoroscopy time, min 13.23±3.90 12.87±3.35 11.47±4.78 0.026*
  Procedure time, min 58.59±17.27 57.65±15.03 50.69±21.12 0.014*†
  Total contrast volume, mL 94.10±40.54 82.08±41.32 72.33±35.76 0.001*

Data are presented as n (%), mean±SD, or median [IQR] as appropriate. IQR indicates interquartile range; IVUS, intravascular ultrasound; MI,
myocardial infarction; NSTEMI, non–ST-segment–elevation myocardial infarction; and OCT, optical coherence tomography.
*P<0.05 for the comparison of OCT vs angiography.
†P<0.05 for the comparison of IVUS vs angiography.

guidance. No significant differences were found in stent
expansion achieved with IVUS and angiography guidance.
Similar mean and minimum stent areas were achieved
with all imaging modalities. Intraprocedural complications
were low and not significantly different among the groups.
OCT Protocols for PCI Guidance
The ILUMIEN III trial8 was the first to report a stent
sizing approach based on the EEM measurement
at the reference segments to achieve larger stent
dimensions by OCT than would occur with sizing to
the reference luminal dimensions.6,7 In iSIGHT, we
validated the efficacy and safety of this approach,
although using a slightly different and more aggres-
sive PCI planning algorithm. Put in perspective against
the results of ILUMIEN III, our more aggressive OCT
protocol resulted in larger MSA (median [interquartile
range], 6.62 [5.19–9.02] mm2 versus 5.79 [4.54–7.34]
mm2) than those reported in the OCT arm of ILUM-
IEN III,8 despite similar vessel diameters in both stud-
ies (median reference vessel diameter of 2.78 mm in

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 Chamié et al iSIGHT: PCI Guided by OCT, IVUS, and Angiography

Table 2.  Postprocedure OCT Results

OCT (n=51 IVUS (n=51 Angiography

lesions) lesions) (n=53 lesions) P value
Average reference
  Mean lumen area, mm2 7.35±2.73 7.68±2.29 8.14±2.87 0.337
  Mean lumen diameter, mm 3.00±0.55 3.07±0.45 3.15±0.55 0.303
In-stent analysis
  Analyzed stent length, mm 28.31±11.29 32.18±12.66 26.10±9.93 0.024*
  No. of analyzed cross-sections 29.02±11.16 33.45±13.09 26.74±9.64 0.011*
  No. of analyzed struts per lesion 16 992 20 026 15 937
  No. of analyzed struts per cross-section 11.48±3.81 11.74±3.85 11.23±3.71 0.722
  Mean stent area, mm2 9.03±3.07 8.92±2.59 8.79±2.87 0.906
  Minimum stent area, mm2 7.18±2.66 6.97±2.09 7.26±2.48 0.820
  Mean stent diameter, mm 3.34±0.56 3.33±0.48 3.30±0.52 0.922
  Stent eccentricity index† 0.11±0.03 0.10±0.03 0.10±0.04 0.208
  Stent expansion, % 98.01±16.14 91.69±15.75 90.53±14.84 0.035‡
  Mean lumen area, mm 2
8.86±2.91 8.91±2.49 8.82±2.83 0.987
  Minimum lumen area, mm2 6.93±2.52 6.89±2.01 7.24±2.44 0.703
  Mean lumen diameter, mm 3.31±0.54 3.33±0.46 3.31±0.52 0.967
  Lumen eccentricity index§ 0.15±0.03 0.14±0.03 0.14±0.04 0.367
  Mean plaque prolapse area, mm2 0.38±0.28 0.29±0.16 0.29±0.20 0.041∥‡

Data are presented as mean±SD or n (%) as appropriate. IVUS indicates intravascular ultrasound; and OCT, optical coherence
tomography.
*P<0.05 for the comparison of IVUS vs angiography.
†Stent eccentricity index was calculated in each cross-section as (maximum stent diameter–minimum stent diameter)/maximum
stent diameter.
‡P<0.05 for the comparison of OCT vs angiography.
§Lumen eccentricity index was calculated in each cross-section as (maximum lumen diameter–minimum lumen diameter)/maxi-
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mum lumen diameter.

‖P<0.05 for the comparison of OCT vs IVUS.

OCT-Guided Versus IVUS-Guided PCI

ILUMIEN III and 2.74 mm in iSIGHT). Furthermore,
specific predetermined guidelines were applied for PCI
guidance in all groups in iSIGHT and not only in the
OCT-guided group. Summary of PCI guidance proto-
cols used in OCT versus IVUS or angiography studies
are presented in the Table VI in the Data Supplement.
Contrary to previous studies, stent expansion achieved with
OCT in our study was numerically higher than that achieved
with IVUS. Notably, vessel references were more frequently
sized to the EEM in the OCT than in the IVUS group,
leading to higher stent expansions with OCT guidance.

Figure 3. Primary and secondary end points.

Left, Noninferiority test for stent expansion (primary end point). Right, Prespecified hierarchical superiority testing for stent expansion. The
red shaded area indicates the noninferiority margin. Angio indicates angiography; IVUS, intravascular ultrasound; OCT, optical coherence
tomography; and PCI, percutaneous coronary intervention.

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 Chamié et al iSIGHT: PCI Guided by OCT, IVUS, and Angiography

Figure 4. Distribution of stent expansion.

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Histograms of stent expansion for each imaging modality. Green-colored bins indicate the frequency of cases that achieved ≥90% expansion
(optimum expansion criterium). Red-colored bins indicate the frequency of cases below the optimum expansion criterium. Doughnut charts
present the proportion of cases that achieved ≥90% expansion. IVUS indicates intravascular ultrasound; OCT, optical coherence tomography;
and PCI, percutaneous coronary intervention.

Paradoxically, despite higher visualization of EEM at the
vessel references with IVUS, awareness of significant
plaque burden at the intended landing zones led to a more
conservative sizing strategy in some cases guided by IVUS.
Importantly, such aggressive OCT guidance protocol
was not associated with higher rates of stent edge com-
plications, despite targeting the mean EEM diameter for
stent sizing rather than the maximum lumen diameter.
Despite similar lesion length by pre-PCI angiography,
stents were longer in the IVUS-guided cases as com-
pared to OCT- and angiography-guided cases. IVUS
acquires images with much slower pullback speeds
(0.5 or 1.0 mm/s) than OCT (36 or 18 mm/s), being
more susceptible to cardiac motion with back-and-forth
movement of the imaging catheter. The search for stent
landing zones with the smaller plaque burden possible
(ideally <50%), might have also contributed to the longer
stent lengths observed in the IVUS group.
Intravascular Imaging Versus Angiography
Guidance of PCI
In previous comparisons with IVUS, angiography-guided
PCI was usually plagued by visual vessel undersizing,
lower frequency of postdilatation, smaller poststent MSA,
and higher rates of geographic miss.1,2
In iSIGHT, attempting to eliminate such bias, we
applied to the angiographic arm contemporary concepts
learned from intravascular imaging. For instance, in cases
guided by angiography alone, stents and postdilatation
balloons were visually over-sized by 13.7% and 22.8%,
respectively—figures similar to what was achieved with
intravascular imaging. As a result, the final MSA achieved
with angiographic guidance was similar to the obtained
with IVUS and OCT. Stent expansion was 90% on aver-
age. These excellent angiographic results were achieved
by operators well-trained on the use of intravascular
imaging, and application of high-pressure noncompliant
balloon postdilatation in virtually all lesions. Even so, OCT
guidance showed room for further optimization with sig-
nificantly higher expansion indices.
Procedural Outcomes
Although absolute MSA associates with improved long-
term stent patency and lower risk of stent failure,13,14 this
metric is limited in individual cases with varying reference
vessel size and does not apply for different expansions

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 Chamié et al
needed in tapered vessels nor does it capture multiple
sites of under-expansion along the treated segment.
Thus, normalizing the MSA to the reference vessel pro-
vides a more realistic metric of how large the MSA has
to be for that particular vessel. Nonetheless, calculation
of stent expansion is dependent on how the vessel ref-
erence dimensions are determined. Accordingly, signifi-
cant variability occurs in the expansion criteria applied
in studies, contributing to the observed lack of associa-
tion between stent expansion and clinical outcomes. In
iSIGHT, we calculated expansion by dividing the MSA by
the average lumen area of both the distal and proximal
references. Although this is the most used method, it can
underestimate expansions in tapered vessels and does
not reflect global stent expansions nor it captures mul-
tifocal regions of underexpansions. Currently, the Expert
Consensus Document of the European Association of
Percutaneous Cardiovascular Interventions support the
use of both an absolute MSA (>5.5 mm2 by IVUS and
>4.5 mm2 by OCT) and relative expansion (MSA/aver-
age reference lumen area >80%) as criteria for optimum
stent expansion.15
Incomplete lesion coverage (geographic miss) is
another important predictor of stent failure and major
adverse cardiac events. Landing the stent borders in a
vessel segment with >50% plaque burden by IVUS and
lipid-rich plaque by OCT has been linked to stent edge
restenosis, dissection, and increased risk of periproce-
dural MI.9,16,17 For OCT guidance, we searched for the
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most normal-looking sites that had the largest lumen
free of lipid-rich plaques, irrespective of the plaque bur-
den. Visibility of at least 180° of the EEM was considered
a surrogate of minimum plaque at the intended landing
zones. The safety of this approach is supported by the
similar amount of residual plaque burden seen at stent
edges in the OCT and IVUS groups, and no significant
differences in the frequency and severity of stent edge
dissections, and periprocedural complications.
To minimize vessel injury at stent edges, our practice
stands for low pressure stent deployment, followed by
high-pressure postdilatation with noncompliant balloons
carefully positioned within the stent margins. The com-
bination of how we selected our vessel references and
techniques of stent and balloon inflations might explain
in part the lower rates of stent edge dissection in iSIGHT
(OCT, 15.7%; IVUS, 11.7%; angiography, 18.9%) than
those reported in ILUMIEN III (OCT, 28%; IVUS, 40%;
angiography, 44%), which recruited simpler lesions and
applied a more conservative guidance protocol.
Due to its superior axial resolution and contrast flush-
ing during image acquisition, OCT prompted more iden-
tification and correction of incomplete stent apposition,
which was more frequent, longer, and larger in the IVUS
and angiography groups. However, the significance of
this data is less clear as there is little evidence linking
acute stent malapposition with adverse clinical events.18
Circ Cardiovasc Interv. 2021;14:e009452. DOI: 10.1161/CIRCINTERVENTIONS.120.009452
iSIGHT: PCI Guided by OCT, IVUS, and Angiography
Contrast Use and OCT Guidance
Contrast overload is a frequently mentioned limitation
of OCT to guide PCI when multiple imaging acquisitions
are predicted. In iSIGHT, we used an average of 94 mL
of contrast in the OCT-guided cases—a figure signifi-
cantly smaller than the amount of contrast dispensed
in the OCT-guided cases in the ILUMIEN III (222
mL)8 and OPINION (Optical Frequency Domain Imag-
ing vs Intravascular Ultrasound in Percutaneous Coro-
nary Intervention; 164 mL)7 studies. Notably, contrast
volume we used in the OCT-guided cases was almost
half of that used in the angiography arm of ILUMIEN
III (183 mL), and much smaller than used in the IVUS
arm of OPINION (138 mL), to treat lesions of higher
complexity in iSIGHT.
Limitations
iSIGHT is a single-center trial in which procedures
were performed by operators experienced in the use
of IVUS and OCT. This may have introduced bias on
how stents and balloons were sized in the angiographic
arm and may not apply to sites where operators have
less experience with intravascular imaging. Although
the presence of an imaging expert in all cases ensured
adherence to the imaging guidance protocols and min-
imized bias operators might have toward a particular
imaging modality, this strategy is not routine in most
catheterization laboratories, and makes reproducibility
difficult. However, our results could encourage cath-
eterization laboratory managers to invest in trained
imaging teams to make application of intravascular
imaging more frequent in daily routine. Although our
study sample reflected the daily clinical practice of a
busy catheter laboratory, more complex scenarios such
as left main disease, bifurcation lesions with upfront
2-stent strategy, chronic total occlusions, and dif-
fusely diseased vessels were not included. Whether
intravascular imaging guidance would have a more
significant impact in this more complex scenario can-
not be extrapolated from our data. Our study was not
powered for clinical outcomes. Therefore, whether the
numerically superior stent expansion achieved by OCT
would translate into improved clinical outcomes than
angiography-guided PCI need to be investigated in
an appropriately sized randomized trial. Routine pre-
dilatation with a 1:1 balloon-to-vessel ratio aiming for
lesion preparation before stent deployment was not
mandated. Whether this strategy would result in further
improvement in stent expansion in addition to what we
obtained with an optimized protocol of stent oversizing
and high-pressure postdilatation is unknown. iSIGHT
is an investigator’s initiated trial conducted without any
external funding support. The procedures had to be
completed within the monthly availability of IVUS and
OCT catheters in our public hospital. This limited the
March 2021 334
 Chamié et al
use of both imaging modalities in the same patient to a
very few occasions per month, limiting patients’ expe-
dited recruitment to an ≈2-year period. Importantly,
recruitment was not selective, based on the complexity
of clinical cases. Instead, enrollment was consecutive
whenever both catheters were available for use in the
same patient. Due to uncertainties regarding the effi-
cacy and safety of OCT-guided PCI at the time iSIGHT
was designed, the local Ethics Committee required
at least 1 year of clinical follow-up for each included
patient. This also contributed to prolonging the analy-
sis and publication of the study data. Nevertheless, the
information resulting from the current study is still con-
temporary. We think our data add to the current knowl-
edge of using OCT as an adjunctive tool to guide PCI.
We also consider our data on the angiography-guided
PCI group unique with practical implications for cen-
ters who do not have intravascular imaging available.
Conclusions
Stent expansion achieved with an OCT-guided protocol
based on EEM sizing was noninferior to a contempo-
rary IVUS-guided strategy and superior to an aggressive
angiography-guided approach. The clinical benefits of
such an OCT-based protocol need to be investigated in
clinical outcomes studies.
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ARTICLE INFORMATION
Received April 30, 2020; accepted November 24, 2020.
Affiliations
Invasive Cardiology Department, Dante Pazzanese Institute of Cardiology, Sao
Paulo, Brazil (D.C., J.R.C., D.S., S.B., R.C., F.B., G.B., R.S., F.F., A.A.). Research In-
stitute, Hospital do Coração, Sao Paulo, Brazil (L.P.D.). International Centre for
Circulatory Health, Imperial College London, United Kingdom (H.S., R.P.).
Sources of Funding
None.
Disclosures
None.
REFERENCES
1. Ahn JM, Kang SJ, Yoon SH, Park HW, Kang SM, Lee JY, Lee SW,
Kim YH, Lee CW, Park SW, et al. Meta-analysis of outcomes after intra-
vascular ultrasound-guided versus angiography-guided drug-eluting
stent implantation in 26,503 patients enrolled in three randomized trials
and 14 observational studies. Am J Cardiol. 2014;113:1338–1347. doi:
10.1016/j.amjcard.2013.12.043
2. Elgendy IY, Mahmoud AN, Elgendy AY, Bavry AA. Outcomes with intravascu-
lar ultrasound-guided stent implantation: a meta-analysis of randomized tri-
als in the era of drug-eluting stents. Circ Cardiovasc Interv. 2016;9:e003700.
doi: 10.1161/CIRCINTERVENTIONS.116.003700
3. Koskinas KC, Nakamura M, Räber L, Colleran R, Kadota K, Capodanno D,
Wijns W, Akasaka T, Valgimigli M, Guagliumi G, et al. Current use of intra-
coronary imaging in interventional practice- results of a European Associa-
tion of Percutaneous Cardiovascular Interventions (EAPCI) and Japanese
Association of Cardiovascular Interventions and Therapeutics (CVIT)
Clinical Practice Survey. Circ J. 2018;82:1360–1368. doi: 10.1253/
circj.CJ-17-1144
Circ Cardiovasc Interv. 2021;14:e009452. DOI: 10.1161/CIRCINTERVENTIONS.120.009452
iSIGHT: PCI Guided by OCT, IVUS, and Angiography
4. Kubo T, Akasaka T, Shite J, Suzuki T, Uemura S, Yu B, Kozuma K,
Kitabata H, Shinke T, Habara M, et al. OCT compared with IVUS in a coro-
nary lesion assessment: the OPUS-CLASS study. JACC Cardiovasc Imag-
ing. 2013;6:1095–1104. doi: 10.1016/j.jcmg.2013.04.014
5. Bezerra HG, Costa MA, Guagliumi G, Rollins AM, Simon DI. Intracoro-
nary optical coherence tomography: a comprehensive review clinical and
research applications. JACC Cardiovasc Interv. 2009;2:1035–1046. doi:
10.1016/j.jcin.2009.06.019
6. Habara M, Nasu K, Terashima M, Kaneda H, Yokota D, Ko E, Ito T, Kurita T,
Tanaka N, Kimura M, et al. Impact of frequency-domain optical coherence
tomography guidance for optimal coronary stent implantation in comparison
with intravascular ultrasound guidance. Circ Cardiovasc Interv. 2012;5:193–
201. doi: 10.1161/CIRCINTERVENTIONS.111.965111
7. Kubo T, Shinke T, Okamura T, Hibi K, Nakazawa G, Morino Y, Shite J,
Fusazaki T, Otake H, Kozuma K, et al; OPINION Investigators. Optical fre-
quency domain imaging vs. intravascular ultrasound in percutaneous coro-
nary intervention (OPINION trial): one-year angiographic and clinical results.
Eur Heart J. 2017;38:3139–3147. doi: 10.1093/eurheartj/ehx351
8. Ali ZA, Maehara A, Généreux P, Shlofmitz RA, Fabbiocchi F, Nazif TM,
Guagliumi G, Meraj PM, Alfonso F, Samady H, et al; ILUMIEN III: OPTIMIZE
PCI Investigators. Optical coherence tomography compared with intravas-
cular ultrasound and with angiography to guide coronary stent implanta-
tion (ILUMIEN III: OPTIMIZE PCI): a randomised controlled trial. Lancet.
2016;388:2618–2628. doi: 10.1016/S0140-6736(16)31922-5
9. Chamié D, Bezerra HG, Attizzani GF, Yamamoto H, Kanaya T, Stefano GT,
Fujino Y, Mehanna E, Wang W, Abdul-Aziz A, et al. Incidence, predictors,
morphological characteristics, and clinical outcomes of stent edge dissec-
tions detected by optical coherence tomography. JACC Cardiovasc Interv.
2013;6:800–813. doi: 10.1016/j.jcin.2013.03.019
10. Porto I, Di Vito L, Burzotta F, Niccoli G, Trani C, Leone AM, Biasucci LM,
Vergallo R, Limbruno U, Crea F. Predictors of periprocedural (type IVa)
myocardial infarction, as assessed by frequency-domain optical coher-
ence tomography. Circ Cardiovasc Interv. 2012;5:89–96, S1. doi: 10.1161/
CIRCINTERVENTIONS.111.965624
11. Moussa ID, Klein LW, Shah B, Mehran R, Mack MJ, Brilakis ES, Reilly JP,
Zoghbi G, Holper E, Stone GW. Consideration of a new definition of clini-
cally relevant myocardial infarction after coronary revascularization: an
expert consensus document from the Society for Cardiovascular Angiogra-
phy and Interventions (SCAI). J Am Coll Cardiol. 2013;62:1563–1570. doi:
10.1016/j.jacc.2013.08.720
12. Cutlip DE, Windecker S, Mehran R, Boam A, Cohen DJ, van Es GA,
Steg PG, Morel MA, Mauri L, Vranckx P, et al; Academic Research Con-
sortium. Clinical end points in coronary stent trials: a case for standard-
ized definitions. Circulation. 2007;115:2344–2351. doi: 10.1161/
CIRCULATIONAHA.106.685313
13. Hong MK, Mintz GS, Lee CW, Park DW, Choi BR, Park KH, Kim YH,
Cheong SS, Song JK, Kim JJ, et al. Intravascular ultrasound predictors of
angiographic restenosis after sirolimus-eluting stent implantation. Eur Heart
J. 2006;27:1305–1310. doi: 10.1093/eurheartj/ehi882
14. Doi H, Maehara A, Mintz GS, Yu A, Wang H, Mandinov L, Popma JJ, Ellis SG,
Grube E, Dawkins KD, et al. Impact of post-intervention minimal stent area
on 9-month follow-up patency of paclitaxel-eluting stents: an integrated
intravascular ultrasound analysis from the TAXUS IV, V, and VI and TAXUS
ATLAS Workhorse, Long Lesion, and Direct Stent Trials. JACC Cardiovasc
Interv. 2009;2:1269–1275. doi: 10.1016/j.jcin.2009.10.005
15. Räber L, Mintz GS, Koskinas KC, Johnson TW, Holm NR, Onuma Y,
Radu MD, Joner M, Yu B, Jia H, et al; ESC Scientific Document Group.
Clinical use of intracoronary imaging. Part 1: guidance and optimization of
coronary interventions. An expert consensus document of the European
Association of Percutaneous Cardiovascular Interventions. Eur Heart J.
2018;39:3281–3300. doi: 10.1093/eurheartj/ehy285
16. Kang SJ, Cho YR, Park GM, Ahn JM, Kim WJ, Lee JY, Park DW, Lee SW,
Kim YH, Lee CW, et al. Intravascular ultrasound predictors for edge reste-
nosis after newer generation drug-eluting stent implantation. Am J Cardiol.
2013;111:1408–1414. doi: 10.1016/j.amjcard.2013.01.288
17. Imola F, Occhipinti M, Biondi-Zoccai G, Di Vito L, Ramazzotti V, Manzoli A,
Pappalardo A, Cremonesi A, Albertucci M, Prati F. Association between
proximal stent edge positioning on atherosclerotic plaques containing lipid
pools and postprocedural myocardial infarction (from the CLI-POOL Study).
Am J Cardiol. 2013;111:526–531. doi: 10.1016/j.amjcard.2012.10.033
18. Romagnoli E, Gatto L, La Manna A, Burzotta F, Taglieri N, Saia F, Amico F,
Marco V, Ramazzotti V, Di Giorgio A, et al. Role of residual acute stent malap-
position in percutaneous coronary interventions. Catheter Cardiovasc Interv.
2017;90:566–575. doi: 10.1002/ccd.26974
March 2021 335