Original Research Article

Optical Coherence Tomography to Optimize Results

of Percutaneous Coronary Intervention in Patients
with Non–ST-Elevation Acute Coronary Syndrome
Results of the Multicenter, Randomized DOCTORS Study (Does Optical
­Coherence Tomography Optimize Results of Stenting)

Editorial, see p 918 Nicolas Meneveau, MD,

PhD
BACKGROUND: No randomized study has investigated the value of optical Geraud Souteyrand, MD
coherence tomography (OCT) in optimizing the results of percutaneous Pascal Motreff, MD, PhD
coronary intervention (PCI) for non–ST-segment elevation acute coronary Christophe Caussin, MD
Nicolas Amabile, MD
syndromes.
Patrick Ohlmann, MD, PhD
METHODS: We conducted a multicenter, randomized study involving 240 Olivier Morel, MD, PhD
Yoann Lefrançois, MD
patients with non–ST-segment elevation acute coronary syndromes to
Vincent Descotes-Genon,
compare OCT-guided PCI (use of OCT pre- and post-PCI; OCT-guided group)
MD
to fluoroscopy-guided PCI (angiography-guided group). The primary end Johanne Silvain, MD, PhD
point was the functional result of PCI assessed by the measure of post Nassim Braik, MD
PCI fractional flow reserve. Secondary end points included procedural Romain Chopard, MD,
Downloaded from http://ahajournals.org by on November 29, 2019

complications and type 4a periprocedural myocardial infarction. Safety was PhD

assessed by the rate of acute kidney injury. Marion Chatot, MD
Fiona Ecarnot, MSc
RESULTS: OCT use led to a change in procedural strategy in 50% of the Hélène Tauzin, PhD
patients in the OCT-guided group. The primary end point was improved in the Eric Van Belle, MD, PhD
OCT-guided group, with a significantly higher fractional flow reserve value Loïc Belle, MD
(0.94±0.04 versus 0.92±0.05, P=0.005) compared with the angiography- François Schiele, MD, PhD
guided group. There was no significant difference in the rate of type 4a
myocardial infarction (33% in the OCT-group versus 40% in the angiography-
guided group, P=0.28). The rates of procedural complications (5.8%) and acute
kidney injury (1.6%) were identical in each group despite longer procedure
time and use of more contrast medium in the OCT-guided group. Post-PCI OCT
revealed stent underexpansion in 42% of patients, stent malapposition in 32%,
incomplete lesion coverage in 20%, and edge dissection in 37.5%. This led
to the more frequent use of poststent overdilation in the OCT-guided group Correspondence to: Nicolas
Meneveau, MD, PhD, Department
versus the angiography-guided group (43% versus 12.5%, P<0.0001) with of Cardiology, EA3920, University
lower residual stenosis (7.0±4.3% versus 8.7±6.3%, P=0.01). Hospital Jean Minjoz, Boulevard
Fleming, 25000 Besançon,
CONCLUSIONS: In patients with non–ST-segment elevation acute coronary France. E-mail nicolas.meneveau@
syndromes, OCT-guided PCI is associated with higher postprocedure univ-fcomte.fr

fractional flow reserve than PCI guided by angiography alone. OCT did not Sources of Funding, see page 915
increase periprocedural complications, type 4a myocardial infarction, or Key Words:  acute coronary
acute kidney injury. syndrome ◼ optical coherence
tomography ◼ stent
CLINICAL TRIAL REGISTRATION: URL: http://www.clinicaltrials.gov. © 2016 American Heart
Unique identifier: NCT01743274. Association, Inc.

906 September 27, 2016 Circulation. 2016;134:906–917. DOI: 10.1161/CIRCULATIONAHA.116.024393


Clinical Perspective
What is New?
• In this first randomized, controlled trial testing opti-
cal coherence tomography (OCT) guidance during
PCI in patients with non–ST-segment elevation acute
coronary syndromes, OCT findings directly affected
physician decision-making, leading to a change in
procedural strategy in half the cases in the OCT-
guided group.
• OCT-guided PCI modestly improved functional out-
come compared with PCI guided by fluoroscopy
alone, as assessed by fractional flow reserve mea-
sured at the end of the procedure.
• This improvement seemed to be explained mostly
by optimization of stent expansion.
• The benefit was obtained at the cost of a longer pro-
cedure with higher fluoroscopy time and more con-
trast use, but without an increase in periprocedural
myocardial infarction or kidney dysfunction.
What Are the Clinical Implications?
• The findings of the DOCTORS study (Does Optical
Coherence Tomography Optimize Results of Stent-
ing) add to the accumulating body of evidence sup-
porting a potential benefit of OCT to guide PCI.
• These results suggest that there may be a role for
OCT as a complement to fluoroscopy for the guid-
ance of PCI procedures in non–ST-segment eleva-
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tion acute coronary syndromes.
• Additional prospective studies with clinical end points
are required before considering incorporating OCT
guidance for standard use in patients with non–ST-
segment elevation acute coronary syndromes.
S
ince the advent of percutaneous coronary interven-
tion (PCI), considerable progress in device technol-
ogy, imaging, and the pharmacologic environment
has led to improved safety and efficacy. Although angio-
graphic guidance is the established standard of care dur-
ing PCI, recent intravascular imaging techniques such as
optical coherence tomography (OCT) offer potential ad-
vantages compared with angiography for the evaluation
of lesion characteristics, as well as for the optimization
of procedural outcome. In the setting of acute coronary
syndrome (ACS), OCT has been shown to identify plaque
morphologies that are associated with worse progno-
sis.1–3 Furthermore, beyond plaque characterization,
OCT also can reveal procedural attributes that cannot
be seen on angiography alone, including optimal lesion
coverage, stent expansion, or apposition. Abnormal find-
ings by OCT imaging are common after procedures con-
sidered to be optimal by angiographic standards,4 and
OCT criteria of suboptimal stent expansion have been
shown to be associated with an increased risk of major
adverse cardiac events.5
Circulation. 2016;134:906–917. DOI: 10.1161/CIRCULATIONAHA.116.024393
OCT Optimizes Stenting: DOCTORS
The additional information yielded by OCT imaging
during PCI affects physician decision-making in two-
thirds of the cases.6 Nonetheless, it remains to be in-
vestigated whether the use of additional interventions
prompted by OCT findings will translate into a benefit
in procedural outcome. In this setting, randomized data
investigating the utility of OCT compared with angiog-
raphy alone to guide PCI are lacking,7,8 specifically in
patients with non–ST-segment elevation acute coronary
syndromes (NSTE-ACS).
ORIGINAL RESEARCH
Therefore, we aimed to evaluate whether the use of
OCT during PCI would provide useful clinical information
ARTICLE
beyond that obtained by angiography alone, and whether
this information would modify physician decision-making,
thus affecting the functional result of angioplasty as as-
sessed by fractional flow reserve (FFR) measured after
stent implantation in a lesion responsible for NSTE-ACS.
METHODS
The DOCTORS study (Does Optical Coherence Tomography
Optimize Results of Stenting) was a multicenter, prospective,
randomized trial conducted in 9 university teaching hospitals
and general (nonacademic) hospitals in France. The details of
the study design have previously been published elsewhere.9
The study protocol was approved by the Institutional Review
Board of the University Hospital of Besancon, France, and all
participants provided written informed consent. The study is reg-
istered on ClinicalTrials.gov under the identifier NCT01743274.
Patient Population
Patients were recruited from among all patients with NSTE-ACS
scheduled to undergo PCI at any of the participating centers.
The inclusion criteria for the study were as follows: Patients
aged 18 to 80 years inclusive, admitted for ACS with the fol-
lowing symptoms: Clinical signs of ischemia (chest pain) at rest
lasting for at least 10 minutes in the previous 72 hours; and at
least 1 of the following 2 criteria: (i) New ST segment depres-
sion ≥1 mm or transitory ST segment elevation (<30 minutes;
≥1 mm) on at least 2 contiguous leads of the electrocardio-
gram; or (ii) elevation (>upper limit of normal, ULN) of cardiac
enzymes (CK-MB, troponin I or T); and presenting an indication
for coronary angioplasty with stent implantation of the target
lesion (single lesion on the culprit artery without diffuse disease
on the same vessel) considered to be responsible for the ACS.
Exclusion criteria were: Left main disease; in-stent restenosis;
presence of coronary artery bypass grafts; cardiogenic shock
or severe hemodynamic instability; severely calcified or tortu-
ous arteries; persistent ST-segment elevation; 1 or more other
lesions considered angiographically significant, or nonsignifi-
cant diffuse disease, located on the target vessel; severe renal
insufficiency (estimated glomerular filtration rate (eGFR) ≤30
mL/min); bacteremia or septicemia; severe coagulation disor-
ders; pregnancy; refusal to sign the informed consent form.
Study End Points
The primary end point was FFR measured at the end of the
procedure.
September 27, 2016 907
 Meneveau et al
Secondary end points were: 1) Procedural complications
defined as occurrence of any one or more of the following:
Presence of no reflow, coronary perforation, occlusive dissec-
tion, spasm, or stent occlusion. 2) Periprocedural (type 4a)
myocardial infarction (MI) as defined by the Third Universal
Definition of Myocardial Infarction.10 3) Identification of a
threshold value for quantitative OCT findings that best predicts
an FFR value >0.90.
Safety end points were: 1) Acute kidney injury defined as
an absolute increase in serum creatinine of ≥0.5 mg/dL from
baseline.11 2) Duration of the procedure, fluoroscopy time,
quantity of contrast media used, and radiation dose delivered.
Randomization
Patients were randomly allocated to 1 of the 2 groups after ini-
tial coronary angiography, once the operator had identified the
lesion responsible for the ACS, with randomization stratified
by center. Randomization was performed using consecutive
sealed opaque envelopes containing the treatment arm allo-
cated to the patient. The attribution schedule was generated
randomly by computer in blocks of 20.
Interventional Procedures
In the angiography-guided group, the angioplasty procedure
was guided by traditional fluoroscopy alone, performed before
and after stent implantation according to standard of care.
In the OCT-guided group, OCT was performed after initial
coronary angiography and repeated after stent implantation.
Several OCT runs could then be performed, as required, and
the OCT run showing a satisfactory result was considered as
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the final run. Thus, per protocol, the number of OCT runs was
at least 2. The operator was encouraged to change proce-
dural strategy according to the data immediately available on
the OCT images, with the possibility of performing additional
interventions in order to optimize the results of the PCI. In
particular, the operator was required to evaluate the following
parameters, based on the OCT images acquired:
1. Before PCI: quantitative measure of the reference diam-
eter and reference area of the vessel and the length of
the lesion; presence and extent of thrombus; presence
and extent of calcification.
2. After PCI with stent implantation: quantitative measure
of in-stent minimal lumen diameter and in-stent minimal
lumen area, reference lumen diameter and reference
lumen area, presence of thrombus, presence of edge
dissection above or below the stent, protrusion of tis-
sue through the stent struts, optimal lesion coverage,
malapposition of the stent struts to the vessel wall, sub-
optimal stent expansion.
In the OCT-guided group, the guidelines for the procedural
strategy incorporating online OCT information were as follows:
1. The length and diameter of the stent to be implanted
were to be chosen based on the quantitative measures
of reference vessel diameter and lesion length by OCT.
2. Additional balloon overdilations were to be performed
in case of stent underexpansion. Stent underexpansion
was deemed to be present when the ratio of in-stent
minimal lumen area to reference lumen area was ≤80%.
Management of malapposition was at the operator’s
discretion.
908 September 27, 2016
3. Additional stent implantation(s) were to be performed to
rectify incomplete lesion coverage. Conversely, manage-
ment of edge dissection was at the operator’s discretion.
4. Use of GP IIb/IIIa inhibitors and aspiration thrombectomy
were to be considered systematically if thrombus was
present.
5. Rotational atherectomy was to be considered in case of
circumferential calcifications.
The operator was required to take these parameters into
account in deciding on subsequent strategy for the rest of the
procedure in order to optimize the final angiographic result.
Fractional Flow Reserve
In both groups, FFR was measured at the end of the procedure,
once the operator considered the result of the angioplasty to
be optimal. FFR was measured using a pressure wire (St. Jude
Medical, Saint Paul, MN) equipped with a pressure sensor
located 30 mm from the distal end of the catheter. The wire
was introduced above the lesion responsible for the ACS symp-
toms, and the FFR was calculated as the ratio between aver-
age distal pressure and the average aortic pressure recorded
during maximal hyperemia induced by injection of an intracoro-
nary bolus of 150 µg of adenosine, followed by a flush of iso-
tonic saline of 10 mL. The average of three consecutive FFR
measures was recorded. The procedure was then considered
to be finished, and no further interventions were undertaken,
regardless of the FFR value obtained at this final measure.
Optical Coherence Tomography Image
Acquisition and Analysis
OCT images were acquired using the FD-OCT Optis system (Lightlab
Imaging Incorporated, Westford, MA) and 6F guide catheter compat-
ible Dragonfly Duo and Dragonfly Optis catheter (Lightlab Imaging
Incorporated, Westford, MA). The catheter was introduced into the
coronary artery via a standard 0.014-inch angioplasty wire, after
prior injection of an intracoronary bolus of nitroglycerin. To remove
all blood adequately from the imaging site, nonocclusive flushing
was performed using continuously injected contrast medium via an
automated power injector, and the OCT catheter was pulled back at
a speed of 18 mm/second to guarantee sufficient time to acquire
images of a 54 mm long segment (frame density: 10 frames/mm).
OCT images were analyzed online and offline using Lightlab soft-
ware. All OCT images were analyzed in a centralized core labora-
tory (University Hospital of Besancon) by 2 independent operators
(N.M., N.B.) blinded to the angiographic findings, procedural strat-
egy, and final FFR value. Discordant OCT analyses were resolved
by consensus. The values retained for final analysis were those
resulting from central core laboratory analysis.
OCT criteria for the definition of the end points were defined
according to recent consensus documents and established
definitions.12–14 The main definitions are given in Section I in
the online-only Data Supplement, as well as representative
images of tissue prolapse, stent malapposition, stent under-
expansion and edge dissection (Figure I in the online-only Data
Supplement).
Quantitative Coronary Angiography
All angiograms were analyzed at the core laboratory in the
coordinating center (University Hospital Besancon, France)
Circulation. 2016;134:906–917. DOI: 10.1161/CIRCULATIONAHA.116.024393
 OCT Optimizes Stenting: DOCTORS

using an automated edge detection algorithm (QAngio XA 7.3,

Medis Medical Imaging Systems BV, Leiden, Netherlands). The
measurements were performed for each pair of orthogonal
views and averaged.

6-Month Follow-Up
All patients were followed up for 6 months to record adverse
events, defined as the occurrence of any one or more of
the following: death, recurrent MI, stent thrombosis defined
according to the ARC definition,15 or repeat revascularization

ORIGINAL RESEARCH
of the target lesion.

ARTICLE
Data Coordination
Data management and analysis was performed centrally at the
Cardiology Department of the coordinating center (University
Hospital of Besancon, France), where a dedicated team of data
managers were responsible for data collection and monitoring.
Formal data monitoring was overseen by the Clinical Research
Management Department (Délégation à la Recherche Clinique
et à l’Innovation) of the coordinating center by sending inde- Figure 1.  Flowchart of the study population and
pendent monitors to each site regularly to monitor files and design.
check data entry. ACS indicates acute coronary syndrome; DOCTORS trial,
Does Optical Coherence Tomography Optimize Results of
Statistical Analysis Stenting trial; MI, myocardial infarction; NSTE-ACS, non–ST-
Quantitative variables are expressed as mean±standard deviation segment elevation acute coronary syndromes; OCT, optical
for normally distributed variables, and median (interquartiles) for coherence tomography; and PCI, percutaneous coronary
non-normally distributed variables. Normality of continuous vari- intervention.
ables was verified using the Kolmogorov-Smirnov test. Categorical
variables are described as number (percentage). Quantitative 31, 2015, among 1935 patients with NSTE-ACS re-
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data were compared using the Student t or Mann-Whitney tests,
and qualitative variables using the χ2 or Fisher exact tests, as
appropriate. The paired Student t test was used for within-patient
comparisons of continuous variables. To compare the perfor-
mance of quantitative OCT parameters to predict an FFR value
>0.90, receiver operating characteristic curves were constructed
and the area under the curve was compared using the Delong
method.16 The Youden index was used to identify the optimal cut-
off values from receiver operating characteristic curves.
Sample Size Calculation
Based on an average FFR value after stent implantation of 0.92
with a standard deviation of 0.0714,17 under the hypothesis
that the use of OCT would improve FFR by 0.03 U, at an α risk
of 5% and a β risk of 10%, it was calculated that 115 patients
would be required in each arm. In order to account for patients
lost to follow-up, technical failures or images unsuitable for
analysis, an additional 5 patients were included in each group,
making a total of 240 patients.9
A P value of <0.05 was considered statistically significant.
All analyses were performed using SAS version 9.4 (SAS
Institute Inc., Cary, NC).
RESULTS
Study Population
The flow chart and study design are presented in Fig-
ure 1. Between September 12, 2013, and December
ferred for PCI in 9 centers, a total of 240 patients
were included (120 in the angiography-guided group
and 120 in the OCT-guided group). There were no
crossovers between groups. There were no significant
differences between groups in the baseline character-
istics, which are presented in Table 1. The majority of
NSTE-ACS patients were non–ST-elevation MI patients
(92.1%), and only 19 patients (7.9%) had unstable an-
gina without troponin elevation. The majority (69.2%)
had single-vessel disease, and the left anterior de-
scending artery was most frequently responsible for
symptoms.
Primary End Point
The primary end point was improved in the OCT-guided
group, with significantly greater FFR value compared
with the angiography-guided group (0.94±0.04 versus
0.92±0.05, P=0.005; Figure 2A). Similarly, the number
of patients with FFR>0.90 at the end of the procedure
was significantly higher in the OCT-guided group com-
pared with the angiography-guided group (99 [82.5%]
versus 77 [64.2%], P=0.0001). Categorization of the
patients by quartiles of FFR showed that the distribution
of patients across the quartiles was significantly differ-
ent between the OCT and angiography-guided groups
(P=0.04; Figure 2B).

Circulation. 2016;134:906–917. DOI: 10.1161/CIRCULATIONAHA.116.024393 September 27, 2016 909

 Meneveau et al

Table 1.  Baseline Characteristics of the Study Population

Angiography-Guided OCT-Guided Group
Variable Overall (N=240) Group (n=120) (n=120) P Value
Age, y 60.5±11.4 60.2±11.3 60.8±11.5 0.72
Male (%) 186 (77.5) 91 (75.8) 95 (79.2) 0.53
Diabetes mellitus (%) 45 (18.8) 19 (15.8) 26 (21.7) 0.25
Obesity (%) 152 (63.3) 77 (64.2) 75 (62.5) 0.79
Hypercholesterolemia (%) 115 (47.9) 56 (46.7) 59 (49.2) 0.70
Hypertension (%) 117 (48.8) 50 (41.7) 67 (55.8) 0.03
Current smokers (%) 98 (40.8) 51 (42.5) 47 (39.2) 0.60
Family history of CAD (%) 78 (32.5) 39 (32.5) 39 (32.5) 1
Unstable angina (%) 19 (7.9) 9 (7.5) 10 (8.3) 0.81
Troponin at admission, µg/L 0.79 [0.2; 2.5] 1.1 [0.2; 4.1] 0.54 [0.2; 1.7] 0.33
eGFR, mL/min 94.3 [73.4; 116.5] 94.5 [74.6; 116.2] 93.9 [72.1; 116.8] 0.32
No. vessels diseased 0.28
1 (%) 166 (69.2) 88 (73.3) 78 (65.0)
2 (%) 54 (22.5) 24 (20.0) 30 (25.0)
3 (%) 20 (8.3) 8 (6.7) 12 (10.0)
Infarct-related artery 0.63
Right coronary artery (%) 70 (29.2) 32 (26.7) 38 (31.6)
Circumflex artery (%) 54 (22.5) 28 (23.3) 26 (21.7)
Left anterior descending artery (%) 116 (48.3) 60 (50.0) 56 (46.7)
ACC/AHA lesion type 0.43
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A (%) 68 (28.3) 38 (31.6) 30 (25.0)

B1 (%) 123 (51.2) 57 (47.5) 66 (55.0)
B2 (%) 25 (10.4) 11 (9.2) 14 (11.7)
C (%) 24 (10) 14 (11.7) 10 (8.3)
ACC/AHA indicates American College of Cardiology/American Heart Association; CAD, coronary artery disease; eGFR, estimated glomerular
filtration rate; and OCT, optical coherence tomography.

Preprocedural Angiographic and OCT Findings
There were no significant differences in preprocedure
quantitative angiographic findings between groups
(Table 2). Approximately half the patients had B1-type
lesions. OCT was successfully performed pre- and
post-PCI in 100% of patients in the OCT-guided group.
However, introduction of the OCT catheter downstream
of the lesion resulted in subtotal occlusion of the ar-
tery in 32 patients (26.7%) in the OCT-guided group
due to the severity of the stenosis or the presence of
thrombus, and required predilation to enable an OCT
run suitable for analysis. Quantitative findings as as-
sessed by OCT are shown in Table 3, and qualitative
OCT findings are detailed in Table I in the online-only
Data Supplement.
Thrombus and calcifications were observed signifi-
cantly more frequently by OCT than by angiography alone
(83 [69%] versus 56 [47%], P=0.0004; 55 [45.8%] ver-
sus 11 [9%], P<0.0001, respectively). Plaque rupture
was present in half of all lesions and intact fibrous cap
in the other half. Two-thirds had lipid-rich plaque compo-
sition, and one-third were composed of fibrous plaque.
Presence of thin-cap fibroatheroma was observed in 70
patients (58.3%).
Impact of Pre-PCI OCT
There was no significant difference in procedural strat-
egy between the 2 groups before stent implantation
(Table 4), except for more frequent use of GP IIb/IIIa in-
hibitors in the OCT-guided group, due to the significantly
higher rate of thrombus visualized by OCT. Otherwise,
antiplatelet and anticoagulant therapy both prior to and
during the procedure was similar in both groups (Table
II in the online-only Data Supplement). Although calcifica-
tions were more frequently observed in the OCT-guided

910 September 27, 2016 Circulation. 2016;134:906–917. DOI: 10.1161/CIRCULATIONAHA.116.024393

 OCT Optimizes Stenting: DOCTORS

ORIGINAL RESEARCH
ARTICLE
Figure 2.  Primary End Point: FFR measured at the end of the procedure.
A, Final fractional flow reserve (FFR) value after percutaneous coronary intervention in the angiography-guided and optical coher-
ence tomography (OCT)-guided groups. B, Distribution of the patients from the angiography-guided and OCT-guided groups
according to quartiles of FFR calculated from the whole study population.

group, this finding did not lead to any difference in pro-
cedural strategy between groups.
Impact of Post-PCI OCT
The first OCT run performed immediately after stent
implantation in the OCT-guided group revealed the exis-
tence of stent malapposition in 38 patients (32%) and
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78.9±12.4% immediately after stent implantation to
84.1±7.3% at the end of the procedure after optimiza-
tion (P<0.0001; Figure 3). The average number of OCT
runs overall was 3.8±1.4.
Receiver Operating Characteristic Curve Analysis
Receiver operating characteristic curve analysis was

stent underexpansion in 50 (42%) (Table 4). Post-stent used to compare the performance of the quantitative
overdilation was performed in all patients with stent
underexpansion, and in 22 out of 38 patients (58%)
with stent malapposition (of whom 20 also had stent Table 2.  Quantitative Angiographic Findings Pre- and
underexpansion, only 2 had isolated malapposition). Postprocedure in the Angiography-Guided and OCT-
Overall, there was a greater rate of poststent overdila- Guided Groups
tion in the OCT-guided group compared with the angi- Angiography-
ography-guided group. Edge dissection was observed Guided Group OCT-Guided
more frequently in the OCT-guided group (45 [37.5%] Variable (n=120) Group (n=120) P Value
versus 5 [4%], P<0.0001). Among the 45 edge dissec- Quantitative findings preprocedure
tions observed in the OCT-guided group, 6 (5%) were
 Reference 2.88±0.39 2.81±0.41 0.18
visible by angiography alone. Additional stent implanta- diameter, mm
tion was performed in 32 patients in the OCT-guided
group (24 for incomplete lesion coverage and 8 for  MLD, mm 0.87±0.29 0.81±0.30 0.12
adventitial edge dissection) and in 22 in the angiogra-  Diameter 69.3±9.4 71.3±9.9 0.12
phy-guided group (20 for incomplete lesion coverage stenosis, %
and 2 for edge dissection). Overall, the use of OCT led  Lesion length, 13.5±6.0 13.7±6.4 0.80
the operator to optimize the procedural strategy in 60 mm
patients (50%), compared with 27 patients (22.5%) in Quantitative findings postprocedure
the angiography-guided group (P<0.0001), leading to
 Reference 3.16±0.37 3.13±0.41 0.48
a significantly lower diameter stenosis at the end of diameter, mm
PCI (7.0±4.3% versus 8.7±6.3%, OCT versus angio,
 MLD, mm 2.90±0.42 2.89±0.40 0.82
P=0.01; Table 2). There was a significant improve-
ment in quantitative OCT data between the OCT run  Diameter 8.7±6.3 7.0±4.3 0.01
performed immediately after stent implantation, and stenosis, %
the final OCT run performed after optimization, at the MLD indicates minimal lumen diameter; and OCT, optical coherence
end of the procedure. Stent expansion increased from tomography.

Circulation. 2016;134:906–917. DOI: 10.1161/CIRCULATIONAHA.116.024393 September 27, 2016 911

 Meneveau et al
Table 3.  OCT Findings Prestenting, Immediately Poststenting, and Post-OCT Optimization of the
PCI Procedure, in the OCT-Guided Group (n=120)
Variable Prestenting
Reference diameter, mm 2.92±0.53
MLD, mm 1.21±0.33
Diameter stenosis, % 58.4±10.9
Reference area, mm 2
7.0±2.23
MLA, mm 2
1.28±0.71
Area stenosis, % 81.1±9.82
MLA, minimal lumen area; MLD, minimal lumen diameter; OCT, optical coherence tomography; and PCI, percutaneous coronary
intervention.
*P values from paired Student t test for the comparison post-OCT optimization versus immediately poststent.
OCT parameters to predict FFR >0.90. The area under
the curve was 0.79 (0.71–0.86; P<0.0001) for minimal
lumen area, 0.77 (0.69–0.84; P<0.0001) for stent ex-
pansion, 0.72 (0.63–0.80; P=0.0002) for minimal lumen
diameter, and 0.69 (0.60–0.77; P=0.003) for diameter
stenosis (Figure II in the online-only Data Supplement).
Direct comparison of the area under the curve did not
reveal any significant difference between these quanti-
tative OCT parameters in terms of predictive capacity.
The optimal cutoff value of minimal lumen area to predict
FFR >0.90 was >5.44 mm2 with a sensitivity of 91.3%
and specificity 60.2%, while the optimal cutoff value of
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stent expansion to predict FFR > 0.90 was >79.4%, with
sensitivity of 83.7% and specificity 65.2% (Table III in the
online-only Data Supplement).
Safety Outcomes
There was no significant difference in the rate of proce-
dural complications between groups (7 [5.8%] events in
each group; Table 5). Similarly, the proportion of type 4a
MI and AKI did not differ between groups. Conversely,
the duration of OCT-guided procedures was significantly
longer than in those guided by angiography alone, with
a significantly greater fluoroscopy time. On average, the
volume of contrast medium and the dose of radiation
delivered were significantly greater in the OCT-guided
group (P<0.0001 for each; Table 5).
Clinical Outcomes at 6-Month Follow-Up
Discharge treatment was similar in both groups (Table II
in the online-only Data Supplement), with 100% prescrip-
tion of P2Y12 inhibitors and 99% and 98% with aspirin
at discharge in the angiography-guided and OCT-guided
groups respectively. One patient (from the angiography-
guided group) was lost to follow-up, but data from mu-
nicipal death registries indicate that this patient was still
alive at the study cut-off date. The rate of major adverse
912 September 27, 2016
Immediately
Poststenting Post-OCT Optimization P Value*
3.10±0.45 3.11±0.48 0.27
2.79±0.46 2.84±0.43 0.001
9.5±6.1 8.4±3.9 <0.0001
7.62±2.42 7.72±2.43 0.10
5.99±2.11 6.41±1.99 <0.0001
21.1±12.4 15.9±7.3 <0.0001
cardiac events was similar in both groups (Table IV in the
online-only Data Supplement). There was 1 death in the
OCT-guided group, and 1 recurrent MI in each group,
both unrelated to the target vessel. No stent thrombosis
was observed during follow-up, and there was no signifi-
cant difference in the rate of target vessel revasculariza-
tion between groups.
DISCUSSION
The DOCTORS trial is the first randomized, prospec-
tive, multicenter trial to investigate the use of OCT on
top of angiographic guidance and to show that in pa-
tients with NSTE-ACS, OCT provided useful additional
information beyond that obtained by angiography alone
and was associated with better functional outcome as
assessed by FFR.
OCT findings affected physician decision-making
and led to a change in procedural strategy in half of all
cases, mainly driven by the optimization of stent expan-
sion, albeit without requiring implantation of a greater
number of stents. This functional benefit was obtained
at the cost of a longer procedure and fluoroscopy time,
greater volume of contrast medium and dose of radia-
tion, but without an increase in periprocedural MI or
kidney dysfunction. Whether this functional benefit will
translate into clinical benefit remains to be determined.
Nevertheless, the proportion of patients with poststent
FFR ≥ 0.90 was increased by 22% in OCT-guided group
compared with patients in the angiography-guided group
in our study, and it has been shown previously that pa-
tients with a poststent FFR of ≥0.90 had event rates
of 4.9 to 6.2% at 6 months, compared with 20.3% in
patients with poststent FFR <0.90.17
We took a pragmatic approach, choosing OCT vari-
ables that are easy to identify and measure, to guar-
antee that OCT guidance could be implemented easily
in routine clinical practice. In this context, most of the
definitions of variables and features were based on avail-
Circulation. 2016;134:906–917. DOI: 10.1161/CIRCULATIONAHA.116.024393
 OCT Optimizes Stenting: DOCTORS

Table 4.  Procedural Data Pre- and Poststenting

Angiography-Guided Group OCT-Guided Group
Variable (n=120) (n=120) P Value
Prestenting
 Predilation (%) 43 (35.8) 42 (35.0) 0.89
 Aspiration thrombectomy (%) 4 (3.3) 2 (1.7) 0.41
 GP IIb/IIIa inhibitors (%) 43 (35.8) 63 (53) 0.007
 Rotational atherectomy (%) 0 1 (0.8) 1

ORIGINAL RESEARCH
Procedural data
 Stent length, mm 17.3±5.5 17.9±5.6 0.44

ARTICLE
 Stent diameter, mm 3.11±0.41 3.11±0.41 0.94
 Inflation pressure, atm 16.8±1.8 16.7±1.9 0.68
 Stent malapposition (%) ... 38 (32.0)†
 Maximal strut-to-vessel-wall distance, 0.39 [0.28; 0.56]
mm
 Length, mm 2.3 [1.1; 4.7]
 Stent underexpansion (%) 13 (10.8)* 50 (42)† <0.0001
 Tissue protrusion (plaque/thrombus) (%) ... 95 (79)†
 Incomplete lesion coverage (%) 20 (17)* 24 (20)† 0.51
 Edge dissection (%) 5 (4)* 45 (37.5)† <0.0001
 Intimal (%) 22 (48.9)
 Medial/adventitial (%) 23 (51.1)
 Proximal (%) 19 (15.8)
Downloaded from http://ahajournals.org by on November 29, 2019

 Distal (%) 22 (18.3)

 Intra-stent (%) 4 (3.3)
 Post-stent overdilation (%) 15 (12.5) 52 (43) <0.0001
 PCI of a side-branch (%) 7 (5.8) 6 (5.0) 0.78
 Additional stenting (%) 22 (18.3) 32 (27) 0.09
 Optimization of procedural strategy (%) 27 (22.5) 60 (50) <0.0001
Postprocedure
 Total number of stents implanted 1.2±0.5 1.3±0.5 0.10
 Total stent length, mm 20.4±9.0 21.9±9.3 0.17
Atm indicates atmospheres; GP, glycoprotein; OCT, optical coherence tomography; and PCI, percutaneous coronary intervention.
*By visual assessment.
†As visualized by OCT.

able expert consensus documents.12–14 The only quanti-
tative criteria that had to be respected were the choice
of the stent diameter and length according to OCT mea-
surements, and the use of poststent overdilation in case
of stent underexpansion. In addition, implantation of an
additional stent was mandatory in case of incomplete
lesion coverage with persistent significant stenosis. Oth-
erwise, the use of other strategies to optimize PCI, such
as rotational atherectomy, thromboaspiration or GP IIb/
IIIa inhibitors, was at the operator’s subjective discretion.
Similarly, in the absence of established critical thresh-
olds beyond which malapposition and tissue prolapse
warrant intervention, the management of these findings
also was left at the operator’s discretion.
Our data suggest that the pre-PCI OCT run did not
seem to affect procedural strategy, with the exception
of greater use of GP IIb/IIIa inhibitors, in response to
more frequent visualization of intracoronary thrombus.
Presence and extent of calcification, plaque composi-
tion, and presence of plaque rupture or thin-cap fibro-
atheroma did not influence physician decision-making.
In the current state of knowledge, there are no data to
justify the use of any particular procedural approach ac-
cording to the composition of the plaque. Quantitative

Circulation. 2016;134:906–917. DOI: 10.1161/CIRCULATIONAHA.116.024393 September 27, 2016 913

 Meneveau et al

Figure 3.  Impact of Post-PCI OCT.

A, Box and whisker plot representing final di-
ameter stenosis as assessed by quantitative
coronary angiography in the angiography-
guided and optical coherence tomography
(OCT)-guided groups. B, Box and whisker
plot representing stent expansion between
the OCT run immediately post stent implan-
tation and the run at the end of the proce-
dure, in the OCT-guided group (n=120).
CI indicates confidence interval; and PCI,
percutaneous coronary intervention.

analysis of the lesion by OCT pre-PCI did not affect the
choice of stent length or diameter compared with visual
assessment by angiography alone. Furthermore, consid-
ering that in 26.7% of cases, predilation was required to
obtain a first interpretable OCT run, the question arises
as to the utility of using OCT prior to stent implantation.
Conversely, the post-PCI prompted a change in
procedural strategy in half of the patients in the OCT-
guided group. This is somewhat different than the non-
randomized ILUMIEN-I study, where it was reported
that pre- and poststenting OCT changed the procedural
strategy in 57% and 27% of cases, respectively.6 The
improvement in FFR observed in the OCT-guided group
in our study was related mainly to the correction of
Downloaded from http://ahajournals.org by on November 29, 2019
previous studies,5,18,19 stent underexpansion was asso-
ciated with an increased risk of major adverse cardiac
events during follow-up. Data from the CLI-OPCI regis-
try (Centro per la Lotta contro l’Infarto-Optimisation of
Percutaneous Coronary Intervention) suggest that the
use of OCT could improve clinical outcomes in patients
undergoing PCI. A significant reduction in the primary
end point of cardiac death or myocardial infarction
was observed in patients undergoing OCT-guided PCI
compared with patients treated with angiographic guid-
ance alone.4 The data from this registry established
that suboptimal stent deployment was associated with
an increased risk of major adverse cardiac events dur-
ing follow-up.4,5,20 The findings of the DOCTORS study

stent underexpansion identified by OCT. Indeed, the
rate of underexpansion observed in our study (42%)
was higher than previously reported registry data
(24%5 and 35%),18 but almost identical to the rate re-
ported in the ILUMIEN I study (41%).6 We found that
stent expansion > 79.4% and final minimal lumen area
> 5.44 mm2 were predictive of FFR value >0.90. In
therefore strengthen the evidence in favor of a potential
benefit of OCT to guide PCI in patients with ACS. The
functional improvement observed in the group with OCT
guidance could be a mechanism mediating the clinical
benefit observed in CLI-OPCI.
The prognostic impact of OCT findings other than stent
underexpansion on FFR value is more difficult to establish.

Table 5.  Secondary and Safety Outcomes Including Peri- and Postprocedural Complications in the
Overall Study Population
Angiography-Guided OCT-Guided
Variable Group (n=120) Group (n=120) P Value
Type 4a myocardial infarction (%) 40 (33) 48 (40) 0.28
Procedural complications (%) 7 (5.8) 7 (5.8) 1
No reflow (%) 3 (2.5) 6 (5) 0.50
Coronary spasm (%) 1 (0.8) 0 1
Occlusion 0 0
Collateral occlusion (%) 3 (2.5) 1 (0.8) 0.62
Acute kidney injury (%) 2 (1.6) 2 (1.6) 1
Contrast medium, mL 120 [90; 160] 190 [140; 250] <0.0001
Fluoroscopy time, min 9 [6;13] 12.7 [8.5; 17] 0.001
Procedural duration, min 36 [25; 50] 56 [49; 77] <0.0001
Radiation, cGy/cm 2
3985 [2585; 6413] 5648 [3397; 9810] <0.0001
cGy indicates centigray; and OCT, optical coherence tomography.

914 September 27, 2016 Circulation. 2016;134:906–917. DOI: 10.1161/CIRCULATIONAHA.116.024393


In our study, OCT did not seem to have a greater discrimi-
natory ability than angiography alone for the detection of
incompletely covered lesions. Conversely, OCT identified a
significantly higher number of edge dissections compared
with angiography alone. The rate of edge dissection ob-
served in DOCTORS is in line with previous reports,21–23
and confirms that a large proportion are not visible by
angiography. However, half of these dissections were su-
perficial, and only 8 adventitial dissections prompted the
operator to implant an additional stent. Indeed, when the
dissection is nonflow-limiting and superficial, it can safely
be left untreated.21 Conversely, deeper dissections may
be associated with an increased risk of target lesion re-
vascularization and type 4a MI, as suggested by literature
data.3,5,24,25 Tissue prolapse was also observed at a very
high rate in our study. The prognostic impact of changing
the procedural strategy in response to prolapse remains
unclear, although there is some evidence to suggest that
prolapse may have a deleterious impact.3,18,22,26 Acute stent
malapposition also was frequent in our study, as previously
reported by other authors.4,5,18,27 Clinical outcomes are re-
ported to be generally favorable without correction,4,5,18,27
although in the PESTO registry (Morphological Parameters
Explaining Stent Thrombosis assessed by OCT), 31% of
patients with late or very late stent thrombosis were found
to have malapposition versus 48% of those with acute or
subacute stent thrombosis.24 This reinforces the claim that
OCT-guided PCI might help prevent early, but not late-ac-
quired malapposition.28
Downloaded from http://ahajournals.org by on November 29, 2019
In terms of safety, the excess interventions prompted
by OCT findings in 50% of the OCT-guided group was not
accompanied by an increased risk of periprocedural type
4a MI. Conversely, the duration of the procedure was sig-
nificantly longer in the OCT-guided group, with a great-
er dose of radiation delivered. Similarly, a significantly
greater volume of contrast medium was administered in
the OCT-guided group, although this did not engender a
greater rate of acute kidney injury. Nonetheless, in view
of the study design, it is likely that there is potential to re-
duce the number of OCT runs and the fluoroscopic time.
Study Limitations
This study suffers has limitations that deserve to be
noted. Firstly, it was an open-label design, and thus, we
cannot exclude the possibility that the knowledge of the
study arm may have influenced the operator’s strategy.
Nonetheless, to minimize potential bias, the study pro-
tocol was designed to direct physician strategy as far
as possible, based on objective criteria recommended
in consensus documents.12–14 Given that the reaction to
qualitative OCT findings was at the operator’s discre-
tion, we cannot exclude the possibility that results may
vary with local practices. For instance, in the absence
of specific recommendations, the management of stent
malapposition was at the operator’s discretion. Thus,
Circulation. 2016;134:906–917. DOI: 10.1161/CIRCULATIONAHA.116.024393
OCT Optimizes Stenting: DOCTORS
the impact of correction of stent malapposition cannot
be ascertained. Secondly, the choice of a surrogate
parameter as the primary end point is open to discus-
sion. However, conducting a study on a clinical end
point would require a substantial number of patients,
although the ongoing randomized OPINION trial (Optical
Frequency Domain Imaging vs. Intravascular Ultrasound
in Percutaneous Coronary Intervention; ClinicalTrials.
gov NCT01873027) aims to compare intravascular ul-
trasound versus OCT guidance directly in terms of clini-
ORIGINAL RESEARCH
cal outcomes after PCI with drug-eluting stent implanta-
tion. Furthermore, it has been established that there is
ARTICLE
a statistical association between FFR and outcome after
PCI,17 in line with the recommendations for validating
surrogate end points.29 Thirdly, we did not perform any
economic evaluation in this study. The economic impli-
cations deserve to be evaluated, given the additional
cost of OCT catheters, and the greater use of GP IIb/
IIIa inhibitors and contrast medium. Lastly, although the
target lesion was a single lesion on the culprit artery
without angiographically diffuse disease on the same
vessel, we cannot exclude the possibility that residual
disease burden may have affected the final FFR value.
CONCLUSIONS
In patients with ACS, OCT guidance during PCI provided
useful information beyond that obtained by angiography
alone. The OCT findings affected physician decision-mak-
ing directly, leading to a change in procedural strategy in
half of cases in the OCT-guided group, and was associated
with a higher FFR at the end of the procedure than PCI
guided by fluoroscopy alone. This improvement was driven
mainly by optimization of stent expansion. The benefit was
obtained at the cost of a longer procedure with higher fluo-
roscopy time and more contrast medium, but without an
increase in periprocedural MI or kidney dysfunction.
ACKNOWLEDGMENTS
We thank Céline Tchaoussoff (University Hospital Jean Minjoz, Be-
sancon, France) for data management and Marie-Line Perruche
(University Hospital Jean Minjoz, Besancon, France) for screening.
SOURCES OF FUNDING
The DOCTORS (Does Optical Coherence Tomography Optimize
Results of Stenting) study was funded by the French govern-
ment’s national hospital research program (Program Hospital-
ier de Recherche Clinique 2013).
DISCLOSURES
N.M. declares consulting fees and speaker honoraria (modest)
from St. Jude Medical, Bayer, Daiichi Sankyo, Astra Zeneca,
BMS-Pfizer, and speaker honoraria from Boehringer Ingelheim.
September 27, 2016 915
 Meneveau et al
E.V.B. declares honoraria (modest) from St. Jude Medical and
Philips/Volcano. P.M. declares consulting fees (modest) from
Terumo and St. Jude Medical. G.S. declares consulting fees
(modest) from Terumo and St. Jude Medical. N.A. declares
consulting fees (modest) from St. Jude Medical. C.C. declares
consulting fees (modest) from St. Jude Medical. J.S. declares
Research Grants to Institution from Fondation de France; con-
sulting fees (modest) from Actelion, Amed, Astra-Zeneca, Bay-
er, Sanofi-Aventis, Daiichi-Sankyo, and Eli Lilly; speaker hono-
raria (modest) from AstraZeneca, Algorythm, Amgen, Daiichi
Sankyo, Eli Lilly, and Iroko Cardio. F.S. declares honoraria from
Amgen, BMS-Pfizer, Merck, Eli-Lilly, Daiichi Sankyo, and Sanofi-
Aventis. The other authors declare no conflicts.
AFFILIATIONS
From Department of Cardiology, EA3920, University Hospital
Jean Minjoz, Besançon, France (N.M., N.B., R.C., M.C., F.E.,
H.T., F.S.); University Hospital Gabriel Montpied, and Univer-
sité d’Auvergne UMR 6284, Clermont Ferrand, France (G.S.,
P.M.); Institut Mutualiste Montsouris, Paris, France (C.C.,
N.A.); Nouvel Hôpital Civil, Strasbourg, France (P.O., O.M.);
Centre Hospitalier, Belfort, France (Y.L.); Centre Hospitalier,
Chambéry, France (V.D.-G.); Sorbonne Université - Univ Par-
is 06 (UPMC), ACTION Study Group, INSERM UMR-S 1166,
ICAN, Institut de Cardiologie, Hôpital Pitié-Salpêtrière (AP-HP),
Paris, France (J.S.); Department of Cardiology, CHRU Lille and
UMR1011, Lille, France (E.V.B.); and Centre Hospitalier, An-
necy, France (L.B.).
Downloaded from http://ahajournals.org by on November 29, 2019
FOOTNOTES
Received July 8, 2016; accepted August 9, 2016.
The online-only Data Supplement is available with this arti-
cle at http://circ.ahajournals.org/lookup/suppl/doi: 10.1161/
CIRCULATIONAHA.116.024393/-/DC1.
Circulation is available at http://circ.ahajournals.org.
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